Å Akdeniz Ãniversitesi 2007 YÄ±lÄ± SCI YayÄ±nlar

2007ŀAkdeniz Üniversitesi2007 Yılı SCI YayınlarAkdeniz Üniversitesi Tıp FakültesiDekanlığı

İçindekilerTEMEL TIP BİLİMLERİAnatomi Anabilim DalıBiyofizik Anabilim DalıFizyoloji Anabilim DalıHistoloji ve Embriyoloji Anabilim DalıTıbbi Biyokimya Anabilim DalıTıbbi Biyoloji Anabilim DalıTıbbi Mikrobiyoloji Anabilim DalıTıp Eğitimi Anabilim DalıDAHİLİ TIP BİLİMLERİAcil Tıp Anabilim DalıAile Hekimliği Anabilim DalıÇocuk Sağlığı ve Hastalıkları Anabilim DalıDeri ve Zührevi Hastalıklar Anabilim DalıEnfeksiyon Hastalıkları Anabilim DalıFiziksel Tıp ve Rehabilitasyon Anabilim DalıGöğüs Hastalıkları Anabilim DalıHalk Sağlığı Anabilim Dalıİç Hastalıkları Anabilim DalıKardiyoloji Anabilim DalıNöroloji Anabilim DalıRadyasyon Onkolojisi Anabilim DalıTıbbi Farmakoloji Anabilim DalıCERRAHİ TIP BİLİMLERİBeyin ve Sinir Cerrahisi Anabilim DalıGöğüs Cerrahisi Anabilim DalıGöz Hastalıkları Anabilim DalıKadın Hastalıkları ve Doğum Anabilim DalıKulak, Burun ve Boğaz Hastalıkları Anabilim DalıOrtopedi ve Travmatoloji Anabilim DalıPlastik ve Rekonstrüktif Estetik Cerrahi Anabilim DalıTıbbi Patoloji Anabilim DalıÜroloji Anabilim Dalı

Anabilim Dalı - 20071-Sarikcioglu L, Arican RY:Wilhelm Heinrich Erb (1840-1921) and his contributions to neuroscience.JNeurol Neurosurg Psychiatry78:(7),732,2007.2-Yildirim FB, Soyuncu Y, Oguz N, Aydin AT, Sindel M, Ustunel I:Anterior intermeniscal ligament: Anultrastructural study.Annals of Anatomy189:(5), 510-4, 2007.3-Yildirim FB, Sarikcioglu L:Marie jean pierre flourens (1794-1867): an extraordinary scientist of histime.J Neurol Neurosurg Psychiatry78:(8),852,2007.4-Sarikcioglu L:Otfrid foerster (1873-1941): one of the distinguished neuroscientists of his time.JNeurol Neurosurg Psychiatry78:(6),650,2007.5-Sarikcioglu L, Demirel BM, Ozsoy U, Gurer EI, Oguz N, Ucar Y:Angiolipoma located inside theobturator canal and supplied by the umbilical artery.Annals of Anatomy189:(1),75-8,2007.6-Sarikcioglu L:Johann bernhard aloys von gudden:an outstanding scientist.J Neurol NeurosurgPsychiatry78:(2),195,2007.7-Sarikcioglu L, Demir N, Demirtop A:A standardized method to create optic nerve crush:Yasargilaneurysm clip.Exp Eye Res.84:(2),373-7,2007.8-Sarikcioglu L, Duygulu E, Aydin H, Gurer EI,Ozkan O, Tuzuner S:Effects of intrathecaladministration of FK506 after sciatic nerve crush J Reconstr Microsurg22:(8),649-54,2006.9-Coskun N, Karaali K, Cevikol C:Anatomical basics and variations of the scapula in TurkishadultsSaudı Medical Journal 27:(9),1320-5,2006.ŀAnatomi10-Sarikcioglu L, Yaba A, Tanriover G, Demirtop A, Demir N, Ozkan O:Effect of severe crush injuryon axonal regeneration: a functional and ultrastructural study.J Reconstr Microsurg23:(3),143,2007.

Amyloidogenic transthyretin variant, Gly53Ala 1954 Blevins G, Macaulay R, Harder S, et al. Oculoleptomeningeal amyloidosis in alarge kindred with a new transthyretin variant Tyr69His. Neurology2003;60:1625–30.5 Herrick MK, DeBruyne K, Horoupian DS, et al. Massive leptomeningeal amyloidosisassociated with a Val30Met transthyretin gene. Neurology 1996;47:988–92.6 Mitsuhashi S, Yazaki M, Tokuda T, et al. MRI analysis on a patient with the V30Mmutation is characteristic of leptomeningeal amyloid. Amyloid 2004;11:265–7.7 Munar-Ques M, Salva-Ladaria L, Mulet-Perera P, et al. Vitreous amyloidosis afterliver transplantation in patients with familial amyloid polyneuropathy: ocularsynthesis of mutant transthyretin. Amyloid 2000;7:266–9.8 Schreiber G, Aldred AR, Jaworowski A, et al. Thyroxine transport from bloodto brain via transthyretin synthesis in choroid plexus. Am J Physiol1990;258(Pt 2):R338–45.9 Dickson PW, Schreiber G. High levels of messenger RNA for transthyretin(prealbumin) in human choroid plexus. Neurosci Lett 1986;66:311–15.10 Stangou AJ, Hawkins PN. Liver transplantation in transthyretin-related familialamyloid polyneuropathy. Curr Opin Neurol 2004;17:615–20.11 Adams D, Samuel D, Goulon-Goeau C, et al. The course and prognostic factorsof familial amyloid polyneuropathy after liver transplantation. Brain2000;123:1495–504.12 Ando Y, Terazaki H, Nakamura M, et al. A different amyloid formationmechanism: de novo oculoleptomeningeal amyloid deposits after livertransplantation. Transplantation 2004;77:345–9.13 Ellie E, Camou F, Vital A, et al. Recurrent subarachnoid hemorrhageassociated with a new transthyretin variant (Gly53Glu). Neurology2001;57:135–7.HISTORICAL NOTE ..............................................................................................Johann Bernhard Aloys von Gudden: an outstanding scientistJohann Bernhard Aloys von Gudden was a visionarypsychiatrist and neuroanatomist. He dedicated himself toneurobiology and was far more than a consulting psychiatristto the Bavarian royal family. Some well-known scientistssuch as Emil Kraepelin (1856–1926), Franz Nissl (1860–1919),Auguste-Henri Forel (1848–1931) and Sigbert Josef MariaGanser (1853–1931) studied under his supervision.von Gudden was born in Kleve, in lower Rhineland near theDutch frontier, on 7 June 1824. He was the third of seven sons ofJohannes Gudden, a landed proprietor, owner of a brewery andmember of the town council. In 1843, he began his studies inphilosophy and medicine at the university in Bonn. For hisdoctoral dissertation, von Gudden studied torsional eye movementunder the supervision of Alfred Volkman (1800–77) at Halle.He received his medical degree in 1848 and in the same yearpassed with distinction the state medical examination in Berlin.Thereafter, he obtained a position at the Siegburg asylum as anassistant under the supervision of Karl Wigand Maximilian Jacobi(1775–1858), one of the leading German psychiatrists.After completing his studies in Berlin in 1849, von Guddenserved in the army for a year. From 1851 to 1855, he worked withChristian Friedrich Wilhelm Roller (1802–78) in the Illenauasylum near Achern, the first modern psychiatric hospital inGermany. He married Roller’s granddaughter Clarissa Voigt in1855, and, in the summer of the same year at the age of 31, wasappointed the director of Werneck, a newly established asylumin northern Bavaria. In October 1869, von Gudden becamedirector of the newly founded Burghölzli psychiatric hospital inZürich, Switzerland, and in 1870, was appointed co-editor ofArchiv für Psychiatry und Nervenkrankheiten. In 1872, he took overthe direction of the Oberbayerische Kreis-Irrenanstalt inMunich, and subsequently became a full professor of psychiatryat the University of Munich.At the height of his career, von Gudden was commissioned toprovide psychiatric care for the Bavarian royal family. He wasthe personal doctor of the mentally diseased Crown PrinceRudolf Otto (1848–1916) for many years. He took responsibilityfor the everyday care of the crown prince, who was secluded inFurstenried, a castle near Munich, and subsequently wasassigned to examine and treat King Ludwig II of Bavaria(1845–86). On 13 July, 2 days after King Ludwig II was arrestedat Castle Neuschwanstein, Ludwig II and Bernhard vonGudden drowned in Starnberg Lake, close to the castle ofBerg. The details surrounding their death remain unclear. Forsome incomprehensible reason, no autopsy was ever performedon von Gudden to determine the cause of death.In the last 14 years of his life, von Gudden devoted himself tothe study of neuroanatomy, a rapidly developing science in the19th century. He was the first neuroanatomist to create lesionsin the nervous system of newborn animals and to study thesubsequent anatomical changes. In this work, he applied thedoi: 10.1136/jnnp.2006.106633technique of secondary degeneration to study important interrelationshipsbetween the cortical and subcortical structures.Today, this method, based on retrograde neuronal cell bodychanges observed after nervous system lesions, is still referredto as the von Gudden method. A published article 1 shows thathe was clearly aware of the limitations of this method; he wasnot so much interested in the description of brain centres, butwas concerned with the independencies and connectionsbetween the centres.Macroscopic observation was widely used in von Gudden’stime, as microscopy was still unsatisfactory. Therefore, hepioneered the development of a microtome, the so-calledGudden’s microtome, 2 for sectioning the human brain, andusing this he described the important neuroanatomical centres.His assistant, Auguste-Henri Forel, subsequently improved themicrotome, and thus he was able to obtain entire human brainsections, at about 55 mm in thickness.von Gudden is perhaps best known for his studies on partialdecussation of the optic paths, a subject that kept him occupiedfor around 30 years. His method of producing secondaryatrophy of central structures after the removal of sense organsor cranial nerves in young animals ushered in a fresh advancein experimental neurology. In fully grown animals, from whicheyes had been removed when they were young, he showed notonly crossed and uncrossed optic fibres but also a supraopticcommissure and the transverse peduncular tract. Both of thesetracts now bear his name. He was the first to describe theinterpeduncular nucleus and the tegmental nuclei, known to allwho work in the midbrain today as the dorsal and ventralnuclei, respectively, of Gudden.One of Gudden’s greatest contributions was his observationin 1870 that destruction of certain areas of the cerebral cortexleads to atrophy of specific thalamic nuclei. Augustus VolneyWaller believed that, after a cut, the cell body and central stumpof the nerve remained normal, but Gudden found that theyshowed signs of atrophy. Accordingly, he launched a series ofinvestigations in which he used his ‘‘secondary degenerationtechnique’’—that is, the Gudden method—to trace connectionsbetween the main centres of the brain.Levent SarikciogluCorrespondence to: Dr L Sarikcioglu, Department of Anatomy, AkdenizUniversity, Faculty of Medicine Campus, Antalya 07070, Turkey;sarikcioglu@akdeniz.edu.trReferences1 von Gudden JBA. Experimentaluntersuchungen bei das peripherischer undcentrale Nervensystem. Arch Psychiatr Nervenkr 1870;2:693–723.2 von Gudden B. Über ein neues microtom. Arch Psychiatr Nervenkr1875;5:229–34.www.jnnp.com

650 J Neurol Neurosurg Psychiatry 2007;78:650HISTORICAL NOTE ..............................................................................................doi: 10.1136/jnnp.2006.112680Otfrid Foerster (1873–1941): one of the distinguished neuroscientists of his timeOtfrid Foerster, German neurologist and neurosurgeon,made innovative contributions to neurology and neurosurgery.He was born in Breslau (now named Wrocław,Poland). He attended the St Maria Magdalena Gymnasium inBreslau and graduated from there in 1892. From 1892 to 1896he studied medicine at the universities of Freiburg, Kiel andBreslau, graduating from Breslau in 1896. In 1897, at the age of24, he completed his doctoral studies on typhoid fewer, the onlyone of his studies not connected directly with the nervoussystem. Foerster was profoundly influenced by Carl Wernicke(1848–1905). By cooperating with Wernicke, Foerster’s interestin the anatomy of the central nervous system was excited.Following a suggestion by Wernicke, he went to Paris andremained there for 2 years as a pupil of Jules-Joseph Déjérine(1849–1917), Pierre Marie (1853–1940) and Joseph FrançoisFelix Babinski (1857–1932). After his return to Breslau hecollaborated with Wernicke in his published atlas of brainsections issued in 1903. 1 In 1908 he was appointed professorextraordinarius and in 1911 he established the first departmentof neurology separate from psychiatry in Germany. 2In 1908, Foerster developed an operation to cut the posteriorsensory root in order to alleviate spasticity (Foerster’s operation).The involvement of spinal reflexes in the genesis ofmuscular spasticity suggested its possible treatment by surgicalinterruption of the sensory branches of the thoracic and lumbarnerves (rhizotomy). Foerster’s studies on posterior rhizotomyled to the determination of dermatome borders. In 1912, Foersterand Alexander Tietze (1864–1927), the German surgeon, transectedthe spinothalamic tract for intractable pain, unaware thatthis procedure had been performed by William Gibson Spiller andEdward Martin several months earlier. After World War I,Foerster published his innovative results concerning war injuries,the surgical treatment of nerve damage by shot wounds and othertypes of spinal cord and brain damage. 1Although not a surgeon, he operated on numerous patientswith spinal cord and peripheral nerve lesions during World WarI. Thereafter, he became a neurosurgeon. After the war,veterans presented to him with cerebral injuries causingepilepsy. Foerster resected the epileptogenic areas, identifiedusing galvanic cortical stimulation under local anaesthesia. Thismade possible the maximal excision of scarred cortex withoutdamage to vital areas. Foerster continued the detailed mappingof the human cortex using local anaesthesia so that the patientcould report sensory responses during the operation. In 1928,Wilder Penfield (1891–1976) spent 6 months with Foerster inBreslau; he was particularly influenced by Foerster andcontinued Foerster’s lifework on the analysis of the braincortex and the study of epilepsy. They published their results onsurgery to treat traumatic epilepsy. 3 Foerster also performed thefirst electrocorticographic studies with Altenburger in 1935. 4Other milestones included the hyperventilation test in patientswith epilepsy 5 and the description of the atonic–astatic from ofinfantile cerebral palsy. 6Although he faced many obstacles, he insisted on living formany years in Breslau. Breslau became a training centre forneurologists and neurosurgeons. Between the two world wars,many internationally well known scientists, Wilder Penfield(1891–1976), Percival Bailey (1892–1973), Paul Bucy (1904–1993), Robert Wartenberg (1897–1956), Herbert Mclean Evans(1882–1971) and Harold Leeming Sheehan (1900–1988),studied under his supervision and made important contributionsto neuroscience.His most famous patient was Vladimir Ilyich Lenin. Lenindied in 1924, having suffered from strokes in his last two years.The Soviet government invited Foerster as a specialist to attendLenin during his illness, and Foerster was appointed Lenin’spersonal physician. Foerster lived in Russia from 1922 to 1924,and was a great admirer of Lenin’s personality and politicalachievements. After Lenin’s death, Foerster participated in theautopsy and Lenin’s brain was removed before his body wasembalmed. Foerster was asked to suggest the name of ascientist who could examine Lenin’s brain and he named theGerman neuroscientist Oskar Vogt to locate the neurons thatare responsible for genius.Foerster made major contributions to neuroscience. Hisinvestigations included studies on the disorders of mobilityand sensation, localisation, muscle physiology, epilepsy, braintumours and pain. His blending of physiology, neurology andneurosurgery was instrumental in his creating his worldfamous cytoarchitectonic map of the human cerebral cortex. 7He was nominated several times for the Nobel Prize inPhysiology or Medicine but never received it. Foerster washonoured posthumously by German neurosurgical and neurologicalsocieties as persona non grata. In his last years during theNazi regime, his activities were restricted because of hisassociation with Russia as Lenin’s physician and his wife’sJewish ancestry. At that period, he was forced to stop hissubscriptions to foreign journals and accepted a position on theadvisory board of the Journal of Neurophysiology. 1 6 Lackinggovernment funding, he underwrote his own research expensesfor 30 years until the Rockefeller Foundation provided financialsupport in 1930. 2 With financial support from the RockefellerFoundation and the support of the State of Prussia, Foersterwas able to open a new Institute of Neurological Research in1934 which later was renamed after him (the Otfrid FoersterInstitut für Neurologie).Foerster and his wife Martha suffered from tuberculosis andwere treated in a sanatorium in Switzerland. He succumbed totuberculosis on 15 June 1941 and Martha followed a day later;they are buried together in Breslau. In 1953, the Otfrid Foersteraward was created by the Deutsche Gesellschaft fürNeurochirurgie, and one of his pupils, Percival Bailey, receivedthe first medal. 2 8Levent SarikciogluCompeting interests: None declared.Correspondence to: Dr Levent Sarikcioglu, Department of Anatomy,Akdeniz University Faculty of Medicine, 07070 Antalya, Turkey;sarikcioglu@akdeniz.edu.trReferences1 Kennard MA, Fulton JF, de Gutiérrez-Mahoney CG. Otfrid Foerster 1873–1941.An appreciation. J Neurophysiol 1942;5:1–17.2 Tan TC. Otfrid Foerster (1873–1941). J Neurol 2003;250:513–14.3 Foerster O, Penfield W. The structural basis of traumatic epilepsy and results ofradical operation. Brain 1930;53:99–119.4 Foerster O, Altenburger H. Elektrobiologische Vorgänge an der menschlichenHirnrinde. Dtsch Z Nervenheilkd 1935;135:277–86.5 Foerster O. Hyperventilationsepilepsie. Dtsch Z Nervenheilk 1924;83:347–56.6 Tan TC, Black PM. The contributions of Otfrid Foerster (1873–1941) to neurologyand neurosurgery. Neurosurgery 2001;49:1231–5.7 Foerster O. The dermatomes of man. Brain 1933;56:1–39.8 Lorenz R. The significance of Otfrid Foerster’s work for the Deutsche Gesellschaftfur Neurochirurgie. Zentralbl Neurochir 1991;52:149–52.www.jnnp.com

732HISTORICAL NOTE ..............................................................................................Wilhelm Heinrich Erb (1840–1921) and his contributions to neuroscienceWilhelm Heinrich Erb was a renowned German neurologistand an eminent physician of his time. He is wellknown for his innovative contributions to neurology.Erb became known primarily for his contributions to diagnosingand treating various neurological disorders. He was one of theclinicians to use electricity in the diagnosis and treatment ofnervous disorders. 1 Duchenne should not be overlooked in thehistory of electrical stimulation. He used his electrical stimulationtechnique, which he called ‘‘électrisation localisée’’ (localisedfaradisation), as a clinical diagnostic and prognostic tool, as wellas a physiological means of exploring the anatomy of the living. 2Apart from Erb’s description of the disorders to which hisname is attached, he pioneered the usage of reflex hammer inneurological examinations. Additionally, he introduced theterm ‘‘tendon reflex’’. He gave his name to paralysis of thebrachial plexus and described important neurological terms. 1Erb was born in Winweiler, the Bavarian Palatinate, on 30November 1840, to a forester, Friedrich Erb. In 1857, he enteredmedical school in Heidelberg and also studied in Erlangen andMunich. When he was 22 years old, he returned to Heidelbergand become an assistant to a well known pathologist andneurologist Nikolaus Friedrich (1825–1882). Erb’s first scientificinterest was toxicology and histology, and he dealt with theeffects of picric acid on the organism and the development oferythrocytes. Under the guidance of Friedrich, Erb becomeattracted to the study of the nervous system. 3 After completinghis habilitation in 1865, he was promoted to Privatdozent andgave lectures at the University of Heidelberg. In 1880, he wentto the University of Leipzig where he served as the director ofthe outpatient neurology clinic and set up an independentneurology unit. 4 Paul Julius Möbius (1853–1907) and EmilKraepelin (1856–1926) worked here as voluntary assistantsunder his guidance. In 1883, he became Fellow Professor ofInternal Medicine at the University of Heidelberg where he washead of a new neurological hospital. In 1891, he contributed tothe foundation of the ‘‘Deutsche Zeitschrift für Nervenheilkunde’’,later renamed ‘‘Zeitschrift für Neurologie’’, which finally becamethe ‘‘Journal of Neurology’’. Erb’s contribution to the first volumeof the journal was a survey on muscular dystrophies. 4Erb was a mentor for many internationally well knownscientists such as Ernst Julius Remak (1849–1911), FriedrichSchultze (1848–1934), Paul Julius Möbius (1853–1907), EmilKraepelin (1856–1926), Ernst Adolf Gustav Gottfried vonStrümpell (1853–1925), Max Nonne (1861–1959), JohannHoffmann (1857–1919), Otto Cohnheim (1873–1953) andHenry M. Thomas (1891–1966).Erb made early observations relating to syphilis and tabesdorsalis. In his studies on tabes dorsalis, he investigated therelationship between them and published several papers. Hereported on juvenile forms of progressive muscular atrophy 5 andelaborated on the difference between myoatrophies and myodystrophies.In 1891, Erb suggested that muscular dystrophies werea primary degeneration of muscle and coined the term ‘‘dystrophiamuscularis progressiva’’. 6 He popularised electrodiagnosticsin neurology and demonstrated increased motor nerve irritabilityin tetanus. His manual entitled ‘‘Handbuch der Elektrotherapie’’ wasa neurological standard work of its time.He was one of the first clinicians to use the reflex hammerduring physical examinations. Interestingly, the deep (orpatellar) tendon reflex was first introduced simultaneouslyinto medical literature by Erb and Carl Otto Friedrich Westphal(1833–1890). Both scientists published their results separatelydoi: 10.1136/jnnp.2007.115956in the January 1875 issue of Archiv fur Psychiatrie undNervenkrankheiten, where Westphal was an editor. Westphalused the term ‘‘the lower limb phenomenon’’(Unterschenkelphänomen in German) whereas Erb used the termpatellar tendon reflex (Patellarsehnenreflex in German) andcorrectly regarded the phenomenon as a true reflex arch. 7 Erbpointed to the spinal cord levels as presumably correspondingto the reflex arches of the various individual tendon reflexes.Several eponyms are named after him, including: Erb–Duchenne palsy (also known as Erb’s palsy), Erb–Charcotparalysis, 8 9 Erb’s point, 1 Erb–Westphal symptom, 10 11 Erb’sdystrophy (also known as Erb’s scapulohumeral dystrophy), 12Erb’s phenomenon, 13 Erb’s reflex (also known as biceps femorisreflex) 10 14 15and Erb–Goldflam disease.Erb was one of the leading figures in neurology. He retired in1907 and became an honorary member of many scientificsocieties. He remained Honorary President of the Society ofGerman Neurologists (Gesellschaft Deutscher Nervenärzte) until hedied. He also experienced much sadness in his life. Only one ofhis four sons survived him. Two of his sons died and the thirddied during World War I. In his last days he caught cold whichprogressed to bronchopneumonia. He closed his eyes toneuroscience and his workaholic life in Heidelberg on 29October 1921.Levent Sarikcioglu, Ramazan Yavuz AricanDepartment of Anatomy, Akdeniz University Faculty of Medicine, Antalya,TurkeyCorrespondence to: Dr Levent Sarikcioglu, Department of Anatomy, AkdenizUniversity Faculty of Medicine, 07070 Antalya, Turkey;sarikcioglu@akdeniz.edu.trCompeting interests: None declared.References1 Tubbs RS, Loukas M, Salter EG, et al. Wilhelm Erb and Erb’s point. Clin Anat (inpress).2 Parent A. Duchenne de Boulogne (1806–1875). Parkinsonism Relat Disord2005;11:411–12.3 Kuhn E, Rudel R. Wilhelm Heinrich Erb (1840–1921). Muscle Nerve1990;13:567–9.4 Jost WH. A tribute to Wilhelm H. Erb. J Neurol 2006;253(Suppl 1):I1–2.5 Erb WH. Über die ‘‘juvenile Form’’ der progressiven Muskelatrophie und ihreBeziehungen zur sogenannten Pseudohypertrophie der Muskeln. Dtsch Arch KlinMed Leipzig 1884;34:467–519.6 Erb WH. Dystrophia muscularis progressiva. Klinische und pathologischanatomischeStudien. Dtsch Z Nervenheilkd 1891;1:13–94.7 Louis ED. Erb and Westphal: simultaneous discovery of the deep tendon reflexes.Semin Neurol 2002;22:385–90.8 Erb WH. Spinaler Symptomenkomplex. Berliner Zeitschrift Psych 1875;32.9 Charcot JM. Du tabes dorsal spasmodique. Progrés Médical Paris 1876;5:737.10 Erb WH. Ueber Sehnenreflexe bei Gesunden und Ruckenmarkskranken. ArchPsychiat Nervenkr 1875;5:792–802.11 Westphal CFO. Über einige durch mechanische Einwirkung auf Sehnen undMuskeln hervorgebrachte Bewegungs-Erscheinungen. Arch Psychiat Nervenkr1875;5:803–34.12 Erb WH. Über die ‘‘juvenile Form’’ der progressiven Muskelatrophie und ihreBeziehungen zur sogenannten Pseudohypertrophie der Muskeln. Dtsch Arch KlinMed 1884;34:467–519.13 Erb WH. Zur Lehre von der Tetanie, nebst Bemerkungen über die elektrischeErregbarkeit motorischer Nerven. Arch Psychiatr Nervenkr 1874;4:271–316.14 Erb WH. Zur Casuistick der bulbären Lähmungen. Arch Psychiatr Nervenkr1879;9:325–50.15 Goldflam S. Über einen scheinbar heilbaren bulbärparalytischen Symptomencomplexmit Betheiligung der Extremitäten. Dtsch Z Nervenheilkd1893;4:312–52.www.jnnp.com

Sarikcioglu L, Demir N, Demirtop A.Department of Anatomy, Akdeniz University, Faculty of Medicine, 07070 Antalya, Turkey.sarikcioglu@akdeniz.edu.trAbstractIt is often difficult to compare results obtained by different investigators on nerve compression injuries, owing todifferences in method of pressure application and noncomparable pressure levels. In the present study, wedescribed a new method to crush the optic nerve by using a specially designed and commercially availabledevice. We think that standardization of the compression methods is necessary to compare interlaboratory resultsŀA standardized method to create optic nerve crush: Yasargil aneurysm clip.

Coskun N, Karaali K, Cevikol C, Demirel BM, Sindel M.Department of Anatomy, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey. nigarc@akdeniz.edu.trAbstractOBJECTIVE: To analyze the anatomical basis of the scapula, acromion, os acromiale, coracoid process, coracoacromialarch, and glenoid cavity in Turkish adults.METHODS: We performed the study at the Faculty of Medicine, Akdeniz University, Turkey between January2004 and December 2005. A total of 90 dry bones of the scapula from human cadavers were randomly selected.The length, width, and anterior thickness of the acromion and the acromial facet of the acromioclavicular jointwere measured with an electronic caliber and was examined visually. For the radiological evaluation, the posterioranterior and the lateral shoulder radiographs of 90 consecutive adult patients with normal findings were used.These films were evaluated and grouped according to the acromial arch morphology.RESULTS: The distribution of the acromial morphologic types according to slope was type I (flat) 10%, type II(curved) 73%, type III (hooked) 17%. Type I was seen in 11%, type II 66%, type III 23% of the specimens. Themorphological shape of the tip of the acromion was 31% cobra shaped, 13% square shaped, and 56%intermediate type. The scapulas, coracoid process and the coraco acromial arch were measured. In 72% of thespecimen, the glenoid notch of the scapulas were absent and oval shaped, whereas in 28% the notch was wellexpressed and the glenoid cavity was pear shaped. The mean vertical length of the glenoid cavity was 36.3 +/- 3mm, and the mean transverse length was 24.6 +/- 2.5 mm. Os acromiale is a rare anatomical condition. Itsincidence has been documented in radiographic and anatomical studies to be between 1-15%. The presence ofos acromiale was 1% in shoulder radiographs (os pre-acromiale), and in dry bones (os meta-acromiale)CONCLUSION: We reported the exact morphological measurements of the bone structures of the scapula inTurkish adult population. Our results present an instructive figures of anatomical preparations and radiologicalcases that can be used to make a more precise radiological and a differential diagnosesŀAnatomical basics and variations of the scapula in Turkish adults.

Angiolipoma located inside the obturator canal and supplied by the umbilicalartery.Sarikcioglu L, Demirel BM, Ozsoy U, Gurer EI, Oguz N, Ucar Y.Department of Anatomy, Akdeniz University, Faculty of Medicine, 07070 Antalya-Turkey. sarikcioglu@akdeniz.edu.trAbstractDuring dissection of the retropubic region of a 55-year-old female cadaver, we encountered an angiolipoma located inside the obturatorcanal which was connected to the wall of the urinary bladder by a fibrous cord. The angiolipoma was supplied by a branch originatingfrom the umbilical artery. Microscopically the benign soft tissue tumor was characterized by lobules of mature adipocytes and denselydistributed networks of small and larger blood vessels, thus resembling typical histological features of an angiolipoma. Both theuncommon location of the angiolipoma and the abnormal branch of the umbilical artery entering the obturator canal should be taken intoaccount during surgical procedures in this region, such as for orthopedic pelvic procedures, hernia repair or bladder/urethra-relatedinterventions (e.g. transobturator tape, tension-free vaginal tape, colposuspension).PMID: 17319612 [PubMed - indexed for MEDLINE]ŀAnn Anat. 2007;189(1):75-8.

Author(s): Sarikcioglu L (Sarikcioglu, Levent) 1 , Yildirim FB (Yildirim, Fatos Belgin) 1Source: JOURNAL OF THE HISTORY OF THE NEUROSCIENCES Volume: 17 Issue: 1 Pages: 109-110 Published: 2008Times Cited: 0 References: 7 Citation MapDocument Type: ArticleLanguage: EnglishReprint Address: Sarikcioglu, L (reprint author), Akdeniz Univ, Fac Med, Dept Anat, TR-07070 Antalya, TurkeyAddresses:1. Akdeniz Univ, Fac Med, Dept Anat, TR-07070 Antalya, TurkeyE-mail Addresses: sarikcioglu@akdeniz.edu.trPublisher: TAYLOR & FRANCIS INC, 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USASubject Category: History & Philosophy Of Science; NeurosciencesIDS Number: 251EAISSN: 0964-704XDOI: 10.1080/09647040701236578ŀArea postrema: One of the terms described by Magnus Gustaf Retzius

Source: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Volume: 78 Issue:8 Pages: 852-852 Published: AUG 2007Times Cited: 0 References: 9 Citation MapDocument Type: Biographical-ItemLanguage: EnglishKeyWords Plus: 19TH-CENTURYReprint Address: Yildirim, FB (reprint author), Akdeniz Univ, Fac Med, Dept Anat, TR-07070 Antalya, TurkeyAddresses:1. Akdeniz Univ, Fac Med, Dept Anat, TR-07070 Antalya, TurkeyE-mail Addresses: yildirimfb@akdeniz.edu.trPublisher: B M J PUBLISHING GROUP, BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDONWC1H 9JR, ENGLANDSubject Category: Clinical Neurology; Psychiatry; SurgeryIDS Number: 190IWISSN: 0022-3050DOI: 10.1136/jnnp.2007.118380ŀAuthor(s): Yildirim FB (Yildirim, Fatos Belgin), Sarikcioglu L (Sarikcioglu, Levent)

Arican RY, Coskun N, Sarikcioglu L, Sindel M, Oguz N.Department of Anatomy, Akdeniz University Faculty of Medicine, 07070 Antalya, Turkey.AbstractDuring the routine dissection studies on the right side of a 56-year-old female cadaver we encountered coexistenceof the pectoralis quartus and pectoralis intermedius muscles. The pectoralis quartus originated from thecostochondral junction of the fifth and sixth ribs, and then extended laterally under the border of pectoralis majormuscle, but it was entirely separate from it. The pectoralis quartus formed a long flat band with an average widthof 1.5 cm. It then inserted as an aponeurosis to the both of lateral lip of the intertubercular groove of the humerusand tendon of the short head of the biceps brachii muscle. Furthermore, the pectoralis intermedius muscle was afleshy slip between the pectoralis minor and pectoralis quartus muscles and arose from the third and fourth ribs. Itthen united to the tendon of the short head of the biceps brachii muscle two cm below the coracoid process.ŀCo-existence of the pectoralis quartus and pectoralis intermedius muscles.

Donmez BO, Agirdir BV, Sindel MM.Department of Anatomy, Nose and Throat, Akdeniz University, Faculty of Medicine, Antalya, Turkey.AbstractOBJECTIVE: The study aimed to investigate the anatomy of the lateral nasal wall to provide a set ofmeasurements among some important anatomical landmarks and to reveal the relationship between them.METHODS: Fifty half heads were dissected to determine the distances between important landmarks in thelateral nasal wall for endoscopic sinus surgery. Landmarks were measured with an electronic caliper. This studywas carried out between December 2002 and February 2003 at the Anatomy Research Laboratory, Faculty ofMedicine, Akdeniz University, Antalya, Turkey.RESULTS: Results were provided as mean +/- standard deviation. In our study, some of the critical distances asin the lateral nasal wall were measured and results showed consistency to the data found in the literature.CONCLUSION: Our results are useful to achieve safe endoscopic sinus surgeryŀImportant anatomical landmarks in the lateral nasal wall.

found 1 article by title matching your search:Ann Anat. 2007;189(5):510-4.Anterior intermeniscal ligament: an ultrastructural study.Yildirim FB, Soyuncu Y, Oguz N, Aydin AT, Sindel M, Ustunel I.Department of Anatomy, Akdeniz University, Faculty of Medicine, 07070 Antalya, Turkey. yildirimfb@akdeniz.edu.trAbstractThe aim of the present study was to investigate the detailed histological characteristics of membranous and cord-like anteriorintermeniscal ligaments (AIMLs) by transmission electron microscopy (TEM) and light microscopy. Ten biopsies of AIMLs were sampledfrom 10 knees during total knee arthroplasty procedures. Three of them were membranous and 7 of them were cord-like. They wereprocessed for light and TEM evaluations. Histologically, the findings in the membranous and cord-like ligaments were similar. Theyconsisted of parallel bundles of collagen fibrils and their posterior surfaces were covered by a layer of loose well-vascularized synovialtissue. The subsynovial region consisted of loose connective tissue and was rich in blood vessels and nerve endings. FibroblastsŀWeembedded between parallel-oriented collagen fibrils were the major cell type that we observed. Free nerve endings were squeezedbetween bundles of collagen fibers. Electron microscopic observations revealed the presence of Ruffini corpuscles. The presence ofneural mechanoreceptors in the membranous and cord-like intermeniscal ligaments may contribute to structural and proprioceptionalfunction of the knee. Protection of those ligaments may be valuable in planning and performing meniscal surgeries.PMID: 17910405 [PubMed - indexed for MEDLINE]

Effects of Intrathecal Administration ofFK506 after Sciatic Nerve Crush InjuryLevent Sarikcioglu, Ph.D., 1 Erdeniz Duygulu, M.D., 2 Hulya Aydin, M.D., 3Elif Inanc Gurer, M.D., 3 Olcay Ozkan, Ph.D., 1 and Serdar Tuzuner, M.D. 4ABSTRACTAlthough various administration routes of FK506 have been published, intrathecaladministration of FK506 has not previously been reported in the literature. A dailydose of 0.05 mg/kg of FK506 was given (a small dose compared with those reported in theavailable literature). The authors used this small dose to obtain lower immunosuppressionand neurotoxicity, and a higher axonal regeneration rate.A total number of 40 female Wistar rats were used and randomly divided into fourgroups: control, sham, FK506-treated, and vehicle-treated. Sciatic nerve regeneration wasevaluated by walking track analysis, an electrostimulation test, and light microscopicevaluation.There was a statistically significant difference ( p < 0.05) between FK506-treatedand vehicle-treated groups at the end of 6 weeks according to both the walking trackanalysis and the electrostimulation test. Comparing the stimulus thresholds of the shamand FK506-treated group, no significant difference ( p < 0.05) was observed.Evaluation of the data revealed that FK506 had a beneficial effect on sciatic nerveregeneration.KEYWORDS: FK506, sciatic nerve crush, recovery, intrathecal administrationDrug administration via chronic catheterizationof the subarachnoid space is widely used in studies ofspinal pharmacology and pain mechanisms in the rat.During the last three decades, changing the route ofcatheterization from the cisterna magna 1 to the lumbosacralroute 2,3 has made the surgery less invasive and hasgreatly decreased the risk of complications. 1,4–10FK506 (Tacrolimus, Prograf TM ) is a new experimentalimmunosuppresive agent isolated from Streptomycestsukubaensis, currently in limited use for preventionof graft rejection following organ transplantation. CyclosporinA (CsA) is also used for the prevention of graftrejection. But FK506 has two noteworthy properties.First, it has been found to be more potent than CsAin vitro, as well as in animals and in humans. Second, itstoxicity in humans is reported to be less than thatassociated with CsA. FK506 has been found to have astronger immunosuppressant effect than CsA, withfewer side effects. 11,12 In addition to its ability to suppressimmune system cells (T-cell activity), it has anumber of non-immune effects. 13–18 Although an increasedrate of axonal regeneration has been noted, 19,20neurotoxic complications from immunosuppressanttherapy with FK506 have also been reported in theDownloaded by: Akdeniz University. Copyrighted material.1 Department of Anatomy, Akdeniz University Faculty of Medicine,Antalya; 2 Department of Orthopaedics and Traumatology, SSK BursaSevket Yilmaz Hospital, Bursa; Departments of 3 Neurology and4 Orthopaedics and Traumatology, Akdeniz University Faculty ofMedicine, Antalya, Turkey.Address for correspondence and reprint requests: Levent Sarikcioglu,Ph.D., Department of Anatomy, Akdeniz University Faculty ofMedicine, Antalya, Turkey.J Reconstr Microsurg 2006;22:649–654. Copyright # 2006 byThieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY10001, USA. Tel: +1(212) 584-4662.Accepted for publication June 26, 2006.DOI 10.1055/s-2006-956239. ISSN 0743-684X.649

Effect of Severe Crush Injury onAxonal Regeneration: A Functionaland Ultrastructural StudyLevent Sarikcioglu, Ph.D., 1 Aylin Yaba, M.Sc., 2 Gamze Tanriover, M.Sc., 2Arife Demirtop, B.Sc., 3 Necdet Demir, Ph.D., 2,3 and Olcay Ozkan, Ph.D. 1ABSTRACTIn the present study, we performed sciatic nerve compression for 30, 45, and 60minutes by the Yasargil aneurysm clip and observed recovery on postoperative days 14, 28,and 42. We observed that as compress time increases, functional recovery and morphologicalregeneration of crushed sciatic nerve needs longer time. Additionally, we showedwhich cells are durable in nerve regeneration after crush injury. Nerve regeneration orrecovery depends on trauma durations in which a longer recovery time is needed afterlongtime pressure. Although Schwann cells are found to be resistant and this might be forthe cleanup of debris and remyelinization at mild injury, macrophage infiltration isnecessary for the cleanup of damaged fragments of cells and fibers. The result indicatesthat a strong relationship exists between nerve damage and subsequent recovery. Thisphenomenon may depend on crush severity that is associated with mechanic pressure andinadequate logistic supports such as malnutrition and hypoxia. Additionally, we found thatthe Yasargil aneurysm clip is an appropriate device to perform a standard experimentalsevere crush injury model.KEYWORDS: Yasargil-Phynox aneurysm clip, crush injury, sciatic nerve, axonalregenerationDownloaded by: Akdeniz University. Copyrighted material.Although crush injury of the peripheral nervehas long been studied, few authors 1,2 have documentedthe correlation between the extent of nerve injury andthe degree of functional recovery, as well as the importanceof crush duration in acute crush injury.In the literature, experimental crush injuries havecommonly been created by forceps or hemostatic forceps,3–12 neither of which allows quantitative or standardapplication of compression. To solve the standardizationproblem, a few authors 1,2,13,14 have described compressionchambers/devices for making peripheral nerve injury.In our previous study, 15 we described a simple andreliable device, the Yasargil aneurysm clip, for makingperipheral nerve injury.Important effective factors in peripheral nerveinjury may be physical trauma and hypoxia that dependson ischemic insult. Our hypothesis was that duration ofpressure time is an important factor for functionalrecovery time and axonal morphology. In the presentstudy, we aimed to show the correlation between severecrush duration and functional recovery and regenerationprocess and to show which cells are influential for therepair of nerve injury created by the Yasargil aneurysmclip.1 Department of Anatomy, 2 Department of Histology and Embryology,3 Electron Microscopy Unit (TEMGA), Akdeniz University Faculty ofMedicine, Antalya, Turkey.Address for correspondence and reprint requests: Dr., LeventSarikciogluDepartment of Anatomy, Akdeniz University Faculty ofMedicine, 07070 Antalya, Turkey.J Reconstr Microsurg 2007;23:143–150. Copyright # 2007 byThieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY10001, USA. Tel: +1(212) 584-4662.DOI 10.1055/s-2007-974649. ISSN 0743-684X.143

1-Yargicoglu P, Sahin E, Gümüşlü S, Ağar AThe effect of sulfur dioxide inhalation on activeavoidance learning, antioxidant status and lipid peroxidation during aging.NeurotoxicolTeratol29(2):211-8,20072-Derin N, Agac A, Bayram Z, Asar M, Izgut-Uysal VN.Effects of L-carnitine on neutrophil-mediatedischemia-reperfusion injury in rat stomachCell biochem Funct.24(5):437-42,20063-Akpinar D., Yargiçoğlu P., Derin N., Alicigüzel Y., Sahin M., Ağar A. The effect of lipoicAcid on lipid peroxidation and visual evoked potentials (veps) in rats exposed to chronicrestraint stress. Int J Neurosci. 117(12), 1691-706 (2007).4-Akpinar D., Yargicoglu P., Derin N., Aslan M., Agar A. Effect of aminoguanidine on visualevoked potentials (VEPs), antioxidant status and lipid peroxidation in rats exposed to chronicrestraint stress. Brain Res. 1186:87-94 (2007).5-Monique C. de Waard, Jolanda van der Velden, Virginie Bito, Semir Ozdemir, LiesbethBiesmans, Nicky M. Boontje, Dick H.W. Dekkers, Kees Schoonderwoerd, Hans C.H.Schuurbiers, Rini de Crom, Ger J.M. Stienen, Karin R. Sipido, Jos M.J. Lamers, Dirk J.Duncker. Circ Res. 2007;100:1079-1088. Early Exercise Training Normalizes MyofilamentFunction and Attenuates Left Ventricular Pump Dysfunction in Mice With a LargeMyocardial Infarction6-Yaras N, Tuncay E, Purali N, Sahinoglu B, Vassort G, Turan B. Sex-related effects ondiabetes-induced alterations in calcium release in the rat heart. Am J Physiol Heart CircPhysiol. 2007 Dec;293(6):H3584-92.7-Tuncay E, Seymen AA, Tanriverdi E, Yaras N, Tandogan B, Ulusu NN, Turan B. Genderrelated differential effects of Omega-3E treatment on diabetes-induced left ventriculardysfunction. Mol Cell Biochem. 2007 Oct;304(1-2):255-63.ŀBiyofizik Anabilim Dalı8-Yaras N, Bilginoglu A, Vassort G, Turan B. Restoration of diabetes-induced abnormal localCa2+ release in cardiomyocytes by angiotensin II receptor blockade. Am J Physiol Heart CircPhysiol. 2007 Feb;292(2):H912-20.

Neurotoxicology and Teratology 29 (2007) 211–218www.elsevier.com/locate/neuteraThe effect of sulfur dioxide inhalation on active avoidance learning,antioxidant status and lipid peroxidation during agingPiraye Yargicoglu a, ⁎ , Erhan Şahin a , Saadet Gümüşlü b , Aysel Ağar ca Akdeniz University, Faculty of Medicine, Department of Biophysics, Arapsuyu, 07070 Antalya, Turkeyb Akdeniz University, Faculty of Medicine, Department of Biochemistry, Turkeyc Akdeniz University, Faculty of Medicine, Department of Physiology, TurkeyReceived 28 June 2006; received in revised form 6 November 2006; accepted 6 November 2006Available online 14 November 2006AbstractThe effect of SO 2 was examined on active avoidance learning, thiobarbituric acid reactive substances (TBARS), and the activities of Cu, Znsuperoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in young (3 months), middle-age (12 months ), and old(24 months) Swiss male albino rats. Ten ppm SO 2 was administered to the animals of SO 2 groups in an exposure chamber for 1 h/day×7 days/week×6 weeks while control groups were exposed to filtered air in the same condition.The most prominent effect of aging on active performance was also observed in the older group. SO 2 exposure significantly decreased theactive avoidance learning in the young group, but it had no effect on this parameter in the middle-aged and the older group compared with theircorresponding control groups.SO 2 exposure resulted in increased levels of Cu, Zn-SOD activity while decreased level of GSH-Px activity in all experimental groupscompared with their corresponding control groups. CAT activities were unaltered. TBARS levels of all SO 2 exposed groups were significantlyincreased compared with their respective control groups.In conclusion, results from the present research showed that SO 2 exposure resulted in an increase in the lipid peroxidation and causedalterations in antioxidant enzyme activities. Additionally, SO 2 exposure impaired cognitive function only in the young rats during the acquisitionphase of active avoidance learning.© 2006 Elsevier Inc. All rights reserved.Keywords: Active avoidance; SO 2 ; Aging; Antioxidant system; Lipid peroxidation; Rat1. Introduction⁎ Corresponding author. Tel.: +90 242 2371625 (Home), +90 242 2276994(Office); fax: +90 242 2274495.E-mail address: pakkiraz@akdeniz.edu.tr (P. Yargicoglu).The biological process of aging is associated with certainbiochemical, morphological and electrophysiological alterationsin the central nervous system [16,22]. The nature of themechanisms underlying the aging process is presently not wellunderstood. However, free radical theory of aging, a currentlypopular hypothesis, has been proposed to be the important causeof aging [5,21,22,40,53,65,66]. Recently, increasing evidenceclaimed that free radicals have been involved in the pathogenesisof several abnormal conditions and diseases including neurodegenerativedisorders, atherosclerosis and diabetes [6,52,54,71].It is well known that free radicals play an important role for theformation of toxic lipid peroxidation products which producemarked damage to the structure and function of cell membranes.In normal conditions, there is a natural protective defense systemwhich performs a vital role for detoxification of free radicals andlipid peroxidation to prevent tissue damage and cell death. Theantioxidant defense is largely provided by several enzymes suchas superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) etc. [12,22,56].SO 2 is one of five major air pollutants worldwide. High levelsof sulfur compounds are continually emitted into the environmentfrom industry, the use of solid-fuel domestic heatingappliances and automobile exhaust. On the other hand, sulfurdioxide (SO 2 ) and its salts are most commonly used as apreservative in food products, like as biscuit, chocolate, jam,0892-0362/$ - see front matter © 2006 Elsevier Inc. All rights reserved.doi:10.1016/j.ntt.2006.11.002

cell biochemistry and functionCell Biochem Funct 2006; 24: 437–442.Published online 30 August 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1027/cbf.1251Effects of L-carnitine on neutrophil-mediatedischemia–reperfusion injury in rat stomachNarin Derin 1 *, Arzu Agac 1 , Zubeyde Bayram 2 , Mevlut Asar 2 and V. Nimet Izgut-Uysal 11 Akdeniz University, Medicine Faculty, Department of Physiology, Antalya, Turkey2 Akdeniz University, Medicine Faculty, Department of Histology, Antalya, TurkeyReactive oxygen metabolites play an important role in ischemia–reperfusion related gastric injury. Primary sources of reactiveoxygen metabolites seem to be the xanthine/xanthine oxidase system and neutrophils accumulating within the reperfusedtissue. Tissue myeloperoxidase activity is an important index of neutrophil accumulation. The purpose of the presentstudy was to clarify the effect of L-carnitine on the accumulation of neutrophils and neutrophil-induced gastric mucosaldamage in rats exposed to ischemia–reperfusion. Rats were randomly divided into three groups: sham-operated, ischemia–reperfusionand ischemia–reperfusion plus L-carnitine groups. Ischemia was induced by clamping the celiac arteryfor 30 min and then reperfusion was established for 60 min. Gastric injury was assessed by measuring myeloperoxidaseactivity in gastric tissue. The neutrophil accumulation and hemorrhagic lesions due to ischemia–reperfusion in gastricmucosa were ascertained in a histological study. L-Carnitine (100 mg kg 1 ) administrated intravenously 5 min before ischemiasignificantly reduced both the gastric injury and myeloperoxidase activity compared with the ischemia–reperfusiongroup. The results suggest that L-carnitine provides marked protection against ischemia–reperfusion-related gastric injurywhich could be due to its ability to reduce neutrophil accumulation in ischemic tissue. Copyright # 2005 John Wiley &Sons, Ltd.key words — ischemia–reperfusion; gastric injury; myeloperoxidase; neutrophils; L-carnitineINTRODUCTIONIschemia–reperfusion has great importance in thepathology of tissue damage. 1 There has been great interestin the role of oxygen radical species in ischemia–reperfusion injury in the heart, small intestine and othertissues. 1–3 Reactive oxygen metabolites (ROM) havebeen reported to play an important role in the pathogenesisof gastric erosions induced by ischemia–reperfusionin rats. 4–6 Primary sources of ROM seem to bethe xanthine/xanthine oxidase system and neutrophilsaccumulating within the reperfused tissue. ROM causeendothelial dysfunction during the early stages of reperfusion,leading to a cascade of events, including leukocyteadhesion and increased vascular permeabilitywhich contribute to organ damage. 7 Ischemia leads to* Correspondence to: Narin Derin, Akdeniz University, MedicalFaculty, Department of Physiology, 07070 Antalya, Turkey.Tel: 090.242.2274343-44144. Fax: 090.242.2274483.E-mail: narinderin@akdeniz.edu.trhypoxanthine accumulation due to ATP catabolismand conversion of the NAD þ -reducing enzyme,xanthine dehydrogenase to xanthine oxidase. 2,8 Withreperfusion, xanthine oxidase can utilize hypoxanthineand oxygen to form superoxide anion (O 2 )andhydrogenperoxide (H 2 O 2 ). Superoxide anion and hydrogenperoxide may then interact to produce the highly reactivehydroxyl radical. 2,9,10 Another potential source ofROM in tissues is neutrophils, which contain NADPHoxidase that reduces molecular oxygen to O 2 , resultingin its conversion to H 2 O 2 . 11,12 Activated neutrophilsproduce ROM and release a variety of cytotoxic proteins,e.g. proteases and lactoferrin and they also secretethe enzyme myeloperoxidase (MPO) that catalyses theformation of such potent cytotoxic oxidants as hypochlorousacid (HOCl) from H 2 O 2 and chloride ionsand N-chloramines. 13 MPO activity in tissues has beenused as an index of neutrophil infiltration. 14 It has beendemonstrated that there was a significant increase inMPO activity accompanying gastric mucosal damageby ischemia–reperfusion in rats and treatment withReceived 2 December 2004Revised 16 March 2005Copyright # 2005 John Wiley & Sons, Ltd. Accepted 7 April 2005

Physiol. Res. 57: 893-901, 2008The Effect of Lipoic Acid on Antioxidant Status and LipidPeroxidation in Rats Exposed to Chronic Restraint StressD. AKPINAR 1 , P. YARGIÇOĞLU 1 , N. DERIN 1 , Y. ALICIGÜZEL 2 , A. AĞAR 31 Akdeniz University, Faculty of Medicine, Department of Biophysics, 2 Department of Biochemistryand 3 Department of Physiology, Arapsuyu, Antalya, TurkeyReceived May 8, 2007Accepted September 26, 2007On-line November 30, 2007SummaryThis study was designed to investigate effect of alpha-lipoic acid(LA) on lipid peroxidation, nitric oxide production and antioxidantsystems in rats exposed to chronic restraint stress. Twenty fourmale Wistar rats, aged three months, were divided into fourgroups: control (C), the group treated with LA (L), the groupexposed to restraint stress (S) and the group exposed to stressand treated with LA (LS). Restraint stress was applied for 21 days(1 h/day) and LA (100 mg/kg/day) was injected intraperitonallyto the L and LS groups for the same period. Restraint stresssignificantly decreased brain copper/zinc superoxide dismutase(Cu,Zn-SOD) and brain and retina glutathione peroxidase (GSH-Px) and catalase (CAT) activities compared with the controlgroup. Thiobarbituric acid reactive substances (TBARS), nitriteand nitrate levels were significantly increased in the tissues ofthe S group compared with the C group. LA produced asignificant decrease in brain and retina TBARS, nitrite and nitratelevels of the L and LS groups compared to their correspondingcontrol groups. LA increased all enzyme activities in the tissues ofthe LS group compared to the S group. Our study indicated thatLA is an ideal antioxidant candidate for the prevention of stressinducedlipid peroxidation.Key wordsRestraint stress • Lipoic acid • Lipid peroxidation • AntioxidantenzymesCorresponding authorP. Yargıçoğlu, Department of Biophysics, Faculty of Medicine,Akdeniz University, Arapsuyu, 07070 Antalya, Turkey. Fax: 0 090-242-2274495. E-mail: pakkiraz@akdeniz.edu.trIntroductionStress is conceived as an aversive stimuluscapable of altering physiological homeostasis, and theability to cope with such stressful stimuli is a crucialdeterminant of health and disease (Masood et al. 2003).Intensive stress has detrimental effects on organism bycausing cellular and tissue injury. The mechanismsunderlying stress-induced tissue damage are not yet fullyunderstood. However, accumulating evidence has impliedthat the production of free radicals plays a critical role inthese processes (Liu et al. 1996, Liu and Mori 1999,Olivenza et al. 2000, Madrigal et al. 2002, Zaidi et al.2003). Previous studies have indicated that stressstimulated numerous pathways leading to increased levelsof free radicals (Liu et al. 1996, Liu and Mori 1999,Olivenza et al. 2000, Liu et al. 1994, Matsumoto et al.1999). One of the reasons for the stress-inducedenhancement of free radicals may be the elevation ofnitric oxide (NO) production (Matsumoto et al. 1999,McCann 1997). NO may interact with oxygen,superoxide anion, and thiol compounds, generatingreactive nitrogen species (NO x ), peroxynitrite (ONOO - )and S-nitrosothiols including S-nitrosoglutathione(GSNO). Lipid peroxidative effect of NO may bemediated through ONOO - which is a potent and longlivedoxidant (Chiueh and Rauhala 1999, Siu et al. 1999,Rubbo et al. 2000).Under normal conditions, there is also a naturaldefense system provided by several enzymes such assuperoxide dismutase (SOD), catalase (CAT) andglutathione peroxidase (GSH-Px) which performs a vitalrole for detoxification of free radicals. However, stressPHYSIOLOGICAL RESEARCH • ISSN 0862-8408 (print) • ISSN 1802-9973 (online)© 2008 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech RepublicFax +420 241 062 164, e-mail: physres@biomed.cas.cz, www.biomed.cas.cz/physiolres

BRAIN RESEARCH 1186 (2007) 87– 94available at www.sciencedirect.comwww.elsevier.com/locate/brainresResearch ReportEffect of aminoguanidine on visual evoked potentials (VEPs),antioxidant status and lipid peroxidation in rats exposed tochronic restraint stressDeniz Akpinar a , Piraye Yargicoglu a, ⁎, Narin Derin a , Mutay Aslan b , Aysel Agar ca Akdeniz University, Faculty of Medicine, Department of Biophysics, Arapsuyu, 07070 Antalya, Turkeyb Akdeniz University, Faculty of Medicine, Department of Biochemistry, Turkeyc Akdeniz University, Faculty of Medicine, Department of Physiology, TurkeyARTICLE INFOArticle history:Accepted 26 September 2007Available online 4 October 2007Keywords:Restraint stressVEPsAminoguanidineLipid peroxidationAntioxidant enzymeABSTRACTThe purpose of the study was to investigate the effect of aminoguanidine (AG) on visualevoked potentials (VEPs), thiobarbituric acid reactive substances (TBARS), the activities of Cu,Zn superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT),and nitrite/nitrate levels. Forty healthy male Wistar rats, aged 3 months, were divided intofour equal groups: Control (C), the group treated with aminoguanidine (A), the group exposedto restraint stress (S), the group exposed to restraint stress and treated with aminoguanidine(AS). Chronic restraint stress was applied for 21 days (1 h/day) and aminoguanidine (50 mg/kg/day) was injected intraperitonally to the A and AS groups for the same period.Aminoguanidine treatment significantly decreased retina and brain TBARS levels in ratsexposed to restraint stress compared to rats exposed to restraint stress alone.Aminoguanidine treatment produced a significant decrease in brain and retina nitrite andnitrate levels with respect to the control groups. Aminoguanidine increased all antioxidantenzyme activities in both brain and retina in rats exposed to restraint stress compared to ratsexposed to restraint stress alone. All VEP components were significantly decreased in AGtreated rats exposed to restraint stress compared to rats exposed to restraint stress alone.Our study clearly showed that AG has the potential to prevent changes caused by stress.© 2007 Elsevier B.V. All rights reserved.1. IntroductionStress is conceived as any physical, psychological and/orenvironmental stimulus which disturbs physiological homeostasisand may result in widespread changes in a variety ofbiological systems (Chrousos, 1998; Masood et al., 2003).Restraint stress is an easy and well-known method to inducechronic physical and emotional stress (Romanova et al., 1994).Accumulating evidence indicates that stress can stimulatenumerous pathways leading to an increased production ofoxidants (Liu et al., 1996; Liu and Mori, 1999; Matsumoto et al.,1999; Shaheen et al., 1993). Under normal conditions, there isalso a natural defense system provided by several enzymessuch as superoxide dismutase (SOD), catalase (CAT) andglutathione peroxidase (GSH-Px) which performs a vital rolefor detoxification of free radicals. However, stress has beenshown to cause depletion of the glutathione-based antioxidantdefense and a decrease in the level of vitamin C (Zaidiet al., 2003; Zaidi and Banu, 2004). The deleterious effects of animbalance between free radical production and the available⁎ Corresponding author. Fax: +90 242 2274495.E-mail address: pakkiraz@akdeniz.edu.tr (P. Yargicoglu).0006-8993/$ – see front matter © 2007 Elsevier B.V. All rights reserved.doi:10.1016/j.brainres.2007.09.066

Early Exercise Training Normalizes Myofilament Functionand Attenuates Left Ventricular Pump Dysfunction in MiceWith a Large Myocardial InfarctionMonique C. de Waard, Jolanda van der Velden, Virginie Bito, Semir Ozdemir, Liesbeth Biesmans,Nicky M. Boontje, Dick H.W. Dekkers, Kees Schoonderwoerd, Hans C.H. Schuurbiers, Rini de Crom,Ger J.M. Stienen, Karin R. Sipido, Jos M.J. Lamers, Dirk J. DunckerAbstract—The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI)is incompletely understood, but may involve blunting of abnormalities in Ca 2 -handling and myofilament function.Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on leftventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LVdimensions, but improved LV fractional shortening from 81 to 121%, and LVdP/dt P30 from 5295207 to5794207 mm Hg/s (both P0.05), and reduced pulmonary congestion. These global effects of exercise wereassociated with normalization of the MI-induced increase in myofilament Ca 2 -sensitivity (pCa 50 0.037). This effectof exercise was PKA-mediated and likely because of improved 1 -adrenergic signaling, as suggested by the increased 1 -adrenoceptor protein (48%) and cAMP levels (36%; all P0.05). Exercise prevented the MI-induced decreasedmaximum force generating capacity of skinned cardiomyocytes (F max increased from 14.30.7 to 18.30.8 kN/m 2P0.05), which was associated with enhanced shortening of unloaded intact cardiomyocytes (from 4.10.3 to7.00.6%; P0.05). Furthermore, exercise reduced diastolic Ca 2 -concentrations (by 30%, P0.05) despite theunchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect onCa 2 -transient amplitude, indicating that the improved LV and cardiomyocyte shortening were principally because ofimproved myofilament function. In conclusion, early exercise in mice after a large MI has no effect on LV remodeling,but attenuates global LV dysfunction. The latter can be explained by the exercise-induced improvement of myofilamentfunction. (Circ Res. 2007;100:1079-1088.)Key Words: cardiac function cardiomyocytes exercise training heart failureLeft ventricular (LV) remodeling after myocardial infarction(MI) is a compensatory mechanism that serves torestore LV pump function. Despite the apparent appropriatenessof LV remodeling to maintain cardiac pump functionearly after MI, remodeling is an independent risk factor forthe development of congestive heart failure. 1 The mechanismunderlying the progression from LV remodeling to overtheart failure remains incompletely understood, but recentevidence indicates that abnormalities in myofilament functionand Ca 2 -handling contribute to the LV dysfunction in theporcine heart, early after MI. 2In contrast to pathological LV remodeling after MI, LVremodeling produced by regular dynamic exercise is associatedwith a decreased risk for coronary artery disease andheart failure. 3 Exercise training is associated with an increasedmyocardial perfusion capacity and with normal oreven increased contractile function in the normal heart. 4,5There is also clinical evidence that exercise after MI has abeneficial effect on disease progression and survival. 6,7 Forexample, physical conditioning in patients with LV dysfunctionresults in an increased exercise capacity which has beenascribed, at least in part, to skeletal muscle adaptations. 8The effects of exercise on LV remodeling and function arestill incompletely understood, as several studies in humansreported contradictory effects of training on LV remodelingafter a MI. 9–18 Careful inspection of these studies suggeststhat after a small MI, exercise has no detrimental effect 11,13 oreven improves 15,17,18 LV geometry and function, independentof whether exercise was started late, ie, 1 year, 17,18 or early,ie, 2 months, 11,13,15 after MI. In contrast, in patients with aOriginal received April 13, 2006; resubmission received January 17, 2007; revised resubmission received February 15, 2007; accepted February 22, 2007.From Experimental Cardiology (M.C.d.W., D.J.D.), Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, TheNetherlands; Laboratory for Physiology (J.v.d.V., N.M.B., G.J.M.S.), VU University Medical Center, Amsterdam, The Netherlands; Laboratory ofExperimental Cardiology (V.B., S.O., L.B., K.R.S.), University of Leuven, Belgium; Department of Biochemistry (D.H.W.D., J.M.J.L.), 5 Cell Biologyand Genetics (K.S., R.d.C.), Vascular Surgery (R.d.C.) and Laboratory for Hemodynamics Thoraxcenter (H.C.H.S.), Erasmus MC, University MedicalCenter Rotterdam, The Netherlands.Correspondence to Dirk J. Duncker MD PhD, Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus MC, UniversityMedical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail d.duncker@erasmusmc.nl© 2007 American Heart Association, Inc.Circulation Research is available at http://circres.ahajournals.orgDOI: 10.1161/01.RES.0000262655.16373.37Downloaded from circres.ahajournals.org 1079 by on November 6, 2010

Am J Physiol Heart Circ Physiol 293: H3584–H3592, 2007.First published September 21, 2007; doi:10.1152/ajpheart.00619.2007.Sex-related effects on diabetes-induced alterations in calcium releasein the rat heartNazmi Yaras, 1 Erkan Tuncay, 1 Nuhan Purali, 2 Babur Sahinoglu, 2 Guy Vassort, 3 and Belma Turan 11Departments of Biophysics, Faculty of Medicine, Ankara University, and 2 Hacettepe University, Ankara, Turkey; and3Institut National de la Santé et de la Recherche Médicale U637, Physiopathologie Cardiovasculaire, CHU Arnaud deVilleneuve, Montpellier, FranceSubmitted 28 May 2007; accepted in final form 19 September 2007Yaras N, Tuncay E, Purali N, Sahinoglu B, Vassort G, Turan B.Sex-related effects on diabetes-induced alterations in calcium release inthe rat heart. Am J Physiol Heart Circ Physiol 293: H3584–H3592, 2007.First published September 21, 2007; doi:10.1152/ajpheart.00619.2007.—The present study was designed to determine whether the properties oflocal Ca 2 release and its related regulatory mechanisms mightprovide insight into the role of sex differences in heart functions ofcontrol and streptozotocin-induced diabetic adult rats. Left ventriculardeveloped pressure, the rates of pressure development and decay(dP/dt), basal intracellular Ca 2 level ([Ca 2 ] i), and spatiotemporalparameters of [Ca 2 ] i transients were found to be similar in male andfemale control rats. However, spatiotemporal parameters of Ca 2sparks in cardiomyocytes isolated from control females were significantlylarger and slower than those in control males. Diabetesreduced left ventricular developed pressure to a lower extent infemales than in males, and the diabetes-induced depressions in bothdP/dt and dP/dt were less in females than in males. Diabeteselicited a smaller reduction in the amplitude of [Ca 2 ] i transients infemales than in males, a smaller reduction in sarcoplasmic reticulum-Ca 2 load, and less increase in basal [Ca 2 ] i . Similarly, the elementaryCa 2 events and their control proteins were clearly different inboth sexes, and these differences were more marked in diabetes.Diabetes-induced depression of the Ca 2 spark amplitude was significantlyless in females than in matched males. Levels of cardiacryanodine receptors (RyR2) and FK506-binding protein 12.6 in controlfemales were significantly higher than those shown in controlmales. Diabetes induced less RyR2 phosphorylation and FK506-binding protein 12.6 unbinding in females. Moreover, total and freesulfhydryl groups were significantly less reduced, and PKC levelswere less increased, in diabetic females than in diabetic males. Thepresent data related to local Ca 2 release and its related proteinsdescribe some of the mechanisms that may underlie sex-relateddifferences accounting for females to have less frequent developmentof cardiac diseases.calcium sparks; calcium transient; ryanodine receptors; Type 1 diabetes;excitation-contraction couplingIT HAS LONG BEEN RECOGNIZED that incidence and prevalence ofcertain diseases vary with sex. Differences exist betweenwomen and men in the impact of risk factors, symptoms, andtherapeutic responses (1). Cardiovascular diseases are the leadingcause of death in adult women in developed countries (1,12). Results of animal studies have also revealed that there aresex differences in cardiac performance and responses topathological conditions (3, 5, 8, 11, 22). However, differencesin age, heart size, physiological status, and otherfactors confound comparisons, leading to variable and conflictingconclusions (20).Influences of sex on intrinsic contractile performance incontrol and in diabetes-induced myocardial mechanical andelectrical dysfunctions were studied by several authors (3, 4, 8,21). Under various conditions, increases in intracellular freeCa 2 concentration ([Ca 2 ] i ) were smaller in cardiomyocytesisolated from control female rats than in male rats (8), andSchwertz et al. (21) reported significant sex-dependent variationsin myocardial Ca 2 regulation. Furthermore, it has beendemonstrated that myocardium from female rats is more resistantto diabetes-induced dysfunction than myocardium frommale rats (3). In view of the important role played [Ca 2 ] i inthe regulation of heart function (16), several studies have beencarried out to investigate changes in [Ca 2 ] i in hearts subjectedto pathological conditions.A change in Ca 2 signaling is a hallmark of cardiomyopathy(16). A comparison of the properties of Ca 2 sparks that reportryanodine-sensitive Ca 2 -release channel receptor (RyR2) behaviorin a cluster and of the status of RyR2 in male and femalerat hearts may provide insight into the possible role of thesefactors in altered Ca 2 signaling, as well as in the mechanismsresponsible for sex differences in cardiac contractile function,particularly under pathological conditions.Evidence from animal models, as mentioned above, stronglysuggests that basic intrinsic mechanisms may play an importantrole in the development of sex-related cardiac dysfunction.Therefore, this study aimed to investigate two importantevents. First, to examine whether there are sex-related differencesin cardiomyocyte [Ca 2 ] i metabolism and local Ca 2release by RyR2 (Ca 2 sparks) in cardiomyocytes isolatedfrom control male and female rats. In addition, the presentstudy was designed to determine whether there are moresex-dependent differences in the alterations in [Ca 2 ] i homeostasisin cardiomyocytes isolated from diabetic animalsthan previously reported for male rats (32). Our resultsdemonstrated that the levels of FK506-binding protein 12.6(FKBP12.6) and RyR2 in control female rat hearts are significantlyhigher than levels in males, whereas diabetes-inducedRyR2 hyperphosphorylation is markedly less (50%) in thefemales than in corresponding males. In addition, a lowerincrease in basal [Ca 2 ] i level and a lower depression insarcoplasmic reticulum (SR)-Ca 2 load in diabetic female withrespect to diabetic male rats indicate that RyR2 and FKBP12.6levels in females may have an important role in the protectionDownloaded from ajpheart.physiology.org on November 6, 2010Address for reprint requests and other correspondence: B. Turan, Dept. ofBiophysics, School of Medicine, Ankara Univ., Ankara, Turkey (e-mail: belma.turan@medicine.ankara.edu.tr).The costs of publication of this article were defrayed in part by the paymentof page charges. The article must therefore be hereby marked “advertisement”in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.H35840363-6135/07 $8.00 Copyright © 2007 the American Physiological Society http://www.ajpheart.org

Mol Cell Biochem (2007) 304:255–263DOI 10.1007/s11010-007-9508-4Gender related differential effects of Omega-3E treatmenton diabetes-induced left ventricular dysfunctionErkan Tuncay Æ A. Aytac Seymen Æ Evrim Tanriverdi ÆNazmi Yaras Æ Berivan Tandogan Æ N. Nuray Ulusu ÆBelma TuranReceived: 27 February 2007 / Accepted: 3 May 2007 / Published online: 26 May 2007Ó Springer Science+Business Media B.V. 2007Abstract The present study was designed to determinewhether there are beneficial effects of intake of W-3E(containing 70% pure omega-3 and 2% natural vitamin E)in cardiac dysfunction of diabetic rats. We also examinedwhether there are gender-related differences in theresponses to the intake of W-3E on the heart dysfunction.Experiments were performed by using Langendorff-perfusedhearts from normal, diabetic (with 50 mg/kgstreptozotocin), and W-3E (50 mg/kg body weight/day)treated diabetic 3-month-old Wistar rats. W-3E treatmentof the diabetics caused small, but significant decrease(13% and 14% female versus male) in the blood glucoselevel. W-3E treatment of the diabetic female rats did notprevent diabetes-induced decrease in left ventriculardeveloped pressure (LVDP) and increase in left ventricularend-diastolic pressure (LVEDP) with respect to thecontrol female rats. On the other hand, the treatment ofdiabetic male rats caused significant recovery in depressedLVDP. Furthermore, such treatment of diabetic femaleand male rats caused significant recovery in depressedrates of changes of developed pressure. This effect wasmore significant in males. Besides, W-3E caused significantfurther lengthening in the diabetes-induced increasedtime to the peak of the developed pressure in females,while it normalized the lengthening in the relaxation ofthe developed pressure in diabetic males. In addition,E. Tuncay A. A. Seymen E. Tanriverdi N. Yaras B. Turan (&)Department of Biophysics, School of Medicine,Ankara University, Ankara, Turkeye-mail: belma.turan@medicine.ankara.edu.trB. Tandogan N. N. UlusuDepartment of Biochemistry, Faculty of Medicine,Hacettepe University, Ankara, TurkeyW-3E treatment caused significant restorations in thediabetes-induced altered activities of antioxidant enzymeswithout any significant gender discrepancy. Present datashow that there are gender related differences in diabeticheart dysfunction and the response to antioxidanttreatment.Keywords Diabetes Oxidant stress Antioxidants Heart function n-3 Polyunsaturated fatty acids Thioredoxin reductaseIntroductionThere is an increasing attention in investigating themechanisms and importance of gender in the etiology ofcardiac dysfunction. A number of investigations in humansand animals suggest that there is an intrinsic gender-associateddifference in cardiac function and a link betweengender and cardiovascular disease [1–3]. For instance,diabetes mellitus is associated with cardiovascular diseases,with women showing a greater increase of risk thanmen [4]. Although controversies regarding the specificgender-related alterations in Ca 2+ pathways that contributeto diabetes-induced cardiac dysfunction persist [5–7] therole of gender in diabetes-induced cardiac dysfunctionremains to be clarified.Oxidative stress plays a key role in the pathogenesis ofcardiac complications in diabetes [8, 9]. Although reactiveoxygen species (ROS) are continuously produced in mostcells under physiological conditions, however, as the productionof ROS becomes excessive, oxidative stress coulddevelop causing functional alterations. Therefore, oxidativedamage to tissues is common end points of chronicdiseases, such as diabetes [8, 9]. Hyperglycemia can123

Am J Physiol Heart Circ Physiol 292: H912–H920, 2007.First published September 29, 2006; doi:10.1152/ajpheart.00824.2006.Restoration of diabetes-induced abnormal local Ca 2 release incardiomyocytes by angiotensin II receptor blockadeNazmi Yaras, 1 Ayca Bilginoglu, 1 Guy Vassort, 2 and Belma Turan 11Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey; and2Institut National de la Santé et de la Recherche Médicale, Physiopathologie Cardiovasculaire,Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, FranceSubmitted 1 August 2006; accepted in final form 19 September 2006Yaras N, Bilginoglu A, Vassort G, Turan B. Restoration ofdiabetes-induced abnormal local Ca 2 release in cardiomyocytesby angiotensin II receptor blockade. Am J Physiol Heart CircPhysiol 292: H912–H920, 2007. First published September 29,2006; doi:10.1152/ajpheart.00824.2006.—Stimulation of local renin-angiotensinsystem and increased levels of oxidants characterizethe diabetic heart. Downregulation of ANG II type 1 receptors(AT 1) and enhancement in PKC activity in the heart point out therole of AT 1 blockers in diabetes. The purpose of this study was toevaluate a potential role of an AT 1 blocker, candesartan, onabnormal Ca 2 release mechanisms and its relationship with PKCin the cardiomyocytes from streptozotocin-induced diabetic rats.Cardiomyocytes were isolated enzymatically and then incubatedwith either candesartan or a nonspecific PKC inhibitor bisindolylmaleimideI (BIM) for 6–8 h at 37°C. Both candesartan and BIMapplied on diabetic cardiomyocytes significantly restored the alteredkinetic parameters of Ca 2 transients, as well as depressedCa 2 loading of sarcoplasmic reticulum, basal Ca 2 level, andspatiotemporal properties of the Ca 2 sparks. In addition, candesartanand BIM significantly antagonized the hyperphosphorylationof cardiac ryanodine receptor (RyR2) and restored the depletedprotein levels of both RyR2 and FK506 binding protein 12.6(FKBP12.6). Furthermore, candesartan and BIM also reduced theincreased PKC levels and oxidized protein thiol level in membranefraction of diabetic rat cardiomyocytes. Taken together, these datademonstrate that AT 1 receptor blockade protects cardiomyocytesfrom development of cellular alterations typically associated withCa 2 release mechanisms in diabetes mellitus. Prevention of thesealterations by candesartan may present a useful pharmacologicalstrategy for the treatment of diabetic cardiomyopathy.heart; candesartan; Type 1 diabetes; thiol oxidationCHRONIC DIABETES ALTERS the structure and function of thehuman heart, and individuals with diabetes mellitus usuallydevelop a specific cardiac dysfunction known as diabeticcardiomyopathy (37). Several mechanisms involved in thedevelopment of cardiomyopathy have been postulated, includingalterations in intracellular ion homeostasis and glucosemetabolism and enhanced oxidative stress. Althoughalteration of Ca 2 signaling via changes in critical processesthat regulate intracellular Ca 2 has become a hallmark ofthis type of cardiomyopathy, controversies, currently goingon, relate to specific alterations in Ca 2 signaling pathwayscontributing to the cardiac defects in diabetes (7, 20).Recently, we reported that these defects result partially fromaltered local Ca 2 signaling due to a dysfunction of cardiacPKA-mediated ryanodine receptor Ca 2 release channel(RyR2) (51).Several mechanisms have been proposed to explain howall of the pathologies involved in the progression of diabeticcardiomyopathy might result from hyperglycemia. IncreasedPKC isoform expression and increased polyol pathway fluxare two main hypotheses presented to describe how hyperglycemiamight cause all of the diabetic complications (6).Furthermore, it has been demonstrated that hyperglycemiaactivates the local renin-angiotensin system (RAS) andenhanced RAS activity in diabetes (33, 40). In addition, it isknown that ANG II has direct effects on cardiomyocytesthrough the ANG II type 1 (AT 1 ) receptor (9–11). Thus,stimulation of the AT 1 receptor generates oxygen-derivedfree radicals, which have detrimental effects on the cardiovascularsystem (28). The AT 1 receptor has been shown tobe coupled to several postreceptor signaling pathways, includingNADPH oxidase (33). Furthermore, there is a significantamount of evidence demonstrating that increasedPKC activity contributes to cardiovascular complicationsassociated with diabetes and that elevated PKC activity hasbeen found in diabetic hearts (25). PKC is known to phosphorylatea number of proteins that are directly involved incardiac excitation-contraction coupling (8, 24, 25). Therefore,upregulation of cardiac RAS and increased PKC activityin diabetic animals suggest the importance of thesepathways in the development of cardiac complications.Defects in cardiac intracellular Ca 2 have been proposed asone possible contributory factor to the depressed myocardialcontractile activity in diabetic cardiomyopathy (1, 32). Mostalterations were attributed to anomalous sarcoplasmic reticulum(SR) pump activity (15), SR-Ca 2 storage (5), and partlyto alterations in RyR2 properties (3, 27, 35, 49, 51). Recently,it has been shown that some cardioprotective agents correct thedefective FK506 binding protein 12.6 (FKBP12.6)-mediatedstabilization of RyR2, leading to an improvement in cardiacfunction of heart failure (29, 50). Recently, Gassanov et al. (16)described marked increases in the ANG II-induced depressedparameters of Ca 2 sparks with candesartan. We and othershave shown that chronic administration of ANG II receptorblockers could protect the heart from the development ofcellular alterations typically related with diabetes (18, 29, 30,33, 34). Although ANG II antagonism leads to an attenuationof the depressed SR-Ca 2 -ATPase (SERCA) and to an improvementin intracellular Ca 2 handling in heart failure (16,Downloaded from ajpheart.physiology.org on November 6, 2010Address for reprint requests and other correspondence: B. Turan, AnkaraUniv., School of Medicine, Dept. of Biophysics, Sihhiye, 06100, Ankara,Turkey (e-mail: belma.turan@medicine.ankara.edu.tr).The costs of publication of this article were defrayed in part by the paymentof page charges. The article must therefore be hereby marked “advertisement”in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.H9120363-6135/07 $8.00 Copyright © 2007 the American Physiological Society http://www.ajpheart.org

1-Uyuklu M, Meiselman HJ, Baskurt OK:Effect of decreased plasma cholesterol by atorvastatintreatment on erythrocyte mechanical properties.Clin Hemorheol Microcirc36: 25-33, 2007.2-Peto K, Nemeth N, Brath E,Takacs IE, Baskurt OK, Meiselman HJ, Furka, I, Miko I:The effects ofrenal ischemia-reperfusion on hemorheological factors: preventive role of allopurinol.Clin HemorheolMicrocirc37: 347-358, 20073-Baskurt OK, Meiselman HJ:Hemodynamic effects of red blood cell aggregation.Indian J Exp Biol45:18-24, 20074-Meiselman HJ, Neu B, Rampling MW, Baskurt OK:RBC Aggregation: Laboratory Data andModels.Indian J Exp Biol45: 9-17, 20075-Sentürk UK, Kuru O, Koçer G, Gündüz F: Biphasic pattern of exercise-induced proteinuria insedentary and trained men. Nephron Physiol 105(2):p22-32, 20076-İzgüt-Uysal VN, Bülbül M, Tan R, Derin N, Üstünel İ, Ağar A, Yargıçoğlu P: Effect of chronic stressand L-carnitine on rat stomach.J Physiol Sci57(3): 187-192, 2007.7-Bülbül M, Tan R, Gemici B, Hacıoğlu G, Ağar A, İzgüt-Uysal VN: Effect of docosahexaenoic acid onmacrophage functions of rats.Immunobiology 583-587, 2007.8-Tan R, Bülbül M, Öngüt G, Tosun O, İzgüt-Uysal VN: Prostaglandins, capsaicin-sensitive sensorynerves and neutrophil infiltration, but not nitric oxide, contribute to cold restraint stress-induced gastricadaptation in rats.Clin Exp Pharmacol Physiol Oct; 33 (10): 946-51, 2006.9-Kucukatay V, Ağar A, Gumuslu S, Yargiçoğlu P:Effect of sulfur dioxide on active and passiveavoidance in experimental diabetes mellitus: relation to oxidant stress and antioxidant enzymes.Int JNeurosci.117(8):1091-107, 2007ŀFizyoloji Anabilim Dalı - 200710-Hacioglu G, Kose O, Aslan M, Agar A:Beneficial effects of docosahexaenoic acid on activeavoidance performance in 1K-1C hypertensive rats.Neurobiol Learn Mem.117(7):971-83, 2007

The effects of renal ischemia-reperfusion on hemorheological factors: preventiverole of allopurinol.Hemorheol Microcirc. 2007;37(4):347-58.Peto K, Nemeth N, Brath E, Takacs IE, Baskurt OK, Meiselman HJ, Furka I, Miko I.Department of Operative Techniques and Surgical Research, Medical and Health Science Centre, Faculty of Medicine, University ofDebrecen, Debrecen, Nagyerdei krt. 98, Hungary. kpeto@jaguar.dote.huAbstractChanges hemorheological parameters were studied dogs following unilateral renal artery clamping (45-minute ischemia thenreperfusion), with and without preoperative administration of allopurinol. Sham-operated animals were also evaluated. Blood sampleswere collected preoperatively, at beginning and at 30, 60 and 120 minutes of reperfusion, then on the 1st, 3rd, 5th and 7th days.Filtration properties of erythrocytes (relative cell transit time, RCTT), whole blood and plasma viscosity (WBV, PV), fibrinogen level andhematology parameter were determined. RCTT significantly increased for both ischemic groups at 30 minutes of reperfusion, andremained elevated on the 1st and 2nd postoperative days; these changes were abolished by allopurinol pretreatment. WBV andhematocrit increased on the 1st day, and PV and fibrinogen level showed elevation on 1st-5th postoperative days. We thus concludeŀClinthat decreases of RBC deformability (i.e., higher RCTT) were characteristic and specific on early postoperative days after renalischemia-reperfusion and that these alterations were prevented by pre-ischemia administration of allopurinol.

J Exp Biol. 2007 Jan;45(1):9-17.RBC aggregation: laboratory data and models.Meiselman HJ, Neu B, Rampling MW, Baskurt OK.Department of Physiology and Biophysics, Keck School of Medicine, 1333 San Pablo Street, MMR 626 Los Angeles, CA 90033, USA.meiselma@usc.eduAbstractThe reversible aggregation of red blood cells (RBC) into linear and three-dimensional structures continues to be of basic science andclinical interest: RBC aggregation affects low shear blood viscosity and microvascular flow dynamics, and can be markedly enhanced inseveral clinical states. Until fairly recently, most research efforts were focused on relations between suspending medium composition(i.e., protein levels, polymer type and concentration) and aggregate formation. However, there is now an increasing amount ofexperimental evidence indicating that RBC cellular properties can markedly affect aggregation, with the term "RBC aggregability" coinedto describe the cell's intrinsic tendency to aggregate. Variations of aggregability can be large, with some changes of aggregationsubstantially greater than those resulting from pathologic states. The present review provides a brief overview of this topic, and includessuch areas as donor-to-donor variations, polymer-plasma correlations, ŀIndianeffects of RBC age, effects of enzymatic treatment, and currentdevelopments related to the mechanisms involved in RBC aggregation.PMID: 17249322 [PubMed - indexed for MEDLINE]

Intern. J. Neuroscience, 117:1091–1107, 2007Copyright C○ 2007 Informa HealthcareISSN: 0020-7454 / 1543-5245 onlineDOI: 10.1080/00207450600934531Int J Neurosci Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/10/10For personal use only.EFFECT OF SULFUR DIOXIDE ON ACTIVEAND PASSIVE AVOIDANCE IN EXPERIMENTALDIABETES MELLITUS: RELATION TO OXIDANTSTRESS AND ANTIOXIDANT ENZYMESVURAL KUCUKATAYDepartment of PhysiologyFaculty of MedicinePamukkale UniversityDenizli, TurkeyAYSEL AĞARDepartment of PhysiologyFaculty of MedicineAkdeniz UniversityAntalya, TurkeySAADET GUMUSLUDepartment of BiochemistryFaculty of MedicineAkdeniz UniversityAntalya, TurkeyPIRAYE YARGIÇOĞLUDepartment of BiophysicsFaculty of MedicineAkdeniz UniversityAntalya, TurkeyReceived 23 January 2006.Address correspondence to Aysel Agar, Department of Physiology, Faculty of Medicine,Akdeniz University Arapsuyu, Antalya, 07070 Turkey. E-mail: ayagar@akdeniz.edu.tr1091

ARTICLE IN PRESSImmunobiology 212 (2007) 583–587www.elsevier.de/imbioEffect of docosahexaenoic acid on macrophage functions of ratsMehmet Bulbul, Ruken Tan, Burcu Gemici, Gu¨lay Hacıoglu,Aysel Agar, V. Nimet Izgut-Uysal Department of Physiology, Faculty of Medicine, Akdeniz University, 07070 Antalya, TurkeyReceived 4 August 2006; received in revised form 14 February 2007; accepted 24 April 2007AbstractDocosahexaenoic acid (DHA) is an omega-3 fatty acid which has been demonstrated to exhibit anti-inflammatoryeffects. The objective of this study was to determine the effect of DHA on phagocytic and chemotactic activities ofperitoneal macrophages obtained from rats. DHA was dissolved in 1 ml of corn oil at dose of 36 mg/kg/day and givenvia oral gavage for 4 weeks. Control rats received 1 ml/day corn oil as vehicle. At the end of the treatment period,peritoneal macrophages were isolated and chemotactic and phagocytic activities were assayed. Chemotactic andphagocytic activities were reduced in rats fed with DHA. These results demonstrated the effect of DHA in modulatingimmune activities of rat peritoneal macrophages.r 2007 Elsevier GmbH. All rights reserved.Keywords: Docosahexaenoic acid; Macrophage; Phagocytosis; ChemotaxisIntroductionInflammatory cells such as neutrophils, monocytesand macrophages are the first line of host defenceagainst invading bacteria (Alvarez et al., 1996; Babior,2000; Djaldetti et al., 2002). These cells recognizebacteria in a specific way and destroy them afterphagocytosis by the subsequent production of superoxideradicals and other reactive oxygen species in therespiratory burst (Babior, 1992; Witko-Sarsat et al.,2000; Kew et al., 2003a). Phagocytosis is a cellularprocess that involves the formation of pseudopodiaaround a pathogenic factor or dead cell and itsendocytosis and destruction (Speert, 1992). It is probablethat this process is related to the fluidity of thephagocyte membrane. It is known that membrane Corresponding author. Tel.: +90 242 2274483.E-mail address: nimetu@akdeniz.edu.tr (V. Nimet Izgut-Uysal).fluidity is influenced by the fatty acid composition ofthe membrane phospholipids (Stubbs and Smith, 1984).In vitro studies have demonstrated that altering the fattyacid composition of macrophages by culturing themwith different fatty acids alters the rate or extent ofphagocytosis (Lokesh and Wrann, 1984; Calder, 2006).Fish oil, which is rich in o-3 polyunsaturated fattyacids, has been shown to suppress a variety of immunefunctions such as lymphocyte proliferation, cytotoxicT-lymphocyte activity, natural killer cell activity,production of cytokines and eicosanoid metabolism(Lokesh and Kinsella, 1987; Lokesh et al., 1988a, b;Lokesh et al., 1989; Calder, 2006). Most of these studiesinvolved the combined effects of the long chain o-3polyunsaturated fatty acids (PUFA), eicosapentaenoicacid (EPA, 20:5 o-3) and docosahexaenoic acid (DHA,22:6 o-3).There is a lack of studies on the effects of long chaino-3 PUFA docosahexaenoic acid on rat peritoneal0171-2985/$ - see front matter r 2007 Elsevier GmbH. All rights reserved.doi:10.1016/j.imbio.2007.04.004

Clinical and Experimental Pharmacology and Physiology (2006) 33, 946–951doi: 10.1111/j.1440-1681.2006.04469.xRBlackwell OriginalPGE TanArticle Publishing Asia2, et NO al. and CGRP in adaptation to stressPROSTAGLANDINS, CAPSAICIN-SENSITIVE SENSORY NERVESAND NEUTROPHIL INFILTRATION, BUT NOT NITRIC OXIDE,CONTRIBUTE TO COLD RESTRAINT STRESS-INDUCEDGASTRIC ADAPTATION IN RATSRuken Tan,* Mehmet Bülbül,* Gözde Öngüt, † Özgür Tosun, ‡ and V Nimet 3zgüt-Uysal*Departments of *Physiology, † Microbiology and Clinical Microbiology and ‡ Biostatistics, Faculty of Medicine,Akdeniz University, Antalya, TurkeySUMMARYIt is well known that stress produces acute haemorrhagic lesionsin the gastric mucosa of experimental animals. 6–8 Cold restraint1. The aim of the present study was to determine the role of stress is a commonly used and clinically relevant experimentalprostaglandins (PG), nitric oxide (NO) and capsaicin-sensitive model for acute gastric damage. 7,9 A sudden reduction of bloodsensory nerves in neutrophil infiltration in gastric adaptation to flow to the gastric mucosa and increased free radical formationcold restraint stress in rats.due to leucocyte activation play fundamental roles the formation of2. Wistar rats were exposed to single or repeated cold ulcers. 9,10 Repeated stress insults have been found to increaserestraint stress for 3.5 h every other day for up to 4 days. Prior the tolerance of the gastric mucosa to stress ulcerogenesis and toto repeated stress, rats were pretreated with N G -nitro-L-arginine attenuate the formation of acute gastric lesions. 11–13methyl ester (L-NAME; 10 mg/kg, s.c.), indomethacin (10 mg/kg, The release of vasoactive mediators is crucial for the gastrics.c.) or capsaicin (125 mg/kg, s.c.). The extent of gastric mucosal mucosa to resist the continual onslaught of agressive factors.lesions was evaluated histologically and myeloproxidase (MPO) Previous findings have suggested that there are interactions betweenactivity, PGE 2 , NO and calcitonin gene-related peptide (CGRP) vasodilator mediators, including prostaglandins (PG) that canlevels were measured in gastric tissue.regulate gastric mucosal microcirculation and integrity and the highly3. Cold restraint stress produced haemorrhagic lesions and labile humoral vasodilator substance nitric oxide (NO). 14,15 However,reduced PGE 2 and CGRP levels in the stomach, with an increase the sensory nerves play an important role in gastroprotection againstin MPO activity and NO levels. Repeated stress insults reduced harmful effects, probably via release of sensory neuropeptides, suchstress-induced gastric damage, NO production and MPO activity,with an increase in PGE 2 and CGRP levels compared with relaxation. 16as calcitonin gene-related peptide (CGRP), which mediates vascularrats exposed to single cold restraint stress. Adaptation to cold The present study was designed to determine whether gastricrestraint stress was prevented by indomethacin and capsaicin adaptation to repeated stress could be related to inhibition ofpretreatment, but not by L-NAME.stress-induced leucocyte infiltration to gastric mucosa and, if so,4. We conclude that the stomach has the ability to adapt to to elucidate the contribution of endogenous PG, NO and capsaicinsensitivesensory nerves to the gastroprotection against repeated coldrepeated exposure to cold restraint stress and that the adaptation,via inhibition of neutrophil infiltration, is mediated, at least restraint stress.in part, by endogenous PG and CGRP.Key words: calcitonin gene-related peptide, capsaicin, coldMETHODSrestraint stress, gastric adaptation, nitric oxide, prostaglandin E 2 .Male Wistar rats, weighing 180–220 g, were used in all experiments. Beforeeach experiment, rats were deprived of food and allowed free access to tapINTRODUCTIONwater for 18 h. All experimental procedures were approved by the AnimalCare and Use Committee of Akdeniz University.Gastric adaptation is a special feature of the stomach to resist thedamage caused by repeated exposure to strong mucosal irritants.Gastric adaptation was originally observed in rats exposed to nonsteroidalanti-inflammatory drugs, 1 but has also been observed inGeneral proceduresAnimals were divided into control (n = 12) and experimental (n = 52) groups.stomachs exposed to topical irritants including 70% ethanol, 2The experimental group was divided into five groups, consisting of one group0.2 mol/L NaOH, 3 hypertonic NaCl 4 and stress. 5 receiving a single exposure to cold restraint stress and four groups receivingmultiple exposures (n = 10 in each group; Table 1) to repeated cold restraintCorrespondence: Dr V Nimet Izgüt-Uysal, Faculty of Medicine, Departmentof Physiology, 07070 Antalya, Turkey. Email: nimetu@akdeniz.edu.tr individual loose-fitting tubular restraint cages made of wire mesh and were keptstress for 4 consecutive days. The single exposure group was put intoReceived 7 September 2005; revision 20 March 2006; accepted 26 March there for 3.5 h at 4∞C. 17 The multiple exposure groups were treated similarly2006.except that after the stress period animals were removed from the cages,© 2006 The Authorsplaced at room temperature and rechallenged with cold restraint stress forJournal compilation © 2006 Blackwell Publishing Asia Pty Ltd3.5 h the next morning. 18 Animals were killed after 4 consecutive days. The

men.Sentürk UK, Kuru O, Koçer G, Gündüz F.Akdeniz University, Faculty of Medicine, Department of Physiology, Antalya, Turkey. uksenturk@akdeniz.edu.trAbstractBACKGROUND/AIMS: Exercise-induced proteinuria is a common consequence of physical activity, although itsmechanism is not clear. Oxidant stress has been proposed as one of different factors involved in postexerciseproteinuria in rats. In this study we investigated whether reactive oxygen radicals generated during exercise playa role in exercise-induced proteinuria in sedentary and trained men.METHODS: The validity of oxidant stress following stepwise maximal exercise on proteinuria was investigated insedentary and trained subjects before and after antioxidant vitamin treatment (A, C, and E) for 2 months. Whileprotein carbonyl content in serum and thiobarbituric acid reactive substances (TBARS) in erythrocytes and urinewere used as oxidant stress markers, total protein, albumin, beta(2)-microglobulin in urine were assayed forproteinuria in five consecutive specimens after exercise. Urines were collected before exercise, then 30 min, 2, 8and 24 h postexercise.RESULTS: Increased urinary protein levels and mixed type proteinuria were determined after 30 min of exercisein sedentary and trained subjects. Proteinuria was normalized at 2 and 8 h specimens. However, glomerular typeproteinuria was identified at 24 h specimen in both groups. Oxidant stress markers were significantly elevated insedentary and trained subjects. Antioxidant treatment prevented the increase in oxidant stress markers, urinaryprotein levels and the occurrence of glomerular type proteinuria after exhaustive exercise at 24 h in both groups.CONCLUSIONS: These findings suggest that the exercise-induced oxidant stress may contribute to exerciseinducedproteinuria in sedentary and trained menŀBiphasic pattern of exercise-induced proteinuria in sedentary and trained

erythrocyte mechanical properties.Uyuklu M, Meiselman HJ, Baskurt OK.Department of Physiology, Akdeniz University Faculty of Medicine, Antalya 07070, Turkey.Comment in:• Clin Hemorheol Microcirc. 2008;40(4):325-6.Abstract3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are the most commonly usedcholesterol-lowering drugs, with recent clinical trends usually aimed at achieving the lowest possible plasmacholesterol levels. Although the effects of increased plasma cholesterol have been previously reported, it is notobvious how very low plasma cholesterol levels would affect membrane composition and the deformability of redblood cells (RBC). The present study investigated the effects of hypocholesterolemia achieved by atorvastatintherapy on RBC membrane and mechanical properties in guinea pigs fed a normal diet. Two groups of animalswere used (atorvastatin-treated, n=12; control n=12), and atorvastatin given orally in isotonic phosphate-bufferedsaline (PBS) at a dose of 20 mg/kg/day for a 21-day period. Our results indicate that the atorvastatin-treatedgroup had significantly lower plasma total cholesterol (17.42+/-1.70 mg/dl), low-density lipoprotein cholesterol(5.25+/-2.22 mg/dl) and triglycerides (42.60+/-3.78 mg/dl) than the control group (34.08+/-1.72, 21.17+/-1.41 and60.64+/-2.43 mg/dl, respectively). In addition, membrane cholesterol content was lower (p

Baskurt OK, Meiselman HJ.Department of Physiology, Akdeniz University Faculty of Medicine, Antalya, Turkey.AbstractThe influence of red blood cell (RBC) aggregation on blood flow in vivo has been under debate since early 1900's,yet a full understanding has still has not been reached. Enhanced RBC aggregation is well known to increaseblood viscosity measured in rotational viscometers. However, it has been demonstrated that RBC aggregationmay decrease flow resistance in cylindrical tubes, due to the formation of a cell-poor zone near the tube wallwhich results from the enhanced central accumulation of RBC. There is also extensive discussion regarding theeffects of RBC aggregation on in vivo blood flow resistance. Several groups have reported increasedmicrocirculatory flow resistance with enhanced RBC aggregation in experiments that utilized intravital microscopy.Alternatively, whole organ studies revealed that flow resistance may be significantly decreased if RBCaggregation is enhanced. Recently, new techniques have been developed to achieve well-controlled, gradedalterations in RBC aggregation without influencing suspending phase properties. Studies using this techniquerevealed that the effects of RBC aggregation are determined by the degree of aggregation changes, and that thisrelationship can be explained by different hemodynamic mechanisms.ŀHemodynamic effects of red blood cell aggregation.

tuberculosis and gamma interferon response.Sallakci N, Coskun M, Berber Z, Gürkan F, Kocamaz H, Uysal G, Bhuju S, Yavuzer U, Singh M, Yeğin O.Akdeniz University Health Sciences Research Centre, Akdeniz University, Faculty of Medicine, Antalya, Turkey.AbstractInterferon-gamma is the most important cytokine in resistance to mycobacterial diseases and common variants ofinterferon-gamma gene could be related to tuberculosis susceptibility. We tested the hypothesis that theinterferon-gamma+874T-A polymorphism is associated with tuberculosis disease, and affects the interferongammaresponse. We determined by pyrosequencing the distribution of the interferon-gamma+874T-Apolymorphism in a Turkish population of 319 patients with pulmonary tuberculosis, 42 children with severe formsof tuberculosis and 115 healthy donors. We also analysed whether any correlation exists between thispolymorphism and interferon-gamma response to Mycobacterium tuberculosis antigens by ELISPOT in 58pulmonary tuberculosis cases, and the results were analysed according to the genotypes. We found that theminor allele (T) frequency was significantly lower in patients with pulmonary tuberculosis when compared tocontrols (P=0.024, OR=0.7), a similarly significant decrease in the frequency of TT genotype was observed inpatients with pulmonary tuberculosis, compared to the control group (P=0.02, OR=0.49). IFN-gamma responsesto PPD antigen in TT genotype was found to be significantly higher than the AA group (P>0.001). Non-parametriccorrelation analysis of ELISPOT data showed significant reverse correlation in PPD, CFP10 and ESAT6 valuesand IFN-gamma +874 genotypes. These results show that the IFN-gamma +874T-A polymorphism is related tothe IFN-gamma response and the magnitude of the response decreases during transition from TT- to TA and toAA genotypes. Our data suggest that similar to various Caucasian populations, in a Turkish population the IFNgamma+874T-A polymorphism is also associated with tuberculosis disease and affects the magnitude of the IFNgammaresponse.ŀInterferon-gamma gene+874T-A polymorphism is associated with

1-Yıldız M, Celik-Ozenci C, Akan S, Akan I, Satı L, Demir R, Savas B, Ozben T, Samur M, OzdoganM, Artac M, Bozcuk H. Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrugresistance protein-1 dependent way: an in vitro study2-Sati L, Seval Y, Yasemin Demir A, Kosanke G, Kohnen G, Demir R:Cellular diversity of humanplacental stem villi: an ultrastructural and immunohistochemical study.Acta Histochem.109(6):468-79,20073-Seval Y, Korgun ET, Demir R.:Hofbauer cells mediate vascularization in early human placentaPlacenta. 2007 Aug-Sep;28(8-9):841-54-Korgun ET, Caylı S, Asar M, Demir R.:Distribution of laminin, vimentin and desmin in the rat uterusJ.Mol. Hist.38: 253-260, 20075-Akkoyunlu G, Erdoğru T, Seval Y, Ustünel I, Köksal T, Usta MF, Baykara M, DemirR:Immunolocalization of glial cell-derived neurotrophic factor (GDNF) and its receptor GFR-alpha1 invaricocele-induced rat testis.Acta Histochem2007;109(2):130-7. 2007 Jan 226-Demir R, Seval Y, Huppertz B.:Vasculogenesis and angiogenesis in the early human placentaActaHistochem. 2007;109(4):257-657-Naftolin F, Garcia-Segura LM, Horvath TL, Zsarnovszky A, Demir N, Fadiel A, Leranth C,Vondracek-Klepper S, Lewis C, Chang A, Parducz A:Estrogen-Induced Hypothalamic SynapticPlasticity and Pituitary Sensitization in the Control of the Estrogen-Induced GonadotrophinSurge.Reprod Sci.14(2):101-116, 20078-Akkoyunlu G, Ustünel I, Demir R:The distribution of transglutaminase in the rat oocytes andembryos.Theriogenology68(6):834-841, 2007.ŀHistoloji ve Embriyoloji Anabilim Dalı - 20079-Demir-Weusten AY, Seval Y, Kaufmann P, Demir R, Yucel G, Huppertz B:Matrixmetalloproteinases-2, -3 and -9 in human term placenta.Acta Histochem. 2007;109(5):403-12.10-Huszar G, Jakab A, Sakkas D, Ozenci CC, Cayli S, Delpiano E, Ozkavukcu S.Fertility testing andICSI sperm selection by hyaluronic acid binding: clinical and genetic aspects.Reprod BiomedOnline.14(5):650-63, 2007

Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrugresistance protein-1 dependent way: an in vitro study.Biol Int. 2006 Mar;30(3):278-82. Epub 2006 Feb 2.Yildiz M, Celik-Ozenci C, Akan S, Akan I, Sati L, Demir R, Savas B, Ozben T, Samur M, Ozdogan M, Artac M, Bozcuk H.Pamukkale University Medical Faculty, Department of Medical Oncology, Denizli, Turkey.AbstractWe have explored the action of zoledronic acid, which has an apoptotic effect and is used as an agent for treating skeletal metastasesand osteoporosis, in the presence of vinblastine, and whether this effect is associated with MRP-1 (multidrug resistance protein-1)expression. HEK (human embryonic kidney) 293 cells were transfected to form the multidrug resistant cell line designated 293MRP(MRP-1 expressing HEK293 cells). Both lines were treated with varying concentrations of vinblastine and zoledronic acid. Apoptosis wasdetermined by the TUNEL (deoxyuridine triphosphate nick end-labeling) method. The type of treatment, MRP-1 expression status, andthe type of treatment with respect to MRP-1 expression status significantly affected (P < 0.001) the degree of apoptosis. The largestincrease in cytotoxicity was noted in HEK293 cells, when 100 micromol zoledronic acid was added to 4 microg/ml vinblastine (anincrement of 80.3%, P < 0.001). This preliminary work shows that zoledronic acid acts synergistically with vinblastine to induce apoptosisŀCellin an MRP-1 dependent way.PMID: 16458542 [PubMed - indexed for MEDLINE]

ARTICLE IN PRESSActa histochemica 109 (2007) 468—479www.elsevier.de/acthisCellular diversity of human placental stem villi: Anultrastructural and immunohistochemical studyLeyla Sati a , Yasemin Seval a , Ayse Yasemin Demir b , Georg Kosanke c ,Gaby Kohnen d , Ramazan Demir a,a Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, 07070 Campus, Antalya, Turkeyb Department of Clinical Chemistry and Hematology, University Medical Center, Utrecht, The Netherlandsc Department of Anatomy II, Klinikum, RWTH, Aachen, Germanyd Department of Obstetrics and Gynecology, Glasgow Royal Infirmary, UKReceived 7 February 2007; received in revised form 25 April 2007; accepted 27 April 2007This study is dedicated to the health of our beloved friend Prof. Dr. Peter KaufmannKEYWORDSHuman placenta;Stem villi;Myofibroblast;Immunohistochemistry;UltrastructureSummaryThe aim of the study was to investigate the distribution and differentiation of celltypes in the stroma of human placental stem villi (SV). A total of 14 human termplacental tissues were studied. Double immunolabeling was performed for desminvimentin,desmin-a-smooth actin and vimentin-a-smooth actin. Cytokeratin 7,proliferating cell nuclear antigen immunolabeling was also performed. Parallel tissuesamples were examined by transmission electron microscopy. HSCORE was performedfor the semi-quantitative analysis of distribution of cells in the stroma of SV. Vimentinlabeledcells were mostly distributed in the subtrophoblastic area. Desmin-vimentindouble immunolabeling was mainly localized in the triangular area and to a lesserdegree in the perivascular area and vessel walls (p ¼ o0.001). However, desmin-asmooth actin labeling was observed predominantly in the vessel wall and perivasculararea. Vimentin-a smooth actin immunoreactivity was significantly stronger in thetriangular and perivascular areas compared to the vessel walls (p ¼ 0.003).Ultrastructurally, cells in the stroma of SV were mesenchyme cells, reticulum cells,fibroblasts, myofibroblasts, smooth muscle cells, and Hofbauer cells, filamented andvacuolated cells. The differentiation of myofibroblasts in the triangular andperivascular areas may play a role in maturation of SV and villous contractility,modulation of the intervillous space and this may have effects on maternofetalplacental circulation.& 2007 Elsevier GmbH. All rights reserved. Corresponding author. Tel./fax: +90 242 227 44 86.E-mail address: rdemir@akdeniz.edu.tr (R. Demir).0065-1281/$ - see front matter & 2007 Elsevier GmbH. All rights reserved.doi:10.1016/j.acthis.2007.04.006

Placenta 28 (2007) 841e845Hofbauer Cells in Early Human Placenta: Possible Implicationsin Vasculogenesis and AngiogenesisY. Seval, E.T. Korgun, R. Demir*Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, 07070 Antalya, TurkeyAccepted 16 January 2007AbstractThe stroma of the placental villi contain numerous macrophages, so-called Hofbauer cells which are of mesenchymal origin and are thoughtto function in many processes. Although there are many studies concerning placental vasculogenesis and angiogenesis, there has been a lack ofevidence on the possible roles of Hofbauer cells in these processes. In this study we hypothesized that Hofbauer cell locations and numbersmight be correlated with the vascular structures within the placental villi core and therefore may be implicated to play roles in placental vasculogenesisand angiogenesis.Placental tissues were obtained from normal first-trimester pregnancies. Tissues were prepared for light microscopic investigations. Doubleimmunohistochemistry staining with CD31/PECAM1 and CD68 was applied to placental tissues. In placental villous core, majority of theHofbauer cells were found to be either in close contact with angiogenic cell cords and primitive vascular tubes or located in between them.Moreover, the number of Hofbauer cells and vasculogenic structures were found to be significantly correlated. The findings of this study suggestfor the first time that Hofbauer cells might be involved in the processes of vasculogenesis and angiogenesis in the placenta.Ó 2007 Elsevier Ltd. All rights reserved.Keywords: Vasculogenesis; Angiogenesis; Hofbauer cells; Human placenta1. IntroductionThe creation, maturation and maintenance of the vascular networkis necessary for successful hemachorial placentation, aswell as normal embryonic development and growth in humans.Two processes vasculogenesis and angiogenesis, whichboth are of critical importance for the fetus and the placenta,are involved in the development of the fetal and placental vasculatures.Whereas vasculogenesis results from the de novoformation of vessels derived from pluripotent precursor cells,angiogenesis, is the creation of new vessels from pre-existingvessels [1e3].Vascularization of the placenta takes place around day 21post conception (p.c.) [4]. At this time, endothelial progenitor* Corresponding author. Tel./fax: þ90 242 227 4486.E-mail address: rdemir@akdeniz.edu.tr (R. Demir).cells appear as cords right beneath the trophoblastic layer;which are called angiogenic cell cords (ACC). Later on, thesecells proliferate, differentiate and migrate to form main vascularpatterns and form primitive vascular tubes (VT), whichdemonstrate a primitive lumen formation [5,6].The stroma of the placental villi contains numerous macrophages,so-called Hofbauer cells. Hofbauer cells are ofmesenchymal origin and are thought to function in manyprocesses.During the early phase of vascularization, the appearance ofHofbauer cells in the villous core, suggests a paracrine role forthese cells during the first stages of placental vasculogenesis[7e10]. Indeed it has been shown that Hofbauer cells expressangiogenic growth factors such as VEGF [11,12]. Furthermoreit has been shown that human villous macrophages enhancehuman trophoblast growth and differentiation in vitro andexpress higher levels of VEGF mRNA than that of peritonealmacrophages [13].0143-4004/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.doi:10.1016/j.placenta.2007.01.010

J Mol Hist (2007) 38:253–260DOI 10.1007/s10735-007-9095-4ORIGINAL PAPERDistribution of laminin, vimentin and desmin in the rat uterusduring initial stages of implantationE. T. Korgun Æ S. Cayli Æ M. Asar Æ R. DemirReceived: 12 March 2007 / Accepted: 26 April 2007 / Published online: 22 May 2007Ó Springer Science+Business Media B.V. 2007Abstract The aim of this study was to investigate theimmunohistochemical distribution of laminin, vimentinand desmin during the implantation period in the rat sinceECM remodelling and the expression of intermediate filaments(Ifs) is essential for successful decidualization andimplantation. On day 4 of pregnancy, laminin was found ina few endometrial stromal cells (ESC), the basementmembrane of the numerous endometrial blood vessels, inendometrial glands and as well as in the uterine epithelium.The localization of vimentin on day 4 of pregnancy waswidespread in the ESC. However, desmin immunoreactivitywas low in ESC on this day of pregnancy. On day 6of pregnancy, laminin and vimentin were localized in thedecidual area underlying luminal epithelium and aroundthe implanting embryo. Additionally, desmin was found tobe present densely in decidual cells of the anti-mesometrialregion where implantation takes place. Finally, on day 8 ofpregnancy, laminin was present in decidual and parietalendodermal cells, whereas vimentin was immunolocalizedin primary and secondary decidual regions in the endometrium.In contrast, desmin was detected in some parts ofthe secondary decidual zone. In conclusion, these proteinscould have crucial roles in decidualization and implantation.Keywords Laminin Vimentin Desmin Decidualization ImplantationE. T. Korgun (&) S. Cayli M. Asar R. DemirDepartment of Histology and Embryology, Akdeniz UniversityMedical Faculty, Campus, Antalya 07070, Turkeye-mail: korgun@akdeniz.edu.trIntroductionIn the rat, at the time of blastocyst implantation, theendometrial cells undergo profound modifications and thestromal cells differentiate into decidual cells. Differencesin the morphology and arrangement of decidual cells allowus to recognize several regions in the endometrium ofimplantation sites, because decidual cell transformation isgradual (Abrahamsohn and Zorn 1993). The process ofimplantation in the rat is denoted by the development ofprimary and secondary decidual zones (Enders andSchlafke 1967). Five different zones can be distinguishedwith decidualization in the pseudo pregnant rat endometrium:I-Basal zone, II-the capsule, III-the antimesometrialdeciduoma, IV-mesometrial deciduoma; and V-glycogenicarea (O’Shea et al. 1983). Decidualization proceeds fromthe sub epithelial stroma towards the deep stroma situatednext to the myometrium and creates regions composed ofcells in different stages of differentiation (Oliveira et al.1998). The mature decidual cells are large polygonalshaped and multinucleated with accumulated organellesthat are associated with the synthesis of macro-molecules,Intermediate filaments (Ifs) and eventually lipid dropletsand glycogen (Abrahamsohn and Zorn 1993). Many functionshave been attributed to decidual cells including, actingas a physical barrier to trophoblast invasion, animmunological barrier to prevent rejection of the conceptusand also supplying nutrients, producing hormones andother specific products (Finn 1971).All eukaryotic cells express intermediate filament proteinsassociated with cytoskeletal functions. Ifs constitute adistinct fibrous network within the cytoplasm of highereukaryotic cells. Approximately 40 different intermediatefilament proteins are known, and can be divided into fivedistinct subclasses (Skalli et al. 1992). Two distinctive123

ARTICLE IN PRESSActa histochemica 109 (2007) 257—265REVIEWVasculogenesis and angiogenesis in the earlyhuman placentaRamazan Demir a, , Yasemin Seval a , Berthold Huppertz bwww.elsevier.de/acthisa Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkeyb Department of Histology and Cell Biology, Faculty of Medicine, Karl Franz University, Graz, AustriaReceived 17 January 2007; received in revised form 15 February 2007; accepted 23 February 2007KEYWORDSAngiogenesis;Early pregnancy;Haemangiogeniccells;Human placenta;Vasculogenesis;ReviewSummaryVasculogenesis and angiogenesis are two consecutive processes during blood vesseldevelopment in the human placenta. While vasculogenesis, which is the formation offirst blood vessels, is achieved by differentiation of pluripotent mesenchymal cellsinto haemangiogenic stem cells. The subsequent step, angiogenesis, is characterizedby development of new vessels from already existing vessels. In this review, we aimto give an overview of vasculogenesis and angiogenesis during the first trimester ofhuman placental development. Recent studies have shown that at the very earlystages of placental development, cytotrophoblasts trigger vasculogenesis andangiogenesis, whereas as pregnancy progresses Hofbauer and stromal cells takeover the task of triggering blood vessel development. Important growth factors inthis scenario are the vascular endothelial growth factor (VEGF) family and theirreceptors, as well as Tie-1 and Tie-2. This review depicts the molecular andmorphological steps of vasculogenesis and angiogenesis, which can give furtherinsights into human placental development and maturation disorders.& 2007 Elsevier GmbH. All rights reserved.ContentsIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258The family of VEGF-related proteins and their receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258VEGF and its receptors during placental vasculogenesis and angiogenesis . . . . . . . . . . . . . . . . . . . . . . 258The differentiation of mesenchymal stem cells into endothelial cell progenitors. . . . . . . . . . . . . . 260Sequential steps during placental vasculogenesis and angiogenesis . . . . . . . . . . . . . . . . . . . . . . 261 Corresponding author. Tel./fax: +90 242 227 44 86.E-mail address: rdemir@akdeniz.edu.tr (R. Demir).0065-1281/$ - see front matter & 2007 Elsevier GmbH. All rights reserved.doi:10.1016/j.acthis.2007.02.008

Estrogen-Induced Hypothalamic Synaptic Plasticity and PituitarySensitization in the Control of the Estrogen-Induced Gonadotrophin SurgeFrederick Naftolin, MD, DPhil, Luis Miguel Garcia-Segura, PhD,Tamas L. Horvath, DVM, PhD, Attila Zsarnovszky, DVM, PhD,Necdet Demir, PhD, Ahmed Fadiel, PhD, Csaba Leranth, MD, PhD,Susanne Vondracek-Klepper, PhD, Carole Lewis, PhD,Aimee Chang, MD, and Arpad Parducz, PhDProper gonadal function requires coordinated (feedback) interactions between the gonads, adenohypophysis, andbrain: the gonads elaborate sex steroids (progestins, androgens, and estrogens) and proteins (inhibin-activin family)during gamete development. In both sexes, the brain-pituitary gonadotrophin-regulating interaction is coordinatedby estradiol through its opposing actions on pituitary gonadotrophs (sensitization of the response togonadotrophin-releasing hormone [GnRH]) versus hypothalamic neurons (inhibition of GnRH secretion).This dynamic tension between the gonadotrophs and the GnRH cells in the brain regulates the circulatinggonadotrophins and is termed reciprocal/negative feedback. In females, reciprocal/negative feedback dominates∼90% of the ovarian cycle. In a spectacular exception, the dynamic tension is broken during the surgeof circulating estrogen that marks follicle and oocyte(s) maturation. The cause is an estradiol-induced disinhibitionof the GnRH neurons that releases GnRH secretion to the highly sensitized pituitary gonadotrophs thatin turn release the gonadotrophin surge (the estrogen-induced gonadotrophin surge [EIGS], also known as positivefeedback). Studies during the past 4 decades have shown this disinhibition to result from estrogen-inducedsynaptic plasticity (EISP), including a reversible ∼50% loss in arcuate nucleus synapses. The disinhibitedGnRH secretion occurs during maximal gonadotroph sensitization and results in the EIGS. Specificimmunoneutralization of estradiol blocks the EISP and EIGS. The EISP is accompanied by increases ininsulinlike growth factor 1, polysialylated neural cell adhesion molecule, and ezrin, 3 proteins that the authorsbelieve are the links between estrogen-induced astroglial extension and the EISP that releases GnRH secretionat the moment of maximal sensitization of the pituitary gonadotrophs. The result is the paradoxical surge ofgonadotrophins at the peak of ovarian estrogen secretion and the triggering of ovulation. This enhanced understandingof the mechanics of gonadotrophin control clarifies elements of the involved feedback loops and opensthe way to a better understanding of the neurobiology of reproduction.KEY WORDS: Periventricular area, luteinizing hormone, follicle-stimulatinghormone, gonadotrophin feedback, hypothalamus, estradiol,synaptic plasticity, pituitary, GnRH.A SYNOPSIS OF PHYSIOLOGICAL ENDOCRINOLOGY SETSTHE STAGE FOR UNDERSTANDING THE ACTUAL ROLEOF SYNAPTOLYTIC EFFECTS OF ESTROGEN IN THEPREOVULATORY GONADOTROPHIN SURGEFor 6 decades, the physiological basis of the preovulatorygonadotrophin surge escaped understanding.The history of the 2 main theories of the seat ofReproductive Sciences Vol. 14 No. 2 February 2007 101-116DOI. 10.1177/1933719107301059© 2007 by the Society for Gynecologic Investigationthe pituitary versus hypothalamus has been describedpreviously. 1 The discovery that electrolytic removal ofgonadotrophin-releasing hormone (GnRH) cells pluspharmacological replacement of GnRH and estrogencould result in a gonadotrophin surge 2 was interpreted asevidence that the hypothalamus played a passive role inthe surge. However, newer physiological evidence hasshown that both the pituitary and hypothalamus playindispensable, active roles. This review covers the newevidence and places it in the context of previouslyobserved data.Downloaded from rsx.sagepub.com at Akdeniz Universitesi on October 11, 2010101

Theriogenology 68 (2007) 834–841www.theriojournal.comThe distribution of transglutaminase in the rat oocytesand embryosG. Akkoyunlu *, İ.Üstünel, R. DemirDepartment of Histology and Embryology, Faculty of Medicine, Akdeniz University, 07070 Antalya, TurkeyReceived 15 March 2007; received in revised form 11 June 2007; accepted 12 June 2007AbstractTransglutaminases (TGs) are calcium-dependent enzymes that catalyze the transamidation of glutamine residues of a proteinsubstrate to form intermolecular isopeptide bonds. The zona pellucida (ZP) is an extracellular, glycoprotein matrix that surrounds theoocytes of all Eutherian mammals. We aimed to identify the immunoreactivity of tissue transglutaminase (tTG) and ultrastructuralchanges occuring in rat oocytes before and after fertilization. Female rats were stimulated to superovulate, then mated with males.Oocytes and embryos were collected and examined by immunohistochemistry and electron microscopy. Before fertilization, tTG waspresent only in the oolemma and the cortical cytoplasm. After fertilization, tTG reactivity increased in the ZP of the early zygote and thepreimplantation embryos, but decreased in the cytoplasm and perivitelline space (PVS). After fertilization, the PVS ultrastructurebecame asymmetrical and large around the polar bodies with many cortical granule contents. In conclusion, tTG immunoreactivity wasfound to be spatially and temporarily heterogeneous in the rat oocytes and embryos, especially in the ZP.# 2007 Elsevier Inc. All rights reserved.Keywords: Transglutaminase; Fertilization; Zona pellucida; Cortical granules; Rat1. IntroductionThe mammalian oocyte is surrounded by anextracellular glycocalyx, or zona pellucida (ZP). Themain functions of ZP in fertilization have beengenerally accepted as the mediation of the relativespecies specificity of sperm binding and penetration,blocking of polyspermy, induction of the spermacrosome reaction, and protection of the growingembryo from fertilization to implantation [1]. The ZP ofmost mammalian species, including human, is composedof three glycoproteins, ZP1, ZP2, and ZP3 [2].According to Wassarman and co-author [3–5], mouse* Corresponding author. Tel.: +90 242 2496879;fax: +90 242 2274486.E-mail address: akkoyunlu@akdeniz.edu.tr (G. Akkoyunlu).ZP2 (mZP2) and ZP3 (mZP3) are present as heterodimers,making up filaments possessing structuralrepeats, which are interconnected by mouse ZP1(mZP1), a dimer of identical polypeptides held togetherby intermolecular disulfide bonds.A crucial step in fertilization is the attachment of thespermatozoon to the ZP, a process that requiresrecognition and interaction between complementarymolecules present on the spermatozoon and on the ZP.Fusion of the spermatozoon with the egg plasmamembrane induces exocytosis of cortical granules (CG)which is referred as CG reaction [6]. The content of theCG alters the ZP glycoproteins, thus establishing ablock to polyspermy [7]. The nature of the alterationswhich the ZP undergoes during fertilization is onlypartially understood. ZP2 undergoes limited proteolysisand is converted to ZP2f [8], while ZP3, which acts asthe primary sperm receptor, loses its ability to bind0093-691X/$ – see front matter # 2007 Elsevier Inc. All rights reserved.doi:10.1016/j.theriogenology.2007.06.015

ARTICLE IN PRESSActa histochemica 109 (2007) 403—412www.elsevier.de/acthisMatrix metalloproteinases-2, -3 and -9 in humanterm placentaAys-e Yasemin Demir-Weusten a , Yasemin Seval b , Peter Kaufmann c ,Ramazan Demir b, , Gultekin Yucel d , Berthold Huppertz ea Department of Clinical Biochemistry, Medical Faculty of Utrecht University, Utrecht, The Netherlandsb Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkeyc Department of Anatomy II, University Hospital RWTH, Aachen, Germanyd Department of Biochemistry, Faculty of Medicine, Akdeniz Universtiy, Antalya, Turkeye Institute of Cell Biology, Histology and Embryology, Medical University of Graz, AustriaReceived 24 January 2007; received in revised form 3 April 2007; accepted 4 April 2007KEYWORDSHuman termplacenta;Matrix metalloproteinases;Immunohistochemistry;ZymographySummaryMatrix metalloproteinases (MMPs) are zinc-dependent enzymes that degrade thecomponents of the extracellular matrix (ECM) and are known to be the main mediatorsof human placentation and parturition. Although there are many studies on the rolesand distribution of MMPs in human term placenta, so far none of the studies hasinvestigated the distribution of MMP-2, -3 and -9 in different cells of various placentalsites. In this study, we aimed to determine the distribution and enzymatic activities ofMMP-2, -3 and -9 with regard to different regions of term human placenta, such asamnion, basal plate, chorionic plate, decidua, chorion laeve, Nitabuch’s stria,umbilical cord and placental villi. Eighteen normal human term placentas wereobtained after vaginal deliveries. Immunohistochemistry and zymography wereperformed for MMP-2, -3 and -9 on placental tissue sections and protein extracts,respectively. Nearly all tissues showed immunoreactivity for MMPs. The strongestenzymatic activity for MMP-2 was seen in areas where invasive trophoblast cellsinvaded maternal tissues. MMP-9 had the highest enzymatic activity at the contactregion of fetal and maternal parts, suggesting the importance of MMP-9 in separationof the placenta from the uterine wall during labor. MMP-3 had a similar localization toMMP-9, suggesting that besides gelatinases like MMP-2 and -9, MMP-3 (stromelysin-1)may also have important roles during labor. This study describes the site-specificdistribution and activities of MMPs and therefore might help in elucidating themolecular mechanisms in pathologies such as premature rupture of membranes.& 2007 Elsevier GmbH. All rights reserved. Corresponding author. Tel./fax: +90 242 2274486.E-mail address: rdemir@akdeniz.edu.tr (R. Demir).0065-1281/$ - see front matter & 2007 Elsevier GmbH. All rights reserved.doi:10.1016/j.acthis.2007.04.001

found 1 article by title matching your search:Reprod Biomed Online. 2007 May;14(5):650-63.Fertility testing and ICSI sperm selection by hyaluronic acid binding: clinical andgenetic aspects.Huszar G, Jakab A, Sakkas D, Ozenci CC, Cayli S, Delpiano E, Ozkavukcu S.The Sperm Physiology Laboratory, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School ofMedicine. 333 Cedar Street, New Haven, CT 06510, USA. gabor.huszar@yale.eduAbstractThe testis-expressed chaperone protein, HspA2 (previously creatine kinase M isoform) was established as a measure of human spermcellular maturity, function and fertility. The presence of HspA2 in the synaptonemal complex is likely to link low HspA2 expression andincreased frequency of chromosomal aneuploidies in arrested-maturity spermatozoa. A relationship also exists between HspA2expression in elongating spermatids and the associated spermatogenetic events, including plasma membrane remodelling and theŀWeformation of zona pellucida and hyaluronic acid (HA) binding sites. The HA receptor of mature spermatozoa, when coupled with HAcoatedslides and/or Petri dishes, allows visual observation of sperm-HA binding, providing a basis for sperm maturity testing, a majorimprovement in semen evaluation, and selection of mature spermatozoa for intracytoplasmic sperm injection (ICSI). Thus, in HAselectedspermatozoa the frequency of chromosomal disomy and diploidy is reduced 4- to 6-fold compared with semen sperm fractions.This reduction is similar to the increase in numerical chromosomal aberrations in ICSI children. Combined studies of sperm shape andchromosome probes demonstrated that sperm morphology does not aid selection of haploid spermatozoa. The HA-mediated spermselection is a novel and efficient technique that may alleviate potential problems related to ICSI fertilization with visually selectedspermatozoa.PMID: 17509211 [PubMed - indexed for MEDLINE]

1-Aslan M, Yucel I, Ciftcioglu A, Savas B, Akar Y, Yucel G, Sanlioglu S: Corneal Protein Nitration inExperimental Uveitis. Exp Biol Med232:1308-1313, 2007.2-Aslan M and Freeman BA: Redox-dependent impairment of vascular function in sickle cell disease.Free Radical Biol Med. 43: 1469-1483, 20073-Aslan M, Canatan D:Nitric Oxide Consumption by Circulating Neutrophils in Sickle Cell DiseaseTheFEBS Journal274: 214, 2007.4-Sahin M, Sagdiç G, Elmas O, Akpinar D, Derin N, Aslan M, Agar A, Alicigüzel Y, Yargiçoglu P:Effectof Chronic Restraint Stress and Alpha-Lipoic Acid on Lipid Peroxidation and Antioxidant EnzymeActivities in Rat Peripheral Organs. PHARMACOLOGICAL RESEARCH 54 (3): 247-252 SEP2006.Pharmacol Res54:247-252, 2006.5-Aslan M, Yücel I, Akar Y, Yücel G, Ciftcioglu MA, Sanlioglu S: Nitrotyrosine formation and apoptosisin rat models of ocular injury. Free Radical Research. 40:147-153, 20066-Aslan M, Canatan D:Neutrophil Nitric Oxide in Sickle Cell Disease Free Radical Biol Med41: S47-S47 Suppl. 1 20067- Şahin E., Gümüşlü S.: Stress-dependent induction of protein oxidation, lipid peroxidation and antioxidantsin peripheral tissues of rats: comparison of three stress models (immobilization, cold andimmobilization-cold).Clin Exp Pharmacol P 34: 425-431, 2007.8-Şahin E., Gümüşlü S.: Immobilization stres in rat tissues: Alterations in protein oxidation, lipidperoxidation and antioxidant defense systemComp Biochem Phys C144(4): 342-347, 2007.9-Toptas B, Baykal A, Yesilipek A, Isbir M, Kupesiz A, Yalcin O, Baskurt OK:L-carnitine deficiencyand red blood cell mechanical impairment in beta-thalassemia major.Clin HemorheolMicrocirc.35:349-57, 2006.10-OZBEN T. Oxidative stress and apoptosis: impact on cancer therapy. Journal of PharmaceuticalSciences 96(9):2181-2196, 2007.11-OZBEN T. Concurrent use of antioxidants in cancer therapy: An update. Expert Review of ClinicalImmunology 2(6):931-939, 2006.12-OZBEN T. Mechanisms and strategies to overcome multiple drug resistance in cancer. FEBSLetters 580: 2903-2909, 2006.ŀTıbbi Biyokimya Anabilim Dalı

Corneal Protein Nitration inExperimental UveitisMUTAY ASLAN,* ,1 İCLAL YUCEL, AKIF CIFTCIOGLU,à BERNA SAVAS,§ YUSUF AKAR,GULTEKIN YUCEL,* AND SALIH SANLIOGLUjjDepartments of *Biochemistry, Ophthalmology, and àPathology, Akdeniz University School ofMedicine, Antalya 07070, Turkey; §Department of Pathology,Ankara University Medical School, Ankara 06100, Turkey; and jjHuman Gene Therapy Unit, AkdenizUnversity School of Medicine, Antalya 07070, TurkeyIncreased expression of inducible nitric oxide synthase (NOS-2)in inflammatory diseases like uveitis suggests that it contributesto the observed pathological state. The aim of this study was toevaluate corneal expression of NOS-2 and corneal proteinnitration in a rat model of uveitis. A single injection of intravitreallipopolysaccharide was used to induce uveitis. Corneal proteinswere separated by sodium dodecyl sulfate-polyacrylamide gelelectrophoresis and visualized by Coomassie blue staining.Expression of NOS-2 and nitrotyrosine (NO 2 Tyr) formation weredetermined via immunohistochemistry and Western blot analysis.Total nitrate/nitrite levels in the vitreous were measured byspectral analysis via the Griess reagent. Immunohistochemicalanalysis revealed increased corneal NOS-2 and NO 2 Tyr immunoreactivityin rats with uveitis compared with controls. NOS-2and NO 2 Tyr immunoreactivity was observed in and around basalcells in the corneal epithelium. Western blot analysis of corneallysates showed multiple nitrated protein bands in uveitic rats.Spectrophotometric measurement of total nitrate/nitrite levels inthe vitreous affirmed significantly increased levels of nitricoxide generation in uveitis (126 6 2.63 lM/mg protein) comparedwith controls (65 6 6.57 lM/mg protein). The presented datasuggests that extensive formation of protein nitration andreactive nitrogen species in the cornea contributes to tissuedestruction in uveitis. Hence, selective inhibition of NOS-2 mayprevent long-term complications and lead to an improvement inthe management of uveitis. Exp Biol Med 232:1308–1313, 2007Key words: uveitis; cornea; nitration; inducible nitric oxide synthaseThis study was supported by a grant from Akdeniz University Research Foundation,Turkey (2003.01.0103.007).1 To whom correspondence should be addressed at Akdeniz University MedicalSchool, Department of Biochemistry, 07070 Antalya, Turkey. E-mail: mutayaslan@akdeniz.edu.trReceived February 16, 2007.Accepted July 9, 2007.DOI: 10.3181/0702-RM-341535-3702/07/23210-1308$15.00Copyright Ó 2007 by the Society for Experimental Biology and MedicineIntroductionIntraocular inflammation, most often called uveitis, is amajor cause of severe visual impairment (1). Uveitis canlead to destruction of intraocular tissues by causing edemaand high intraocular pressure (2). Multiple sclerosis,idiopathic optic neuritis, autoimmune corneal endotheliopathy,sarcoidosis, thyroid diseases, and inflammatory boweldiseases have all been associated with uveitis (3) Endotoxininduceduveitis (EIU) has been widely used as anexperimental model of uveitis (4, 5). Leukocyte adhesion,retinal cell injury, and apoptosis have all been reported inthe eye after injection of a single dose of sublethal bacteriallipopolysaccharide (LPS) (6).Nitric oxide (NO) is synthesized by a family of NOsynthase (NOS) enzymes. Physiological amounts of NOsynthesized by endothelial NOS (eNOS or NOS-3) andneuronal NOS (nNOS or NOS-1) participate in neurotransmissionand vascular signaling, whereas acceleratedNO production by inducible NOS (iNOS or NOS-2) resultsin cytotoxicity (7). Previous studies in uveitic rats havereported the presence of NOS-2 immunoreactivity in vitrealinflammatory cells, the iris, the ciliary body, and innerretinal layers (5, 8). Similarly, intravitreal injection of LPSinto rabbits resulted in NOS-2 expression in cornealfibroblasts and corneal epithelium (9). Accelerated NOproduction by NOS-2 results in cytotoxicity via directreactions of NO and the formation of secondary speciescapable of oxidation and nitration reactions. Indeed,reduction of corneal edema is seen in uveitic rats afterapplication of N G -nitro-L-arginine methyl ester, an NOSinhibitor (10).The oxidation and nitration of lipids, amino acids, andproteins will alter biomolecular structure and function and atthe same time reveal the pathogenic actions of reactivespecies (11). Corneal protein nitration has been observed inhuman corneal diseases such as keratoconus, Fuchsendothelial dystrophy, and in stored human cornealepithelium (12). Photoablated rabbit corneas have also1308

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptNIH Public AccessAuthor ManuscriptFree Radic Biol Med. Author manuscript; available in PMC 2007 December 14.Published in final edited form as:Free Radic Biol Med. 2007 December 1; 43(11): 1469–1483.Redox-Dependent Impairment of Vascular Function in Sickle CellDiseaseMutay Aslan 1 and Bruce A. Freeman 21 Department of Biochemistry, Akdeniz University School of Medicine, 07070 Antalya, Turkey2 Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania15261, USAAbstractThe vascular pathophysiology of sickle cell disease (SCD) is influenced by many factors includingadhesiveness of red and white blood cells to endothelium, increased coagulation and homeostaticperturbation. The vascular endothelium is central to disease pathogenesis because it displays adhesionmolecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall andregulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances.Occurrence of intermittent vascular occlusion in SCD leads to reperfusion injury associated withgranulocyte accumulation and enhanced production of reactive oxygen species. The participation ofnitric oxide (NO) in oxidative reactions causes a reduction in NO bioavailability and contributes tovascular dysfunction in SCD. Therapeutic strategies designed to counteract endothelial,inflammatory and oxidative abnormalities may reduce the frequency of hospitalization, bloodtransfusion, the incidence of pain and the occurrence of acute chest syndrome and pulmonaryhypertension in patients with SCD.KeywordsSickle cell disease; endothelium; nitric oxideIntroductionThe presence of abnormal hemoglobin (Hb) in red cells of sickle cell disease (SCD) patientswas demonstrated by Pauling and colleagues in 1949 (1). By 1957, Vernon Ingram identifiedthe biochemical difference between normal and sickle hemoglobin (HbS) (2). Sicklehemoglobin results from a glutamic acid to valine substitution at the sixth amino acid positionof the β globin chain, with minimal structural differences between hemoglobin A (HbA) andHbS when the Hb molecule is liganded with oxygen. When HbS is deoxygenated however, themutant valine residue on the deoxy-HbS molecule participates in an intermolecular contact byfitting into a hydrophobic pocket on a nearby Hb molecule present in both HbA and HbS (3).This interaction leads to reversible polymer formation, with subsequent depolymerizationoccurring without delay upon oxygenation. Irreversible polymerization only occurs in aminority of severely dehydrated and oxidatively damaged cells (4).Corresponding Author: Mutay Aslan, MD, Ph.D., Akdeniz University School of Medicine, Department of Biochemistry, 07070, Antalya,Turkey. Tel: 90-242-2496891, Fax: 90-242-2274482, Email: mutayaslan@akdeniz.edu.tr.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customerswe are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resultingproof before it is published in its final citable form. Please note that during the production process errors may be discovered which couldaffect the content, and all legal disclaimers that apply to the journal pertain.

Source: FEBS JOURNAL Volume: 274 Pages: 214-214 Supplement: Suppl. 1 Published: JUL 2007Times Cited: 0 References: 0 Citation MapConference Information: 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS)Vienna, AUSTRIA, JUL 07-12, 2007Federat European Biochem SocDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Sch Med, TR-07058 Antalya, Turkey2. Suleyman Demirel Univ, Sch Med, Isparta, ItalyPublisher: BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLANDSubject Category: Biochemistry & Molecular BiologyIDS Number: 264JOISSN: 1742-464XŀAuthor(s): Aslan M (Aslan, M.) 1 , Canatan D (Canatan, D.) 2

Pharmacological Research 54 (2006) 247–252Effect of chronic restraint stress and alpha-lipoic acid on lipid peroxidationand antioxidant enzyme activities in rat peripheral organsMehmet Şahin a , Gamze Sağdıç a ,Oğuz Elmas a , Deniz Akpınar b , Narin Derin b ,Mutay Aslan a , Aysel Agar c , Yakup Alıcıgüzel a,∗ , Piraye Yargıçoğlu ba Department of Biochemistry, Akdeniz University Medical School, 07070 Antalya, Turkeyb Department of Biophysics, Akdeniz University Medical School, 07070 Antalya, Turkeyc Department of Physiology, Akdeniz University Medical School, 07070 Antalya, TurkeyAccepted 12 May 2006AbstractObjectives: The aim of this study was to evaluate the effect of chronic restraint stress and alpha-lipoic acid (LA) administration on lipid peroxidationand antioxidant enzyme activities in rat peripheral organs.Methods: Forty male wistar rats, aged 3 months were randomized to one of the following groups: control, restraint stress, LA treated and restraintstress + LA treated. Chronic restraint stress was applied for 21 days (1 h/day) and LA (100 mg/kg/day) was administered intraperitoneally for thesame period.Results: Restraint stress had no statistically significant effect on lipid peroxidation, copper/zinc superoxide dismutase (Cu/Zn SOD), catalase(CAT) and glutathione peroxidase (GPx) activity in rat liver and heart, when compared to the control group. Lipid peroxidation, determined bymeasuring malondialdehyde (MDA) levels, was found to be increased in the kidney of restraint stress treated rats, compared to controls. Restraintstress-induced lipid peroxidation in the kidney was significantly decreased via LA treatment. Administration of LA also enhanced GPx anddecreased Cu/Zn SOD activity in rat kidney, liver and heart, compared to the control group.Conclusions: The presented data shows that LA is a protective agent against restraint stress—the inducer of lipid peroxidation in the kidney. Thesefindings also suggest that LA-induced changes in antioxidant enzyme activities in rat peripheral organs may contribute to their versatile effectsobserved in vivo.© 2006 Published by Elsevier Ltd.Keywords: Restraint stress; Lipoic acid; Lipid peroxidation; Antioxidant1. IntroductionStress, both psychological and physical is common in everydaylife and is known to induce circulatory diseases and ulcerationof the digestive tract [1]. The term “restraint stress” involvesa specific procedure that limits movement. Early restraint stressprocedures were validated as “stressful” through studies ofadrenocortical response [2], ulcer induction and stress-inducedanalgesia [3]. Two major types of experimental restraint stressmodels have been confirmed. The first model includes confinement,where the animal’s movement is limited by restrictedspace. The second model utilizes immobilization, where thelimbs and body of the animal are held immobile by tape or∗ Corresponding author. Tel.: +90 242 227 43 54; fax: +90 242 227 44 82.E-mail address: yakup@akdeniz.edu.tr (Y. Alıcıgüzel).plaster [4]. Previous studies have shown that restraint stressincreases plasma lipid peroxidation and decreases plasma protectionagainst oxidation [5]. Furthermore, administration ofreduced glutathione has been shown to be protective againststress-induced ulceration and oxidative damage [5].In mammals, LA can be supplied by both de novo synthesisor by dietary intake. Alpha-LA is synthesized de novofrom octanoic acid by the addition of two sulfur atoms to theoctanoyl group. This reaction takes place in the mitochondriaand is catalyzed by LA synthase [6]. Endogenously synthesizedLA is used for lipoylation of LA-requiring enzyme complexes.Lipoyltransferase catalyzes the transfer of the lipoylgroup to a lysine residue of specific enzyme proteins [7].The lipoyllysine arm is then responsible for shuttling intermediatesand reducing equivalents between the active sites ofenzyme complexes that serve a critical role in energy metabolism[8].1043-6618/$ – see front matter © 2006 Published by Elsevier Ltd.doi:10.1016/j.phrs.2006.05.007

Free Radical Research, February 2006; 40(2): 147–153Nitrotyrosine formation and apoptosis in rat models of ocular injuryMUTAY ASLAN 1 ,İCLAL YÜCEL 2 , YUSUF AKAR 2 ,GÜLTEKIN YÜCEL 1 , M. AKIFÇIFTÇIOĞLU 3 , & SALIH SANLIOGLU 4Free Radic Res Downloaded from informahealthcare.com by Akdeniz Universitesi on 11/06/10For personal use only.Department of Biochemistry, Akdeniz University Medical School, Antalya 07070, Turkey, Department of Ophthalmology,Akdeniz University Medical School, Antalya 07070, Turkey, Department of Pathology, Akdeniz University Medical School,Antalya 07070, Turkey, and Department of Human Gene Therapy Unit, Akdeniz University Medical School, Antalya 07070,TurkeyAccepted by Dr T. Grune(Received 25 July 2005; in revised form 30 September 2005)AbstractThis study was performed to examine inducible nitric oxide synthase (NOS-2) expression, nitrotyrosine formation and apoptosisin rats with elevated intraocular pressure (IOP) and/or ocular inflammation. Ocular inflammation was induced via injection ofintra-vitreal lipopolysaccharide (LPS) while IOP was elevated by episcleral vessel cauterization. Animals were randomized to oneof the following conditions: elevated IOP, LPS, elevated IOP þ LPS, and control. Immunohistochemical staining and westernblot analysis of retinal lysates revealed NOS-2 and nitrotyrosine immunoreactivity in all disease groups. NOS-2 expression andprotein nitration was significantly greater in rats with elevated IOP þ LPS compared to elevated IOP, LPS, and control groups.Nitrite levels in the retina affirmed significantly increased levels of nitric oxide generation in LPS-treated rats with elevated IOP(346 ^ 23.8 mM) vs LPS-treated, elevated IOP and control groups (195.6 ^ 12.6, 130 ^ 2.5 and 76.6 ^ 15.6 mM,respectively). Retinal TUNEL staining showed apoptosis in all diseased groups. Percent of apoptotic cells was significantlygreater in the elevated IOP þ LPS group compared to LPS-treated or elevated IOP groups. Presented data illustrates that bothelevated IOP and ocular inflammation augment NOS-2 expression, retinal protein nitration and apoptosis in rats.Keywords: Nitrotyrosine, inducible nitric oxide synthase, apoptosis, intraocular pressure, lipopolysaccharideAbbreviations: GCL, ganglion cell layer; INL, inner nuclear layer; IOP, intraocular pressure; IPL, inner plexiform layer;LPS, lipopolysaccharide; NO, nitric oxide; NO 2 2 , nitrite; NO 2 Tyr, nitrotyrosine; NO 3 2 , nitrate; NOS-2, inducible nitric oxidesynthase; ONL, outer nuclear layer; OPL, outer plexiform layer; PBS, phosphate buffered saline; PMN, polymorphonuclear;VCL, photoreceptor cell layerIntroductionGlaucoma is a degenerative eye disease and is theleading cause of blindness in the United States andother industrialized countries [1]. Experimentalstudies of induced pressure elevation in nonhumanprimates results in typical glaucomatous optic nervedamage [2,3]. Intraocular inflammation, most oftentermed as uveitis, is also a major cause of severevisual impairment [4]. Recent studies have highlightedthe role of nitric oxide (NO) in uveitis andglaucoma by reporting the presence of NOS-2 inthe iris-ciliary body [5], retina [6] and in theglaucomatous optic nerve head of experimental ratmodels [7].Nitric oxide is an important mediator of homeostaticprocesses in the eye, such as regulation ofaqueous humor dynamics, retinal neurotransmissionCorrespondence: M. Aslan, Department of Biochemistry, Akdeniz University Medical School, 07070 Antalya, Turkey. Tel: 90 242 227434344126. Fax: 90 242 2274482. E-mail: mutayaslan@akdeniz.edu.trISSN 1071-5762 print/ISSN 1029-2470 online q 2006 Taylor & FrancisDOI: 10.1080/10715760500456219

Experimental Hematology 2008;36:1535–1544Modulation of redox pathways in neutrophils from sickle cell disease patientsMutay Aslan a and Duran Canatan ba Akdeniz University School of Medicine. Department of Biochemistry, Antalya, Turkey; b SuleymanDemirel University School of Medicine. Department of Pediatric Hematology, Isparta, Turkey(Received 5 March 2008; revised 19 May 2008; accepted 9 July 2008)Objective. Interaction of nitric oxide (NO) with enzymatic sources of reactive species exertsmodulatory actions on inflammatory signaling mechanisms.Materials and Methods. NADPH oxidase, total peroxidase, cyclooxygenase (COX) activity, andNO consumption were measured in neutrophils isolated from sickle cell disease (SCD) patientsand healthy controls. Glutathione (GSH) levels and expression of inducible NO synthase(NOS-2) were also analyzed to assess intracellular redox state and NO production,respectively.Results. Functional assay of NADPH oxidase was performed by measuring superoxiderelease, which was similar in control and SCD, both at basal conditions and in response toN-formyl-methionyl-leucyl-phenylalanine stimulation. Peroxidase activity, assessed spectrophotometrically,was not significantly different in SCD neutrophils compared to controls.Total COX activity, measured via an assay kit, was significantly increased in SCD neutrophils.The increase in total COX activity observed in SCD was due to enhanced activity of COX-2,differentiated by using the isoform-specific inhibitors DuP-697 and SC-560. Western blot analysisof COX-2 protein in SCD and control neutrophils confirmed increased enzyme activity inthe diseased group. Western blot analysis of neutrophil lysates from SCD patients showed significantlyincreased NOS-2 protein content, compared to controls. Spectrophotometric measurementof GSH and nitrate/nitrite levels showed a decrease in GSH and an increase innitrate/nitrite content in SCD neutrophils. Electrochemical measurement of NO consumptionboth under basal conditions and after N-formyl-methionyl-leucyl-phenylalanine stimulationrevealed a significant decrease in SCD neutrophils compared to controls.Conclusions. Depletion of GSH in SCD neutrophils may impact on rates of NO consumption andreflects increased oxidative stress associated with neutrophil activation. Ó 2008 ISEH - Societyfor Hematology and Stem Cells. Published by Elsevier Inc.Participation of leukocytes in the pathophysiology of sicklecell disease (SCD) is supported by large epidemiologicstudies that show high baseline leukocyte counts as a riskfactor for disease severity [1], acute chest syndrome [2],and silent cerebral infarcts [3]. Notably, the administrationof granulocyte colony-stimulating factor causes fatal andsevere sickle cell crisis in SCD patients [4,5].Recurrent vaso-occlusive crisis and tissue ischemia inSCD induce tissue macrophages to secrete proinflammatorymediators, including interleukin-1 (IL-1), IL-6, IL-8, andtumor necrosis factor-a (TNF-a) [6], which are all elevatedin the plasma of SCD patients [7–10]. Once secreted, IL-1Offprint requests to: Mutay Aslan, M.D., Ph.D., Department of Biochemistry,Akdeniz University Medical School, 07070 Antalya, Turkey;E-mail: mutayaslan@akdeniz.edu.trand TNF-a activate sickle endothelium, leading to increasedexpression of E-selectin, P-selectin, vascular celladhesion molecule–1, and intercellular adhesion molecule–1[11], which function as receptors for leukocyteadhesive proteins. Interleukin-1, TNF-a, and IL-6 alsoactivate hepatocytes to synthesize acute-phase proteins,which are also elevated in SCD patients [12].The activation state of neutrophils from SCD patients isdetermined by the expression of several surface antigensand levels of circulating proteins released by neutrophils.The high-affinity Fc receptor (FcgR1/CD64) expressed onimmature neutrophils is considered a marker of polymorphonuclearleukocytes (PMN) activation [13] and is significantlyincreased in SCD patients, especially in crisis [14,15]. Anothersensitive marker of neutrophil activation is decreasedsurface expression of L-selectin (CD62L), which is shed0301-472X/08 $–see front matter. Copyright Ó 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.doi: 10.1016/j.exphem.2008.07.004

Comparative Biochemistry and Physiology, Part C 144 (2007) 342–347www.elsevier.com/locate/cbpcImmobilization stress in rat tissues: Alterations in protein oxidation, lipidperoxidation and antioxidant defense systemEmel Şahin, Saadet Gümüşlü ⁎Department of Biochemistry, Faculty of Medicine, Akdeniz University, 07070 Antalya, TurkeyReceived 6 February 2006; received in revised form 7 July 2006; accepted 21 October 2006Available online 27 October 2006AbstractWe determined the effects of immobilization stress on antioxidant status, protein oxidation and lipid peroxidation in brain, liver, kidney, heartand stomach of rats. Sixteen male Wistar rats (3 months old) were divided into controls (C) and immobilization stress group (IS). IS rats wereimmobilized for 180 min/day for 15 days. Plasma corticosterone levels were increased in IS group. Copper,zinc-superoxide dismutase activitieswere increased in brain, liver and kidney, but decreased in the heart and stomach after immobilization. Catalase activities were increased in brain,kidney and heart, and decreased in liver and stomach. Selenium-dependent glutathione peroxidase activities were decreased in brain and kidney,but increased in heart and stomach. Reduced glutathione levels were decreased, while protein carbonyl, conjugated dienes and thiobarbituric acidreactivesubstances levels were increased in all tissues. Our results showed that the response of antioxidant defense system to stress differs for eachtissue, and protein oxidation and lipid peroxidation is induced by immobilization stress in peripheral tissues.© 2006 Elsevier Inc. All rights reserved.Keywords: Immobilization stress; Copper,zinc-superoxide dismutase; Catalase; Glutathione peroxidase; Reduced glutathione; Protein oxidation; Lipid peroxidation;Corticosterone; Tissues; Rat1. IntroductionStress can be defined as physical and psychologicalmodifications that disrupt the homeostasis and the balance oforganisms. Stress is known as one of the most important reasonsof several diseases (Johnson et al., 1992).Recently various stress models have been associated withenhanced free radical generation and altered antioxidant enzymeactivities (Giralt et al., 1993; Liu et al., 1994; Bian et al.,1997; Seckin et al., 1997; Gumuslu et al., 2002). Alves deAlmeida et al. (in press) also reported that both oxidativedamage levels and antioxidant defense systems were stronglyaffected by the different environmental stresses in marinebivalves from the Brazilian coast. These alterations areexplained as a resisting mechanism to the negative effects ofreactive oxygen species (ROS), e.g. hydrogen peroxide ( H 2 O 2 ),hydroxyl radical ( HO U ) and superoxide anion radical (O 2− U ) that⁎ Corresponding author. Tel.: +90 242 2496896; fax: +90 242 227 4495, 2274482.E-mail address: sgumuslu@akdeniz.edu.tr (S. Gümüşlü).cause the peroxidation of membrane lipids (Selman et al., 2000;Heise et al., 2003). The membrane injury following lipidperoxidation causes disruption of the tissue integrity (Bagchiet al., 1999). Therefore, to neutralize ROS, the body uses mainlyenzymatic copper,zinc-superoxide dismutase (Cu,Zn-SOD),catalase (CAT) and selenium-dependent glutathione peroxidase(Se-GSH-Px) and non-enzymatic antioxidants, e.g. reducedglutathione (GSH).It is reported that immobilization/restraint stress is an easy andconvenient method to induce both psychological (escapereaction) and physical stress (muscle work) resulting in restrictedmobility and aggression (Singh et al., 1993; Ramanova et al.,1994).In our previous study, we investigated the influences ofdifferent stress models on the antioxidant status and lipidperoxidation in rat erythrocytes (Gumuslu et al., 2002) and theeffects of cold stress on different tissues (Sahin and Gumuslu,2004a). Although stress and its effects on organism have beeninvestigated in several tissues, plasma and erythrocytes in earlierstudies (Ohno et al., 1991; Sosnowski et al., 1993; Shaheen et al.,1996), there is no detailed and comparable study investigating1532-0456/$ - see front matter © 2006 Elsevier Inc. All rights reserved.doi:10.1016/j.cbpc.2006.10.009

Clinical and Experimental Pharmacology and Physiology (2007) 34, 425–431doi: 10.1111/j.1440-1681.2007.04584.xSTRESS-DEPENDENT INDUCTION OF PROTEIN OXIDATION, LIPIDPEROXIDATION AND ANTI-OXIDANTS IN PERIPHERAL TISSUES OFBlackwell OriginalStress-dependent E Error!ArticleBookmarkPublishingoxidative notAsiadefined.ah[yacute]n modifications and S Gümü[thorn ]lüRATS: COMPARISON OF THREE STRESS MODELS (IMMOBILIZATION,COLD AND IMMOBILIZATION–COLD)Emel 1ahın and Saadet Gümü2lüDepartment of Biochemistry, Faculty of Medicine, Akdeniz University, Antalya, TurkeySUMMARY1. It is known that stress causes disruption of homeostasis andan imbalanced anti-oxidant status in several organs. The aim ofthe present study was to determine the effects of three stressmodels on protein oxidation, lipid peroxidation and anti-oxidantenzyme activities in the liver, kidney and heart, and to investigatethe relationship between corticosterone and some oxidative stressparameters. In addition, we investigated the most effective stressmodel for each parameter in each tissue.2. Thirty-six male Wistar rats (aged 3 months old, weighing220 ± 20 g) were divided randomly into four groups of nine ratseach: control (C), immobilization stress (IS), cold stress (CS),and immobilization–cold stress (ICS).3. Results showed that corticosterone levels were increased inall stress groups. Levels of protein carbonyl (PC), conjugateddienes (CD) and thiobarbituric acid-reactive substances (TBARS)were increased, whereas reduced glutathione (GSH) levels weredecreased in all tissues of all stress groups. Copper, zinc-superoxidedismutase (Cu,Zn-SOD) activities were increased in the liver andkidney of all stress groups, but were decreased in heart of theIS and CS groups. Catalase (CAT) activities were increased inliver of the CS group and in kidney and heart of all stress groups,but were decreased in liver of the IS and ICS groups. Seleniumdependentglutathione peroxidase (Se-GSH-Px) activities wereincreased in liver of the CS and ICS groups and in heart of allstress groups, but were decreased in kidney of the IS group. Also,Se-GSH-Px activity levels remained unchanged in liver of the ISgroup and in kidney of the CS and ICS groups. The increasedCAT activity and unchanged Se-GSH-Px activity observed inkidney suggest that H 2 O 2 may be primarily scavenged by CAT.4. The strong correlations between corticosterone and oxidativedamage markers (e.g. protein oxidation, lipid peroxidationand GSH levels) suggest a relationship between these parameters.Liver was affected most by the CS model, whereas kidneyand heart were affected most by ICS model. Stress-inducedchanges in the activities of anti-oxidant enzymes and GSH levelswere found to be tissue- and enzyme-specific. In conclusion,Correspondence: Prof. S Gümüslü, Department of Biochemistry,Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey. Email:sgumuslu@akdeniz.edu.trReceived 13 June 2006; revision 16 October 2006; accepted 26 October 2006.© 2007 The AuthorsJournal compilation © 2007 Blackwell Publishing Asia Pty Ltdresults of the present study suggest that each stress model affectsthe different organ tissues in different ways.Key words: anti-oxidant enzymes, cold stress, glutathione,immobilization stress, immobilization–cold stress, lipid peroxidation,protein oxidation, rat.INTRODUCTIONIt is well known that stress response stimulates various damagingpathways, causing increased production of reactive oxygen species(ROS), such as hydrogen peroxide (H 2 O 2 ), hydroxyl radicals (HO·)−and superoxide anion radicals (· O 2 ), which lead to lipid peroxidation,protein oxidation, DNA damage and cell death, and contributes tothe occurrence of pathological conditions. 1–3 Therefore, to neutralizeROS the body uses mainly enzymatic (e.g. copper, zinc-superoxidedismutase (Cu,Zn-SOD), catalase (CAT) and selenium-dependentglutathione peroxidase (Se-GSH-Px)) and non-enzymatic anti-oxidants(e.g. reduced glutathione (GSH)).There have been many reports that investigate the stress-inducedcompensatory changes that take place in the anti-oxidant systemand lipid peroxidation in the plasma, 4 erythrocytes 5–7 and differenttissues 8–12 of animals. In our previous studies, we investigated theinfluences of different stress models on the anti-oxidant status andlipid peroxidation in rat erythrocytes, 5 and the effects of cold stresson different tissues. 11 However, there is no detailed and comparablestudy investigating the effects of different stress models on proteinmodification and lipid peroxidation in different tissues. In addition,we could not find any study clarifying the most effective stress modelin relation to these oxidative parameters.In the present study, we investigated the hypothesis that threestress models (immobilization stress, cold stress and immobilization–cold stress) alter anti-oxidant enzyme activities, cause increased proteinoxidation and lipid peroxidation, and that there may be a relationshipbetween glucocorticoids (corticosterone in rats) and some oxidativestress parameters. In addition, we investigated which is the mosteffective stress model for each of the liver, kidney and heart.AnimalsMETHODSThirty-six male Wistar rats, aged 3 months old and weighing 220 ± 20 g,were used. Rats were divided randomly into four groups of nine rats each: controlgroup (C), immobilization stress group (IS), cold stress group (CS), andimmobilization–cold stress group (ICS). Three animals were housed per cage.

REVIEWSOxidative Stress and Apoptosis: Impact on Cancer TherapyTOMRIS OZBENDepartment of Biochemistry, Medical Faculty, Akdeniz University, 07070 Antalya, TurkeyReceived 26 October 2006; accepted 11 December 2006Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jps.20874ABSTRACT: It is well established that some chemotherapeutic agents and radiationtherapy generate reactive oxygen species (ROS) in patients during cancer therapy. Freeradicals, particularly ROS have been proposed as common mediators for apoptosis.Recent studies have demonstrated that the mode of cell death depends on the severity ofthe oxidative damage. This review will address some of the current paradigms ofoxidative stress, and antioxidants on apoptosis, and discuss the potential mechanismsby which oxidants can regulate apoptotic pathways. It will also review new developmentsin eliminating cancer cells by selectively inducing apoptosis. ß 2007 Wiley-Liss, Inc.and the American Pharmacists Association J Pharm Sci 96:2181–2196, 2007Keywords: cancer chemotherapy; cancer; cell lines; oxidation; oligonucleotides;multidrug resistanceINTRODUCTIONOxidative stress is a biochemical condition that ischaracterized by the imbalance between thepresence of relatively high levels of toxic reactivespecies, principally consisting of reactive oxygenspecies (ROS), reactive nitrogen species (RNS),and the antioxidative defense mechanisms. 1–3ROS and RNS are organic or inorganic moleculesthat have an odd number of electrons. These moleculesare formed in vivo via oxidation-reductionreactions and are highly reactive. While oxygen isan important substrate in oxidative metabolism, itcan also be partially reduced to form ROS. 4 ROSare essential for life because of their role in manyvital processes such as signal transduction andCorrespondence to: Tomris Ozben (Telephone:þ 90-242-2496895; Fax: þ 90-242-2274482;E-mail: ozben@akdeniz.edu.tr)Journal of Pharmaceutical Sciences, Vol. 96, 2181–2196 (2007)ß 2007 Wiley-Liss, Inc. and the American Pharmacists Associationbactericidal activity of phagocytes. 5 ROS includesfree radicals, such as hydroxyl and superoxideradicals, and nonradicals, including hydrogenperoxide and singlet oxygen. 5 Superoxide (O 2 ),not highly toxic, is the primary free radical formedwithin the cell by the reduction of molecularoxygen. The spontaneous or mitochondrial superoxidedismutase (SOD)-catalyzed dismutation ofsuperoxide anion (O 2 ) generates hydrogen peroxide(H 2 O 2 ), which yields the highly toxic hydroxylradical (OH ) in the presence of reduced iron orcopper via Fenton or Haber–Weiss reactions. 5,6Autoxidation of mitochondrial respiratory chaincomponents and oxidases, like NADPH oxidase,xanthine oxidase, prostaglandin endoperoxidesynthase, lipooxygenase, and cytochrome P-450serve as sources of ROS in various cell types. 4,7The cytochrome P-450 monooxygenase system ofthe hepatic endoplasmic reticulum (microsomes)generates a substantial amount of ROS in theprocess of metabolizing most of the drugs andenvironmental substances. 5JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 96, NO. 9, SEPTEMBER 2007 2181

FEBS Letters 580 (2006) 2903–2909MinireviewMechanisms and strategies to overcome multiple drug resistance in cancerTomris Ozben *Akdeniz University, Faculty of Medicine, Department of Biochemistry, 07070 Antalya, TurkeyReceived 30 January 2006; accepted 9 February 2006Available online 17 February 2006Edited by Horst FeldmannAbstract One of the major problems in chemotherapy is multidrugresistance (MDR) against anticancer drugs. ATP-bindingcassette (ABC) transporters are a family of proteins that mediateMDR via ATP-dependent drug efflux pumps. Many MDRinhibitors have been identified, but none of them have been provenclinically useful without side effects. Efforts continue to discovernot toxic MDR inhibitors which lack pharmacokineticinteractions with anticancer drugs. Novel approaches have alsobeen designed to inhibit or circumvent MDR. In this review,the structure and function of ABC transporters and developmentof MDR inhibitors are described briefly including various approachesto suppress MDR mechanisms.Ó 2006 Federation of European Biochemical Societies. Publishedby Elsevier B.V. All rights reserved.Keywords: Multidrug resistance; ATP-binding cassettetransporters; Cancer chemotherapy; Multidrug resistanceinhibitorsThe cytotoxic drugs that are most frequently associated withMDR are hydrophobic, amphipathic natural products, such asthe taxanes (paclitaxel and docetaxel), vinca alkaloids (vinorelbine,vincristine, and vinblastine), anthracyclines (doxorubicin,daunorubicin, and epirubicin), epipodophyllotoxins (etoposideand teniposide), antimetabolites (methorexate, fluorouracil,cytosar, 5-azacytosine, 6-mercaptopurine, and gemcitabine)topotecan, dactinomycin, and mitomycin C [4,6–8].Overexpression of ATP-binding cassette (ABC) transportershas been shown to be responsible for MDR [5]. Therefore elucidationof the structure and function for each ABC transporter isprerequisite for understanding how these transporters work andfor reversing MDR. One strategy for reversal of MDR in cellsexpressing ABC transporters is combined use of anticancerdrugs with chemosensitizers. Inhibitors of ABC transporterscan be used to enhance oral bioavailability or the brain penetrationof various drugs. Downregulation of MDR transportersand circumventing MDR mechanisms are other approachesto overcome MDR [3,5].1. IntroductionThe failure of the curative treatment of cancer patients oftenoccurs as a result of intrinsic or acquired drug resistance of thetumor to chemotherapeutic agents. The resistance of tumorsoccurs not only to a single cytotoxic drug used, but also occursas a cross-resistance to a whole range of drugs with differentstructures and cellular targets. This phenomenon is called multipledrug resistance (MDR). Once MDR appears, using highdoses of drugs to overcome resistance is ineffective, toxic effectsappear and resistance are further stimulated. Multidrug resistance(MDR) severely limits the effectiveness of chemotherapyin a variety of common malignancies and is responsible for theoverall poor efficacy of cancer chemotherapy [1–5].* Fax: +90 242 2274495.E-mail address: ozben@akdeniz.edu.tr (T. Ozben).Abbreviations: MDR, multidrug resistance; MRP, multidrug resistanceprotein; ATP, adenosinetriphosphate; ABC, ATP-binding cassette;TMD, transmembrane domains; P-gp, P-glycoprotein; MRP1, MDRrelated protein; BCRP, breast cancer resistance protein; ABC-P, ABCtransporter in placenta; LRP, lung resistance-related protein; MVP,major vault protein; CMOAT, canalicular multi-organic anion transporter;CYP3A4, Cytochrome p450 3A4; SXR, steroid and xenobioticreceptor; GC, glucosylceramide; GCS, glucosylceramide synthase;GSH, glutathione; NAC, N-acetylcysteine; BSO, DL-buthionine(S,R)-sulfoximine; HEK, human embryonic kidney; ROS, reactiveoxygen species2. ATP-binding cassette (ABC) transportersIdentifying the mechanisms leading to intrinsic or acquiredmultidrug resistance (MDR) is important in developing moreeffective therapies [2]. The drug resistance in cancer cells oftenresults from elevated expression of particular proteins, such ascell-membrane transporters, which can result in an increasedefflux of the cytotoxic drugs from the cancer cells, thus loweringtheir intracellular concentrations [4,6,9]. The resistancemechanism is called typical or classical MDR when overexpressionof the membrane efflux pumps is involved in MDR[5]. The classical MDR is due mostly to increased efflux pumpsin the cell membrane of cells pumping anticancer drugs out ofcells [1–3,5].ATP-binding cassette (ABC) transporters are a family oftransporter proteins that contribute to drug resistance viaadenosinetriphosphate (ATP)-dependent drug efflux pumps[10]. Up to date, more than 100 ABC transporters from prokaryotesto humans and 48 human ABC genes have been identifiedthat share sequence and structural homology [4,5,10,11].Not more than 10 of the ATP transporters are reported to conferthe drug-resistant phenotype [4,9]. The functions of 16genes have been determined and 14 genes are related with severaldiseases present in humans [5,11,12]. Although the resistantproteins belong to the ABC superfamily, they are quitedifferent with respect to gene locus, amino acid sequence,structure and substrate [5]. ABC proteins are present in all0014-5793/$32.00 Ó 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.doi:10.1016/j.febslet.2006.02.020

found 1 article by title matching your search:Clin Hemorheol Microcirc. 2006;35(3):349-57.L-carnitine deficiency and red blood cell mechanical impairment in betathalassemiamajor.Toptas B, Baykal A, Yesilipek A, Isbir M, Kupesiz A, Yalcin O, Baskurt OK.Department of Biochemistry, Akdeniz University School of Medicine, Antalya, Turkey.AbstractL-carnitine is an essential element of intermediary metabolism and also was shown to be effective in maintaining normal red blood cell(RBC) function. This study aimed at investigating plasma free L-carnitine concentrations and effectiveness of L-carnitinesupplementation in protecting deterioration of RBC properties in beta-thalassemia major patients. Plasma free L-carnitine concentrationswere determined in the blood samples obtained before their regular transfusion (about one month after the previous transfusion). Eachpatient received 100 mg/kg/day oral L-carnitine supplementation. RBC deformability, lipid peroxidation and intracellular free calciumŀWeconcentrations were investigated before and after this treatment. Plasma free L-carnitine levels and RBC deformability before thetreatment were found to be lower whereas lipid peroxidation and intracellular calcium concentration in RBC were higher compared tothose of the control subjects before the L-carnitine treatment. After one month supplementation of L-carnitine lipid peroxidation andintracellular calcium concentrations were found to be decreased and RBC deformability was improved, accompanying the significantlyincreased plasma L-carnitine concentrations. These results suggest that L-carnitine can be used as a supplement in beta-thalassemicpatients, to prevent RBC deterioration.

Biyoloji Anabilim Dalı1-Terzioglu E, Bisgin A, Sanlioglu AD, Ulker M, Yazisiz V, Tuzuner S, and Sanlioglu S. Concurrentgene therapy strategies effectively destroy synoviocytes of patients with rheumatoid arthritis.Rheumatology (Oxford)46(5): 783-789, 20072-Aydin C, Sanlioglu AD, Karacay B, Ozbilim G, Dertsiz L, Ozbudak O, Akdis CA and Sanlioglu S8. ADcR2 siRNA strategy employing three different siRNA constructs in combination defeats adenovirustransferred TRAIL resistance in lung cancer cells. Human Gene Therapy18: 39-50, 20073-Dajani R, Sanlioglu S, Zhang Y, Li Q, Monick MM, Lazartigues E, Eggleston T, Davisson RL,Hunninghake GH, Engelhardt JFPleiotropic Functions of TNF alpha Determine Distinct IKK beta-Dependent Hepatocellular Fates in Response to LPSAm J Physiol Gastrointest Liver Physiol292(1):G242-252, 20074-Sanlioglu AD, Koksal IT, Ciftcioglu MA, Baykara M, Luleci G and Sanlioglu SDifferential expressionof TRAIL and its receptors in benign and malignant prostate tissuesJournal of Urology177(1): 359-364, 20075-Nal N., Morell R.J., Erkal E., Ahmed Z., Riazuddin S., Alper, Ö.M., Lüleci G., Dinç O., FriedmanT.B. .“Spectrum of mutations of MYO15A associated with hearing loss gives insight into the functionof myosin XVA” Human Mutation28 (10): 1014- 1019, 20076-Lee-Jun C. Wong, Mei-Hui Lee, Ming Chen, Özgül M. Alper, Long-Yen Tsao, and Bao-Tyan Wang.First prenatal exclusion of cystic fibrosis in East Asia. Pediatrics International 49: 686-687,2007.7-Karaüzüm SB,Yasar D,Dirice E,İmir N,Lüleci G,Ozes ONLack of BCL-2 confers interferon-alphasensitivity to B-cell lymphomas.Growth Factors 1-7,ifirst article;20078-Keser I, Manguoglu E, Kayisli O, Yesilipek A, Luleci G. Combination of hb Knossos ŀTıbbi[Cod 27 (G-T)]and IVSII-745 (C-G) in a Turkish patient with beta-thalassemia major. GENETIC TESTING,11(3):228-230, 2007.9-Doherty R, Lubinski J, Manguoglu E, Luleci G, Christie M, Craven P, Bancroft E, Mitra A, Morgan S,Eeles R; IMPACT steering committee and collaborators..Short report. The AIDIT and IMPACTconference 2006: Outcomes and future directions.Hered Cancer Clin Pract. 2007 Mar 15;5(1):53-5.

Rheumatology 2007;46:783–789Advance Access publication 19 February 2007doi:10.1093/rheumatology/kel448Concurrent gene therapy strategies effectively destroy synoviocytesof patients with rheumatoid arthritisE. Terzioglu 1, 2 , A. Bisgin 1, 3 , A. D. Sanlioglu 1, 3 , M. Ulker 1 , V. Yazisiz 1, 2 , S. Tuzuner 1, 4and S. Sanlioglu 1, 3Objectives. Rheumatoid arthritis (RA) is characterized by the chronic inflammation of the synovial joints resulting from the hyperplasia ofsynovial cells and the infiltration of lymphocytes, macrophages and plasma cells. Currently, the aetiology of RA is not known, and newtreatment modalities are needed to prevent the disease progression. Apoptosis induction of synovial cells through the use of death ligandshas been explored as a treatment modality for RA. Thus, the primary objective of this study was the testing of the efficacy of adenovirusdelivery of human TRAIL (Ad5hTRAIL) for the treatment of patients with RA.Methods. Primary synovial cell cultures were established from eight patients with RA. Adenovirus permissiveness of synovial cells wasdetermined by the infection of synoviocytes with adenovirus vector encoding green fluorescent protein (AdEGFP). TRAIL sensitivity ofsynoviocytes was assessed through the infection with Ad5hTRAIL vector using Live/Death Cellular Viability/Toxicity kit from Molecular Probe.TRAIL receptor profiles of synoviocytes were revealed by real-time RT-PCR assays followed by flow cytometric analyses.Results. While the presence of TRAIL death receptors were necessary for the induction of cell death, high levels of TRAIL-R4 decoy receptorexpression on surface were correlated with TRAIL resistance. A DcR2 siRNA approach in combination with Ad5hTRAIL infection eliminatedapoptosis-resistant RA synovial fibroblasts.Conclusion. Because a DcR2 siRNA approach in combination with Ad5hTRAIL infection exterminated RA synoviocytes to a greater extentthan Ad5hTRAIL alone, the modulation of TRAIL receptor expression might be a new gene therapy strategy to sensitize RA synoviocytes toTRAIL.KEY WORDS: Rheumatoid arthritis, Adenovirus, TRAIL, siRNA.Rheumatoid arthritis (RA) is a disease in which synovial cells arephenotypically transformed to proliferate abnormally invadingboth bone and cartilage [1]. In RA, apoptosis-resistant synovialcells provoke tissue degradation through the production ofelevated levels of pro-inflammatory cytokines and metalloproteinases[2]. Therefore, abnormal synoviocyte proliferation andlymphocyte–macrophage activation are the two major pathogenichallmarks of RA [3]. Several strategies including gene therapywere explored for the treatment of RA in order to overcomecurrent drug delivery problems to articular tissues [4]. With thisperspective, prospected goals were to inhibit the production ofpro-inflammatory cytokines [1] and matrix degrading enzymes [5]to prevent the activation of specific signal transduction pathwayssuch as NF-kB [6] and finally to promote apoptosis insynoviocytes and immune cells [7].Induction of apoptosis is a common property of death ligands,which belong to tumour necrosis factor (TNF) family.TNF-related apoptosis inducing ligand (TRAIL) is a type IImembrane protein of the TNF super family [8]. Five differentreceptors were identified to interact with TRAIL and these areTRAIL-R1 (DR4), TRAIL-R2 (DR5), TRAIL-R3 (DcR1),TRAIL-R4 (DcR2) and osteoprotegrin [9, 10]. While the existenceof multiple TRAIL receptors indicates that TRAIL is involved inmultiple processes in the cell, the precise role of TRAIL in healthand disease is unclear at this moment [11]. While TRAIL-R1 andTRAIL-R2 function as authentic death receptors inducing1 Human Gene Therapy Unit,2 Department of Rheumatology—Allergy andImmunology, 3 Department of Medical Biology and Genetics and 4 Department ofOrthopedic Surgery, Akdeniz University Faculty of Medicine, Antalya 07070,Turkey.Submitted 16 October 2006; revised version accepted 16 October 2006.Correspondence to: S. Sanlioglu, Director of the Human Gene Therapy Unit,Akdeniz University, Faculty of Medicine, B-Block, 1st floor, Campus,Antalya 07070, Turkey. E-mail: sanlioglu@akdeniz.edu.tr The first two authors E.T. and A.B. contributed equally to this article.apoptosis, TRAIL-R3 and TRAIL-R4 are unable to inducesuch signalling but can serve as decoy receptors [12]. Comparedwith the other members of TNF family such as FasL and TNF,TRAIL has some distinct apoptosis-inducing properties.For example, unlike TNF-, which initiated and exacerbatedautoimmune diseases, TRAIL was reported to down-regulateimmune responses. This was demonstrated in TRAILnull mice, which were more susceptible to collagen-inducedarthritis (CIA) due to the failure to properly silence activated Tcells [13].Even though, TRAIL and TRAIL receptors are expressedconstitutively in various tissues, TRAIL does not induce apoptosisof most non-transformed cells [11, 14, 15]. Even today, no singlemechanism is thought to be responsible for the TRAIL resistancein normal cells. There are at least two different hypotheses claimedfor TRAIL resistance. The first hypothesis supports that normalcells carry decoy receptors (TRAIL-R3, TRAIL-R4), whichcompete with apoptosis-inducing TRAIL receptors (TRAIL-R1,TRAIL-R2) for binding to TRAIL [14, 15]. Here it is thought thatdecoy receptors either serve to dilute out TRAIL ligands (likeTRAIL-R3) or provide anti-apoptotic signals (like TRAIL-R4) tocells. For instance, TRAIL-R4 binding activated anti-apoptoticNF-kB signalling pathway, which led to the obstruction ofTRAIL-mediated apoptosis [16]. More interestingly, activationof death receptors such as TRAIL-R1 and TRAIL-R2 alsoactivated NF-kB pathway [17, 18]. Under these circumstances,how cells undergo apoptosis despite the induction of bothapoptotic and anti-apoptotic pathways is not known. The secondhypothesis proposes the presence of apoptosis inhibitory substances.Such a molecule, cFLIP (FLICE inhibitory protein),a caspase 8 homologue, was shown to obstruct death ligandinducedapoptosis before [19, 20]. Despite these hypotheses,no clear evidence to account for TRAIL resistance has beenasserted yet.As gene delivery vehicles, vectors derived from retrovirus [21],adenovirus [2] and herpes simplex virus [22] as well as cationicliposomes and naked plasmid DNA were all tested to deliver783ß The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.orgDownloaded from rheumatology.oxfordjournals.org at Akdeniz University on October 12, 2010

Decoy receptor-2 small interfering RNA (siRNA) strategy employing three differentsiRNA constructs in combination defeats adenovirus-transferred tumor necrosisfactor-related apoptosis-inducing ligand resistance in lung cancer cellsAuthor(s): Aydin C (Aydin, Cigdem), Sanlioglu AD (Sanlioglu, Ahter D.), Karacay B (Karacay, Bahri), Ozbilim G(Ozbilim, Gulay), Dertsiz L (Dertsiz, Levent), Ozbudak O (Ozbudak, Omer), Akdis CA (Akdis, Cezmi A.), SanliogluS (Sanlioglu, Salih)Source: HUMAN GENE THERAPY Volume: 18 Issue: 1 Pages: 39-50 Published: JAN 2007Times Cited: 17 References: 40 Citation MapAbstract: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis incancer cells but not in normal cells. However, studies have indicated that more than half of human tumors exhibitTRAIL resistance. Although the mechanism of TRAIL resistance is not understood, it represents a barrier to anyTRAIL-mediated gene therapy approach. In addition, no correlation between TRAIL receptor (TRAIL-R)expression profile and TRAIL resistance has been demonstrated in cancer cells. In this study, three different lungcancer cell lines and three different primary cell cultures established from patients with lung cancer (two patientswith squamous cell lung carcinoma and one with adenocarcinoma) were screened for sensitivity to adenoviraldelivery of TRAIL. Whereas TRAIL-resistant primary lung cell cultures and the A549 lung cancer cell line exhibitedhigh levels of surface decoy receptor-2 (DcR2/TRAIL-R4) expression, TRAIL-sensitive lung cancer cell lines (HBEand H411) failed to express it. A DcR2 short interfering RNA (siRNA) approach involving three different siRNAconstructs in combination downregulated DcR2/TRAILR4 expression and sensitized lung cancer cells to TRAILinducedapoptosis. Immunohistochemical staining of samples from 10 patients with lung carcinoma suggestedthat high-level DcR2/TRAIL-R4 expression is a common phenotype observed in patients with non-small cell lungcarcinoma.Document Type: ArticleLanguage: EnglishKeyWords Plus: TRAIL-INDUCED APOPTOSIS; NF-KAPPA-B; MEDIATED APOPTOSIS; INHIBITORYPROTEIN; DEATH DOMAIN; GENE; EXPRESSION; FAMILY; CHEMOTHERAPY; MECHANISMSReprint Address: Sanlioglu, S (reprint author), Akdeniz Univ, Fac Med, Human Gene Therapy Unit, B-Block,1stFloor Campus, TR-07070 Antalya, TurkeyAddresses:1. Akdeniz Univ, Fac Med, Human Gene Therapy Unit, TR-07070 Antalya, Turkey2. Akdeniz Univ, Fac Med, Dept Med Biol & Genet, TR-07070 Antalya, Turkey3. Akdeniz Univ, Fac Med, Dept Pathol, TR-07070 Antalya, Turkey4. Akdeniz Univ, Fac Med, Dept Thorac Surg, TR-07070 Antalya, Turkey5. Akdeniz Univ, Fac Med, Dept Pulm Dis, TR-07070 Antalya, Turkey6. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA7. Univ Iowa, Ctr Gene Therapy, Iowa City, IA 52242 USA8. Swiss Inst Allergy & Asthma Res, CH-7270 Davos, SwitzerlandE-mail Addresses: sanlioglu@akdeniz.edu.trPublisher: MARY ANN LIEBERT INC, 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USASubject Category: Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research &ExperimentalIDS Number: 126QLISSN: 1043-0342DOI: 10.1089/hum.2006.111

Am J Physiol Gastrointest Liver Physiol 292: G242–G252, 2007.First published August 24, 2006; doi:10.1152/ajpgi.00043.2006.Pleiotropic functions of TNF- determine distinct IKK-dependenthepatocellular fates in response to LPSRana Dajani, 1 Salih Sanlioglu, 4 Yulong Zhang, 1,3 Qiang Li, 1,3 Martha M. Monick, 2 Eric Lazartigues, 1Timothy Eggleston, 1 Robin L. Davisson, 1 Gary W. Hunninghake, 2,3 and John F. Engelhardt 1,2,31Department of Anatomy and Cell Biology, 2 Department of Internal Medicine-Division of Pulmonary andCritical Care, 3 Center for Gene Therapy at the University of Iowa College of Medicine, Iowa City, Iowa;and 4 Human Gene Therapy, Faculty of Medicine at the Akdeniz University, Antalya, TurkeySubmitted 24 January 2006; accepted in final form 23 August 2006Dajani, Rana, Salih Sanlioglu, Yulong Zhang, Qiang Li, MarthaM. Monick, Eric Lazartigues, Timothy Eggleston, Robin L.Davisson, Gary W. Hunninghake, and John F. Engelhardt. Pleiotropicfunctions of TNF- determine distinct IKK-dependent hepatocellularfates in response to LPS. Am J Physiol Gastrointest LiverPhysiol 292: G242–G252, 2007. First published August 24, 2006;doi:10.1152/ajpgi.00043.2006.—TNF- influences morbidity andmortality during the course of endotoxemia. However, the complexpleiotropic functions of TNF- remain poorly understood. We evaluatedhow hepatic induction of NF-B and TNF- influence survivaland hepatocellular death in a lethal murine model of endotoxic shock.Using dominant-negative viral vectors to inhibit the IKK complex, wedemonstrate through this study that the liver is a major source ofTNF- during the course of lethal endotoxemia and that IKK (butnot IKK) is predominantly responsible for activating NF-B andTNF- in the liver after LPS administration. Using TNF- knockoutmice and hepatic-specific inhibition of IKK, we demonstrate that thestatus of TNF- and NF-B balances necrotic and apoptotic fates ofhepatocytes in the setting of endotoxemia. In the presence of TNF-,inhibiting hepatic IKK resulted in increased survival, reduced serumproinflammatory cytokines, and reduced hepatocyte necrosis in responseto a lethal dose of endotoxin. In contrast, inhibiting hepaticIKK in TNF- knockout mice resulted in decreased survival andincreased caspase 3-mediated hepatocyte apoptosis after endotoxinchallenge, despite a reduced proinflammatory cytokine response. Inthe presence of TNF-, NF-B-dependent hepatocellular necrosispredominated, while in the absence of TNF-, NF-B primarilyinfluenced apoptotic fate of hepatocytes. Changes in JNK phosphorylationafter LPS challenge were also dynamically affected by bothIKK and TNF-; however, this pathway could not solely explain thedifferential outcomes in hepatocellular fates. In conclusion, our studiesdemonstrate that induction of NF-B and TNF- balances protective(antiapoptotic) and detrimental (proinflammatory) pathways todetermine hepatocellular fates during endotoxemia.nuclear factor-B; endotoxic shock; inflammation; apoptosis; c-junNH 2 -terminal kinaseLPS IS a component of the gram-negative bacterial cell wall thatplays a major role in the pathogenesis of the sepsis syndrome(11). During the course of sepsis, the production of proinflammatorycytokines such as TNF- leads to systemic inflammatoryresponse syndrome (29). Moreover, TNF- has beenshown to be a major player in endotoxin-induced lethalityduring the course of sepsis (3). Numerous animal studies havebeen conducted in an effort to understand the pathophysiologyAddress for reprint requests and other correspondence: J. F. Engelhardt,Dept. of Anatomy and Cell Biology, Univ. of Iowa, College of Medicine, 51Newton Rd., Rm. 1–111 BSB, Iowa City, IA 52242 (e-mail: johnengelhardt@uiowa.edu).of sepsis. For example, mice lacking TNF- or TNF receptor1 are resistant to endotoxin (33, 34). In addition, neutralizingantibodies to TNF- or soluble recombinant TNF receptor,protect against LPS injury (1, 22, 40). These studies suggestedthat downregulation of TNF- production, or its neutralization,might prove useful in the treatment of sepsis.LPS induction of TNF- is largely dependent on NF-Bactivation (38). NF-B nuclear translocation is regulated bytwo IB kinases: IKK (IKK-1) and IKK (IKK-2) (30, 46).Although a direct link between TNF- induction and endotoxin-inducedcell death has been clearly established, the in vivorole of NF-B in producing a proinflammatory state duringendotoxemia, while at the same time modulating cell survival,has remained unclear. For example, although NF-B is knownto induce TNF- gene expression after LPS exposure (38),NF-B activity has also been shown to be an importantantiapoptotic factor during liver development and regeneration(19, 23, 24). Similarly, reports have suggested that TNF-inducedapoptosis can be abrogated through NF-B activation(42). Hence, the manner by which NF-B balances the inductionof proinflammatory and antiapoptotic pathways remainsambiguous.Using in vivo liver-directed gene transfer techniques, wehave evaluated whether hepatic-derived NF-B-regulatedTNF- production is an important pathophysiologically relevantcomponent in endotoxemic death. Results from thesestudies suggest that hepatic IKK, but not IKK, plays apredominant role in NF-B activation and the subsequent risein serum TNF- levels during the course of lethal endotoxemia.Inhibition of IKK using a dominant-negative adenoviralvector resulted in increased survival, reduced serum TNF-,and reduced liver injury in response to a lethal dose ofendotoxin. Such findings suggest that during the course oflethal endotoxemia, NF-B activation has a predominantlynegative proinflammatory effect on the liver through the inductionof TNF-. In contrast, in TNF--knockout mice,inhibition of IKK decreased survival and increased liverapoptosis after LPS challenge. These data suggest that duringthe course of lethal endotoxemia, TNF- influences the roleNF-B as an antiapoptotic factor in the liver.MATERIALS AND METHODSRecombinant adenovirus vectors and infections. For functionalstudies, the following recombinant adenoviral vectors were used: 1) aThe costs of publication of this article were defrayed in part by the paymentof page charges. The article must therefore be hereby marked “advertisement”in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.Downloaded from ajpgi.physiology.org on October 12, 2010G2420193-1857/07 $8.00 Copyright © 2007 the American Physiological Society http://www.ajpgi.org

HUMAN MUTATION 28(10), 1014^1019, 2007RESEARCH ARTICLEMutational Spectrum of MYO15A:The Large N-Terminal Extension of Myosin XVAIs Required for HearingNevra Nal, 1,2 Zubair M. Ahmed, 1 Engin Erkal, 3 Özgül M. Alper, 2 Güven Lüleci, 2 Oktay Dinc-, 3Ali Muhammad Waryah, 4 Quratul Ain, 4 Saba Tasneem, 4 Tayyab Husnain, 4 Parna Chattaraj, 1Saima Riazuddin, 1 Erich Boger, 1,5 Manju Ghosh, 6 Madhulika Kabra, 6 Sheikh Riazuddin, 4Robert J. Morell, 1 and Thomas B. Friedman 11 Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health(NIH), Rockville, Maryland; 2 Department of Medical Biology and Genetics, Akdeniz University, Antalya, Turkey; 3 Department ofOtolaryngology, Akdeniz University, Antalya, Turkey; 4 National Center of Excellence in Molecular Biology, University of the Punjab, Lahore,Pakistan; 5 Department of Biology, University of Maryland, College Park, Maryland; 6 Genetic Unit, Department of Pediatrics, All India Institute ofMedical Sciences, New Delhi, IndiaCommunicated by Henrik DahlHuman MYO15A is located on chromosome 17p11.2, has 66 exons and encodes unconventional myosin XVA.Recessive mutations of MYO15A are associated with profound, nonsyndromic hearing loss DFNB3 in humans,and deafness and circling behavior in shaker 2 mice. In the inner ear, this motor protein is necessary for thedevelopment of hair cell stereocilia, which are actin-filled projections on the apical surface and the site ofmechanotransduction of sound. The longest isoform of myosin XVA has 3,530 amino acid residues. Twoisoform classes of MYO15A are distinguished by the presence or absence of 1,203 residues preceding the motordomain encoded by alternatively-spliced exon 2. It is not known whether this large N-terminal extension ofmyosin XVA is functionally necessary for hearing. We ascertained approximately 600 consanguineous familiessegregating hereditary hearing loss as a recessive trait and found evidence of linkage of markers at the DFNB3locus to hearing loss in 38 of these families ascertained in Pakistan (n 5 30), India (n 5 6), and Turkey (n 5 2).In this study, we describe 16 novel recessive mutations of MYO15A associated with severe to profound hearingloss segregating in 20 of these DFNB3-linked families. Importantly, two homozygous mutant alleles—c.3313G4T (p.E1105X) and c.3334delG (p.G1112fsX1124) of MYO15A—located in exon 2 are associatedwith severe to profound hearing loss segregating in two families. These data demonstrate that isoform 1,containing the large N-terminal extension, is also necessary for normal hearing. Hum Mutat 28(10),1014–1019, 2007. Published 2007 Wiley-Liss, Inc. yKEY WORDS:DFNB3; hereditary deafness; genotype–phenotype; myosin; MYO15AINTRODUCTIONMyosins are molecular motor proteins that hydrolyze ATP togenerate a small conformational change in the globular motordomain that is translated into movement along actin filaments[Mooseker and Cheney, 1995; Mermall et al., 1998; Sellers, 1999;Schliwa and Woehlke, 2003]. Based upon phylogenetic analysesof motor domains, 37 distinct classes of heavy chain myosins havebeen cataloged in plants, fungi, amoebas, invertebrates, andvertebrates [Sellers, 2000; Berg et al., 2001; Richards andCavalier-Smith, 2005; Foth et al., 2006]. Within the humangenome, there are at least 39 myosin genes assigned to 12 classes[Berg et al., 2001].Myosins are implicated in cellular functions including musclecontraction, cell movement, cytokinesis, exocytosis, endocytosis,transcription, vesicle and cargo trafficking, organelle localization,signal transduction, and anchoring and differential elongationof inner ear hair cell stereocilia [Baker and Titus, 1998; Vale,2003; Belyantseva et al., 2005; Krendel and Mooseker, 2005;The Supplementary Material referred to in this article can beaccessed at http://www.interscience.wiley.com/jpages/1059-7794/suppmat.Received 17 January 2007; accepted revised manuscript 3 April2007. Correspondence to:Thomas B. Friedman, Ph.D., Section on HumanGenetics, Laboratory of Molecular Genetics, National Instituteon Deafness and Other Communication Disorders, National Institutesof Health,5 Research Court, Rockville, MD 20850.E-mail: friedman@nidcd.nih.govGrant sponsors: Higher Education Commission (HEC) Islamabad,Pakistan; Ministry of Science and Technology (MoST) Islamabad,Pakistan; National Institute on Deafness and Other CommunicationDisorders (NIDCD), National Institutes of Health (NIH);Grant numbers:1 ZO1 DC000035 - 09 and 1 ZO1 DC000039 - 09.Nevra Nal and Zubair M. Ahmed contributed equally to this study.DOI 10.1002/humu.20556Published online1June 2007 inWiley InterScience (www.interscience.wiley.com).y This article is a US Government work and, as such, is in the publicdomain in the United States of America.PUBLISHED 2007 WILEY-LISS, INC.

Pediatrics International (2007) 49, 686–687doi: 10.1111/j.1442-200X.2007.02437.xPatient ReportFirst prenatal exclusion of cystic fibrosis in East AsiaLEE-JUN C. WONG , 1 MEI-HUI LEE ,2MI NG CH EN , 2,3 ÖZGÜL M. ALPER ,1, †LONG-YEN TSAO2AND BAO-TYAN WANG 2,4, *1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas,4Quest Diagnostics, Nichols Institute, California, USA, 2 Center for Medical Genetics and3Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, TaiwanKey words Asian CF , CFTR , cystic fibrosis , prenatal diagnosis .Although cystic fibrosis (CF; OMIM number 219700) is oneof the most common autosomal recessive diseases in Caucasians,it is very rare in Asian populations. 1 – 3 A recent survey ofreported CF cases in Asia documented 15 patients whosemutations have been molecularly characterized. 4 The reportedAsian specific CFTR mutations were diverse, novel, and raremutations, and mostly involved nonsense or splice site mutationsthat resulted in truncated proteins. 4 Because this diseaseis not commonly recognized in Asian countries, many patientsdied in early childhood without diagnosis due to the severity ofthe disease, and lack of adequate medical care in underdevelopedcountries. Although the incidence of CF is rare in Asia,considering that one-third of the world population is Asian,the absolute number of carriers is in the millions. Thus,mutational analysis cannot be overlooked. Using the recentlydeveloped temporal temperature gradient gel electrophoresis(TTGE),5 – 7mutations in CFTR gene of six Taiwanese CFpatients were identified. 8 Mutations in Thai CF patients havealso been recently reported. 9 With the increasing number ofmutations identified in the Asian CF population, the mutationspectrum can be determined and molecular diagnosis of carriersand prenatal testing will become available. Here we reportthe first prenatal exclusion of CF in a family with previouslyaffected children in Taiwan.Case reportA 28-year-old, gravida 3, para 2, 8 week-pregnant, Vietnamesewoman, was referred for prenatal diagnosis because herCorrespondence: Boris Bao-Tyan Wang, PhD, Center for GeneticCounseling and Medical Genetics, Changhua Christian Hospital,Changhua , Taiwan. Email: 90486@cch.org.tw* Present address: Department of Molecular and Human Genetics,Baylor College of Medicine, Houston, TX 77030, USA.†Present address: Department of Medical Biology-Genetics,School of Medicine, Akdeniz University, Antalya 07070, Turkey.Received 20 May 2005; revised 8 November 2005; accepted 29November 2005.previous children had died of CF. Her husband was a47-year-old Taiwanese man. Consanguinity was denied.Their first two children had CF. The autopsy of their deceaseddaughter showed evidence of CF but DNA analysis was notperformed. The affected son suffered from intestinal obstructionat 7 months of age, had a history of severe cough,poor appetite, and recurrent respiratory tract infection withpneumonia. Cultured sputum showed colonization ofPseudomonas aeruginosa and Staphylococcus epidermidis .Based on the mucosal plugging, bronchiectasis, echogenicbowel, developmental delay, steatorrhea, and elevated sweatchloride (89 mEq/L), the diagnosis of CF was made. Analysisof a panel of 86 pan-ethnic mutations by Genzyme GeneticsInc. (Framingham, MA, USA) did not find any CFTR mutations.Because autopsy analysis of his deceased older sisterdemonstrated evidence of CF, the strong family history andclinical indication led to a comprehensive mutational analysisof the entire CFTR gene using TTGE. 4,5 Two novel nullmutations were identified: c.19G>T in exon 1, whichchanged a glutamate at amino acid residue 7 to a stop codon(p.E7X), and c.857 – 860insA, which caused frameshift and atruncated CFTR protein of 306 amino acids. 8 The patientdied at 1 year and 6 months of age. Analysis of parents’ DNAconfirmed their carrier status ( Fig. 1 ).Two years later, the woman was pregnant. Because theCFTR mutations in this family had been identified, prenataldiagnosis was offered. DNA isolated from cultured amniocyteswas analyzed and the fetus was found to be heterozygousfor c.857 – 860insA, a frameshift mutation resultingin a truncated CFTR protein. 4,8 Routine cytogenetic analysisshowed the fetus to have a 46, XY, normal male karyotype.In December 2004 a healthy baby weighing 3500 gwas delivered in Vietnam at full term. The child has survivedwell and healthy beyond 10 months of age at time ofwriting. Tests for pancreatic function including 72 h fecalfat excretion and fecal elastase showed no evidence of pancreaticinsufficiency. The sweat chloride analysis was notperformed.© 2007 Japan Pediatric Society

Author(s): Karauzum SB (Karauzum, Sibel Berker), Yasar D (Yasar, Duygu), Dirice E (Dirice, Ercument), Imir N(Imir, Nilufer), Luleci G (Luleci, Guven), Ozes ON (Ozes, Osman Nidai)Source: GROWTH FACTORS Volume: 25 Issue: 2 Pages: 94-100 Published: 2007Times Cited: 0 References: 30 Citation MapAbstract: Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with pathologicalmanifestations usually including splenomegaly and panctopenia. Interferons ( IFNs), specifically of the alphasubtypes have shown a significant anti-tumor effect in HCL patients, with improvement of hematologicalparameters within the first few months of treatment. However, the therapeutic effect of IFN-alpha is still ratherlimited. The mechanisms responsible for the beneficial action of IFN-alpha in HCL patients are unclear. Acontinuous line of cells (Eskol) from a patient diagnosed with HCL was established and shown to have severalproperties of HCL. Even though, Eskol cells are very resistant to anti-proliferative activity of IFN-alpha, Daudicells, another human B-cell-derived cell line, are very sensitive to anti-proliferative activity of IFN-alpha and arecommonly used as a model cell to test anti-proliferative effect of IFN-alpha. To understand the molecularreason(s) behind the observed obvious differences to IFN sensitivity of above cells, we have analyzed theexpression levels of BCL2, caspase-1, Laminin and PARP in these cells. We found that Daudi cells do notexpress BCL2 at all, and probably because of that, these cells have constantly cleaved, and probably activatedform of caspase-1. However, when we overexpresed BCL2 in these cells, they lost processed form of caspase-1and became resistant to anti-proliferative activity of IFN-alpha. These results let us to suggest that IFN-alphasensitivity of B-cell lymphomas, once again, depends on the presence or absence of BCL2.Document Type: ArticleLanguage: EnglishAuthor Keywords: BCL2; HCL; IFN alpha; daudi; eskolKeyWords Plus: CONVERTING-ENZYME EXPRESSION; INTERLEUKIN-1-BETA-CONVERTING ENZYME;IMMUNE-SYSTEM; CARD PROTEIN; C-MYC; CASPASE-1; LEUKEMIA; DEATH; IDENTIFICATION;ACTIVATIONŀLack of BCL-2 confers interferon-alpha sensitivity to B-cell lymphomasReprint Address: Ozes, ON (reprint author), ON OzesInterMune Inc, 3280 Bayshore Blvd, Brisbane, Qld 94005AustraliaAddresses:1. ON OzesInterMune Inc, Brisbane, Qld 94005 Australia2. Akdeniz Univ, Dept Med Biol & Genet, TR-07070 Arapsuyu, TurkeyE-mail Addresses: oozes@intermune.comPublisher: TAYLOR & FRANCIS LTD, 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON,ENGLANDSubject Category: Cell Biology; Endocrinology & MetabolismIDS Number: 213DIISSN: 0897-7194DOI: 10.1080/08977190701345515

prostate tissues.Sanlioglu AD, Koksal IT, Ciftcioglu A, Baykara M, Luleci G, Sanlioglu S.Human Gene Therapy Unit, Faculty of Medicine, Akdeniz University, Antalya, Turkey.AbstractPURPOSE: Because TRAIL (tumor necrosis factor related apoptosis inducing ligand) selectively kills cancer cellswithout damaging normal cells, a gene therapy approach using TRAIL is feasible for treating patients with cancer.However, recent publications suggest that significant portions of human tumors appear to be TRAIL resistant.Furthermore, there is some controversy about whether TRAIL receptor composition influences TRAIL sensitivity incancer cells. Our recent studies suggest that TRAIL receptor composition is the major modulator of TRAILsensitivity, as demonstrated using prostate, breast and lung cancer cells. We investigated TRAIL and TRAILreceptor expression profiles during prostate carcinogenesis to evaluate their potential as biomarkers and predictthe feasibility of a related gene therapy approach.MATERIALS AND METHODS: Paraffin embedded prostate tissues of 44 patients with benign prostatichyperplasia, 28 with organ confined prostate carcinoma and 26 with advanced prostate carcinoma were analyzedusing immunohistochemical staining procedures.RESULTS: Significant levels of TRAIL-R4 decoy receptor expression were detected in patients with benignprostatic hyperplasia, and organ confined and advanced prostate carcinoma. All TRAIL markers tested appear tobe valuable markers for separating patients with benign prostatic hyperplasia from patients with organ confinedprostate carcinoma or advanced prostate carcinoma.CONCLUSIONS: Due to high TRAIL-R4 expression in all patient groups complementary gene therapy modalitiesmight be needed to bypass potential TRAIL-R4 induced resistance.ŀDifferential expression of TRAIL and its receptors in benign and malignant

Hereditary Cancer in Clinical Practice 2007; 5(1) pp. 53-55Short report. The AIDIT and IMPACT conference 2006:Outcomes and future directionsR Doherty 1 , J Lubinski 2 , E Manguoglu 3 , G Luleci 3 , M Christie 4 , P Craven 4 , E Bancroft 5 , A Mitra 1 , S Morgan 1 , R Eeles 1,4 on behalfof the IMPACT steering committee † and collaborators*1 Translational Cancer Genetics Team, The Institute of Cancer Research, London, United Kingdom; 2 International Hereditary Cancer Centre, Pomeranian MedicalUniversity, Szczecin, Poland; 3 Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, Antalya, Turkey; 4 Research Services, The Instituteof Cancer Research, London, United Kingdom; 5 The Royal Marsden NHS Foundation Trust, London, United KingdomCorresponding author: Rosalind Eeles MA, PhD, FRCR, FRCP, Reader in Clinical Cancer Genetics and Honorary Consultantin Cancer Genetics and Clinical Oncology, Cancer Genetics Unit, The Royal Marsden NHS Foundation Trust, Downs Road,Sutton, Surrey, SM2 5PT, United Kingdom, phone +44 20 866 138 97, fax +44 20 877 014 89Submitted: 12 January 2007Accepted: 1 February 2007IntroductionIMPACT (Identification of Men with a geneticpredisposition to ProstAte Cancer: Targeted screening inBRCA1/2 mutation carriers and controls) is aninternational collaboration investigating the utility oftargeted prostate-specific antigen (PSA) screening for menat increased risk of prostate cancer due to inheritedpredisposition. Although the majority of prostate canceroccurs sporadically, it is recognized that family historyplays a role in a significant number of cases: a familyhistory either of prostate cancer alone [1], or of othercancers including breast and ovarian cancer [2]. Evidenceof the link between single genes and prostate cancer riskis strongest for the BRCA1 and BRCA2 genes [3-5], withBRCA2 in particular thought to lead to a relative risk of4.65 (95%CI 3.48-6.22). This relative risk may be ashigh as 7.33 in men under the age of 65 years.Population prostate cancer screening remainscontroversial because of the potential for detection ofclinically insignificant disease in young men and the riskof over-treatment. There is increasing interest andconcern in European countries about whether prostatecancer screening should be offered to the generalpopulation and whether this would lead to a reductionin mortality from prostate cancer. IMPACT raises thehypothesis that targeting screening at the men in thepopulation who are known to have an increased risk ofthe disease might improve the effectiveness of prostatecancer screening. Beginning with a pilot of 100 patients,the IMPACT study ultimately aims to recruit a total of 850carriers of mutations in BRCA1 and BRCA2 and 850controls (men shown not to carry familial BRCA1/2mutations by predictive genetic testing). Recruitment willbe open for five years, followed by five years of follow-up.In 2005, a project known as AIDIT (AdvancingInternational co-operation and Developing Infrastructurefor Targeted screening of prostate cancer inmen with genetic predisposition) was awarded fundingthrough the EC Framework 6 Programme as part of anendeavour to reduce research fragmentation andduplication, and to facilitate research collaborationacross Europe. IMPACT currently includes collaboratorsfrom 24 countries. AIDIT’s aim is to expand theIMPACT consortium within the associated candidatecountries (ACCs) and new member states of the EU.The expansion of IMPACT is likely to benefit both thestudy and the research teams: a higher number ofcollaborating centres will allow access to a largernumber of men at risk, making it possible to recruit asmany carriers as are needed for the study, particularlyin populations likely to harbour founder mutations; andfor all collaborators – both new and existing – it ishoped that participation in AIDIT and IMPACT will fosteran environment of ongoing interaction and learning.Hereditary Cancer in Clinical Practice 2007; 5(1) 53

Combination of Hb Knossos [Cod 27 (G-T)] and IVSII-745 (C-G) in aTurkish patient with beta-thalassemia major.Test. 2007 Fall;11(3):228-30.Keser I, Manguoglu E, Kayisli O, Yesilipek A, Luleci G.Department of Medical Biology and Genetics, Medical School, Akdeniz University, 07070, Antalya, Turkey.keser@akdeniz.edu.trAbstractBeta-thalassemia is the most common disease among hemoglobinopathies in Antalya, Turkey, as well as worldwide.Mutations found in Turkish beta-thalassemia patients constitute a heterogeneous group, consisting mostlyof point mutations. Only in very rare cases did deletions or insertions cause affected or carrier phenotypes. HbKnossos [beta 27 (B9) Ala-Ser] is a rare variant with a normal HbA2 level. In this study, we aimed to investigatethe effect of compound heterozygosity for Hb Knossos [Cod 27 (G-T)] and IVSII-745 (C-G). To our knowledge,this is the first report of such a combination related with beta-thalassemia major phenotype in a Turkish family,where reverse dot blot hybridization (RDBH) and DNA sequencing analysis were used. Heterozygous inheritanceŀGenetof the mutation results in mild beta-thalassemia phenotype, whereas homozygous inheritance leads tointermediate beta-thalassemia. As a result, the compound heterozygosity of Hb Knossos with IVSII-745 appearsas the cause of the beta-thalassemia major phenotype in our case. The combination of these mutations [HbKnossos, Cod 27 (G-T), and IVSII-745, C-G] causes the beta-thalassemia major phenotype, and this is importantfor genetic counseling.PMID: 17949282 [PubMed - indexed for MEDLINE]

1-Sener B, Tunçkanat F, Ulusoy S, Tünger A, Söyletir G, Mülazımoğlu L, Gürler N, Öksüz L,Köksal I, Aydın K, Yalçın AN, Ogunc D, Acar A, Sievers J:A survey of antibiotic resistance inStreptococcus pneumoniae and Haemophilus influenzae in Turkey, 2004 2005.J AntimicrobChemother60(3):587-593, 2007.2-Ataman S, Colak D, Günseren F, Senol Y, Colak T, Aktekin MR, Gültekin M. [Investigationof cytomegalovirus seroepidemiology in Antalya with a population-based cross-sectionalstudy and review of related data in Turkey] Mikrobiyol Bul. 2007 Oct;41(4):545-55.ŀTıbbi Mikrobiyoloji Anabilim Dalı

A survey of antibiotic resistance in Streptococcus pneumoniae and Haemophilusinfluenzae in Turkey, 2004 2005.Antimicrob Chemother. 2007 Sep;60(3):587-93. Epub 2007 Jun 26.Sener B, Tunçkanat F, Ulusoy S, Tünger A, Söyletir G, Mülazimoğlu L, Gürler N, Oksüz L, Köksal I, Aydin K, Yalçin AN, Oğünç D, AcarA, Sievers J.Department of Microbiology and Clinical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.AbstractOBJECTIVES: To determine the prevalence of antimicrobial resistance among Streptococcus pneumoniae and Haemophilus influenzaeisolated in Turkey as part of Survey Of Antibiotic Resistance, a surveillance programme in the Africa and Middle East region examiningthe antimicrobial susceptibility of key bacterial pathogens involved in community-acquired respiratory tract infections (CARTIs).METHODS: Susceptibility was evaluated against a range of antimicrobial agents using disc diffusion and Etest methods.RESULTS: Six centres in five cities collected 301 S. pneumoniae and 379 H. influenzae isolates between October 2004 and November2005. Among S. pneumoniae, the prevalence of isolates with intermediate susceptibility (MICs 0.12-1 mg/L) and resistance to penicillin(MICs >or=2 mg/L) was 24.6% and 7.6%, respectively; there was a wide variation between cities (2.4% to 36.9% intermediate and 0% toŀJ23.8% resistant phenotypes). Macrolide-azalide resistance rates exceeded those of penicillin resistance in all cities. Overall, 5.0% ofisolates were co-resistant to penicillin and erythromycin and 10.0% were multidrug-resistant (joint resistance to erythromycin, cotrimoxazoleand tetracycline). Agents tested to which over 90% of countrywide S. pneumoniae isolates remained susceptible wereamoxicillin/clavulanate (98.7%), chloramphenicol (94.7%) and cefprozil (90.6%). Overall, the percentage of H. influenzae isolatesproducing beta-lactamase was 5.5%, differing widely across the country with the highest prevalence of beta-lactamase productiondetected in Trabzon (14.0%) and no beta-lactamase-positive isolates found in Izmir. H. influenzae had the highest per cent susceptibilityto amoxicillin/clavulanate (99.5%) and ofloxacin (99.2%) while >20% were resistant to co-trimoxazole.CONCLUSIONS: Prevalence of penicillin and macrolide-azalide resistance among S. pneumoniae appears to be on the increase inTurkey while overall beta-lactamase production in H. influenzae remains relatively low. To adequately monitor the spread of drugresistantphenotypes among these two important CARTI pathogens, ongoing collection of resistance surveillance data is required-wherepossible locally as resistance patterns can vary substantially between cities and institutions.PMID: 17597058 [PubMed - indexed for MEDLINE]

Bul. 2007 Oct;41(4):545-55.[Investigation of cytomegalovirus seroepidemiology in Antalya with apopulation-based cross-sectional study and review of related data inTurkey]Ataman S, Colak D, Günseren F, Senol Y, Colak T, Aktekin MR, Gültekin M.Akdeniz Universitesi Tip Fakültesi, Tibbi Mikrobiyoloji Anabilim Dali, Antalya.AbstractSince there are numerous studies on CMV seroprevalence in various groups in Turkey, the number of populationbased, age-stratified cross-sectional studies which include epidemiological characteristics of the virus are limited.The aim of the study was to investigate the age-stratified seroprevalence and epidemiological characteristics ofCMV infection in Antalya (a province located in Mediterranean region of Turkey). Study group was selected bycluster sampling method. The sample size was calculated as 360 subjects (151 male, 209 female; age range: 1-49 years, mean age: 22.5 +/- 14.4 years), with an expected prevalence rate of 80%, at a confidence level of 95%and a sample error less than 5%. With the thought of the presence of maternal antibodies, 0-1 year age groupŀMikrobiyolwas not included to the study. Serum samples have been screened for CMV-IgG, and those given negativeresults were also searched for CMV-IgM by a commercial microELISA (Radim, Italy) test. The overallseroprevalence of CMV-IgG was found as 93.6% (337/360) in Antalya municipality and IgM positivity was notdetected in CMV-IgG negative sera. An increase in the seroprevalence rates was observed with age (p < 0.001),and the rate was found quite high (93.3%) for the first year of life. The seropositivities in the age groups of 1-6, 7-14 and 14-49 years were detected as 82.1%, 92% and 97.8%, respectively. The seroprevalence rate of 82.1%before the age of seven has rised to 96.8% after that age, and being > or =7 years old was found statisticallysignificant in terms of CMV infection (p < 0.001, OR: 6.635). Ages one and seven were found to be the criticalages for CMV infection in our region. CMV seropositivity was 97.4% in woman at childbearing age (15-49 years).Gender, marital status, education, living area, residence, income, history of sexually transmitted diseases,surgery, blood transfusion and day care attendance did not contribute independently to the seroepidemiology ofCMV (p > 0.01). In addition, the data of this study were evaluated and discussed together with the resultsobtained from the other Turkish studies, as far as accessible. In conclusion, since CMV seroepidemiology inTurkey differs as the socioeconomic changes occur, the changes in CMV serostatus and dire consequences ofhigh seroprevalence rates on public health should be evaluated with prospective, population based studies infurther years.

1-Cubukcu S, Alimoglu MK, Samancıi N, Gurbuz UIsokinetic and isometric muscle strength of theknee flexors and extensors in patients with the Fibromyalgia syndromeand chronic Myofascial painsyndromeJOURNAL OF MUSCULOSKELETAL PAIN15(3): 49-55,20072-Turkay M, Senol Y, Alimoglu MK, Aktekin MR, Deger N.Missed opportunities for coronary heartdisease diagnoses:Primary care experienceCMJ48(3)3: 362-370,2207ŀTıp Eğitimi Anabilim Dalı - 2007

Public HealthMissed Opportunities for Coronary Heart Disease Diagnoses: Primary CareExperienceMehtap Turkay 1 , Yesim Senol 1 , Mustafa Kemal Alimoglu 1 , Mehmet R. Aktekin 2 ,Necmi Deger 3> Correspondence to:1Department of MedicalEducation, Akdeniz UniversityFaculty of Medicine,Antalya, Turkey2Department of Public Health,Akdeniz University Faculty ofMedicine,Antalya, Turkey3Department of Cardiology,Akdeniz University Faculty ofMedicine,Antalya, TurkeyMehtap TurkayDepartment of Medical EducationAkdeniz University Faculty of Medicine07059 Antalya, Turkeymehtapturkay@akdeniz.edu.tr> Received: October 9, 2006> Accepted: March 14, 2007> Croat Med J. 2007;48:362-70Aim To investigate missed opportunities to reveal existing but not formerlydiagnosed coronary heart disease cases and related risk factors inprimary health care.Methods The study comprised 850 people aged over 30 years with noknown history of coronary heart disease, receiving health services froma primary care center located in a suburban area of Antalya, Turkey.Data on their age, gender, education level, health insurance status, income,smoking behavior, and physical activities were collected. Undiagnosedcoronary heart disease patients were determined by the Rosequestionnaire, physical examination, and electrocardiogram. Heightand weight, blood pressure, serum glucose and cholesterol levels weremeasured, and body-mass index and waist-hip ratio calculated. Eachpatient was given a risk score regarding age, smoking behavior, systolicblood pressure, and cholesterol levels. Estimated risk ratio of eachperson for developing coronary heart disease in the next decade wasdetermined.Results The number of formerly undiagnosed coronary heart diseasecases was 126 (14.8%). Overall mean (±standard deviation) risk scorefor developing coronary heart disease in the next decade in study groupwas 6.1 ± 6.8. Diseases facilitating development of coronary heart disease:hypertension, diabetes, and hypercholesterolemia were presentin 255 (30.4%), 70 (8.2%), and 364 (43.4%) participants, respectively.Obesity was detected in 315 (37.1%) subjects and there were 222(26.1%) current smokers. For patients who attended primary healthcare, the estimated percentage risk for developing coronary heart diseasein the next ten years was 7 to 45% in men and 2 to 45% in women.Conclusion Opportunities to reveal coronary heart disease and its riskfactors are being missed in primary care. Measures should be taken toensure timely diagnosis of coronary heart disease and related risk factors.362 www.cmj.hr

and isometric muscle strength of the knee flexors and extensors in patientswith the Fibromyalgia syndrome and chronic Myofascial pain syndromeAuthor(s): Cubukcu S (Cubukcu, Sibel), Alimoglu MK (Alimoglu, Mustafa Kemal), Samanci N (Samanci, Nehir),Gurbuz U (Gurbuz, Ulku)Source: JOURNAL OF MUSCULOSKELETAL PAIN Volume: 15 Issue: 3 Pages: 49-55 Published:2007Times Cited: 1 References: 25 Citation MapAbstract: Objectives: To compare Muscular performance of the patients with the fibromyalgia syndrome [FMS]and chronic myofascial pain syndrome [MPS] with each other and with healthy normal controls [HNCs].Methods: Maximum voluntary isokinetic and isometric muscle strength of the knee extensors and flexors in thedominant limb was measured using an isokinetic dynamometer in 18 patients with FMS. 16 patients with NIPS,and 36 HNCs. The participants performed five repetitions of flexion and extension at 60 degrees per second[degrees/s] and 180 degrees/s for isokinetic measurements. Isometric performance was measured at 30degrees/s and 60 degrees/s.Results: Gender [all were female], age, physical activity levels, body mass index of the three groups. anddisease duration of the two patient 0 groups were similar. Peak torques and total work in both flexion andextension were lower both patient groups compared to HNCs. Mean peak torque of the knee flexors was lowerin FMS than NIPS. Total work did not differ between FMS and NIPS. Flexor and extensor endurance ratio inthe FMS and MPS groups were not different from each other and from that of HNCs. Isometric strength of theknee flexors and extensors were lower both patient groups than in HNCs. Isometric strength of knee flexors at30/s was lower FMS compared to MPS.Conclusion: Muscular performance both of FMS and NIPS patient groups was low compared to HNCs. The FMSpatients showed lower isokinetic flexion and isometric extension strength than the MPS patients at someparticular speeds.Document Type: ArticleŀIsokineticLanguage: EnglishAuthor Keywords: muscle strength; the knee; fibromyalgia syndrome; chronic myofascial painKeyWords Plus: MAGNETIC-RESONANCE-SPECTROSCOPY; PHYSICAL-ACTIVITY QUESTIONNAIRE;ABNORMALITIES; RHEUMATOLOGY; RELIABILITY; PERFORMANCE; VALIDITY; WOMEN; WORKReprint Address: Alimoglu, MK (reprint author), Akdeniz Univ Fac Med, Dept Med Educ, TR-07059 Antalya,TurkeyAddresses:1. Akdeniz Univ Fac Med, Dept Med Educ, TR-07059 Antalya, Turkey2. Akdeniz Univ Fac Med, Dept Phys Med & Rehabil, TR-07059 Antalya, TurkeyE-mail Addresses: scuhukcu@akdeniz.cdu.tr, kalimoglu@akdeniz.edu.tr, nehirsamanci@akdeniz.edu.tr,ulkugurbuz@akdeniz.edu.trPublisher: HAWORTH PRESS INC, 10 ALICE ST, BINGHAMTON, NY 13904-1580 USASubject Category: Rehabilitation; RheumatologyIDS Number: 203SLISSN: 1058-2452DOI: 10.1300/J094v15n03_07

1-Ozdem S, Bayraktar T, Oktay C, Sari R, Gultekin M.The prevalence of asymptomatic pyuria indiabetic patients: Comparison of Sysmex UF-100 automated urinalysis analyzer with Fuchs-Rosenthal hemacytometer.Clin Biochem39:873-878, 20062-Soyuncu S, Oktay C, Berk Y, Eken C.Abamectin intoxication with coma and hypotension.ClinToxicol45(3):299-300, 20073-Soyuncu S, Cete Y, Bozan H, Kartal M, Akyol AJ. Accuracy of physical and ultrasonographicexaminations by emergency physicians for the early diagnosis of intraabdominal haemorrhage inblunt abdominal traumaInjury38;5, 564-69, 20074-Eken C.Statistical or clinical significance? A critical point in interpreting medical data. Am J EmergMed25:589, 20075-Eken C, Kilicaslan I.Differences between various glomerular filtration rate calculation methods inpredicting patients at risk for contrast-induced nephropathy. Am J Emerg Med25:487, 20076-Eken C. The relationship of air pollution to ED visits for asthma differs between children and adults.Am J Emerg Med. 2007 Sep;25(7):852ŀAcil Tıp Anabilim Dalı

Clinical Toxicology (2007) 45, 299–300Copyright © Informa HealthcareISSN: 1556-3650 print / 1556-9519 onlineDOI: 10.1080/15563650601072225LCLTCASE REPORTAbamectin intoxication with coma and hypotensionAbamectin Intoxication with Coma and HypotensionSECGIN SOYUNCU, CEM OKTAY, YELIZ BERK, and CENKER EKENAkdeniz University Faculty of Medicine, Department of Emergency Medicine, Antalya, TurkeyClinical Toxicology Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/11/10For personal use only.Abamectin is a potent antihelmintic, insecticide, and miticide used to control pests of humans, veterinary animals, and crops. The toxiceffects of abamectin are usually seen after oral ingestions. These are altered mental status, respiratory failure, and hypotension. We report acase of acute abamectin intoxication who presented with altered mental status to the emergency department after oral ingestion.KeywordsIntroductionAbamectin intoxication; AvermectinsAbamectin is a potent antihelmintic, insecticide, and miticideused to control pests of humans, veterinary animals, andcrops. Avermectins were first derived in 1977 from Streptomycesavermitilis (species of Actinomyces) as a product ofnatural fermentation. These macrocyclic lactones have twokinds of series, A and B. The B series are effective againsthelminths and arthropods (1,2).Abamectin is a mixture of avermectins containing >80%avermectin B1a and

Injury, Int. J. Care Injured (2007) 38, 564—569www.elsevier.com/locate/injuryAccuracy of physical and ultrasonographicexaminations by emergency physicians for theearly diagnosis of intraabdominal haemorrhage inblunt abdominal traumaS. Soyuncu *, Y. Cete, H. Bozan, M. Kartal, A.J. AkyolDepartment of Emergency Medicine, Faculty of Medicine, Akdeniz University,Dumlupinar Bulvari 07059, Antalya, TurkeyAccepted 10 January 2007KEYWORDSUltrasound;Blunt abdominaltrauma;Emergency physician;Physical examinationSummaryObjective: To determine the accuracy of physical examination and ultrasonographicevaluation performed by emergency physicians in cases of blunt abdominal trauma forthe early diagnosis of intraabdominal haemorrhage.Methods: In this clinical prospective study, trauma patients were evaluated withfour-quadrant ultrasonography by emergency physicians after initial stabilisation andphysical examination. Diagnoses based on demographic data, physical examinationand emergency physician’s ultrasonography were compared with the subsequentclinical course.Results: A total of 442 patients participated in the study. The sensitivity andspecificity of emergency physician’s ultrasonographic examination to detect intraabdominalhaemorrhage were 86 and 99%, respectively. Pre-test sensitivity and specificityof physical examination to detect intraabdominal haemorrhage were 39 and90%, respectively.Conclusions: Physical examination was not a reliable method to detect intraabdominalhaemorrhage in cases of blunt abdominal trauma. In contrast, abdominal ultrasonographyperformed by emergency physicians was a reliable diagnostic tool.Emergency physicians should be familiar with abdominal ultrasonographic examination,which should be routine in cases of blunt abdominal trauma.# 2007 Elsevier Ltd. All rights reserved.* Corresponding author. Tel.: +90 242 249 6183; fax: +90 242 2274490.E-mail address: ssoyuncu@akdeniz.edu.tr (S. Soyuncu).0020–1383/$ — see front matter # 2007 Elsevier Ltd. All rights reserved.doi:10.1016/j.injury.2007.01.010

Correspondence 589doi:10.1016/j.ajem.2006.10.015ReferencesMichel Baer MDMarcel Chauvin MD, PhDDominique Fletcher MD, PhDH˛ôpital Raymond PoincaréAP-HP, 92380 Garches, France[1] ACC/AHA guideline update for the management of patients withunstable angina and non-ST segment elevation myocardial infarction—2002. A report of the American College of Cardiology/American HeartAssociation Task Force on practice guidelines. Circulation2002;1:1893-900.[2] Task Force report: management of acute coronary syndromes inpatients presenting without persistent ST-segment elevation SH. EurHeart J 2002;23:1809-40.[3] Newby LK, Storrow AB, Gibler WB, et al. Bedside multimarker testingfor risk stratification in chest pain units. The chest pain evaluation bycreatine kinase-MB, myoglobin and troponin I (CHEKMATE) study.Circulation 2001;103:1832-7.[4] Wu AH, Apple FS, Gibler WB, et al. National academy of clinicalbiochemistry standards of laboratory practice: recommendations for theuse of cardiac markers in coronary artery diseases. Clin Chem 1999;45:1104-21.[5] Hudson MP, Christenson RH, Newby LK, et al. Cardiac markers: pointof-caretesting. Clin Chim Acta 1999;284:223-37.[6] Gust R, Gust A, Bottiger W, et al. Bedside Troponin T testing is notuseful for early out-of-hospital diagnosis of myocardial infarction. ActaAnaesthesiol Scand 1998;42:414-7.[7] Hsu LF, Koh TH, Lim YL. Cardiac marker point-of-care testing:evaluation of rapid on site biochemical marker analysis for diagnosis ofacute myocardial infarction. Ann Acad Med Singapore 2000;29:421-7.[8] Panteghini M, Cuccia C, Pagani F, et al. Comparison of thediagnostic performance of two rapid bedside biochemical assays inthe early detection of acute myocardial infarction. Clin Cardiol 1998;21:394-8.Statistical or clinical significance? A critical point ininterpreting medical dataTo the Editor,First of all, I would like to thank Drs Vukmir and Katzfor their great article, bSodium bicarbonate improvesoutcome in prolonged prehospital cardiac arrestQ [1], andto Dr Pallin for his comments touching on the statisticalerror in the article, which we have also noticed, and theinformation about the subset analysis [2].However, there are 2 important errors in Dr Pallin’scomments.First problem. After showing the erroneous structuring of2 2 cross table for prolonged (N15 minutes) cardiac arrest,he reported a P value of .15 for the comparison of19 (32.8%) of 58 vs 8 (15.4%) of 52. However, a samplesize with 97 patients is enough to detect a difference of 17%(http://stat.ubc.ca/~rollin/stats/ssize/b2.html). And therewere 137 patients in this v 2 analysis. The correct P valuefor this analysis is .035, which was calculated with acommercial statistical software (SPSS 13.0 for Windows)and also manually. Drs Vukmir and Katz also stated thecorrect P value in their reply.Second problem. Dr. Pallin distracted our attention to the2 important risks in the subset analyses. But he overlooked amore important risk in subset analyses in that the subsetsusually have lack of power to detect significant differencesbecause of their smaller sample size than the total, like in thearticle by Drs Vulkin and Katz [1]. To make a definitecomment that bicarbonate is not effective for the treatment ofcardiopulmonary arrest in the prehospital setting after the v 2analysis for 19 (12%) of 158 vs 8 (6%) of 135 patients with aP value of .07 is a huge error—because to interpret theresults by just considering the P value does not give the trueanswer. Let me explain why. A total of 356 patients areneeded to detect a 6% difference with 80% power and ana value of .05. So, if you increase the sample size adequately,you can obtain a statistically significant result. For instance,if you take 2-fold of the 2 2 cross table noted previously,you will obtain a new cross table of 38 (12%) of278 vs 16 (6%) of 254. As you see, the difference andproportions are still the same but now the P value is .011.Thus the difference becomes statistically different. Tointerpret the results just considering the P value like DrPallin did or according to the proportions that Dr Vukmir andKatz stated, that there was a 2-fold increase in survival rate inthe bicarbonate group, are both incorrect. Thus, a criticalquestion emerges: how do you interpret the results of thisarticle [1]? Calculating only the number of patients who needto be treated should be an alternative way of interpretingthese results. The absolute risk reduction in the bicarbonategroup in prolonged cardiac arrest is 6%. So the number ofpatients needing treatment is 17 (1/0.06). This means that1 patient is going to live for every 17 patients givenbicarbonate. This should make more sense to physicians.Patients who experience cardiac arrest longer than 15 minutescan lead physicians to despair because of its closeness todeath. A survival rate of 1 patient for every 17 patients givenbicarbonate in prolonged cardiac arrest may also beimportant for some physicians but not for others.The article by Drs Vukmir and Katz concludes that theseresults need to be validated by a further study with asufficient sample size to detect the significant difference inprolonged cardiac arrest.Cenker Eken MDAkdeniz University School of MedicineDepartment of Emergency Medicine07059 Antalya, TurkeyE-mail address: cenkereken@akdeniz.edu.trdoi:10.1016/j.ajem.2006.10.016References[1] Vukmir RB, Katz L. Sodium bicarbonate improves outcome inprolonged prehospital cardiac arrest. Am J Emerg Med 2006;24:156-61.[2] Pallin DJ. Sodium Bicarbonate improves outcome in prolongedprehospital cardiac arrest. Am J Emerg Med 2006;24:645-6.

ORIGINAL PAPERdoi: 10.1111/j.1742-1241.2005.00788.xThe consistency of emergency physicians’ and cardiologists’ ECGinterpretation and likelihood classification of chest pain patientsC. EKEN, 1 E. GOKSU, 1 O. ERAY, 1 S. YALCINKAYA 2Department of Emergency, 1 Department of Cardiology, 2 Akdeniz University Hospital, Antalya, TurkeySUMMARYPatients presenting to the emergency department withchest pain are evaluated by emergency physicians in hospitalswithout cardiology cover 24 h a day.The purpose of this study is to determine the consistencyof electrocardiography (ECG) interpretation andchest pain likelihood classification between emergencyphysicians and cardiologists.This randomised prospective cross-sectional study wasperformed in a tertiary care university hospital emergencydepartment. The study form included ECG interpretationand chest pain likelihood classification according toAmerican College of Cardiology (ACC) ⁄ American HeartAssociation (AHA) guideline which were recorded byemergency physicians and cardiologists separately in ablinded fashion. All chest pain patients who consultedwith a cardiologist were enrolled into the study duringthe study period. The consistency between the two groupsand the kappa value were calculated.Recorded study forms of 133 patients with cardiologyconsultations were evaluated. The consistency in the interpretationof ECG between the emergency physicians and cardiologistswas found to be 94.6% (kappa ¼ 0.85) for ST segmentelevation, 78.6% (kappa ¼ 0.57) for ischaemic ECG findingsand 79.3% (kappa ¼ 0.36) for dynamic ECG changes. Theconsistency for the likelihood classification between twogroups for predicting the pain as angina or non-cardiac was90.8% (kappa ¼ 0.30), for classifying as acute coronary syndromeor stable angina pectoris (SAP) was 95.6%(kappa ¼ 0.26) and for classifying patients as low likelihoodor intermediate-high likelihood was 86.3% (kappa ¼ 0.61).A strong consistency was shown between the emergencyphysicians’ and cardiologists’ ECG interpretation especiallyin determining the ST segment elevation. And also, there isa strong concordance in the likelihood classification ofchest pain patients.Keywords: Chest pain; ECG; emergency; cardiologyª 2006 Blackwell Publishing LtdINTRODUCTIONChest pain is the second most common cause of emergencydepartment presentations and still remains problematic foremergency department (ED) physicians (1). Most chest painpatients are evaluated firstly in the ED, and one-third of chestpain patients are ultimately diagnosed with an acute coronarysyndrome (ACS) (2). Because of the high mortality and morbidityrates due to ACS, these patients must be diagnosed and treatedrapidly. Despite clinical acumen, electrocardiography (ECG) andcardiac enzymes, 2–5% of patients with acute myocardial infarction(AMI) are discharged inappropriately from EDs (3–5).The ECG is non-diagnostic in 63.9% of patients with AMI inthe ED. Furthermore, ACS patients may present with atypicalCorrespondence to:Oktay Eray, Department of Emergency, Akdeniz UniversityHospital, Antalya, TurkeyTel.: þ 90 242 227 4343Fax: þ 90 242 227 4320Email: oktayeray@akdeniz.edu.trsymptoms (6,7). Despite the high sensitivity and specificity ofcardiac troponins, they may be normal in the first 6 h after onsetof symptoms. Therefore, the accurate interpretation of the ECGand the likelihood stratification of chest pain patients for coronaryarterydisease(CAD)areimportant.AsEDsarenotcoveredby cardiologists 24 h a day in most countries, ECG interpretationand pain classification of the chest pain patients are still mostlyperformed by emergency physicians or other practitioners workingin the emergency department. Although there are manystudies reporting a wide range of concordances between theemergency physicians and cardiologists, there is no study in theliterature comparing the emergency physicians’ and cardiologists’decision making regarding likelihood stratification of chest painpatients. The purpose of this study is to determine the consistencybetween these two physician groups in the management of chestpain patients by determining the concordance in ECG interpretationand the likelihood classification of chest pain which definesthe possibility of ACS secondary to CAD in a patient presentedwith chest pain to ED. It is not related to the future adversecardiac events defined by a risk classification tool in the sameguideline by American College of Cardiology (ACC) andAmerican Heart Association (AHA) (8).ª 2006 The AuthorsJournal compilation ª 2006 Blackwell Publishing Ltd Int J Clin Pract, October 2006, 60, 10, 1194–1197

852doi:10.1016/j.ajem.2007.01.012ReferencesFarnaz Gorouhi MDDepartment of Surgery22-Bahman HospitalMasjedsoleiman, IranDepartment of SurgeryIran University of Medical SciencesTehran, IranAli Jalali MDFarzam Gorouhi MDDepartment of SurgeryIran University of Medical SciencesTehran, Iran[1] Andersson RE, Hugander A, Ravn H. Repeated clinical and laboratoryexaminations in patients with an equivocal diagnosis of appendicitis.World J Surg 2000;24:479-85.[2] Surana R, Quinn F, Puri P. Is it necessary to perform appendicectomy inthe middle of the night in children? BMJ 1993;306:1168.[3] Alvarado A. A practical score for early diagnosis of acute appendicitis.Ann Emerg Med 1986;15:557- 65.[4] Winn RD, Laura S, Douglas C, et al. Protocol-based approach tosuspected appendicitis, incorporating the Alvarado score and outpatientantibiotics. A N Z J Surg 2004;74:324-9.[5] Eriksson S, Granstrom L. Randomized control trial of appendectomyversus antibiotic therapy for acute appendicitis. Br J Surg 1995;82:166-9.The relationship of air pollution to ED visits for asthmadiffers between children and adultsTo the Editor,I would like to thank to Sun et al for their article [1]investigating the relationship between air pollution andemergency department (ED) visits of asthma patients.However, there were some methodological and statisticalproblems in the article confusing the results.A critical question for the ED visits of asthmatic patientsis whether a seasonal change would be seen if the airpollution had not existed throughout the year. The responsewould most probably be yes. This is because asthma is adisease that is affected by so many factors such as pollensand viral epidemics, which Sun et al also stated in theirarticle; and these factors are important in the seasonaldistribution of asthma visits to the ED. Therefore, we canaccept them as confounding variables affecting asthmavisits to the ED. However, the critical point here is thesimilar seasonal distributions between these confoundingvariables and air pollution. Viral epidemics and airpollution were mostly seen in winter and autumn, whichwere also seen in the graphics depicted in the study of Sunet al. Therefore, to reveal the actual relation between airpollution and asthma attacks, we have to remove the effectsof confounding variables. Thus, we need a more homogenoussample free of confounding variables. For instance,we can constitute this sample by only using the months inwinter and autumn that we can control viral epidemics andpollens. In such a case, how can we determine the relationbetween air pollution and asthma attacks? To determine theED asthma visits and air pollution day by day is an option.After assigning days to have air pollution or not by using acutoff point, comparing asthma visits of the days that wereclassified as with and without air pollution by using v 2analysis should be a more accurate way both for themethodological construction and the statistical analysis ofthe study.Another incorrect analysis is to use the Pearsoncorrelation analyses to evaluate the relationship betweenair pollution and asthma. Pearson correlation analysesshould be carried out only by variables normally distributed.In this data set, there were only 12 values that belongto the months of the year. These data are probably notnormally distributed. We can also realize this error by usingthe graphics in the article. For example, SO 2 and NO 2 havesimilar seasonal distributions according to the graphics; butthe Pearson correlation coefficient was 0.128 for SO 2 and0.720 for NO 2 .Finally, there is probably a relation between asthma andair pollution that was also stated by other articles before.However, to prove this relation, another methodologicaldesign excluding confounding variables associated withseasons and using v 2 analysis instead of Pearson correlationcoefficient should be conducted to reveal a more accurateinformation about the relationship between asthma visits tothe ED and air pollution.ReferenceCenker Eken MDDepartment of Emergency MedicineAkdeniz University Medical Faculty07059 Antalya, TurkeyE-mail address: cenkereken@akdeniz.edu.trWe read with great interest the article by Williamson andcolleagues [1], who reviewed in detail the current knowldoi:10.1016/j.ajem.2007.01.022[1] Sun HL, Chou MC, Lue KH. The relationship of air pollution to EDvisits for asthma differs between children and adults. Am J Emerg Med2006;24(6):709- 13.Electrocardiographic prediction of acute left maincoronary artery occlusionTo the Editor,Correspondence

1-Yaman H, Atay E.PhD theses in Turkish sports sciences: A study covering the years 1988-2002.Scientometrics2007; 71(3): 415-4212-Haeri A, Hemmati P, Yaman H.What kind of curriculum can better address community needs?Problems arisen by Hypothetical-deductive reasoning.Journal of Medical Systems.2007;31:173-177.3-Yaman H, Kara IH.The Evaluatıon of Internatıonal Peer-Revıewed Publıcatıons In Turkısh FamılyMedıcıne.Medıcal Scıence Monıtor2007 Sep;13(9):SR24-27.4-Tufan I, Yaman H, Arun O. Disability in Turkey: Suggestions for overcoming currentproblems.International Social Work2007 50: 839-845.5-Soler JK, Yaman H, Esteva M. Burnout in European General Practice/Family Medicine-One PageResearch NoteSocial Behavior And Personality2007, 35 (8), 1149-11506- Kara IH, Aydın N, Gemalmaz A, Aktürk Z, Yaman H, Bozdemir N, Habitual Tea Drinking and BoneMineral Density in Postmenopausal Turkish Women: Investigation of Prevalence of PostmenopausalOsteoporosis in Turkey (IPPOT Study). International Journal for Vitamin and utrition Research2007;77(6):389-397 (SCI-Expanded)7- Yaman H, Soler JK. Reportage - MRCGP(International) development day. Br J Gen Pract. 2007Dec;57(545):1004-5.ŀAile Hekimliği Anabilim Dalı

py is for personal use only - distribution prohibited. This copy is for personal use only - distribution prohibited. This copy is for personal use only - distribution prohibited. This copy is for personal use only - distribution prohibited. This copy is for personal use only - distribu© Med Sci Monit, 2007; 13(9): SR24-27PMID: 17767133Received: 2006.10.11Accepted: 2007.05.16Published: 2007.09.03Background:Material/Methods:Results:Conclusions:key words:Full-text PDF:Word count: 1760Tables: —Figures: 7References: 13Author’s address:SR24An evaluation of articles in international peer-reviewedpublications in Turkish family medicineHakan Yaman 1 , İsmail Hamdi Kara 21Akdeniz University, Faculty of Medicine, Department of Family Medicine, Antalya, Turkey2Dicle University, Faculty of Medicine, Department of Family Medicine, Diyarbakır, TurkeySource of support: This study was supported by the Akdeniz University Research FoundationSummaryScientific publication in Turkish family medicine (FM) has currently increased and a systematic assessmentof the quantity and quality of the published research is the aim of this study.The data were obtained from the Institute for Scientific Information Citation Databases (SCI,SCI-Expanded, SSCI, and A&HSCI) and the period between 1975–2005 was searched. Key wordssuch as “family practice”, “family medicine”, “primary care”, “primary medical care”, and “Turkey”were used and publications were classified according to the type of research, the number of authors,first authorship, the number of citations, and address. The classification was performed bytwo investigators and the inter-rater-reliability was found to be Cramer’s V=0.79 (p

1-R.Artan, A.Yılmaz, N.Aksoy, M.Akçam. Liver biopsy in the diagnosis of visceral leishmaniasis.Journal of Gastroenterology and Hepatology.2006; 21(1 pt2): 299-302.2-Akcam M, Elmas O, Yilmaz A, Caglar S, Artan R, Gelen T, Aliciguzel Y.Myeloperoxidase, xanthineoxidase and superoxide dismutase in the gastric mucosa of helicobacter pylori positive and negativepediatric patients. Mol Cell Biochem.2006, 290(1-2):125-130.3- Akcam M, Yildiz M, Yilmaz A, Artan R.Bone mineral density in response to two different regimes inrickets.Indian Pediatr.2006;43(5):423-7.4-Guven AG, Koyun M, Artan R, Dursun O, Baysal YE, Akman S.Severe lactic acidosis andnephrolithiasis in an infant-etiology?: Question.Pediatr Nephrol. 2006; 21(6):761-2.5-Kansu A, Doganci T, Akman SA, Artan R, Kuyucu N, Kalayci AG, Dikici B, Dalgic B, Selimoglu A,Kasirga E, Ozkan TB, Kuloglu Z, Aydogdu S, Bosnak M, Ertekin V, Tanir G, Haspolat K, Girgin N,Yagci RV.Comparison of two different regimens of combined interferon-alpha2a and lamivudinetherapy in children with chronic hepatitis B infection.Antivir Ther.2006;11(2):255-61.6-Yilmaz A, Akcam M, Gelen T, Artan R.Lamivudine and high dose interferon alpha 2a combinationtreatment in naive HBeAg positive immunoactive chronic hepatitis B in children: An EastMediterranean experience.European Journal of Pediatrics2007;166(3):195-9.7-Akcam M, Ozdem S, Yilmaz A, Gultekin M, Artan R.Serum ferritin, vitamin B(12), folate, and zinclevels in children infected with Helicobacter pylori.Dig Dis Sci.2007; 52(2):405-10.8-Akcam M, Artan R, Gelen T, Yilmaz A, Eren E, Uygun V, Cig H.Long-term aspects of nodulargastritis in children.Pediatr Int.2007; 49(2):220-5.ŀÇocuk Sağlığı ve Hastalıkları Anabilim Dalı9-Akcam M, Artan R, Yilmaz A, Akkaya B.An unusual cause of ascites: hemophagocyticlymphohistiocytosis.Indian Pediatr.2007; 44(5):371-4.10-Mihçi E, Taçoy S, Yakut S, Ongun H, Keser I, Kiliçarslan B, Bağci G, Lüleci G:Maternal origin andclinical findings in a case with trisomy 22.Turk J Pediatr49(3): 322-6, 2007.11-Mihci E, Tacoy S, Ozbilim G, Franco B:Oral-Facial Digital Syndrome Type 1.Indian Pediatr 44(11):854-856, 200712-Artac H, Coskun M, Karadogan I, Yegin O, Yesilipek A.Transferrin receptor in proliferation of Tlymphocytes in infants with iron deficiency.Int J Lab Hematol. 2007 Aug;29(4):310-5.13-Johnson CM, Lyle EA, Omueti KO, Stepensky VA, Yegin O, Alpsoy E, Hamann L,Cutting edge: Acommon polymorphism impairs cell surface trafficking and functional J Immunol. 2007Jun15;178(12):7520-4.14-Sallakci N, Coskun M, Berber Z, Gürkan F, Kocamaz H, Uysal G, Bhuju S, Yavuzer U, Singh M,Yeğin O.Interferon-gamma gene+874T-A polymorphism is associated with tuberculosis and gammainterferon response.Tuberculosis (Edinb). 2007 May;87(3):225-30.15- Yılmaz A, Bahat E, Yılmaz GG, Hasanoğlu A, Akman S, Guven AG. Adjuvant effect of vitamin Aon recurrent lower urinary tract infections. Pediatr Int. Jun;49(3):310-3 (2007)16- Koyun M, Gur Guven A, Filiz S, Akman S, Akbas H, Baysal YE, Dedeoglu N. Screening forhypercalciuria in schoolchildren: what should be the criteria for diagnosis?Pediatr Nephrol. 22(9):1297-301 (2007).

17- Bahat E, Kılıçarslan B, Akman S, Karpuzoğlu G, Gur Guven A. Comparison of pulse and oralsteroid in childhood membranoproliferative glomerulonephritis.J Nephrol. 2007 Mar-Apr;20(2):234-45.18- Bayazıt AK, Yalçınkaya F, Çakar N, Düzova A, Bircan Z, Bakkaloğlu A, Canpolat N, Kara N, ŞirinA, Ekim M, Öner A, Akman S, Mir S, Baskın E, Poyrazoğlu HM, Noyan A, Akil I, Bakkaloğlu S, SoyluA. Reno-vascular hypertension in childhood: a nationwide survey. Pediatr Nephrol. 22(9):1327-33(2007).

Blackwell Publishing AsiaMelbourne, AustraliaJGHJournal of Gastroenterology and Hepatology0815 93192006 Blackwell Publishing Asia Pty Ltd211299302Original Article Liver biopsy in visceral leishmaniasisR Artanet al.Journal of Gastroenterology and Hepatology ISSN 0815-9319HEPATOLOGYLiver biopsy in the diagnosis of visceral leishmaniasisReha Artan,* Aygen Yilmaz,* Mustafa Akçam* and Nazif Hikmet Aksoy †Departments of *Pediatric Gastroenterology, Hepatology and Nutrition, and † Pathology, Akdeniz University School of Medicine, Antalya, TurkeyKey wordsbiopsy, child, diagnosis, leishmaniasis, liver.Accepted for publication 19 December 2004.CorrespondenceDr Reha Artan, Department of PediatricGastroenterology, Hepatology and Nutrition,Akdeniz University School of Medicine,Dumlupinar, Bulvari 07070, Antalya, Turkey.Email: artan@akdeniz.edu.trdoi:10.1111/j.1440-1746.2006.04172.xAbstractAim: To determine whether liver biopsy might be useful in the diagnosis of visceralleishmaniasis when bone marrow examination and serologic tests are inconclusive.Methods: Over a 10-year period, liver biopsy was performed in five children with suspectedvisceral leishmaniasis when indirect hemagglutination tests and bone marrowaspirations were not diagnostic.Results: Leishmania amastigotes were seen in Kupffer cells in all patients. The accompanyingliver histopathological findings were ischemic necrosis in two children, macrovesicularsteatosis in two children, portal inflammatory inflammation in two children, andpiecemeal necrosis in one child. During the study period, 32 additional pediatric visceralleishmaniasis cases were diagnosed by bone marrow examination.Conclusion: Liver biopsy can be recommended for diagnosing suspected visceral leishmaniasisin children when serology and bone marrow aspiration are inconclusive.© 2006 Blackwell Publishing Asia Pty LtdIntroductionVisceral leishmaniasis (VL) typically affects children below5 years of age in the Mediterranean region (Leishmania infantum),America (L. chagasi) and older children and young adults inAfrica and Asia (L. donovani). 1 VL is particularly prevalent inIndia, China, Russia, north-east Africa, the Middle East, South andCentral America, and in European countries bordering theMediterranean. 2,3 The classic clinical features of high fever,marked splenomegaly, hepatomegaly and cachexia typicallydevelop approximately 6 months after the onset of the illness. Atthe terminal stages of VL the hepatosplenomegaly is massive,there is gross wasting, the pancytopenia is profound, and jaundice,edema, and ascites may be present. Elevated hepatic transaminaselevels and hyperglobulinemia that is mostly immunoglobulin G(IgG) are among detectable laboratory findings. 1The late stage of the illness is often complicated by secondarybacterial infections, which frequently are a cause of death. 4 Ayounger age at the time of infection and underlying malnutritionmay be risk factors for the development and more rapid evolutionof active VL. 1For the diagnosis of VL, leishmania amastigotes must be demonstratedin tissues. Results of smears or cultures of material frombone marrow, liver or spleen aspirations are usually diagnostic. 5Serologic testing by enzyme immunoassay, indirect fluorescenceassay, or direct agglutination is very useful in VL because of thevery high level of anti-leishmania antibodies.A negative serologic test result in an immunocompetent adult isstrong evidence against a diagnosis. 6 Serodiagnostic tests havepositive findings in only about half of the patients who are coinfectedwith HIV. 1In our setting, bone marrow aspirations or biopsies and indirecthemagglutination are used for the diagnosis of VL.We studied the diagnostic usefulness of liver biopsy for childrensuspected as having VL when the diagnosis is not apparenton bone marrow examination and indirect hemagglutinationtest.MethodsBetween 1993 and 2003, 32 children were diagnosed with pediatricVL by bone marrow aspiration and/or biopsy. During the sametime period, five additional children were suspected as having VLbut this was not proved by bone marrow aspiration or hemagglutinationtests.These five patients underwent liver biopsy. The biopsy specimenswere fixed in 10% formalin. Tissue sections were stainedwith hematoxylin-eosin and leishman’s stain (eosin-polychromemethylene blue; L-6254, Sigma, Taufkirchen, Germany). All specimenswere examined by the same pathologist.ResultsThe details of the five patients are summarized in Table 1. The ageof the patients ranged from 11 months to 14 years, and there werefour boys and one girl. Symptoms were mostly fever and abdominaldistention. Physical examination revealed hepatosplenomegalyand pallor.Journal of Gastroenterology and Hepatology 21 (2006) 299–302 © 2006 Blackwell Publishing Ltd 299

Pediatr Nephrol (2006) 21: 761–762DOI 10.1007/s00467-006-0077-7CLINICAL QUIZAyfer Gür Güven . Mustafa Koyun . Reha Artan .Oğuz Dursun . Yunus Emre Baysal . Sema AkmanSevere lactic acidosis and nephrolithiasis in an infant—etiology?:QuestionReceived: 12 October 2005 / Revised: 19 November 2005 / Accepted: 30 November 2005 / Published online: 25 April 2006# IPNA 2006Case summaryA 4.5-month-old girl was admitted to the pediatric emergencyroom with dyspnea and tachypnea. Two weeks priorto admission the patient presented to a local hospital withrestlessness and was diagnosed with a urinary tract infection;she later developed gastroenteritis. She was feedingwith breast milk only. No history of increased susceptibilityto infections was described. Her brother died because ofsepsis and metabolic acidosis at the age of three months.There was also consanginuity between the parents.She exhibited Kussmaul breathing with a respiratory rateof 60/min, and tachycardia (176/min) without fever or anyfinding of heart failure. Height, weight and blood pressurepercentiles were in the normal ranges. Marked hepatosplenomegalywas detected on physical examination. The eyeexamination was normal.Laboratory studies revealed blood pH of 7.05, pCO 29.6 mm Hg, bicarbonate 2.4 mmol/L, base excess−25.1 mmol/L, sodium 143 mmol/L, potassium 3.9 mmol/L,chloride 94 mmol/L, anion gap 50.5 mmol/L, blood ureanitrogen 15 mg/dL, serum creatinine 0.44 mg/dL, total protein4.6 g/dL and albumin 3.0 g/dL. Serum had lipemic appearancewith a triglyceride level of 1988 mg/dL and cholesterol of296 mg/dL, HDL 68 mg/dL; SGOT 570 U/L (0–50), SGPT200 U/L (0–40), total bilirubin 0.15 mg/dL, calcium 9.7 mg/dL, phosphorus 4.3 mg/dL, uric acid 17.9 mg/dL, ammonia200 μg/dL, lactic acid 17.3 mmol/L (0.5–2.2), initial bloodglucose 63 mg/dL (while hypoglycemia levels of 22 and35 mg/dL glucose values were obtained during hospitalizationperiod), hemoglobin 10.2 g/dl, WBC 12,200/mm 3 with56% lymphocyte, thrombocyte count 733,000 mm 3 (control133,000). Urine pH was 6, specific gravity 1.030;glucose, reducing substances and ketone bodies werenegative.Urinary system ultrasonography demonstrated enlarged(80–81 mm) kidneys with normal echogenity and hyperdenseareas of 7 mm diameter on left inferior region, 3 mmon middle calicea and 5 mm on right middle calicea; liver115 mm, spleen 91 mm (Fig. 1). During follow-up shepassed a stone, which revealed Weddellite (CaC 2 O 4 .2.25 H 2 0) upon infrared spectroscopy analysis.Amino acid/acylcarnitine profile tests by tandem massspectrometry were found to be normal.The answer to this question can be found at http://dx.doi.org/10.1007/s00467-006-0078-6.A. G. Güven . M. Koyun . R. Artan .O. Dursun . Y. E. Baysal . S. AkmanDepartments of Pediatric Nephrologyand Pediatric Gastroenterology,Akdeniz University, School of Medicine,Antalya, TurkeyM. Koyun (*)Department of Pediatric Nephrology,Akdeniz University Medical Faculty,07070 Antalya, Turkeye-mail: mustafakoyun2@yahoo.comTel.: +90-242-2274343Fax: +90-242-2274490Fig. 1 Renal ultrasonography showing a stone in the left kidney

Comparison of two different regimens of combined interferon-alpha2a andlamivudine therapy in children with chronic hepatitis B infection.Kansu A, Doğanci T, Akman SA, Artan R, Kuyucu N, Kalayci AG, Dikici B, Dalgiç B, Selimoğlu A, Kasirga E, Ozkan TB, Kuloğlu Z,Aydoğdu S, Boşnak M, Ertekin V, Tanir G, Haspolat K, Girgin N, Yağci RV.Department of Pediatric Gastroenterology, Hepatology and Nutrition, Akdeniz University School of Medicine, Antalya, Turkey.aydankansu@gmail.comAbstractAIM: To evaluate the efficacy of two regimens of combined interferon-alpha2a (IFN-alpha2a) and lamivudine (3TC) therapy in childhoodchronic hepatitis B.METHODS: A total of 177 patients received IFN-alpha2a, 9 million units (MU)/m2 for 6 months. In group I (112 patients, 8.7 +/- 3.5years), 3TC (4 mg/kg/day, max 100 mg) was started simultaneously with IFN-alpha2a, in group II (65 patients, 9.6 +/- 3.8 years) 3TCwas started 2 months prior to IFN-alpha2a. 3TC was continued for 6 months after antiHBe seroconversion or stopped at 24 months innonresponders.RESULTS: Baseline alanine aminotransferase (ALT) was 134.2 +/- 34.1 and 147.0 +/- 45.3; histological activity index (HAI) was 7.4 +/-ŀAntivir Ther. 2006;11(2):255-61.2.7 and 7.1 +/- 2.3; and HBV DNA levels were above 2,000 pg/ml in 76% and 66% of patients in groups I and II, respectively (P > 0.005).Complete response was 55.3% and 27.6% in groups I and II, respectively (P < 0.01). AntiHBe seroconversion was higher and earlier,and HBV DNA clearance was earlier in group I (P < 0.05). HBsAg clearance was 12.5% and 4.6% and antiHBs seroconversion was9.8% and 6.2% in groups I and II, respectively (P > 0.05). Breakthrough occurred in 17.9% and 24.6%; breakthrough times were 15.9 +/-4.6 and 14.1 +/- 5.1 months; and relapse rates were 6.8% and none in groups I and II, respectively (P > 0.05, P > 0.05, P > 0.05).Responders had higher HAI (HAI > 6) and higher pre-treatment ALT than non-responders.CONCLUSION: Simultaneous 3TC+IFN-alpha2a yields a higher response and earlier antiHBe seroconversion and viral clearance thanconsecutive combined therapy. Relapse rate is low. Predictors of response are high basal ALT and high HAI scores. 3TC can beadministered for 24 months without any side effect and breakthrough rate is comparable with previous studies.

Eur J Pediatr (2007) 166:195–199DOI 10.1007/s00431-006-0220-2ORIGINAL PAPERLamivudine and high-dose interferon alpha 2a combinationtreatment in naïve HBeAg-positive immunoactive chronichepatitis B in children: an East Mediterranean center’sexperienceAygen Yilmaz & Mustafa Akcam & Tekinalp Gelen &Reha ArtanReceived: 25 May 2006 /Accepted: 7 June 2006 / Published online: 31 August 2006# Springer-Verlag 2006Abstract Chronic hepatitis B virus infection is among themost common causes of chronic liver disease in children.The aim of this study was to document prospectively ourexperiences related to lamivudine and high-dose interferonα2acombination in naïve, e antigen positive, chronichepatitis B virus infection treatment in children. Thirtythreechildren diagnosed as naïve, immunoactive chronichepatitis B were treated with lamivudine (3 mg/kg/day) andinterferon-α2a (10 MU/m 2 , thrice weekly). Initially, lamivudinewas initiated three months before interferon-α forinduction, and after June 2002, both drugs were startedsimultaneously. After interferon-α was stopped, lamivudinealone was continued for six months. HBeAg seroconversionwith the normalization of serum ALT was achieved atthe end of treatment and at the end of follow-up for 20/33patients. Initial mean alanine aminotransferase, 142.9 IU/L,decreased to a mean value of 31.4. End-treatment responseand sustained response rates were 66.7% (14/21) and 50%(6/12), respectively, in patients that underwent lamivudineinduction before interferon-α and in patients that began toreceive the two drugs simultaneously (p=0.4). Flu-likesyndrome and anorexia were the most common complaints.As our conclusions, we propose that interferon-α2a pluslamivudine combination therapy is highly successful andsafe in children suffering from chronic hepatitis B.A. Yilmaz (*) : M. Akcam : R. ArtanPediatric Gastroenterology,Akdeniz University,Pediatri Anabilim Dali, Arapsuyu,Antalya 07059, Turkeye-mail: aygen@akdeniz.edu.trT. GelenPathology, Akdeniz University,Patoloji Anabilim Dali, Arapsuyu,Antalya 07059, TurkeyLamivudine induction before interferon does not seem tobe necessary.Keywords Chronic hepatitis B . Interferon alpha .Lamivudine . Naïve . Immunoactive . ChildrenAbbreviationsCHB chronic hepatitis B virus infectionHBeAg hepatitis B e antigenIFN-α interferon alphaLMV lamivudineHBV-DNA hepatitis B virus DNAHBsAg hepatitis B surface antigenAntiHBs hepatitis B surface antibodyAntiHBe hepatitis B e antibodyUS abdominal ultrasonographyELISA enzyme-linked immunosorbent assaysHAI histologic activity indexETR end-treatment complete responseSR sustained complete responseIntroductionChronic hepatitis B virus infection (CHB) is among themost common causes of chronic liver disease in children.Clearance of hepatitis B e antigen (HBeAg) indicates thetransition to a state of low-level viral replication that isaccompanied by biochemical remission of liver disease andprolonged survival [1]. Interferon alpha (IFN-α), which isthe first therapeutic option for CHB, has antiviral, immunomodulatory,antitumoral, and antiproliferative effects. Ithas been shown to be effective in approximately one thirdof patients and the response to treatment seems to be

Pediatrics International (2007) 49, 220–225doi: 10.1111/j.1442-200X.2007.02329.xOriginal ArticleLong-term aspects of nodular gastritis in childrenMUSTAFA AKCAM , REHA ARTAN , TEKINALP GELEN , 1 AYGEN YILMAZ , ERDAL EREN , 3VEDAT UYGUN 2 AND HIKMET CIG 2Medical School, Departments of 1 Pathology and2Pediatrics, Akdeniz University, Antalya , and3MedicalSchool, Department of Pediatrics, Suleyman Demirel University, Isparta, TurkeyAbstractBackground : Close association of nodular gastritis and Helicobacter pylori infection has been initially provedby various studies. There have been some studies reporting microscopic and histologic recovery in a short timeafter eradication therapy. But there is not enough data about the long-term course of this condition. The aim ofthis study is to document current clinical conditions, presence of H. pylori and results of endoscopic and histologicexamination, after a long-term period, in children with endoscopically diagnosed antral nodularity.Methods : A total of 35 patients diagnosed as nodular antral gastritis by upper gastrointestinal endoscopy duringa 2 year period, were invited for re-evaluation and re-endoscopy after 3 years. Histopathologically, H. pyloridetected ones had been treated with standard triple eradication therapy. In total, 27 patients were accepted forenrollment in the study. Repeated endoscopy could be performed in all 27 patients.Results : The persistence of antral nodularity was detected in 18 of 27 patients. Decrease in symptoms, absenceof symptoms and presence of H. pylori infection were detected in 6, 8 and 16 (89%) of them, respectively.There was no statistical significance between the first and last endoscopic biopsies when activity, atrophy, intestinalmetaplasia and presence of follicles were regarded. Malt lymphoma could not be detected in any of thepatients.Conclusion : There is a strong association between nodular gastritis and H. pylori . Presence of antral nodularityin the long-term period may be related to H. pylori re-infection. New therapeutic approaches are requiredfor treatment and management of the patients diagnosed as nodular gastritis and living in areas endemic forH. pylori infection.Key words childhood , course , Helicobacter pylori , nodular gastritis .Correspondence: Mustafa Akcam, Department of Pediatrics, Divisionof Pediatric Gastroenterology, Hepatology and Nutrition,Akdeniz University, Medical School, Çocuk Sağlığ ı ve Hastal ı klar ıAD, Antalya 07059, Turkey. Email: makcam@akdeniz.edu.trReceived 11 October 2005; revised 1 December 2005; accepted26 December 2005.Nodular gastritis (NG) is usually characterized as presentingwith an endoscopic appearance that has been described as‘goose flesh’. 1 It is also characterized by intense inflammatorycell infiltration consisting mainly of monocytes and by increasednumbers of lymphoid follicles with a germinal center, in gastricmucosa. 2It has been known that common and universally distributedHelicobacter pylori infection is the most frequent reason forgastritis and peptic ulcer disease. This infection, predominantlyacquired in childhood, has been accepted as directly associatedwith gastric carcinoma and mucosa-associated lymphoidtissue (MALT) lymphoma. 3 The inflammation that H. pyloricauses in the gastric mucosa is not always observed macroscopicallywith endoscopy, but it is identified on the histologicexamination of gastric biopsies. 4A strong association between endoscopic detection of NGand presence of H. pylori has been established in previousstudies. 1,2,5 – 8 There are a few reports mentioning recovery ofthis nodular appearance after eradication treatment. 5,9 Thereis no definite reason for antral nodularity, and we could notrecognize any study about long-term follow up and evaluationof endoscopic and histologic changes after this time in theliterature.In the present study, re-evaluation of clinical conditions,presence of H. pylori and results of endoscopic and histologicexamination of children diagnosed as NG is aimed after amean 3 years follow up.

Case ReportsAn Unusual Cause of Ascites:Hemophagocytic LymphohistiocytosisMustafa AkcamReha ArtanAygen YilmazBahar Akkaya*Hemophagocytic lymphohistiocytosis is characterizedby fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia,hypofibrinogenemia, and hemophagocytosis.Ascites is not mentioned as a symptom ofhemophagocytic syndrome. We report a one month-oldgirl suffering from familial erythrophagocytic lymphohistiocytosis,who presented with ascites.Key words: Hemophagocytosis, ascites, childhood.Hemophagocytic lymphohistiocytosis (HLH) isa rare disease affecting infants and children. It hastwo forms with similar presentation: familialerythrophagocytic lymphohistiocytosis (FEL) andinfection-associated hemophagocytic syndrome(IAHS)(1). The former has autosomal recessiveinheritance with an incidence of 0.12 per 100.000children(2). The hallmark of the disease isthe accumulation of lymphohistiocytes in thereticuloendothelial system with features ofhemophagocytosis. Although children with IAHSmay present at an older age, children with FEL arealways younger than 4 years(1-3).Ascites is rarely reported in patients with HLH inFrom the Division of Pediatric Gastroenterology,Hepatology and Nutrition, Departments of Pediatricsand *Pathology, Akdeniz University School ofMedicine, Antalya/Turkey.Correspondence to: Mustafa Akcam, Celebiler Mahallesi137, Cadde, Hubanlar Apt: No: 10, 32100, Isparta,Turkey. E-mail: makcam@sdu.edu.trManuscript received: February 6, 2006;Initial review completed: July 12, 2006;Revision accepted: December 13, 2006.the literature(4,5). In this report, we are presentingan infant with FEL, who had an unusual presentationof ascites, and who was younger than the previouslypublished ones.Case ReportThirty-five-days old female baby was referred toour hospital with convulsive movements and alteredconsciousness. She was born at 33 weeks ofgestation with 3300 g birth weight as a firstpregnancy of non-consanguineous parents and thatshe had fever, abdominal swelling and vomiting forsix days.On physical examination, she was lethargic andhad abdominal distention, mild hepato-splenomegaly,and ascites. Fundoscopic examination wasnormal.Laboratory analysis showed; Hb 11 g/dL,leukocytes 11300/mm 3 , platelets 31000/mm 3 ,alanine transferase (ALT) 57 U/L, aspartatetransferase (AST) 148 U/L, alkaline phosphatase(ALP) 450 U/L, total bilirubin 3 mg/dL, conjugatedbilirubin 1.5 mg/dL, ferritin 20000 ng/mL, lactatedehydrogenase (LDH) 2243 mg/dL, totalcholesterol 83 mg/dL (N ≤60), triglyceride 158 mg/dL (N = 32-99), d-dimer 368 mg/dL, total protein4.7 g/dL, albumin 3.1 g/dL, blood ammoniac109 µg/dL (N = 19-94) and blood lactate 5.03 mmol/L (N = 0.5-2.2). Urinanalysis, blood glucose, serumelectrolytes, amino acids, and amylase were normal.Prothrombin time (PT) and partial thromboplastintime (PTT) were elevated. Fibrinogen was lowerthan measurable levels. Direct coombs test wasnegative. Analysis of cerebrospinal fluid (CSF)revealed normal findings. Blood, urine, feces, andCSF were sterile. Serology for cytomegalovirus,Epstein-Barr virus, rubella, toxoplasmosis, parvovirus,Human 1mmunodeficiency Virus and syphiliswere all negative. Brain computed tomography (CT)was normal. Abdominal CT and ultra-sonographyrevealed hepatomegaly (90 mm), splenomegaly (90mm), and ascites; there was no solid mass. Atypicalmononuclear cells were found in peripheral blood,INDIAN PEDIATRICS 371 VOLUME 44 __ MAY 17, 2007

Mihci E (Mihci, Ercan), Tacoy S (Tacoy, Suekran), Yakut S (Yakut, Sezin), Ongun H (Ongun, Hakan),Keser I (Keser, Ibrahim), Kilicarslan B (Kilicarslan, Bahar), Bagci G (Bagci, Guelseren), Luleci G (Lueleci,Gueven)Source: TURKISH JOURNAL OF PEDIATRICS Volume: 49 Issue: 3 Pages: 322-326 Published: JUL-SEP 2007Times Cited: 0 References: 23 Citation MapAbstract: We report a newborn girl with multiple congenital anomalies whose chromosomal analysis showedcomplete trisomy 22. Her phenotype included microcephaly, epicanthus, hypertelorism, micrognathia, cleft palate,microtia, and preauricular tag. She died in the 24,h post-natal hour. Trisomy 22 was shown by fluorescence in situhybridization technique and the parental origin of the extra chromosome was found to be maternal by DNAmicrosatellite marker analysis of chromosome 22. Postmortem examination revealed the presence of atrioseptaldefect and stasis in the biliary canals. We believe that this patient will contribute to the literature both by clinicalfindings and short life span associated with maternal origin of extra chromosome 22.Document Type: ArticleLanguage: EnglishAuthor Keywords: trisomy 22; atrioseptal defect (ASD); fluorescence in situ hybridization (FISH); cleft palate;newborn infant; maternal originKeyWords Plus: INFANT; NEWBORNReprint Address: Mihci, E (reprint author), Akdeniz Univ, Fac Med, Dept Pediat, Antalya, TurkeyAddresses:1. Akdeniz Univ, Fac Med, Dept Pediat, Antalya, Turkey2. Akdeniz Univ, Fac Med, Dept Med Biol & Genet, Antalya, Turkey3. Akdeniz Univ, Fac Med, Dept Pathol, Antalya, TurkeyPublisher: TURKISH J PEDIATRICS, P K 66 SAMANPAZARI, 06240 ANKARA, TURKEYŀAuthor(s):Subject Category: PediatricsIDS Number: 220NRISSN: 0041-4301

CASE REPORTSOral-Facial-Digital Syndrome Type 1Ercan MihciSukran TacoyGulay Ozbilim*Brunella Franco**The oral-facial-digital syndrome type 1 ischaracterized by following abnormalities: pseudocleft ofthe upper lip, tongue lobulation, hamartomata on thetongue, alveolar frenulae, and clefting of the soft palate.We report a 9-month-old girl who was referred to ourclinic due to facial dysmorphology in addition to cleftpalate and multiple masses on the tongue which resultedin feeding problems. Surgical intervention was done.Molecular analysis revealed absence of OFD gene.Key words: Feeding disorders of childhood, Mutationanalysis, Oral-facial-digital syndrometype 1.Oral-facial-digital syndromes are a heterogeneousgroup of developmental disorders of whichat least nine different forms have been described(1).It is transmitted as an X-linked dominant conditionand is characterized by malformations of the face,oral cavity and digits(1-4). The gene for the disorderwas mapped to Xp22.3-p22.2(3-7) and mutationanalysis identified CXORF5, which was thenrenamed OFD1 as the gene responsible for thisdiosorder(5,7).The facial features include frontal bossing, facialasymmetry, hypertelorism, a broadened nasalbridge, and facial milia. Oral features includepseudoclefting of the upper lip, cleft palate andFrom the Akdeniz University School of MedicineDepartment of Pediatrics, *Pathology, Antalya,Turkey, and **Telethon Institute of Genetics andMedicine, Naples, Italy.Correspondence to: Ercan Mihci, Akdeniz UniversityFaculty of Medicine, Department of Pediatrics,Division of Clinical Genetics, Antalya 07059, Turkey.E-mail: emihci@akdeniz.edu.trManuscript received: December 27, 2006;Initial review completed: February 6, 2007;Revision accepted: June 4, 2007.tongue, high arched palate, ankyloglossia togetherwith abnormal dentition. Malformations of the digitsof the hands are more common than those of the feetand include syndactyly, brachydactyly, clinodactylyand less commonly polydactyly. In addition polycystickidneys have been found in patients withOFD 1 at necropsy(2).Here we report a child, displaying clinicalfindings of OFD 1, who was negative for mutationsin the OFD 1 gene.Case ReportA 9-month-old female was referred for clinicalgenetic examination because of multiple masses onthe tongue, cleft palate and facial dysmorphology.The patient was born to a 30-year-old gravida 1 para1 mother and a 30- year old father. The parents werehealthy and unrelated. Her family history wasremarkable: her grandmother’s one brother hadsevere irregular placement of teeth, another sisterand brother’s sister had lobulation of the tongue,and one aunt had partial alopecia on the vertex. Hermother reported to have taken metamizol anderitromysin, for upper respiratory system infection,for one week during the 6-gestational-week.Pregnancy and delivery were normal and her birthweight was 2900 g, length 50 cm.On physical examination, her height, weight,head circumference were 64 cm (50-75th centile),7800 g (10-25th centile), 42.7 cm (10-25th centile)respectively. She had hypertelorism, depressednasal bridge, sulcus of the nasal tip, median partialcleft of the upper lip, hyperplastic multiple oralfrenuli, cleft palate, bifid, lobulated tongue withmultiple hamartoma, milia of ears, partial alopeciaon the vertex hair and brachydactyly of all fingersand clinodactyly of the bilateral fifth fingers (Figs. 1& 2). The left thumb had radial deviation Hermental and motor development, as well as audiologicalexamination were normal. She did not haveany skeletal anomaly.Her echocardiography showed third degreemitral valve insufficiency. Cranial magneticresonance imaging, abdominal and renalultrasounds were normal. She was operated for cleftpalate and hamartoma of tongue. Pathologicalexamination of tongue biopsies showed normalINDIAN PEDIATRICS 854 VOLUME 44 __ NOVEMBER 17, 2007

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGYTransferrin receptor in proliferation of T lymphocytesin infants with iron deficiencyH.ARTAC*,M.COSKUN † , I. KARADOGAN ‡ ,O.YEGIN § ,A.YESILIPEK –*Division of Immunology andAllergy, Department of Pediatrics,Meram Medical Faculty, SelcukUniversity,Konya,Turkey† Department of Immunology,MedicalFaculty,AkdenizUniversity,Antalya,Turkey‡ Division of Hematology,Department of Internal Medicine,MedicalFaculty,AkdenizUniversity,Antalya,Turkey§ Division of Immunology,Department of Pediatrics, MedicalFaculty, Akdeniz University,Antalya, Turkey– Division of Haematology andOncology, Department of Pediatrics,MedicalFaculty,AkdenizUniversity,Antalya,TurkeyCorrespondence:Hasibe Artac, Selcuk UniversitesiMeram Tip Fakultesi, ÇocukImmunoloji ve Allerji Bilim Dalı,Beyşehir Yolu, 42080-Konya,Turkey. Tel.: +90 332 223 73 05;Fax: +90 332 223 61 82; E-mail:hasibeartac@yahoo.comSUMMARYThe aim of this study was to contribute to clarify the mechanism ofcellular immune insufficiency occurring during iron deficiency. Westudied the expression of the transferrin receptor (TfR) which is calledas CD71, on the surface of T lymphocytes in infants with irondeficiency (with and without anemia). A total of 33 infants, agedbetween 7 and 26 months were included in this study. These subjectsweredividedintothreegroups:(i)latent iron deficiency (LID) (group1), (ii) iron deficiency anemia (IDA) (group 2), and (iii) healthy infants(group 3). Both CD3 levels and CD71 expression of T lymphocyteswere analysed by flow cytometry before and after phytohaemagglutinin(PHA) stimulation. The percentage of CD3 + lymphocytes ininfants with IDA was lower than that in controls after PHA stimulation(mean ± SD, 48.6 ±10.5% vs. 70.7 ±7.8%, P < 0.001). The TfRexpression of T lymphocytes (CD3 + CD71%) increased in all threegroups after PHA stimulation (P < 0.001). No significant difference wasseen among the three groups with respect to CD3 + CD71%. Althoughthere was a reduction in the proliferative capacity of T lymphocytes ininfants with IDA, their ability to express transferrin receptor onT-lymphocyte cell surface was normal.doi:10.1111/j.1365-2257.2006.00848.xReceived 31 March 2006; acceptedfor publication 27 August 2006KeywordsIron deficiency, infant, T lymphocyte,transferrin receptorINTRODUCTIONIron is vital to all cells and particularly to proliferatingcells such as activated T cells (Bowlus, 2003). Proliferatingcells require iron and, therefore, express thetransferrin receptor (TfR) that mediate cellular ironuptake. This study was planned to evaluate alternationin TfR expression of T lymphocytes in theÓ 2006 The Authors310 Journal compilation Ó 2006 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2007, 29, 310–315

This information is current asof October 11, 2010Cutting Edge: A CommonPolymorphism Impairs Cell SurfaceTrafficking and Functional Responsesof TLR1 but Protects against LeprosyReferencesSubscriptionsPermissionsEmail AlertsChristopher M. Johnson, Elizabeth A. Lyle, Katherine O.Omueti, Vitaly A. Stepensky, Olcay Yegin, ErkanAlpsoy, Lutz Hamann, Ralf R. Schumann and Richard I.TappingJ. Immunol. 2007;178;7520-7524http://www.jimmunol.org/cgi/content/full/178/12/7520This article cites 26 articles, 11 of which can be accessed free at:http://www.jimmunol.org/cgi/content/full/178/12/7520#BIBL8 online articles that cite this article can be accessed at:http://www.jimmunol.org/cgi/content/full/178/12/7520#otherarticlesInformation about subscribing to The Journal of Immunology isonline at http://www.jimmunol.org/subscriptions/Submit copyright permission requests athttp://www.aai.org/ji/copyright.htmlReceive free email alerts when new articles cite this article. Signup at http://www.jimmunol.org/subscriptions/etoc.shtmlDownloaded from www.jimmunol.org on October 11, 2010The Journal of Immunology is published twice each month byThe American Association of Immunologists, Inc., 9650Rockville Pike, Bethesda, MD 20814-3994.Copyright ©2007 by The American Association ofImmunologists, Inc. All rights reserved.Print ISSN: 0022-1767 Online ISSN: 1550-6606.

ARTICLE IN PRESSTuberculosis (2007) 87, 225–230Available at www.sciencedirect.comjournal homepage: http://intl.elsevierhealth.com/journals/tubeInterferon-c gene+874T–A polymorphism is associatedwith tuberculosis and gamma interferon responseNilgün Sallakcı a,1 , Mesut Coskun a,1 , Zafer Berber b , Fuat Gürkan c ,Halil Kocamaz c ,Gülnar Uysal d , Sabin Bhuju b , Ugur Yavuzer a,e ,Mahavir Singh b , Olcay Yeğin a,a Akdeniz University Health Sciences Research Centre, Akdeniz University, Faculty of Medicine, Antalya, Turkeyb Department of Genome Analysis, GBF, German National Center for Biotechnology, Germanyc Department of Pediatric Infectious Diseases, Dicle University, Diyarbakır, Turkeyd Dıs-kapı Childrens Hospital, Ankara, Turkeye Department of Physiology, Akdeniz University Health Sciences Research Centre,Akdeniz University, Faculty of Medicine, Antalya, TurkeyReceived 26 April 2006; received in revised form 9 October 2006; accepted 17 October 2006KEYWORDSTuberculosis;Interferon g gene+874T–Apolymorphism(IFN-g+874 T–A);ELISPOT;Gamma-InterferonSummaryInterferon-g is the most important cytokine in resistance to mycobacterial diseases andcommon variants of interferon-g gene could be related to tuberculosis susceptibility. Wetested the hypothesis that the interferon-g+874T–A polymorphism is associated withtuberculosis disease, and affects the interferon-g reponse. We determined by pyrosequencingthe distribution of the interferon-g+874T–A polymorphism in a Turkish population of319 patients with pulmonary tuberculosis, 42 children with severe forms of tuberculosisand 115 healthy donors. We also analysed whether any correlation exists between thispolymorphism and interferon-g response to Mycobacterium tuberculosis antigens byELISPOT in 58 pulmonary tuberculosis cases, and the results were analysed according to thegenotypes. We found that the minor allele (T) frequency was significantly lower in patientswith pulmonary tuberculosis when compared to controls (P ¼ 0.024, OR ¼ 0.7), a similarlysignificant decrease in the frequency of TT genotype was observed in patients withpulmonary tuberculosis, compared to the control group (P ¼ 0.02, OR ¼ 0.49). IFN-gresponses to PPD antigen in TT genotype was found to be significantly higher than the AAgroup (P40.001). Non-parametric correlation analysis of ELISPOT data showed significantreverse correlation in PPD, CFP10 and ESAT6 values and IFN-g +874 genotypes. Theseresults show that the IFN-g +874T-A polymorphism is related to the IFN-g response and themagnitude of the response decreases during transition from TT- to TA and to AA genotypes.Our data suggest that similar to various Caucasian populations, in a Turkish population the Corresponding author. Tel.: +90 2422496000.E-mail address: yegin@akdeniz.edu.tr (O. Yeğin).1 These authors contributed equally.1472-9792/$ - see front matter & 2006 Elsevier Ltd. All rights reserved.doi:10.1016/j.tube.2006.10.002

Dig Dis Sci (2007) 52:405–410DOI 10.1007/s10620-006-9422-8ORIGINAL ARTICLESerum Ferritin, Vitamin B 12 , Folate, and Zinc Levels in ChildrenInfected with Helicobacter pyloriMustafa Akcam · Sebahat Ozdem · Aygen Yilmaz ·Meral Gultekin · Reha ArtanReceived: 3 December 2005 / Accepted: 1 May 2006 / Published online: 9 January 2007C○ Springer Science + Business Media, Inc. 2006Abstract We sought to explore the relationship betweenHelicobacter pylori infection and serum ferritin, vitamin B 12 ,folate, and zinc status among children. Fifty patients aged5–18 years who underwent upper gastrointestinal endoscopybecause of dyspeptic symptoms, were studied, prospectively.Patients were grouped as H. pylori positive (group 1, n = 32)or H. pylori negative (group 2, n = 18) by histopathologicexamination and rapid urease test. Fasting serum ferritin,vitamin B 12 , folate, and zinc levels of patients were measured.Both groups were indifferent according to age, gender,height standard deviation score (H SDS ), and weight standarddeviation score (W SDS ). Serum ferritin levels were 33 ± 26and 50 ± 46 ng/mL (P = .098), vitamin B 12 levels were303 ± 135 and 393 ± 166 pg/mL (P = .042), folate levelswere 9.64 ± 3.2 and 9.61 ± 2.8 ng/mL (P = .979), and zinclevels were 95 ± 48 and 87 ± 31 µg/dL (P = .538), in groups1 and 2, respectively. Ferritin levels of 14 (43.8%) patientsin group 1 and 6 (33.3%) patients in group 2 were belowthe normal range (P = .470). Serum vitamin B 12 levels of 9children (28%) in group 1 and 2 children (11%) in group 2M. Akcam () · A. Yilmaz · R. ArtanAkdeniz University, Medical School, Department of Pediatrics,Division of Pediatric Gastroenterology, Hepatology and Nutrition,Antalya, Turkey 07059e-mail: makcam@sdu.edu.trS. OzdemAkdeniz University, Medical School,Department of Central Lab, Biochemistry Unit,Antalya, TurkeyM. GultekinAkdeniz University, Medical School,Department of Biochemistry,Antalya, Turkeywere below the normal range (P = .287). The findings of thepresent study suggest that H. pylori infection has a negativeeffect on serum ferritin and vitamin B 12 levels in children.This negative effect on vitamin B 12 levels is rather markedin contrast to that on ferritin levels. H. pylori infection hasno significant effect on serum folate or zinc levels amongchildren.Keywords Helicobacter pylori . Child . Vitamin B 12.Folate . Zinc . MicronutrientIntroductionHelicobacter pylori has been recognized as the major etiologicfactor of gastritis and peptic ulcer disease in adults andchildren. This infection is frequently acquired during childhoodand lasts into adult life, which has been linked to thedevelopment of gastric cancer [1, 2].Because this infection particularly develops in the stomach,it naturally affects stomach functions. Although thereis no direct absorption of nutrients in the stomach, it playsa very important role, such as acid secretion, for facilitatedabsorption of nutrients in small intestine. H. pylori also impairsthe normal secretion of hydrochloric acid, provokingachlorhydria in infected patients [3, 4]. Additionally, bacteriamay metabolize some nutrients that are important forits continued survival, and may cause deficiencies in thismanner. As a result of its interference, H. pylori may modifythe absorption of many nutrients and then compromisethe nutritional status of infected patients, resulting in diverseclinical manifestations [5–8]. It has been reported to be associatedwith various unexpected manifestations in childrenand adults.Springer

Molecular and Cellular Biochemistry 290: 125–130, 2006.DOI: 10.1007/s11010-006-9176-9 c❣ Springer 2006Myeloperoxidase, xanthine oxidase andsuperoxide dismutase in the gastric mucosa ofhelicobacter pylori positive and negativepediatric patientsMustafa Akcam, 1 Oguz Elmas, 2 Aygen Yilmaz, 1 Serkan Cağlar, 2Reha Artan, 1 Tekinalp Gelen 3 and Yakup Alıcıgüzel 21 Akdeniz University, Medical School, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology andNutrition, Antalya, Turkey; 2 Akdeniz University, Medical School, Department of Biochemistry, Antalya, Turkey; 3 AkdenizUniversity, Medical School, Department of Pathology, Antalya, TurkeyReceived 28 December 2005; accepted 2 March 2006AbstractThe aim of this study was determination and comparison of the levels of myeloperoxidase (MPO), xanthine oxidase (XO), andsuperoxide dismutase (SOD) in gastric mucosa of children who were infected and noninfected with Helicobacter pylori (HP).The MPO, and XO enzyme activities were detected via kinetic measurement, and the MPO, XO and SOD enzyme protein levelswere detected via Western blot, in antral mucosa specimens of 43 patients who underwent upper gastrointestinal endoscopy withvarious indications. The diagnosis of HP infection was made with a positive rapid urease test and histopathologic detection.MPO activity and enzyme protein levels were measured in 14 [8 HP (+) and6HP(−)], and in 9 [5 HP (+) and4HP(−)]while XO activity and enzyme protein levels were measured in 16 [10 HP (+)and6HP(−)] and in 9 [5 HP (+)and4HP(−)]patients, respectively. SOD protein level was detected in 13 [7 HP (+) and 6 HP (−)] patients. Of 43 patients 25 were HP (+)and 18 were HP (−). MPO activities were 75.6 ± 40.5 and 98.8 ± 44.1 U/g. protein (p = 0.302) while XO activities were 0.5± 0.3 and 0.4 ± 0.2 U/g. protein in HP (+) and HP (−) patients, respectively (p = 0.625). Measured enzyme protein levels ofMPO, XO and SOD were found statistically indifferent in HP (+) and HP (−) patients (p = 0.327, p = 0.086, and p = 0.775,respectively). The results of this study revealed that, MPO, XO and SOD conditions in gastric mucosa alone were not affectedfrom HP presence. That’s why MPO, XO, and SOD may not have important roles in the pathogenesis of HP related gastricdisease in children. (Mol Cell Biochem 290: 125–130, 2006)Key words: myeloperoxidase, xanthine oxidase, superoxide dismutase, gastric mucosa, Helicobacter pylori, childhoodIntroductionHelicobacter pylori infection is a worldwide pathogenic conditionin the development of infection causing different problemsin the gastric mucosa. It is strongly associated withthe pathogenesis of acute, chronic and atrophic gastritis, intestinalmetaplasia, peptic ulcer disease and MALT (mucosaassociatedlymphoid tissue)-lymphoma. Although these HPrelated diseases are predominantly observed in adults, the infectionmay start at very early in life [1, 2]. Early childhoodAddress for offprints: M. Akcam, Akdeniz University, Medical School, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology andNutrition, Antalya, Turkey 07059 (E-mail: makcam@sdu.edu.tr)

adolescents with type 1 diabetes mellitus.Karagüzel G, Akçurin S, Ozdem S, Boz A, Bircan I.Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, Akdeniz University, Antalya,Turkey. gulaykg@akdeniz.edu.trAbstractOBJECTIVES: To analysis bone mineral density (BMD) and bone turnover markers in children and adolescentswith type 1 diabetes mellitus (DM1) and to establish possible correlations with duration of the disease and degreeof metabolic control.PATIENTS AND METHODS: Fifty-eight (26 prepubertal, 32 pubertal) children (29 boys) with DM1 (age: 11.7 +/-3.1 years) and 44 (20 prepubertal, 24 pubertal) healthy children (21 boys) as controls (age: 10.8 +/- 3.2 years)were included in the study. BMD was measured by dual energy X-ray absorptiometry (DEXA). Scans of thelumbar spine (LS2-4) and femoral neck (FN) were carried out. Serum levels of osteocalcin, amino-terminalpropeptide of type I procollagen (PINP), and alkaline phosphatase, as markers of bone formation, and urinarycalcium/creatinine (Ca/Cr) ratio and levels of N-telopeptide (Ntx), as markers of bone resorption, were assessed.Anthropometrics, duration of DM1, presence of complications, insulin dose, and degree of metabolic control wereobtained from the patients' records.RESULTS: In children with DM1 and controls, the mean measurements of LS2-4 BMD were 0.698 +/- 0.178g/cm2 and 0.669 +/- 0.192 g/cm2, respectively (p >0.05), and FN-BMD measurements were 0.743 +/- 0.147g/cm2 and 0.744 +/- 0.170 g/cm2, respectively (p >0.05). Children with DM1 had lower serum levels of calcium,intact parathyroid hormone, osteocalcin and PINP, and higher serum levels of 25-hydroxyvitamin D and urinaryCa/Cr (p

Pediatrics International (2007) 49, 310–313doi: 10.1111/j.1442-200X.2007.02370.xOriginal ArticleAdjuvant effect of vitamin A on recurrent lower urinary tractinfectionsAYGEN YILMAZ ,1EL IF BA HAT , 2 GULSUN GULAY YILMAZ ,3ALEV HASANOGLU ,4SEMA AKMAN5AND AYFER GUR GUVEN5Departments of1Pediatric Gastroenterology and5Pediatric Nephrology, Akdeniz University,3Departmentof Pediatric Nephrology, Antalya Public Hospital, Antalya, 2 Department of Pediatric Nephrology,Karadeniz Technical University, Trabzon and 4 Department of Pediatric Metabolism, Gazi University,Ankara, TurkeyAbstractBackground : The purpose of the present paper was to investigate the effects of vitamin A supplementation onrecurrent lower urinary tract infections (RUTI).Methods : Twenty-four patients with non-complicated RUTI were included in a placebo-controlled, doubleblindedstudy. Twelve patients received a single dose of 200 000 IU vitamin A in addition to antimicrobial therapy.Patient and control groups (each containing 12 patients) were followed for up to 1 year and were evaluatedfor eradication and frequency of lower urinary tract infections (UTI). Serum levels of vitamin A and -carotenewere determined periodically.Results : During the first 6 months follow-up period the infection rate of the vitamin A-supplemented groupreduced from 3.58 to 0.75 per 6 months, and in the subsequent 6 months the infection rate was 1.75 per6 months. These values were calculated as 2.75, 2.83 and 2.66, respectively, in the placebo group.Conclusion : Vitamin A supplementation may have an adjuvant effect on the treatment of RUTI.Key words immunity , urinary tract infection , vitamin A .Vitamin A has been known as an anti-infective vitamin sincethe 1920’s. 1 Vitamin A deficiency mimics immunodeficiencydisorders in which there are disturbances in immunity, includingpathological alterations in mucosal surfaces, impaired antibodyresponses to protein antigens, changes in lymphocytesubpopulations and altered T- and B-cell function. 2,3 Mucosalimmunity is an important factor in urinary tract infections(UTI).4Although many clinical trials demonstrate a positiverelationship between vitamin A supplementation and decreasedmortality and morbidity rates from measles, diarrhea and respiratorydiseases, there are no data on the relationship betweenrecurrent UTI (RUTI) and vitamin A status. 5 – 7Based on these findings, a prospective, randomized, doubleblind,placebo-controlled trial was undertaken at the outpatientclinic of the pediatric nephrology unit at Akdeniz University toinvestigate whether vitamin A supplementation effects the frequencyof RUTI in children.Correspondence: Aygen Yilmaz, MD, Akdeniz Universitesi, TipFakultesi, Cocuk Sagligi ve Hastaliklari Anabilim Dali, 07070Antalya, Turkey. Email: aygen@akdeniz.edu.trReceived 1 February 2005; revised 27 January 2006; accepted1 February 2006.MethodsTwenty-four patients diagnosed as having non-complicatedlower RUTI were included in the study. The patients sufferingfrom immune deficiency disorders, diabetes mellitus,complicated UTI such as urinary tract stone disease, congenitalurinary anomalies; voiding dysfunction, vesicoureteralreflux, and presence of nephrostomia or permanent urinarycatheterization were excluded via renal and pelvic ultrasonographyand interrogation of parents. Uroflowmetry andprospective measurement of residual urine could not be done.Because of increased probability of complicated UTI anddifficulties in their follow-up examinations, patients youngerthan 12 months were also excluded. Dietary habits directingto vitamin A resources were also questioned. Completephysical examination including ophthalmologic evaluationwas performed. Children selected for the trial were randomlyassigned to either vitamin A group or a placebo group. Sealedenvelopes containing cards indicating group designationwere used for randomization. A pharmacist who had noknowledge of the clinical status of the children carried outthe randomization.

Pediatr Nephrol (2007) 22:1297–1301DOI 10.1007/s00467-007-0528-9ORIGINAL ARTICLEScreening for hypercalciuria in schoolchildren:what should be the criteria for diagnosis?Mustafa Koyun & Ayfer Gür Güven & Serkan Filiz &Sema Akman & Halide Akbas & Yunus Emre Baysal &Necati DedeogluReceived: 1 December 2006 /Revised: 27 March 2007 /Accepted: 3 April 2007 / Published online: 5 June 2007# IPNA 2007Abstract The methodologies to diagnose hypercalciuriahave not yet been standardized. The aims of this study wereto assess the correlation between urinary calcium/creatinineratio (UCa/Cr)≥0.21 (mg/mg) and 24 h urinary calciumexcretions and to determine the reference values of theUCa/Cr ratio among a large population of schoolchildren insouthern Turkey. Non-fasting, second morning urine sampleswere collected from 2,143 children aged 7–14 years. Inchildren with suspected hypercalciuria [UCa/Cr≥0.21(mg/mg)], 24 h urine samples were collected. The 95thpercentile values of the UCa/Cr ratio for each age werecalculated and showed a decrease in value with advancingage. In all, 269 (12.5%) of the children had UCa/Cr≥0.21M. Koyun : Y. E. BaysalPediatric Nephrology, School of Medicine,Akdeniz University,Antalya, TurkeyM. Koyun (*) : A. G. Güven : S. AkmanDepartment of Pediatric Nephrology, Medical Faculty,Akdeniz University,Antalya 07070, Turkeye-mail: mustafakoyun2@yahoo.comS. FilizDepartment of Pediatrics, School of Medicine,Akdeniz University,Antalya, TurkeyH. AkbasDepartment of Biochemistry, School of Medicine,Akdeniz University,Antalya, TurkeyN. DedeogluDepartment of Public Health, School of Medicine,Akdeniz University,Antalya, Turkey(mg/mg), of whom 66 (24.5%) had daily urinary calciumexcretion ≥4 mg/kg per day. A weak correlation was foundbetween spot UCa/Cr ratios and daily urinary calciumexcretions in children with UCa/Cr≥0.21 (r=0.27). Weconclude that a spot UCa/Cr ratio of 0.21 (mg/mg) as theupper limit of normal cannot be used universally to definehypercalciuria. Age-specific reference values for UCa/Crshould be established for each population, to be used as ascreening test for hypercalciuria, and the definite diagnosisshould be established with 24 h urinary calcium excretionwhenever possible.Keywords Hypercalciuria . Urinary calcium-to-creatinineratio . 24 h urinary calcium excretion . Percentile .SchoolchildrenIntroductionIdiopathic hypercalciuria is one of the most common causesof both urolithiasis and isolated microscopic hematuria inchildren [1, 2]. However, the precise definition of hypercalciuriahas not yet been established, and the methodologiesfor quantitating urinary calcium excretion have notbeen standardized [3]. Although urinary calcium excretionis best measured as a 24 h collection, it is not alwayssuitable as a test because of difficulties in samplecollection. Urinary calcium/creatinine ratio (UCa/Cr) isoften used in this circumstance; however, there areconflicting data in the literature about the correlationbetween UCa/Cr and 24 h urinary calcium excretion. Insome studies it was found that this correlation was strong[4, 5], while in others it was not convincing [6]. Moreover,the value of UCa/Cr to define hypercalciuria is not wellestablished. Recently, the 95th percentile value of UCa/Cr

Comparison of pulse and oral steroid in childhood membranoproliferativeglomerulonephritis.Nephrol. 2007 Mar-Apr;20(2):234-45.Bahat E, Akkaya BK, Akman S, Karpuzoglu G, Guven AG.Department of Pediatric Nephrology, Karadeniz Technical University, Trabzon, Turkey. elifbahat@yahoo.comAbstractBACKGROUND: There has been no controlled study comparing efficacy of pulse versus oral steroid therapy inchildhood membranoproliferative glomerulonephritis (MPGN). This study aimed to compare these therapies andrenal outcome over a long-term period for MPGN.METHODS: Outcome measures in 11 patients with MPGN treated with pulse methylprednisolone (MP) werecompared with 8 patients with MPGN treated with oral prednisolone (P).RESULTS: Nineteen children with idiopathic MPGN (mean age 9.75 years, range 3.7-14 years) were followed fora mean period of 68.21 months (range 4-124 months). Both treatment groups were similar in demographic,clinical, laboratory and histopathological characteristics on presentation. In the pulse MP group, only 1 patient outŀJof 11 progressed to end-stage renal failure (ESRF), compared with 4 patients out of 8 in the oral P group(p=0.041). For long-term renal survival, those patients with more than 8 years of follow-up were further evaluated.Twelve patients had completed 8 years of follow-up; in the pulse MP group, 1 of 7 patients, compared with 4 of 5patients in the oral P group progressed to ESRF (p=0.039). Chronic damage in the presentation biopsy and lackof remission in patients with nephrotic syndrome (NS) were positively associated with adverse renal outcome(p=0.02, p=0.006, respectively).CONCLUSIONS: Pulse MP therapy may be superior to oral P therapy in children with MPGN in preserving renalfunction without any increase in steroid-related side effects. Chronic damage in the presentation biopsy and lackof remission of NS are adverse features.PMID: 17514629 [PubMed - indexed for MEDLINE]

Pediatr Nephrol (2007) 22:1327–1333DOI 10.1007/s00467-007-0520-4ORIGINAL ARTICLEReno-vascular hypertension in childhood:a nationwide surveyAysun K. Bayazit & Fatos Yalcinkaya & Nilgun Cakar &Ali Duzova & Zelal Bircan & Aysin Bakkaloglu &Nur Canpolat & Nazl1 Kara & Aydan Sirin &Mesiha Ekim & Ayse Oner & Sema Akman & Sevgi Mir &Esra Baskin & Hakan M. Poyrazoglu & Aytul Noyan &Ipek Akil & Sevcan Bakkaloglu & Alper SoyluReceived: 29 January 2007 /Revised: 24 April 2007 /Accepted: 25 April 2007 / Published online: 30 May 2007# IPNA 2007Abstract Renovascular disease accounts for 8–10% of allcases of paediatric hypertension, whereas, in adults, itsincidence is approximately 1%. The Turkish PaediatricHypertension Group aimed to create the first registry databasefor childhood renovascular hypertension in Turkey. Twentyof the 28 paediatric nephrology centres in Turkey respondedto the survey and reported 45 patients (27 girls, 18 boys) withrenovascular hypertension between 1990 and 2005. The ageat presentation ranged from 20 days to 17 years. The meanblood pressure at the diagnosis was 169/110 mmHg. ChiefA. K. Bayazit (*) : A. NoyanDepartment of Paediatric Nephrology, School of Medicine,Cukurova University,01330, Balcali,Adana, Turkeye-mail: ayskar@yahoo.comF. Yalcinkaya : M. EkimPaediatric Nephrology, School of Medicine, Ankara University,Ankara, TurkeyN. Cakar : N. KaraPaediatric Nephrology, SSK Diskapi Hospital,Ankara, TurkeyA. Duzova : A. BakkalogluPaediatric Nephrology, Faculty of Medicine,Hacettepe University,Ankara, TurkeyZ. BircanPaediatric Nephrology, School of Medicine, Kocaeli University,Izmit, TurkeyN. CanpolatPaediatric Nephrology, School of Medicine,Cerrahpasa University,Istanbul, TurkeyA. SirinPaediatric Nephrology, School of Medicine,Istanbul University,Istanbul, TurkeyA. OnerPaediatric Nephrology, Dr. Sami Ulus Children’s Hospital,Ankara, TurkeyS. AkmanPaediatric Nephrology, School of Medicine, Akdeniz University,Antalya, TurkeyS. MirPaediatric Nephrology, School of Medicine, Ege University,Izmir, TurkeyE. BaskinPaediatric Nephrology, School of Medicine, Baskent University,Ankara, TurkeyH. M. PoyrazogluPaediatric Nephrology, School of Medicine, Erciyes University,Kayseri, TurkeyI. AkilPaediatric Nephrology, School of Medicine,Celal Bayar University,Manisa, TurkeyS. BakkalogluPaediatric Nephrology, School of Medicine, Gazi University,Ankara, TurkeyA. SoyluPaediatric Nephrology, School of Medicine,Dokuz Eylul University,Izmir, Turkey

1-Bacanli A, Yerebakan Ö, Parmaksizoglu B, Yılmaz E, Alpsoy E:Topical Granulocyte-ColonyStimulating Factor For The Treatment Of Oral And Genital Ulcers Of Patients With Behçet's DiseaseJEur Acad Dermatol Venereol 2006;20:931-52-Akman A, Yilmaz E, Ciftcioglu MA, Alpsoy E:Unilateral erythema nodosum-like lesions andsuperficial thrombophlebitis together with ipsilateral thrombosis of the vena femoralis in Behcet'sdiseaseEur J Dermatol2006;16:703-43-Akman A, Kaçaroğlu H, Dönmez L, Bacanli A, Alpsoy E:Relationship between periodontal findingsand Behçet’s disease: a controlled study. J Clin Periodontol 2007;34(6):485-91.4-Akman A, Savas B, Uguz A, Ozhak B, Heper AO, Basaran E, Alpsoy E:Invasive Trichophtonrubrum infection resembling blastomycosis in a patient with altered immune status during the courseof chronic superficial Trichophyton rubrum Infection. Eur J Dermatol 2007;17(6):8-9.5-Akman A, Sallakci N, Coskun M, Bacanli A, Yavuzer U, Alpsoy E, Yegin O.TNF-alpha gene 1031T/C polymorphism in Turkish patients with Behçet's disease.Br J Dermatol. 2006 Aug;155(2):350-66-Alpsoy E, Zouboulis CC, Ehrlich GE:Mucocutaneous lesions of Behçet’s disease. Yonsei MedicalJournal2007; 48(4):573-85.7-Bacanli A, Sallakci N, Yavuzer U, Alpsoy E, Yegin O:Toll-like receptor 2 Arg753Gln genepolymorphism in Turkish patients with Behcet's disease. Clin Exp Dermatol. 2006;31(5):699-701.ŀDeri ve Zührevi Hastalıklar Anabilim Dalı - 2007

1- Leblebicioglu H, Rosenthal VD, Arikan OA, Yalcin AN, Turhan O,Device-associated hospitalacquiredinfection rates in Turkish intensive care units. Findings of the International NosocomialInfection Control Consortium (INICC) JOURNAL OF HOSPITAL INFECTION Volume: 65 Issue: 3Pages: 251-257 Published: MAR 20072-Sener B, Tunçkanat F, Ulusoy S, Tünger A, Söyletir G, Mülazimoğlu L, Gürler N, Oksüz L,Köksal I, Aydin K, Yalçin AN, Oğünç D, Acar A, Sievers J. A survey of antibiotic resistance inStreptococcus pneumoniae and Haemophilus influenzae in Turkey, 2004 2005.J AntimicrobChemother. 2007 Sep;60(3):587-93. Epub 2007 Jun 26.ŀEnfeksiyon Hastalıkları Anabilim Dalı

Journal of Hospital Infection (2007) 65, 251e257www.elsevierhealth.com/journals/jhinDevice-associated hospital-acquired infectionrates in Turkish intensive care units. Findingsof the International Nosocomial Infection ControlConsortium (INICC)H. Leblebicioglu a , V.D. Rosenthal b, *,Ö.A. Arıkan c ,A.Özgültekin d ,A.N. Yalcin e , I. Koksal f , G. Usluer g , Y.C. Sardan h , S. Ulusoy i ,the Turkish Branch of INICC 1a Ondokuz Mayis University Medical School, Samsun, Turkeyb Medical College of Buenos Aires, Buenos Aires, Argentinac Ankara University School of Medicine, Ibni Sina Hospital, Ankara, Turkeyd Haydarpasa Hospital, Istanbul, Turkeye Akdeniz University, Antalya, Turkeyf Karadeniz Technical University School of Medicine, Trabzon, Turkeyg Osmanganzi University, Eskisehir, Turkeyh Hacettepe University School of Medicine, Ankara, Turkeyi Ege University Medical Faculty, Izmir, TurkeyReceived 7 December 2005; accepted 18 October 2006Available online 25 January 2007* Corresponding author. Address: Department of Infection Control, Medical College of Buenos Aires, Arengreen 1366, 1405 BuenosAires, Argentina. Tel.: þ54 11 4432 7740; fax: þ54 11 4431 6476.E-mail address: victor_rosenthal@inicc.org1 Turkish branch of INICC:1. S. Esen, F. Ulger, Ondokuz Mayis University Medical School, Samsun.2. M. Tulunay, M. Oral, N. Ünal, Ankara University School of Medicine, Ibni Sina Hospital, Ankara.3. G. Turan, N. Akgün, Haydarpasa Hospital, Istanbul.4. G. Yildirim, A. Topeli, S. Unal, Hacettepe University School of Medicine, Ankara.5. O. Turhan, S. Keskin, Akdeniz University, Antalya.6. K. Aydin, R. Caylan, Karadeniz Technical University School of Medicine, Trabzon.7. I. Ozgúnes, N. Erben, Osmanganzi University, Eskisehir.8. B. Arda, F. Bacakoglu, Ege University Medical Faculty, Izmir.9. R. Ozturk, Y. Dikmen, G. Aygún, Istanbul University Cerrahpasa Medical School, Istanbul.10. S. Fatma, C. Mustafa, Y. Leyla, Harran University, Faculty of Medicine, Sanliurfa.11. I. Sencan, D. Ozdemir, S. Erdogan, Duzce Medical School, Duzce.12. E. Alp, B. Aygen, Erciyes University, Faculty of Medicine, Kayseri.0195-6701/$ - see front matter ª 2006 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.jhin.2006.10.012

1-Gilgil E, Kaçar C, Tuncer T:Reply the report:epidemi ology of rheumatoid arthritis in Turkey Clinrheumatol 25(5):772, 2006.2-Baser S, Cubukcu S, Ozkurt S, Sabir N, Akdag B, Diri E.Pulmonary involvement starts in earlystage ankylosing spondylitisScan J Rheumatol35(4):325-327 Jul 20063- Musculoskeletal sarcoidosis with a dermatologic clue for diagnosis: a case report. Cay F, Sezer I,Kacar C, Butun B, Tuncer T. Rheumatol Int. 2007 Mar;27(5):497-9.4-Legg-Perthes disease-like joint involvement and diagnosis delay in Scheie syndrome: a casereport.Melikoglu MA, Kocabas H, Sezer I, Cay HF, Cassidy AG, Balci N. Clin Rheumatol. 2007Nov;26(11):1937-9.Epub2007Jan315-Cay HF, Gungor HA, Sezer I, Kacar C, Balcı N:Adverse effect of TNF-alpha blocker?Demyelinationin an ankylosing spondylitis patient:a case report.J. of Clinical Pharmacy and Therapeutics.31:645-648,2006.ŀFiziksel Tıp ve Rehabilitasyon Anabilim Dalı - 2007

Clin Rheumatol (2006) 25: 772DOI 10.1007/s10067-006-0341-zLETTER TO THE EDITORErdal Gilgil . Cahit Kaçar . Tiraje TuncerReply to the report: epidemiology of rheumatoid arthritisin Turkey (by N. Akkoc, S. Akar)Published online: 24 May 2006# Clinical Rheumatology 2006Dear Editor,We thank Dr. Akkoç and Dr. Akar for their interest in ourarticle and for their valuable contribution of the previousliterature on the epidemiology of rheumatoid arthritis (RA)in Turkey. None of the former surveys were nationwide; onthe contrary, these surveys were mostly limited to a narrowregion, such as the one conducted on Balkan immigrants[1]. The study of Dr. Akkoç and Dr. Akar was conducted,as well, in only two quarters of Izmir and did not cover theother quarters, especially those that were inhabitedconsiderably by the people of rural origin [2]. This mightbe regarded as providing a sampling bias. Taking intoaccount the rapidly ongoing urbanization process inTurkey, we therefore made our sampling representing theurban Antalya as a whole [3]. Nevertheless, it is surprisingthat both they and we have estimated comparable prevalencerates of RA in surveys conducted in different citiesbut at time intervals close to each other. However, we donot agree with Dr. Akkoç and Dr. Akar as to the directstandardization of our findings to the general population ofTurkey, because for direct standardization, one needs toknow the specific rates of each population to be compared.Because neither a specific nor a crude prevalence rate ofRA for the general population of Turkey exists for the timebeing, even an indirect standardization cannot be estimated.So, the kind of standardization that they proposeremains undetermined.Although we intended to estimate a cumulative prevalencerate in our study, recall errors due to a “memorydecay”, especially for the patients in prolonged remission,might result in a cumulative prevalence rate lower thanexpected [4]. On the other hand, as we stated earlier, asystematic recording is not available in the Turkish healthcare system, and we attained only one patient’s record [3].This might be regarded as a drawback of our study;however, missing some of the cases in remission isunavoidable in epidemiological studies conducted indeveloping countries, at least owing to the inaccessibilityof the cases to the health care system and inadequaterecording of diseases.References1. Yenal O, Lav I, Bilecen L (1968) Epidemiological study on theinfectious rheumatic syndrome in Turkey. II. Occurrenceof rheumatoid arthritis in the Sagmalcilar district ofIstanbul. Influencing of various factors and tuberculosis. ZRheumaforsch 27:215–2232. Akar S, Birlik M, Gurler O, Sari I, Onen F, Manisali M, TirpanK, Demir T, Meral M, Akkoc N (2004) The prevalence ofrheumatoid arthritis in an urban population of Izmir–Turkey.Clin Exp Rheumatol 22:416–4203. Kacar C, Gilgil E, Tuncer T, Butun B, Urhan S, Arikan V,Dundar U, Oksuz MC, Sunbuloglu G, Yildirim C, Tekeoglu I,Yucel G (2005) Prevalence of rheumatoid arthritis in Antalya,Turkey. Clin Rheumatol 24:212–2144. Volinn E (1997) The epidemiology of low back pain in the restof the world: a review of surveys in low- and middle-incomecountries. Spine 22:1747–1754The online version of the original article can be found at: http://dx.doi.org/10.1007/s10067-005-0092-2.E. GilgilÖzel Gözde Medical Center,Adiyaman, TurkeyC. Kaçar (*) . T. TuncerAkdeniz University Faculty of Medicine,Antalya, Turkeye-mail: ckacar@akdeniz.edu.tr

Rheumatol Int (2007) 27:497–499DOI 10.1007/s00296-006-0245-xCASE REPORTMusculoskeletal sarcoidosis with a dermatologicclue for diagnosis: a case reportFatih Cay · Ilhan Sezer · Cahit Kacar · Bulent Butun ·Tiraje TuncerReceived: 11 September 2006 / Accepted: 18 September 2006 / Published online: 18 October 2006© Springer-Verlag 2006Abstract Sarcoidosis is a multisystem, inXammatorydisorder characterized by inWltration of any organ withnon-caseating granuloma. Clinical picture depends onwhich system(s) involved. Pulmonary, lymphatic andmusculoskeletal systems are the most commonlyaVected systems. Skin is one of the frequently involvedorgans. Its involvement may provide a direct diagnosticclue. Here we have presented a young man with systemicsarcoidosis. The major complaint from him wasthe musculoskeletal pain. But the route to diagnosisstarts from a lesion over the scalp.Keywords Scar sarcoidosis · MusculoskeletalinvolvementIntroductionSarcoidosis is a multisystem, inXammatory disordercharacterized by non-caseating granulomas, which caninWltrate any organ [1]. Disease may present at any age,but it is most frequently seen in early adulthood [2, 3].Chest (90%), eyes (20–80%) and skin are the mostcommonly aVected systems [4].Symmetrical, migratory, transient arthralgias withmyalgias and periarticular swellings are common complaintsin acute sarcoidosis. In chronic cases, articularinvolvement may mimick rheumatoid arthritis. Synovialand soft tissue biopsy may show the presence ofF. Cay (&) · I. Sezer · C. Kacar · B. Butun · T. TuncerPhysical Medicine Rehabilitation and RheumatologyDepartment, Akdeniz University School of Medicine,Dumlupinar Bulvari, Antalya, 07100, Turkeye-mail: fatihcay@akdeniz.edu.tr; drfatihcay@gmail.comgranulomas [3]. The cutaneous manifestation of sarcoidosis(20–35%) consists of non-speciWc and speciWcskin lesions [3, 5]. SpeciWc skin lesions are characterizedby granuloma formation [5]. In this case report wehave presented a young man who has sarcoidosis withmusculoskeletal complaints and scar sarcoidosis.Case reportA 29-year-old man was admitted to us with a complaintof arthralgias initially on his ankles then on knees,wrists and elbows, which began 3 months ago. The painwas most intense at night with a history of morningstiVness lasting for 2 h. Patient had blurred vision in hisleft eye for 1 week before admission to hospital. Hewas not complaining of fever, night sweats, weight loss,chest pain and cough. The past medical history ofpatient and his family were unremarkable.During physical examination we found swelling ofhands, tenderness on palpation over wrists, elbows,ankles and proximal interphalangeal joints of hands.Range of motion of wrists and right elbow was limited.The most surprising Wnding was an ulcerative scar overthe left parietal scalp. This was a sharp-edged, yellowish,edematous lesion with a diameter of about 4 cm(Fig. 1). Patient said that it was an old scar resultingfrom a trauma of scalp in childhood, and was inactivefor years and no ulceration was noticed. Ophtalmologicexamination revealed the presence optic neuritisand anterior uveitis on left eye. An enlarged lymphnode was palpated over the scalenius region. The restof systemic examination was normal.Laboratory Wndings of the patient are shown inTable 1. Chest X-ray revealed bilateral hilar prominence123

Clin Rheumatol (2007) 26:1937–1939DOI 10.1007/s10067-007-0549-6CASE REPORTLegg–Perthes disease-like joint involvementand diagnosis delay in Scheie syndrome: a case reportMeltem Alkan Melikoglu & Hilal Kocabas & Ilhan Sezer &Hasan Fatih Çay & Aysegul Guller Cassidy &Nilufer BalciReceived: 8 January 2007 /Accepted: 13 January 2007 / Published online: 31 January 2007# Clinical Rheumatology 2007Abstract Mucopolysaccharidosis (MPS) type I is aninherited disease caused by the absence or malfunctioningof lysosomal enzymes. Three subtypes, based on severity ofsymptoms, were described, and Scheie syndrome (also calledMPS I S) is the mildest form. Although there may be sometypical extra-articular manifestations, musculoskeletal involvementmay be the only presenting sign in the absenceof other symptoms in the patients with less severe forms. Thepatients with MPS I S, especially in attenuated phenotypes,may be sometimes difficult to recognize for physicians notfamiliar with the disease. With this case presentation, it isaimed to draw attention to this disease, which could bedelayed for the correct diagnosis. An increased awareness ofthe disease may contribute to more accurate diagnosis, andpatients may benefit from early intervention.Keywords Hip . Legg–Perthes disease .Mucopolysaccharidosis . Scheie syndromeIntroductionThe mucopolysaccharidoses (MPS) are a group of inheriteddiseases caused by the absence or malfunctioning ofM. A. Melikoglu (*) : H. Kocabas : I. Sezer : H. F. Çay :A. G. Cassidy : N. BalciDepartment of Physical Medicine and Rehabilitation,School of Medicine, Akdeniz University,Antalya, Turkeye-mail: mamelikoglu@gmail.comM. A. MelikogluTıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı,Romatoloji Bilim Dalı, Akdeniz Universitesi,Antalya, Turkeylysosomal enzymes. They are characterised by the accumulationof glycosaminoglycans (GAGs) in the lysosomesof all cells in the body except red blood cells and increasedGAG excretion in the urine. Seven distinct clinical typesand numerous subtypes of MPS have been identified [1].MPS I is divided into three subtypes based on severity ofsymptoms, and Scheie syndrome (also called MPS I S) isthe mildest form. Clinical features include joint involvementsand some extra-articular manifestations such ascardiac valvular problems, inguinal hernias, hearing lossand clouding of the cornea. Musculoskeletal involvementmay be the only presenting sign in the absence of othertypical symptoms in patients with the less severe forms.The aim of this case report is to draw attention to thepossible early articular involvements of this disease with aMPS I S case.CaseA 15-year-old male patient was referred to our departmentwith the complaints of deformity in hands, difficulty inwalking and limitation in movements of hips. At 6 years ofage, he presented to another medical centre with pain andlimitation in hips, without any other complaint or significantfamily or past medical history. A diagnosis of Legg–Perthesdisease was made depending on roentgenograms of hipjoints, and he was followed up with this diagnosis for 7 years.Two years ago, deformity in hands added to the firstcomplaints. After newly developed symptoms, his bloodand urine samples were evaluated, and MPS I S wasdiagnosed at 13 years of age. Furthermore, he had undergonean aortic valvuloplasty due to aortic insufficiency 5 monthsago.

Journal of Clinical Pharmacy and Therapeutics (2006) 31, 645–648CASE REPORTAdverse effect of TNF-alpha blocker? Demyelination inan ankylosing spondylitis patient: a case reportH. F. Cay* MD, H.A.Gungor MD, I.Sezer* MD, C.Kacar* MD and N. Balci* MD*PM&R and Rheumatology Department, Medical Faculty, Akdeniz University, Antalya, Turkey andNeurology Department, Medical Faculty, Akdeniz University, Antalya, TurkeySUMMARYAnti-tumour necrosis factor (TNF)-alpha agentspromise better disease control for treatment ofinflammatory arthritides which are resistant toclassical disease-modifying treatment and providebetter functional outcome. But these agentsare not free of adverse events. The exact relationshipbetween use of anti-TNF drugs anddevelopment of demyelination cannot be establishedyet. Here we present a case of a 36-year-oldman who developed demyelination in the cervicalspinal cord while he was being treated withetanercept for ankylosing spondylitis.Keywords: ankylosing spondylitis, anti-tumournecrosis factor-alpha drugs, transverse myelitisINTRODUCTIONAcute transverse myelitis (ATM) is a pathogeneticallyheterogenous inflammatory disorder affectingthe spinal cord at one or more segments, causingeither bilateral or partial, unilateral disease. Clinicalpresentation of ATM usually evolves overhours or days as para- or tetraparesis, a sensorylevel or sphincter dysfunction. It occurs in associationwith different viral and bacterial infections,systemic autoimmune diseases, multiple sclerosis,acute disseminated encephalomyelitis, neuromyelitisoptica and infrequently with Behcet’s disease(1, 2).Etanercept is one of the tumour necrosis factor(TNF)-alpha blocking agents, which are used forReceived 1 August 2006, Accepted 14 September 2006Correspondence: H. Fatih Cay, Physical Medicine Rehabilitationand Rheumatology Department, Faculty of Medicine, AkdenizUniversity, Dumlupınar Bulvarı, Antalya, Turkey. Tel.: +90 2422274343-55283; fax: +90 242 2274951; e-mail: fatihcay@akdeniz.edu.tr; drfatihcay@gmail.comthe treatment of inflammatory arthritides includingrheumatoid arthritis, ankylosing spondylitis andpsoriatic arthritis. TNF-alpha blocking agents maybe associated with neurological adverse eventsincluding central (3, 4) and peripheral (5) nervoussystem demyelination. We presented a case of ayoung man with ankylosing spondylitis, whosubsequently developed ATM at cervical spinalcord while he was being treated with etanercept.CASE REPORTA 36-year-old man with ankylosing spondylitispresented with a 5-day history of numbness thatbegan over the dorsum of the foot and graduallyextended to the axilla on the left side of the body.He was not complaining of any muscular weakness,imbalance, disturbance of gait, urinary orbowel incontinence or any change in mental status.The right side of the patient was free of anysymptom. He had been diagnosed with ankylosingspondylitis at age 21. He was being treated withetanercept (25 mg twice weekly) for about6 months. Etanercept improved his complaintsdramatically. Family history was significant forankylosing spondylitis and multiple sclerosis in hisbrother; the latter was treated with interferon beta.On neurological examination we found loss of painand touch sensations on the left side, distal to thesecond thoracic dermatomal level. Deep tendonreflexes were hyperactive on the left lowerextremity. Plantar response was absent on the leftside. The remaining neurological examination andsystemic evaluation were normal. His arthritis wassilent at the time of evaluation. Magnetic resonanceimaging (MRI) of the spinal cord revealed ahyperintense lesion at the right fifth and sixth cervical(C5–C6) levels on T2 – weighted images withintense contrast enhancement after gadoliniumÓ 2006 The Authors. Journal compilation Ó 2006 Blackwell Publishing Ltd 645

1-Cilli A, Ozkaynak C, Onur R, Erogullari I, Ogus C, Cubuk M, Arslan G, Ozdemir T:Lung cancerdetection with LDCT in COPD patients.Acta Radiol48(4):405-11, 20072- The effects of recurrent Pseudomonas aeruginosa infection on pulmonary parenchyma andvasculature in rats fed on a cholesterol-rich diet. Ozbudak O, Ogus C, Saba R, Turkay C, Sahin N,Ozbilim G, Kiliçarslan B. Exp Lung Res. 2006 Aug;32(7):275-85.ŀGöğüs Hastalıkları Anabilim Dalı - 2007

Experimental Lung Research, 32:275–285, 2006Copyright # Informa HealthcareISSN: 0190-2148 print/1521-0499 onlineDOI: 10.1080/01902140600880240THE EFFECTS OF RECURRENT PSEUDOMONAS AERUGINOSAINFECTION ON PULMONARY PARENCHYMA AND VASCULATUREIN RATS FED ON A CHOLESTEROL-RICH DIETExp Lung Res Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/11/10For personal use only.Ömer Özbudak and Candan Ogus & Department of Respiratory Diseases,Akdeniz University Faculty of Medicine, Antalya, TurkeyRabin Saba & Department of Infectious Diseases, Akdeniz University Facultyof Medicine, Antalya, TurkeyCengiz Turkay & Department of Cardiovascular Surgery, Akdeniz UniversityFaculty of Medicine, Antalya, TurkeyNursel Sahin & Department of Anaesthesiology, Akdeniz University Facultyof Medicine, Antalya, TurkeyGülay Özbilim and Bahar Kiliçarslan & Department of Pathology, AkdenizUniversity Faculty of Medicine, Antalya, Turkey& It has been demonstrated that both hypercholesterolemia and infectious agents are contributingfactors in atherosclerosis but their combined effect on the pulmonary vascular bed is not known. Toanswer this question, the authors tried to demonstrate the effects of recurrent infection on pulmonaryparenchyma and vascular system in cholesterol-fed rats. Sixty-six rats were randomly dividedinto 4 groups: Groups I (control), II (cholesterol-rich diet), III (recurrent pulmonary Pseudomonasaeruginosa infection), IV (cholesterol-rich diet þ recurrent infection). After 6 months serumcholesterol levels didn’t increase in any of the groups. Central pulmonary artery wall thicknesswas increased in group IV (P < .0001). Although not significant, peripheral pulmonary arterywall thickness was increased in group IV. In rats fed on a cholesterol-rich diet, recurrent infectioncaused a significant increase in atherosclerosis, although serum cholesterol levels didn’t increase.Infection and cholesterol-rich diet have a synergistic effect on atherosclerosis in the pulmonary vascularsystem in rats even in the absence of hypercholesterolemia.Received 22 March 2006; accepted 1 June 2006.The authors would like to thank Medical Veterinarian S. Atalay (Akdeniz University ExperimentalAnimal Laboratory) for his assistance in the rat intratracheal inoculation during the initial stage of thestudy. This study was supported by the Akdeniz University Scientific Project Unit.Address correspondence to Ömer Özbudak, Department of Respiratory Diseases, Akdeniz UniversityFaculty of Medicine, Antalya, Turkey. E-mail: ozbudak@akdeniz.edu.tr

ORIGINAL ARTICLEACTA RADIOLOGICALung Cancer Detection with Low-Dose Spiral Computed Tomography inChronic Obstructive Pulmonary Disease PatientsA. CILLI, C.OZKAYNAK, R.ONUR, I.EROGULLARI, C.OGUS, M.CUBUK, G.ARSLAN &T.OZDEMIRAkdeniz University School of Medicine, Departments of Respiratory Diseases and Radiology, Antalya, TurkeyActa Radiol Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/11/10For personal use only.Cilli A, Ozkaynak C, Onur R, Erogullari I, Ogus C, Cubuk M, Arslan G, Ozdemir T.Lung cancer detection with low-dose spiral computed tomography in chronic obstructivepulmonary disease patients. Acta Radiol 2007;48:405–411.Purpose: To determine whether low-dose spiral computed tomography (LDCT) canimprove the lung cancer detection rate in chronic obstructive pulmonary disease (COPD)subjects.Material and Methods: From October 1999 to December 2003, 374 COPD patientsunderwent LDCT for lung carcinoma screening. All subjects with an abnormal baselineCT scan were followed with serial CT scans as part of our protocol. Follow-up wascontinued until the demonstration of no change over a minimum of 24 months, orresolution. Sputum samples were also obtained for cytological analysis.Results: On the baseline spiral CT scan, 132 of 374 patients (35.2%) had at least one noncalcifiednodule that required periodic follow-up with CT scans. The median follow-uptime was 21 months (range 2–48 months). Of the 374 COPD subjects, nine patients withprimary lung cancer (2.4%) were detected: six were squamous cell carcinomas, two weresmall-cell lung carcinomas (SCLC), and one was adenosquamous carcinoma. Three ofthe nine tumors were in stage IA, two in stage IIB, two in stage IIIA, and two werelimited SCLC. Potentially curative pulmonary resection was performed in four patients,pulmonary lobectomy in three, and wedge excision in one. One subject with stage IAsquamous cell carcinoma received radiotherapy, as pulmonary function was severelyimpaired. In addition, four patients underwent removal of benign lesions. Sputum wascollected in 205 (54.8%) of 374 patients. There were 154 (75 %) metaplasia, 14 (6%)moderate dysplasia, and one (0.4%) malignant case.Conclusion: LDCT increases early lung carcinoma detection rate in COPD patients, butpulmonary function impairment may reduce its benefit.Key words: Adults; chronic obstructive airways disease; CT; lung; screening; thoraxCan Ozkaynak, Akdeniz Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, DumlupınarBulvarı, 07070, Antalya, Turkey (tel. +90 242 249 60 00 ext. 6444, fax. +90 242 2278575,e-mail. can@akdeniz.edu.tr)Accepted for publication 5 January 2007In Turkey, lung cancer is the most common cause ofcancer-related death among men (24). With anannual age-standardized incidence rate of 61.6 per100,000, Turkey has the highest lung cancerincidence rate among men worldwide (6). It hasalso been reported that non-small-cell lung cancer(NSCLC) is diagnosed at more advanced stages inTurkey than in developed countries (7). Theincidence is closely related to the high prevalenceof smoking (63% of males) in our population (3).Turkey alone smoked 2% of the global and 14% ofthe regional cigarette consumption in 2001 (23).A number of randomized, controlled screeningtrials using chest radiographs and sputum cytologyhave failed to demonstrate a reduction of lungcancer-related mortality in the screened population.Low-dose computed tomography (LDCT) is atechnique that allows a low-resolution image ofthe entire thorax to be obtained in a single breathholdwith low radiation exposure. Low-dose CTdetects lung cancer at an earlier stage and smallersize compared to chest X-ray. Currently, due to theabsence of evidence regarding mortality and concernsabout overdiagnosis, screening with LDCT forindividuals without symptoms or a history of canceris not recommended (1).Several studies have shown that airway obstructionis associated with an increased risk of lungDOI 10.1080/02841850701227776# 2007 Taylor & Francis

1-Isikoglu M (Isikoglu, M.), Senol Y (Senol, Y.), Berkkanoglu M (Berkkanoglu, M.), Ozgur K(Ozgur, K.), Donmez L (Donmez, L.)Considerations of third-party reproduction in Iran - ReplyHUMAN REPRODUCTION Volume: 22 Issue: 3 Pages: 902-903 Published: MAR 20072- Ozgur K, Isikoglu M, Donmez L, Is hysteroscopic correction of an incomplete uterineseptum justified prior to IVF? Conference Information: 59th Annual Meeting of the American-Society-for-Reproductive-Medicine, OCT 11-15, 2003 SAN ANTONIO, TX REPRODUCTIVEBIOMEDICINE ONLINE Volume: 14 Issue: 3 Pages: 335-340 Published: MAR 2007ŀHalk Sağlığı Anabilim Dalı

Author(s): Isikoglu M (Isikoglu, M.), Senol Y (Senol, Y.), Berkkanoglu M (Berkkanoglu, M.), Ozgur K (Ozgur, K.),Donmez L (Donmez, L.)Source: HUMAN REPRODUCTION Volume: 22 Issue: 3 Pages: 902-903 Published: MAR 2007Times Cited: 0 References: 3 Citation MapDocument Type: LetterLanguage: EnglishReprint Address: Isikoglu, M (reprint author), Antalya IVF, Halide Edip Cad 7, TR-07080 Antalya, TurkeyAddresses:1. Antalya IVF, TR-07080 Antalya, TurkeyE-mail Addresses: misikoglu@hotmail.comPublisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLANDSubject Category: Obstetrics & Gynecology; Reproductive BiologyIDS Number: 147OGISSN: 0268-1161DOI: 10.1093/humrep/del444ŀConsiderations of third-party reproduction in Iran - Reply

Is hysteroscopic correction of an incomplete uterine septum justified prior toIVF?Biomed Online. 2007 Mar;14(3):335-40.Ozgur K, Isikoglu M, Donmez L, Oehninger S.Antalya IVF, Halide Edip Cad. No:7, Dokuma, 07080 Antalya, Turkey.AbstractThis retrospective study examined the effect of hysteroscopic correction of an incomplete uterine septum on IVFoutcome. Measurement of the Fm (fundal myometrial thickness) and Cm (cornual myometrial thickness) wasperformed by sonohysterography. Group 1 included patients diagnosed with incomplete septum (n = 119),fulfilling the two criteria of Fm >11 mm and Fm-Cm >5 mm, who underwent hysteroscopic incision of theincomplete septum. Group 2 consisted of 116 age-matched control patients with a normal uterine cavity whounderwent IVF within the same time period. Main outcome measures were clinical pregnancy and spontaneousabortion rates. Patients in group 1 had a history of more spontaneous abortions than patients in group 2 (14.20versus 6.03%, P = 0.04) as well as higher previous IVF failure (32.7 versus 20.6%, P = 0.04). After surgicalŀReprodcorrection of the septum in group 1, IVF pregnancy outcome was similar in both groups (clinical pregnancy andpregnancy loss of 47.80 versus 46.50% and 10.52 versus 20.3% respectively). A similar pregnancy outcome wasfound after the incision of the incomplete septum compared with a group with normal uterine cavity. Largerprospective and randomized controlled studies are needed to prove the positive effect of correction of anincomplete uterine septum on IVF outcome.PMID: 17359587 [PubMed - indexed for MEDLINE]

Hastalıkları Anabilim Dalı1-Artaç M, Sarı R.Brucellosis in febrile neutropeniaLeuk Lymphoma. 2007 Apr;48(4):827-8.2-Ozturk OH, Bozcuk H, Burgucu D, Ekinci D, Ozdogan M, Akca S,Cisplatin cytotoxicity is enhancedwith zoledronic acid in A549 lung cancer cell line: preliminary results of an in vitro studyCell Biol Int.2007 Sep;31(9):1069-71. Epub 2007 Feb 253-Ozdogan M, Samur M, Artac M, Yildiz M, Savas B, Bozcuk HS.Factors related to truth-tellingpractice of physicians treating patients with cancer in Turkey.J Palliat Med. 2006 Oct;9(5):1114-94-Coban E, Yilmaz A, Sari R.The effect of weight loss on the mean platelet volume in obesepatients.Platelets.18(3): 212-216, 20075-Asuman Yavuz, Fevzi F. Ersoy , Ploumis S. Passadakis ,et al.Phosphate control in peritonealdialysis patients (Kidney International’a kabul edildi.)6-Kocak H, Gumuslu S, Ermis C, Mahsereci E, Sahin E, Gocmen AY, Ersoy F, Suleymanlar G,Yakupoglu G, Tuncer M. Oxidative stress and asymmetric dimethylarginine is independentlyassociated with carotid intima media thickness in peritoneal dialysis patients.Am J Nephrol.2008;28(1):91-6. Epub 2007 Oct 3.7-Taskapan H, Ersoy FF, Passadakis PS, et alSevere vitamin D deficiency in chronic renal failurepatients on peritoneal dialysis Clin Nephrol. 2006 .Oct;66(4):247-558-Gurkan A, Yakupoglu U, Yavuz A, Dikici H, Yakupoglu YK, Tuncer M, Demirbas A, ErsoyF.Hemophagocytic syndrome in kidney transplant recipients: report of four cases from a single centerActa Haematol. 2006;116(2):108-139-Çakır M, Arıcı C, Alakus H, Altunbas H, Balcı MK, ŀİçKarayalçın Ü: Incidental thyroid carcinoma inthyrotoxic patients treated by surgeryHormone Res 67(2): 96-99, 200710-Sari R., Balcı MK, Balci N, Karayalçın Ü.Acute effect of exercise on plasma leptin level and insulinresistance in obese women with stable caloric intake.Endocrine Research32(1-2): 9-17, 200711-Seckin Y, Harputluoğlu MMM, Batcioglu K, Karincaoglu m,Gastric tissue oxidative change in portalhypertansion and cirrosicDig Dis Sci52: 1154-1158, 200712-Kosar F, Ates F, Sahin I, Karincaoglu M, Yildirim B QT interval analysisin patients with chronic liverdisease: A prospective study.Angiology58: 218-224, 200713- Coban E, Yazicioglu G, Ozdogan M. Platelet activation in subjects with subclinicalhypothyroidism. Med Sci Monit 2007;13 (4): CR211-214.14- Coban E, Kucuktag S, Basyigit S. Platelet activation in subjects with impaired glucosetolerance. Platelets 2007;18 (8): 591-594.15- Ozdogan M, Bozcuk H, Coban E. Low-grade inflammation in subjects with white-coathypertension. Med Sci Monit 2007;13 (12): CR570-573.

Leukemia & Lymphoma, April 2007; 48(4): 827 – 828LETTER TO THE EDITORBrucellosis in febrile neutropeniaMEHMET ARTAC & RAMAZAN SARIDepartment of Internal Medicine, School of Medicine, Akdeniz University, Antalya, TurkeyLeuk Lymphoma Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/11/10For personal use only.(Received 10 August 2005; accepted 11 November 2005)Neutropenia is the major factor predisposing cancerpatients to infection, chiefly by bacteria. In neutropenicpatients, antimicrobial or antifungal therapyshould be instituted before the microbiologicaldiagnosis is made; therapy is optimally guided by aspecific microbiological diagnosis [1]. In the etiologyof febrile neutropenia, 50% of cases are establishedmicrobiologically and 25% of them are documentedclinically. In the remaining 25% of cases, the originof fever is unknown but most cases respond toempirical antibiotic treatment [2].Brucellosis is one of the causes of a fever ofunknown origin, which still comprises one of themost prevalent diseases in endemic areas [3]. Theincidence of brucellosis in humans is between 0.62%and 7%. Annually, there are 500 000 new cases ofbrucellosis reported worldwide, although it is estimatedthat only approximately 4% of cases arerecognized and reported [3]. The disease has beenknown for hundreds of years in the Mediterranenregion and is still a public health problem in someparts of the world where unpasteurized or unboiledmilk is frequenty used [4].Transmission of brucellosis to humans occursthrough the consumption of infected, unpasteurrizedanimal-milk products, through direct contact withinfected animal parts, and through the inhalation ofinfected aerosolized particles [5]. It can be alive inphagocytes and continue to reproduce. It can spreadhematogenously in the neutrophils and is phagocytosedin the reticuloendothelial system. Althoughreproduction still continues in the reticuloendothelialsystem, sensitized T-lymphocytes and cytokines activatethe macrophages, which become resistant tointracellular reproduction and the bactericidal responsestarts. After this period, the outcome ofinfection depends on microbial virulance and cellularimmunity. However, humoral immunity also takespart in prevention of the disease. After entering thehuman body, the inoculation period ranges from 2 to 8weeks, although it can be longer in endemic areas [3].The majority of cases are attributed to Brucellamelitensis, although Brucella abortus, Brucella suis andBrucella canis are the other species of brucella that cancause human disease. The most common clinical signis fever, which can be spiking and accompanied byrigors, if bacteremia is present, or may be relapsing,mild and protracted [6]. Constitutional symptoms(e.g. malaise, arthralgias) are generally present. Physicalexamination is generally nonspecific [7 – 9], butlymphadenopathy, hepatomegaly, or splenomegalymay be present. The classic signs and symptoms ofbrucellosis may not be encountered in cancer patientsdue to humoral and cellular immune immunedeficiency, decreased inflammatory response and adecreased neutrophil count. The most commonlaboratory findings are hematologic (relative lymphocytosis,thrombocytopenia, leukopenia andpancytopenia) and transaminasemia [6]. Leukocytosisis rarely seen but leukopenia may appear in 30%of patients [10]. Brucellosis should be considered asa possible diagnosis among patients with pancytopeniain endemic areas [6]. Pancytopenia was transientand resolved after the antibiotic treatment of Brucellainfection [6].Blood cultures are most useful in acute disease,and cultures of infected tissues, bone marrowbiopsies and pus from abscesses may also be helpful[11]. The microorganism can be grown in blood andbone marrow cultures in 70% and 90% of cases,Correspondence: Ramazan Sari, Department of Internal Medicine, School of Medicine, Akdeniz University, TR-07070, Antalya, Turkey.E-mail: rsari@akdeniz.edu.trISSN 1042-8194 print/ISSN 1029-2403 online Ó 2007 Informa UK Ltd.DOI: 10.1080/10428190500518842

We found 1 article by title matching your search:Cell Biol Int. 2007 Sep;31(9):1069-71. Epub 2007 Feb 25.Cisplatin cytotoxicity is enhanced with zoledronic acid in A549 lung cancer cellline: preliminary results of an in vitro study.Ozturk OH, Bozcuk H, Burgucu D, Ekinci D, Ozdogan M, Akca S, Yildiz M.Akdeniz University, Department of Biochemistry, Antalya, Turkey.AbstractWe tested whether zoledronic acid, a biphosphonate with proposed apoptotic activity, augmented the cytotoxicity of cisplatin and/orgemcitabine in A549 lung cancer cell line. This cell line was subjected to different concentrations of the above chemotherapeutic agentsand zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay.Particularly, zoledronic acid in 100 micromolar (microM) concentration augmented the cytotoxicity by cisplatin 1microg/ml from 25% to70% (Z=3.22, P=0.0072). A significant portion of cells underwent apoptosis with or without zoledronic acid, but more so with thecombination treatment as assessed by an Annexin V-FITC apoptosis detection kit. However, 100microM zoledronic acid showed 50%cytotoxicity on its own, but failed to improve cytotoxicity by Gemcitabine. Thus, we show for the first time in a lung cancer cell line thatzoledronic acid bears cytotoxic potential on its own and in conjunction with cisplatin. The clinical potential of this finding should be furtherstudied.PMID: 17418595 [PubMed - indexed for MEDLINE]

Factors related to truth-telling practice of physicians treating patients with cancerin Turkey.Palliat Med. 2006 Oct;9(5):1114-9.Ozdogan M, Samur M, Artac M, Yildiz M, Savas B, Bozcuk HS.Department of Medical Oncology, Akdeniz University School of Medicine, Antalya, Turkey. mustafa0051@hotmail.comAbstractBACKGROUND: In the practice of oncology, effective communication between physician and patient is very important. Although manystudies have indicated that a large majority of physicians, especially from Western countries, tell the truth about diagnosis and prognosis,little is known about attitudes of physicians in Turkey toward truth-telling.OBJECTIVE: In this study, we tried to determine the truth-telling practice of physicians and explore potential related factors with a selfreportedquestionnaire.DESIGN: Using a questionnaire, 131 cancer specialists were interviewed during the 15th National Oncology Meeting in April 2003.RESULTS: The percentage of physicians who never, rarely, generally, and always prefer truthtelling about a cancer diagnosis were 9%,39%, 45%, and 7%, respectively. In univariate logistic regression analysis for the truth-telling practice, significant variables included "doŀJnot tell" requests from family, experiences from medical training and clinical practice, and medical specialty. In the multivariate analysis,"do not tell" requests from relatives and medical training factors retained their significance.CONCLUSION: Professional training in breaking bad news is important and is associated with the self-reported truth-telling practices ofphysicians.PMID: 17040149 [PubMed - indexed for MEDLINE]

Platelets, May 2007; 18(3): 212–216The effect of weight loss on the mean platelet volume in obese patientsERKAN COBAN 1 , ALPARSLAN YILMAZ 1 , & RAMAZAN SARI 21 M.D., Department of Internal Medicine, Akdeniz University Faculty of Medicine, Antalya, Turkey and2 M.D., Department of Internal Medicine, Division of Endocrinology and Metabolism, Akdeniz UniversityFaculty of Medicine, Antalya, Turkey(Received 15 August 2006; accepted 24 August 2006)Platelets Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/11/10For personal use only.AbstractObesity is a chronic metabolic disorder associated with cardiovascular disease and atherosclerosis. Platelet activationand aggregation are central processes in the pathophysiology of cardiovascular disease. Mean platelet volume (MPV),a determinant of platelet activation, is a newly emerging risk marker for atherothrombosis. Our objective was to evaluate theeffect of weight loss on the MPV in obese patients. We selected 30 obese women patients and 30 non-obese healthy womensubjects. All obese patients took the same content and caloric diet treatment for 3 months. Body mass index (BMI),metabolic parameters and MPV were measured at baseline and after 3 months diet treatment. Before diet treatment, obesegroup had significantly higher MPV levels than in the non-obese control group (8.18 1.09 fl vs. 8.01 0.95 fl, p ¼ 0.004).MPV showed positive correlations with BMI level in the obese group (r ¼ 0.43, p ¼ 0.017). BMI significantly decreasedafter diet treatment (36.2 3.2 kg/m 2 vs. 34.7 3.6 kg/m 2 , p50.001), in the obese group. MPV significantly decreasedafter diet treatment in the obese group (8.18 1.09 fl vs. 8.08 1.02 fl, p ¼ 0.013). There was a positive correlationbetween weight loss and reduction in MPV (r ¼ 0.41, p ¼ 0.024). In addition to its well-known positive effects oncardiovascular disease risk, weight loss may also possess significant anti-platelet activation properties that can contributeits antiatherogenic effects in obese patients.Keywords: Obesity, weight loss, mean platelet volumeIntroductionCoronary heart disease is the major cause of deathin the developed world [1]. Platelet activation andaggregation are central processes in the pathophysiologyof coronary heart disease [2, 3]. Allen et al.described that platelets normally circulate in aquiescent disc-shaped state and as they activate theyundergo a disc-to-sphere transformation with thedevelopment of pseudopodia, causing a subsequentincrease in size [4]. Mean platelet volume (MPV) is amarker of platelet activation [5]. Elevated MPV levelshave been identified as an independent risk factor formyocardial infarction in patients with coronary heartdisease [6] and for death or recurrent vascular eventsafter myocardial infarction [7]. Moreover, increasedplatelet size has been reported in patients withvascular risk factors such as diabetes [8], hypercholesterolemia[9], smoking [10], and in patients withrenal artery stenosis [11]. Recently, we found thatelevated MPV in obese patients [12].Obesity is a chronic metabolic disorder associatedwith cardiovascular disease (i.e., insulin resistance andtype 2 diabetes mellitus, dyslipidemia, hypertension),and there is evidence that weight loss has positiveeffects on cardiovascular disease risk [13–16].Moreover, these metabolic benefits are often foundafter only modest weight loss (5% of initial weight)and continue to improve in a continuous fashionwith increasing weight loss [17]. According to ourknowledge, there have been only two studies withconflicting results about the effect of weight loss on theMPV level, in obese patients [18, 19]. Therefore, ourobjective was to evaluate the effect of weight loss on thelevels of MPV in obese patients.Material and methodsPatientsThis study was performed at the outpatients clinicin the Department of Internal Medicine of AkdenizUniversity Hospital. We selected 30 obese womenpatients (mean age 48.1 13.5 years) having a bodymass index (BMI) 30 kg/m 2 and matched for age(mean age 47.2 12.3 years) and 30 non-obesehealthy women subjects who attended our outpatientsclinic. All patients gave their informedCorrespondence: Erkan Coban, M.D., Akdeniz University Faculty of Medicine, Department of Internal Medicine, 07070, Antalya, Turkey. Tel: þ90 2422496000/55141. Fax: þ90 242 2274490. E-mail: ecoban@akdeniz.edu.trISSN 0953–7104 print/ISSN 1369–1635 online ß 2007 Informa UK Ltd.DOI: 10.1080/09537100600975362

Int Suppl. 2008 Apr;(108):S152-8.Phosphorus control in peritoneal dialysis patients.Yavuz A, Ersoy FF, Passadakis PS, Tam P, Evaggelos DM, Katopodis KP, Ozener C, Akçiçek F, Camsari T, Ateş K, Ataman R,Vlachojannis GJ, Dombros NA, Utaş C, Akpolat T, Bozfakioğlu S, Wu G, Karayaylali I, Arinsoy T, Stathakis CP, Yavuz M, Tsakiris DJ,Dimitriades AC, Yilmaz ME, Gültekin M, Süleymanlar G, Oreopoulos DG.Akdeniz University, Antalya, Turkey.AbstractHyperphosphatemia is independently associated with an increased risk of death among dialysis patients. In this study, we haveassessed the status of phosphate control and its clinical and laboratory associations in a large international group of patients on chronicperitoneal dialysis (PD) treatment. This cross-sectional multicenter study was carried out in 24 centers in three different countries(Canada, Greece, and Turkey) among 530 PD patients (235 women, 295 men) with a mean+/-s.d. age of 55+/-16 years and meanduration of PD of 33+/-25 months. Serum calcium (Ca(2+)), ionized Ca(2+), phosphate, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D(3), 1,25-dihydroxy vitamin D(3), total alkaline phosphatase, and bone alkaline phosphatase concentrations were investigated,along with adequacy parameters such as Kt/V, weekly creatinine clearance, ŀKidneyand daily urine output. Mean Kt/V was 2.3+/-0.65, weeklycreatinine clearance 78.5+/-76.6 l, and daily urine output 550+/-603 ml day(-1). Fifty-five percent of patients had a urine volume of or =9.5 mg per 100 ml in 250 patients (49%), between 8.5 and 9.5 mg per100 ml in 214 patients (40%), and lower than 8.5 mg per 100 ml in 66 patients (12%). Ca x P product was >55 mg(2)dl(-2) in 136patients (26%) and lower than 55 mg(2)dl(-2) in 394 patients (74%). Serum phosphorus levels were positively correlated with serumalbumin (P

Oxidative stress and asymmetric dimethylarginine is independently associatedwith carotid intima media thickness in peritoneal dialysis patients.J Nephrol. 2008;28(1):91-6. Epub 2007 Oct 3.Kocak H, Gumuslu S, Ermis C, Mahsereci E, Sahin E, Gocmen AY, Ersoy F, Suleymanlar G, Yakupoglu G, Tuncer M.Department of Nephrology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.AbstractBACKGROUND: Oxidative stress (OS) and asymmetric dimethylarginine (ADMA) are accepted as nonclassical cardiovascular riskfactors in end-stage renal disease patients. To clarify the role of these factors in the atherosclerotic process, we investigated if OS andADMA are associated with common carotid artery intima media thickness (CIMT) in peritoneal dialysis (PD) patients.METHODS: Thirty PD patients without known atherosclerotic disease and classical cardiovascular risk factors as well as age- andgender-matched 30 healthy individuals were included. We measured serum thiobarbituric acid-reactive substances (TBARS),malondialdehyde (MDA), advanced glycation end product (AGE), pentosidine, advanced oxidation protein products (AOPP), ADMA andCIMT in each subjects.RESULTS: TBARS, MDA, AOPP, AGE, pentosidine and ADMA levels were significantly higher in PD patients than in controls (p

Nephrol. 2006 Oct;66(4):247-55.Severe vitamin D deficiency chronic renal failure patients on peritoneal dialysis.Taskapan H, Ersoy FF, Passadakis PS, Tam P, Memmos DE, Katopodis KP, Ozener C, Akcicek F, Camsari T, Ates K, Ataman R,Vlachojannis JG, Dombros NA, Utas C, Akpolat T, Bozfakioglu S, Wu G, Karayaylali I, Arinsoy T, Stathakis CP, Yavuz M, Tsakiris DJ,Dimitriades AD, Yilmaz ME, Gültekin M, Oreopoulos DG.Inonu University Medical School, Department of Medicine, Division of Nephrology, Malatya, Turkey. hulyataskapan@yahoo.comAbstractThe aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis(PD) and to correlate the findings with various demographic and renal osteodystrophy markers.METHOD: This cross-sectional, multicenter study was carried out 273 PD patients with a mean age of 61.7 +/- 10.9 years and meanduration of PD 3.3 +/- 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that areon the same latitude, namely, 36-42 degrees north. We measured 25(OH)D3 and 1.25(OH)2D3 levels and some other clinical andlaboratory indices of bone mineral metabolism.ŀClinRESULTS: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D3 levels less than 15 ng/ml, 119(43.6%) had severe vitamin D deficiency i.e., serum 25(OH)D3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiencyi.e., serum 25(OH)D3 levels, 5-15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e., serum 25(OH)D3 levels 15 - 30 ng/ml and only 10 (3.6%)had adequate vitamin D stores. We found no correlation between 25(OH)D3 levels and PTH, serum albumin, bone alkalinephosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D3 were age, presence of diabetes(DM-CRF), levels of serum calcium and serum 1.25(OH)2D3.CONCLUSION: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom hadsevere vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findingssuggest that these patients should be considered for vitamin D supplementation.PMID: 17063991 [PubMed - indexed for MEDLINE]

Hemophagocytic syndrome in kidney transplant recipients: report of four casesfrom a single center.Haematol. 2006;116(2):108-13.Gurkan A, Yakupoglu U, Yavuz A, Dikici H, Yakupoglu YK, Tuncer M, Demirbas A, Ersoy F.Akdeniz University Organ Transplantation Center, Antalya, Turkey.AbstractBACKGROUND: The prognosis of hemophagocytic syndrome (HPS) in kidney transplant recipients is reported to be poor, however theoptimal therapeutic approach is still unclear.PATIENTS AND METHODS: The clinical and follow-up data of the 4 patients with HPS (3 male, 1 female; age 39.7 +/- 11.3 years)among 368 kidney transplant recipients during a 5-year period were retrospectively analyzed.RESULTS: HPS developed 35-61 days in the post-transplant period. All 4 patients presented with fever. Hepatosplenomegaly andlymphadenopathy were observed only in the first patient. Laboratory tests revealed pancytopenia and hyperferritinemia in all patients,but elevated liver enzymes were observed in 3. Two patients had cytomegalovirus infection, and 1 had Epstein-Barr virus infection.Three patients died despite aggressive supportive therapy, however the fourth case survived after graft nephrectomy.ŀActaCONCLUSION: HPS pathogenesis in kidney transplants appears to be related with the graft itself. Graft nephrectomy may be thepreferable therapeutic approach for kidney transplant recipients with HPS resistant to standard supportive therapy.PMID: 16914905 [PubMed - indexed for MEDLINE]

Res. 2007;67(2):96-9. Epub 2006 Oct 17.Incidental thyroid carcinoma in thyrotoxic patients treated by surgery.Cakir M, Arici C, Alakus H, Altunbas H, Balci MK, Karayalcin U.Division of Endocrinology and Metabolism, Department of General Surgery, School of Medicine, Akdeniz University, Antalya, Turkey.cakirmehtap@yahoo.comAbstractBACKGROUND AND AIMS: Thyroid malignancy detected incidentally in patients who are operated for thyrotoxicosis has been reportedat different rates. The aim of this study was to investigate the rate of incidental thyroid carcinoma in thyrotoxic patients managed withsurgery in our institution.METHODS: Of the 375 thyrotoxic patients who had thyroid surgery between the years of 1997-2004, 70.7% were females and 29.3%were males. Among thyrotoxic patients 65.3% (n=245) had toxic multinodular goiter (TMG), 16.8% (n=63) had toxic adenoma (TA) and17.9% (n=67) had Graves' disease.RESULTS: Twenty-six (6.9%) of all thyrotoxic patients had thyroid carcinoma. Eighteen (7.3%) of TMG, 4 (6.3%) of TA and 4 (6%) ofGraves' disease patients had thyroid carcinoma. Histologic examination ŀHormrevealed 18 papillary (9 microscopic), 5 follicular, 2 hurthle celland 1 anaplastic carcinoma.CONCLUSION: In our study, incidental thyroid carcinoma was found in 6.9% of subjects with thyrotoxicosis. Papillary thyroidmicrocarcinomas constituted 34.6% (26/9) of these newly diagnosed thyroid carcinomas. The incidence of thyroid carcinoma was nothigher in subjects with Graves' disease compared to TMG and TA. The rate of incidental thyroid carcinoma in subjects withthyrotoxicosis treated with surgery was similar to previous studies reported from different countries.PMID: 17047344 [PubMed - indexed for MEDLINE]

218Angiology Volume 58, Number 2, 2007QT Interval Analysis in Patients WithChronic Liver Disease: A Prospective StudyFeridun Kosar, MD,* Fehmi Ates, MD, † Ibrahim Sahin, MD, ‡Melih Karincaoglu, MD, † and Bulent Yildirim, MD, † Malatya, TurkeyIn previous studies, it has been shown that QT interval prolongation is related to an increasedmortality rate in chronic liver disease (CLD). But QT dispersion (QTd) and its clinical significancein CLD has not been well studied. The objectives of this study were to investigate the relationbetween QTd and severity of the disease and determine its prognostic value in cirrhoticpatients. Thirty-three consecutive patients with cirrhosis and 35 sex- and age-matched healthysubjects were studied. QT intervals and QT dispersions were measured on admission, and allintervals were corrected for heart rate according to Bazett’s formula. The authors analyzed thepotential relationship between QT parameters and the disease severity according to Child-Pugh classification and compared these values between survivors and nonsurvivors after a 3-year follow-up. Child-Pugh classification is used to assess liver function in cirrhosis. CorrectedQT (QTc) prolongations were found in 32% of patients with cirrhosis and 5.7% of the healthycontrols (p 70 ms) corrected QT dispersion (QTcd) was45% in patients with cirrhosis. According to Child-Pugh criteria: QTd, maximum QT interval(QTmax), corrected QTmax (QTcmax), and QTcd in class C were significantly higher than thoseof class A and B (p

Dig Dis Sci (2007) 52:1154–1158DOI 10.1007/s10620-006-9139-8ORIGINAL PAPERGastric Tissue Oxidative Changes in PortalHypertension and CirrhosisYuksel Seckin · Murat M. M. Harputluoglu ·Kadir Batcioglu · Melih Karincaoglu · Bulent Yildirim ·Ramazan I. Oner · Burcin Uyumlu ·Nurettin Aydogdu · Fatih HilmiogluReceived: 13 May 2005 / Accepted: 10 November 2005 / Published online: 8 March 2007C○ Springer Science+Business Media, Inc. 2006Abstract Gastric mucosal lesions are very common in portalhypertension and cirrhosis. The aim of this study was toassess for oxidative gastric tissue damage in cirrhosis andevaluate relations with portal hypertension and cirrhosis parameters.The study included 30 patients with cirrhosis and30 controls. Each patient’s history, physical examination, andlaboratory findings were recorded, and multiple biopsies ofthe gastric antrum were obtained at endoscopy. A set ofantral biopsies was also collected from each control subject.Each tissue specimen was analyzed for levels of glutathioneperoxidase (GPX), superoxide dismutase (SOD), and catalase(CAT) activity and level of malondialdehyde (MDA).Patients’ gastric GPX, SOD, and CAT levels were significantlylower, and MDA levels were higher, than in the controlgroup. The GPX activity level in the specimens was moderatelynegatively correlated with portal vein diameter (P

Acute effect of exercise on plasma leptin level and insulin resistance in obesewomen with stable caloric intake.Res. 2007;32(1-2):9-17.Sari R, Balci MK, Balci N, Karayalcin U.Division of Endocrinology and Metabolism, Akdeniz University, School of Medicine, Antalya, Turkey. drsari@hotmail.comAbstractObese individuals are frequently hyperleptinemic and insulin resistant. Chronic exercise is associated with improvements in plasmaleptin level and insulin sensitivity; however, little is known about the acute effect of exercise on these parameters. The aim of this studywas to evaluate the acute effect of aerobic exercise on plasma leptin and insulin sensitivity in obese women with stable caloric intake.Patients and Methods: Twenty-three obese women (age 41.2 +/- 10.3 years, body mass index 40.7 +/- 6.7 kg/m2) were included to thestudy. All subjects were admitted to an exercise program (45-minute walking sessions at 60-80% of maximum heart rate) every dayexcept weekends for four weeks (total 20 exercise sessions). Insulin resistance was evaluated by HOMA model. Plasma glucose, insulinand leptin levels were determined at baseline and at the end of the first, seventh, and twentieth exercise session. RESULTS: Baselineand at the end of the first, seventh, and twentieth exercise session plasma leptin levels were 59.1 +/- 20.1, 58.5 +/- 21.0, 53.4 +/- 21.9,ŀEndocrand 51.2 +/- 20.5 ng/ml and HOMA-r were 2.75 +/- 1.47, 1.77 +/- 0.71, 1.73 +/- 0.89, 1.62 +/- 0. 70, respectively. Compared to baseline,at the end of the seventh (p = 0.021) and twentieth exercise session (p = 0.003), plasma leptin levels were significantly low. Plasmaleptin level did not change significantly at the end of the first exercise session (p > 0.05). At the end of the first exercise session (p =0.005), end of the seventh (p = 0.003) and twentieth exercise session (p = 0.007) HOMA-r was lower than baseline. There was nocorrelation between weight loss during exercise period and the change of leptin, and HOMA-r. Fasting plasma glucose, insulin and leptinlevels were determined at baseline and at the end of the first, seventh, and twentieth exercise session. CONCLUSION: Our studysuggests that acute exercise decreases insulin resistance at the first exercise session with no effect on leptin levels. Significant leptindecrement was evident at the first week and lasted during the entire four weeks exercise session.PMID: 18271502 [PubMed - indexed for MEDLINE]

py is for personal use only - distribution prohibited. This copy is for personal use only - distribution prohibited. This copy is for personal use only - distribution prohibited. This copy is for personal use only - distribution prohibited. This copy is for personal use only - distribu© Med Sci Monit, 2007; 13(4): CR211-214PMID: 17392654Received: 2006.03.06Accepted: 2007.03.02Published: 2007.03.30Authors’ Contribution:A Study DesignB Data CollectionC Statistical AnalysisD Data InterpretationE Manuscript PreparationF Literature SearchG Funds CollectionBackground:Material/Methods:Results:Conclusions:key words:Platelet activation in subjects with subclinicalhypothyroidismErkan CobanABCDEF, Gokhan YaziciogluABF, Mustafa OzdoganDEFDepartment of Internal Medicine, Akdeniz University Faculty of Medicine, Antalya, TurkeySource of support: Departmental sourcesSummaryCoronary heart disease is the major cause of death in the developed world. Platelet activation andaggregation are central processes in the pathophysiology of coronary heart disease. Mean plateletvolume (MPV), a determinant of platelet function, is a newly emerging risk factor for atherothrombosis.The present study was designed to evaluate levels of MPV in subclinical hypothyroidicsubjects compared with euthyroidic subjects in a cross-sectional study.Thirty-six subclinical hypothyroidic subjects and 20 euthyroidic control subjects matched for age,gender, and body mass index were selected.Metabolic parameters and platelet counts were not different among the study groups (p>0.05). Thelevel of MPV was significantly higher in the subclinical hypothyroidic group than in the euthyroidicgroup (9.9±0.9 fl vs. 9.2±0.7 fl, p

Platelets, December 2007; 18(8): 591–594ORIGINAL ARTICLEPlatelet activation in subjects with impaired glucose toleranceERKAN COBAN, S. KUCUKTAG, & S. BASYIGITFaculty of Medicine, Department of Internal Medicine, Akdeniz University, Antalya, Turkey(Received 11 June 2007; revised 17 July 2007; accepted 17 July 2007)Platelets Downloaded from informahealthcare.com by Akdeniz Universitesi on 11/07/10For personal use only.AbstractImpaired glucose tolerance (IGT), a prediabetic state, is associated with an increased risk of cardiovascular disease.Mean platelet volume (MPV), a determinant of platelet activation, is a newly emerging risk factor for atherothrombosis.This study was designed to answer the following questions: (i) Do MPV levels change in IGT? (ii) Is there any relationbetween MPV levels and 2 h plasma glucose levels after 75 g oral glucose tolerance test. We selected 48 subjects with IGT,and 48 healthy subjects with normal glucose tolerance matched for age, gender, and body mass index. MPV wassignificantly higher in IGT group than in control group (9.06 1.5 fl vs. 8.28 0.8 fl, p ¼ 0.002). Also, MPV was positivelycorrelated with 2 h plasma glucose concentration in IGT group (r ¼ 0.39, p ¼ 0.006). In conclusion, our results suggest thatsubjects with IGT tend to have increased platelet activation. Increased platelet activity could contribute to increasing therisk of cardiovascular disease in IGT.Keywords: Cardiovascular risk, impaired glucose tolerance, mean platelet volume, platelet activationIntroductionDiabetes Mellitus is a common chronic metabolicdisorder associated with atherosclerotic cardiovasculardisease [1]. However, evidence of cardiovasculardisease risk can also be traced to glucose regulationabnormalities antecedent to diabetes status [2, 3].The American Diabetes Association (ADA) and theWorld Health Organization both recognize‘‘impaired’’ glucose categories, metabolic stages ofglucose homeostasis intermediary between normaland diabetes [4, 5]. Impaired fasting glucose (IFG)and impaired glucose tolerance (IGT) representintermediate states of abnormal glucose regulationthat exist between normal glucose homeostasis anddiabetes mellitus. IGT is defined by an elevated 2 hplasma glucose concentration (140 and5200 mg/dl)after a 75 g glucose load on the oral glucose tolerancetest (OGTT) in the presence of an fasting plasmaglucose (FPG) concentration5126 mg/dl [6].IGT is important to recognize because of at leasttwo major implications: increased risk for futurediabetes and for atherosclerotic cardiovasculardiseases [7–13]. In the Diabetes Epidemiology:Collaborative analysis of Diagnosis Criteria inEurope (DECODE) study, investigators analyseddata from 13 prospective studies and found anincreased risk of cardiovascular death and all-causemortality in patients with IGT compared withnormal subjects [14].Atherosclerosis accounts for about 80% of alldeaths from type 2 diabetes mellitus, of whichapproximately 75% are due to coronary arterydisease [15]. Platelets and their interaction with thevessel wall play a role in atherogenesis and in theformation of the coronary thrombus [16]. Meanplatelet volume (MPV), a determinant of plateletactivation, is a newly emerging risk factor foratherothrombosis [17]. Elevated MPV levels havebeen identified as an independent risk factor formyocardial infarction in patients with coronary heartdisease [18] and for death or recurrent vascularevents after myocardial infarction [19]. Moreover,increased platelet size has been reported in patientswith vascular risk factors such as diabetes mellitus[20], in patients with acute ischemic stroke [21],hypercholesterolaemia [22], obesity [23], smoking[24] and in patients with renal artery stenosis [25].Altered platelet morphology and function havebeen reported in patients with diabetes mellitus.Correspondence: Erkan Coban, M.D., Faculty of Medicine, Department of Internal Medicine, Akdeniz University, 07070, Antalya, Turkey. Tel: þ90 242249 6611. Fax: þ90 242 227 4490. E-mail: ecoban@akdeniz.edu.trISSN 0953–7104 print/ISSN 1369–1635 online ß 2007 Informa UK Ltd.DOI: 10.1080/09537100701609019

py is for personal use only - distribution prohibited. This copy is for personal use only - distribution prohibited. This copy is for personal use only - distribution prohibited. This copy is for personal use only - distribution prohibited. This copy is for personal use only - distribu© Med Sci Monit, 2007; 13(12): CR570-573PMID: 18049438Received: 2006.04.10Accepted: 2006.10.06Published: 2007.12.01Authors’ Contribution:A Study DesignB Data CollectionC Statistical AnalysisD Data InterpretationE Manuscript PreparationF Literature SearchG Funds CollectionBackground:Material/Methods:Results:Conclusions:key words:Low-grade infl ammation in white-coat hypertensionMustafa OzdoganAEF, Hakan BozcukAC, Erkan CobanABDEFDepartment of Internal Medicine, Akdeniz University Faculty of Medicine, Antalya, TurkeySource of support: Departmental sourcesSummaryC-reactive protein (CRP), a marker of systemic low-grade inflammation, is frequently elevated inessential hypertension and predicts cardiovascular prognosis independently of conventional riskfactors. The risk profile of white-coat hypertension is not yet completely clear. The aim of this studywas to determine the levels of high-sensitivity CRP (hs-CRP) in white-coat hypertensive subjects.Thirty-six age-, sex-, and body mass index-matched white-coat hypertensive subjects, 36 essentialhypertensive patients, and 36 normotensive subjects were included in the study.Hs-CRP levels were significantly higher in the essential hypertensive and white-coat hypertensivegroups than in the normotensive group (0.66±0.29, 0.47±0.32, and 0.27±0.22 mg/dl, respectively,p

1-Basarici I, Yilmaz H, Demir I, Yalcinkaya S:Imminent pulmonary embolism : A fatal mobile rightatrial thrombus.Int J Cardiovasc Imaging22(1):55-58, 2006.2-Basarici I, Demir I, Yilmaz H, Altekin R.E:Obstructive Metastatic Malignant Melanoma Of The Heart:Imminent Pulmonary Arterial Occlusion Due To Right Ventricular Metastasis With Unknown Origin OfThe Primary Tumor. Heart Lung35(5):351-354, 2006.3-Basarici I:Determination of TIMI frame counts and slow coronary flow/ Relationship between theslow coronary flow and carotid artery intima-media thicknessAnadolu Kardiyol Derg7(3):333-334,2007.4-Basarici I, Altekin R.E, Demir I, Yilmaz H:Associations of isoprostanes-related oxidative stress withsurrogate subclinical indices and angiographic measures of atherosclerosis.Coron ArteryDis18(8):615-620, 2007.5- Basarici I, Suleymanlar G. Angiotensinogen M235T gene polymorphism in essentialhypertension/angiotensinogen M235T polymorphism and left ventricular indices in treated ypertensivepatients with normal coronary arteries. Anadolu Kardiyol Derg. 2007;7(4):449.ŀKardiyoloji Anabilim Dalı

Pathophysiology and natural history 615Associations of isoprostanes-related oxidative stress withsurrogate subclinical indices and angiographic measuresof atherosclerosisIbrahim Basarici a , Refik Emre Altekin a,b , Ibrahim Demir a and Huseyin Yilmaz aObjectives Cardiovascular diseases are the mostcommon cause of death in the world. Oxidative stress hasbeen proved to play a role in atherosclerotic diseases and8-isoprostane is one of the most valid markers of in-vivooxidative stress. We aimed to investigate the 8-isoprostanelevels in relation to surrogate and direct angiographicindexes of atherosclerosis.Methods Urinary 8-isoprostane levels were measured anda B-mode carotid ultrasound examination was performedin 100 consecutive patients scheduled for coronaryangiography.Results In patients with angiographic coronary arterydisease (CAD) urinary 8-isoprostane levels weresignificantly (P < 0.001) higher than in patients without CAD(68.75 ± 5.5 vs. 38.27 ± 3.7 pg/ml). Moreover, 8-isoprostanelevels of patients with increased carotid intima mediathickness (CIMT) were higher (P < 0.001) than in patientswith normal CIMT values (75.12 ± 6.4 vs. 38.72 ± 2.7 pg/ml).Moreover log(8-isoprostane) levels were significantlycorrelated with maximum and mean CIMT values(P < 0.001) and across univessel and multivessel CADgroups levels of log(8-isoprostane) showed a significantly(P < 0.001) increasing trend. Logistic regression analysisrevealed that 8-isoprostane levels were an independentpredictor for both intima-media thickening andangiographic CAD.Conclusion These findings indicate that elevated urinarylevels of 8-isoprostane are associated with both subclinicalatherosclerosis and manifest CAD. The results thereforesupport the hypothesis that isoprostanes-related oxidativestress is involved in the whole atheroscleroticprocess. Coron Artery Dis 18:615–620 c 2007 WoltersKluwer Health | Lippincott Williams & Wilkins.Coronary Artery Disease 2007, 18:615–620Keywords: carotid intima media thickness, coronary angiography, coronaryartery disease, isoprostanes, subclinical atherosclerosisa Akdeniz University School of Medicine, Department of Cardiology, Antalya andb Burdur State Hospital, Department of Cardiology, Burdur, TurkeyCorrespondence to Dr Ibrahim Basarici, MD, Akdeniz Üniversitesi Tip Fakultesi,Kardiyoloji Anabilim Dalı, 07070 Antalya, TurkeyTel: + 90 242 249 6806 249 6775; fax: + 90 242 227 44 90;e-mail: ibasarici@akdeniz.edu.trReceived 15 January 2007 Accepted 7 August 2007IntroductionCardiovascular diseases (CADs) are the most importantcause of death in both developed and developing countries[1]. CAD is the most common manifestation of atherosclerosis.Owing to the systemic nature of atherosclerosis,the cerebrovascular and peripheral arterial bed, might alsohowever, be diseased [2]. Carotid intima media thickness(CIMT) is a reliable and surrogate marker of subclinicalatherosclerosis and a screening test nominee for futurecardiovascular events [3–5].Among novel putative markers of atherosclerosis oxidativestress has gathered special attention and sufficient datahave proved the role of oxidative stress in atherogenesis[6]. F 2 -isoprostanes including 8-epiprostaglandin F 2a(8-isoprostane) are prostaglandin-like free radical mediatedperoxidation products of arachidonic acid and theyare accepted as valid markers of in-vivo oxidative stress[6,7]. Although the increased levels of 8-isoprostaneshave been shown in clinical CAD [8] and angiographicCAD [9,10], evidence for its association with CIMT iscurrently lacking.0954-6928 c 2007 Wolters Kluwer Health | Lippincott Williams & WilkinsWe designed this study to document the role of 8-isoprostanes in the atherosclerotic process, assessingCIMT as a surrogate marker of atherosclerosis besidecoronary angiography as a direct measure of coronaryatherosclerosis.MethodThe study was approved by the local ethics board of ouruniversity and 120 consecutive patients undergoingcoronary angiography for suspected CAD were asked toparticipate. As 20 patients declined to participate andwere excluded, 100 patients were enrolled after aninformed consent form was obtained. All patients underwentB-mode carotid ultrasound examination beforecoronary angiography. First morning spot urine and fastingplasma samples were drawn from each patient forlaboratory analyses. Patients with an established diagnosisof cardiovascular diseases (whether coronary or cerebrovascular),or patients with systemic diseases (such aschronic renal failure or connective tissue diseases) andmalignancies were excluded. Cardiovascular risk factorswere assessed according to the following criteria:Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

334Editöre MektuplarLetters to the EditorAnadolu Kardiyol Derg2007; 7: 331-47lik eden kofaktörlere göre düzeltme yap›larak KYA’›n intima media kal›nl›¤›için ba¤›ms›z bir belirleyici olup olmad›¤›n›n çok de¤iflkenli analizles›nanmas›n›n daha uygun olaca¤›n› düflünmekteyim.Sonuç olarak; an›lan çal›flmada (1) bir tak›m metodolojik sorunlaroldu¤u görülmektedir. Yöntemler k›sm›n›n detayland›r›lmas› ve baz› düzeltmelerle(referans hatas›) bu sorunlar›n bir k›sm› giderilebilecek olsada KYA kriterlerinde yukar›da anjiyografi kay›t h›zlar› ve yavafl ak›m kriterininsaptanmas›ndan do¤an hatalar baz› hastalar›n normal ak›m veKYA gruplar› aras›nda kaymaya (özellikle LAD için KYA saptanan hastalar›nsay›s› azalacakt›r) yol açaca¤›ndan bu metodolojik hatalar “tümverilerin bafltan afla¤› tekrar de¤erlendirilmesini gerektirecek kadarönemlidir”. Bu nedenle bu tip çal›flmalarda TIMI kare say›lar›n› etkileyebilecekanjiyografi kay›t h›z›, ifllem s›ras›ndaki kalp h›z›n›n ve KYA kriterlerininanlafl›l›r ve detayl› biçimde yöntemler k›sm›nda belirtilmesi bukonuda çal›flan tüm araflt›r›c›lar için vurgulanmal›d›r.‹brahim Baflar›c›Akdeniz Üniversitesi T›p Fakültesi,Kardiyoloji Anabilim Dal›, Antalya, TürkiyeKaynaklar1. Avflar Ö, Demir ‹, Ekiz Ö, Altekin RA, Yalç›nkaya S. Koroner yavafl ak›m ilekarotis intima-media kal›nl›¤› aras›ndaki iliflki. Anadolu Kardiyol Derg2007; 7: 19-23.2. Wright RS, Kottke TE, Gau GT. Hyperlipidemia and other risk factors foratherosclerosis. Mayo Clinic Cardiology Review. 2nd. Edition 2001; 10: 133-45.3. Gibson CM, Cannon CP, Daley WL, Dodge JT, Alexander B, Marble SJ, etal. TIMI frame count. A quantitative method of assessing coronary arteryflow. Circulation 1996; 93: 879-88.4. Vijayalakshimi K, Ashton VJ, Wright JA, Hall JA, Stewart MJ, Davies A, etal. Corrected TIMI frame count: Applicability in modern digital catheterlaboratories when different frame acquisition rates are used. CatheterCardiovasc Interv 2004; 63: 426-32.Yaz›flma Adresi: Dr. ‹brahim Baflar›c›, Akdeniz Üniversitesi T›p FakültesiKardiyoloji Anabilim Dal›, Antalya, TürkiyeE-posta: ibasarici@akdeniz.edu.trYazar›n yan›t›Say›n Editör,Öncelikle halen üzerinde çok fazla çal›flma yap›lmayan bu konuüzerinde editöre mektubun yazar›n› yapt›klar› çal›flma için kutlar›m. Birçok bilgi olmas›na ra¤men koroner yavafl ak›m›n (KYA) halen tam anlam›ile klinik önemi ve asl›nda “ne oldu¤u” anlafl›lmam›flt›r. Makaleyi ilgive dikkatle okudu¤unuz ve akl›n›zda soru iflareti bulunan bölümleri tekrargündeme getirdi¤iniz için de ayr›ca teflekkürler. Cevaplamam içinbana verilen bu k›sa sürede tüm sorular›n›z› yan›tlamaya çal›flaca¤›m.Bahsetti¤iniz gibi Gibson’ un TIMI kare say›s› yöntemi için at›fta bulunulan“8” numaral› kaynak (1) hatal›d›r, çal›flmam›z›n orijinal makalesindesizinde belirtti¤iniz kaynak kullan›lm›flt›r (2) ve benzer tüm makalelerdede bu kayna¤a at›fta bulunulmufltur. Gönderim s›ras›nda veyasonras›nda dizgi hatas› olabilir. Üzüntülerimi bildiririm.TIMI kare say›s›n›n hesaplanmas› ile ilgili yöntem olarak, bunu ilkuygulayan ve “Gibson yöntemi” olarak literatüre geçen yöntemi kulland›¤›m›belirtmifltim. Bu yöntemde koroner arterlerin dolmas› için gerekenve koroner arter uzunlu¤una göre normal kare say›lar› olarak, solön inen arter (LAD) için 36.2±2.6 , sirkümfleks arter (Cx) için 22.2±4.1, vesa¤ koroner arter (RCA) için 20.0±3.0 de¤erleri belirlenmifltir (2). Ve ayr›caGibson ve ark. (2) yapt›¤› bu çal›flmada LAD için düzeltme katsay›-s› 1.7 belirlenmifltir. Buna göre LAD için s›n›r de¤er 21.1±1.5 olmal›d›r.Ancak çal›flmam›zda her üç koroner arter için “cut-off” de¤erleri belirlenirken,Cx ve RCA için bu referans standart ortalama de¤erlerin 2 karefazlas› al›nm›flt›r, bu flekilde LAD için 38, Cx için 30 ve RCA için 26 de-¤erlerinin üzeri KYA olarak kabul edilmifltir.Benzer uygulamay› yapan yay›nlarda mevcuttur, örne¤in TIMI karesay›s› ile ‹ntravasküler ultrason (IVUS) ile belirlenen koroner arter“intima-media” kal›nl›¤› iliflkisini belirten çal›flman›n yöntem bölümünde“cut-off” de¤erler benzer flekilde belirlenmifltir; “TIMI frame countingwas undertaken by 2 separate cardiologists. In the case of a conflictthe frames were referred to a third cardiologist. The corrected cut-offvalues due to the length for normal visualization of coronary arterieswere 36.2 ± 2.6 frames for LAD, 22.2 ± 4.1 frames for Cx, and 20.4 ± 3 framesfor RCA. Any values obtained above these thresholds were consideredas slow coronary flow.” (3). Ayr›ca bu dergide yay›nlanan TIMIkare say›s› ile metabolik parametrelerin iliflkisini inceleyen bir çal›flman›nda yöntem bölümünde bu de¤erler benzer flekilde belirtilmifltir; “Koronerarterlerin dolmas› için gereken ve koroner arter uzunlu¤una göredüzeltilmifl normal kare say›lar› olarak, LAD için 36±1, Cx için 22.2±4, veRCA için 20.4±3 ortalama referans de¤erlerini elde etmifltir” (4).As›l sorun sizinde belirtti¤iniz gibi Gibson’ un çal›flmas›n›n ‘sineanjiyografi’döneminde yap›lm›fl olmas› ve bu görüntülerin 30 pencere/saniyeh›zda kaydedilmifl olmas› ve bizim çal›flmam›zda bilgisayar disklerinekaydedilen say›sal görüntüler üzerinde inceleme yapm›fl olmam›zd›.Ancak kay›t sisteminin DICOM standard› olarak zaten 30 pencere/saniyeolmas› bunu olanakl› k›ld›. En yeni DICOM standard› olan DICOM3.0’da ise 60 pencere/saniye h›z›nda dahi kay›t yapabilmektedir. Bütünbu kay›tlar taraf›m›zca ACOM PC program›nda 15 ve 30 pencere/saniyeseçeneklerinden 30 pencere/saniye h›z›nda izlenmifltir. Bu nedenle bizimçal›flmam›zda h›z de¤erleri orijinal makaleden farkl›l›k göstermemesinedeni ile ayr›ca belirtilmemifltir. Bunlar makalede ad› geçen gelifltiricifirmalar›n internet sitelerinde tek tek belirtilmektedir.Ben “cut-off” de¤erleri üzerinde bu kadar durulmas›n›n da gereksizoldu¤unu düflünmekteyim çünkü benzer çal›flmalar içerisinde, bizimçal›flmam›zdaki hasta say›s›na ulafl›lan makale mevcut de¤ildi. Kendimize,yaklafl›k 11 y›l önce tan›mlanan›n yerine, yeni dijital kay›t sistemistandartlar›na uygun bir “cut-off” (s›n›r) de¤er belirleyebilece¤imizi düflünmekteyim.Biz bunu bu çal›flmam›zda baflaramad›k, ancak sonrakiyap›lacak daha genifl populasyonlu ve hatta çok merkezli çal›flmalarla(bizim veya sizlerin), kendimize ait uluslararas› geçerlili¤i de olan yavaflkoroner arterleri tan›mlamada s›n›r de¤erleri tespit edebiliriz.Taraf›m›zca yap›lan KYA ile karotis arter “intima-medya” kal›nl›¤›aras›ndaki iliflkiyi inceleyen bu çal›flmada normal ve yavafl koronerak›m olan hastalar aras›nda kan flekeri, kan bas›nçlar›, lipid de¤erleri vevücut kitle indeksleri aç›s›ndan anlaml› farkl›l›k bulunmufltur. Bu farkl›-l›klar çok de¤iflkenli analizle s›nanm›fl ve hatta taraf›m›zca bu baflka birmakalede (Türk Giriflimsel Kardiyoloji Dergisi A¤ustos 2006 say›s›) taraf›m›zcayay›nlanm›flt›r.Makale üzerindeki elefltirilerinizin, flekilcilikten çok, içeri¤e ve vurgulanankoroner yavafl ak›m›n aterosklerozun erken dönemine ait de¤ifliklikleriüzerine olsayd› daha faydal› olabilece¤ini düflünmekteyim. Daha geniflserilerle bu konuyu araflt›rmaya devam etmeniz ve bunun dünya literatürlerinegeçmesi temennilerimle elefltirilerinizi yan›tlamay› tamaml›yorum.Özgür AvflarÖzel ‹bni Sina Hastanesi Kardiyoloji Anabilim Dal›Osmaniye, TürkiyeKaynaklar1. Wright RS, Kottke TE, Gau GT. Hyperlipidemia and other risk factors foratherosclerosis. Mayo Clinic Cardiol Rev 2nd Ed. 2001; 10: 133-45.2. Gibson CM, Cannon CP, Daley WL, Dodge JT, Alexander B, Marble SJ, etal. TIMI frame count. A quantitative method of assessing coronary arteryflow. Circulation 1996; 93: 879-88.3. Cin VG, Pekdemir H, Camsar A, Ciçek D, Akkus MN, Parmaksiz T, et al.Diffuse intimal thickening of coronary arteries in slow coronary flow. JpnHeart J. 2003; 44: 907-19.4. Yaz›c› M, Demircan S, Aksakal E, fiahin M, Meriç M, Dursun ‹, ve ark.Yavafl koroner ak›ml› hastalarda plazma insülin, glükoz, lipid düzeyleri vedüzeltilmifl TIMI kare say›s› ile iliflkisi. Anadolu Kardiyol Derg 2003; 3: 222-6.

The International Journal of Cardiovascular Imaging (2006) 22: 55–58 Ó Springer 2005DOI 10.1007/s10554-005-7438-3Case ReportImminent pulmonary embolism: a fatal mobile right atrial thrombusIbrahim Basarici, Huseyin Yilmaz, Ibrahim Demir & Selim YalcinkayaKardiyoloji Anabilim Dali Sekreterligi, Akdeniz U¨niversitesi Tip Faku¨ltesi, 07070, Antalya, TurkeyReceived 28 April 2005; accepted in revised form 18 May 2005Key words:cardiac thrombus, echocardiography, malignancy, mobile thrombus, pulmonary embolismAbstractRight sided heart thrombi are infrequent and if they are mobile they may cause serious morbidity andmortality due to massive pulmonary embolism or paradoxical embolism. Malignancies are one of theimportant etiological factors for right heart thrombi. A patient with operated but recurrent ovarian carcinoma,presented with symptoms of heart failure was admitted to oncology department. Rapidly progressingdyspnea and a pre-syncope attack required consultation of a cardiologist and echocardiography revealed amobile thrombus in the right atrium. Urgent open heart surgery was decided but imminent massive pulmonaryembolism complicated the case leading to irreversible cardiogenic shock. By means of the presentedcase this paper overviews etiological factors and treatment options for right sided heart thrombi.Abbreviations:PE – pulmonary embolism; TEE – transoesophageal echocardiographyIntroductionRight sided heart thrombi are relatively unusualechocardiographic finding. In case if these thrombiare mobile they may cause life threatening complicationssuch as massive pulmonary embolism(PE) or paradoxical embolism. Within etiologicalfactors malignancies deserve a special attention,because these patients are in a hypercoagulablestate predisposing for thromboembolic events.Although clinical consequences of mobile rightsided heart thrombi may be serious if they areundiagnosed; usually the diagnosis can be establishedby imaging techniques. Because a treatmentconsensus has not been formed yet due to lack ofprospective randomized trials; transthoracic andtransoesophageal echocardiography especiallymay help establishing diagnosis and also individualizingappropriate treatment strategies. Thispaper reports a patient with right atrial mobilethrombus and discusses etiological factors andtreatment options.Case reportSeventy-two-years-old diabetic and hypertensivewoman who underwent debulking surgery9 months ago was diagnosed as having a serousovarian carcinoma and adjuvant chemotherapywas applied. In the follow-up patient refusedplanned second look operation and rising tumormarker CA-125 was regarded as recurrence. Shecomplained about fatigue, ankle edema and

CASE STUDIES IN CARDIOVASCULAR NURSINGObstructive metastatic malignant melanoma ofthe heart: Imminent pulmonary arterial occlusioncaused by right ventricular metastasis withunknown origin of the primary tumorİbrahim Basarici, MD, İbrahim Demir, MD, Huseyin Yilmaz, MD, and R. Emre Altekin, MDWhether primary or metastatic, cardiac neoplastic diseases are relatively uncommon disorders. Althoughany malignancy may involve the heart, malignant melanoma (MM) has a significant tendency tometastasize to the heart. Cardiac involvement may occur during the course of MM or years after surgicaltherapy, but rarely metastasis may be the initial manifestation of the disease. This article reports ametastatic MM case that was initially manifested by heart failure symptoms because of right ventricleoutflow obstruction and for which the primary focus could not be determined. (Heart Lung® 2006;35:351–354.)From the Akdeniz University School of Medicine, Antalya, Turkey.Reprint requests: İbrahim Basarici, Akdeniz Üniversitesi TıpFakültesi, Kardiyoloji Anabilim Dalı, 07070 Antalya/Turkey.0147-9563/$ – see front matterCopyright © 2006 by Mosby, Inc.doi:10.1016/j.hrtlng.2005.11.001Cardiac tumors are relatively rare disorders.Both benign and malignant cardiac tumorsmay result in serious consequences such aslimitation of blood flow through cardiac chambersby obliterative masses, disturbed ventricular contractilityor arrhythmia caused by infiltrativemasses, and the risk of tumor embolization. Myxomasand sarcomas constitute the majority of primarybenign and malignant tumors of the heart,respectively, whereas metastatic tumors of the heartare uncommon with the exception of malignantmelanoma (MM) 1 MM has a tendency to metastasizeto the heart, and in approximately more thanhalf of the cases, the heart is involved, generally asa part of disseminated disease. Antemortem diagnosis,however, is rare because the clinical course issilent. This article presents a case of a patient admittedto the hospital on symptomatic heart failurewith obliterative right ventricular masses later diagnosedas metastatic melanoma. The metastatic ventricularmasses obstructed the pulmonary artery,which necessitated surgical intervention.CASE REPORTA 46-year-old woman, otherwise healthy in thepast, was admitted to our cardiology departmentwith symptoms of dyspnea and chest discomfort.Clinical history revealed the beginning of dyspneaon exertion 2 months before, which progressed andturned into orthopnea in the days preceding admissionwith accompanying chest discomfort and dizziness.On physical examination, the patient’s respiratoryfindings were normal, whereas cardiacauscultation revealed a pansystolic murmur in themesocardiac area and an ejection murmur bestheard at the second and third left intercostalspaces. The patient’s enlarged liver was palpated 3cm in midclavicular line. The rest of the systemicexamination results were otherwise normal. Cardiacrhythm was sinus. Incomplete right bundle branchblock was present on electrocardiography. Telecardiographydisplayed cardiomegaly. Routine biochemistryanalysis, complete blood count, anderythrocyte sedimentation rate were all normal. Todetermine the cause of symptoms and cardiac murmurs,transthoracic echocardiographic examinationwas performed. Left ventricular systolic functionHEART & LUNG VOL. 35, NO. 5 www.heartandlung.org 351

Editöre Mektuplar Letters to the Editor449Angiotensinogen M235T genepolymorphism in essentialhypertension/Angiotensinogen M235Tpolymorphism and left ventricularindices in treated hypertensive patientswith normal coronary arteriesEsansiyel hipertansiyonda anjiyotensinojen M235Tgen polimorfizmi/Antihipertansif tedavi alan normalkoroner arterli hastalarda anjiyotensinojen M235Tpolimorfizminin sol ventrikül parametreleri ile iliflkisiDear Editor,Genetic predisposition to the essential hypertension is an unsolvedpuzzle. Polymorphisms of angiotensin converting enzyme orangiotensinogen (AGT) genes and AGT II type 1 receptor genes are themost investigated factors. However, results of these studies areconflicting (1). Olcay et al. provided important data on this issue inTurkey (2). We would like to contribute to their work by sharing ourexperience based upon a thesis project (3).The prevalence of T allele for the AGT M235T polymorphism is racedependent and majority of the trials indicate an association betweenhypertension and TT homozygotes (1) whereas some reports do not(2, 4). According to our experience (3) distribution of AGT M235T allelesfor normotensives and hypertensives was similar (30 vs. 23 %, 53 vs. 55% and 17 vs. 21 % for MM, MT and TT alleles in order for hypertensiveand normotensive subjects respectively) and was in agreement withHardy-Weinberg equilibrium. Another Turkish study reported coherentpercentages for normotensives (25, 55 and 19 % for MM, MT and TTalleles respectively) compared to our results (5). Confirming previousreports (2, 4) we found no association between AGT polymorphism andleft ventricular hypertrophy (LVH) (left ventricular mass indexes were117, 111 and 126 gr/m 2 for MM, MT and TT alleles, respectively). But,when gender was considered TT allele was significantly associatedwith higher left ventricular mass index in males (3). I wonder whetherauthors performed a similar subgroup analysis (2). Can expression ofthese genes be different for each gender? Moreover, we found norelationship between the carotid intima- media thickness and AGTM235T polymorphism (3) where there are also conflicting results (1).These contradictory results are not surprising. Regarding racialdifferences in genetic polymorphisms, data from other races andnations predominantly indicating an association with TT allele andhypertension will not necessarily be confirmed by the studies carriedout in Turkish population. Also methodological pitfalls limit“comparability” of this kind of studies. Different echocardiographiccriteria for LVH influence clinical results. So, rather than handling LVHas a categorical variable, utilizing left ventricular mass index as acontinuous variable would serve a better comparative tool. Anotherpitfall is the medical treatment of patients. When relationship betweenLVH and genetic polymorphism is questioned, it will be misleading tocompare results of two studies if the study populations are different(where patients are treated in one and not treated in the other). Finally,we would like to note some considerations regarding Olcay et al.’swork. The reported rate (70%) of LVH seems considerably high for a“controlled hypertensive disease”. Lack of documentation of bloodpressure data and antihypertensive medications is a major limitation.Effect on the regression of LVH is different for various antihypertensivemedications and heterogeneity of antihypertensive medications makethe interpretation of the results inconvenient.Consequently, the authors’ precious work will stay as a comparativefor future trials in Turkey. A powered study is needed to comprehensivelydetermine the genetic predisposition in Turkish hypertensivesubjects and to determine the relationship between LVH and differentgene polymorphisms. Implementing a multicenter protocol enrollinguntreated hypertensives or enrolling patients receiving the same groupof antihypertensives and assessment of the patients’ “hypertensioncontrol status” and utilizing a standardized protocol for definition ofechocardiographic LVH will make such a study more valuable.‹brahim Baflar›c›, Gültekin Süleymanlar*From Departments of Cardiology and *Nephrology,Faculty of Medicine, Akdeniz University, Antalya, TurkeyReferences1. Ji-Guang Wang, Jan A. Staessen. Genetic polymorphisms in therenin-angiotensin system: relevance for susceptibility to cardiovasculardisease. Eur J Pharmacol 2000; 410: 289-302.2. Olcay A, Niflanc› Y, Ekmekçi CG, Özbek U, Sezer M, Umman B, et al.Angiotensinogen M235T polymorphism and left ventricular indices intreated hypertensive patients with normal coronary arteries. AnadoluKardiyol Derg 2007; 7: 257-61.3. Koyuncu E. Primer hipertansiyonlu hastalarda hedef organ hasarlar› ileanjiyotensin converting enzim gen ve anjiyotensinojen gen polimorfizmlerininiliflkisi. Antalya: Akdeniz Üniversitesi; 2005 (Diss).4. Shlyakhto EV, Schwartz EI, Nefedova YB, Zukova AV, Vinnic TA, ConradyAO. Lack of association of the renin-angiotensin system genespolymorphisms and left ventricular hypertrophy in hypertension. BloodPres 2001; 10: 135-41.5. Sekuri C, Cam FS, Ercan E, Tengiz I, Sagcan A, Erhan Eser E, et al.Renin-angiotensin system gene polymorphisms and premature coronaryheart disease. JRAAS 2005; 6: 38-42.Address for Correspondence/Yaz›flma Adresi: Dr. ‹brahim Baflar›c›,Akdeniz Üniversitesi T›p Fakültesi, Kardiyoloji Anabilim Dal› Sekreterli¤i07059 Antalya, TurkeyTel: +90 242 249 68 06 Fax: +90 242 227 44 90 E-mail: ibasarici@akdeniz.edu.trAuthor’s replyDear Editor,We thank the author of the letter for sharing their study results. Weperformed a subgroup analysis, which was not previously published inthe article. Expressions of the genes were not different between genders(Table 1). When left ventricular hypertrophy presence was analyzedaccording to genders there was no statistically significant difference insubgroups (Table 2).Table 1. Expression of genes according to genderMale Female p*MM, n (%) 7 (21.2) 15 (26.8)MT, n (%) 22 (66.7) 25 (44.6) 0.97TT, n (%) 4 (12.1) 16 (28.6)* significance by Chi-Square test

1-Mıhçı E, Kardelen F, Dora B, Balkan S:Orthostatic heart rate variability analysis in idiopathicParkinson's disease.Acta Neurol Scand113(5):288-293,2006.2-Mıhçı E, Dora B, Balkan S:Transcranial Doppler ultrasonographic evaluation of cerebral circulationduring passive tilting in patients with Parkinson's disease.J Clin Ultrasound35(3):138-43,2007.3-Dora B;SUNCT syndrome with dramatic response to oxcarbazepine.Cephalalgia26:1171-1173,2006.4-Ozbudak Demir S, Oktay F, Uysal H, Selçuk B:Upper extremity shortness in children withhemiplegic cerebral palsyJ Pediatr Orthop26:764-768,2006.5-Yerdelen D, Uysal H, Koç F, Sarıca Y:Effect of sex and age on strength-duration properties.ClinicalNeurophysiology117:2069-2072,2006.6-Erkin G, Uysal H, Keleş I, Aybay C, Özel S:Acute unlar neuropathy at the wrist:a case report andrewiev of the literature.Rheumatol Int27:191-196,2006.7-Yerdelen D, Uysal H, Koç F, Sarıca Y:The effect of hyperventilation on strength-duration propertiesin diabetic polyneurathy.Clinical Neurophysiology118:105-110,2007.8-Selçuk B, Uysal H, Aydoğdu İ, Akyüz M, Ertekin C:Effect of temperature on electrophysiologicalparameters of swallowing.Journal of Rehabilitation Research and development44(3),373-380,2007.9-Saka E, Doğan EA, Topçuoğlu MA, Şenol U, Balkan S:Linear measures of temporal lobe atrophy onbrain magnetic resonance imaging but not visual rating of white matter changes can helpdiscrimination of mild cognitive impairment and Alzheimer's disease.Arch gerontol geriatr.44(2):141-51, 2007.ŀNöroloji Anabilim Dalı - 2007

Intern. J. Neuroscience, 117:1457–1464, 2007Copyright C○ 2007 Informa Healthcare USA, Inc.ISSN: 0020-7454 / 1543-5245 onlineDOI: 10.1080/00207450601125808EFFECTS OF BOTULINUM TOXIN ONSTRENGTH–DURATION PROPERTIESInt J Neurosci Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/11/10For personal use only.DENİZ YERDELENFİLİZ KOCYAKUP SARICADepartment of Neurology,Cukurova University Medical SchoolAdana, TurkeyAxonal excitability studies have been used in several diseases to investigatethe underlying pathophysiology. The threshold tracking technique was developedto measure noninvasively several indices of axonal excitability, such asstrength–duration properties. This study investigated the possible effects ofbotulinum toxin on strength–duration time constant (SDTC) in patients with thesymptoms and signs of botulism. The clinical and electrophysiological findings of 13patients who were admitted to the authors’ clinic with botulism signs and symptomswere evaluated in a 5-day period after exposure to the toxin prospectively. Afterroutine diagnostic electroneuromyographic examinations and electromyogram withrepetitive nerve stimulation at 20–50 Hz, SDTC was studied. The results werecompared with 13 age- and sex-matched healthy volunteers. The SDTCs were381 ± 60 µs and 471 ± 84 µs in patients and controls, respectively. There wasa statistical difference between the two groups (p = .003, Mann Whitney U test).These findings suggest a possible effect of botulinum toxin, known to be effective atneuromuscular junction, on Na + /K + pump activity, and Na + or K + conductance.Keywordsbotulinum toxin, strength–duration time constantReceived 23 August 2006.Deniz Yerdelen’s present address: Department of Neurology, Baskent University Faculty ofMedicine, Adana Teaching and Medical Research Center, 01250, Adana-Turkey.Address correspondence to Dr. Filiz Koc, Cukurova University Medical School, Departmentof Neurology, 01330, Adana-Turkey. E-mail: koc.filiz@gmail.com1457

ORIGINAL ARTICLEUpper Extremity Shortness in Children With HemiplegicCerebral PalsySibel Özbudak Demir, MD,* Fügen Oktay, MD,* Hilmi Uysal, MD,Þ and Barin Selçuk, MD*Objective: To evaluate upper extremity shortness in patients withhemiplegic cerebral palsy (HCP) and to investigate the associationbetween extremity shortness, motor level, and muscle tone.Design: Prospective, controlled study.Subjects: Forty-two children with HCP and 29 healthy children.Methods: Radiographs of the involved and the uninvolved humerus,forearm, and hands were obtained with a radiographic ruler placedadjacent to the extremity. The lengths and the diameters of both thediaphyses and metaphyses of the humerus, ulna, radius, and thesecond and the fifth metacarpal bones were measured in patients andthe control group. The discrepancy was calculated as a percentagecompared with the normal side. The Ashworth Scale was used in theevaluation of spasticity, and the Brunnstrom recovery staging wasused in the motor evaluation.Results: Children with HCP had significant differences in bonelengths and diameters compared with control children. There was nosignificant correlation between the upper extremity Brunnstromstagings and the differences of bone length and diameter. A significantcorrelation was observed between the hand Brunnstrom stagingand percentage difference of the bone length and diameter. Thespasticity level showed no relation to the differences in bone lengthand diameter.Conclusions: Children with HCP have significant side-to-side limblengthdiscrepancy when compared with control children. The discrepancyincreases with age. The extent of shortening did not appearto be related to upper extremity function and spasticity. The extremityshortness showed a relation to hand function.Key Words: hemiplegic cerebral palsy, upper extremity shortness(J Pediatr Orthop 2006;26:764Y768)Cerebral palsy is defined as a motion, posture, and tonedisorder caused by a nonprogressive lesion or defect ofthe immature brain. Approximately 35% to 40% of childrenwith cerebral palsy have spastic hemiplegia, with 1 side oftheir body more severely affected than the other. The arm isusually more affected than the leg. 1 Clinicians have observedthat children with hemiplegic cerebral palsy (HCP) often haveresidual limb shortening on the affected side. 2 Previous studies*Ankara Physical Medicine, Rehabilitation, Education and Research Hospitalof the Ministry of Health, Ankara; and †Akdeniz University Faculty ofMedicine, Antalya, Turkey.None of the authors received financial support for this study.Reprints: Sibel Özbudak Demir, MD, Y. Dikmen Mah. Turan Günez BulvarN,12.Cadde No: 11/4 (Aytekinler apt.) 06450, Oran, Ankara, Turkey.E-mail: sibiozbudak@hotmail.com.Copyright * 2006 by Lippincott Williams & Wilkinshave documented delayed skeletal maturation and muscularunderdevelopment in the affected limb of children with hemiplegia.3,4 However, there is no established view about the causeof the limb shortness. Biomechanical forces applied to thegrowing bone play an important role on its growth andformation. 5 Abnormal muscle function leads to the absence ofhealthy mechanical stresses that are critical to early skeletaldevelopment. 6 Muscle growth is affected by increased tone inchildren with hypertonia; however, muscle growth and longbone growth rate are not proportionately correlated. 7 Sensorydeficits may also play a role in extremity shortness. 8,9 Whereassome studies contradict the role of sensory deficits in extremityshortness, others state that sensory deficits increase extremityshortness. 9,10Very few studies have been published on the effectof central neurological defects on bone growth. 8,9 Thereports have analyzed the relationship between cerebralpalsy and anthropometric measurements. There have beenno studies to date, however, focusing on bone shortnessmeasurements by direct radiographic evaluation includinga control group.This study was planned to evaluate upper extremityshortness in children with HCP and to investigate its relationshipwith motor level and muscle tone.METHODSSubjectsForty-two children with HCP caused by prenatal orperinatal etiology, admitted to an inpatient rehabilitation programat the Ankara Physical Medicine and RehabilitationEducation and Research Hospital, Pediatric RehabilitationClinic, Ankara, Turkey, between April 2001 and May 2005were enrolled in the study. Twenty-nine healthy childrencomprised the control group. Children with normal lineargrowth and a normal nutritional status were included in thestudy. Exclusion criteria were as follows: upper extremityfractures, peripheral nerve lesion, upper extremity surgery,muscular or skeletal defect on either the hemiplegic or unaffectedextremity, and patients with serious contracturespreventing position. As we intended to evaluate the effect ofbrain damage on developing bones starting from birth,patients with postnatal etiology that had normal bone growthfor a certain period of time were not included in the study. Allparents were informed about the procedures, and their consentsfor participation in the study were obtained.Clinical AssessmentPrenatal, natal, and postnatal histories of the patientswere investigated. The neurological examination and764 J Pediatr Orthop & Volume 26, Number 6, November/December 2006Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

J Pediatr Orthop & Volume 26, Number 6, November/December 2006Upper Extremity Shortness in Hemiplegic Cerebral PalsyTABLE 1. Brunnstrom Stages of the ArmStage 1: Presynergy, flaccid, no active movementStage 2: Resistance to passive movement, no voluntary movementStage 3: Marked spasticity, synergistic voluntary movementStage 4: Spasticity decreases, synergies begin to wane and weakest synergiescan be overcomeStage 5: Isolated movement, stronger synergies can be overcome, waningspasticityStage 6: Isolated joint movement freely performed, normal to near normalcoordination, no spasticityexamination of active and passive joint movement rangewere performed by the same physiatrist on all the children.Motor evaluation was performed using the Brunnstromrecovery staging (Tables 1 and 2), which evaluates armcontrol and hand control separately. 11,12 Severe paresis wasdefined as a score of 1 to 3, moderate as a score of 4, and mildas a score of 5 to 6. The Ashworth Scale, which classifiesmuscle tone in 5 stages, was used for spasticity evaluation: 0,no increase in tone; 1, slight increase in tone; 2, mild increasein tone, extremity can be bent easily; 3, marked increase intone, passive movement is difficult; 4, the extremity is rigidlyflexed or extended. 13Radiological AssessmentRadiographs of both the involved and uninvolved humerus,forearm, and hands were obtained for each child,with a radiographic ruler placed adjacent to the extremity.Using standardized anatomical landmarks, measurements ofeach limb segment were obtained, and the length discrepancywas calculated in centimeters and as a percentagecompared with the normal side. Humeral length wasmeasured from an anteroposterior radiograph from the topof the humeral head to the most distal part of the humerus.The radiography of the forearm was performed by placingthe affected and healthy sides in the pronation position onthe x-ray cassette and attaching it with a wide adhesiveplaster. Radiography was performed under the supervisionof a doctor who participated in the study to provide astandard position. Radial length was measured from themost proximal part of the radius to the most distal point ofthe radial styloid process, and ulnar length was measuredfrom the top of the olecranon to the most distal point of theulna on the anteroposterior forearm radiography. Accordingly,metacarpal length was measured from the mostproximal to the most distal part of the second and fifthmetacarpal bones. The growth rates are diverse for differentphyses. The growth of the upper extremity is mainlyprovided by the proximal epiphyses of the humerus and thedistal epiphyses of the radius and ulna, which are furtheraway from the elbow. The metaphysis that lies below thephysis is the bone area where transverse and longitudinalbone growth takes place. 14 Hence, the proximal metaphysesof the humerus and metacarpals and the distal metaphyses ofthe radius and ulna were preferred for diameter measurements.The diaphysis’ diameter measurements were performedat the center of the diaphysis of each bone. Thepercentage of shortness for each bone was calculated withthe following formula as a ratio:The percentage of shortness for each boneðUninvolved bone lengthjInvolved bone lengthÞ¼ 100Uninvolved bone lengthIn the control group, the difference between the dominantand nondominant sides was divided by the dominant sideand was expressed as a percentage of difference.Statistical AnalysisThe SPSS for Windows, release 10.0 (SPSS Inc,Chicago, IL), was used for the statistical analysis in thestudy. The percentage differences of the shortness for eachbone according to age groups in both patient and controlgroups were investigated using the univariate general linearmodel for the significance of the difference between the 2groups. Lengthening of the bone with the increase in age is anexpected natural result, and it shows its influence on theincrease in percentages of shortness as well. Therefore, theeffect of age according to the diagnostic group over the relevantparameters is expected to be insignificant when control andHCP groups are compared with an analysis including the age asan independent variable. The difference was accepted to besignificant when the P G 0.05. The correlation between thepercentage differences of bone shortness and the Brunnstromand Ashworth Scales was evaluated with the Spearmancorrelation test.RESULTSThe mean age of the patients (boys, 53%; girls, 47%)was 4.47 T 1.8 years. The mean age of controls (boys, 52%;girls, 48%) was 4.46 T 1.61 years. The mean birth weight ofpatients was 2816.5 T 321.7 g. The involved extremity was theright one in 59.6% and the left in 40.5% of the patients. Thedistributions of the motor levels according to the Brunnstromstaging and the tone according to the Ashworth Scale areshown in Table 3. Patients with HCP and controls were separatedinto 2 groups according to their ages: group 1, 1 to4 years old; group 2, 4 to 8 years old. The difference in bonelength between the patient and healthy control children accordingto age groups are shown in Table 4. The difference inbone length increases with age in HCP patients. Whereas therewas no significant difference in bone length between patientsand the control subjects in group 1, significant differencesTABLE 2. Brunnstrom Stages of the HandStage 1: Flaccid, no voluntary movementStage 2: Little or no active finger flexionStage 3: Mass grasp or hook grasp, no voluntary finger extension or releaseStage 4: Lateral prehension with release by thumb movement, semivoluntaryfinger extensionStage 5: Palmar prehension, possibly cylindrical and spherical grasp,voluntary mass finger extensionStage 6: All types of prehension (improved skill), voluntary finger extension,individual finger movements* 2006 Lippincott Williams & Wilkins 765Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Transcranial Doppler UltrasonographicEvaluation of Cerebral Circulationduring Passive Tilting in Patientswith Parkinson’s DiseaseEbru Mihci, Babür Dora, Sevin BalkanDepartment of Neurology, Akdeniz University Faculty of Medicine, Arapsuyu 07059, Antalya, TurkeyReceived 8 June 2004; accepted 6 October 2006ABSTRACT: Purpose. To assess the effects of the tilttest on cerebral blood flow velocity (CBFV), blood pressure,and heart rate in patients with Parkinson’s disease(PD) without symptomatic orthostatic dysautonomia.Methods. Thirty patients with idiopathic PD and 15healthy controls were included. Mean middle cerebralartery blood flow velocity (CBFV) was recorded withtranscranial Doppler sonography, while systolic(SBP), diastolic (DBP), and mean (MBP) blood pressureand heart rate were measured in the supine positionand after passive tilting.Results. There was no difference in resting SBP,DBP, or MBP between patients and controls. CBFVwas lower at rest in patients than in controls anddropped significantly and similarly after tilting in bothgroups. SBP decreased in patients during the first5 minutes of tilting (p < 0.05), whereas it increasedprogressively after the first minute in controls. Inpatients, DBP decreased slightly and MBP droppedduring the first 2 minutes, then increased. Baselineheart rate was higher in patients than in controls (p

Blackwell Publishing LtdOxford, UKCHACephalalgia0333-1024Blackwell Science, 2006200626911711173Clinical CorrespondenceSUNCT syndrome with dramatic response to oxcarbazepineB DoraCLINICAL CORRESPONDENCESUNCT syndrome with dramatic response to oxcarbazepineB DoraDepartment of Neurology, Akdeniz University Medical School, Antalya, TurkeyDr Babür Dora, Akdeniz Üniversitesi Hastanesi, Nöroloji Anabilim Daly, Arapsuyu,Antalya, Turkey. Tel. + 90 53 2206 4080/90 24 2227 4343 (66343), e-mailbdora@akdeniz.edu.tr Received 16 January 2006, accepted 7 March 2006Short-lasting unilateral neuralgiform headache withconjunctival injection and tearing (SUNCT) is a syndromecharacterized by very brief unilateral orbitalor periorbital attacks of pain of moderate to severeintensity, which are accompanied by simultaneousipsilateral cranial autonomic symptoms, mainly conjunctivalinjection and lacrimation (1, 2). The frequencyof attacks can range from one to >100 crisesper day and pain may be precipitated by manoeuvresof the neck or from cutaneous trigger zonesmainly in a trigeminal topography (1, 3, 4).Various treatments have been tried for SUNCTsyndrome with no or only slight to moderate benefit.Of the antineuralgic drugs, carbamezapine has beentried with only half of patients having a slight tomoderate response (5–17). Oxcarbazepine has neverbeen reported in the treatment of SUNCT syndrome(3). We present a patient with SUNCT whoresponded dramatically to treatment with low-doseoxcarbazepine.Case reportA 57-year-old white female patient presented to ourheadache out-patient clinic with a 1-year history ofpain attacks in the left periorbital region. At thebeginning the pain attacks had continued for3 months, after which they had disappeared for afurther 3 months but recurred and had been troublingher for 8 months without remission. Theattacks tended to recur four to five times daily butnever occurred during sleep. The pain attack consistedof a brief, sharp stab of moderate to severeintensity which lasted 5 s and was always restrictedto the left periorbital region. It could be precipitatedby washing the face or sometimes even touching theface.All attacks were accompanied by ipsilateral conjunctivalinjection, nasal congestion and lacrimation,which were invariable accompanying symptomsright from the first attack.When she admitted to our hospital she had beendiagnosed as having trigeminal neuralgia at anotherhospital and had been started on oxcarbazepine2 × 300 mg/day. She had responded dramatically tothis treatment with cessation of her attacks from thefirst day of treatment. After a few weeks of completeremission she had forgotten to take her pills once,which caused an immediate recurrence, making herpanic and seek a second opinion.Her neurological and clinical examinations werenormal, as were personal and family history. Cranialmagnetic resonance imaging as well as routine bloodtests revealed no abnormality.The patient was diagnosed as SUNCT syndromeand, because of the history of excellent response,restarted on oxcarbazepine 2 × 300 mg/day. Thenext day the attacks dissappeared completely. After1 month she was still pain free. After that she confessedthat she had forgotten to take her pills againfor a day and the attacks had recurred. Just after sherestarted the treatment, the attacks ceased again.DiscussionAlthough SUNCT syndrome is a distinct entity, it isvery rare and should be differentiated from someother pain disorders. As in the other trigeminal autonomiccephalalgias, cluster headache and paroxysmalhemicrania, the pain is located orbitally andis of severe intensity accompanied by autonomicsymptoms. SUNCT is more easily differentiatedfrom the other trigeminal autonomic cephalalgiasdue to its very short duration. Although brief attacksof paroxysmal hemicrania may last as little as 2 min,attacks of SUNCT usually last

Rheumatol Int (2006) 27:191–196DOI 10.1007/s00296-006-0166-8CASE REPORTAcute ulnar neuropathy at the wrist: a case report and reviewof the literatureGülten Erkin · Hilmi Uysal · IoÂk Keleo ·Canan Aybay · Sumru ÖzelReceived: 27 January 2006 / Accepted: 1 July 2006 / Published online: 2 August 2006© Springer-Verlag 2006Abstract Acute ulnar neuropathy at the wrist is anextremely uncommon condition, at times requiring ahigh index of suspicion for the diagnosis. Clinical presentationsof ulnar nerve lesions at the wrist and handshow variations due to the complex anatomic course ofthe nerve in distal sites. We report a case of acute ulnarneuropathy at the wrist caused by a ganglion inGuyon’s canal, being initially misinterpreted as Xexortenosynovitis. The accurate diagnosis of selective distalmotor neuropathy of ulnar nerve was made electrophysiologically.Magnetic resonance imaging revealeda well deWned soft tissue mass consistent with a ganglion,compressing the ulnar nerve in Guyon’s canal.Entrapment neuropathies are one of the common conditionshandled by physiatrists. Ulnar nerve lesions atthe wrist should be kept in mind in the diVerential diagnosisof patients with wrist or hand pain. Magnetic resonanceimaging is a useful method in the anatomicalevaluation of acute focal neuropathies.Keywords Ulnar neuropathy · Entrapmentneuropathy · Guyon’s canal · Ganglion ·Magnetic resonance imaging · Focal neuropathyG. Erkin · H. Uysal · C. Aybay · S. ÖzelAnkara Physical Medicine and Rehabilitation Educationand Research Hospital, Ministry of Health,Ankara, TurkeyI. KeleoDepartment of Physical Medicine and Rehabilitation,Faculty of Medicine, KÂrÂkkale University,KÂrÂkkale, TurkeyG. Erkin (&)Mektep sokak. 16/3, Kurtuluo, Ankara, Turkeye-mail: gultenerkin@yahoo.comIntroductionThe ulnar nerve may be compressed at various criticalanatomic sites along its pathway at the wrist and hand[1]. The wrist is the second most common site ofentrapment for ulnar nerve following the elbow [2].However, the clinical diagnosis of ulnar nerve lesions isnot always easy, particularly when sensory complaintsare absent or atypical. Moreover, it is usually diYcultclinically and sometimes electrophysiologically tolocalize the lesion [3].Ulnar nerve lesion at the wrist is not a common conditionamong the entrapment neuropathies [3], andmost of the reported cases were associated with the historyof chronic signs and/or symptoms [4–15].Although physiatrists are one of the foremost physiciansusually confronted with the nerve entrapmentsyndromes, a review of the medical literature indicatesthat the majority of reported cases with ulnar nervelesion at the wrist were published in surgical journals[4, 5, 8, 12–22].Herein, we report a case of acute ulnar neuropathyat the wrist caused by a ganglion in Guyon’s canal thatwas initially misinterpreted as Xexor tenosynovitis dueto atypically clinical presentation.Case reportA 40-year-old right-handed saleswoman, previously inexcellent health, presented with a 1-week history ofacute pain in the left wrist and hand. She complained ofdiYculty in holding objects at work due to left wristpain. She denied any sensory or motor changes in upperlimbs. Her past medical history was unremarkable.123

Acta Neurol Scand 2006: 113: 288–293 DOI: 10.1111/j.1600-0404.2006.00580.xCopyright Ó 2006 The AuthorsJournal compilation Ó 2006 Blackwell MunksgaardACTA NEUROLOGICASCANDINAVICAOrthostatic heart rate variability analysis inidiopathic Parkinson’s diseaseMihci E, Kardelen F, Dora B, Balkan S. Orthostatic heart ratevariability analysis in idiopathic Parkinson’s disease.Acta Neurol Scand 2006: 113: 288–293.Ó 2006 The Authors Journal compilation Ó 2006 Blackwell Munksgaard.Objectives – We evaluated time and spectral analyses of 24-h heart ratevariability (HRV) and the heart rate responses to passive tilt in patientswith idiopathic Parkinson’s disease (IPD) in order to investigatecardiovascular autonomic functions. Material and methods – Twentythreesubjects with IPD without autonomic symptoms and 15 agematchedhealthy controls were enrolled. Frequency- and time-domainHRV parameters were studied during resting and passive head-up tilt(HUT) test. Results – All time-domain parameters were found to below in patients with IPD. In patients with IPD, both low frequency(LF) and high frequency (HF) decreased during HUT period andno significant change in LF to HF ratio was noted. Both timeandfrequency-domain HRV indices showed no correlation withage, disease severity and duration, and with l-dopamedication. Conclusion – The results indicate that impairment ofautonomic nervous system function in IPD without autonomicsymptoms is frequent, and does not show clear association with clinicalstage and the age of the patients.E. Mihci 1 , F. Kardelen 2 , B. Dora 1 ,S. Balkan 11 Departments of Neurology and 2 Paediatric Cardiology,Akdeniz University School of Medicine, Antalya, TurkeyKey words: idiopathic Parkinson's disease; heart ratevariability; tilt test; autonomic functionEbru Mihci, Department of Neurology, Akdeniz UniversitySchool of Medicine, Arapsuyu 07059, Antalya,TurkeyTel.: 0 90 242 2274343Fax: 0 90 242 2274320e-mail: ebrumihci@akdeniz.edu.trAccepted for publication October 27, 2005Autonomic nervous system (ANS) dysfunctionresults in significant morbidity and mortality inpatients with Parkinson’s disease (PD). ANSsymptoms in PD include derangements of cardiovascularregulation, particularly orthostatic hypotension,in addition to bowel and bladder, sleepand sexual dysfunction (1–4). Subclinical autonomicdysfunction involving both the sympatheticand parasympathetic systems has also been demonstratedin PD using cardiovascular reflex testsbased on heart rate and blood pressure responsesto various stimuli (5, 6).The conventional time- and frequency-domainheart rate variability (HRV) measures, previouslyproved useful in predicting cardiac arrhythmiaoccurrence and mortality risk in coronary heartdisease, are diminished in various central nervoussystem disorders such as stroke, epilepsy, braininjuries, and in some degenerative cerebral diseases(7–9). Recently, diminished variability of standardRR intervals and spectral measures of HR variabilityhave also been reported in PD (5, 10, 11).Using spectral analysis of HRV, the presentstudy aimed to evaluate the magnitude ofcardiovascular ANS dysfunction in patients withPD without orthostatic dysregulation and cardiovascularANS symptoms. The measurements of theHRV were analyzed in relation to age, durationand severity of disease and l-dopa dose.Material and methodsWe performed HRV analysis on combined 24-hambulatory electrocardiographic (ECG) recordingsfrom 23 patients with idiopathic Parkinson’sdisease (IPD) and 15 control subjects withoutsymptoms of orthostatic dysregulation.Full neurologic and systemic examinations wereperformed in all patients and control subjects bythe same physician. Patient diagnosis was based onclinical, laboratory and radiological findings.Patients showing signs suggesting multiple systematrophy, progressive supranuclear palsy or otherParkinson plus syndromes were excluded.Exclusion criteria for patients and control subjectswere presence of history of cardiac, gastrointestinaland respiratory disease, any intercurrentillness and consumption of medications (such as288

Clinical Neurophysiology 118 (2007) 105–110www.elsevier.com/locate/clinphThe effect of hyperventilation on strength–duration propertiesin diabetic polyneuropathyDeniz Yerdelen a, *, Hilmi Uysal b , Filiz Koç a , Yakup Sarica aa Department of Neurology, Cukurova University Faculty of Medicine, Adana, Turkeyb Department of Neurology, Akdeniz University Faculty of Medicine, Adana, TurkeyAccepted 21 September 2006Available online 13 November 2006AbstractObjective: Hyperventilation and ischaemia increase axonal excitability by changing Na + conductance in healthy subjects. However, thechanges in excitability during and after ischaemia in diabetic patients are less than in healthy controls. This is known as ischaemic resistance.In this study, we investigated the effects of hyperventilation for 20 min on strength–duration time constant (SDTC) of motor axonsof the median nerve of diabetic patients with polyneuropathy to determine whether diabetics are less affected by hyperventilation, a formof resistance similar to the ischaemic resistance of diabetics.Methods: The SDTC of 14 diabetic patients with polyneuropathy and 10 healthy volunteers were measured following stimulation of rightmedian nerve at the wrist prior to and after hyperventilation for 20 min.Results: There was a significant increase in the SDTC in control subjects, but no significant change in the SDTC for patients with diabeticpolyneuropathy. The score of the clinical response (paraesthesiae and carpopedal spasm) to hyperventilation of controls was alsosignificantly greater in the controls than the patients.Conclusion: Hyperventilation for 20 min has little influence on SDTC in patients with diabetic polyneuropathy.Significance: The ‘resistance’ of diabetic nerve is not confined to ischaemia but involves other manoeuvres that can alter axonalexcitability.Ó 2006 Published by Elsevier Ireland Ltd on behalf of International Federation of Clinical Neurophysiology.Keywords: Strength–duration properties; Hyperventilation; Diabetic polyneuropathy1. IntroductionAxonal excitability studies have been used in several diseasesto investigate the underlying pathophysiology (Burkeet al., 2001). Many of the diseases which have been studiedshare mechanisms disturbing Na + /K + pump activity, andNa + or K + conductances. Strength–duration time constant(SDTC) is a measure of axonal excitability that depends onthe biophysical properties of the axonal membrane at the* Corresponding author. Present address: Baskent University Faculty ofMedicine, Department of Neurology-Adana, Posta kodu: 01250,Dadaloğlu mah. 39 sok. Yüreğir-Adana, Turkey. Tel.: +90 32232727272; fax: +90 322 3386586.E-mail address: wvdeniz@superonline.com (D. Yerdelen).node of Ranvier and can provide some information aboutNa + channel function (Burke et al., 2001). In healthy subjects,an increase in axonal excitability occurs duringhyperventilation and ischaemia. The changes in excitabilityoccurring during both hyperventilation and ischaemiainvolve persistent Na + channels but, transient Na + channelsare inactivated during ischaemia due to membranedepolarization and relatively unaffected during hyperventilation(Mogyoros et al., 2000).Diabetic polyneuropathy is one of the most frequentlyseen polyneuropathies, but its pathophysiology and changesin axonal ion channels have not been clarified completely.It has been demonstrated that the normal increase inaxonal excitability during ischaemia is attenuated in diabeticpolyneuropathy. This has been termed ‘ischaemic1388-2457/$32.00 Ó 2006 Published by Elsevier Ireland Ltd on behalf of International Federation of Clinical Neurophysiology.doi:10.1016/j.clinph.2006.09.017

Archives of Gerontology and Geriatrics 44 (2007) 141–151www.elsevier.com/locate/archgerLinear measures of temporal lobe atrophy onbrain magnetic resonance imaging (MRI) butnot visual rating of white matter changes canhelp discrimination of mild cognitiveimpairment (MCI) and Alzheimer’sdisease (AD)Esen Saka a, *, Ebru Apaydin Dogan b , Mehmet Akif Topcuoglu a ,Utku Senol c , Sevin Balkan ba Department of Neurology, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkeyb Department of Neurology, Faculty of Medicine, Akdeniz University, 07059 Antalya, Turkeyc Department of Radiology, Faculty of Medicine, Akdeniz University, 07059 Antalya, TurkeyReceived 7 October 2005; received in revised form 4 April 2006; accepted 10 April 2006Available online 24 May 2006AbstractClinical discrimination of the early stages of AD and MCI is challenging. MRI indices whichare simple enough to be applied by non-radiologists on hard copies would be of practicalimportance in the discrimination. We studied 45 consecutive patients (17 with MCI, 25 withAD, 3 with normal cognitive findings) with at least one white matter lesion (WML) on axialfluid-attenuated inversion recovery (FLAIR) MRI sequences. WML load was evaluated by Fazekas’scoring system; temporal lobe atrophy by interuncal distance (IUD) measurement. WML pattern hadno significant discriminative value of AD and MCI. No significant correlation between periventricular/subcorticalWML scores and neuropsychological test results was observed. The mean IUDwas significantly smaller in patients with MCI compared to those with AD. The cut-off value of IUDwas 28.3 mm with receiver operating curve (ROC) analysis. Area under the curve was 0.925 (95% CI:0.800–0.983). A significant negative correlation between IUD and the mini mental state examination(MMSE), verbal fluency, clock drawing, and Rey Auditory verbal learning test (AVLT) was noted.The results indicate that measurement of IUD is a clinically useful test in discrimination of AD and* Corresponding author. Tel.: +90 312 3051809; fax: +90 312 3093451.E-mail address: esensaka@yahoo.com (E. Saka).0167-4943/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.archger.2006.04.006

142E. Saka et al. / Archives of Gerontology and Geriatrics 44 (2007) 141–151MCI patients with WML(s) on brain MRI. However, severity of these lesions is not useful fordistinctions.# 2006 Elsevier Ireland Ltd. All rights reserved.Keywords: Mild cognitive impairment (MCI); Alzheimer’s disease (AD); Brain MRI; Fluid-attenuated inversionrecovery (FLAIR); Temporal lobe atrophy; White matter lesion (WML); Lacune1. IntroductionAD is common in elderly persons. Since there still has no absolute cure for AD,diagnosis of preclinical cases can be important. As a great body of information has beengathered on the pathophysiology of AD, we can expect that it will be possible to delay theonset of AD, slow its progress, or even prevent it in the near future. MCI has been regardedas the pre-clinical form of dementia, a high-risk condition that may precede AD, and thereliable diagnosis of MCI cases can be the key point in AD prevention. Differentiation ofMCI from AD is also important, since not the all cases of MCI will convert to AD(Knopman et al., 2003).Unfortunately, there is no laboratory marker present for diagnosis of pre-clinical casesof AD. To help this problem, finding of a correlate of cognitive decline in MCI and ADgains high attention in neuroimaging studies. Besides identifying structural brain lesions,MRI can reliably detect hippocampal atrophy, and help to differentiate AD cases fromhealthy subjects (Jack et al., 1997; Laakso et al., 1998; Pucci et al., 1998; Juottonen et al.,1999; Wahlund et al., 2000). Several studies demonstrated that hippocampal atrophymeasured by MRI can also differentiate preclinical AD cases from controls (Kaye et al.,1997; Jack et al., 1999; Killiany et al., 2000).Besides hippocampal and cortical atrophy, WML are common in AD. Consequently,clinical and neuropsychological impact of WML on MRI images is another focus ofinterest in dementia, MCI and apparently normal elderly subjects. Numerous studiesemployed various techniques in analyzing WML, some are being very complicated andothers are being very simplistic (Fazekas et al., 2002; Kapeller et al., 2003; Wardlaw et al.,2004). Different neuropsychological tests were employed in different studies. Samplingmethod and subjects also differed in those studies. Most of these studies addressed differentquestions, but the main point in all was unrevealing of the clinical importance of WML(Desmond, 2002). Verbal memory performances in some studies (Capizzano et al., 2004)and various frontal lobe functions in others correlated with WML (Starkstein et al., 1996;Leaper et al., 2001; Desmond, 2002). Some of the studies focusing on AD alsodemonstrated WML may be linked to the cortical or hippocampal atrophy in the way thatpatients with higher degree of atrophy also have higher WML (Capizzano et al., 2004; DeLeeuw et al., 2004). It was reasonable to postulate that WML may be leading hippocampalatrophy by way of disconnecting input from cortical association areas.MRI studies, in which WML and hippocampal volume were measured to differentiateMCI from AD, provided variable results: some of these studies demonstrated that theseMRI indices were useful (Jack et al., 2000; Karas et al., 2004), but others did not (Bonannoet al., 2000). Besides the discrepancies of the result of these studies, the imaging analysis

E. Saka et al. / Archives of Gerontology and Geriatrics 44 (2007) 141–151 143techniques employed for volumetric measurements are demanding and time-consuming,and therefore not usually available to the clinicians for routine use. Thus, more simple butsensitive methodologies are needed. In this context, measurement of hippocampal atrophyon routine MRI hard copies, which usually obtained for exclusion of structural lesion, is ofcritical importance.In this study, we aim to study the usefulness of IUD, which is proposed as a simple toolto detect atrophy of medial temporal lobe and can reliably be measured on MRI hardcopies, for discrimination of MCI and mild/moderate stages of AD. Additionally,contribution of WML severity for this distinction is assessed.2. Materials and methods2.1. SubjectsAmong the patients referred to the dementia out-patients clinic of Akdeniz UniversityHospital for neuropsychological evaluation between July 2004 and May 2005, patientswith hyperintense lesion(s) on brain MRI were evaluated for this study. All of the cases hadthe complaint of memory impairment. Because of its low prevalence, additional patientswith the diagnosis of MCI and hyperintense lesion on MRI, who were seen by one of theauthors (SB) during the last 3 years, were also included to the study. After excludingvascular dementia cases, hyperintense MRI lesions were observed in 58 subjects (diagnosisafter evaluation: mild/moderate AD in 25, severe AD in 13, MCI in 17 and normal in 3). Ofthem, patients with mild/moderate AD and those with MCI were included into the study. Adetailed medical history was re-obtained from these subjects, including presence ofcerebrovascular disorders and other active neurologic or psychiatric disorders, systemicillnesses such as diabetes mellitus, hypertension, coronary heart disease, currentmedication use, smoking, alcohol use, and incidence of head trauma. A detailedneurologic examination was performed. Complete blood count, biochemistry for hepaticand renal functions, thyroid function tests and Vitamin B 12 level were reviewed, andTable 1Demographic featuresMCIADN 17 25Age 68.9 5.8 74.7 6.4Sex (female/male) 12/5 14/11Family history of dementia 1 (6) 6 (24)Education (in years) 7.4 4.0 6.4 4.9Hypertension 11 (65) 11 (44)Coronary heart disease 3 (18) 4 (16)Diabetes mellitus 0 (0) 6 (24)Hyperlipidemia 2 (12) 5 (20)GDS 7.3 5.2 9.6 6.4MMSE 26.3 2.5 18.2 4.1Notes: Data in parentheses are %.

144E. Saka et al. / Archives of Gerontology and Geriatrics 44 (2007) 141–151studied in their absence. The mean age of the patients with the diagnosis of MCI was lowerthan those with AD (68.9 5.8 and 74.7 6.4 years, respectively). In patients with MCI,gender ratio and education levels (in schooling years) were comparable (Table 1).Frequencies of vascular risk factors are also displayed in Table 1.2.2. Cognitive assessmentA screening of general cognitive function was carried out by MMSE (Folstein et al.,1975). Geriatric depression scale (GDS) was introduced in all. Extensive neuropsychologicaltesting, including digit span, reciting months forwards and backwards, trial A andB, Rey AVLT (Lezak, 1995), clock drawing, verbal fluency, category fluency, Bostonnaming test were administered to eligible patients (according to their education level andcognitive functioning). Diagnosis of dementia was done according to DSM-IV criteria(American Psychiatric Association, 1994). MMSE of patients with dementia were 24 orless. Patients with AD met the criteria for ‘‘probable AD’’ according to NINCDS-ADRDAWork Group (McKhann et al., 1984). Patients who did not met DSM-IV criteria ofdementia and were independent in activities of daily living, assessed through theInstrumental Activities of Daily Living (IADL) (Lawton and Brody, 1969), were furtherevaluated for the objective evidences of cognitive impairment. Patients demonstratedimpairment of memory and/or executive functions and met the Mayo Clinic Criteria forMCI (Petersen et al., 2001) were classified as MCI. As expected, MMSE scores weresignificantly lower for patients with AD than for patients with MCI.2.3. WML assessmentThe FLAIR MRI sequences were used for analysis of load and extent of hyperintenselesion(s). A semi-quantitative rating scale described by Fazekas et al. (1987) was used.This system scores on a four-point scale of increasing severity of subcortical deep WML,and periventricular WML separately. Subcortical WML severity was scored as normal(Grade-0); punctate (Grade-1); coalescing (Grade-2) and confluent (Grade-3). PeriventricularWML severity was scored as normal (Grade-0); pencil lines and/or caps (Grade-1);smooth haloes (Grade-2) and larger, patchy and irregular (Grade-3). Examples ofsubcortical and periventricular WML are shown in Fig. 1. The subcortical andFig. 1. Examples of the rating scores 0, 1, 2 and 3 for severity and extents of the WML and PVL.

periventricular WML were defined as punctate when their maximum diameter was lessthan 5 mm and as patchy when were larger than 10 mm. Small (diameter < 15 mm)FLAIR hypointense lesions with peripheral hyperintense rim were defined as lacunarinfarcts, and were not included for lesion-load or severity scores. Enlarged perivascularspaces were also excluded on the basis of their characteristic appearance (hypointenselinear or small punctate lesions) on FLAIR images. Only the supratentorial lesions wereconsidered for the analyses. Lesions were considered as periventricular when directlyadjacent to the ventricles or located within 10 mm perpendicularly from the ventricleborder. The extending part of this type lesion was scored in subcortical WML (Fazekaset al., 2002).The inter-rater reproducibility of subcortical and periventricular WML scores wastested with k statistics between 2 raters (US and MAT), both of whom were unaware of theclinical information of the subjects and of the results of the other rater, in randomly selected14 patients (7 MCI, 6 AD, and 1 normal). For subcortical and periventricular WML scores,weighted k = 0.814 and 0.899 values were obtained, respectively, indicating an excellentagreement.2.4. Measurement of IUD and normalization of the valuesAxial T1 weighted MRI scans were used for linear measurement of IUD, bitemporaldistance (BTD) and intracranial width (ICW) (see Fig. 2). All were measured at the level ofsuprasellar cystern. IUD is the distance between the unci of temporal lobes. BTD is thedistance between outer margins of temporal lobes at the level where IUDs were obtained.ICW is the horizontal distance between the inner cranium at the level of the unci. IUD wasnormalized against ICW (nIUD = IUD/ICW 100) to exclude the effect of individualhead size. We considered that a ratio of IUD to BTD, called uncotemporal index(UTI) = IUD/BTD 100 would be more sensitive measure for temporal lobe atrophybecause IUD increases and BTD decreases with atrophy of temporal lobes progress. Andalso, this index helps to normalize the effect of brain sizes in the patients without cerebralatrophy. Cases in which the unci were not on the same horizontal plane were excluded. AllMRIs were scanned and measurements were performed with the image analyzing software(UTHSCSA Image Tool 1 , Version 3; obtained from http://ddsdx.uthscsa.edu/dig/itdesc.html).In 14 patients, measurements were performed on hard copies with a ruler. The mean ofIUD was 29.4 for rater 1 (US, with ruler) and 30.6 for rater 2 (MAT, with Image tool 1 ) witha correlation coefficient of 0.82, indicating satisfactory inter-observer and inter-techniquereliability.2.5. Statistical analysisE. Saka et al. / Archives of Gerontology and Geriatrics 44 (2007) 141–151 145The data were analyzed by using SPSS 1 13.0 and MedCalc 1 statistical softwareprograms. The results were expressed as mean S.D., or percentages as appropriate.Mann–Whithney U and 2-tailed Student’s t-tests were used for analysis of numericalvariables. Chi-square and Fisher’s exact tests were used for comparison of categoricaldata. ROC analysis was used for calculation of cut-off values and for estimation of

146E. Saka et al. / Archives of Gerontology and Geriatrics 44 (2007) 141–151Fig. 2. Demonstration of IUD, BTD and ICW measurements on Axial T1 weighted MRI.discriminative potential of the linear measurements of atrophy (IUD, nIUD and UTI)between AD and MCI. Positive and negative likelihood ratios (+LR and LR) werecalculated for WMLs and PVLs scores for the same purposes. The relation betweenatrophy (IUD) and white matter disease (WMLs and PVLs) were tested with Spearman’scorrelation analysis and one-way analysis of variance (ANOVA) statistics. For the latter,pair-wise multiple comparisons of the mean IUD values per categories of WMLs and PVLsscores were tested with Tamhane’s T2 following ANOVA. p values and 95% confidenceintervals were given. A value of p < 0.05 was considered as statistically significant.3. ResultsThe MR data are summarized in Table 2. No significant difference was detectedbetween the patients with AD and those with MCI in terms of subcortical WML scores 0–3( p = 0.285, chi square test for 4 2 table). When test was repeated after combining thescores as absent/minimal lesion (scores 0 and 1) versus more significant lesions (scores 2and 3), Fisher’s exact test failed again to show any difference between AD and MCI( p = 0.109, for 2 2 table). However, periventricular WML scores were significantlyhigher in patients with AD, compared to those with MCI ( p = 0.021 for 4 2 table, andp = 0.027 for 2 2 table). To discriminate MCI from AD, subcortical WML scores of 0and 1 showed low positive and negative likelihood ratios (1.59 and 0.45, respectively) over

E. Saka et al. / Archives of Gerontology and Geriatrics 44 (2007) 141–151 147Table 2Imaging characteristicsMCIADn 17 25Subcortical WML0 3 (18) 3 (12)1 10 (58) 9 (36)2 2 (12) 9 (36)3 2 (12) 4 (16)Periventricular WML0 6 (35) 1 (4)1 9 (53) 13 (52)2 2 (12) 8 (32) a3 0 (0) 3 (12) aIUD (mm) 27.3 2.7 34.6 4.1 anIUD (%) 20.1 1.6 25.9 2.2 aUTI (%) 21.2 1.8 27.8 3.0 aNotes: Data in parentheses are %.a p < 0.05.the scores of 2 and 3. Positive and negative likelihood ratios for periventricular WMLscores (score 0–1 over score 2–3) were 1.58 and 0.27, respectively.MMSE scores did not show any significant difference across subcortical WML scores:22.7 7.4, 22.0 5.9, 21.8 3.7, and 20.3 5.1 for from score 0 to score 3, respectively(F = 0.213, p = 0.887). Albeit a trend of negative correlation was available, MMSE scoresagain did not show any significant difference across periventricular WML scores: 24.3 5.1,22.7 5.2, 19.7 5.3, and 17.3 4.7 for score 0 to score 3 (F = 2.072, p = 0.119). Nosignificant correlation of the MRI-scores of subcortical and periventricular WML with theresults of the neuropsychological tests was observed except than a negative correlationbetween periventricular WML severity and categorical fluency (r = 0.457; p = 0.003).The mean IUD, normalized IUD and UTI are significantly smaller in patients with MCIcompared to those with AD (Table 2). The cut-off value of IUD is 28.3 mm with ROC curveanalysis. Lower values than 28.3 mm have sufficient sensitivity (88.2%, 95% CI: 63.5%–98.2%) and specificity (96%, 95% CI: 79.6%–99.3%) for discrimination of MCI from AD.The area under curve (AUC) is 0.925 (S.E.M. = 0.041, 95% CI: 0.800–0.983). The positiveand negative likelihood ratios are 22.06 and 0.12, respectively. Normalization of IUD withthe intracranial width resulted in an increase of sensitivity (94.1%, 95% CI: 71.2–99.0)along with no change of specificity with the cut-off value of 23.2%. This index is alsouseful for discrimination of MCI and AD (AUC = 0.958; S.E.M. = 0.031, 95% CI: 0.846–0.994; +LR: 23.53; LR: 0.06). The cut-off value of UTI is 21.5% and measurement ofUTI has almost a similar degree of diagnostic yield (AUC = 0.962; S.E.M. = 0.029; 95%CI: 0.853–0.935; +LR: 23.53; LR: 0.06). Pair-wise comparison of these three ROCcurves failed to show any significant difference ( p = 0.235 between IUD and nIUD;p = 0.334 IUD and UTI; p = 0.697 nIUD and UTI).Overall (for 45 subjects), IUD showed a moderate but significant relationship to age(r = 0.342; p = 0.022). However, absence of correlation in the individual subgroups

148E. Saka et al. / Archives of Gerontology and Geriatrics 44 (2007) 141–151Fig. 3. Correlations of IUD and age in normal, MCI and AD groups. R 2 = r 2 .(r = 0.026, p = 0.920 in MCI and r = 0.025; p = 0.906 in AD) and a significant overlap seenacross the subgroups in the scatter-plots of the IUD against age (Fig. 3) indicate thatcorrelation observed in entire population reflects the effect of the diagnostic categories, butnot the direct effect of the age.A significant negative correlation between IUD and MMSE scores was noted(r = 0.541, p < 0.0001). IUD showed significant correlation with the tests of verbalfluency (r = 0.344, p = 0.032), clock drawing (r = 0.392; p = 0.022) and AVLT(r = 0.573, p = 0.041).While there was no significant correlation between IUD and subcortical WML(r = 0.215, p = 0.155; 95% CI: 0.0837–0.4785), a moderate but significant correlationbetween IUD and periventricular WML was present (r = 0.464, p = 0.0013; 95% CI:0.1977–0.6669). And also, the mean values of IUD increased with increasedperiventricular WML scores (28.3 3.3 for score 0: 30.7 4.8 for score 1; 34.6 4.7for score 2; 35.7 4.0 for score 3; F = 3.986, p = 0.014).4. Discussion and conclusionThis study demonstrates that IUD, which is a simple linear measurement method ofmedial temporal lobe atrophy, is a useful tool to differentiate between MCI and AD patientswith hyperintense lesion(s) on brain MRI. Measures of WML severity are not useful fordiscrimination of AD and MCI in this particular population.The IUD was introduced by Dahlbeck et al. (1991) as a simple method obtainable from asingle section of an MRI scan for the diagnosis of AD. These authors suggested that theIUD value higher than 30 mm was highly specific for AD, and not present in the normalelderly population. However, subsequent studies produced conflicting data on the

E. Saka et al. / Archives of Gerontology and Geriatrics 44 (2007) 141–151 149screening potential of IUD measurement because of the significant overlap observed with ADand normal controls (Doraiswamy et al., 1993; Howieson et al., 1993; İshii, 1994). For thediagnosis of mild or early stages of AD, the data available on the usefulness of IUD is evenmore conflicting. Some studies suggested that the IUD and other linear measures of medialtemporal lobe atrophy (width of the temporal horn, width of the choroid fissure, andhippocampal height) could contribute to the discrimination of control subjects or patientswith MCI from patients with mild AD (Frisoni et al., 1996), but others claimed that IUD wasnot a reliable diagnostic tool for this purpose (Laakso et al., 1995). Because the available dataare inconclusive, we decided to study the usefulness of IUD to distinguish AD and MCI.Beyond the inconsistency of literature on record, it is clear from the pathological studies thatthe medial temporal lobe structures such as hippocampus, entorhinal area, subiculum areharbored early in AD, therefore, the IUD is expected to be a useful tool for diagnosis of earlyAD unless it has a poor reproducibility. With ROC curve analysis, we demonstrated that a cutoff value of 28.3 mm can reliably distinguish AD and MCI, because the 95% CI of the areaunder curve (0.800–0.983) did not include 0.50 (Hanley and McNeil, 1982). Furthermore, thereasonable positive and negative likelihood ratios (22.06 and 0.12, respectively) supportedthe usefulness of IUD. It is established that good tests have positive likelihood ratio valuebetween 5 and 10 and negative likelihood ratio of less than 0.1–0.2 (Jaeschke et al., 1994a,b).Moreover, IUD was correlated with MMSE and other neuropsychological tests. We alsodemonstrated that measurement of IUD with a ruler on the hard copies of MRI and computerbasedmeasurements were well correlated. Therefore, we suggest that any physician involvedin the care of these patients can easily and objectively measure this useful index on the printedforms of the routine MRIs. Because, no additional benefit was observed in our study afteradjustment of the IUD for brain (temporal lobe) and head (cranial vault) size, a cut-offnumber of IUD can be used alone as a criterion. We also demonstrated that there was no needto adjust for age. Contrary to some previous data indicating a significant effect of age on IUD(Doraiswamy et al., 1993; Laakso et al., 1995), the effect of age in our study was found only tobe indirect (Fig. 3). In this context, it is worth mentioning that IUD can only be measured andevaluated on previously obtained MRI hard copies when there are no significant artifacts andimproper head positioning.Several studies had shown that WML and hippocampal atrophy are almost linearlyrelated (Capizzano et al., 2004; De Leeuw et al., 2004). Our study confirms theseobservations by revealing a significant correlation between IUD and scores ofperiventricular WML severity. We found that subcortical deep WML severity is notuseful to distinguish AD and MCI, but when the score is low (0 and 1) periventricularWML load can be accepted as a weak but still valuable parameter. Relative importance ofperiventricular WML over subcortical deep WML on disturbed cognitive performance hadbeen demonstrated in a few studies previously (Ylikoski et al., 1993; Fukui et al., 1994).This locational preponderance is proposed to be due to the high density of inter-corticalconnection pathways running through periventricular regions (Desmond, 2002).It is important to note that in the absence of concomitant atrophy, WML load especiallyin the subcortical white matter location, is not directly associated with the severity ofcognitive deficit (Desmond, 2002). Furthermore, some patients with severe subcorticalWML, corresponding to one third of our study population with score 3 of subcorticalWML, may appear to be relatively intact in cognition. This underlines the relative

150E. Saka et al. / Archives of Gerontology and Geriatrics 44 (2007) 141–151importance of strategic distribution of the lesions over a threshold of total lesion load indevelopment of clinically meaningful cognitive deficit.Our small-sized but well-documented case series highlights the importance of IUDmeasurements as an easy-to-obtain, objective and useful tool to improve the diagnosticreliability of AD and its discrimination from MCI. In the absence of temporal lobe atrophy,WML load and its location has minimal or no yield in this respect.ReferencesAmerican Psychiatric Association, 1994. DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, fourthed. American Psychiatric Association, Washington.Bonanno, M.R., Russo, M.S., Leonardo, M., Santangelo, A., Calanna, A., Barbagallo, P., Speciale, S., Panebianco,P., Maugeri, D., 2000. Leukoaraiosis, cognitivity and affectivity in elderly patients: on the lack of correlationsbetween neurodiagnostic and psychometric findings. Arch. Gerontol. Geriatr. 30, 101–108.Capizzano, A.A., Acion, L., Bekinschtein, T., Furman, M., Gomila, H., Martinez, A., Mizrahi, R., Starkstein, S.E.,2004. White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease.J. Neurol. Neurosurg. Psychiatry 75, 822–827.Dahlbeck, J.W., McCluney, K.W., Yeakley, J.W., Fenstermacher, M.J., Bonmati, C., Van Horn 3rd, G., Aldag, J.,1991. The interuncal distance: a new MR measurement for the hippocampal atrophy of Alzheimer’s disease.Am. J. Neuroradiol. 12, 931–932.De Leeuw, F.E., Barkhof, F., Scheltens, P., 2004. White matter lesions and hippocampal atrophy in Alzheimer’sdisease. Neurology 62, 310–312.Desmond, D.W., 2002. Cognition and white matter lesions. Cerebrovasc. Dis. 13 (Suppl. 2), 53–57.Doraiswamy, P.M., McDonald, W.M., Patterson, L., Husain, M.M., Figiel, G.S., Boyko, O.B., Krishnan, K.R.,1993. Interuncal distance as a measure of hippocampal atrophy: normative data on axial MR imaging. Am. J.Neuroradiol. 14, 141–143.Fazekas, F., Chawluk, J.B., Alavi, A., Hurtig, H.I., Zimmerman, R.A., 1987. MR signal abnormalities at 1.5 T inAlzheimer’s dementia and normal aging. Am. J. Roentgenol. 149, 351–356.Fazekas, F., Barkhof, F., Wahlund, L.O., Pantoni, L., Erkinjuntti, T., Scheltens, P., Schmidt, R., 2002. CT and MRIrating of white matter lesions. Cerebrovasc. Dis. 13 (Suppl. 2), 31–36.Folstein, M.F., Folstein, S.E., McHugh, P.R., 1975. Mini-mental state: a practical method for grading the cognitivestate of patients for the clinician. J. Psychiat. Res. 12, 189–198.Frisoni, G.B., Beltramello, A., Weiss, C., Geroldi, C., Bianchetti, A., Trabucchi, M., 1996. Linear measures ofatrophy in mild Alzheimer disease. Am. J. Neuroradiol. 17, 913–923.Fukui, T., Sugita, K., Sato, Y., Takeuchi, T., Tsukagoshi, H., 1994. Cognitive functions in subjects with incidentalcerebral hyperintensities. Eur. Neurol. 34, 272–276.Hanley, J.A., McNeil, B.J., 1982. The meaning and use of the area under a receiver operating characteristic (ROC)curve. Radiology 143, 29–36.Howieson, J., Kaye, J.A., Holm, L., Howieson, D., 1993. Interuncal distance: marker of aging and Alzheimerdisease. Am. J. Neuroradiol. 14, 647–650.İshii, K., 1994. Value of interuncal distance measure in diagnosis of Alzheimer disease questioned. Am. J.Neuroradiol. 15, 1286.Jack C.R.JJr., Petersen, R.C., Xu, Y.C., Waring, S.C., O’Brien, P.C., Tangalos, E.G., Smith, G.E., Ivnik, R.J.,Kokmen, E., 1997. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease.Neurology 49, 786–797.Jack C.R.JJr., Petersen, R.C., Xu, Y.C., O’Brien, P.C., Smith, G.E., Ivnik, R.J., Boeve, B.F., Waring, S.C.,Tangalos, E.G., Kokmen, E., 1999. Prediction of AD with MRI-based hippocampal volume in mild cognitiveimpairment. Neurology 52, 1397–1403.Jack C.R.JJr., Petersen, R.C., Xu, Y.C., O’Brien, P.C., Smith, G.E., Ivnik, R.J., Boeve, B.F., Tangalos, E.G.,Kokmen, E., 2000. Rates of hippocampal atrophy correlate with change in clinical status in aging and AD.Neurology 55, 484–489.

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JRRD Volume44, Number 3, 2007Pages 373–380Journal of Rehabilitation Research & DevelopmentEffect of temperature on electrophysiological parameters of swallowingBarin Selçuk, MD; 1* Hilmi Uysal, MD; 2 Ibrahim Aydogdu, MD; 2 Müfit Akyuz, MD; 1 Cumhur Ertekin, MD 31 Ankara Physical Medicine and Rehabilitation Education and Research Hospital of Ministry of Health, Ankara,Turkey; 2 Neurology Department, Faculty of Medicine, Akdeniz University, Antalya, Turkey; 3 Neurophysiology andNeurology Department, Faculty of Medicine, Ege University, Izmir, TurkeyAbstract—The effect of three different temperature ranges onthe triggering of voluntary-induced swallowing and on the durationof the pharyngeal phase of oropharyngeal swallowing wasstudied electrophysiologically. The relationship between volumeand temperature of liquids swallowed was also explored.This study included 40 nondisabled volunteers (23 male and17 female). Laryngeal vertical movements and submental electromyographicactivity were recorded as each subject swallowedwater at three different temperature ranges: normal (23–25 °C), cold (8–10 °C), and hot (58–60 °C). The time for triggeringof the pharyngeal phase of swallowing was found to beshorter for cold and hot water than for normal temperature water(p < 0.01). The duration of the pharyngeal phase of oropharyngealswallowing was also shorter for cold and hot water than fornormal temperature water (p < 0.05). The maximum capacity ofa single bolus (dysphagia limit) was >20 mL of water in all nondisabledsubjects for different temperatures. However, thecapacity was significantly less for hot water relative to normaltemperature water and cold water (p < 0.05). In conclusion, thetemperature ranges used in this study were found to be effectivein triggering voluntary-induced swallowing.Key words: deglutition, dysphagia, electrophysiological method,laryngeal sensor, neurophysiology, rehabilitation, sensory, submentalEMG, swallowing, temperatures, thermal stimulation.INTRODUCTIONThe sensory receptors in the oropharyngeal mucosaeare involved with initiating voluntary-induced swallows,and they relay the information to the brain about the size,viscosity, and temperature of the bolus to be swallowed.The importance of sensory inputs during swallowing hasbeen shown in research without [1–3] and with humansubjects [4–10]. Among the sensory variables, the effectsof bolus volume and viscosity on swallowing have beenfrequently studied [9–12]. On the other hand, the effects ofbolus temperature on oropharyngeal swallowing have beenscarcely documented [13–16]. Logemann has proposedthat thermal stimulation increases oral awareness, providesan alerting sensory stimulus to the pharyngeal swallow,and is triggered more rapidly by initiation of swallowing atthe oral cavity [13]. Other research has shown that atherapy technique called “thermal stimulation” is helpfulin shortening the duration of delay of pharyngeal phaseswallowing in dysphagic patients [11,13–14,16–18]. However,Shaker et al. has shown that temperature does nothave any significant effect on the threshold volume fortriggering pharyngeal swallowing [15].Previous studies have mainly focused on the triggeringof swallows, especially around the mucosae of the posteriororal cavity, but none has focused on the changes to thepharyngeal phase of swallowing in different temperatures.The effects of extreme temperature changes (cold vs hot)Abbreviations: CPG = central pattern generator, EMG = electromyographical,SM-EMG = submental EMG.* Address all correspondence to Barin Selçuk, MD; KasimGülek Sok (50. Sok) 1/10 Bahçelievler, 06500 Ankara, Turkey;+90-312-213-8356; fax: +90-312-310-4242.Email: barinselcuk@yahoo.comDOI: 10.1682/JRRD.2006.08.0089373

1-Korcum AF, Karadogan I, Aksu G, Aralasmak A, Erdogan G Primary follicular lymphoma ofthe cervix uteri: a review.. Ann Hematol. 2007 Sep;86(9):623-30. Epub 2007 Jun 22.ŀRadyasyon Onkolojisi Anabilim Dalı

Ann Hematol (2007) 86:623–630DOI 10.1007/s00277-007-0328-0REVIEW ARTICLEPrimary follicular lymphoma of the cervix uteri: a reviewAylin Fidan Korcum & Ihsan Karadogan &Gamze Aksu & Ayse Aralasmak & Gulgun ErdoganReceived: 2 April 2007 /Accepted: 2 June 2007 /Published online: 22 June 2007# Springer-Verlag 2007Abstract Primary non-Hodgkin’s lymphoma of the cervix isa rare disease, of which a subgroup of follicular lymphomaconstitutes only 8.5%. There is not an established treatmentprotocol neither for primary cervical lymphoma nor for itsfollicular subgroup. We presented a case with Ann Arborstage IEA (Extra-nodal involvement and absence of weightloss, fever, night sweat) primary follicular lymphoma of thecervix. She was treated with chemotherapy followed by pelvicradiotherapy. Upon relapse with a nodal neck mass, she wastreated with rituximab alone. She remained well for 23months after rituximab. In the 39 months of follow-up, therewas no evidence of disease. In the light of our case, wereviewed the reported cases of primary follicular lymphomaof the cervix while discussing their treatment protocols andthe cases of primary cervix lymphoma treated with rituximab.Keywords Primary cervix lymphoma . Follicular .Radiotherapy . ChemotherapyA. F. Korcum (*) : G. AksuDepartment of Radiation Oncology,Akdeniz University, School of Medicine,Antalya 07070, Turkeye-mail: aylinf@hotmail.comI. KaradoganDepartment of Hematology,Akdeniz University, School of Medicine,Antalya 07070, TurkeyA. AralasmakDepartment of Radiology,Akdeniz University, School of Medicine,Antalya 07070, TurkeyG. ErdoganDepartment of Pathology,Akdeniz University, School of Medicine,Antalya 07070, TurkeyIntroductionPrimary non-Hodgkin’s lymphoma (NHL) of the cervix isextremely rare. Only 0.5% of extranodal lymphomas inwomen are likely to originate in the female genital tract [1,2]. Until now, more than 130 cases of primary NHL of thecervix have been reported. The most common histologicalsubtype is diffuse large B-cell lymphoma [3]. Only 11 caseswith low-grade follicular lymphoma of the cervix were reportedcomprising 8.5% of the primary cervix lymphomas[2–9].In the cervical lymphoma, the median age at presentation is44 years, ranging from 27 to 80 years [5, 10]. The mostfrequent complaint is abnormal vaginal bleeding [7]. Fever,night sweats, and weight loss are usually not the features ofprimary lymphoma of the cervix. Other gynecologic symptomscan occur including pelvic pain, postcoital bleeding,postmenopausal bleeding, and dyspareunia [11–13]. Differentialdiagnosis of primary cervical lymphomas includesbenign inflammatory and malignant disease such as cervicalcarcinomas, sarcomas, and lymphoma-like lesions [3, 14,15]. For a definitive diagnosis, a deep cervical biopsy withhistopathological evaluations and immunophenotyping arerequired [14, 15]. Because such located lymphomas aresubepithelial and unless there is ulceration and exfoliation,Papanicolaou smear plays a very insignificant role in thediagnosis of cervical lymphoma [7]. Ann Arbor stage, size,and extent of disease, age, number of extranodal sites, performancestatus, serum lactate dehydrogenase (LDH) values,and grade of lymphoma are significant prognostic features[4, 6, 11, 16].Because of the rarity, there is not an established treatmentprotocol for primary NHL of the cervix. Radiotherapy,chemotherapy, and surgery, either alone or in combination,are the mainstay of treatment [10–12, 17, 18]. Some suggested

1-Nacitarhan, C., Bayram, Z., Eksert, B., Usta,C., Golbasi, I., Ozdem, S.S.. The Effect of HydrogenPeroxide in Human Internal Thoracic Arteries: Role of Potassium Channels, Nitric Oxide andCyclooxygenase Products. Cardiovascular Drugs and Therapy21: 257-262, 20072-Tasatargıl A, Cadir B, Dalaklıoglu S,et.alEffects of vitamin K1 supplementation on vascularresponsiveness and oxidative stressina rat osteotomy modelCell Biochem Func25(5):485-490,20073-Tasatargıl A, Sadan G, Karasu EHomocysteine-induced changes in vascular reactivity of guinea-pigpulmonary arteries:Role of the oxidative stress and poly(ADP-ribose) polymerase activationPulPharmacol Therap20(3):265-272,20074-Nacitarhan C, Sadan G, Kayacan N, Ertugrul F, Arici G, Karsli B, Erman M.The effects of opioids,local anesthetics and adjuvants on isolated pregnant rat uterine muscles.Methods Find Exp ClinPharmacol. 2007 May;29(4):273-6.ŀTıbbi Farmakoloji Anabilim Dalı - 2007

Cardiovasc Drugs Ther (2007) 21:257–262DOI 10.1007/s10557-007-6037-zThe Effect of Hydrogen Peroxide in Human InternalThoracic Arteries: Role of Potassium Channels,Nitric Oxide and Cyclooxygenase ProductsCahit Nacitarhan & Zeliha Bayram & Bilsen Eksert &Coskun Usta & Ilhan Golbasi & Sadi S. OzdemPublished online: 12 July 2007# Springer Science + Business Media, LLC 2007AbstractIntroduction We investigated both the effect and the role(s)of potassium channels, nitric oxide (NO) and cyclooxygenase(COX) products in the effect of hydrogen peroxide(H 2 O 2 ) in human internal thoracic artery (ITA) rings.Materials and methods Samples of redundant ITA obtainedfrom patients undergoing a coronary artery bypass graftsurgery were cut into 3 mm wide rings and suspended in20 ml organ baths. Isometric tension was continuouslymeasured with an isometric force transducer connected to acomputer-based data acquisition system.Results H 2 O 2 (10 −7 –10 −4 M) produced concentrationdependentrelaxation responses in human ITA precontractedby phenylephrine. The relaxant responses to H 2 O 2 did not differsignificantly between endothelium-intact and endotheliumdenudedpreparations. Incubation of human ITA rings withsuperoxide dismutase (50 U/ml) did not affect the relaxantresponses to H 2 O 2 , while 1,000 U/ml catalase caused asignificant decrease. Incubation of endothelium-intact orendothelium-denuded human ITA rings with voltagedependentpotassium channel blocker 4-aminopyridine(5 mM) significantly inhibited the relaxant responses toH 2 O 2 . COX inhibitor indomethacin (10 −5 M) also caused asignificant inhibition. Incubation with ATP-dependentpotassium channel blocker glibenclamide (10 −6 M) orCa 2+ -activated potassium channel blocker iberiotoxinC. Nacitarhan : Z. Bayram : B. Eksert : C. Usta : S. S. Ozdem (*)Department of Pharmacology, Medical Faculty,Akdeniz University,07070 Antalya, Turkeye-mail: sozdem@akdeniz.edu.trI. GolbasiDepartment of Cardiovascular Surgery, Medical Faculty,Akdeniz University,Antalya, Turkey(10 −7 M) or NO synthase (NOS) blocker N w -nitro-Largininemethyl ester (10 −4 M) did not alter relaxantresponses of ITA rings to H 2 O 2 .Conclusion The findings of the present study suggestedthat H 2 O 2 -induced relaxation responses in human ITA wereneither dependant on the endothelium nor blocked by NOSinhibition but they rather seem to depend on the activationof voltage-dependent potassium channels and COX.Key words arterial grafts . hydrogen peroxide . nitric oxide .potassium channels . prostaglandins . thoracic arteryIntroductionReactive oxygen species (ROS) have been implicated in thepathophysiology of several cardiovascular diseases such asischemic stroke, myocardial ischemia and stunning, andischemia–reperfusion injury [1]. Hydrogen peroxide (H 2 O 2 )is a non-radical ROS produced from superoxide anions inseveral different cell types in the human body, includingvascular endothelial and smooth muscle cells via enzymaticconversion by superoxide dismutase (SOD). The steadystateconcentration of H 2 O 2 in human plasma, blood cells,and vascular cells is unknown but is most likely in thelower micromolar range or less [2, 3]. Recent clinical evidencealso indicated that plasma from hypertensive individualscontained higher levels of H 2 O 2 than plasma fromnormotensive subjects [3].In addition to the well-known detrimental effects, it hasbeen reported that H 2 O 2 is a primary endothelium-derivedhyperpolarizing factor in animals and humans [4]. H 2 O 2was also shown to improve postischemic functionalrecovery and coronary blood flow [5]. The vasoactiveproperties of ROS were described previously by Rubayni

The effects of opioids, local anesthetics and adjuvants on isolated pregnant ratuterine muscles.Find Exp Clin Pharmacol. 2007 May;29(4):273-6.Nacitarhan C, Sadan G, Kayacan N, Ertugrul F, Arici G, Karsli B, Erman M.Department of Pharmacology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.AbstractLocal anaesthetics, opioids and adjuvants are often used for managing labor pain. Some others of these agents are reported to causealterations on uterine contractility during labor. However, there are controversies and the effects of some others are unknown. In thepresent study, we aimed to elucidate the effects of opioids such as alfentanyl, meperidine, remifentanyl; local anesthetics such asmepivacaine, ropivacaine, bupivacaine; and adjuvants such as clonidine and midazolam on isolated pregnant rat uterine muscle. Stripsof longitudinal uterine smooth muscle obtained from rats pregnant for 18-21 days were suspended in 20 ml organ baths. Isometrictension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Theeffects of cumulative concentrations of alfentanyl, meperidine, remifentanyl, mepivacaine, ropivacaine, bupivacaine, clonidine andmidazolam (10(-8) - 10(-4) M, for all) on contractions induced by oxytocin (1 mU/ml) were studied. Alfentanyl (10(-5) M), meperidine (10(-ŀMethods5) M), remifentanyl (10(-4) M), bupivacaine (10(-4) M), ropivacaine (10(-4) M) and midazolam (3 x 10(-5) M) caused significantdecreases in contractile responses of uterine strips to oxytocin. Contrastingly, mepivacaine increased (33.1% +/- 7.2%) oxytocin-inducedcontractions of uterine strips while clonidine exerted no significant effect. The sensitivity of myometrial preparations to tested localanesthetics or opioids did not differ significantly. The findings of the present study demonstrated that some local anesthetics, opioids andadjuvants caused significant and agent-specific alterations on contractility of the pregnant rat myometrium. Therefore, they seemed tohave a potential to influence uterine contractility during clinical management of pain during labor. However, further research is needed toextrapolate these finding to clinical practice.PMID: 17609740 [PubMed - indexed for MEDLINE]

ARTICLE IN PRESSPulmonary Pharmacology & Therapeutics 20 (2007) 265–272www.elsevier.com/locate/ypuptHomocysteine-induced changes in vascular reactivity of guinea-pigpulmonary arteries: Role of the oxidative stress and poly (ADP-ribose)polymerase activationArda Tasatargil , Gulay Sadan, Edibe KarasuFaculty of Medicine, Department of Pharmacology, Akdeniz University, 07070, Antalya, TurkeyReceived 7 November 2005; received in revised form 28 December 2005; accepted 28 February 2006AbstractThis study was aimed to examine the effects of homocysteine (Hcy) on vascular responsiveness of guinea-pig isolated pulmonaryarteries and to investigate possible underlying mechanisms. In order to evaluate vascular reactivity, isometric tension studies wereperformed in response to potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP).Incubation of pulmonary artery rings with Hcy (10 3 M, 180 min) resulted in significant inhibition of response to ACh (an endotheliumdependentvasodilator)(E max : 55.376.7 vs. 13.172.0 * , Po0.05) while SNP (an endothelium-independent vasodilator)-induced relaxationwas not changed significantly. Furthermore, Hcy enhanced KCl- and Phe-induced contraction of pulmonary artery rings (E max :1568781 vs. 21017145 * mg for KCl and 10817101 vs. 15447117 * mg for Phe, Po0.05). Pulmonary artery ring contractions induced bystepwise addition to Ca 2+ to high KCl solution with no Ca 2+ were also significantly augmented by Hcy incubation (E max : 17507121 vs.22957134 * mg, Po0.05). To investigate mechanisms of Hcy action, additional sets of experiments involving rings incubation with Hcyalone or with addition of Tiron (an intracellular superoxide anion scavenger, 10 2 M), PJ34 (an inhibitor of polyADP-ribose polymerase,3 10 6 M), and combination of two antioxidant enzymes superoxide dismutase (SOD, 100 U/ml) and catalase (CAT, 120 U/ml) for180 min. The findings of our study clearly show that all these co-treatments significantly prevented the development of endothelialdysfunction induced by Hcy. Furthermore, the effect of Hcy on KCl- and Phe-induced contraction was significantly inhibited by theconcomitant incubation with either SOD plus CAT, Tiron or PJ34. This study demonstrates that Hcy causes a significant alteration invascular reactivity of pulmonary arteries, and this alteration seems to be via oxidative stress in pulmonary artery endothelium withsubsequent DNA damage and activation of poly(ADP-ribose) polymerase (PARP) pathway.r 2006 Elsevier Ltd. All rights reserved.Keywords: Pulmonary artery; Homocysteine; Oxidative stress; PARP pathway1. IntroductionIdiopathic pulmonary arterial hypertension (IPAH) is afatal disease characterized by marked endothelial dysfunction,hypercontraction and proliferation of vascularsmooth muscle cells (VSMCs), and migration of inflammatorycells, for which no satisfactory treatment has yetbeen developed [1]. This state is defined by a raised pressurein the pulmonary arterial circulation [2]. Althoughpulmonary artery pressure could be affected by several Corresponding author. Tel.: +90 242 2274343; fax: +90 242 2274482.E-mail address: ardatas@akdeniz.edu.tr (A. Tasatargil).factors, one of the possible factor among them, endothelium,plays an important role in regulating the vasculartone by releasing both endothelium-dependent relaxing andcontracting factors [3]. Previous studies have clearly shownthat the relaxation responses to endothelium-dependentvasodilator agents are reduced with the development ofpulmonary hypertension [4,5]. Impairment of endotheliumdependentrelaxation responses contributes to both hyperreactivityof pulmonary artery and development ofpulmonary hypertension [6]. Thus, factors that can affectthe vascular reactivity of pulmonary arteries seem to beimportant for development and /or progression of pulmonaryhypertension.1094-5539/$ - see front matter r 2006 Elsevier Ltd. All rights reserved.doi:10.1016/j.pupt.2006.02.004

cell biochemistry and functionCell Biochem Funct 2007; 25: 485–490.Published online 13 July 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1027/cbf.1335Effects of vitamin K1 supplementation on vascularresponsiveness and oxidative stress in a rat femoralosteotomy modelArda Tasatargil 1 *, Bilge Cadir 2 , Selvinaz Dalaklioglu 1 , Ebru Yurdakonar 3 ,Serkan Caglar 3 and Cengiz Turkay 41 Department of Pharmacology, Medical Faculty, Akdeniz University, Antalya, Turkey2 Department of Oral and Maxillofacial Surgery, Suleyman Demirel University, Isparta, Turkey3 Department of Biochemistry, Medical Faculty, Akdeniz University, Antalya, Turkey4 Department of Cardiovascular Surgery, Medical Faculty, Akdeniz University, Antalya, TurkeyThe main function of vitamin K1 is to act a co-factor for gamma-glutamyl carboxylase. However, it has also been shown tolessen oxidative stress. This study was aimed to evaluate the effect of vitamin K1 supplementation on vascular responsivenessand oxidative status in rats that underwent femoral osteotomy. Twenty-four male rats were divided into three groups to serveas sham, osteotomy and vitamin K1 groups. Indices of oxidative stress (catalase), and oxidative damage (malondialdehyde)were analysed in erythrocytes. In order to evaluate vascular reactivity, concentration-response curves to phenylephrine,angiotensin II, 5-hydroxytryptamine, bradykinin and histamine were constructed. The findings of this study clearly show thatoxidative stress clearly increases after femoral osteotomy in rats. Also, this operation causes a significant depression invascular responsiveness to contracting agents and endothelium-dependent vasodilators. However, vitamin K1 supplementationprevents vascular hyporeactivity by reducing oxidative stress and may represent a novel approach during osteotomyhealing. Copyright # 2006 John Wiley & Sons, Ltd.key words — osteotomy; oxidative stress; vascular reactivity; vitamin K1INTRODUCTIONThe main function of K vitamins is to act as co-factorsfor gamma-glutamyl carboxylase. 1 It is well establishedthat vitamin K is essential for the posttranslationalmodification of a number of plasmacoagulation proteins such as factors II (prothrombin),VII, IX, and X. 2 Although vitamin K is usuallyidentified as a critical factor in blood coagulation,recent research has shown that vitamin K is also a cofactorin bone metabolism. 3–5 Accumulating evidencesupports an important role for vitamin K in boneformation because it is required as a co-factor for the* Correspondence to: A. Tasatargil, Department of Pharmacology,Medical Faculty, Akdeniz University, 07070 Antalya, Turkey. Tel:þ90-242-2274343. Fax: þ90-242-2274482.E-mail: ardatas@akdeniz.edu.trtransformation of glutamic acid residues on proteinsto gamma-carboxyglutamic acid (Gla) residues. 6 Boneformation involves the vitamin K-dependent smallpeptide osteocalcin (bone-Gla-protein) that is secretedby osteoblasts. Vitamin K deficiency is thought tocause impaired activation of bone matrix proteinosteocalcin, and reduction of osteoblast function,resulting in impaired bone formation. 7 Moreover, lowconcentrations of circulating vitamin K have beenassociated with low bone mineral density. 8 In addition,supplementation with vitamin K has been associatedwith improved bone density. 9,10 The results ofFeskanich’s study also support the suggestion thatdietary vitamin K requirements should be based onbone health. 11 Therefore, vitamin K1 supplementationmay be an important approach during bone healing.Oxidative stress is defined as a state in which thelevel of reactive oxygen species (ROS) overcomes theCopyright # 2006 John Wiley & Sons, Ltd.Received 16 November 2005Revised 2 February 2006Accepted 9 February 2006

ve Sinir Cerrahisi Anabilim Dalı1-Göksu E, Akyüz M, Gürkanlar D, Tuncer R. Bilateral abducens nerve palsy following rupturedanterior communicating artery aneurysm: report of 2 cases. Neurocirugia (Astur). 2007 Oct;18(5):420-2.2-Gürkanlar D, Akyuz M, Acikbas C, Ermol C, Tuncer R. Difficulties treatment of CSF leakageassociated with a temporal meningocele. Acta Neurochir (Wien). 2007 Dec;149(12):1239-42. Epub2007 Oct 18.3-Gürkanlar D, Gonul M. Cervical lipomyelomeningocele: case illustration. Neurocirugia (Astur). 2007Dec;18(6):505-4-Gurkanlar D, Acikbas C, Cengiz GK, Tuncer R. Lumbar epidural hematoma following lumbarpuncture: the role of high dose LMWH and late surgery. A case report.Neurocirugia (Astur). 2007Feb;18(1):52-55-Akyuz M, Arslan G, Gurkanlar D, Tuncer R. CSF rhinorrhea from a transclival meningocele: a casereport. J Neuroimaging. 2008 Apr;18(2):191-3. Epub 2007 Oct 18.ŀBeyin

Neurocirugía2007; 18: 420-422Bilateral abducens nerve palsy following ruptured anterior communicating arteryaneurysm: report of 2 casesE. Göksu; M. Akyüz; D. Gürkanlar and R. TuncerDepartment of Neurosurgery. Akdeniz University School of Medicine. Antalya. Turkey.SummaryIsolated abducens nerve palsies associated with intracranialaneurysms have rarely been reported. Their associationwith anterior communicating artery (ACoA) is evenrarer. Intracisternal clot formation and elevated intracranialpressure has been proposed to be the responsible mechanisms.Herewith, we report two cases of bilateral abducens palsiesfollowing ruptured ACoA aneurysms and speculatedthe possible mechanisms.Opening of Liliequist's membrane provides clinicalimprovement due to CSF release.KEY WORDS: Abducens nerve palsy. Liliequist's membrane.Aneurysm.Parálisis bilateral del nervio abductor después de laruptura de un aneurisma de la arteria comunicanteanterior. Presentación de dos casosResumenRara vez se ha publicado un caso de parálisis aisladadel nervio abductor craneal, asociada a un aneurisma. Suasociación con un aneurisma de la arteria comunicanteanterior (ACoA) es todavía más rara. Los mecanismos propuestosson la formación de un coágulo intracisternal y lahipertensión intracranealAportamos dos casos de parálisis bilateral del sexto par,después de la ruptura de aneurismas de la ACoA y discutimoslos mecanismos posibles.La apertura de la membrana de Liliequist da lugar a unamejoría clínica , debido a la liberación de l.c.r.PALABRAS CLAVE: Parálisis nervio abductor. Aneurisma.Menbrana de LiliequistRecibido: 13-10-06. Aceptado: 2-01-07IntroductionAbducens nerve originates from pontomedullary junction.It crosses between anterior inferior cerebellary artery(AICA) and labyrinthine artery and passes through the prepontinecistern, Dorello's canal, cavernous sinus, superiororbital fissure and orbita respectively. Due to its extremelylong extracerebral intracranial course the abducens nerve isthe most frequently involved cranial nerve in a number ofdisorders 3 . About 10% of patients with sixth nerve paresishave bilateral involvement 2 . Isolated abducens nerve palsiesassociated with intracranial aneurysms have rarelybeen reported. Their association with anterior communicatingartery (ACoA) is even rarer.CasesCase 1A-51-year old woman was admitted with sudden onsetof headache, vomiting and diplopia. Neurologic examinationshowed bilateral sixth nerve palsy (Hunt-Hess gradeII). Computed tomography (CT) revealed subarachnoidhemorrhage (Fischer grade II) (Figure l A). ACoA aneurysm,determined with digital substraction angiography(DSA) (Figure l B), was clipped succesfully on the sixthday of her admission. Seven days after the operation herleft side abducens palsy recovered gradually and onemonth later she had normal ocular movements.Case 2A-53-year old woman suffering from sudden headache,nausea and temporary disturbance of consciousness wasadmitted to our clinic. Bilateral abducens nerve palsieswere determined on neurologic examination (Hunt-Hessgrade II) (Figure 2 A, B). CT scan showed subarachnoidand intraparanchymal hemorrhage located in basal cisterns,anterior interhemisferic fissure and right frontal lobe(Fischer grade IV) (Figure 3 A) and cerebral angiograhyrevealed ACoA aneurysm (Figure 3 B). Microsurgical clip-420

Acta Neurochir (Wien) (2007) 149: 1239–1242DOI 10.1007/s00701-007-1273-3Printed in The NetherlandsShort Illustrated ReviewDifficulties in treatment of CSF leakage associated with a temporalmeningoceleD. Gürkanlar, M. Akyuz, C. Acıkbas, C. Ermol, R. TuncerDepartment of Neurosurgery, Akdeniz University School of Medicine, Antalya, TurkeyReceived 17 July 2007; Accepted 23 July 2007; Published online 18 October 2007# Springer-Verlag 2007SummaryTemporal meningocele is a rarely encountered pathology.It is caused by communication between the subarachnoidspace of the middle fossa and lateral extension of thesphenoid sinus.Cerebrospinal fluid (CSF) pressures and the hydrostaticpulsatile forces may lead to the development of pitholeson the middle fossa at the sites of arachnoid villiwith herniation of dura=arachnoid or brain tissue intothe sinus.We describe an adult patient who presented with spontaneousCSF rhinorrhea due to a temporal meningocele.She was first operated on transsphenoidally, but the CSFrhinorrea did not cessate, therefore she was operated transcraniallyfive days after the first operation. There hasbeen no CSF rhinorrhea for three and a half years.Transcranial temporal encephalocele repairment ismore effective than transsphenoidal surgery. RecurrentCSF leaks can occur due to both the increased CSFpressure and the insufficient operation technique.Keywords: Cerebrospinal fluid fistula; temporalmeningocele; surgical approach.IntroductionAn encephalocele is the protrusion of intracranial contents,including brain matter and meninges through aCorrespondence: Doga Gürkanlar, MD, Yes°ilbahc°e Mah.Portakalc°ic°egi Bulvarı, 1447 sk. B. Gürkanlar Apt. 3=11., Antalya,Turkey. e-mail: dgurkanlar2000@yahoo.co.ukdefect in the cranium or skull base [16]. Intrasphenoidalencephaloceles are a rare subset of this disease process[3, 7, 17, 24].Basal meningoencephaloceles, which occur with anestimated incidence of one in every 35,000 live births[19] have been further subdivided, depending on thelocation of the bone defect, into transethmoidal, sphenoethmoidal,spheno-orbital, transsphenoidal [26].Abiko et al. noted two types of transsphenoidalmeningoencephaloceles: the intrasphenoidal and the truetranssphenoidal. Intrasphenoidal encephaloceles describethose extending into the sphenoid sinus but confined byits floor [1].Encephaloceles within the sphenoid sinus are subdividedby their location into medial-perisellar type and alateral sphenoid recess type [16].We present a case of lateral intrasphenoidal meningoencephalocele(temporal meningocele), review the literature,and discuss the management modalities and theetiopathogenesis of this unusual cranial base defect.Literature reviewA MEDLINE search by PubMed was performed to findall articles describing temporal meningoceles associatedwith spontaneous CSF fistula and included all languagepublications from 1980 to 2006 (May).AnalysisTwo articles with the keywords ‘‘middle fossa, spontaneouscerebrospinal fluid fistula, sphenoid sinus’’,

Neurocirugía2007; 18: 505-507Cervical lipomyelomeningocele: case IllustrationD. Gürkanlar and *M. GonulAkdeniz University School of Medicine, Department of Neurosurgery Antalya, Turkey. *Ankara Numune Hospital, Department of DermatologyAnkara, Turkey.SummaryCervical lipomyelomeningocele is a rare congenitalspinal pathology. Lipomyelomeningocele is the commonestcause of congenital tethering, which causesneurological deterioration due to the conus medullarisand root ischemia. Early intervention is recommendedeven in cases with normal neurological examinations inorder to prevent deterioration but our patient with cervicallipomyelomeningocele had a normal neurologicalexamination despite his age (22 year-old) and had nourodynamic dysfunction.KEY WORDS: Lipomyelomeningocele. Cervical. Occultspinal dysraphism.Lipomielomeningocele cervical. Caso clínicoResumenEl lipomielomeningocele cervical es una patologíaraquídea congénita rara. El lipomielomeningocele es lacausa más frecuente de anclaje medular, que da lugar adeterioro neurológico, debido a isquemia del cono medulary de las raíces. Se recomienda la intervención precoz,incluso en casos con examen neurológico normal, con elfin de prevenir un deterioro, pero nuestro paciente con lipomielomeningocelecervical tenía un examen neurológiconormal, a pesar de su edad (22 años) y no tenía ningunadisfunción urinaria.PALABRAS CLAVE: Lipomielomeningocele. Cervical.Disrafismo espinal oculto.IntroductionLipomyelomeningocele is a type of congenital occultspinal dysraphism consisting of the presence of lipomatoustissue attached to the dorsal spinal cord, which protrudesRecibido: 29-11-06. Aceptado: 6-06-07though a spinal defect along with the menings or spinalcord to form a posterior mass under the skin, usually inthe lumbosacral region. Neural ectoderm separates fromthe cutaneous ectoderm and periaxial mesoderm comesin intact with the unfused ventral neural ectoderm. Themesoderm then differentiates into fatty tissue, thus preventingthe neural canal and the posterior aspect of the spinefrom fusing 4,5 .Lipomyelomeningocele is the commonest cause of congenitaltethering and causes neurological deterioration dueto the conus medullaris and root ischemia 1 .Here we presented a 22 year-old patient harboring alipomyelomeningocel in the cervical region without anyneurological deficit and tethered cord.CaseA 22 year-old man suffering from a posterior mass inthe cervical region was admitted to our out-patient clinic(Figure 1). Neurological examination of the patient wasunremarkable and he had no urinary dysfunction. Plain x-ray films of the cervical vertebrae revealed C5-6 posteriorfusion defect (Figure 2).The magnetic resonance imaging(MRI) of the cervical spine revealed a lipomyelomeningocelat C6 level ( Figure 3).The patient was operated under general anesthesia inprone position and the lipomyelomeningocele was correctedwithout any complication. Postoperative neurologicalexamination of the patient was unremarkable.DiscussionThe lipomyelomeningocele rate has been estimated tobe 2,5 per 10000 births 5 . Their occurrence in the cervicalregion is even rarer 6 . The defect is more commonly foundin females 2 . An autosomal inheritance is also suggested forlipomyelomeningocele 3 .Cervical and upper thoracic myelomeningocelesaccount for only 1-5% of all spinal dysraphism andlipomyelomeningocele as an additional congenital spinalpathology is very rare 6 . Although lipomyelomeningocele505

Neurocirugía2007; 18: 52-55Lumbar epidural hematoma following lumbar puncture: the role of high doseLMWH and late surgery. A case reportD. Gurkanlar; C. Acikbas; G.K. Cengiz and R. TuncerDepartment of Neurosurgery. Akdeniz University. School of Medicine. Antalya. Türkiye.SummarySpinal epidural hematoma (SEH) is a knowncomplication of spinal surgery, but the incidence ofpost-surgical SEHs that result in neurologic deficits isextremely rare (0.1%). Patients that require multilevellumbar procedures and/or have a preoperative coagulopathyare at a significantly higher risk of developing anepidural hematoma. The introduction of higher dose oflow molecular weight heparin (LMWH) twice daily 30mg regimen) increased the reported incidence of neuroaxialhematomas. Surgery performed within 8 hoursmakes good or partial recovery of neurologic function.Our patient was also started on higher dose ofLMWH and developed neurological deficits due to aSEH following lumbar puncture. She underwent operationafter six days and she had a mild recovery followingthe operation.Current administration of high doses of LMWH cancause SEH even after a lumbar puncture, which wasperformed without multiple attempts.Although surgery performed within 8 hours makesgood or partial recovery of neurologic function, laminectomyand epidural hematoma evacuation performedafter three days can also have successful results.KEY WORDS: Lumbar. Epidural hematoma. Surgery.LMWH. Myelography.Hematoma lumbar epidural postpunción lumbar; influenciade dosis altas de LMWH y cirugía diferidaResumenEl hematoma espinal epidural (HEE) es una complicaciónconocida en la cirugía espinal, pero la incidenciadel HEE que da lugar a déficit neurológico es muy rara(0,1%). Los pacientes que necesitan intervenciones enRecibido: 26-06-05. Aceptado26-04-06varios niveles lumbares y/o que tienen una coagulopatíapreoperatoria tienen un riesgo significativamente mayorde desarrollar un hematoma epidural. La introducciónde dosis altas de heparina de bajo peso molecular(HBPM), (30 mgrs. dos veces al día) aumentan la incidenciade hematomas neuroaxiales. La cirugía llevada acabo dentro de las 8 horas da lugar a un recuperaciónbuena o parcial de la función neurológica.Nuestro paciente fue tratada con dosis altas deHBPM y desarrolló un déficit neurológico debido a unHEE, después de una punción lumbar. Fue operada alcabo de seis días y se recuperó parcialmente de su déficitdespués de la intervención.La administración actual de dosis altas de HBPMpuede dar lugar a HEE, incluso después de una punciónlumbar, que se hizo en pocos intentos.Aunque la cirugía realizada en las primeras 8horas produce una recuperación buena o parcial, lalaminectomía y evacuación del hematoma llevada acabo después de tres días también puede dar lugar abuenos resultados.PALABRAS CLAVE: Lumbar. Hematoma epidural. Cirugía.HBPS. Mielografía.IntroductionMultilevel lumbar procedures, anatomic abnormalities,traumatic puncture with multiple attempts, and coagulationdisorders or anticoagulation therapy are significant risk factorsfor spinal epidural hematoma development 11,5 . As wellas most of them are clinically insignificant, but may causesevere and rapid neurological deterioration.We report a case of a woman developing epiduralhematoma with neurological deterioration three days afterAbbreviations. CMT: computerized myelo-tomography. CT: computerizedtomography. HBPM: heparina de bajo peso molecular.HEE: hematoma epidural espinal. LMWH: low molecular weightheparin. MRI: resonancia magnética. SEH: spinal epiduralhematoma.52

Neuroimaging. 2008 Apr;18(2):191-3. Epub 2007 Oct 18.CSF rhinorrhea from a transclival meningocele: a case report.Akyuz M, Arslan G, Gurkanlar D, Tuncer R.Department of Neurosurgery, Akdeniz University School of Medicine, Antalya, Turkey.mahmutakyuz@akdeniz.edu.trAbstractThe most common site of cerebrospinal fluid (CSF) leakage is through the floor of the anterior fossa, whichcommunicates with the ethmoid or frontal sinuses or with the nasal fossa. The sphenoid sinus is rarely implicatedas a source of spontaneous CSF fistula. Transclival meningocele is an extremely rare lesion. A 36-year-oldwoman with a 1-year history of intermittent CSF rhinorrhea was found to have a transclival meningocele. Thediagnosis of transclival meningocele was made by magnetic resonance (MR), 3-dimension-computerizedtomography (CT). At operation, by a transsphenoidal approach, the transclival meningocele was packed with fasiaŀJlata graft, fat tissue, and bio-glue. This is the third case of transsphenoidal transclival meningocele producingrhinorrhea in an adult. Transclival meningocele should be taken into consideration in patients with spontaneousCSF rhinorrhea.PMID: 18298681 [PubMed - indexed for MEDLINE]

1-Erdogan A, Gurses G, Keskin H, Demircan A:The sealing effect of a fibrin tissue patch on theesophageal perforation area in primary repair. World J of Surg31:2199-2203, 2007.2-Bozkurt AK, Koksal C, Demirbas MY, Erdogan A, Rahman A, Demirkilic U, Ustunsoy H, Metin G,Yillik L, Onol H, Cinar B, Karacelik M, Erdinc I, Bolcal C, Sayin AG.A randomized trial of intravenousiloprost (a stable prostacyclin analogue) versus lumbar sympathectomy in the management ofBuerger’s disease. Int angiol25:162-168, 2006.ŀGöğüs Cerrahisi Anabilim Dalı - 2007

World J Surg (2007) 31:2199–2203DOI 10.1007/s00268-007-9207-zThe Sealing Effect of a Fibrin Tissue Patch on the EsophagealPerforation Area in Primary RepairAbdullah Erdogan Æ Gulsum Gurses ÆHakan Keskin Æ Abid DemircanPublished online: 29 August 2007Ó Société Internationale de Chirurgie 2007AbstractBackground The aim of this study was to investigate theefficacy of the fibrin tissue patch and to analyze its use inpatients with esophageal perforation.Methods We studied 28 patients who were diagnosedwith esophageal perforation between January 1990 andJanuary 2006 at Akdeniz University Hospital. Sixteen(57.14%) were male. The average age was 59 ± 9 years.We performed surgery and primary repair reinforcementeven if the diagnosis of esophageal perforation was late.Results Twenty-three (82.14%) perforations were theresult of endoscopic instruments; spontaneous perforationsoccurred in three (10.71%) patients. Postoperative complication(Heller myotomy) caused perforation in onepatient (3.57%) and blunt trauma in one patient (3.57%).Three (10.71%) patients had cervical perforation, and 25(89.29%) patients had thoracic esophageal perforation.Twelve (42.86%) patients underwent emergency surgery(within the first 24 h). Ten (35.71%) patients underwentsurgery within 48 h, and the remaining 6 (21.43%)underwent surgery after 48 h. Nine (32.14%) patients hadprimary repair, 7 (25%) had reinforcement of the primaryrepair with fibrin tissue patch, 7 (25%) had esophagectomyand gastric pull-up, and 2 (7.14%) had drainage andplacement of metallic stents. In four patients of the ninewho had primary repair, fistula complication was detected,whereas in only one of the seven who had reinforcement ofthe primary repair with fibrin tissue patch was a fistuladetected. Three patients (10.71%), two of whom had Boerhaave’ssyndrome, died.A. Erdogan (&) G. Gurses H. Keskin A. DemircanDepartment of Thoracic Surgery, Akdeniz University School ofMedicine, Antalya 07070, Turkeye-mail: erdogana@akdeniz.edu.trConclusions Surgical primary repair with fibrin tissuepatch is the most successful treatment option in the managementof esophageal perforation.Esophageal perforation continues to have a significant riskof mortality and morbidity [1]. The mortality rate risessteeply if there is a delay in diagnosis and in the initiationof optimum treatment. The reported mortality from treatedesophageal perforation is between nearly 4% and 20%when therapy is initiated within 24 h of perforation, but itcould rise to more than double this mortality rate when thetreatment is delayed beyond 48 h [2, 3].The rate of perforation of the esophagus by medicalapparatus has increased as a result of the recent and rapiddevelopment in esophagoscopy [4]. In the last two decades,advances in surgery, anesthesia, postoperative care,hyperalimentation, and powerful and selective antibioticshave caused substantial improvements in the outcome ofthe treatment of esophageal perforation [5].The choice of treatment of a delayed or a missed ruptureof the esophagus is not very clear and is still controversial.The fact that many procedures have been described in theliterature is indicative that no single surgical procedure canbe considered a gold standard for the treatment of esophagealperforation [6]. Different procedures for delayedesophageal perforation include primary repair with orwithout reinforcement [7], simple drainage of the thoraciccavity [8], exclusion diversion operation [9], occlusion ofthe perforation site with prosthesis such as expandablemetallic stents [10], and single-stage esophageal resectionwith or without primary reconstruction [11].The purpose of this study was to review the etiology,management, and outcome of 28 esophageal perforations123

A randomized trial of intravenous iloprost (a stable prostacyclin analogue) versuslumbar sympathectomy in the management of Buerger's disease.Angiol. 2006 Jun;25(2):162-8.Bozkurt AK, Köksal C, Demirbas MY, Erdoğan A, Rahman A, Demirkiliç U, Ustünsoy H, Metin G, Yillik L, Onol H, Cinar B, Karaçelik M,Erdinç I, Bolcal C, Sayin AG; Turkish Buerger's Disease Research Group.Department of Cardiovascular Surgery, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey. akbozkurt@yahoo.comAbstractAIM: The aim of this study was to compare the effects of iloprost and lumbar sympathectomy (LS) in the treatment of Buerger's disease.METHODS: Two hundred patients with rest pain and/or ischemic ulcers were randomized to undergo LS or 28-day intravenoustreatment of iloprost. The primary endpoint was complete healing without pain or major amputation at 4 and 24 weeks. The secondaryendpoints were analgesic requirement, reduction in the ulcer size, 50% reduction of the ulcer, and shift in the modified SVS/ISCVSclinical status grading scale.RESULTS: The comparison was carried out in 162 patients (iloprost: n=84; LS: n=78). Complete healing rate was 61.9% in the iloprostgroup, but 41% in the LS group at the 4th week (P=0.012); respective values for the 24th week were 85.3%, 52.3%, P

Hastalıkları Anabilim Dalı - 20071-Unal M, Yücel I, Akar Y, Akkoyunlu G, Ustünel I: Recurrence of keratoconus in two corneal graftsafter penetrating keratoplastyCornea26(3):362-4,Apr 20072-Unal M, Yücel I, Akar Y, Oner A, Altin M:Outbreak of toxic anterior segment syndrome associatedwith glutaraldehyde after cataract surgery.J Cataract Refract Surg. 32(10).1696-701,OCT;20063-Unal M, Yücel I, Akar Y:Brinzolamide 1% versus apraclonidine 0.5% to prevent intraocular pressureelevation after neodymium:YAG laser posterior capsulotomy. elevation after neodymium:YAG laserposterior capsulotomy.J Cataract Refract Surg. 32(9):1499-502,Sep;20064-Duman O,AralaflmakA,Duranoğlu Y,et al:Torticollis secondary to monocular viewing in an infantwith unilateral hypoplasia of the internal carotid artery.Developmental Medicine and Child neurology49(11):876-877nov 20075-Duranoğlu Y:Effectiveness of disinsertion- resection and tucking of the inferior oblique muscle inpatient with unilateral long-standing superior oblique opthalmology and strabismus musclepalsy.Journal of pediatric 44(5):283-287 sep-oct 20076-Duranoğlu Y ,Yücel I,Kıvrakdal S:Comparison of the inferior weaking bydisinsetion -resection andtucking in the patient with infantile esotropia.Annals of opthalmology 38(1):29-33 spr 20067-Duranoğlu Y:Optic Nerve Topographic Analysis and Retinal Nerve Fiber Layer Thicness instrabismic and anisometropic ambylopia.Annals of opthalmology December 2007,volume 39, İssue 4pp:291-958-Güven M, Unal M, Sarici A, Ozaydin A, Batar B, Devranoğlu K. Glutathione-S-transferase M1 andT1 genetic polymorphisms and the risk of cataract development: a study in the Turkish populationCurrEye Res. 32(5):447-54;May.2007ŀGöz9-Bahçecioglu H, Unal M, Artunay O, Rasier R, Sarici A.Posterior vitrectomy under topicalanesthesiaCan J Ophthalmol. 42(2):272-7.Apr.200710-Güven M, Unal M, Batar B, Eroğlu E, Devaroğlu K, Tamçelik N, Uçar D, Sarici A.Polymorphisms ofDNA repair genes XRCC1 and XPD and risk of primary open angle glaucoma (POAG).MolVis.5;13:12-7.Jan 200711-Unal M, Sarici A. Filamentary keratopathy caused by corneal occlusion by large-angle paralyticstrabismus.Conea.25(9):1105-5.Oct.200612-Griffin RY, Sarici A, Unal M.Acquired ptosis secondary to vernal conjunctivitis in youngadults.Ophthal Plast Reconstr Surg. 22(6):438-40.Nov-Dec;2006

Ophthalmic Plastic and Reconstructive SurgeryVol. 22, No. 6, pp 438–440©2006 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.Acquired Ptosis Secondary to Vernal Conjunctivitis in YoungAdultsRengin Yıldırım Griffin, M.D.*, Ahmet Sarıcı, M.D.*, and Mustafa Unal, M.D.†*Department of Ophthalmology, Cerrahpasa Medical School, Istanbul University, İstanbul, Turkey; and the †Department ofOphthalmology, Akdeniz University, Antalya, TurkeyPurpose: To establish a relation between prolonged severe vernal conjunctivitis and upper eyelid ptosis.Methods: The study consisted of 12 patients between the ages of 19 and 32 years with acquired ptosis whopresented in our clinic between September 2001 and February 2005. Potential factors responsible for acquiredptosis were investigated in all patients, with specific attention to the history and severity of vernal conjunctivitis.Results: We found vernal conjunctivitis to be the identifiable cause in 8 men and 4 women with acquiredptosis. There was neither contact lens usage nor trauma or ocular surgery history in their medical records. Theblepharoptosis was caused by levator disinsertion and recession of the aponeurosis. The pathology improved ineach case after reattachment of the aponeurosis to the superior tarsal border.Conclusions: These findings suggest that prolonged severe vernal conjunctivitis may induce a lower positionof the upper eyelid and eventually lead to ptosis through levator disinsertion that is similar to involutional ptosis.We believe that chronic inflammation of the upper eyelid with giant papillary conjunctivitis and persistentrubbing of the eyelids may be responsible for the development of this pathology.Aponeurotic blepharoptosis is caused by disinsertion,or thinning, of the levator muscle aponeurosis.Typically, the levator function is good, and a high eyelidcrease is usually found. 1 In the elderly, it is most often aninvolutional disorder. In the younger population, a periodof rigid contact lens wear is reported to be the mostcommon cause. 2,3 Intraocular surgery, postoperativeedema, ocular inflammation, and topically applied steroidsare other factors related to acquired blepharoptosisin this age group. 4,5 However, we noticed that among ourpatients there were also young adults with acquiredptosis without a history of contact lens use, trauma, orintraocular surgery. These patients tend to have mild tomoderate ptosis, good levator function, and elevatedeyelid creases. The common problem in these cases wasthe history of severe vernal keratoconjunctivitis (VKC).This study investigated how and why aponeuroticblepharoptosis developed in patients with a history ofVKC.METHODSWe retrospectively reviewed the records of patients under 35years of age with acquired ptosis who underwent surgery in ourclinic from September 2001 to February 2005. Patients whoAccepted for publication May 19, 2006.Address correspondence and reprint requests to Dr. Rengin YıldırımGriffin, Adakent Sitesi ND Blok Daire 9 Levent 34340, I˚stanbul,Turkey. E-mail: rengingriffin@yahoo.comDOI: 10.1097/01.iop.0000246609.39499.dahad trauma or a history of contact lens use and intraocularsurgery were excluded from the study. A standard ophthalmicexamination was performed on all patients, with special emphasison extraocular muscle balance and pupillary function.Tear function and tear film stability were assessed in allsubjects.Patients completed a questionnaire requiring responses concerningtheir VKC history, the duration of the disease, childhoodocular itching and eye rubbing, hand dominance, and theonset of ptosis and its progression.Each ptosis case was graded mild to severe, according to theupper eyelid position in primary gaze. Levator muscle functionand eyelid contour were tested in all cases (Table). The distancebetween the upper eyelid margin and the corneal light reflex inprimary position (margin reflex distance [MRD1]) was recordedbefore and after surgery.All surgeries were performed by one surgeon on an outpatientbasis after informed consent was obtained. Local anesthesiawas administered with topical tetracaine drops and subcutaneousinfiltration of 1.5 ml 2% lidocaine solution containing1/100,000 epinephrine. The standard anterior approach to levatoradvancement was performed in all patients through aneyelid crease incision, using a carbon dioxide (CO 2 ) laser.During the operation, the orbital septum was opened horizontallyand the preaponeurotic fat space, levator aponeurosis,levator muscle, and Müller muscle were observed. The conditionof the levator muscle and the bond with the tarsus weredocumented. The levator aponeurosis or muscular portion orboth were sutured to the tarsus by using one horizontal mattresssuture of 5–0 polyglactin. The height and contour werechecked with the overhead lights off and with the patient inboth the supine and sitting positions. The height was judged by438

CASE REPORTFilamentary Keratopathy Caused by Corneal Occlusionby Large-Angle Paralytic StrabismusMustafa Ünal, MD,* and Ahmet Sarıcı, MDPurpose: To report a case of filamentary keratopathy in a patientwith large-angle paralytic strabismus.Methods: A 31-year-old man who had a traffic accident was diagnosedto have third cranial nerve palsy and a large-angle exotropia inhis right eye. The patient complained of foreign body sensation in hisright eye 2 months after the accident.Results: Slit-lamp examination showed multiple filaments on theright cornea. Debridement of the filaments and artificial tears relievedthe symptoms and were used until the paralysis resolved.Conclusion: Large-angle paralytic strabismus with ptosis and poorelevation and depression of the eye may occlude the cornea and leadto filamentary keratopathy.Key Words: filamentary keratopathy, paralytic strabismus(Cornea 2006;25:1105–1106)Filamentary keratopathy is associated with keratoconjuctivitissicca, corneal infections, diabetes mellitus, ectodermaldysplasia, neuropathic keratopathy, superior limbic keratoconjunctivitis,prolonged eye patching, conjunctival cicatrization,sarcoid, bullous keratopathy, trauma, and cataract orcorneal transplant surgery. 1 It has been reported in a largeanglecongenital esotropia caused by lid occlusion. 2 We evaluateda man with large-angle paralytic exotropia who hadsymptoms caused by filamentary keratopathy.MATERIALS AND METHODSA 31-year-old man who had had a traffic accident wasdiagnosed with third cranial nerve palsy in his right eye. Thepatient presented to the outpatient department with ptosis inhis right eye 6 days after the accident. His history revealedcranial trauma, and ptosis developed immediately after theaccident. A large exotropia (;70 prism D) caused byunopposed action of lateral rectus, ptosis, and cornealReceived for publication August 3, 2005; accepted April 4, 2006.From the *Ophthalmology Department, Akdeniz University Medical Faculty;Antalya, Turkey and †Ophthalmology Department, Istanbul UniversityMedical Faculty, Istanbul, Turkey.Reprints: Mustafa Ünal, Akdeniz Ünivers, tesi Tıp Fakültesi Göz Hastalıkları,A.D. Antalya, Turkey (e-mail: drmustafaun@hotmail.com).Copyright Ó 2006 by Lippincott Williams & Wilkinsocclusion by the upper lid, as well as limited adduction,elevation, and depression, were detected in the ophthalmologicexamination of the right eye. The cornea was covered by theupper lid because of ptosis and the large-angle exotropia.The pupil was spared. Visual acuity was 20/20, and intraocularpressure was 17 mm Hg.We performed cranial magnetic resonance imaging(MRI) to rule out structural causes of the palsy, and the patienthad a cerebral angiography after a normal head MRI. Withserious etiologies being ruled out, the palsy was left to bemonitored for spontaneous resolution.RESULTSThe patient complained of foreign body sensation in hisright eye 2 months after the accident. Slit-lamp examinationshowed multiple filaments presenting only on the right cornea.Although most of the filaments were attached to the centralcornea, limbal regions were also affected. He had no history ofeye surgery, corneal disease, or infection, and he did not haveany symptoms in his left eye. Corneal sensation was normal,and there were no corneal scars. Basal aqueous tear productionafter a topical anesthetic administration was 13 mm in5 minutes in both eyes.Debridement of the filaments and artificial tears relievedthe symptoms. Debridement was performed 6 times until theparalysis resolved. Resolution of the paralysis was almostcomplete without aberrant regeneration at 7 months afterthe accident. Filaments also resolved with resolution of theparalysis.DISCUSSIONThe etiology of the filamentary keratopathy in thispatient was presumed to be occlusion of the right cornea byupper lid. Occlusion was caused by the ptosis and poorelevation and depression of the eye. The absence of otherpredisposing factors in the involved right eye and the absenceof corneal filaments in his left eye suggested that cornealocclusion by the lid should be the primary factor in developingfilaments.Prolonged eyelid closure, such as in patching and insleep, causes hypoxia, reduced tear volume, or both and isa risk factor in the pathogenesis of a variety of cornealconditions, including filamentary keratopathy. 4 Filamentsdeveloped in a relatively short time after the paralysis. It isalso possible that eccentric positioning of the cornea caused byCornea Volume 25, Number 9, October 2006 1105Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

CASE REPORTRecurrence of Keratoconus in Two Corneal GraftsAfter Penetrating KeratoplastyMustafa Ünal, MD,* _Iclal Yücel, MD,* Yusuf Akar, MD,* Gökhan Akkoyunlu, PhD,†and _Ismail Üstünel, PhD†Purpose: To report the recurrence of postkeratoplasty keratoconusin 2 corneal grafts harvested from the same donor.Design: Interventional case reports.Methods: A 21-year-old-man with advanced keratoconus in hisright eye and a 28-year-old-woman with corneal leucoma in her righteye underwent penetrating keratoplasty with 2 grafts coming from thesame donor. Approximately 1.5 years after grafting, cornealirregularity and astigmatism caused visual acuities of the patientsto decrease to counting fingers. Clinical findings and cornealtopography suggested the recurrence of keratoconus. A repeatkeratoplasty was performed in both patients.Results: Histopathology of the excised corneal grafts was consistentwith keratoconus and confirmed the preoperative diagnosis.Conclusions: Recurrence of keratoconus in a patient who had nopreexisting keratoconus and in 2 corneal grafts coming from the samedonor suggested transmission of the disorder from the donor insteadof true recurrence.Key Words: penetrating keratoplasty, recurrence of keratoconus(Cornea 2007;26:362–364)Keratoconus is a noninflammatory, nonvascular axialcorneal ectasia that progresses to create irregular myopicastigmatism. Penetrating keratoplasty (PKP) is performed onapproximately 10% to 15% of patients with keratoconus afterother forms of visual rehabilitation have failed. 1Recurrence of keratoconus has been reported to occurafter PKP in several studies. 2–10 However, it is still not knowndefinitely whether recurrence of the disease results from thetransmission of the keratoconus from the donor or recurrenceof the host’s disease. This study is the first to report theclinicopathologic features of 2 further cases of recurrentkeratoconus in which corneal grafts came from the samedonor.Received for publication July 22, 2006; revision received October 2, 2006;accepted October 17, 2006.From the *Department of Ophthalmology, Akdeniz University MedicalFaculty, Antalya, Turkey; and the †Department of Histology andEmbryology, Akdeniz University Medical Faculty, Antalya, Turkey.Reprints: Mustafa Ünal, Demircikara mah. 1426. sk. Zeybek, Apt. B Blok.14/12, Muratpasxa/Antalya, Turkey (e-mail: mustafaunalmd@gmail.com).Copyright Ó 2007 by Lippincott Williams & WilkinsCASE REPORTSThe first patient was a 21-year-old-man who presented to theoutpatient department with decreased vision in both eyes. Onexamination, he had a best-corrected visual acuity of counting fingersat 2 m in the right eye and 8/10 in the left eye. Slit-lampbiomicroscopy of both eyes revealed features suggestive ofkeratoconus. Retinoscopy revealed scissored retinoscopic reflex.Apical scarring of the cornea was noted in the right eye. Intraocularpressures were within reference limits. The funduscopic examinationwas unremarkable. Keratometry revealed distorted mires. Cornealtopography showed Sim K and Min K readings of 63.19 3 84degrees/53.08 3 174 degrees, and 52.89 3 3 degrees in the right eyeand 45.82 3 73 degrees/43.78 3 163 degrees and 43.55 3 148degrees in the left eye. A PKP was planned for the right eye.The second patient was a 28-year-old-woman presenting withdecreased vision in her right eye. She had a history of keratitis5 years ago. Visual acuities were hand movements in the right eyeand 10/10 in the left eye. Biomicroscopic examination revealedsimple leucoma without any vascularization in the center of the rightcornea. The left eye was normal. Intraocular pressures were normal.The funduscopic examination was unremarkable. A PKP was plannedfor the right eye.Both patients underwent corneal transplantation in their righteyes by using a 7.75-mm graft in a 7.50-mm incision in the same day.Suturing of the grafts was performed using a combination of 8interrupted 10-0 nylon sutures and a tight 8-bite 10-0 nylon continoussuture. The grafts came from a 24-year-old donor who had died ina traffic accident. The donor had a history of wearing eyeglassesbut no ocular disease or contact lens wear and had normal-appearingcorneas. There was no information on best spectacle-corrected acuityof the donor.The early postoperative period was initially uneventful for bothpatients. Sim K and Min K readings were 49.77 3 79 degrees/44.33 3169 degrees and 44.27 3 172 degrees in the first patient and 46.73 31 degree/41.26 3 90 degrees and 40.38 3 107 degrees in the secondpatient 3 months after surgery. Uncorrected visual acuities were 2/10and 4/10, respectively. Topical prednisolone was used 6 times a dayfor the first 2 postoperative months and then tapered slowly andstopped at the ninth month. Both patients underwent selectiveremoval of sutures at the steepest meridian if associated with greaterthan 3 D of astigmatism starting at 10 weeks postoperatively. Allsutures were removed at postoperative year 1. However, astigmatismdid not show significant regression after suture removal and evenbegan to increase toward the end of the first year. Progression of theastigmatism was more prominent after all sutures were removed.Approximately 1.5 years after grafting (15 months in the firstcase and 17 months in the second case), visual acuities of the patientsdeteriorated. Corneal topography revealed a pattern compatible withkeratoconus in both patients (Figs. 1A, B). Corneal irregularity andastigmatism continued to increase, and visual acuities dropped tocounting fingers. There were fine vertical striae at Descemetmembrane and Fleischer ring and minimal central corneal thinning362 Cornea Volume 26, Number 3, April 2007Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Current Eye Research, 32:447–454, 2007Copyright ○c Informa HealthcareISSN: 0271-3683 print / 1460-2202 onlineDOI: 10.1080/02713680701338108Curr Eye Res Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/11/10For personal use only.Glutathione-S-transferase M1 and T1Genetic Polymorphisms and the Risk ofCataract Development: A Study in theTurkish PopulationMehmet GüvenDepartment of Medical Biology,Cerrahpasa Faculty ofMedicine, University ofIstanbul, Istanbul, TurkeyMustafa ÜnalDepartment of Ophthalmology,Akdeniz University MedicalFaculty, Antalya, TurkeyAhmet SarıcıDepartment of Ophthalmology,Cerrahpasa Faculty ofMedicine, University ofIstanbul, Istanbul, TurkeyAhmet Özaydın andBahadır BatarDepartment of Medical Biology,Cerrahpasa Faculty ofMedicine, University ofIstanbul, Istanbul, TurkeyKazım DevranoǧluDepartment of Ophthalmology,Cerrahpasa Faculty ofMedicine, University ofIstanbul, Istanbul, TurkeyReceived 19 October 2006Accepted 13 March 2007Correspondence: Mustafa Ünal,Demircikara mah. 1426. sk. Zeybekapt., B blok. No. 14/12,Muratpaşa/Antalya, Turkey 07070.E-mail: mustafaunalmd@gmail.comABSTRACT In this study, we aimed to determine the effects of geneticpolymorphisms of glutathione-S-transferase M1 (GSTM1) and glutathione-StransferaseT1 (GSTT1) on risk of developing different subtypes of age-relatedcataract in the Turkish population. Using a multiplex polymerase chain reaction(PCR), GSTM1 and GSTT1 gene polymorphisms were analyzed in 195patients with age-related cataract (75 patients with cortical, 53 with nuclear, 37with posterior subcapsular, and 30 with mixed type) and in 136 patients of anotherwise healthy control group of similar age. GSTM1 null genotype had asignificant association with the development of cataract in female subjects (p< 0.0029; OR, 2.98; 95% CI, 1.41–6.34). This relationship in female subjectswas only in nuclear and mixed types cataract cases (p < 0.002; OR, 4.58; 95%CI, 1.67–12.78 and p < 0.03, respectively). There was also a statistically significantassociation between the combination of GSTM1-null and GSTT1-positivegenotypes and the risk of cataract development in female subjects (p = 0.01;OR = 2.87; 95% CI = 1.25–6.69). Stratification by the subtypes revealed thatthis association was only in nuclear type cataract (p = 0.001; OR, 3.92; 95%CI, 1.34–11.71). GSTM1-null genotype or combination of the GSTM1-null andGSTT1-positive genotypes in females may be associated with increased risk ofcataract development in the Turkish population.KEYWORDSglutathione-S-transferase; polymorphism; senile cataractINTRODUCTIONCataract, or opacification of the lens, is one of the most common causes ofloss of useful vision. Currently, surgery is the only approach for the treatment ofcataract. The etiology of age-related changes in the lens is not fully understoodand is likely to be multifactorial. 1Oxidative stress has been identified as one of the major causes of agerelateddiseases, including cardiovascular diseases, arthritis, brain dysfunction,447

Duman O (Duman, Ozgur), Aralaflmak A (Aralaflmak, Ayfle), Duranoglu Y (Duranoglu, Yaflar), KaraaliK (Karaali, Kamil), Haspolat S (Haspolat, Senay)Source: DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY Volume: 49 Issue: 11 Pages: 876-877 Published: NOV 2007Times Cited: 0 References: 9 Citation MapDocument Type: LetterLanguage: EnglishKeyWords Plus: OPTIC-NERVE HYPOPLASIAReprint Address: Duman, O (reprint author), Akdeniz Univ, Fac Med, Dept Child Neurol, Antalya, TurkeyAddresses:1. Akdeniz Univ, Fac Med, Dept Child Neurol, Antalya, Turkey2. Akdeniz Univ, Fac Med, Dept Radiol, Antalya, Turkey3. Akdeniz Univ, Fac Med, Dept Ophthalmol, Antalya, TurkeyE-mail Addresses: oduman@akdeniz.edu.trPublisher: BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLANDSubject Category: Clinical Neurology; PediatricsIDS Number: 225DIISSN: 0012-1622ŀAuthor(s):

J Ophthalmol. 2007 Apr;42(2):272-7.Posterior vitrectomy under topical anesthesia.Bahçecioglu H, Unal M, Artunay O, Rasier R, Sarici A.Department of Ophthalmology, Istanbul University Faculty of Medicine, Istanbul, Turkey.AbstractBACKGROUND: To determine the safety and efficacy of topical anesthesia in posterior vitrectomy.METHODS: A total of 93 patients (93 eyes) with various vitreoretinal diseases not needing scleral buckling and with short predictedduration of surgery underwent posterior vitrectomy under topical (49 eyes) or retrobulbar (44 eyes) anesthesia. Patients in the topicalgroup were sedated with neuroleptic anesthesia. Postoperatively, patients were shown a visual analogue pain scale (VAPS) from 0 (nopain) to 10 (unbearable pain) to rate the levels of pain. The main outcome measures were overall and worst intraoperative pain scores,duration of surgery, and pain score during the administration of the retrobulbar anesthetic agent.RESULTS: Mean surgical time was 57.9 minutes in the topical group and 56.6 minutes in the retrobulbar group (p > 0.05). The painscores were not significantly different. Mean overall pain scores were 1.71 (SD 1.04, range 0-5) in the topical group and 1.38 (SD 1.04,range 0-3) in the retrobulbar group (p > 0.05). Mean worst pain scores ŀCanwere 3.20 (SD 1.30, range 1-7) and 2.95 (SD 0.73, range 1-4),respectively (p > 0.05). There was no significant correlation between duration of surgery and overall pain score in either group (r = 0.146,p = 0.356, and r = 0.174, p = 0.385, respectively). No patient required additional injection anesthesia in the topical group.INTERPRETATION: Topical anesthesia combined with systemic sedation and analgesia in posterior vitrectomy procedures providedsufficient analgesic effects in selected patients needing no scleral buckling and with short predicted surgery time.PMID: 17392852 [PubMed - indexed for MEDLINE]

Outbreak of toxic anterior segment syndrome associated with glutaraldehyde aftercataract surgery.Cataract Refract Surg. 2006 Oct;32(10):1696-701.Unal M, Yücel I, Akar Y, Oner A, Altin M.Department of Ophthalmology, Akdeniz University Medical Faculty, Antalya, Turkey. drmustafaun@hotmail.comAbstractPURPOSE: To present clinical findings of a cluster of cases of toxic anterior segment syndrome (TASS) after uneventfulphacoemulsification cataract surgery.SETTING: Department of Ophthalmology, Akdeniz University, Antalya, Turkey.METHODS: Six eyes of 6 patients developed TASS after uneventful phacoemulsification cataract surgery with implantation of a 3-pieceacrylic IOL performed by 2 ophthalmologists on the same day. Clinical findings included corneal edema, Descemet's membrane folds,anterior chamber reaction, fibrin formation, and irregular, dilated, and unreactive pupils.RESULTS: Glutaraldehyde 2% solution was used inadvertently by the operating room staff who cleaned and sterilized reusable ocularinstruments before autoclaving. None of the affected corneas improved. Additional surgical procedures were required and includedŀJpenetrating keratoplasty, trabeculectomy, and glaucoma tube implantation.CONCLUSIONS: Glutaraldehyde in concentrations generally used for cold sterilization is highly toxic to the corneal endothelium. Theoperating room staff involved in sterilizing instruments should be well educated about and careful to follow the protocols to properly cleanand sterilize reusable ocular instruments.

Effectiveness of disinsertion-resection and tucking of the inferior oblique musclein patients with unilateral long-standing superior oblique muscle palsy.Pediatr Ophthalmol Strabismus. 2007 Sep-Oct;44(5):283-7.Duranoglu Y.Akdeniz University School of Medicine, Department of Ophthalmology, Antalya, Turkey.AbstractPURPOSE: To investigate the effectiveness and safety of disinsertion-resection and tucking of the inferior oblique muscle in patientswith unilateral long-standing superior oblique muscle palsy and secondary inferior oblique muscle overaction.METHODS: Between April 2000 and January 2005, the records of 31 patients who underwent disinsertion-resection and tucking of theinferior oblique muscle for treatment of unilateral long-standing (> 6 months) superior oblique muscle palsy were retrospectivelyreviewed. A comprehensive ocular examination including best-corrected visual acuity measurements, ductions, versions, and deviationsat near and distance in the diagnostic positions of gaze, head tilt test, abnormal head position, dilated fundus, field of binocular fixation,and Lee screen test was performed prior to and after surgery.RESULTS: All patients had Knapp's class I unilateral superior oblique muscle palsy. The mean preoperative score of inferior obliqueŀJmuscle overaction was +3.03 and the mean vertical deviation was 15.9 PD in primary position. The follow-up period ranged from 4 to 82months. Inferior oblique muscle overaction diminished in 29 patients, and 2 patients had +1.0 overaction in adduction of the affected eye.The vertical deviation in these patients had some residual but smaller hypertropia.CONCLUSIONS: Disinsertion-resection and tucking of the inferior oblique muscle was safe, simple, and effective in eliminating inferioroblique muscle overaction and abnormal head posture, and in reducing the hyperdeviation in patients with unilateral long-standingsuperior oblique muscle palsy.PMID: 17913170 [PubMed - indexed for MEDLINE]

Ann Ophthalmol (Skokie). 2007 Dec;39(4):291-5.Optic nerve head topographic analysis and retinal nerve fiber layer thickness instrabismic and anisometropic amblyopia.Duranoglu Y.Department of Ophthalmology, Akdeniz University School of Medicine, Antalya, Turkey. yduranoglu@hotmail.comAbstractWe compared the optic nerve head topography and retinal nerve fiber layer (RNFL) thickness of the strabismic and anisometropicamblyopic eyes with the normal fellow eyes and age-matched controls and concluded that, although amblyopia is a functional visualloss, RNFL thickness and optic nerve head topographic changes in strabismic and anisometropic amblyopic eyes may be affected byamblyopia. Further histopathological and clinic confirmations are needed.PMID: 18025648 [PubMed - indexed for MEDLINE]ŀWe found 1 article by title matching your search:

Molecular Vision 2007; 13:12-17 Received 27 October 2006 | Accepted 29 December 2006 | Published 5 January 2007©2007 Molecular VisionPolymorphisms of DNA repair genes XRCC1 and XPD and risk ofprimary open angle glaucoma (POAG)Mehmet Güven, 1 Mustafa Ünal, 2 Bahadir Batar, 1 Ebru Eroğlu, 3 Kazim Devranoğlu, 3 Nevbahar Tamçelik, 3 DidarUçar, 3 Ahmet Sarici 31Department of Medical Biology, Cerrahpasa Faculty of Medicine, University of Istanbul, Istanbul, Turkey; 2 Department of Ophthalmology,Akdeniz University Medical Faculty, Antalya, Turkey; 3 Department of Ophthalmology, Cerrahpasa Faculty of Medicine,University of Istanbul, Istanbul, TurkeyPurpose: Oxidative DNA damage has been shown to have some role in the development of primary open angle glaucoma(POAG). In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, Xerodermapigmentosum complementation group D (XPD) codon 751 and X-ray cross-complementing group 1 (XRCC1) codon 399,in a sample of Turkish patients with POAG, and to evaluate their association with POAG development.Methods: We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), to analyzeXRCC1-Arg399Gln and XPD -Lys751Gln polymorphisms in 144 patients with POAG and in 121 disease-free controls,who were of a similar age.Results: There was no significant difference in the genotype distribution between POAG patients and controls for eachpolymorphism (p>0.05). Allele frequencies were also not statistically different between the groups (p=0.46; OR: 0.77;95% CI:0.42-1.43 for XRCC1 399Gln and p=0.88; OR: 0.92 95% CI: 0.50-1.67 for XPD 751Gln).Conclusions: Polymorphisms in XPD codon 751 and XRCC1 codon 399 were not associated with risk of POAG in asample of Turkish patients.Glaucoma is an optic neuropathy characterized by aspecific structural alteration of the head of the optic nerve accompaniedby progressive damage to the visual field. Primaryopen-angle glaucoma (POAG) is the most common form ofglaucoma, and it is one of the leading causes of irreversibleblindness worldwide [1].Although increased intraocular pressure (IOP) is a majorrisk factor for POAG, other concomitant factors affecting theeye play important roles including reactive oxygen species(ROS)-mediated oxidative damage. Oxidative DNA damageis significantly increased in the trabecular meshwork (TM) ofglaucoma patients compared to controls, and the existence ofa significant correlation between oxidative DNA damage andIOP in glaucoma patients has been reported [2-7]. Izzotti [8]reported that DNA damage may result in chronic degenerativediseases, including glaucoma, depending on the replicationrate of the target cell population.Recently, it has been hypothesized in many studies thatpolymorphisms in DNA repair genes reduce their capacity torepair DNA damage and thereby lead to a greater susceptibilityto cancer or age-related diseases [9,10]. Although the exactpathogenetic mechanism of open angle glaucoma has not yetbeen fully clarified, the possible involvement of oxidativedamage to DNA in POAG pathogenesis may indicate the roleof DNA repair enzymes. Consistent with this hypothesis, ChenCorrespondence to: Mustafa Ünal, Demircikara mah. 1426. sk. Zeybekapt. B blok. No:14/12 Muratpașa, Antalya, Turkey; phone: +902422496000; FAX: +90242 2274490; email: mustafaunalmd@gmail.com12and Kadlubar [7] stated that polymorphisms in genes involvedin antioxidant defenses and DNA damage repair may be geneticfactors that predispose to an increased risk of glaucoma.DNA repair enzymes continuously monitor chromosomesto correct damaged nucleotide residues generated by exposureto cytotoxic compounds or carcinogens. Repair of oxidativeDNA damage is mediated by both base excision repair (BER)and nucleotide excision repair (NER) mechanisms [11,12].Although hundreds of polymorphisms in DNA repair geneshave been identified [13,14], their effects on repair functionhave not been well characterized. Among them, Xerodermapigmentosum complementation group D (XPD), X-ray crosscomplementinggroup 1 (XRCC1), and X-ray cross-complementinggroup 3 (XRCC3) have been frequently studied, andthere is a growing body of evidence that polymorphisms ofthese genes may have some phenotypic significance [9,13].XRCC1, a DNA repair protein involved in single-strandbreaks (SSBs) and BER pathway, has been reported to beresponsible for the efficient repair of DNA damage caused byactive oxygen, ionization, and alkylating agents [15,16]. Itis a multidomain protein that interacts with the nicked DNAand participates with at least three different enzymes, poly-ADP-ribose polymerase (PARP), DNA ligase III, and DNApolymerase β, to repair SSBs [17]. Three polymorphismsoccurring at conserved sequences in the XRCC1 gene werereported by Shen et al. [16]. These coding polymorphisms,resulting in amino acid substitutions, were detected at codons194 (Arg-Trp), 280 (Arg-His), and 399 (Arg-Gln). In particular,the 399Gln polymorphism resulting from a guanine to adenine

1-Onoglu A, Taskin O, Inal M, Sadik S, Simsek M, Akar M, Kursun S, Mendilcioglu I, Postaci ,İspahiCComparison of the long-term histopathologic and morphologic changes after endometrial rollerballablation and resection: a prospective randomized trial.J Minim Invasive Gynecol. 2007 Jan-Feb;14(1):39-42. J Minim Invasive Gynecol. 2007 Jan-Feb;14(1):39-42.2-Kayacan N, Ertugrul F, Cete N, Coskunfirat N, Akar M, Karsli B, Erman M.Comparison of epiduraland combined spinal-epidural analgesia in the management of labour without pain. J Int MedRes2006 Nov-Dec;34(6):596-602.3-Kayacan N, Ertugrul F, Arici G, Karsli B, Akar M, Erman M.In vitro effects of opioids on pregnantuterine muscle.Adv Ther2007 Mar-Apr;24(2):368-754-Simsek M, Burak F, Taskin O.Effects of micronized purified flavonoid fraction (Daflon) on pelvic painin women with laparoscopically diagnosed pelvic congestion syndrome: a randomized crossovertrial.Clin Exp Obstet Gynecol2007;34(2):96-8.5-Satilmiş A, Güra A, Ongun H, Mendilcioğlu I, Colak D, Oygür N.CMV seroconversion in pregnantsand the incidence of congenital CMV infectionTurk J Pediatr. 2007 Jan-Mar;49(1):30-6.6-Simsek M,Mendilcioglu I,Mihci E, Karaguzel G, Taskin OPrenatal diagnosis and early treatment offetal goitrous hypothyroidism and treatment results with two-year follow-up.J Matern Fetal NeonatalMed2007 Mar;20(3):263-5.7-Mendilcioglu IRecurrent periclitoral abscess: treatment of a rare cause of vulvar painEur J ObstetGynecol Reprod Biol2007 Mar;131(1):101-2. Epub 2006 Jun 2.ŀKadın Hastalıkları ve Doğum Anabilim Dalı - 2007

Comparison of the long-term histopathologic and morphologic changes afterendometrial rollerball ablation and resection: a prospective randomized trial.Minim Invasive Gynecol. 2007 Jan-Feb;14(1):39-42.Onoglu A, Taskin O, Inal M, Sadik S, Simsek M, Akar M, Kursun S, Mendilcioglu I, Postaci H, Ispahi C.SSK Tepecik Hospital, Antalya and Izmir, Turkey.AbstractSTUDY OBJECTIVE: To compare long-term histologic features of endometrial rollerball ablation versus resection.DESIGN: Randomized clinical trial (Canadian Task Force classification I).SETTING: Akdeniz University School of Medicine.PATIENTS: Women with menorrhagia undergoing endometrial ablation.INTERVENTION: Comparison of patients with menorrhagia undergoing endometrial resection and ablation.MEASUREMENTS AND MAIN RESULTS: Endometrial rollerball ablation (n = 23 women) and resection (n = 25) were followed bysecond-look office hysteroscopy with endometrial biopsy. Mean follow-up to second look hysteroscopy after rollerball ablation and loopresection was 33.4 +/- 2.1 and 31.1 +/- 2.6 months, respectively. Complete atrophy and partial adhesion or obliteration of the cavity andŀJfibrosis were observed at second-look hysteroscopy and were similar in both groups. Whereas all random biopsy specimens after bothablation and resection revealed diminished endometrial glands with varied necrosis and scarring, the number of endometrial glands perfield was not correlated with amount of bleeding or menstrual pattern. Bleeding patterns were similar between the groups. Noprecancerous or malignant lesion was found after the procedures.CONCLUSION: Although efficacy of both endometrial ablation and resection is related to initial thermal destruction and correlated withpostablation hysteroscopic and histologic findings, endometrial regrowth may be expected and is not a failure of ablation. Bothprocedures revealed histopathologically and clinically similar results.PMID: 17218227 [PubMed - indexed for MEDLINE

The Journal of International Medical Research2006; 34: 596 – 602Comparison of Epidural andCombined Spinal–Epidural Analgesiain the Management of Labourwithout PainN KAYACAN 1 , F ERTUGRUL 1 , N ÇETE 1 , N COSKUNFIRAT 1 ,M AKAR 2 , B KARSLI 1 AND M ERMAN 11Department of Anaesthesiology and Reanimation, Faculty of Medicine, and 2 Departmentof Obstetrics and Gynaecology, Akdeniz University, Antalya, TurkeyThe effects of combined spinal–epiduralanalgesia (CSEA) and epidural analgesia(EA) were studied in 50 healthyparturients randomly allocated toreceive bupivacaine plus fentanyleither epidurally, or intrathecally andepidurally. Significant differences frombaseline values were seen in systolic bloodpressure at all time-points except for 4 h inthe EA group and at 3 and 4 h in the CSEAgroup. Significant differences frombaseline values were seen in diastolicblood pressure at 1, 2, 3 and 4 h in the EAgroup, whereas no significant differencesfrom baseline were seen in the CSEAgroup. Pain scores in both groups weresignificantly decreased compared withbaseline and all scores, except at 2h, weresignificantly lower in the CSEA groupcompared with the EA group. Theduration of labour and total amount ofdrugs used were significantly decreasedand cervical dilatation was faster withCSEA compared with EA. In conclusion,CSEA was associated with more rapidonset of analgesia and faster progress incervical dilatation compared with EA, andcan be used safely for labour analgesia.KEY WORDS: LABOUR ANALGESIA; EPIDURAL ANALGESIA; COMBINED SPINAL–EPIDURAL ANALGESIA;LOCAL ANAESTHETICS; OPIOIDSIntroductionAnalgesia for labour without pain shouldideally be safe and non-invasive, and shouldnot affect the progress of labour. 1 Regionalanalgesia techniques decrease the depressanteffects of opioids and sedatives on the fetusand improve placental perfusion and fetaloxygenation. 2Epidural analgesia (EA) has been shownto be associated with a late-onset drug effect,increased oxytocin usage, delay in theprogress of labour and an increasedincidence of operative delivery. 3,4 Inrecent years, combined spinal–epiduralanaesthesia (CSEA) has been usedincreasingly as an alternative to EA. Theintrathecal component in the combinedtechnique provides fast analgesia withoutproducing a motor block; the epiduralcomponent provides further analgesia. 3 – 6596

Ther. 2007 Mar-Apr;24(2):368-75.In vitro effects of opioids on pregnant uterine muscle.Kayacan N, Ertugrul F, Arici G, Karsli B, Akar M, Erman M.Department of Anesthesiology, Akdeniz University Medical Faculty, Antalya, Turkey. fertug@hotmail.comAbstractOpioids are often used for obstetric analgesia. Ideal obstetric analgesia is attained with optimal pain relief and minimal risk for theparturient. Therefore, investigators in the present study explored the effects of different opioids on the myometrium of pregnant rats.Myometrial strips were exposed to increased concentrations of fentanyl (10(-8) M to 10(-6) M), alfentanil (10(-8) M to 10(-4) M),remifentanil (10(-8) M to 10(-4) M), and meperidine (10(-8) M to 10(-4) M). Decreased contractile activity was observed in myometrialstrips isolated from pregnant rats at cumulative concentrations of fentanyl, alfentanil, remifentanil, and meperidine. The amplitude ofcontractions was reduced with increasing concentrations of opioids; this effect was statistically significant at a concentration of 10(-4) M.When administered at higher concentrations, opioids may decrease contractions in pregnant rat myometrium.PMID: 17565928 [PubMed - indexed for MEDLINE]ŀAdv

Effects of micronized purified flavonoid fraction (Daflon) on pelvic pain in womenwith laparoscopically diagnosed pelvic congestion syndrome: a randomizedcrossover trial.Exp Obstet Gynecol. 2007;34(2):96-8.Simsek M, Burak F, Taskin O.Department of Obstetrics and Gynecology, Akdeniz University, Antalya, Turkey.AbstractBACKGROUND: We evaluated the effects of daflon, a venomimetic agent that regulates the circulatory tonus of the venous system, onpelvic pain and investigated the role of enlarged veins the pathophysiology of pelvic congestion syndrome.METHODS: Twenty women (age 28-35 yrs) with chronic pelvic pain were diagnosed with the syndrome at laparoscopy. They all hadprominent broad ligaments and ovarian veins without other pathologies such as endometriosis to explain the etiology of pelvic pain. Tenwomen were randomized a fashion to receive 500 mg of Daflon twice/daily for six months, and ten a vitamin pill for placebo effect;they were crossed over for another six months.RESULTS: At the end of the third month, the frequency and severity of pelvic symptoms began to decrease with daflon compared withthe pretreatment and vitamin arm. The mean scores were significantly ŀClinless at the end of six months, respectively, p < 0.05.CONCLUSIONS: Pharmacologic enhancement of venous tonus may restore pelvic circulation and relieve pelvic symptomatology.

J Pediatr. 2007 Jan-Mar;49(1):30-6.CMV seroconversion in pregnants and the incidence of congenital CMV infection.Satilmiş A, Güra A, Ongun H, Mendilcioğlu I, Colak D, Oygür N.Department of Pediatrics, Akdeniz University Faculty of Medicine, Antalya, Turkey.AbstractIn this study, it was aimed to determine the ratio of CMV seroconversion in pregnant women, the prevalence of maternal CMV infectionand also the incidence of congenital CMV infection in their newborns in the Antalya region of Turkey. During a one-year period, CMVspecificIgG and IgM were determined in all (n: 1027) pregnant women admitted at 8 to 20 weeks of gestation, an according to thepresence or absence of anti CMV-IgM and CMV-IgG, pregnant women were classified as seropositive, seronegative and havingmaternal CMV infection. Differentiation of primary and recurrent CMV infection in women with both CMV-IgM (+) and CMV-IgG (+)antibody was determined by the avidity index (AI) of anti-CMV IgG. Ultrasonographic examination was done and amniocentesis wasperformed at 21 to 23 weeks of gestation in pregnants with primary infection. CMV DNA was investigated in the amniotic fluid byquantitative polymerase chain reaction (qPCR). Pregnants with recurrent infection were followed only by ultrasonography for thepresence of fetal abnormalities. Neonates born to mothers with CMV ŀTurkinfection were examined for the findings of congenital CMVinfection and screened for anti- CMV-IgM, CMV DNA and CMV antigenemia in the first two weeks of life. The rate of seropositivity wasfound as 98.5% and the rate of seronegativity as 1.5% in pregnant women. The prevalence of maternal CMV infection was found as1.2% and among these pregnant women, the incidence of primary and recurrent maternal CMV infection was 0.3% (3 women) and 0.8%(12 women), respectively. Congenital CMV infection was detected in one of the newborns born to mothers with primary infection while noinfection was detected in any of the newborns of mothers with recurrent CMV infection, so the incidence of congenital CMV infection wasfound as 0.1% and the rate of intrauterine infection following the primary maternal infection was 33%. In conclusion, seroprevalence rateof CMV in pregnants is high and most (66%) infections are recurrent maternal CMV infection in our region. Thus, it does not seem to becost-effective to screen all pregnant women for CMV infection, as in the other countries with high seropositivity rate.PMID: 17479641 [PubMed - indexed for MEDLINE]

The Journal of Maternal-Fetal and Neonatal Medicine, March 2007; 20(3): 263–265LETTER TO THE EDITORPrenatal diagnosis and early treatment of fetal goitroushypothyroidism and treatment results with two-year follow-upJ Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/11/10For personal use only.MEHMET S_IMSEK 1 , INANC MEND_ILC_IOGLU 1 , ERCAN M_IHC_I 2 ,GÜLAY KARAGÜZEL 2 , & OMUR TASKIN 11 Department of Obstetrics and Gynecology, Akdeniz University School of Medicine, Antalya, Turkey and 2 Departmentof Pediatry, Akdeniz University School of Medicine, Antalya, Turkey(Received 10 September 2006; revised 1 October 2006; accepted 1 October 2006)A 24-year-old primiparous woman with no priorhistory of thyroid problems was referred to ourprenatal unit at 25 weeks of gestation for evaluationof a fetal neck mass incidentally detected byultrasound. A fetal ultrasound scan was performedfor measurements of thyroid gland size (diameter;Figure 1). Sonography showed a large anteriorcervical symmetrical blobbed mass (17623622 mm) with mild hyperextension of the fetal neck.No other anomaly was noted in the fetus. Theamniotic fluid volume was normal. Fetal growthand movements were normal. Maternal serumthyroid function tests were normal. Ultrasound ofthe maternal thyroid was unremarkable. Cordocentesiswas performed at 25 weeks of gestation toevaluate the fetal thyroid function. Fetal hypothyroidismwas detected with a low concentration ofthyroxin in the fetal serum (FT4 0.65 ng/dL) andTSH markedly elevated in fetal serum (100 mU/L).Normal values at 19–27 weeks: FT4 7.79 + 2.02 mg/mL and TSH 4.1 + 1.4 mU/L. Fetal karyotype 46XX was confirmed.The fetus was treated with a 500-mg injection oflevothyroxine sodium into the amniotic fluid at 26weeks of gestation at the request of both parents afterconsent. Nine intraamniotic injections were performedweekly, with the last injection given at 38weeks of gestation. Meanwhile, regular ultrasoundevaluations showed a progressive decrease in thethyroid volumes. At 39 weeks of gestation, a livefemale was delivered weighing 3600 g.Neonatal airway obstruction was not found andresuscitation was not required. The newborn had norespiratory problems. Measurement of serum TSHand iodothyronines confirmed the diagnosis ofprimary hypothyroidism. Thyroid hormone therapystarted on the first day of life with a daily oral dose of50-mg levothyroxine. She has returned for regularfollow-up at the pediatric endocrinology outpatientclinic. After two years of follow-up, she has beeneuthyroid on 80-mg/day levothyroxine treatment, andher physical and neurological development is normal.Congenital hypothyroidism has an incidence ofone in every 4000 live births and is one of the mostcommon treatable causes of mental retardation [1].Congenital hypothyroidism presenting with a goiteris very rare (1/40 000) and can be found in onlyabout 10–15% of all cases of congenital hypothyroidism[2]. Of primary congenital hypothyroidism,85% is due to developmental defects of thethyroid gland. Of the remaining 15% of cases, 10%are attributable to an inborn error of thyroxinsynthesis and 5% are the result of transplacentalmaternal thyrotropin receptor blocking antibody [3].Fetal hypothyroidism is usually unrecognizedwithout a maternal history of thyroid disease oranti-thyroid medication. However, the consequencesof both fetal goiter and impaired thyroid function areserious. Long-term follow-up of children with fetalhypothyroidism shows that it may be associated withmental retardation, delayed skeletal maturation,hearing defects, and deficit in focusing, even withimmediate postnatal screening and replacementtherapy [4]. A large fetal goiter may result in dystociaduring delivery because of neck hyperextension andenlargement of the thyroid [5]. The particularimpairment correlates with severity and duration offetal hypothyroidism [6].Fetal goiter may sometimes be difficult to diagnoseultrasonographically when moderate, so it must beISSN 1476-7058 print/ISSN 1476-4954 online Ó 2007 Informa UK Ltd.DOI: 10.1080/14767050601134728

European Journal of Obstetrics & Gynecology andReproductive Biology 131 (2007) 101–106www.elsevier.com/locate/ejogrbLETTERS TO THE EDITOR – BRIEF COMMUNICATIONRecurrent periclitoral abscess: Treatment of a rarecause of vulvar painDear Editor,Periclitoral abscess is a very rare disorder causing severevulvar pain. To date only a few cases have been reported andthe etiology was unclear except as the result of femalecircumcision in a group of patients [1–5]. Periclitoral abscesscan be recurrent and has also been seen in premenarchal girls[1,3,4]. Antibiotic treatment and marsupialization are thetreatment options.We report a case of recurrent periclitoral abscesspresenting with vulvar tenderness and swelling.A 33-year-old woman presented with severe tendernessand swelling of her clitoris. On physical examination atender, fluctuant, mildly erythematous, 4 cm 3 cm mass inthe periclitoral region was noted (Fig. 1). The prepuce wasenlarged because of the abscess localized underneath it. Theclitoris was covered with the prepuce and difficult tovisualize due to tenderness. Vaginal speculum examinationwas unremarkable. In her past medical history, at the age of12, she had had the same symptoms due to a tender swellingof the periclitoral region, which resolved followingspontaneous drainage. She has no history of sexuallytransmitted disease. Ampicillin/sulbactam was begun orally.On the third day of antibiotic treatment, the abscess wasdrained from a 2-cm wide incision on the lateral side of theprepuce avoiding injury to the clitoris, and marsupializationwas carried out by suturing the abscess cavity to the edges ofthe skin. Hair was extracted from the abscess cavity.Pathologic examination of the discharge revealed granulomatousinflammation. No identification could be made fromthe culture.One week later the patient was free of symptoms and theswelling completely resolved without any drainage. Onemonth later healing was complete.Periclitoral abscess has been described in several cases inthe literature. Some of the cases were complication offemale circumcision [5]. In other cases the cause of theabscess is unknown [3,4]. No venereal etiology has beenreported. In our case, the patient had her first occurrence of apericlitoral abscess before sexual activity. A similar case in apatient who had a periclitoral abscess during the premenarchaltime has been reported [1]. Evidence suggeststhat sexually transmitted diseases do not seem to be thecause of periclitoral abscess. Pilonidal abscess of thepericlitoral region has also been reported with similarfindings in some other patients with periclitoral abscess[6]. In our case a few hairs were observed in the abscesscavity. Although it may be difficult to find hair in theabscess cavity, pilonidal sinus is the most likely cause of thedisorder.Marsupialization has been described as a successfulmethod for treating periclitoral abscesses [3,4].However,insome reports injury to the clitoris was described as alimitation of this treatment and antibiotic treatment has beenadvocated [1,2]. In premenarchal girls medical treatmentshould be the first option because of its noninvasiveness.However, in recurrent cases, marsupialization should be thepreferred treatment as it facilitates exploring the cavityand extracting potential causes such as hair. The incisionshould be made as laterally as possible so as not to damagethe clitoris. Postoperatively, no additional medical care isneeded. In our case, healing was not delayed and nodiscomfort has been reported postoperatively.ReferencesFig. 1. Periclitoral abscess.[1] Lara-Torre E, Hertweck SP, Kives SL, Perlman S. Premenarchalrecurrent periclitoral abscess: a case report. J Reprod Med 2004;49:983–5.0301-2115/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved.

264 Letter to the EditorJ Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/11/10For personal use only.carefully sought during the routine anatomy scan.Fetal thyroid function tests must be carried out whena goiter is detected at a gestational age too early forsafe delivery. Amniotic fluid concentrations of TSHaccurately reflect fetal serum levels [7], but Brunerand Dellinger [8] consider cord blood and measurementmore reliable, thus rendering evaluationthrough amniocentesis doubtful. Fetal thyroid statuscan be accurately assessed by fetal blood sampling[9], but this procedure is riskier with about 1% fetaldemise in experienced hands [10]. Maternal hormones,along with compensatory deiodinase actionconfer some protection to fetal central nervoussystem development [11], but the maternal contributiononly accounts for about 30–40% of neartermfetal needs [12].We postulated that early fetal hypothyroidism maybe particularly deleterious to the central nervoussystem, so we attempted to correct the deficiencyquickly. Currently, this is achieved through 500 mglevothyroxine intra-amniotic weekly injections [13].Monitoring therapeutic efficacy is still problematic.Serial cordocentesis is reliable but repetitivesampling carries unacceptably high fetal risks. Closethyroid function monitoring by repeated cordocentesisto adjust fetal treatment did not appear essentialand may be substituted by an ultrasonographicfollow-up of the fetal goiter decrease [14]. Hence,we relied on ultrasonographic measurements ofgoiter size, speculating that a reduction of goitercircumference and/or diameter indicated improvedfetal thyroid status. In our pregnancy, the fetal goiterdecreased rapidly in size with treatment.In conclusion, we have shown that a fetal goiter wassuccessfully treated with intra-amniotic administrationFigure 1. Image of ultrasound examination at 25 weeks.of levothyroxine. With this regimen, fetal goiter wasshown to regress, and fetal and newborn TSH levelswere normalized. After two years of follow-up andthyroxin sodium, bone maturation and neurologicaldevelopment of the child appear normal.ReferencesMehmet SimsekDepartment of Obstetrics and GynecologyAkdeniz University School of MedicineAntalya, TurkeyTel: 090-242-2496000Fax: 090-242-2694965E-mail: drmsimsek@hotmail.com1. Delange F. Neonatal screening for congenital hypothyroidism:Results and perspectives. Horm Res 1997;48:51–61.2. Fisher DA. Fetal thyroid function: Diagnosis and managementof fetal thyroid disorders. Clin Obstet Gynecol1997;40:16–31.3. Refetoff S, Dumont J, Vassart G. Thyroid disorders.In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. Themetabolic and molecular basis of inherited disease. New York:McGraw-Hill; 2001. pp 4029–4076.4. Haddow JE, Palomaki GE, Allan WC, Williams JR,Knight GJ, Gagnon J, O’Heir CE, Mitchell ML, Hermos RJ,Waisbren SE, et al. Maternal thyroid deficiency duringpregnancy and subsequent neuropsychological developmentof the child. N Engl J Med 1999;341:549–555.5. Volumenie JL, Polak M, Guibourdenche J, Oury JF,Vuillard E, Sibony O, Reyal F, Raccah-Tebeka B,Boissinot C, Madec AM, et al. Management of fetal thyroidgoitres: A report of 11 cases in a single perinatal unit. PrenatDiagn 2000;20:799–806.6. Rovet J, Alvarez M. Thyroid hormone and attention incongenital hypothyroidism. J Pediatr Endocrinol Metab1996;9:63–66.

1-Agirdir BV, Bozova S, Derin AT, Turhan M.Chronic otitis media with effusion and HelicobacterpyloriInt J Pediatr Otorhinolaryngol. 2006 May;70(5):829-342- Guney K, Ozbilim G, Derin AT, Expression of PTEN protein in patients with laryngealsquamous cell carcinoma AURIS NASUS LARYNX Volume: 34 Issue: 4 Pages: 481-486Published: DEC 20073- Nal N (Nal, Nevra), Ahmed ZM (Ahmed, Zubair M.), Erkal E (Erkal, Engin), Alper OM(Alper, Oezguel M.), Luleci G (Lueleci, Gueven), Dinc O (Dinc, Oktay) Mutational spectrum ofMYO15A: The large N-terminal extension of myosin XVA is required for hearing HUMANMUTATION Volume: 28 Issue: 10 Pages: 1014-1019 Published: OCT 2007ŀKulak Burun Boğaz Hastalıkları Anabilim Dalı

International Journal of Pediatric Otorhinolaryngology (2006) 70, 829—834www.elsevier.com/locate/ijporlChronic otitis media with effusion andHelicobacter pyloriBulent V. Agirdir *, Selami Bozova, Alper T. Derin, Murat TurhanAkdeniz University, Medical Faculty, ENT & HNS, Arapsuyu, Akdeniz, Antalya 07070, TurkeyReceived 22 July 2005; received in revised form 17 September 2005; accepted 17 September 2005KEYWORDSChronic otitis mediawith effusion;Helicobacter pylori;CLO testing;Urease testSummaryObjective: The aim of this study is to investigate the presence of Helicobacter pylori(HP) in the middle ear effusion by Campylobacter-like organism (CLO) test andwhether it has a role in the ethiopathogenesis of chronic otitis media with effusion(OME).Study design: A prospective randomized and controlled study.Methods: This study was performed with 45 patients with the diagnosis of chronicOME and adenoid hypertrophy, between the ages 3 and 13 (median 6). Thirty patientsconstituted the study group (18 male (60%) and 12 (40%) female). Adenoidectomy withmyringotomy with ventilation tube insertion were performed to this group. Middle eareffusion and adenoid tissue pieces were collected and H. pylori presence wasinvestigated by ‘‘CLO’’ testing. Fifteen patients of the matching age group (9 male(66.7%) and 6 (33.3%) female) constituted the control group to whom adenoidectomywith myringotomy were performed but no middle ear effusion could be determined(empty myringotomy patients). The wash out liquid of middle ear and pieces ofadenoid tissue samples were also collected from the control group. By using CLOtesting, the presence of H. pylori was investigated in the adenoid tissues and middleear of the empty myringotomy patients.Results: In 20 (66.6%) patients of the study group, CLO testing was positive in themiddle ear effusions. None of the patients demonstrated positive CLO test in the washout liquid of middle ear. There was significant difference of positive CLO testing in themiddle ear effusions of two groups ( p < 0.001).Conclusions: These findings showed us that presence of HP in the middle ear effusionusing CLO testing and this may be responsible for the ethiopathogenesis of chronicOME.# 2005 Elsevier Ireland Ltd. All rights reserved.* Corresponding author. Tel.: +90 242 227 4343/24106.E-mail address: abulent@akdeniz.edu.tr (B.V. Agirdir).0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.ijporl.2005.09.026

Auris Nasus Larynx 34 (2007) 481–486www.elsevier.com/locate/anlExpression of PTEN protein in patients with laryngealsquamous cell carcinomaKenan Guney a, *, Gulay Ozbilim b , Alper Tunga Derin a , Safiye Cetin ba Department of Ear Nose Throat Head and Neck Surgery, Akdeniz University Medical Faculty, Antalya, Turkeyb Department of Pathology, Akdeniz University Medical Faculty, Antalya, TurkeyReceived 15 June 2006; accepted 26 March 2007Available online 1 May 2007AbstractObjective: PTEN (phosphatase and tensin homologue deleted on chromosome 10), also referred to as MMAC1 (mutated in multipleadvanced cancers) gene was recently identified as a putative tumor suppressor in a variety of malignant tumors. PTEN expression has beeninvestigated in some squamous cell carcinomas (SCC) of head and neck. However, there is only little knowledge about laryngealmalignancies. Therefore, we examined PTEN product protein immunohistochemically in 30 consecutive laryngeal specimens from patientswith laryngeal SCC and compared the results according to the clinicopathologic characteristics of the patients.Method: Surgical resection specimens of patients with laryngeal SCC were stained for PTEN protein using a primary rabbit polyclonal anti-PTEN antibody. Standard avidin–biotin immunohistochemical analysis was used to process the sections. The extent and intensity of PTENstaining in the specimens were compared according to the age and sex of the patients and localization, differentiation, size and stage of thetumor.Results: Out of 30 tumoral specimens (23 glottic and 7 supraglottic) 22 showed decreased PTEN staining intensity compared to the adjacentnormal tissue. The extent of cytoplasmic PTEN staining was significantly less in supraglottic tumors ( p < 0.05). When characteristics of thepatients were analyzed according to the extent of cytoplasmic PTEN staining no difference was observed according to age, sex, measure,differentiation, T or N status.Conclusion: A significant decrease in the extent of PTEN staining was observed in supraglottic SCC. It could be worthwhile to test if PTENexpression is diminished in patients with more aggressive laryngeal tumors, with special attention to tumor localization in larger series.# 2007 Elsevier Ireland Ltd. All rights reserved.Keywords: PTEN; Larynx; Cancer1. BackgroundAs more knowledge accumulates about the role of genesin tumorigenesis, more candidates have been searched indifferent kinds of tumors. PTEN (phosphatase and tensinhomologue deleted on chromosome 10), also referred to asMMAC1 (mutated in multiple advanced cancers), gene wasidentified recently as a putative tumor suppressor in a varietyof malignant tumors [1]. Abnormalities of PTEN are* Corresponding author at: Akdeniz Universitesi Tip Fakultesi, KBBAnabilim Dali, 07060 Antalya, Turkey.Tel.: +90 242 249 68 49/533 433 51 13; fax: +90 242 227 43 20.E-mail address: sevtapv@akdeniz.edu.tr (K. Guney).localized on chromosome 10q23 [1–3]. The predictedPTEN/MMAC1 protein contains sequence motives withsignificant homology to the catalytic domain of proteinphosphatases and to the cytoskeletal proteins tensin andauxilin [1–3]. Based on the sequence homologies of PTEN/MMAC1 protein and protein phosphatases, the PTEN/MMAC1 protein was defined as a dual specificityphosphatase with a high degree of substrate specificity[2,4]. This enzymatic activity is necessary for PTEN/MMAC1 to function as a tumor suppressor. The target lipid,called phosphatidylinositol-3,4,5-triphosphate, PIP3, is akey component of the major cell growth control pathways,acting both to stimulate cell growth and to inhibit tumor cellproliferation blocking apoptosis [2,4]. Mutations of this0385-8146/$ – see front matter # 2007 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.anl.2007.03.014

HUMAN MUTATION 28(10), 1014^1019, 2007RESEARCH ARTICLEMutational Spectrum of MYO15A:The Large N-Terminal Extension of Myosin XVAIs Required for HearingNevra Nal, 1,2 Zubair M. Ahmed, 1 Engin Erkal, 3 Özgül M. Alper, 2 Güven Lüleci, 2 Oktay Dinc-, 3Ali Muhammad Waryah, 4 Quratul Ain, 4 Saba Tasneem, 4 Tayyab Husnain, 4 Parna Chattaraj, 1Saima Riazuddin, 1 Erich Boger, 1,5 Manju Ghosh, 6 Madhulika Kabra, 6 Sheikh Riazuddin, 4Robert J. Morell, 1 and Thomas B. Friedman 11 Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health(NIH), Rockville, Maryland; 2 Department of Medical Biology and Genetics, Akdeniz University, Antalya, Turkey; 3 Department ofOtolaryngology, Akdeniz University, Antalya, Turkey; 4 National Center of Excellence in Molecular Biology, University of the Punjab, Lahore,Pakistan; 5 Department of Biology, University of Maryland, College Park, Maryland; 6 Genetic Unit, Department of Pediatrics, All India Institute ofMedical Sciences, New Delhi, IndiaCommunicated by Henrik DahlHuman MYO15A is located on chromosome 17p11.2, has 66 exons and encodes unconventional myosin XVA.Recessive mutations of MYO15A are associated with profound, nonsyndromic hearing loss DFNB3 in humans,and deafness and circling behavior in shaker 2 mice. In the inner ear, this motor protein is necessary for thedevelopment of hair cell stereocilia, which are actin-filled projections on the apical surface and the site ofmechanotransduction of sound. The longest isoform of myosin XVA has 3,530 amino acid residues. Twoisoform classes of MYO15A are distinguished by the presence or absence of 1,203 residues preceding the motordomain encoded by alternatively-spliced exon 2. It is not known whether this large N-terminal extension ofmyosin XVA is functionally necessary for hearing. We ascertained approximately 600 consanguineous familiessegregating hereditary hearing loss as a recessive trait and found evidence of linkage of markers at the DFNB3locus to hearing loss in 38 of these families ascertained in Pakistan (n 5 30), India (n 5 6), and Turkey (n 5 2).In this study, we describe 16 novel recessive mutations of MYO15A associated with severe to profound hearingloss segregating in 20 of these DFNB3-linked families. Importantly, two homozygous mutant alleles—c.3313G4T (p.E1105X) and c.3334delG (p.G1112fsX1124) of MYO15A—located in exon 2 are associatedwith severe to profound hearing loss segregating in two families. These data demonstrate that isoform 1,containing the large N-terminal extension, is also necessary for normal hearing. Hum Mutat 28(10),1014–1019, 2007. Published 2007 Wiley-Liss, Inc. yKEY WORDS:DFNB3; hereditary deafness; genotype–phenotype; myosin; MYO15AINTRODUCTIONMyosins are molecular motor proteins that hydrolyze ATP togenerate a small conformational change in the globular motordomain that is translated into movement along actin filaments[Mooseker and Cheney, 1995; Mermall et al., 1998; Sellers, 1999;Schliwa and Woehlke, 2003]. Based upon phylogenetic analysesof motor domains, 37 distinct classes of heavy chain myosins havebeen cataloged in plants, fungi, amoebas, invertebrates, andvertebrates [Sellers, 2000; Berg et al., 2001; Richards andCavalier-Smith, 2005; Foth et al., 2006]. Within the humangenome, there are at least 39 myosin genes assigned to 12 classes[Berg et al., 2001].Myosins are implicated in cellular functions including musclecontraction, cell movement, cytokinesis, exocytosis, endocytosis,transcription, vesicle and cargo trafficking, organelle localization,signal transduction, and anchoring and differential elongationof inner ear hair cell stereocilia [Baker and Titus, 1998; Vale,2003; Belyantseva et al., 2005; Krendel and Mooseker, 2005;The Supplementary Material referred to in this article can beaccessed at http://www.interscience.wiley.com/jpages/1059-7794/suppmat.Received 17 January 2007; accepted revised manuscript 3 April2007. Correspondence to:Thomas B. Friedman, Ph.D., Section on HumanGenetics, Laboratory of Molecular Genetics, National Instituteon Deafness and Other Communication Disorders, National Institutesof Health,5 Research Court, Rockville, MD 20850.E-mail: friedman@nidcd.nih.govGrant sponsors: Higher Education Commission (HEC) Islamabad,Pakistan; Ministry of Science and Technology (MoST) Islamabad,Pakistan; National Institute on Deafness and Other CommunicationDisorders (NIDCD), National Institutes of Health (NIH);Grant numbers:1 ZO1 DC000035 - 09 and 1 ZO1 DC000039 - 09.Nevra Nal and Zubair M. Ahmed contributed equally to this study.DOI 10.1002/humu.20556Published online1June 2007 inWiley InterScience (www.interscience.wiley.com).y This article is a US Government work and, as such, is in the publicdomain in the United States of America.PUBLISHED 2007 WILEY-LISS, INC.

1-Y. Söyüncü, Mıhçı, E., Özcanlı, H., Özenci, M., Akyıldız, F., ve Aydın A.T., Reconstruction ofquadriceps tendon with Achilles tendon allograft in older children with congenital dislocation of thekneeKnee Surg Sports Traumatol Arthrosc 2006 Nov;14(11):1171-11752-Y.Söyüncü, Özdemir H., Söyüncü, S., Bigat, Z., ve Gür, S.Posterior spinal epidural abscess: anunusual complication of vertebroplastyJoint Bone Spine 2006, Dec;73(6).753-7553-Aydın, A.T., Özcanlı H., Y. Söyüncü, Dabak, T.KA New Noninvasive Controlled IntraarticularAnkle Distraction Technique on a Cadaver ModelArthroscopy 2006, Aug. 22 (8):905. e1-34- Ozenci AM, Inanmaz E, Ozcanli H, Soyuncu Y, Samanci N, Dagseven T, Balci N, Gur S.Proprioceptive comparison of allograft and autograft anterior cruciate ligament reconstructions. KneeSurg Sports Traumatol Arthrosc. 2007 Dec;15(12):1432-7.5- Ozcanli H, Ozenci AM, Ozcanli C, Ibis S, Gurer IE.Angiolymphoid hyperplasia: a case of a rarearterial involvement and successful recurrence treatment with laser therapy. J Eur Acad DermatolVenereol. 2007 Sep;21(8):1106-7.ŀOrtopedi ve Travmatoloji Anabilim Dalı

Technical NoteA New Noninvasive Controlled Intra-articular Ankle DistractionTechnique on a Cadaver ModelAhmet T. Aydin, M.D., Haluk Ozcanli, M.D., Yetkin Soyuncu, M.D., and Tayyar K. Dabak, M.D.Abstract: Effective joint distraction is crucial in arthroscopic ankle surgery. We describe an effectiveand controlled intra-articular ankle distraction technique that we have studied by means of afresh-frozen cadaver model. Using a kyphoplasty balloon, which is currently used in spine surgery,we tried to achieve a controlled distraction. After the fixation of the cadaver model, standard anteromedialand anterolateral portals were used for ankle arthroscopy. From the same portals, the kyphoplastyballoon was inserted and placed in an appropriate position intra-articularly. The necessary amount ofdistraction was achieved by inflating the kyphoplasty balloon with a pressure regulation pump. Allanatomic sites of the ankle joint were easily visualized with the arthroscope during surgery by changingthe pressure and the intra-articular position of the kyphoplasty balloon. Ankle distraction was clearly seenon the arthroscopic and image intensifier view. The kyphoplasty balloon is simple to place through thestandard portals and the advantage is that it allows easy manipulation of the arthroscopic instruments fromthe same portal. Key Words: Ankle arthroscopy—Distraction—Intra-articular distraction.Arthroscopic procedures are widely used for anklesurgery. Depending on the location and the sizeof the intra-articular disease, effective joint distractionmay be an appropriate surgical procedure. The purposeof this study is to describe an effective andcontrolled intra-articular ankle distraction techniqueperformed on a cadaver model.DESCRIPTION OF THE TECHNIQUEThis ankle arthroscopy model was formed with 2fresh-frozen cadaver models. We tried to achieve aFrom the Department of Orthopaedics and Traumatology,Akdeniz University School of Medicine, Antalya, Turkey.Address correspondence and reprint requests to Haluk Ozcanli,M.D., Department of Orthopaedics and Traumatology, AkdenizUniversity School of Medicine, Dumlupinar Blvd, 07070 Antalya,Turkey. E-mail: ozcanli@akdeniz.edu.tr© 2006 by the Arthroscopy Association of North AmericaCite this article as: Aydin AT, Ozcanli H, Soyuncu Y, Dabak TK.A new noninvasive controlled intra-articular ankle distractiontechnique on a cadaver model. Arthroscopy 2006;22:905.e1-905.e3 [doi:10.1016/j.arthro.2005.12.062].0749-8063/06/2208-5140$32.00/0doi:10.1016/j.arthro.2005.12.062controlled distraction with use of the Kyphon kyphoplastyballoon (Kyphon, Sunnyvale, CA), which iscurrently used in surgery of the spine. Following fixationof the cadaver model, standard anteromedial andanterolateral portals were used in ankle arthroscopy.From the same portals, the kyphoplasty balloon wasinserted intra-articularly and placed in an appropriateposition. The required amount of distraction was establishedthrough inflation of the kyphoplasty balloon witha pressure regulation pump. During the surgical procedure,all anatomic sites of the ankle joint were easilyvisualized through the arthroscope with changes in thepressure and the intra-articular position of the kyphoplastyballoon (Fig 1). Distraction of the ankle was demonstratedthrough arthroscopic and image intensifierviews (Fig 2). The most important advantage of thekyphoplasty balloon was its simple placement from standardportals, which allowed easy manipulation of arthroscopicinstruments from the same portal.DISCUSSIONAnkle arthroscopy has been widely used as a diagnosticand surgical procedure, and most practitionersArthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 22, No 8 (August), 2006: pp 905.e1-905.e3905.e1

Joint Bone Spine 73 (2006) 753–755Case reportPosterior spinal epidural abscess: an unusual complication of vertebroplastyYetkin Söyüncü a, * , Hakan Özdemir a , Seçgin Söyüncü b , Zekiye Bigat c , Semih Gür aa Department of orthopedics and traumatology, school of medicine, Akdeniz university, Dumlupınar street, Campus, 07070 Antalya, Turkeyb Department of emergency medicine, school of medicine, Akdeniz university, Antalya, Turkeyc Department of anesthesiology, school of medicine, Akdeniz university, Antalya, TurkeyReceived 22 October 2005; accepted 31 January 2006Available online 25 April 2006http://france.elsevier.com/direct/BONSOI/AbstractObjective: Complications after vertebroplasty are rare. There are few reported infectious complications requiring surgical management suchas corpectomy with anterior reconstruction and posterior stabilization, although we have not seen any reports about epidural abscess in theliterature. We present a patient in whom posterior epidural abscess developed after vertebroplasty in which drainage and antibiotherapy wererequired for treatment.Methods: A 70-year-old female with a painful T 12 osteoporotic compression fracture underwent percutaneous vertebroplasty using polymethylmethacrylatewithout complication. One week after vertebroplasty, however, she had fever and increased back pain. On clinical examination,soft tissue abscess formation was determined at the vertebroplasty site. This was drained surgically and antibiotic treatment was started. Atfollow-up, she had progressive neurological deterioration (paraparetic) on the 18th day after abscess drainage. MRI of the thoracolombar spinerevealed posterior spinal epidural abscess at the T 11/12 level. Partial laminectomy and drainage were performed. She had complete neurologicalrecovery in the follow-up period.Conclusion: An epidural abscess, which is an unusual complication of vertebroplasty, represents a medical and surgical emergency. Treatmentis generally urgent surgical drainage combined with antibiotics. The patient should be evaluated in detail for systemic infectious disease andcomorbid conditions before the vertebroplasty procedure.© 2006 Elsevier Masson SAS. All rights reserved.Keywords: Vertebroplasty; Infection; Epidural abscess; Osteoporosis1. IntroductionVertebroplasty and kyphoplasty are relatively new techniquesthat are being used to treat painful vertebral compressionfractures. Vertebroplasty is the percutaneous injection of a vertebralbody with bone cement. Use of percutaneous vertebroplastyfor the treatment of painful hemangiomas was first reportedduring the late 1980s [1]. Recently, its indication hasbeen expanded to include osteoporotic compression fractures,traumatic compression fractures, and painful vertebral metastasis[2,3]. Infectious complications requiring surgical managementafter vertebroplasty in an osteoporotic patient have rarely* Corresponding author. Tel.: +90 242 22 74343/66249;fax: +90 242 22 74329.E-mail address: ysoyuncu@hotmail.com (Y. Söyüncü).been reported in the literature. Only a few English-languagearticles were found in which postvertebroplasty infections weredetailed [4–7] and only three reported cases of pyogenic spondylitisfollowing vertebroplasty were identified [6,7]. We presenta patient in whom posterior epidural abscess complicatedwith neurological deterioration developed after vertebroplastyin which surgical drainage and antibiotherapy were required fortreatment. To the best of our knowledge, this is the first reportedcase of posterior epidural abscess without pyogenicspondylitis as a complication of vertebroplasty.2. Case reportA 70-year-old female with osteoporotic compression fractureof the 12th thoracic vertebral body confirmed by radiographywas admitted to our hospital. She had a medical history for1297-319X/$ - see front matter © 2006 Elsevier Masson SAS. All rights reserved.doi:10.1016/j.jbspin.2006.01.015

Knee Surg Sports Traumatol Arthrosc (2006) 14:1171–1175DOI 10.1007/s00167-006-0083-0KNEEReconstruction of quadriceps tendon with Achilles tendonallograft in older children with congenital dislocation of the kneeYetkin Söyüncü Æ Ercan Mıhçı Æ Haluk Özcanlı ÆMerter Özenci Æ Feyyaz Akyıldız Æ A. Turan AydınReceived: 6 July 2005 / Accepted: 19 October 2005 / Published online: 7 June 2006Ó Springer-Verlag 2006Abstract This is a case report of two children withcongenital dislocation of the knee. They have beentreated surgically with Z-lengthening of the quadricepstendon and additional reconstruction of thequadriceps tendon with Achilles tendon allograft tofill in the remaining average 6 cm gap of the tendon.The patients were two girls, 6 and 9 years old. Oneof them had an operative treatment previously with atendon lengthening procedure and it was failed andthe other patient was untreated before. Preoperatively,untreated case was unable to walk. The otherpatient was limping. None of them was able to flextheir knees beyond the neutral extension position.Postoperatively, both patients were able to walk andthe knees were reduced to a range of motion of0°–95° of flexion. The mean follow-up time was20 months.Keywords Quadriceps tendon Æ Congenital kneedislocation Æ Tendon allograft Æ ReconstructionY. Söyüncü (&) Æ H. Özcanlı ÆM. Özenci Æ F. Akyıldız ÆA. T. AydınDepartment of Orthopedics and Traumatology,Faculty of Medicine, Akdeniz University,Dumlupınar caddesi, Kampüs,07070 Antalya, Turkeye-mail: ysoyuncu@hotmail.comE. MıhçıDepartment of Pediatrics, Genetic Section,Faculty of Medicine, Akdeniz University,Antalya, TurkeyIntroductionCongenital dislocation of the knee (CDK) is a rarecondition with an estimated incidence of 1/100,000live births [5]. The etiology of CDK remains unknown.Various pathologic findings characteristic ofCDK have been reported including fibrosis of thequadriceps muscle or obliteration of the suprapatellarpouch and abnormalities of the anterior cruciate ligament(ACL) that may be secondary to CDK [5, 6,10, 13, 19].Congenitally dislocated knees are classified into fivegroups (Table 1)[7]. Patients classified in groups 3 and 4often respond to nonoperative measures if they aretreated early. Group 5 patients normally require surgicalintervention. Refractory cases or those treatedafter the first 3–4 months of life may require surgicaltreatment. Multiple procedures have been reported foroperative management of CDK. These include openquadricepsplasty, including Z-plasty of the quadricepsmechanism (or V–Y advancement), and release ofinterarticular adhesions [5]. Roy and Crawford [16]described a method of percutaneous quadriceps release.Arthroscopic release of intraarticular adhesions maybe combined with minimal incision quadricepsplastyand casting. In longstanding extension contractures, toobtain wound closure with the knee in full flexion mayrequire Z-plasty, rhombic Z-plasty, tissue expansionand/or rotational flaps.Although allograft in tendon lengthening is previouslyreported and lengthening of the quadriceps inCDK is a common procedure, to the best of ourknowledge there are no reports in the literature onreconstruction of the quadriceps tendon with Achillestendon allograft in older children who have CDK.123

Plastik, Rekonstrüktif ve Estetik Cerrahisi Anabilim Dalı - 20071-Tetik Menevse G, Islamoglu K, Ege Ozgentas H.Expansion of surviving skin paddle ofneurocutaneous island flaps in rats byJ Reconstr Microsurg. 23(2):99-105.20072-Islamoglu K, Dikici MB, Ozgentas HE.Permanence of diced cartilage, bone dust and diced cartilageJ Craniofac Surg. 17(5):905-8. 2006.3- Feng GM, Cigna E, Lai HK, Chen HC, Gedebou TM, Ozkan O,, Chana J. Deltopectoral flaprevisited: role of the extended flap in reconstruction of the head and neck.Scand J Plast ReconstrSurg Hand Surg 40:275-280,20064-Coskunfirat OK, Özkan Ö. Reversed anterior interosseous flap.J Plast Reconstr Aesthet Surg59:1336-1341, 20065-Özkan Ö, Coskunfirat OK, Dogan O, Ozgentas HE. A reverse-flow flap model in the rat. J PlastReconstr Aesthet Surg60:556-562,2007

Expansion of Surviving Skin Paddle ofNeurocutaneous Island Flaps in Rats by VEGFGulsum Tetik Menevse, M.D., 1 Kemal Islamoglu, M.D., 1and Halil Ege Ozgentas, M.D. 1ABSTRACTThe purpose of this study was to investigate whether vascular endothelial growthfactor (VEGF) can enlarge the skin paddles of neurocutaneous flaps in rats. Wistar albinorats were used in four groups: Group 1, (n ¼ 10): neurocutaneous island flap; Group 2,(n ¼ 10): neurocutaneous island flap, surgical delay; Group 3, (n ¼ 10): neurocutaneousisland flap, VEGF; Group 4, (n ¼ 10): graft. A 3 3-cm, neurocutaneous island flap waselevated on the anterolateral skin of the thigh of the rats. The surviving flap areas were29.7 1.43 percent in Group 1, 41.3 3.24 percent in Group 2, 94.2 1.46 percent inGroup 3. There were no surviving areas in Group 4. The vascular networks of Group 3animals were more intensive and diffused on microangiography and the histopathologicfindings were better in this group. The surviving flap areas in Group 3 animals wereenlarged approximately three times over the original size.KEYWORDS: VEGF, flap, neurocutaneous, paddle expansionNeurocutaneous flaps are elevated on a nervepedicle without using any major artery. The blood supplyof these flaps is provided by the vessels supplying thenerve. The skin paddle of neurocutaneous flaps is restrictedas in other cutaneous flaps. When a neurocutaneousflap is elevated larger than its original sizefor closing large defects, flap necrosis will be inevitable.If the blood circulation of neurocutaneous flap areas canbe increased by chemical or surgical means, larger andmore reliable flaps can be elevated. Vascular endothelialgrowth factor (VEGF) is one of the most powerfulangiogenetic factors. 1 It increases vascular permeability,builds up growth of endothelial cells, and induces angiogenesis.2 The purpose of this study was to investigatewhether VEGF can enlarge the dimensions of thesurviving skin paddle of the neurocutaneous flap inrats. The effects of VEGF were compared in this studywith the surgical delay phenomenon, another method forincreasing flap vascularity and enhancing the resistanceof flap against ischemia.MATERIALS AND METHODSWistar albino rats, (n ¼ 44) 6-month-old females, wereused for this study. The weights of the rats rangedbetween 200 and 260 gr (mean: 230 gr). The studywas approved by the Animal Care Committee of AkdenizUniversity School of Medicine and supported by theAkdeniz University Research Foundation. Surgical andmicroangiographic studies were done under generalanesthesia with 100 mg/kg intraperitoneal ketamineand 20 mg/kg intramuscular xylazine. The right thighof the rat was shaved and cleaned with povidone iodinebefore surgery. Tramadol HCl (20 mg/kg) was given foranalgesia after surgery. All rats were housed undertemperature- and light-controlled laboratory conditionsDownloaded by: Akdeniz University. Copyrighted material.1 Department of Plastic and Reconstructive Surgery, Antalya, Turkey.Address for correspondence and reprint requests: KemalIslamoglu, M.D., Department of Plastic Reconstructive Surgery,Akdeniz University School of Medicine, 07059 Antalya, Turkey.J Reconstr Microsurg 2007;23:99–106. Copyright # 2007 byThieme Medical Publishers, Inc., 333 Seventh Avenue, New York,NY 10001, USA. Tel: +1(212) 584-4662.Accepted for publication October 11, 2006.DOI 10.1055/s-2007-970190. ISSN 0743-684X.99

Experimental StudyPermanence of Diced Cartilage, Bone Dustand Diced Cartilage/Bone Dust Mixture inExperimental Design in Twelve WeeksKemal Islamoglu, MD, Mustafa Bahadir Dikici, MD, Halil Ege Özgentas$, MDAntalya, TurkeyBone dust and diced cartilage are used for contourrestoration because their minimal donor site morbidity.The purpose of this study is to investigatepermanence of bone dust, diced cartilage and bonedust/diced cartilage mixture in rabbits over 12 weeks.New Zealand white rabbits were used for this study.There were three groups in the study: Group I: 1 mLbone dust. Group II: 1 mL diced cartilage. Group III:0.5 mL bone dust + 0.5 mL diced cartilage mixture.They were placed into subcutaneous tissue of rabbitsand removed 12 weeks later. The mean volumes ofgroups were 0.23 T 0.08 mL in group I, 0.60 T 0.12 mLin group II and 0.36 T 0.10 mL in group III. Thedifferences between groups were found statisticallysignificant. In conclusion, diced cartilage was foundmore reliable than bone dust aspect of preserving itsvolume for a long period in this study.Key Words: Bone dust, diced cartilage, filling material,resorptionAlot of filling materials have been using forcontour restoration in craniofacial surgeryfor aesthetic and reconstructive purposes.These may be heterogenic or autogenicmaterials. 1 Heterogenic materials may expose orcause infection and need secondary surgery for removingof them. Although autogenic materials aremore biocompatible than heterogenic materials, thereare two main handicaps for them: First is donor sitemorbidity. On the other hand, avoidance from donorsite morbidity is first preference reason for heterogenicmaterials. For this reason, bone dust andFrom the Department of Plastic and Reconstructive Surgery,Akdeniz University School of Medicine, 07059 Antalya, Turkey.Address correspondence and reprint requests to Kemal Islamoglu,MD,Akdeniz University School of Medicine, Department of Plasticand Reconstructive Surgery, 07059 Antalya, Turkey; E-mail:islamoglu@akdeniz.edu.trdiced cartilage, whose donor site morbidity is moreminimal than other autogenic materials, are used inaesthetic and reconstructive cases. Second handicapis resorption of autogenic filling materials by thetime. If they can be brought to defect with theirvascular pedicle, any resorption can not be expected.Nevertheless, pedicled or free flaps may be a ponderousprocedure for medium or small defects infacial or cranial bones. Purpose of this study is toinvestigate permanence of bone dust, diced cartilageand bone dust- diced cartilage mixture in rabbitsduring 12 weeks.METHODSNew Zealand white rabbits, N = 18, were used forthis study. The weights of rabbits rangedbetween 1.8Y3 kg (Mean: 2.39 T 0.39 kg). The rabbitswere anesthetized with xylazine hcl 2 mg/kg andketamin hcl 25 mg/kg IV. All animals were housed inindividual cages in a temperature- and light-controlledholding room. They were fed with standard rabbitchowandtapwateradlibitum.There were three groups in the study: Group I,(N = 6): 1 mL bone dust; group II, (N = 6): 1 mL dicedcartilage and group III, (N = 6): 0.5 mL bone dust +0.5 mL diced cartilage (Total 1 mL). Bone dusts wereharvested on parietal bone of the rabbit via micromotorsystem (Fig 1). The bone was not cooled asthe dust was harvested. Cartilages were removedfrom the ears of the rabbits and then cut in pieces of0.5Y1 mm using a #11 blade (Fig 2). Their volumeswere adjusted as 1 mL by using a syringe (Fig 3). Allfilling materials were pressed tightly not to leave anyair cavity inside of them (Fig 4). They were placedunder subcutanous tissue at the right retroauricularregion of the rabbits, after wrapping of them withsurgicell (Oxidized cellulose) (Fig 5).They were removed from the rabbits 12 weekslater. Volumes of filling materials were measuredwithin a vitreous container: The filling material wasplaced into a filled container. The fluid amount caused905Copyright @ 2006 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.

Scand J Plast Reconstr Surg Hand Surg, 2006; 40: 275280ORIGINAL ARTICLEDeltopectoral flap revisited: Role of the extended flap in reconstructionof the head and neckScand J Plast Surg Recontr Surg Hand Surg Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/12/10For personal use only.GUAN-MING FENG 1 , EMANUELE CIGNA 2,3 , HSING-KUANG LAI 2 ,HUNG-CHI CHEN 2 , TEWEDOROS M. GEDEBOU 2 ,ÖMER ÖZKAN 2 &JAGDEEP CHANA 2Departments of Plastic and Reconstructive Surgery, 1 Kaohsiung Armed Forces General Hospital, Kaohsiung, 2 E-Da Hospital/I-Shou University, Yan-chau Shiang, Taiwan, 3 University of Rome ‘‘La Sapienza’’, Rome, ItalyAbstractThe extended deltopectoral flap is still the best choice in selected cases. During the period 1987-2004, 34 patients requiredreconstruction of the head and neck using this flap. Twenty-nine had had one or more failed attempts at microsurgicalreconstruction after excision of cancer. Five were treated primarily. The flap was divided at least three weeks after theprimary operation. All 34 survived, and there were no donor site complications. Twenty-seven patients had anuncomplicated outcome, but the remaining seven required later closure or skin grafting, usually under local anaesthesia,for complications. The extended deltopectoral flap has been used successfully to provide stable coverage of defects in thehead and neck and should remain in the armamentarium of reconstructive microsurgeons.Key Words: Deltopectoral flap, extended deltopectoral flap, head and neck reconstruction, free flap failure, perforator flapIntroductionIn 1917 Aymard reported a flap from the chest thatis now identified as the deltopectoral (DP) flap,which was further refined by Joseph in the 1930s andwas popularised only 40 years ago (in 1965) byBakamjian [1,2]. Many authors have since describedthe versatility of this flap (with various modifications)including microsurgical transfer [38]. Severalattempts have been made to extend the length ofthe flap beyond the anterior axillary line, incorporatingthe delay phenomenon, which requires anotheroperation [6,8,9]. Initially popular, the DP pedicledflap was used routinely for reconstruction of defectsof the lower head and neck. The unattractive scar ofthe donor site, the limited arc of rotation, and thehigh rate of complications led the DP flap to fallfrom grace as soon as other methods of tissuetransfer to the head and neck had been developed[10]. The pedicled pectoralis major flap provides alonger, bulkier flap, and is somehow better hidden,although still leaving an unattractive donor scar[1016].Nowadays the treatment of head and neck cancerrequires a multidisciplinary approach. Surgery,radiotheraphy, and chemotherapy compromisewound healing resulting in weak tissues. Whenprevious reconstruction has failed, or when there islocal recurrence, a poor prognosis, or compromisedgeneral health, even covering the defect may be achallenge for a plastic surgeon. Although the advantagesof free tissue transfer have led to theabandonment of pedicled flaps from the chest, thereare still indications for the extended DP flap.Patients and methodsWe identified 34 patients with disease of the oralcavity that required reconstruction with an extendedDP flap between 1987 and 2004, and reviewed themretrospectively. Clinical details, characteristics of theflap, operation, and outcome were reviewed.Correspondence: Chen Hung-Chi, MD, MHA, FACS, Department of Plastic Surgery, 1, E-Da Road, Jiau-shu Tsuen, Yan-chau Shiang, Kaohsiung County,Taiwan R.O.C., 824. Tel: /886-7-615-0011. Fax.: /886-7-615-5581. E-mail: ed100002@edah.org.tw(Accepted 17 March 2006)ISSN 0284-4311 print/ISSN 1651-2073 online # 2006 Taylor & FrancisDOI: 10.1080/02844310600759574

Journal of Plastic, Reconstructive & Aesthetic Surgery (2007) 60, 556e562A reverse-flow composite flap in the ratÖmer Özkan a, *, O. Koray Cosxkunfırat a ,Özlenen Dogan b ,H. Ege Özgentasxa Akdeniz Üniversitesi Hastanesi, Plastik ve Rekonstrüktif Cerrahi Anabilim Dalı,B Blok kat 5, 07059 Antalya, Turkeyb Department of Plastic and Reconstructive Surgery, Akdeniz University Faculty of Medicine,Antalya, TurkeyReceived 15 October 2004; accepted 18 January 2006KEYWORDSReverse-flow flap;Rat;EarSummary Reverse-flow flaps are currently particularly used for the reconstructionof defects of the distal part of the extremities. Despite their common usage therehave been many reports of postoperative complications, especially resulting in partialor total flap necrosis. There is insufficient knowledge of flap haemodynamics,physiology and wound healing properties in reverse-flow flaps. Development ofthe proper experimental models is needed to investigate these issues. The purposeof this study was to describe a new reverse-flow flap model in the rat. A total of 20adult Wistar rats weighing 200e250 g were used in this experiment. In five rats, thevascular anatomy of the auricle of the rat was determined by anatomic dissectionand microangiography. In the experimental group (N ¼ 5), 1 1 cm reverse-flowcomposite flaps were harvested as a semi-island shape, based on the distal courseof the medial branch of the anterior auricular artery. In the control group, consistingof five rats, the flap was designed and raised based on the proximal course of themedial auricular artery, again in a semi-island shape. In the remaining five animals,a square-shaped composite tissue of the whole layer of the auricle, 1 1 cm in size,was harvested dividing all the bases circumferentially. The composite tissue was replacedin situ. While the former was considered a conventional antegrade-flow flapsubgroup, the latter was designated as a graft subgroup. All flaps were replaced insitu. The survival of the flap was evaluated on postoperative day 7 by direct observationand microangiography. The skin island of all the reverse-flow flaps and conventionalantegrade-flow flaps survived completely giving a success rate of 100%,whereas all grafts in the control group underwent complete necrosis. Microangiographicstudies revealed the vascularity of the reverse-flow and antegrade-flow* Corresponding author.E-mail address: omozkan@hotmail.com (Ö. Özkan).1748-6815/$ - see front matter ª 2006 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.bjps.2006.01.034

Journal of Plastic, Reconstructive & Aesthetic Surgery (2006) 59, 1336e1341Reversed anterior interosseous flapO. Koray Coskunfirat*, Ömer ÖzkanDepartment of Plastic and Reconstructive Surgery, Akdeniz University School of Medicine,Dumlupinar Bulvari, Kampus, 07059 Antalya, TurkeyReceived 8 May 2006; accepted 6 June 2006KEYWORDSReversed flap;Anterior interosseousSummary Reversed flaps from the forearm have been firmly established for handcoverage. Each has its own advantages and disadvantages. The reversed anteriorinterosseous flap is one option with special advantages in hand reconstruction.From January 2002 to July 2003 we used this flap in five consecutive male patientsaged between 36 and 59. The defects were located on the first web space (2), onthe dorsal side of the thumb (1), on the first metacarpal bone (1), and on the volarside of the wrist (1). Flap size was between 6 3 cm and 11 7 cm. All flaps healedwithout any problem and no complication was observed during the postoperativeperiod.The major advantage of this flap is the preservation of the main arteries of theupper limb. Other advantages are as follows: good texture and colour for hand reconstruction,satisfactory rotation arc, and availability of composite and fascialflaps. Besides its advantages, the major disadvantages are unsightly donor area scarand the need for meticulous technique.As a conclusion, we found this flap very useful in hand reconstruction for coverageof small and moderate sized soft tissue defects of the hand.ª 2006 Published by Elsevier Ltd on behalf of British Association of Plastic,Reconstructive and Aesthetic Surgeons.In search of flap options to cover hand defects, forearmhas become an appealing donor site with various flapalternatives. 1 Pedicled flaps from the forearm enablesfaster and reliable reconstruction. The consistent* Corresponding author. Akdeniz Üniversitesi Tıp Fakültesi,Plastik ve Rekonstrüktif Cerrahi AD, Dumlupınar Bulvarı, 07059Antalya, Turkey. Tel.: þ90 242 3118627.E-mail address: coskunfirat@superonline.com (O.K.Coskunfirat).well-described vascular anatomy of the upperlimb has allowed surgeons to introduce differentkinds of reversed flaps for hand reconstruction.The ideal flap should be reliable and robust andit should have constant anatomy and minimummorbidity.The most common flap used as reversed pedicledis the radial forearm flap, and the ulnar forearm flapwas also popularized for the same purposes. 2e5Although major arteries of the upper limb have to1748-6815/$-seefrontmatterª2006BritishAssociationofPlastic, Reconstructiveand AestheticSurgeons. PublishedbyElsevier Ltd. All rightsreserved.doi:10.1016/j.bjps.2006.06.021

Patoloji Anabilim Dalı1-Gökhan G, Akyüz M,Gürer İE,Tuncer R: Epitheloid hemangioendothelioma derived from the spineregion: case report and review of the literature Wiener Klinische wochen schrift. The MiddleEuropean J.of Medicine118)11-12):358-361,2006.2-Güney K, YıldaşB, Özbilim G, Sarıhan Ş, Balkan E:Detection of micrometastatic tumor clls in headand neck squamous cell carcinoma. A possible predictor of recurrences?.Saudi MedJ28(2): 216-220,2007.3-Yorulmaz G, Erdoğan G, Peştereli HE,Erdogan G Savaş B, Karaveli F:Epitheloid leuiomyocarcomawith rhabdoid features.Wiener Klinische Wochenschrift119(17-18): 557-560,2007.4-Demir D, Mendilcioğlu I, Peştereli E, et al. :Prenatal diağnosis of partial trisomy 18 (18p11.2-gter) ina fetus associated with increased nuchal translucency.Chromosome Research 15: 129-129suppl.,2007.5-Peştereli HE,Çolak T, Erdogan G, Karaveli Ş :Effect of hormone receptor positivity in c-erbB-2positive breast carcinomas.Virchows Archiv451(2):203-204,2007.6-Erdoğan G, Peştereli HE, Çolak T, Karaveli Ş : Fascin expression in invasive ductal carcinoma ofbreast.Virchows Archiv451(2):206-206,2007.7-Erdogan G, Başsorgun CI, Peştereli HE, Şimşek T, Karaveli Ş :C-kit protein expression in uterineand ovarian mesenchymal tumours.APMİS115(3):204-209,2007.8-Arici S, Ataizi C, Ayhan S, Bilezikci B, Demirkan N, Dizdaroğlu F, Dogusoy G, Doran F, Dursun A,Elpek O, et al:Gastrointestinal epithelial dysplasia/neoplasia: Where do Turkish pathologists stand-East or West?.Vırchows Archiv 451 (2): 179, AUG 2007.ŀTıbbi9-Gokhan GA, Kupesiz GY, Elpek GO:Hepatocyte antigen expression in subtypes of intestinalmetaplasia of the stomach.Vırchows Archiv 451 (2): 233, AUG 2007.10-Ozbey C, Gokhan GA, Elpek GO, et al.:Undifferentiated embryonal sarcoma of the liver: A casereport .Vırchows Archiv 451 (2): 367-368 AUG 2007.11-Bozova S, Elpek GO:Hypoxia-inducible factor-1 alpha expression in experimental cirrhosis:correlation with vascular endothelial growth factor expression and angiogenesis.APMIS 115 (7): 795-801 JUL 2007.12-Elpek GO, Bozova S, Kupesiz GY, et al.:An unusual cause of cholecystitis: Heterotopic pancreatictissue in the gallbladder.World Journal of Gastroenterology 13 (2): 313-315 JAN 14 2007.13-Akcam M, Artan R, Gelen T, et al. : Long-term aspects of nodular-gastritis in children.PediatricsInternational49(2): 220-225 APR.2007.14-Kupesiz G, Sakr W, Cher M.et al: Effect of soy isoflavone supplementation on prostatetissue,markers of prolifretion and apoptosts and histopathological endpoints of tumor grade.,volumeand stage.Wirchows Archiv451 (2):412-412 AUG 2007.15- Kupesiz GY, Butler C, Pansari V, et al: Is the auter perpheral zone/sub capsula, tissuecompartment of the prostate more susceptible to carcinogenesis and early neoplastic transformation?A topographic morphologic and tissue micro array immunohistochemical study.Virchows Archiv451(2):416-416 AUG 2007.16-Kupesiz GY, Powell I, Grignon D,et al. :Pathologic characteristics of prostate cancer in AfricanAmerican and caucasian mendiagnosed and treated at of below 50 years of age: Racial differencesare most evident in the younger age bracket.Wirchows Archiv451 (2):417-418 AUG 2007.

17-Kupesiz GY,Powell I,Grignon D, et al.:Potential differences in the clinicopathological profile offamilial/hereditary and sporadic prostate cancer.Wirchows Archiv451 (2):418-418 AUG 2007.18-Kupesiz GY, Akkaya B, Tezcan G, et al. :Cox 2 and CD 34 exqression in wilms tumor(nephroblastoma).Wirchows Archiv451 (2):514-514 AUG 2007.19-Ozbudak IH, Shilo K, Galvin JR, et al.:Pulmonary angiomyolipoma: Clinicopathological analysis of2 new cases and 10 previously reported cases.Wirchows Archiv451 (2):423-423 AUG 2007.20-Ozbudak IH, Shilo K, Galvin JR, et al.:Extramedullary hematopoiesis in pulmonary spindle celltumors: Rare and unusual association.Wirchows Archiv451 (2):423-423 AUG 2007.21-Ozbudak IH, Tavora f, Rassaei N, et al.:Glucose transporter-1 expression in pulmonaryneuroendocrine carcinoma.Wirchows Archiv451 (2):524-524 AUG 2007.22-Tavora F, Ozbudar I, Shilo K, et al. :İnflamatorymyofibroblasttic tumors of the lunf are negative forHHV-8. Wirchows Archiv451 (2):423-424 AUG 2007.23-Burke A, Tavora F, Ozbudak IH, et al.:Pediatric cardiac sarcomas, a series of 16 new cases withliterature review.Wirchows Archiv451 (2):489-490 AUG 2007.24-Rassaei N, Tavora F, Ozbudak I, et al.: Thyroid transcription factor-1 (TTF-1) expression inpulmonary neuorendocrine carcinomas: Clone -based variability.Modern Pathology20:329A-329,1515suppl.2 MAR 2007.25-Tavora F, Shilo K, Ozbudak IH, et al.:Absence of human herpesvirus-8 in pulmonary inflammatorymyofibroblastic tumor: immunohistochemical and molecular analysis of 20 cases.ModernPathology20(9): 995-999, SEP 2007.26-Frazier AA, Granks TJ, Mohammed TLH, Ozbudak IH, et al. : From the archives of the AFIP-Pulmonary veno-occlusive disease andpulmonary capillaryhemangiomatosis.Radiographics27(3):867-882,MAY-JUN 2007.27-Başsorgun CI,Unal B, Ozbudak IH, Akkaya B, Çiftçioğlu A: p27 and high molecular weighcytokeratin expression in prostatic atrophy and postatrophic hyperplasia.Wirchows Archiv451(2): 415-415 AUG 2007.28-Kalay S, Akman S, Akkaya B, et al.:Beneficial effect triple treatment (ACEI, ATIRB, statin) plusimmunoglobulin in experimental nephrotic syndrome.Clinical Chemistry53 (6):A160-A160 D-6 Suppl.S JUN 2007.29-Özbilim G, Uğuz A, Özbudak İH, et al.: Cliarry dysmorphology. Ultrastructural findings in 12patients. VIRCHOWS ARCHIV, 451:2, 427, AUG 2007.30- Başsorgun CI, Özbilim G, Özbudak İH: Expression of the c-kit and ki-67 proliferation index inpatients with lung cancer. VIRCHOWS ARCHIV, 451:2, 427, AUG 2007

358 Gokhan et al., Epithelioid hemangioendothelioma derived from the spine regionCase ReportWien Klin Wochenschr (2006) 118/11–12: 358–361DOI 10.1007/s00508-006-0582-5WIENER KLINISCHEWOCHENSCHRIFTThe Middle European Journalof MedicinePrinted in AustriaEpithelioid hemangioendothelioma derived from the spine region:Case report and review of the literatureGuzide Ayse Gokhan 1 , Mahmut Akyuz 2 , Inanc Elif Gurer 1 , and Recai Tuncer 21Department of Pathology, Akdeniz University Faculty of Medicine, Antalya, Turkey2Department of Neurosurgery, Akdeniz University Faculty of Medicine, Antalya, TurkeyReceived May 4, 2005, accepted after revision January 5, 2006© Springer-Verlag 2006Epitheloides Hämangioendotheliom der WirbelsäuleZusammenfassung. Epitheloide Hämangioendotheliome(EHE) sind seltene Gefäßtumore, die im Allgemeinenim Weichteilgewebe entstehen. Primäre KnochenEHEs, besonders solche im Wirbelsäulenbereich, sindsehr selten.Wir präsentieren den Fall eines 30-jährigen Mannes,der mit lumbalen Schmerzen, Gehproblemen, Harninkontinenzund einem tauben Gefühl in der kaudalen Regionstationär aufgenommen wurde.Die Röntgenaufnahme zeigte einen lytischen Prozessam Wirbelkörper L2 und einen Kollaps des WirbelkörpersL1. Es wurden eine operative Entfernung desWirbels L1 und eine totale Resektion des Tumors durchgeführt.Die histopathologische und immunhistochemischeUntersuchung des Tumorgewebes unterstützte dieDiagnose des EHE.In dem vorliegenden Bericht wird der nach unseremWissen fünfte Fall eines EHE in der Wirbelsäule mit allenklinisch-pathologischen Befunden in der Literatur präsentiert.Summary. Epithelioid hemangioendotheliomas (EHE)are rare vascular tumors which generally originate fromsoft tissues and visceral organs. Primary bone EHEs,especially those occurring in the spine region, are extremelyrare.Our case is that of a 30-year-old man who wasadmitted to hospital with low back pain, difficulty in walking,post-voiding urinary incontinence and numbness inthe caudal area. X-ray showed a lytic process affectingthe vertebra L2 and collapse of L1. Vertebrectomy ofL1and gross total tumor resection were performed. Histopathologicaland immunohistochemical findings of the tumortissue supported the diagnosis of EHE. The case,which to the best of our knowledge is only the fifth suchreported case, is presented with its clinicopathologicalfindings and a review of the literature.Key words: Epithelioid hemangioendothelioma, vertebra.IntroductionHemangioendotheliomas (HEs) are vascular tumorswith biologic behavior intermediate between hemangiomasand angiosarcomas. Histopathologic subtypes of HEshave been classified as epithelioid, kaposiform, Dabskatumor (papillary intralymphatic angioendothelioma), retiform(hobnail hemangioendothelioma) or composite. Thetumors have variable ability to recur and metastasize;EHE is the most aggressive member of this family. It istherefore important to distinguish EHE from other subtypesof HE and epithelioid counterparts of hemangiomaand angiosarcoma. EHEs affect all age groups and mostlyoriginate from soft tissues of the extremities, lung andliver [1–4]. Bones, especially vertebrae, are rare presentingsites for these tumors.CaseA 39-year-old man was admitted to our hospital with a2-year history of low back pain radiating to both legs, a3-month history of difficulty in walking and a 2-day history ofpost-voiding urinary incontinence and numbness in the caudalarea. Neurological examination revealed bilateral weakness andloss of reflexes in the lower extremities, as well as bilateralsensory loss to pinprick at the level of Th 12. The patient alsohad markedly decreased anal sphincter tonus. Routine laboratoryevaluation, including erythrocyte sedimentation rate, wasfound to be in normal range. Postoperatively, the patient wasmobilized and discharged.Radiographic evaluationA review of the initial anteroposterior and lateral spineradiographs revealed a lytic lesion affecting vertebrae L1 andL2 and collapse of L1. On magnetic resonance imaging (MRI)the lesion had low signal intensity on T1-weighted studies, withslightly high signal intensity on T2-weighted studies (Fig. 1).A T1-weighted study after contrast administration showed anextramedullary mass extending from the level of L1 to L2(Fig. 2). The mass destroyed L1 and extended anteriorly andlaterally into the retroperitoneal area, and posteriorly into thespinal canal. Spinal arteriography was performed to evaluate

Detection of micrometastatic tumor cells in head and neck squamous cellcarcinoma. A possible predictor of recurrences?Med J. 2007 Feb;28(2):216-20.Guney K, Yoldas B, Ozbilim G, Derin AT, Sarihan S, Balkan E.Department of Otolaryngology and Head and Neck Surgery, Akdeniz University Faculty of Medicine, Antalya,Turkey.sevtapv@akdeniz.edu.trAbstractOBJECTIVE: To evaluate the presence of micrometastatic tumor cells in the peripheral blood samples of the patients with head andneck squamous cell carcinoma (HNSCC) and to determine whether the presence of micrometastatic cells had any biological relevance interms of local recurrences or metastasis during a follow-up period of 3 years.METHODS: We included 21 consecutive patients with untreated primary HNSCC admitted to the Ear Nose and Throat Department ofAkdeniz University Medical School, Antalya, Turkey between February and October 2002. Squamous carcinoma cells in peripheral bloodsamples of these patients prior to surgery were detected via a magnetic cell separation technique using anti-epithelial cell adhesionmolecule antibody, and thereafter evaluated by light microscopy with hematoxylin and eosin staining.ŀSaudiRESULTS: Seven out of 21 patients showed squamous carcinoma cells in peripheral blood samples. Patients with stage III and IVtumors were nearly 5 times more likely to show micrometastatic cells compared with those with stage I and II tumors (6/12 versus 1/9).During the follow-up, 2 patients out of 7 with micrometastasis had recurrences. None in the micrometastasis negative group relapsed.CONCLUSION: We suggest that HNSCC patients with detectable tumor cells in peripheral blood represent a subset of patients whoshould be followed up more closely for possible recurrences.PMID: 17268699 [PubMed - indexed for MEDLINE]

Case ReportWien Klin Wochenschr (2007) 119/17–18: 557–560DOI 10.1007/s00508-007-0822-3WIENER KLINISCHEWOCHENSCHRIFTThe Middle European Journalof MedicinePrinted in AustriaEpithelioid leiomyosarcoma with rhabdoid featuresGülnur Yorulmaz 1 , Gülgün Erdogan 1 , Hadice Elif Pestereli 1 , Burhan Savas 2 ,and Fatma Seyda Karaveli 11Akdeniz University, Department of Pathology, Antalya, Turkey2Akdeniz University, Department of Medical Oncology, Antalya, TurkeyReceived November 29, 2006, accepted after revision April 16, 2007© Springer-Verlag 2007Epitheloides Leiomyosarkom mit rhabdoidenEigenschaftenZusammenfassung. Uterine Sarkome gehören zuden seltener auftretenden malignen Neoplasien, wobeidie Leiomyosarkome (LMS) die am häufigsten vorkommendenWeichteilsarkome repräsentieren. Die meistenLeiomyosarkome besitzen die für sie typischen histologischenCharakteristika. Nur außerordentlich seltene Variantenbeinhalten Riesenzellen, epitheloide und myxoideZellen. Heterologe mesenchymale Komponenten (skelettartigerMuskel, Fettgewebe, Gefäße) können ebenfallsin diesen Tumoren vorkommen.Das Auftreten von rhabdoiden Zellen wurde in verschiedenenArten maligner Neoplasien berichtet. Es wurdefestgestellt, dass das Vorkommen dieser Zellen dasVerhalten von Neoplasien ins Maligne beeinflussen kann.Wir berichten über einen Fall eines epitheloiden Leiyomyosarkomsmit rhabdoiden Eigenschaften bei einer 56-jährigen Patientin – eine bislang nur selten beschriebeneKombination.Summary. Leiomyosarcomas (LMS) are the mostcommon type of uterine sarcoma. Most LMS have typicalhistologic features, and variants such as epithelioid LMS,myxoid LMS, LMS with osteoclast-like giant cells andLMS with rhabdoid features occur only rarely.Rhabdoid cells were first described in rhabdoid tumor,a distinctive renal neoplasm of infancy. Such tumorsare composed of diffuse proliferation of rhabdoid cellsthat are round or polygonal in shape with eccentric nuclei,prominent nucleoli and glassy eosinophilic cytoplasmcontaining hyaline-like inclusion bodies. In the literature,extrarenal localizations of malign rhabdoid tumors havebeen described in a variety of primary sites such as thecentral nervous system, liver, skin and soft tissues. Thesecharacteristic rhabdoid cells have been reported in sarcomasand carcinomas of various types and in a fewcases of uterine sarcomas. The presence of rhabdoidcells in tumors is considered to be a predictor of aggressivetumor behavior.Our case is that of a 56-year-old woman who wasadmitted to the state hospital with left inguinal mass.Microscopically the tumor was admixed of three differenttypes of cell with spindle, epithelioid or rhabdoid features.Immunopositive cytoplasmic staining for myoglobulin anddesmin was seen in rhabdoid cells, and cytokeratin immunopositivitywas observed in epithelioid and somerhabdoid cells. Epithelioid cells and spindle cells werealso SMA positive. The histopathologic and immunohistochemicalfindings support the diagnosis of epithelioidLMS with rhabdoid features. We report this very uncommonLMS variant; to the best of our knowledge there areonly a few cases in the English literature.Key words: Epithelioid leiomyosarcoma, rhabdoidfeatures.IntroductionUterine sarcomas are relatively rare neoplasms. Leiomyosarcoma(LMS) represents the most common pureuterine sarcoma and comprises slightly over 1% of alluterine malignancies with an incidence reported to be0.3–0.4/100,000 women per year [1]. Most LMS are of aconventional and/or well differentiated type [2] and aresubdivided into several variants such as epithelioid, myxoid,inflammatory, pleomorphic, dedifferentiated and withosteoclast-like giant cells and rhabdoid cells [2, 3].Rhabdoid cells are characterized by a large abundanteosinophilic cytoplasm with an irregular eccentric nucleusand round eosinophilic cytoplasmic inclusions correspondingto whorls of intermediate filament [4]. Thesecharacteristic cells are present in malignant rhabdoid tumors,a distinct subtype of pediatric renal neoplasm. Inthe literature, several soft-tissue sarcomas such as synovialsarcoma, extraskeletal myxoid chondrosarcoma,LMS, distal type epithelioid sarcoma, malignant mesotheliomaand rhabdomyosarcoma are reported to containrhabdoid cells as well as characteristic sarcomatous cells[5]. In addition, several epithelial tumors with a rhabdoidcell have been described in a variety of primary sites suchas renal cell carcinoma, urothelial carcinoma and muci-

(Karaveli, F. Seyda)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 203-204 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀAuthor(s): Pestereli HE (Pestereli, H. Elif), Colak T (Colak, Taner), Erdogan G (Erdogan, Gulgun), Karaveli FS

Quant Cytol Histol. 2010 Apr;32(2):90-101.Comparison of the desmoplastic reaction and invading ability in invasive ductalcarcinoma of the breast and prostatic adenocarcinoma based on the expression ofheat shock protein 47 and fascin.Nese N, Kandiloglu AR, Simsek G, Lekili M, Ozdamar A, Catalkaya A, Coskun T.Department of Pathology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey. nalannese@hotmail.comAbstractOBJECTIVE: To investigate the diversity within invasive ductal carcinoma (IDC) and prostatic adenocarcinoma (PCa) by evaluatingimmunohistochemical expression of heat shock protein 47 (HSP47) and fascin, the molecules that are related to desmoplasia andinvasion, and analyze its correlation with clinicopathologic parameters.STUDY DESIGN: HSP47 and fascin immunoreactivity (IR) was evaluated in 49 mastectomies diagnosed as IDC and 57 radicalprostatectomies diagnosed as PCa. IR was evaluated as: 0: < 5%, 1+: 5-25%, 2+: 25-50%, 3+: > 50%.RESULTS: HSP47 and fascin were localized to cytoplasm, and HSP47 and fascin IR were higher in IDC and PCa than benign groups (p< 0.05). HSP47 IR in neoplastic cells was 42.1% and 28.6%, in stroma was 81.6% and 15.8% in IDC and PCa, respectively; fascin IR inneoplastic cells was 65.3% in IDC and 15.8% in PCa. Fascin expression ŀAnalcorrelated with estrogen receptor and progesterone receptornegativity, tumor size and stage in IDC and surgical margin status in PCa. HSP47 expression correlated bilaterality in PCa. HSP47positively correlated with survival in IDC.CONCLUSION: HSP47 and fascin expression may play role in the pathogenesis of IDC and PCa because their expression issignificantly higher in IDC and PCa than their normal counterpart. Although there is no relationship with recurrence or metastatic status,fascin overexpression correlated with tumor size, which may prompt its use as a prognostic factor in IDC.PMID: 20701077 [PubMed - indexed for MEDLINE]

APMIS 115: 204–209, 2007Printed in Denmark . All rights reservedC 2007 The AuthorsJournal Compilation C 2007 APMISISSN 0903-4641C-kit protein expression in uterine andovarian mesenchymal tumoursGÜLGÜN ERDOGAN, 1 C. IBRAHIM BASSORGUN, 1 H. ELIF PESTERELI, 1 TAYYÜP SIMSEK 2 andSEYDA KARAVELI 1Departments of 1 Pathology and 2 Obstetrics and Gynaecology, Akdeniz University, Antalya, TurkeyErdogan G, Bassorgun CI, Pestereli HE, Simsek T. Karaveli S. C-kit protein expression in uterine andovarian mesenchymal tumours. APMIS 2007;115:204–209.The protooncogene c-kit encoding transmembrane tyrosine kinase receptor protein plays an importantrole in the signal transduction pathway that regulates cellular growth and repair. Gene product KIToverexpression has been shown in a number of different neoplasms, particularly in mastocytosis andgastrointestinal stromal tumours (GIST). The morphologic similarity of uterine mesenchymal tumoursand GIST, and the presence of KIT protein in normal uterine tissue, suggests that uterinesarcomas may have the same c-kit overexpression. The purpose of this study was to determine theoverexpression of c-kit protein in uterine and ovarian sarcomas. Immunohistochemical staining usinga polyclonal anti-c-kit antibody was performed on tissue blocks from 12 carsinosarcomas, 14 leiomyosarcomas,8 endometrial stromal sarcomas, 2 adenosarcomas, 1 atypical leiomyoma, 1 leiomyomawith limited experience, and 10 leiomyomas. The slides were evaluated by a semiquantitativemethod. C-kit was positive in 10 of 12 (83%) carcinosarcomas, 10 of 14 (71%) leiomyosarcomas, 6 of8 75(%) endometrial stromal sarcomas, 1 of 2 (50%) adenosarcomas, 1 leiomyoma with limited experience,and 1 of 10 (10%) leiomyomas. The uterine sarcomas express c-kit, like GISTs. It seems thatKIT may have a significant role in the oncogenesis of mesenchymal tumours of the uterus and ovary.Key words: c-kit; uterine sarcomas.Gülgün Erdogan, Akdeniz Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, 07070 Antalya, Turkey.e-mail: gerdogan/akdeniz.edu.trThe protooncogene c-kit encodes a 145-kdtransmembrane tyrosine kinase receptor (KIT),which is located on chromosome 4(4q11–12) inthe human genome (1). The KIT receptor whoseligand is the stem-cell factor belongs to the familyof receptors for platelet-derived growth factorand colony-stimulating factor (2). It playsan important role in the signal transductionpathway that regulates cellular growth on repair(2). Somatic mutations of the c-kit gene causeconstitutive ligand-independent activation ofthe KIT receptor and up-regulation of cellulargrowth (2). Normally, KIT shows weak-to-moderateexpression in a wide variety of humanReceived 6 January 2006.Accepted 16 October 2006.cells, including mast cells, melanocytes, hematopoieticstem cells, germ cells, interstitial cells ofCajal, and normal ductal epithelia of the breast(1, 3). It is also expressed in normal tissues ofthe female genital tract (2–4). In addition, KITexpression has been identified in a number ofdifferent neoplasms, including mastocytosis/mast cell leukemia, acute myeloblastic leukemia,seminoma/dysgerminoma and gastrointestinalstromal tumours (GIST) (1, 2, 5). The morphologicsimilarity of uterine mesenchymal tumoursto GIST and the presence of KIT proteinin normal uterine tissue suggest that c-kit mayhave a significant role in the development andprogression of uterine sarcomas. In the literatureseveral gynaecological malignancies appearto produce the Kit receptor and there have been204

epithelial dysplasia/neoplasia: Where do Turkish pathologists stand -East or West?Author(s): Arici S (Arici, Sema), Ataizi C (Ataizi, Cigdem), Ayhan S (Ayhan, Semin), Bilezikci B (Bilezikci, Banu),Demirkan N (Demirkan, Nese), Dizdaroglu F (Dizdaroglu, Ferhunde), Dogusoy G (Dogusoy, Gulen), Doran F(Doran, Figen), Dursun A (Dursun, Ayse), Elpek O (Elpek, Ozlem), Ensari A (Ensari, Arzu), Gedikoglu G(Gedikoglu, Gokhan), Gokse S (Gokse, Suha), Gurbuz Y (Gurbuz, Yesim), Gursan N (Gursan, Nesrin), Kapran Y(Kapran, Yersu), Karabacak T (Karabacak, Tuba), Kayaselcuk F (Kayaselcuk, Fazilet), Kirimlioglu H (Kirimlioglu,Hale), Pak I (Pak, Isin), Polat A (Polat, Ayse), Sakiz D (Sakiz, Damlanur), Tuncyurek M (Tuncyurek, Muge), YerciO (Yerci, Omer), Ushiku T (Ushiku, Tetsuo), Ota S (Ota, Satoshi), Imura G (Imura, George), Itabashi M (Itabashi,Masayuki)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 179-179 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Istanbul Univ, Istanbul, Turkey2. Ankara Univ, TR-06100 Ankara, Turkey3. Ankara Onkol Hosp, Ankara, Turkey4. Univ Tokyo, Ibaraki Prefectural Cent Hosp, Tokyo, JapanPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀGastrointestinal

Author(s): Gokhan GA (Gokhan, Guzide Ayse), Kupesiz GY (Kupesiz, Gokben Yildirim), Elpek GO (Elpek,Gulsum Ozlem)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 233-233 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀHepatocyte antigen expression in subtypes of intestinal metaplasia of the stomach

Note: This copy is for your personal non-commercial use only. To order presentation-readycopies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights.AFIP ARCHIVES 867From the Archives of the AFIPPulmonary Veno-occlusive Disease andPulmonary Capillary Hemangiomatosis 1CME FEATURESee accompanyingtest at http://www.rsna.org/education/rg_cme.htmlLEARNINGOBJECTIVESFOR TEST 6After reading thisarticle and takingthe test, the readerwill be able to: Discuss the clinicalchallenge of discerningPVOD and PCHfrom other causes ofpulmonary arterialhypertension and theunique hemodynamicsof these two diseases. Identify the radiologicmanifestationsof PVOD and PCHthat strongly suggesttheir diagnosis. Describe the underlyinghistopathologicfeatures ofPVOD and PCH.TEACHINGPOINTSSee last pageAletta Ann Frazier, MD ● Teri J. Franks, MD ● Tan-Lucien H.Mohammed, MD, FCCP ● Irem H. Ozbudak, MD ● Jeffrey R. Galvin,MDPulmonary veno-occlusive disease (PVOD) and pulmonary capillaryhemangiomatosis (PCH) are two unusual idiopathic disorders that almostuniformly manifest to the clinician as pulmonary arterial hypertension(PAH). Impressive clinical signs and symptoms often obscurethe true underlying capillary or postcapillary disorder, thus severelycompromising timely and appropriately directed therapy. The hemodynamicsof PVOD and PCH are the consequence of a widespreadvascular obstructive process that originates in either the alveolar capillarybed (in cases of PCH) or the pulmonary venules and small veins(in PVOD). Since the earliest descriptions of PVOD and PCH, therehas been a debate as to whether these are two distinct diseases or variedexpressions of a single disorder. The cause of PVOD or PCH has notyet been identified, although there are several reported associations.Without curative lung or heart-lung transplantation, patients withthese conditions face inexorable clinical deterioration and death withinmonths to a few short years of initial presentation. Surgical lung biopsyis the definitive diagnostic test, but it is a risky undertaking in suchcritically ill patients. The imaging manifestations of PVOD and PCHoften reflect the underlying hemodynamic derangements, and thesefindings may assist the clinician in discerning PAH from an underlyingcapillary or postcapillary process with findings of septal lines, characteristicground-glass opacities, and occasionally pleural effusion.Abbreviations: PAH pulmonary arterial hypertension, PCH pulmonary capillary hemangiomatosis, PCWP pulmonary capillary wedge pressure,PPH primary pulmonary hypertension, PVOD pulmonary veno-occlusive diseaseRadioGraphics 2007; 27:867–882 ● Published online 10.1148/rg.273065194 ● Content Code:1 From the Departments of Radiologic Pathology (A.A.F., J.R.G.) and Pulmonary and Mediastinal Pathology (T.J.F.), Armed Forces Institute of Pathology,14th St and Alaska Ave NW, Washington, DC 20306; Department of Diagnostic Radiology, University of Maryland School of Medicine, Baltimore,Md (A.A.F., J.R.G.); Section of Thoracic Imaging, Division of Radiology, Cleveland Clinic Foundation, Cleveland, Ohio (T.-L.H.M.); andDepartment of Pathology, Akdeniz University School of Medicine, Antalya, Turkey (I.H.O.). Received December 6, 2006; revision requested December18 and received January 18, 2007; accepted January 25. All authors have no financial relationships to disclose. Address correspondence toA.A.F. (e-mail: frazier@afip.osd.mil ).The opinions and assertions contained herein are the private views of the authors and are not to be construed as official nor as representing the views ofthe Department of the Navy, Army, or Defense.

Pediatrics International (2007) 49, 220–225doi: 10.1111/j.1442-200X.2007.02329.xOriginal ArticleLong-term aspects of nodular gastritis in childrenMUSTAFA AKCAM , REHA ARTAN , TEKINALP GELEN , 1 AYGEN YILMAZ , ERDAL EREN , 3VEDAT UYGUN 2 AND HIKMET CIG 2Medical School, Departments of 1 Pathology and2Pediatrics, Akdeniz University, Antalya , and3MedicalSchool, Department of Pediatrics, Suleyman Demirel University, Isparta, TurkeyAbstractBackground : Close association of nodular gastritis and Helicobacter pylori infection has been initially provedby various studies. There have been some studies reporting microscopic and histologic recovery in a short timeafter eradication therapy. But there is not enough data about the long-term course of this condition. The aim ofthis study is to document current clinical conditions, presence of H. pylori and results of endoscopic and histologicexamination, after a long-term period, in children with endoscopically diagnosed antral nodularity.Methods : A total of 35 patients diagnosed as nodular antral gastritis by upper gastrointestinal endoscopy duringa 2 year period, were invited for re-evaluation and re-endoscopy after 3 years. Histopathologically, H. pyloridetected ones had been treated with standard triple eradication therapy. In total, 27 patients were accepted forenrollment in the study. Repeated endoscopy could be performed in all 27 patients.Results : The persistence of antral nodularity was detected in 18 of 27 patients. Decrease in symptoms, absenceof symptoms and presence of H. pylori infection were detected in 6, 8 and 16 (89%) of them, respectively.There was no statistical significance between the first and last endoscopic biopsies when activity, atrophy, intestinalmetaplasia and presence of follicles were regarded. Malt lymphoma could not be detected in any of thepatients.Conclusion : There is a strong association between nodular gastritis and H. pylori . Presence of antral nodularityin the long-term period may be related to H. pylori re-infection. New therapeutic approaches are requiredfor treatment and management of the patients diagnosed as nodular gastritis and living in areas endemic forH. pylori infection.Key words childhood , course , Helicobacter pylori , nodular gastritis .Correspondence: Mustafa Akcam, Department of Pediatrics, Divisionof Pediatric Gastroenterology, Hepatology and Nutrition,Akdeniz University, Medical School, Çocuk Sağlığ ı ve Hastal ı klar ıAD, Antalya 07059, Turkey. Email: makcam@akdeniz.edu.trReceived 11 October 2005; revised 1 December 2005; accepted26 December 2005.Nodular gastritis (NG) is usually characterized as presentingwith an endoscopic appearance that has been described as‘goose flesh’. 1 It is also characterized by intense inflammatorycell infiltration consisting mainly of monocytes and by increasednumbers of lymphoid follicles with a germinal center, in gastricmucosa. 2It has been known that common and universally distributedHelicobacter pylori infection is the most frequent reason forgastritis and peptic ulcer disease. This infection, predominantlyacquired in childhood, has been accepted as directly associatedwith gastric carcinoma and mucosa-associated lymphoidtissue (MALT) lymphoma. 3 The inflammation that H. pyloricauses in the gastric mucosa is not always observed macroscopicallywith endoscopy, but it is identified on the histologicexamination of gastric biopsies. 4A strong association between endoscopic detection of NGand presence of H. pylori has been established in previousstudies. 1,2,5 – 8 There are a few reports mentioning recovery ofthis nodular appearance after eradication treatment. 5,9 Thereis no definite reason for antral nodularity, and we could notrecognize any study about long-term follow up and evaluationof endoscopic and histologic changes after this time in theliterature.In the present study, re-evaluation of clinical conditions,presence of H. pylori and results of endoscopic and histologicexamination of children diagnosed as NG is aimed after amean 3 years follow up.

Author(s): Ozbey C (Ozbey, Caner), Gokhan GA (Gokhan, Guzide Ayse), Elpek GO (Elpek, Gulsum Ozlem),Melikoglu M (Melikoglu, Mustafa)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 367-368 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Sch Med, Dept Pathol, Antalya, Turkey2. Akdeniz Univ, Sch Med, Dept Pediat Surg, Antalya, TurkeyPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀUndifferentiated embryonal sarcoma of the liver: A case report

APMIS 115: 795–801, 2007Printed in Denmark . All rights reservedC 2007 The AuthorsJournal Compilation C 2007 APMISISSN 0903-4641Hypoxia-inducible factor-1a expression inexperimental cirrhosis: correlation with vascular endothelialgrowth factor expression and angiogenesisSEVGI BOZOVA and GÜLSÜM ÖZLEM ELPEKAkdeniz University, Medical School, Department of Pathology, Antalya, TurkeyBozova S, Elpek GO. Hypoxia-inducible factor-1a expression in experimental cirrhosis: correlationwith vascular endothelial growth factor expression and angiogenesis. APMIS 2007;115:795–801.Angiogenesis progresses together with fibrogenesis during chronic liver injury. Hypoxia-inducible factor-1a(HIF-1a), a master regulator of homeostasis, plays a pivotal role in hypoxia-induced angiogenesisthrough its regulation of vascular endothelial growth factor (VEGF). The association betweenhypoxia, angiogenesis and VEGF expression has been demonstrated in experimental cirrhosis. However,expression of HIF-1a has yet to be reported. The aim of this study was to investigate thesignificance of HIF-1a expression during experimental liver fibrosis and the relationships betweenHIF-1a expression, VEGF expression and angiogenesis. Cirrhosis was induced in male Wistar ratsby intraperitoneal administration of diethyl nitrosamine (DEN) (100 mg/kg, once a week). The serialsections from liver tissues were stained with anti-HIF-1a, anti-VEGF and anti-CD34 antibodies beforebeing measured by light microscopy. Our results showed that HIF-1a expression gradually increasesaccording to the severity of fibrosis (p0.01). Moreover, its expression was found to be correlatedwith angiogenesis (rΩ0.916) and VEGF expression (rΩ0.969). The present study demonstrates thatHIF-1a might have a role in the development of angiogenesis via regulation of VEGF during experimentalliver fibrogenesis and suggests that this factor could be a potential target in the manipulationof angiogenesis in chronic inflammatory diseases of the liver.Key words: HIF-1a; VEGF; cirrhosis; angiogenesis; immunohistochemistry.Gülsüm Özlem Elpek, Akdeniz University, Medical School, Yeni Tıp, Dekanlık, 07070, Antalya, Turkey.e-mail: elpek/akdeniz.edu.trAngiogenesis is frequently associated with hepaticfibrogenesis in the wound healing responseto chronic liver injury (1, 2). At present it is notclear whether this process is a simple response tomaintain homeostasis or one that exerts an additionalpathogenic role contributing to liverdamage (2–4). Nevertheless, the fact that chronicliver diseases respond poorly to conventionaltherapies suggests that the manipulation ofangiogenesis could be a promising approach totreatment. Consequently, efforts are being di-Received 29 September 2006.Accepted 19 January 2007.rected to revealing the exact role of angiogenesisduring liver inflammation and fibrogenesis, andthe cellular and molecular mechanisms that areinvolved in its development.A growing body of evidence indicates hypoxiato be an important inducer of angiogenesis duringhepatic injury and repair (2, 5–8). Furthermore,results of some studies suggest that duringfibrogenesis hepatocellular hypoxia mightplay an important role in the induction of vascularendothelial growth factor (VEGF) expression,a potent angiogenic mediator (6, 8). Hypoxia-induciblefactor-1 (HIF-1a), a master regulatorof homeostasis, plays a pivotal role in795

of human herpesvirus-8 in pulmonary inflammatory myofibroblastic tumor:immunohistochemical and molecular analysis of 20 casesAuthor(s): Tavora F (Tavora, Fabio), Shilo K (Shilo, Konstantin), Ozbudak IH (Ozbudak, Irem H.), Przybocki JM(Przybocki, Jean M.), Wang G (Wang, Guanghua), Travis WD (Travis, William D.), Franks TJ (Franks, Teri J.)Source: MODERN PATHOLOGY Volume: 20 Issue: 9 Pages: 995-999 Published: SEP 2007Times Cited: 4 References: 27 Citation MapDocument Type: ArticleLanguage: EnglishAuthor Keywords: inflammatory myofibroblastic tumor (IMT); human herpesvirus-8 (HHV-8); lungŀAbsenceAbstract: Inflammatory myofibroblastic tumors are uncommon lesions composed of spindled myofibroblastswithin a variable background of collagen and inflammatory cells. Although the true nature of these lesions is notfully elucidated, identification of consistent cytogenetic alterations in the anaplastic lymphoma kinase ( ALK) genesuggests that they may be neoplastic. A small number of inflammatory myofibroblastic tumors have been reportedto harbor human herpesvirus-8 ( HHV-8), implicating the virus in its pathogenesis. In this study, 20 cases ofpulmonary inflammatory myofibroblastic tumor were analyzed for the presence of HHV-8 withimmunohistochemical and molecular methods. In all cases, antibodies to the latent nuclear antigen of the viruswere applied. Four open reading frames ( ORFs), including ORFs K2, 16, 26, and 72, were targeted utilizingrealtime polymerase chain reaction ( PCR). The cohort included 9 men and 11 women with a mean age of 37years ( range, 1-81). Microscopically, the tumors were composed of cytologically bland spindle cells withmyofibroblastic differentiation. On immunohistochemical studies, 20% of cases ( 4/ 20) demonstrated diffusecytoplasmic positivity with ALK. Immunohistochemical staining for the latent nuclear protein of the virus wasnegative in all cases ( 0/20). All tumors ( 100%, 20/20) tested with real-time PCR were negative for all four ORFs,whereas 100% ( 10/10) of positive control Kaposi sarcoma cases were positive. Her2 gene expression waspresent in all ( 20/ 20) inflammatory myofibroblastic tumors confirming the presence of amplifiabledeoxyribonucleic acid in the tissue lysate. This study documents the absence of HHV-8 in pulmonaryinflammatory myofibroblastic tumors, suggesting that further investigation is required to clarify the pathogenesis ofthis lesion.KeyWords Plus: EPSTEIN-BARR-VIRUS; FIBROBLAST CELLS; LYMPHOMA-KINASE; DNA-SEQUENCES;PSEUDOTUMOR; INFECTION; DISEASE; 2P23; GENE; AMPLIFICATIONReprint Address: Shilo, K (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, 6825 16thSt NW, Washington, DC 20306 USAAddresses:1. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA2. Univ Akdenniz, Sch Med, Dept Pathol, Antalya, Turkey3. Armed Forces Inst Pathol, Mol Diagnost Lab, Washington, DC USA4. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USAE-mail Addresses: shilok@afip.osd.milPublisher: NATURE PUBLISHING GROUP, 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917USASubject Category: PathologyIDS Number: 203BGISSN: 0893-3952

experimental nephrotic syndromeAuthor(s): Kalay S (Kalay, S.), Akman S (Akman, S.), Akkaya B (Akkaya, B.), Koyun M (Koyun, M.), Akbas H(Akbas, H.), Baysal Y (Baysal, Y.), Guven AG (Guven, A. Gur)Source: CLINICAL CHEMISTRY Volume: 53 Issue: 6 Pages: A160-A160 Supplement: Suppl.S Meeting Abstract: D-6 Published: JUN 2007Times Cited: 0 References: 0 Citation MapConference Information: 59th Annual Meeting of the American-Association-for-Clinical-ChemistrySan Diego, CA, JUL 15-19, 2007Amer Assoc Clin ChemDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Fac Med, Antalya, TurkeyPublisher: AMER ASSOC CLINICAL CHEMISTRY, 2101 L STREET NW, SUITE 202, WASHINGTON, DC20037-1526 USASubject Category: Medical Laboratory TechnologyIDS Number: 172ZJISSN: 0009-9147ŀBeneficial effect of triple treatment (ACEI, AT1RB, statin) plus immunoglobulin in

PO Box 2345, Beijing 100023, China World J Gastroenterol 2007 January 14; 13(2): 313-315www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327wjg@wjgnet.com© 2007 The WJG Press. All rights reserved.CASE REPORTAn unusual cause of cholecystitis: Heterotopic pancreatictissue in the gallbladderGülsüm Özlem Elpek, Sevgi Bozova, Gökben Yıldırım Küpesiz, Mehmet ÖğüşGülsüm Özlem Elpek, Sevgi Bozova, Gökben YıldırımKüpesiz, Akdeniz University, Medical School, Department ofPathology, Yeni Tıp, Dekanlık, 07070, Antalya, TurkeyMehmet Öğüş, Akdeniz University, Medical School, Departmentof General Surgery, Yeni Tıp, Dekanlık, 07070, Antalya, TurkeyCorrespondence to: Gülsüm Özlem Elpek, Akdeniz University,Medical School, Yeni Tıp, Dekanlık, 07070, Antalya,Turkey. elpek@akdeniz.edu.trTelephone: +90-242-2274488 Fax: +90-242-2274488Received: 2006-09-29 Accepted: 2006-12-05lacking anatomical or vascular continuity with the pancreasproper [1] . In 85% to 90% of reported cases, HP has beenfound in stomach, duodenum, upper jejunum, whereasits presence in the gallbladder is very rare [1-3] . Similar toHP of other organs, HP of the gallbladder itself has noclinical importance and is found incidentally in most cases.However, there have been some reports of symptomaticgallbladder disease [4-7] . Herein we report a case of HP inthe neck of the gallbladder who presented with clinicalfindings of cholecystitis.AbstractGallbladder localization of heterotopic pancreas (HP)is uncommon and very rarely gives rise to symptoms.Herein we report a case of HP found in the gallbladderneck presented with signs and symptoms of cholecystitis.The patient was a 40-year old male, suffering fromepigastric pain, abdominal fullness and fever. On physicalexamination, the right upper abdomen was tender witha positive Murphy’s sign. Ultrasonographic examinationshowed a hydropic gallbladder without stones and heunderwent a cholecystectomy. Pathological examinationrevealed an intramural nodule (9 mm) in the neck regionwhich is consisted of acini, ducts and islet cells of anaberrant pancreatic tissue. Although HP is encounteredrarely in the gallbladder and is found incidentally duringpathological studies, this case emphasizes that HP mightcause symptoms and present clinically as cholecystitis.For this reason, in patients presenting with symptomaticgallbladder diseases, including cholecystitis without anyother pathology, HP should be taken into considerationbefore it is diagnosed as "idiopathic’’.© 2007 The WJG Press. All rights reserved.Key words: Heterotopic tissues; Pancreas; Acalculouscholecystitis; GallbladderElpek GÖ, Bozova S, Küpesiz GY, Öğüş M. An unusualcause of cholecystitis: Heterotopic pancreatic tissue in thegallbladder. World J Gastroenterol 2007; 13(2): 313-315http://www.wjgnet.com/1007-9327/13/313.aspINTRODUCTIONHeterotopic pancreas (HP) is defined as the presence ofpancreatic tissue lying outside its normal location andCASE REPORTA 40-year old male presented to the hospital withepigastric pain, abdominal fullness and fever three daysago. On physical examination, the right upper abdomenwas tender with a positive Murphy’s sign. His laboratorydata revealed total bilirubin = 1.5 mg/dL, direct bilirubin= 0.8 mg/dL, ALP = 398 U/dL, SGOT = 70 U/dL,SGPT = 60 U/dL, GGT = 90U/dL. Ultrasonographic (US)examination showed a hydropic gallbladder without stones.A cholecystectomy was performed. The macroscopicfindings were as follows: gallbladder measuring 80 mm× 50 mm × 40 mm, wall thickness 3-12 mm. In the neckregion, a yellowish-white intramural nodule measuring9 mm × 8 mm × 8 mm was observed. Microscopicexamination revealed aberrant pancreatic tissue consistingof acini, ducts and chromogranin A expressing islet cells.No direct connection with the gallbladder lumen wasobserved (Figure 1). The whole specimen was embeddedstepwise for further microscopic evaluation, but anyother pancreatic tissue was not detected. The diagnosiswas thereby established as chronic cholecystitis withheterotopic pancreas. All symptoms disappeared followingcholecystectomy and the patient recovered completely.DISCUSSIONAlthough HP is the second most prevalent pancreaticanomaly, the incidence in gastrointestinal tract is estimatedto be from 0.55% to 13.7% on autopsy, and 0.2% inlaparatomy [6] . Despite the frequent occurrence of HPin the stomach, duodenum and upper jejunum, thegallbladder localization is extremely rare. Since the firstpublication by Poppi in 1916, only 29 more cases of HPworldwide in the gallbladder have been reported in areview of the literature up to the present [8] . In these casesthere is a higher incidence of female patients between 40and 50 years of age [9] . However, similar to our case, itswww.wjgnet.com

Author(s): Kupesiz GY (Kupesiz, Gokben Yildlrim), Akkay B (Akkay, Bahar), Tezcan G (Tezcan, Gulsun),Kupesiz A (Kupesiz, Alphan), Unal B (Unal, Betul), Gulkesen H (Gulkesen, Hakan), Hazar V (Hazar, Volkan),Karpuzoglu G (Karpuzoglu, Gulten)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 514-514 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Sch Med, Dept Pathol, Antalya, Turkey2. Akdeniz Univ, Sch Med, Dept Pediat, Div Hematol & Oncol, Antalya, Turkey3. Akdeniz Univ, Sch Med, Dept Stat, Antalya, TurkeyPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀCox 2 and CD 34 expression in wilms tumor (nephroblastoma)

of soy isoflavone supplementation on prostate tissue, markers of proliferationand apoptosts and histopathological endpoints of tumor grade, volume and stageAuthor(s): Kupesiz GY (Kupesiz, Gokben Yildirim), Sakr W (Sakr, Wael), Cher M (Cher, Michael), Banerjee M(Banerjee, Mousumi), Pontes E (Pontes, Edson), Parnes H (Parnes, Howard), Kucuk O (Kucuk, Omer)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 412-412 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Dept Pathol, Antalya, Turkey2. Wayne State Univ, Barbara Ann Karmanos Canc Inst, Dept Pathol, Detroit, MI 48202 USA3. Wayne State Univ, Barbara Ann Karmanos Canc Inst, Dept Urol, Detroit, MI 48202 USA4. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA5. NCI, Div Canc Prevent, Rockville, MD USA6. Wayne State Univ, Barbara Ann Karmanos Canc Inst, Dept Hematol & Oncol, Detroit, MI 48202 USAPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀEffect

associationAuthor(s): Ozbudak IH (Ozbudak, Irem Hicran), Shilo K (Shilo, Konstantin), Galvin JR (Galvin, Jeffrey R.), FranksTJ (Franks, Teri J.)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 423-423 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Univ Akdeniz, Sch Med, Dept Pathol, Antalya, Turkey2. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA3. Armed Forces Inst Pathol, Dept Soft Tissue Pathol, Washington, DC 20306 USAPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀExtramedullary hematopoiesis in pulmonary spindle cell tumors: Rare and unusual

Author(s): Ozbudak IH (Ozbudak, Irem Hicran), Tavora F (Tavora, Fabio), Rassaei N (Rassaei, Negar), Shilo K(Shilo, Konstantin), Chu WS (Chu, Wei-Sing), Fukuoka J (Fukuoka, Junya), Jen J (Jen, Jin), Travis WD (Travis,William D.), Franks TJ (Franks, Teri J.)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 524-524 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Univ Akdeniz, Sch Med, Dept Pathol, Antalya, Turkey2. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA3. Armed Forces Inst Pathol, Dept Sci Labs, Washington, DC 20306 USA4. Toyama Med & Pharmaceut Univ, Pathol Lab, Toyama, JapanPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀGlucose transporter-1 expression in pulmonary neuroendocrine carcinoma

Author(s): Tavora F (Tavora, Fabio), Ozbudak IH (Ozbudak, Irem Hicran), Shilo K (Shilo, Konstantin), PrzybockiJM (Przybocki, Jean M.), Wang GH (Wang, Guanghua), Travis WD (Travis, William D.), Franks TJ (Franks, TeriJ.)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 423-424 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Armed Forces Inst Pathol, Dept Pulm & Mediastinal pathol, Washington, DC 20306 USA2. Univ Akdeniz, Sch Med, Dept Pathol, Antalya, Turkey3. Armed Forces Inst Pathol, Dept Mol Pathol, Washington, DC 20306 USA4. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USAPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀInflammatory myofibroblastic tumors of the lung are negative for HHV-8

the outer peripheral zone/sub capsular tissue compartment of the prostate moresusceptible to carcinogenesis and early neoplastic transformation? A topographicmorphologic and tissue micro array immunohistochemical studyAuthor(s): Kupesiz GY (Kupesiz, Gokben Yildirim), Butler C (Butler, Charles), Pansari V (Pansari, Vashali), SakrW (Sakr, Wael)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 416-416 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Dept Pathol, Antalya, Turkey2. Harper Univ Hosp, Karmanos Canc Inst, Detroit, MI 48202 USA3. Wayne State Univ Hosp, Karmanos Canc Inst, Detroit, MI 48202 USAPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀIs

postatrophic hyperplasiaAuthor(s): Bassorgun CI (Bassorgun, Cumhur Ibrahim), Unal B (Unal, Betul), Ozbudak IH (Ozbudak, ItemHicran), Akkaya B (Akkaya, Bahar), Ciftcioglu MA (Ciftcioglu, Mehmet Akif)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 415-415 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Sch Med, Dept Pathol, Antalya, TurkeyPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀp27 and high molecular weight cytokeratin expression in prostatic atrophy and

characteristics of prostate cancer in African American and caucasian mendiagnosed and treated or below 50 years of age: Racial differences are mostevident in the younger age bracketAuthor(s): Kupesiz GY (Kupesiz, Gokben Yildirim), Powell I (Powell, Isaac), Grignon D (Grignon, David), Sakr W(Sakr, Wael)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 417-418 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Dept Pathol, Antalya, Turkey2. Harper Univ Hosp, Karmanos Canc Inst, Dept Urol, Detroit, MI USA3. Wayne State Univ Hosp, Detroit, MI USA4. Harper Univ Hosp, Karmanos Canc Inst, Dept Pathol, Detroit, MI USAPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀPathologic

Author(s): Burke A (Burke, Allen), Tavora F (Tavora, Fabio), Ozbudak I (Ozbudak, Irem), Franks T (Franks,Teri), Miettinem M (Miettinem, Markku)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 489-490 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. CVPath Inst Inc, Bethesda, MD USA2. Armed Forces Inst Pathol, Washington, DC 20306 USA3. Akdeniz Univ, Sch Med, Antalya, TurkeyPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀPediatric cardiac sarcomas, a series of 16 new cases with literature review

differences in the clinicopathological profile of familial/hereditary andsporadic prostate cancerAuthor(s): Kupesiz GY (Kupesiz, Gokben Yildirim), Powell I (Powell, Isaac), Grignon D (Grignon, David), Sakr W(Sakr, Wael)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 418-418 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Dept Pathol, Antalya, Turkey2. Harper Univ Hosp, Karmanos Canc Inst, Dept Urol, Detroit, MI USA3. Wayne State Univ Hosp, Detroit, MI USA4. Harper Univ Hosp, Karmanos Canc Inst, Dept Pathol, Detroit, MI USAPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀPotential

Artery Obstruction due to Papillary Fibroelastoma on the PulmonaryValve: A Rare Cardiac TumorAuthor(s): Mete A (Mete, A.)ŀPulmonary 1 , Erbasan O (Erbasan, O.) 1 , Kemaloglu C (Kemaloglu, C.) 1 , Ozbudak IH (Ozbudak,I. H.) 2 , Turkay C (Turkay, C.) 1Source: THORACIC AND CARDIOVASCULAR SURGEON Volume: 57 Issue: 2 Pages: 116-118 Published: MAR 2009Times Cited: 1 References: 10 Citation MapDocument Type: ArticleLanguage: EnglishAuthor Keywords: Papillary fibroelastoma; pulmonary valve; pulmonary artery obstruction; cardiac tumorReprint Address: Erbasan, O (reprint author), Univ Hosp Akdeniz, Dept Cardiac & Vasc Surg, Akdeniz UnivHastanesi, TR-07058 Antalya, TurkeyAddresses:1. Univ Hosp Akdeniz, Dept Cardiac & Vasc Surg, Akdeniz Univ Hastanesi, TR-07058 Antalya, Turkey2. Univ Hosp Akdeniz, Dept Pathol, TR-07058 Antalya, TurkeyE-mail Addresses: ozzan70@gmail.comAbstract: Papillary fibroelastomas (PFEs) are primary cardiac tumors. They are rare benign tumors that occur onthe endocardium of the heart, especially on the heart valves. The majority of these benign tumors have beenobserved on the left side of the heart and involved the aortic and mitral valves; however, Occurrence on the rightside of the heart has been infrequently reported, with only a few cases documented on the pulmonary valve. Mostpatients with PFEs are asymptomatic and the tumors are usually found incidentally. The tumors have the potentialto cause systemic or pulmonary embolism or obstructive phenomena. We present a rare case of a papillaryfibroelastoma occurring on the pulmonary valve with clinical presentation due to pulmonary artery obstruction.The tumor was removed surgically.Publisher: GEORG THIEME VERLAG KG, RUDIGERSTR 14, D-70469 STUTTGART, GERMANYSubject Category: Cardiac & Cardiovascular Systems; Respiratory System; SurgeryIDS Number: 424CGISSN: 0171-6425DOI: 10.1055/s-2008-1038726

transcription factor-1 (TTF-1) expression in pulmonary neuroendocrinecarcinomas: Clone-based variabilityAuthor(s): Rassaei N (Rassaei, N.), Tavora F (Tavora, F.), Ozhudak I (Ozhudak, I.), Chu WS (Chu, W-S), JaynesE (Jaynes, E.), Sobin L (Sobin, L.), Travis WD (Travis, W. D.), Jen J (Jen, J.), Shilo K (Shilo, K.), Franks TJ(Franks, T. J.)Source: LABORATORY INVESTIGATION Volume: 87 Pages: 329A-329A Supplement: Suppl.1 Meeting Abstract: 1515 Published: MAR 2007Times Cited: 0 References: 0 Citation MapConference Information: 96th Annual Meeting of the United-States-and-Canadian-Academy-of-PathologySan Diego, CA, MAR 24-30, 2007US & Canadian Acad PatholDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. AFIP, Washington, DC USA2. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA3. NIH, Bethesda, MD 20892 USAPublisher: NATURE PUBLISHING GROUP, 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917USASubject Category: Medicine, Research & Experimental; PathologyIDS Number: 146LGISSN: 0023-6837ŀThyroid

Author(s): Ozbilim G (Ozbilim, Gulay), Uguz A (Uguz, Aysen), Ozbudak IH (Ozbudak, Irem Hicran), Celmeli F(Celmeli, Fatih), Er H (Er, Hakan)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 427-427 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Sch Med, Dept Pathol, Antalya, Turkey2. Akdeniz Univ, Sch Med, Dept Pediat, Antalya, Turkey3. Akdeniz Univ, Sch Med, Dept Histol, Antalya, TurkeyPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀCiliary dysmorphology: Ultrastructural findings in 12 patients

cancerAuthor(s): Basorgun CI (Basorgun, Cumhur Ibrahim), Ozbilim G (Ozbilim, Gulay), Ozbudak IH (Ozbudak, IrernHicran), Sarper A (Sarper, Alpay), Erdogan A (Erdogan, Abdullah)Source: VIRCHOWS ARCHIV Volume: 451 Issue: 2 Pages: 427-427 Published: AUG 2007Times Cited: 0 References: 0 Citation MapDocument Type: Meeting AbstractLanguage: EnglishAddresses:1. Akdeniz Univ, Sch Med, Dept Pathol, Antalya, Turkey2. Akdeniz Univ, Sch Med, Dept Thorac Surg, Antalya, TurkeyPublisher: SPRINGER, 233 SPRING STREET, NEW YORK, NY 10013 USASubject Category: PathologyIDS Number: 210KHISSN: 0945-6317ŀExpression of the c-kit and ki-67 proliferation index in patients with lung

Anabilim Dalı - 20071-Koksal IT, Ishak Y, Usta, M, Danisman A, Guntekin E, Bassorgun IC, Ciftcioglu, A:Varicoceleinducedtesticular dysfunction may be associated with disruption of blood-testis barrier ARCHANDROLOGY53 (1): 43-48, 2007.2-Danısman A, Kutlu Ö, Akkaya E, Karpuzoglu G, Erdogru T Tibial ner ve stimulation dimirishesmastcell infiltration in the bladder wall in duced by interstitial cystitis ürine.Scan j of urology andnephrology 41:98-102,2007.3-Yong W, Yang Z, Periyasamy S, Chen H, Yucel S, Li W, Lin LY, Wolf IM, Chon MJ.Essential role forCo-chaperone Fkbp52 but not Fkbp51 in androgen receptor- mediated signaling and physiology J BiolChem2007 Feb16;282 (7) : 5026-364-Snodgrass W, Yucel S.Tubularized incised plate for mid shaft and proximal hypospadias repair.JUrol.2007 Feb;177 (2):698-7025-Yucel S, Samuelson ML, Nguyen Mt, Baker LA.Usefulness of short-term retrievable ureteral stent inpediatric laparoscopic pyeloplastyJ Urol.2007 Feb;177 (2):720-5; discussion 7256-Yucel S, Gupta A, Snodgrass W.Multivariate analysis of factors predicting success withdextranomer/hyaluronic acid injection for vesicoureteral refluxJ Urol.2007 Apr;177 (4) :1505-97-Yucel S, Tarcan T, Simşek FDurability of a single successful endoskopic polytetrafluoroethyleneinjection for primary vesicoureteral reflux: 14-year followup resultsJ Urol.2007 Jul;178 (1) :265-8;discussion 268. Epub 2007 May 178-Usta MEditorial Comment on: Investigation of the Antifibrotic Effect of IFN-gamma on Fibroblasts ina Cell Culture Model of Peyronie's Disease.Eur Urol. 2007 Nov 29;ŀÜroloji9-Bivalaqua TJ, Deng W, Kendirci M, Usta MF et al:Mesenchymal stem cells alone or ex vivo genemodified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction.Am JPhysiol Heart Circ Physiol. 2007 Mar10-Maldonado-Valadez R, Teber D, Erdogru T, Safi KC, Frede T, Rassweiler J.The impact ofneoadjuvant hormonal therapy on the outcome of laparoscopic radical prostatectomy: a matched pairanalysis.J Urol2006 Jun;175(6):2092-611-Rassweiler JJ, Gözen AS, Erdogru T, Sugiono M, Teber D.Ureteral reimplantation formanagement of ureteral strictures: a retrospective comparison of laparoscopic and opentechniquesEur Urol2007 Feb;51(2):512-2212-Erdogru TEditorial Comment on: The Contribution of the Levator Ani Nerve and the PudendalNerve to the Innervation of the Levator Ani Muscles: A Study in Human FetusesEur UrolEur Urol.2007 Nov 2013-Erdogru T, Sanlı A, Celik O, Baykara M.Laparoscopic transvesical repair of recurrentvesicovaginal fistula using with fleece-bound sealing system.Arch Gynecol Obstet.2007 Nov 22

Varicocele-induced testicular dysfunction may be associated with disruption ofblood-testis barrier.Androl. 2007 Jan-Feb;53(1):43-8.Koksal IT, Ishak Y, Usta M, Danisman A, Guntekin E, Bassorgun IC, Ciftcioglu A.Department of Urology, Akdeniz University, Antalya, Turkey. tkoksal@akdeniz.edu.trAbstractThe objective of this study was to examine E-cadherin and alpha-catenin expression at the junctions between adjacent Sertoli cells intesticular specimens from patients with varicocele in order to determine the presence of a possible link between blood-testis barrier andpathophysiology of varicocele. A total of 51 testicular biopsies were obtained from 28 infertile men with unilateral or bilateral varicocele.Twenty-three patients had bilateral and 5 had unilateral varicocele, Grade I varicocele was detected in 30 (59%), grade II in 15 (29%)and grade III in 6 (12%) patients. Abnormal expression of E-cadherin and alpha-catenin at the junctions between adjacent Sertoli cellswas demonstrated in 100% and 90% of the patients with varicocele, respectively. In those with grade I-III varicocele, the mean E-cadherin and alpha-catenin expression were 7.6 +/- 11.4 and 39 +/- 36; 7.6 +/- 0.0 and 49 +/- 30; 8.3 +/- 9.3 and 58 +/- 33, respectively,but the difference was not significant. Reduced E-cadherin and alpha-catenin expression at the junctions between adjacent Sertoli cellsŀArchmay be associated with disruption of blood-testis barrier in varicocele.PMID: 17364465 [PubMed - indexed for MEDLINE]

Scandinavian Journal of Urology and Nephrology, 2007; 41: 98102ORIGINAL ARTICLETibial nerve stimulation diminishes mast cell infiltration in the bladderwall induced by interstitial cystitis urineScand J Urol Nephrol Downloaded from informahealthcare.com by Akdeniz Universitesi on 10/12/10For personal use only.AHMET DANIŞMAN 1 ,ÖMER KUTLU 1 , ERDEM AKKAYA 1 ,GÜLTEN KARPUZOĞLU 2 &TIBET ERDOĞRU 1Departments of 1 Urology and 2 Pathology, Faculty of Medicine, Akdeniz University, Antalya, TurkeyAbstractObjectives. To investigate whether the urine of interstitial cystitis (IC) patients has a toxic effect on the bladder wall, asdetermined by mast cell infiltration, and to evaluate the preventive effect of tibial nerve electric stimulation (TNES) onbladder mastocytosis induced by IC urine. Material and methods. The bladders of female rats were catheterized and instilledwith IC urine (Group IC; n/10) and normal urine (Group NU; n/5) obtained from humans, saline (Group S; n/5) andprotamine sulphate (Group PS; n/10) for 6 weeks. Additionally, in five rats instilled with IC urine and five instilled withPS, TNES was also performed (Groups IC/TNES and PS/TNES). Results. In the lamina propria of the bladder, themean number of mast cells per square millimetre was significantly higher in Groups IC (32.59/12.3) and PS (39.49/11.1)than in Groups S (11.99/4.3) and NU (13.79/3.5). After TNES, the corresponding values were decreased significantly to15.39/5.4 and 15.39/4.1 in Groups IC/TNES and PS/TNES, respectively (p B/0.001). A significant reduction in mastcell infiltration in the detrusor was also determined after TNES compared with the value in Group IC (4.69/1.6 vs 12.19/3.0; p B/0.001). Conclusions. We demonstrated that IC urine may result in increased mast cell infiltration in the bladder wall.TNES may play a therapeutic role by diminishing the mast cell count in the bladder wall, which has a strong relationshipwith nociceptive neural endings.Key Words: Interstitial cystitis, mast cell, electroacupuncture, tibial nerveIntroductionInterstitial cystitis (IC) is a syndrome used todescribe a severe and debilitating disorder of thebladder. It is characterized by severe urinary frequency,urgency and/or lower abdominal pain.Histopathologic examination is not absolutely essentialfor diagnosing IC as the condition has nopathognomonic signs. However, several investigators[1,2] have pointed out the close relationship betweenmast cells in the bladder wall and IC. In spite of thefact that it has not been universally advocated asa valid diagnostic tool, ‘‘detrusor mastocytosis’’,i.e./10 mast cells/mm 2 in the detrusor muscle,has been proposed as a diagnostic criterion for IC[2]. Although several controversies exist, a deficiencyof the glycosaminoglycan (GAG) layer has continuedto be an attractive hypothesis [3]. Ruggieri et al. [3]and Baykara et al. [4] have previously described theeffect of instillation of urine from symptomatic ICpatients into experimental bladders, demonstratingchanges in the bladder by means of histological andcystoscopic findings compatible with IC. In addition,Keay et al. [5] have suggested that the bladderurothelium in IC patients may not be appropriatelyregenerated due to the presence of antiproliferativefactors in urine. In spite of unsatisfactory results withacupuncture or transcutaneous electric stimulationin patients with IC or overactive bladder [6], it wasdemonstrated [7,8] that peripheral neuromodulationwith afferent nerve stimulation utilizing the posteriortibial nerves for transcutaneous access to the S3spinal region could successfully treat patients withurgency/frequency and/or pelvic pain syndrome.Moreover, a significant inhibitory impact of electroacupunctureperformed at the spleen-6 (Sp6) acupointwas described on expression of nociceptiveCorrespondence: Ahmet Danişman, MD, Department of Urology, Faculty of Medicine, Akdeniz University, Dumlupinar Bulvari Kampüs, 07059 Antalya,Turkey. Fax: /90 242 2274490. E-mail: danisman@akdeniz.edu.tr(Received 23 September 2005; accepted 9 June 2006)ISSN 0036-5599 print/ISSN 1651-2065 online # 2007 Taylor & FrancisDOI: 10.1080/00365590600911233

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptNIH Public AccessAuthor ManuscriptJ Biol Chem. Author manuscript; available in PMC 2008 November 3.Published in final edited form as:J Biol Chem. 2007 February 16; 282(7): 5026–5036. doi:10.1074/jbc.M609360200.Essential Role for Co-Chaperone FKBP52 but not FKBP51 inAndrogen Receptor-Mediated Signaling and PhysiologyWeidong Yong 1,# , Zuocheng Yang 1,2,# , Sumudra Periyasamy 3 , Hanying Chen 1 , SelculYucel 4 , Wei Li 1 , Leanne Y Lin 1 , Irene M Wolf 3 , Martin J. Cohn 5 , Laurence S Baskin 4 , EdwinR. Sánchez 3 , and Weinian Shou 11Herman B Wells Center for Pediatric Research, Section of Pediatric Cardiology, Department of Pediatrics,Indiana University School of Medicine, Indianapolis, IN 462022Department of Pediatrics, Third Xiang-Ya Hospital, Central South University, Xiang-Ya School of Medicine,Changsha, P.R. China3Department of Pharmacology, Medical University of Ohio, Toledo, OH436144Department of Urology, University of California School of Medicine, San Francisco, CA 941435Department of Zoology, University of Florida, Gainesville, FL 32611, USAAbstractFKBP52 and FKBP51 are tetratricopeptide repeat (TPR) proteins found in steroid receptor complexesand FKBP51 is an androgen receptor (AR) target gene. Although in vitro studies suggest that FKBP52and FKBP51 regulate hormone-binding and/or subcellular trafficking of receptors, the roles ofFKBP52 and FKBP51 in vivo have not been extensively investigated. Here, we evaluate theirphysiological roles in FKBP52-deficient and FKBP51-deficient mice. FKBP52-deficient malesdeveloped defects in select reproductive organs (e.g., penile hypospadias, prostate dysgenesis, butnormal testis), pointing to a role for FKBP52 in AR-mediated signaling and function. Surprisingly,ablation of FKBP52 did not affect AR hormone-binding or nuclear translocation in vivo and invitro. Molecular studies in MEF cells uncovered that FKBP52 is critical to AR transcriptional activity.Interestingly, FKBP51 expression was down-regulated in FKBP52-deficient males but only inaffected tissues, providing further evidence of tissue-specific loss of AR activity and suggesting thatFKBP51 is an AR target gene essential to penile and prostate development. However, FKBP51-deficient mice were normal, showing no defects in AR-mediated reproductive function. Our workdemonstrates that FKBP52 but not FKBP51 is essential to AR-mediated signaling, and providesevidence for an unprecedented FKBP52 function – direct control of steroid receptor transcriptionalactivity.Androgen receptor (AR) is a hormone-induced transcription factor that controls male sexualdevelopment and other important physiologies. Similar to other members of the nuclearreceptor family (1,2), AR has three major functional domains: an N-terminal transactivationdomain, a DNA-binding domain, and a C-terminal ligand-binding domain (3), (4), (5).Mutations found in each of these domains lead to a series of AR functional defects associatedwith androgen insensitivity syndrome (AIS) or partial androgen insensitivity syndrome (PAIS)in humans (6,7). The majority of AIS and PAIS patients have developmental defects in themale reproductive system. Loss-of-function AR mutations in mice recapitulate many of theAddress correspondence to: Weinian Shou, Herman B Wells Center for Pediatric Research, R4-368, 1044 West Walnut, Indianapolis,IN 46202, Tel: (317)274-8952; Fax: (317)278-5413; email: wshou@iupui.edu.# These authors contributed equally to this work.

Tubularized Incised Plate forMid Shaft and Proximal Hypospadias RepairWarren Snodgrass* and Selcuk YucelFrom the Division of Pediatric Urology, Children’s Medical Center and University of Texas Southwestern Medical Center, Dallas, TexasPurpose: We report outcomes from tubularized incised plate repair of mid shaft and proximal hypospadias by a singlesurgeon.Materials and Methods: Chart review of all patients undergoing mid shaft and proximal hypospadias was performed. Thosewith tubularized incised plate were divided into 2 groups for mid shaft and proximal repairs. Group 1 underwent single layerurethroplasty using chromic catgut suture, while group 2 underwent 2-layer polyglactin subepithelial closure. All patientshad a dartos barrier flap, while spongioplasty was also done in group 2 when possible.Results: A total of 30 patients underwent mid shaft repairs, while 35 had more proximal defects. Complication rates for midshaft repairs did not differ between the 2 groups, and averaged 13%. However, complications in mid shaft vs proximal repairs(37%) were significantly different (p 0.04). Overall complications (53% vs 25%) and incidence of fistulas (33% vs 10%)decreased in proximal repairs from group 1 to 2.Conclusions: Tubularized incised plate repair was applicable for all mid shaft hypospadias cases and for those moreproximal cases when ventral curvature could be straightened without plate transection and the incised plate was grosslysupple. Outcomes were improved using 2-layer subepithelial tubularization of the neourethra. Results of mid shaft vsproximal hypospadias repairs are significantly different and should be reported separately.Key Words: hypospadias; urologic surgical procedures, male; surgical flaps; urethraSubmitted for publication August 1, 2006.Study received institutional review board approval.* Correspondence: 6300 Harry Hines Blvd., Suite 1401, Dallas,Texas 75235 (telephone: 214-456-2481; FAX: 214-456-8803; e-mail:warren.snodgrass@childrens.com).Tubularized incised plate urethroplasty for mid shaftand penoscrotal hypospadias was first reported from amulticenter experience in 1998. 1 Since then, an additional6 publications have reviewed outcomes for this technique,extending its use to scrotal and perineal defects. 2–7Outcomes compare favorably with those from preputialflaps, resulting in increased reliance on TIP for mid shaftand proximal cases when ventral curvature does not lead toplate transection for straightening. 8 However, there is potentialselection bias in these studies, since neither thenumber of mid shaft and proximal cases undergoing alternativerepairs nor factors in decision making favoring 1technique over another were provided.Our earlier study of TIP for mid shaft to scrotal hypospadiasrevealed complications in 33% of cases. 4 Most ofthese complications were fistulas occurring despite a dartosbarrier flap over the neourethra. Dehiscence and recurrentventral curvature occurred in 1 patient each with penoscrotaldefects, thought intraoperatively to have an “unhealthy”appearing incised urethral plate. Following this experienceseveral technical modifications were made, primarily to decreasefistulas, and it was determined that patients with anunhealthy plate would not undergo TIP repair.We report decision making for mid shaft and proximalhypospadias repair in consecutive patients by a single surgeon(WS). Tubularized incised plate outcomes followingtechnical modification are compared to the original series.MATERIALS AND METHODSWe queried the database of the senior author (WS) for allpatients undergoing primary repair for mid shaft and proximalhypospadias. The intent was to perform TIP urethroplastyunless specifically contraindicated. Initially, ventralcurvature judged too severe to straighten with a single dorsalplication using 6-zero polypropylene was the sole contraindication,since it resulted in urethral plate transection.Following recognition of an unhealthy appearing incisedplate, the finding of grossly deficient subepithelial tissueswith inelasticity of the plate constituted a second contraindicationfor TIP.Patients undergoing TIP were divided into 2 groups accordingto variations in surgical technique. Group 1 underwenttubularization in a single layer using 7-zero chromiccatgut and various suturing methods, including interruptedor running stitches placed through all layers or subepithelial(not recorded in 2 patients). 8,18 A de-epithelialized dartosflap harvested from the dorsal prepuce and shaft was usedas a barrier layer in all cases. These cases were initiallyreported in 2002, 4 and recognition of a 21% fistula rate led toseveral modifications in group 2.In patient group 2 plate tubularization was performedusing 7-zero polyglactin in 2 layers, turning all epitheliuminto the lumen. For all proximal and 5 mid shaft cases thefirst layer was interrupted and the second running, while inthe remaining 12 mid shaft repairs running closure was0022-5347/07/1772-0698/0 698Vol. 177, 698-702, February 2007THE JOURNAL OF UROLOGY ®Printed in U.S.A.Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATIONDOI:10.1016/j.juro.2006.09.104

Usefulness of Short-Term RetrievableUreteral Stent in Pediatric Laparoscopic PyeloplastySelcuk Yucel,* Mindy L. Samuelson, Michael T. Nguyen and Linda A. Baker†From the Department of Urology, University of Texas Southwestern Medical Center at Dallas and Children’s Medical Center,Dallas, Texas, and Department of Urology, Akdeniz University School of Medicine, Antalya, Turkey (SY)Purpose: Methods of stenting after laparoscopic pyeloplasty have included indwelling Double-J® stents and percutaneousnephrostomy tubes. The disadvantages of these methods are that they necessitate a second surgery for stent removal orrequire an external drainage bag. To circumvent these issues, the tolerance, safety and outcomes of using a Double-J ureteralstent with a dangler, permitting early office removal, was investigated in a series of pediatric laparoscopic pyeloplasties.Materials and Methods: Medical records from a consecutive series of pediatric patients undergoing transperitoneallaparoscopic pyeloplasties were reviewed. Indications for surgery included ipsilateral flank pain with severe hydronephrosis(12 patients), recurrent pyelonephritis with severe hydronephrosis (2), and hematuria and flank pain (6). All patients weredischarged home within 24 to 48 hours of the procedure with prophylactic oral antibiotics. The stent was removed bypostoperative day 18 during a followup office visit. Patient tolerance of the indwelling stent, outpatient removal and successof pyeloplasty were assessed.Results: A total of 20 patients underwent transperitoneal laparoscopic pyeloplasty by 1 surgeon (LAB) between 2001 and2005. All patients underwent cystoscopy and retrograde Double-J ureteral stent placement before pyeloplasty under the sameanesthesia. Mean patient age at operation was 11.3 years (median 11.3, range 4.6 to 17.2). Stents were left indwelling for amean of 10.3 days (median 10, range 7 to 18). All patients tolerated the Double-J stent well, with 2 requiring anticholinergictherapy for mild urgency symptoms and 1 demonstrating urinary tract infection. All patients tolerated outpatient stentremoval via the dangler at the office without discomfort. One patient was lost to followup. At a mean followup of 1.04 years(range 0.1 to 2.88) 17 of 19 patients (89%) had resolution of flank pain/urinary tract infections, with sonographic improvementin hydronephrosis with or without endoscopic intervention. Six patients (30%) had flank pain with or without continuoushydronephrosis and required re-stenting, and 3 also required balloon dilation. Of these 6 patients 2 (10%) had recurrentureteropelvic junction obstruction and required open pyeloplasty. All patients are now clinically and radiologically unobstructedand asymptomatic.Conclusions: Pediatric transperitoneal laparoscopic pyeloplasty with indwelling Double-J ureteral stent with a dangler issuccessful and the stent is well tolerated. Whether the duration of ureteral stenting affects the surgical success will requirefurther controlled long-term studies.Key Words: laparoscopy, urologic surgical procedures, ureteral obstruction, childThe gold standard for management of UPJ obstructionhas been open pyeloplasty, with success ratesgreater than 90%. Since the first description of successfullaparoscopic pyeloplasty in 1993, 1 this procedurehas been shown to have success rates similar to openpyeloplasty of 83% to 100%. 2–9 The use of ureteral stentingin pyeloplasty has been a controversial subject. Historically,stenting was thought to cause infection, fibrosisand eventually stricture. 10 However, subsequent studieshave demonstrated less urinary leakage with stent, yethigher infection rates. 11,12In the adult population a Double-J ureteral stent caneasily be removed at the clinic at around 4 to 6 weeks afterSubmitted for publication July 23, 2006.* Supported by Akdeniz University Scientific Research andProject Unit.† Correspondence: Department of Urology, University of Texas SouthwesternMedical Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas75390-9110 (telephone: 214-648-2278, 214-456-2480; FAX: 214-648-8786,214-456-2497; e-mail: linda.baker@UTSouthwestern.edu).pyeloplasty. 5 In contrast, Double-J stents in children necessitatea second anesthetic for removal. For this reason somepediatric urologists prefer to use nephrostomy drainage.However, the use of a Double-J ureteral stent provides improvedcosmesis and eliminates the drainage bag, whileaccomplishing urinary diversion across the anastomosis.Double-J stents are often packaged with a string or a “dangler”at the distal tip. The dangler is positioned across theurethra to permit external retrieval of the stent with thepatient awake.In the pediatric literature on laparoscopic pyeloplastyeither no stent is used or stenting is achieved via percutaneousnephrostomy tube or internal Double-J ureteralstent. 2,4,6–9,13,14 To our knowledge there is no description ofthe use of the Double-J ureteral stent with a dangler inpediatric laparoscopic pyeloplasty permitting outpatientawake removal of the stent. We report our consecutive initialseries of transperitoneal laparoscopic pyeloplastieswherein we explored the use of Double-J stenting with adangler as the stenting option.0022-5347/07/1772-0720/0 720Vol. 177, 720-725, February 2007THE JOURNAL OF UROLOGY ®Printed in U.S.A.Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATIONDOI:10.1016/j.juro.2006.10.017

430european urology 53 (2008) 425–431[10] Lutz M, Knaus P. Integration of the TGF-beta pathwayinto the cellular signaling network. Cell Signal 2002;14:977–88.[11] Hellstrom WJG, Bivalacqua TJ. Peyronie’s disease: etiology,medical, and surgical therapy. J Androl 2000;21:347–54.[12] Hellstrom WJG, Kendirci M, Matern R, et al. Single-blind,multi-center, placebo controlled, parallel study to assessthe safety and efficacy of intralesional interferon a-2b forminimally invasive treatment for Peyronie’s disease.J Urol 2006;176:394–8.[13] Kendirci M, Usta MF, Matern RV, Nowfar S, Sikka SC,Hellstrom WJ. The impact of intralesional interferonalpha-2b injection thrapy on penile hemodynamics inmen with Peyronie’s disease. J Sex Med 2005;2:709–15.[14] Brake M, Loertzer H, Horsch R, Keller H. Treatment ofPeyronie’s disease with local interferon-a 2b. BJU Int2001;87:654–7.[15] Wegner HE, Andresen R, Knispel HH, Miller K. Local interferon-alpha2b is not an effective treatment in early-stagePeyronie’s disease. Eur Urol 1997;32:190–3.[16] Duncan MR, Berman B, Nseyo UO. Regulation of the proliferationand biosynthetic activities of cultured humanPeyronie’s disease fibroblasts by interferons-alpha, -betaand -gamma. Scand J Urol Nephrol 1991;141:89–94.[17] Blobe GC, Schiemann WP, Lodish HF. Role of transforminggrowth factor b in human disease. N Engl J Med 2000;342:1350–8.[18] Ulloa L, Doody J, Massagué J. Inhibition of transforminggrowth-factor-beta/ SMAD signaling by the Interferongamma/STATpathway. Nature 1999;397:710–3.[19] Kuga H, Morisaki T, Nakamura K, et al. Interferon-gammasuppresses transforming growth factor-beta-inducedinvasion of gastric carcinoma cells through cross-talkof Smad pathway in a three-dimensional culture model.Oncogene 2003;22:7838–47.Editorial Comment on: Investigation of theAntifibrotic Effect of IFN-g on Fibroblasts in a CellCulture Model of Peyronie’s DiseaseMustafa F. UstaAkdeniz University School of Medicine, Department ofUrology, Section of Andrology, Antalya, Turkeymusta@akdeniz.edu.trNonsurgical treatment of Peyronie’s disease (PD)remains one of the most debated issues. Althoughthe disease was described more than 250 yr ago, itsprecise etiology is still unclear. Many treatmentoptions have been performed in men with PDincluding oral, topical, and injectable agents toresolve the symptoms of the disease. On the otherhand, conservative therapies have limited evidence-baseddata to support their usage. Interferons(IFNs) are considered to influence thedeposition of collagen and therefore may promotecollagenase-like effects [1]. Actually, an increasingamount of current research is assessing the effectof IFN injection therapy in men with PD. However,if we look at the liteature the effect of INFs on PDseems obscure. Results obtained from differentstudy groups are controversial. Although someauthors reported that IFN-a2b has some beneficialeffects on penile hemodynamic parameters and PDsymptoms [2], others have indicated that it doesnot have any proven effect on the disease [3].Recently, in a single-blind, multicenter, placebocontrolled,parallel study, Hellstrom et al haveassessed the safety and efficacy of intralesionalIFN-a2b for the treatment of PD. The resultsshowed that improvements in penile curvature,plaque size and density, and pain relief weresignificantly greater in patients treated with IFNa2binjections versus placebo (10-ml saline injection).Furthermore, although penile blood flowimprovement was observed in patients treatedwith IFN-a2b but not in those treated with placebo,there was no significant difference in the InternationalIndex of Erectile Function scores betweenthe groups. Interestingly, intralesional injection of10 ml saline caused statistically significantimprovement in penile curvature and plaque sizeand density. The authors concluded that thissituation may be the result of hydrostatic pressureexerted by saline, which leads to induction of localfactors, contributing to plaque remodeling [4].However, to explain the exact mechanism of anytreatment option we need more scientific proofs aswell as more basic research related to that topic.Investigations, focusing on the pathologic pathways(eg, transforming growth factor b 1 [TGF-b 1 ])will broaden our understanding about the diseaseas well as about any related treatment options. Inthe present study Haag et al try to answer someunexplained mechanisms related to this enigmaticdisease, which may help us for future investigations.Briefly, the effect of INF-g on fibroblastsstimuated with TGF-b 1 , obtained from patientswith PD and a control group, was investigated.Cultured fibroblasts were stimulated with TGF-b 1 ,bone marrow protein 2, and INF-g alone or indifferent combinations. The results of the presentstudy revealed an agonistic effect of INF-g andTGF-b 1 , suggesting that INF-g should not beconsidered as a treatment option for acute-phase

european urology 51 (2007) 512–523available at www.sciencedirect.comjournal homepage: www.europeanurology.comReconstructive UrologyUreteral Reimplantation for Management of UreteralStrictures: A Retrospective Comparison of Laparoscopic andOpen TechniquesJens J. Rassweiler *, Ali S. Gözen, Tibet Erdogru, Marto Sugiono, Dogu TeberDepartment of Urology, SLK Kliniken Heilbronn, University of Heidelberg, GermanyArticle infoArticle history:Accepted August 1, 2006Published online ahead ofprint on August 17, 2006Keywords:LaparoscopyUreteral reimplantationUreteral injuryHydronephrosisAbstractObjectives: To compare the results of laparoscopic ureteral reimplantationwith a previous series of open surgery.Materials and methods: We compared ten patients who underwent laparoscopicvesicopsoas-hitch with (n = 4) or without Boari-flap (n = 6) techniquefor ureteral obstructions with ten patients treated by open ureteroneocystostomyfor similar pathologies. Patient demographics, preoperativesymptoms, radiologic imaging, and postoperative outcomes were analyzed.Postoperative observation time averaged 17 mo (range: 9–23) inthe laparoscopic and 65 mo (range: 18–108) in the open group. Successwas defined as relief of obstruction in postoperative imaging studies andrelief of pain.Results: Mean length of stricture (28.5 vs. 25 mm) was comparable in bothgroups. In laparoscopy versus open surgery, mean operative time (228 vs.187 min) was longer, blood loss (370 vs. 610 ml) and analgesic requirement(4.9 vs. 21.5 mg) were significantly lower, and mean time to oralintake (1.5 vs. 2.9 d), hospital stay (9.2 vs. 19.1 d), and convalescence time(2.3 vs. 4.2 wk) were significantly shorter. Success rates yielded 10 of 10after laparoscopy and 8 of 10 after open surgery. No intra- or postoperativemajor complications occurred in the laparoscopic series. After opensurgery, two patients had major postoperative complications, includingurinary extravasation with abdominal haematoma and anastomosticstricture, respectively.Conclusions: Laparoscopic ureteroneocystostomy is feasible, providingfunctional outcomes comparable to open surgery while offering the advantagesof a minimal invasive technique (e.g., less postoperative analgesics,and shorter hospitalization and convalescence). Nevertheless, it requires ahigh level of laparoscopic expertise and should be carried out only inspecialist centers.# 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.* Corresponding author. Department of Urology, SLK Klinikum Heilbronn, Am Gesundbrunnen20, D-77074 Heilbronn, Germany. Tel. +49 7131 492400; Fax: +49 7131 492429.E-mail address: jens.rassweiler@slk-kliniken.de (J.J. Rassweiler).0302-2838/$ – see back matter # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2006.08.004

Durability of a Single Successful Endoscopic PolytetrafluoroethyleneInjection for Primary Vesicoureteral Reflux: 14-Year Followup ResultsSelçuk Yücel, Tufan Tarcan* and Ferruh ŞimşekFrom the Department of Urology, Pediatric Urology Section, Akdeniz University School of Medicine, Antalya (SY) and Department ofUrology, Pediatric Urology Section, Marmara University School of Medicine, Istanbul, TurkeyPurpose: We reviewed our 14-year experience with successful single endoscopic subureteral polytetrafluoroethylene injectionfor the treatment of primary vesicoureteral reflux in children.Materials and Methods: We retrospectively reviewed the charts of 42 patients with primary vesicoureteral reflux who weretreated with a single successful subureteral polytetrafluoroethylene injection between 1989 and 1993 and followed withroutine 1, 3 and 10-year voiding cystourethrography.Results: The study included 30 girls and 12 boys 2 to 14 years old (median age 6 years). Four patients were lost to followup.Of the 38 remaining patients 28 had unilateral and 10 had bilateral primary vesicoureteral reflux. Endoscopic treatment withsubureteral polytetrafluoroethylene injection was performed in 48 ureters. Followup ranged from 10 to 14 years (mean 12.5 2.1). Voiding cystourethrography in 38 patients and 48 ureters revealed that 35 ureters (73%) remained free of reflux,whereas reflux recurred in 13 (27%) at a median of 2 years. Of these 13 ureters recurring reflux was grade I to II in 5 andgrade III to V in 8. Reflux recurred in 11 of 24 ureters with grade IV to V reflux. Of the 13 recurrences 10 presented as febrileurinary tract infections and only 3 grade I recurrences were detected on voiding cystourethrography alone. No untowardeffects were seen in any of these patients with injection of polytetrafluoroethylene.Conclusions: Long-term followup may be warranted after a single successful endoscopic injection for vesicoureteral reflux,particularly high grade reflux. However, followup voiding cystourethrography is unnecessary in patients presenting withfebrile urinary tract infection.Key Words: vesico-ureteral reflux, endoscopy, polytetrafluoroethylene, treatment failure, follow-up studiesSubmitted for publication October 19, 2006.Supported by Akdeniz University Scientific Research and ProjectUnit (SY).* Correspondence: Department of Urology, Marmara UniversitySchool of Medicine, Tophanelioglu cad. No. 13-15, Istanbul, Turkey(telephone: 90-216-325-2052; FAX: 90-216-325-8579; e-mail: tufan@marmara.edu.tr).Since approval by the Food and Drug Administration ofdextranomer/hyaluronic acid copolymer for vesicoureteralreflux correction, there has been a worldwideshift in the treatment of vesicoureteral reflux, withendoscopic injection now being recommended as the primarytreatment. 1 Recently, a committee assembled to update theAmerican Urological Association Pediatric VesicoureteralReflux Treatment Guidelines published a meta-analysis onthe outcomes of endoscopic correction by different injectableagents, including PTFE, polydimethylsiloxane, collagen anddextranomer. 2 Although the meta-analysis clearly showed areasonable success rate with endoscopic correction, concernsregarding the durability of outcomes in the long term haveremained unanswered. We still do not know how and howlong we have to follow these refluxing ureters after successfulendoscopic correction.Although there are few studies addressing the long-termdurability of success after endoscopic correction, 3–8 parentsmust be informed of the long-term outcomes when decidingon a treatment modality. Are we going to continue to dovoiding cystourethrography after documenting reflux resolutionin early followup? Or are we going to reserve voidingcystourethrography for urinary tract infections? If reflux hasthe possibility of recurring, when should we expect it? Parentswould like to know if endoscopically corrected refluxreally is a lifelong correction.As the meta-analysis indicates, success rates change significantlyafter subsequent injections (85.05% vs 74.13%),possibly as a result of better injection placement and morevolume injected. 2 Recently, success rates have been reportedto be associated with injected volume and injection technique,particularly in dilating reflux. 9 Diamond et al recentlystudied the minimal critical injection volume requiredto correct reflux. 10 It is reasonable that recurrent injectionswill have a higher injected volume, and although there is agradual volume loss with time, the critical volume can bereached after reinjection. To assess the long-term durability,we homogenized our study population into single successfulinjections. We report our 14-year followup in ureters withsingle successful endoscopic PTFE injection, with specialreference to long-term durability and morbidity.MATERIALS AND METHODSWe retrospectively reviewed the charts of 42 patients withprimary vesicoureteral reflux who were successfully treatedwith a single subureteral PTFE injection between 1989 and1993 at Marmara University. Four patients were lost tofollowup after the first year of control, and were excluded0022-5347/07/1781-0265/0 265Vol. 178, 265-268, July 2007THE JOURNAL OF UROLOGY ®Printed in U.S.A.Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATIONDOI:10.1016/j.juro.2007.03.060

european urology 54 (2008) 1136–1144 1143Editorial Comment on: The Contribution of theLevator Ani Nerve and the Pudendal Nerve to theInnervation of the Levator Ani Muscles: A Studyin Human FetusesTibet ErdogruDepartment of Urology, Akdeniz University,Antalya, Turkeyterdogru@akdeniz.edu.trAs a brief introduction about pelvic neuroanatomy,the somatic nerve supply to the pelvis comesfrom the lumbosacral plexus, which has two mainorigins: lumbar level and sacral level. Iliohypogastric,ilioinguinal, genitofemoral, femoral, andobturator nerves arise above from lumbar level L5.However, the lumbosacral trunk consists of thenerves from the L4–5 and S2–4 levels. Pelvicbranches from the sacral nerve include (1) theposterior femoral cutaneous nerve, (2) the pudendalnerve (S2–4), (3) the nervi erigentes (pelvicsplanchnic nerve) (S2–4) to the autonomic plexus,and (4) the pelvic somatic efferent nerves, whichgive branches to the levator ani. The parasympatheticautonomic nerve supply is given by nervierigentes (S2–4) with a contribution from thehypogastric nerves arising from the sympatheticsuperior hypogastric plexus and branches of thesacral sympathetic ganglia from the inferiorhypogastric (pelvic) plexus [1]. Classically, somaticnerves are below the endopelvic fascia (extrapelvic)and autonomic nerves are above the fascia(intrapelvic). There have been many issues abouturethral sphincteric control and its possible dualinnervation. It was suggested that there was anintrapelvic somatic nerve originating from S2–4[2], or a fascia traversing branch from the dorsalnerve of penis/clitoris [3]. Recently, it was shownthat a traversing branch of the pudendal nerveinnervates the urethral sphincter at a differentlevel than the autonomic nerve innervationpoint [4].The present study [5] basically claims thatthere are two somatic nerves innervating thelevator ani muscle, including one originatingdirectly from sacral plexus (pelvic somatic efferentnerves) and the other from the pudendalnerve. It also points out that sometimes there is aconnection between the levator ani nerve and thepudendal nerve. When the authors refer to dualinnervation, it has to be clarified that bothinnervations are of somatic origin and not ofautonomic origin. The authors have also speculatedon urinary continence mechanisms andlevator ani muscle function. As well seen in theirfetal specimens, embryologically sphincters andpelvic floor muscles have different origins andseparate morphologic counterparts. It is a verynaïve thought to completely depend on pelvicmusculature for preserving or restructuringurinary control and possibly bowel control. Agenuine dual innervation (somatic and autonomic)occurs in the urinary sphincter controland the pudendal nerve branch supplies thesomatic control [4,6]. Biofeedback or electricalstimulation of the pelvic floor, indeed, maystimulate the pudendal nerve and eventuallythe branch to the urethral sphincter from thepudendal nerve to restore urinary continence insome patients. In this respect, this study [5] is ofmerit because it demonstrates the pudendalnerve branch to the levator ani for the first timeto my knowledge. However, sphincters aredifferentially innervated and primarily responsiblefor continence and the pelvic floor is anadditive to sphincteric control at most. Threedimensionalimage reconstruction using histologicspecimens truly brought a new perspective toanatomy and its surgical understanding. I believethat pelvic neuroanatomy studies, as the presentstudy, will be extremely helpful to understand ifthe difference between the surgical techniquessuch as with or without opening endopelvicfascia in radical pelvic surgeries (laparoscopicor robotic radical prostatectomy, radical cystoprostatectomycombined with orthotopic neobladderreconstruction) might have an effecton the postoperative early recovery of continence.References[1] Brooks JD. Anatomy of the lower urinary tract andmale genitalia. In: Walsh PC, Retik AB, Vaughan ED,Wein AJ, editors. Campbell’s urology, ed. 8. 2002. p.54–5.[2] Borirakchanyavat S, Aboseif SR, Carroll PR, Tabagho EA,Lue TF. Continence mechanism of the isolated femaleurethra: an anatomical study of the intrapelvic somaticnerves. J Urol 1997;158:822–6.[3] Narayan P, Konety B, Aslam K, Aboseif S, Blumenfald W,Tanagho E. Neuroanatomy of the external urethralsphincter: implications for urinary continence preservationduring radical prostate surgery. J Urol 1995;153:337–41.

Arch Gynecol Obstet (2008) 277:461–464DOI 10.1007/s00404-007-0499-xCASE REPORTLaparoscopic transvesical repair of recurrent vesicovaginalWstula using with Xeece-bound sealing systemTibet Erdogru · Ahmet SanlÂ · Orcun Celik ·Mehmet BaykaraReceived: 19 August 2007 / Accepted: 18 October 2007 / Published online: 22 November 2007© Springer-Verlag 2007AbstractBackground Vesicovaginal Wstula (VVF) is an epithelium-linedcommunication between the urinary bladder andvagina. Most of VVFs are repaired by conventional opensurgery. Laparoscopic repair of VVFs is rare and so far noreport is available about laparoscopic repair of persistentVVF using Xeece-bound sealing system as a tissue barrierin the literature. Here we describe the operative techniqueand brieXy review the literature.Case We present the case of a 37-year-old woman withrecurring VVF in two times after abdominal and transvaginalrepairs caused by a massive bleeding during caesariansectiondue to placenta previa and underwent hysterectomy.During the laparoscopic repair of the Wstula and excision ofthe vaginal cuV, Xeece-bound sealing system (TachoSil ® )was used as tissue barrier. Laparoscopic transperitonealtransvesical repair was successfully performed by suturingthe defects and Wxing two TachoSil between the bladderand vagina. The postoperative period of the patient wasuneventful and after a follow up of 6 months no recurrencewas found.Conclusion We believe that laparoscopic repair of vesicovaginalWstula is a feasible and eYcacious minimally invasiveapproach for the management of this entity. Whilstproper identiWcation of tissue planes and good laparoscopicsuturing technique are required, using Xeece-bound sealingsystem might be convenient especially for persistent VVF.Keywords Vesicovaginal Wstula · Laparoscopy ·ReconstructionIntroductionThe initial repair of vesicovaginal Wstulas has the highestprobability of success with 65–96% [1]. The successful closureis dependent on size, site, and associated scarring.However, in the persistent cases, the outcome of the additionalsurgical treatment can be negatively aVected by theprevious surgeries due to decreased tissue viability, whichis crucial for the wound healing. Therefore in the recurrentWstulas a failure rate of 10% has been reported [2]. Persistentvesicovaginal Wstula (VVF) following transabdominaland transvaginal reconstructive open surgeries is a majorlimiting factor for the surgeons in further treatment alternativesand a devastating impact on the lives of women.Transabdominal transvesical repair has been the standardtreatment for diYcult VVF [1]. In here, we describe a laparoscopictransvesical technique that minimizes the surgicalmorbidity, achieves better exposure under magniWcationand the impact of using of the Xeece-bound sealing systemin the treatment of the persistent Wstulas. For assistance tothe wound healing in persistent VVF cases, Xeece-boundsealing system (TachoSil) including combination of a collagensponge coated with a dry layer of the human coagulationfactors Wbrinogen and thrombin can be used as a tissuebarrier between the bladder and vaginal cuV.T. Erdogru (&) · A. SanlÂ · O. Celik · M. BaykaraFaculty of Medicine, Department of Urology,Akdeniz University, Dumlupinar Bulvari Kampus,07059 Antalya, Turkeye-mail: terdogru@akdeniz.edu.trTechniqueWe are describing our technique of laparoscopic managementof supratrigonal VVF in a 37-year-old lady in whom a123

The Impact of Neoadjuvant Hormonal Therapy on the Outcomeof Laparoscopic Radical Prostatectomy: A Matched Pair AnalysisRafael Maldonado-Valadez, Dogu Teber, Tibet Erdogru, Khalid C. Safi, Thomas Frede andJens Rassweiler*From the Department of Urology, Klinikum Heilbronn, University of Heidelberg, Heilbronn, GermanyPurpose: We evaluated the effect of androgen ablation treatment on laparoscopic radical prostatectomy operative andpostoperative parameters.Materials and Methods: A total of 50 patients (group 1) on neoadjuvant androgen deprivation, followed by laparoscopicradical prostatectomy, were compared to 50 (group 2) without any treatment who were matched for prostate volume,laparoscopic pelvic lymphadenectomy, nerve sparing procedure, surgical access type and pathological stage. We analyzedoperative time, blood loss, intraoperative and postoperative complications, catheter time, procedure difficulty as scored by thesurgeon and surgical margin status.Results: There was no significant difference between the neoadjuvant and nonneoadjuvant groups with respect to meanoperative time SD (228.6 62.9 vs 219.4 65.1 minutes), mean blood loss (667.6.1 217.1 vs 729.8 285.1 ml) andmedian catheter time (7 vs 7.5 days). We also found no difference related to the complication rate. Ten of 50 prostatedissections (20%) in group 1 were classified as difficult, whereas in group 2 only 4 of 50 (8%) were scored as difficult(p 0.084). The positive surgical margin rates did not differ.Conclusions: There was no significant difference with respect to operative or postoperative parameters in patientsundergoing neoadjuvant androgen ablation therapy compared to controls. At centers where there is experience laparoscopicradical prostatectomy can be safely performed in patients who have undergone neoadjuvant hormonal therapy.Key Words: prostate, prostatic neoplasms, prostatectomy, laparoscopy, androgensThe literature is contradictory on whether neoadjuvanttherapy does or does not complicate open RP. Accordingto Monfette et al an advantage of hormonal treatmentis a decrease in blood loss and better operability, 1whereas Soloway et al found intense periprostatic reactiontogether with seminal vesicle adhesions after 3 months ofneoadjuvant treatment, making RP more difficult. 2 However,this had no impact on operative time or intraoperativebleeding. Similarly others did not find any significant differencesin operative parameters. 3–5 There is evidence thatneoadjuvant therapy for more than 3 6 and 8 7 months doesnot increase intraoperative morbidity. According to Powellet al RP is feasible after 4 months of treatment for clinicalT3/T4 prostate carcinoma. 8To decrease the morbidity of conventional prostatectomyseveral groups advocate a laparoscopic technique. 9–11 Weintroduced transperitoneal ascending LRP, which is comparableto the retropubic open technique. 12 With respect to theimpact of neoadjuvant antiandrogen treatment on LRP resultsfew comments can be found in the literature. After ourfirst 180 patients we reported that those who underwentneoadjuvant therapy required longer operative time and hada higher transfusion rate. 13 However, in a more recent studyafter 450 cases we did not see any differences. 14 In the sameway Gregori et al could not find any substantial differencesin operative parameters. 15 El-Feel et al reported that androgendeprivation did not significantly affect operative timeduring LRP, 16 and according to Brown et al LRP representsa safe procedure in patients who have received neoadjuvanttherapy. 17NEO has been performed to decrease the rate of positivesurgical margins and improve patient outcome after RP.However, its value in terms of survival remains uncertain.Two prospective, randomized trials state that 3 months ofandrogen deprivation before RP resulted in a significantdecrease in positive surgical margins. 2,4 In addition, Schulmanet al found a lower percent of positive margins inpatients with a clinical T2 tumor who were on neoadjuvanthormonal therapy. 5 However, these findings were not confirmedby a lower PSA progression rate.To evaluate the impact of neoadjuvant hormonal treatmenton LRP outcomes we designed a matched pair analysiscomparing LRP with the Heilbronn technique alone vs LRPa mean of 3.5 months (range 3 to 9) after androgen ablationtherapy.MATERIALS AND METHODSSubmitted for publication March 14, 2005.* Correspondence: Department of Urology, SLK-Kliniken HeilbronnGmbH, Am Gesundbrunnen 20, D-74078 Heilbronn, Germany(telephone: 49-71 31-49-2400; FAX: 49-7131-49-2429;e-mail: jens.rassweiler@slk-kliniken.de).Of the more than 1,100 patients treated with LRP sinceMarch 1999, a comparative study was performed in 50(group 1) who were on neoadjuvant androgen deprivation,followed by LRP, compared to 50 (group 2) without any0022-5347/06/1756-2092/0 2092Vol. 175, 2092-2096, June 2006THE JOURNAL OF UROLOGY ®Printed in U.S.A.Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATIONDOI:10.1016/S0022-5347(06)00260-6

Multivariate Analysis of Factors Predicting Success WithDextranomer/Hyaluronic Acid Injection for Vesicoureteral RefluxSelcuk Yucel, Amit Gupta and Warren Snodgrass*From the Department of Urology, Pediatric Urology Section, University of Texas Southwestern Medical Center at Dallas and Children’sMedical Center Dallas, Dallas, TexasPurpose: Factors influencing outcomes of dextranomer/hyaluronic acid injection for vesicoureteral reflux remain poorlydefined. We performed multivariate analysis of the experience of 1 surgeon (WS).Materials and Methods: The study group contained 168 patients and 259 refluxing units. Goal of injection was coaptationof the orifice with creation of a volcanic mound. Outcomes were determined by cystography obtained 12 weeks followinginjection. Intraoperative photographs of mounds were independently reviewed by 2 authors (WS, SY) without knowledge ofresults, and classified as “satisfactory” or “other.” Univariate and multivariate logistic regression analysis was doneevaluating influence of gender, age, voiding dysfunction, reflux grade, unilateral vs bilateral reflux, ureteral duplication,orifice laterality, subureteral vs intraureteral injection, volume injected and mound appearance.Results: A single injection resolved reflux in 70% of patients and 78% of ureters. Additional injection resulted in overallsuccess in 82% of patients and 86% of ureters. Multivariate analysis demonstrated that reflux grade, volume of dextranomer/hyaluronic acid injected and mound appearance correlated with outcomes. A satisfactory mound was achieved in 81% ofureters, of which 87% no longer refluxed.Conclusions: The ability to create a satisfactory mound was the most important factor determining success of dextranomer/hyaluronic acid injection. Increasing reflux grade was associated with a decreased likelihood of achieving a volcanic mound,and increasing volume injected suggested difficulty in creating a mound.Key Words: vesico-ureteral reflux, dextranomer-hyaluronic acid copolymerSubmitted for publication September 1, 2006.* Correspondence: Department of Urology, Pediatric UrologySection, Children’s Medical Center and University of Texas SouthwesternMedical Center, 6300 Harry Hines Blvd., Suite 1401,Dallas, Texas 75235 (telephone: 214-456-2481; FAX: 214-456-8803;e-mail: warren.snodgrass@childrens.com).For another article on a related topic see page 1546.Despite increasing use of Dx/HA injection to resolvevesicoureteral reflux, there is uncertainty regardingfactors influencing success, with few published reportsof outcomes. In the original clinical trials Lackgrenet al emphasized therapy for children with dilating reflux. 1Accordingly, only 5% of patients had grade II reflux, while26% had grade IV reflux. Consequently, their series is notrepresentative of cases referred in the United States formanagement, the majority of which are grades I to III reflux.Subsequently, Kirsch et al published their observationsfollowing Dx/HA injection in children with grades I to IVreflux, and examined factors potentially predicting outcomes.2 They noted a learning curve with improvement aftertheir initial 20 cases but otherwise found no difference insuccess vs failure on the basis of reflux grade or injectedvolume. However, in a subsequent article these authorsreported increased success after modifying the injectiontechnique and using greater injection volumes. 3 Lavelle et alanalyzed outcomes and similarly found no difference in successby reflux grade or injected volume, noting creation of adesired mound was the only factor identified correlatingwith outcome. 4 In contrast, Elder et al performed metaanalysisof injection therapy for reflux and found outcomesdepended on reflux grade. 5 Given these conflicting observations,we performed multivariate analysis of the experienceof 1 surgeon (WS) with Dx/HA injection for reflux resolution.MATERIALS AND METHODSA total of 213 children (32 males, 181 females) underwentDx/HA injection for vesicoureteral reflux by 1 surgeon (WS)between March 2002 and June 2005. For this analysis patientswith neurogenic bladder (12) and those without postoperativecystography (33) were excluded from further consideration,resulting in a study group of 168 patients (26males, 142 females) and 259 refluxing renal units. Meanpatient age was 4.2 years (range 7 months to 15 years).Indications for injection included breakthrough febrileurinary tract infection despite antibiotic prophylaxis, persistentreflux and/or parental preference for injection over antibioticprophylaxis. Preoperative evaluation included renalultrasonography and voiding cystourethrography. Detailedquestioning was used to diagnose the urge syndrome, infrequentvoiding and/or constipation with therapy, includingtimed voiding, anticholinergics and/or laxatives as indicated,initiated before injection. Grade I reflux was treatedwhen associated with contralateral reflux of higher grade,and in 4 patients following febrile urinary tract infectionwhose parents preferred injection over antibiotic prophylaxis.Cystoscopy was performed with the bladder nearlyempty, with the orifice location visually categorized as “A” to“D,” following the description of Mackie and Stephens. 60022-5347/07/1774-1505/0 1505Vol. 177, 1505-1509, April 2007THE JOURNAL OF UROLOGY ®Printed in U.S.A.Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATIONDOI:10.1016/j.juro.2006.11.077

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