Endothelin-1 Immunoreactivity in plasma is elvated in HIV-1 infected ...

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Volume 72 • 1994 ©linical Investigator Continuation of Klinische Wochenschrift Editor in Chief Ν. Zöllner, Munich Editorial Board G. Adler, Ulm K.-H. Usadel, Frankfurt a.M. ι ν ι α ι ι \£- M.J. Mihatsch, Basle M.E. Bertrand, Lille G. Vantrappen, Louvain B.S. Mitchell, Chapel Hill T. Brandt, Munich P. von Wiehert, Marburg O.-A. Müller, Munich Ε. Erdmann, Munich K.G. Wormsley, Dundee J.G. Puig, Madrid W. Gerok, Freiburg E.O. Riecken, Berlin G. Giebisch, New Haven E. Ritz, Heidelberg F.-D. Goebel, Munich Advisory Board R. Ritz, Basle D. Häussinger, Freiburg Advisory Board S. Sacks, London H. Kaess, Munich R. Arnold, Marburg H. Schuster, Munich J.R. Kalden, Erlangen W.G. Daniel, Hannover H.-P. Schuster, Hildesheim G.J. Krejs, Graz A. Distler, Berlin W. Seeger, Glessen W. Kubier, Heidelberg H.L. Fehm, Lübeck H.-G. Sieberth, Aachen H. Löffler, Kiel R. Ferlinz, Mainz F.-A. Spengel, Munich J. Lubsen, Rotterdam 0. Götze, Göttingen G. Steinbeck, Munich P.M. Mannucci, Milan F.A. Gries, Düsseldorf J.A. Tischfield, Indianapolis P.A. Miescher, Geneva W.L. Gross, G. Utermann, Innsbruck G. Paumgartner, Munich Lübeck/Bad Bramstedt H. Vetter, Bonn H.D. Pohle, Berlin E.G. Hahn, Erlangen C. Wagener, Hamburg D.L. Scott, London H.-L. Hahn, Wiesbaden M. Wienbeck, Augsburg P.C. Scriba, Munich D. Hoelzer, Frankfurt a.M. G. Wolfram, Munich D. Seidel, Munich C. Keller, Munich R. Ziegler, Heidelberg G. Seifert, Hamburg H.J. Kramer, Bonn de,

Transcript of Endothelin-1 Immunoreactivity in plasma is elvated in HIV-1 infected ...

Volume 72 • 1994 ©linical Investigator Continuation of Klinische Wochenschrift

Editor in Chief Ν. Zöl lner , Munich

Editorial Board

G. Adler, Ulm K.-H. Usadel , Frankfurt a.M. ιν ια ι ι \£-M.J. Mihatsch, Basle

M.E. Bert rand, Li l le G. Vantrappen, Louvain B.S. Mi tche l l , Chapel Hill T. Brandt, Munich P. von Wiehert, Marburg O.-A. Mül le r , Mun ich Ε. Erdmann, Munich K.G. Wormsley, Dundee J.G. Puig, Madr id W. Gerok, Freiburg E.O. Riecken, Ber l in G. Giebisch, New Haven E. Ritz, He ide lberg F.-D. Goebel , Munich Advisory Board R. Ritz, Bas le D. Häussinger, Freiburg

Advisory Board S. Sacks, London H. Kaess, Munich R. Arno ld , Marburg H. Schuster, Mun ich J.R. Kalden, Er langen W.G. Danie l , Hannover H.-P. Schuster, H i ldeshe im G.J. Krejs, Graz A. Dist ler, Ber l in W. Seeger, Glessen W. Kubier, Heidelberg H.L. Fehm, Lübeck H.-G. S ieber th , Aachen H. Löffler, Kiel R. Ferl inz, Mainz F.-A. Spenge l , Munich J. Lubsen, Rotterdam 0 . Götze, Gött ingen G. Steinbeck, Mun ich P.M. Mannucci , Mi lan F.A. Gr ies, Düsseldorf J.A. T ischf ie ld , Ind ianapol is P.A. Miescher, Geneva W.L. Gross, G. Utermann, Innsbruck G. Paumgartner, Munich Lübeck/Bad Bramstedt H. Vetter, Bonn H.D. Pohle, Berl in E.G. Hahn, Er langen C. Wagener, Hamburg D.L. Scott, London H.-L. Hahn, Wiesbaden M. Wienbeck, Augsburg P.C. Scr iba, Munich D. Hoelzer, Frankfurt a.M. G. Wol f ram, Mun ich D. Seidel , Munich C. Kel ler, Munich R. Z ieg ler , He ide lberg G. Seifert, Hamburg H.J. Kramer , Bonn

de,

Contents of Volume 72 No 1: PP 1 - 84 publ ished December 6, 1993 No 2: PP 8 5 - 166 publ ished January 3 1 , 1994 No 3: PP 167- 250 publ ished February 28, 1994 No 4: PP 2 5 1 - 330 publ ished March 31 , 1994 No 5: PP 3 3 1 - 414 publ ished May 6, 1994 No 6: PP 415 - 480 publ ished June 23, 1994 No 7: PP 4 8 1 - 554 publ ished July 26, 1994 No 8: PP 555 - 638 publ ished August 30, 1994 No 9: PP 639 - 730 publ ished September 19, 1994 No 10: PP 7 3 1 - 814 publ ished October 19, 1994 No 11 : PP 815 - 936 publ ished November 2, 1994 No 12: PP 937 - 1098 publ ished December 16, 1994

Supplement to Volume 72/lssue 6: Erythropoiet in and Auto logous Transfusion, Dresden, September 14-18, 1993

Abe Κ - * Mizunashi Κ Aboudan F -> Evers J Ackermann Μ -> Krämer BK Adamek RJ, Wegener M, Wienbeck Μ, Köh­

ler Η, Hoffmann Κ, A l tmeyer Ρ: Long-term manomet ry of tubular esophagus in progress ive systemic sclerosis 343

Adams Ο -» Jablonowski Η Adlkofer F -> Einhaus Μ Adorf D, Gra jer KH, Kaboth W, Neri C:

Agranulocytos is induced by ant i thyroid therapy: effects of t reatment with g ranu­locyte colony st imulat ing factor 390

Agnati LF -» Fuxe Κ A g u i l a r M —• Gomez JM Ahmad Μ -»· Syed TA Ahmad SA -» Syed TA Albert i Β -> Antonel l i A Albrecht Η - • Stel lbr ink HJ Albrecht Η, Stel lbr ink HJ, Gross G, Berg B,

Helmchen U, M e n s i n g H : Treatment of atypical le ishmanias is wi th interferon γ result ing in progression of Kaposi 's sar­coma in an AIDS patient 1041

Alexander Κ --> Ranke C A l l e r b e r g e r F -> VogetsederW Al tmeyer Ρ - * Adamek RJ Andbjer Β Fuxe Κ Andresen D Behrens S Angermann CE -> Stempfle HU Antonel l i A, Campatel l i A, Di Vito A, Alber­

ts B, Baldi V, Salv ioni G, Fallahi P, Ba-schier i L: Compar ison between ethanol sc lerotherapy and empty ing with injec­t ion of sal ine in t reatment of thyro id cysts 971

Anzai Κ -> Nagafuchi S Arno ld JC, Hei l ig Β, Kal l inowski Β, Otto G,

Kommere l l Β, The i lmann L: Soluble tumor necrosis factor receptors in patients wi th recurrent hepatit is C v i ­rus infect ion after l iver t ransplantat ion 470

Atzpodien J -> Buer J Auberger Κ -> Wintergerst U Aufenanger J Ensenauer R Avenar ius H-J Ranke C

Baart de la Fail le Η Lupus therapy 749 Bacher Β - * Wang Χ

Bäcker A Bokemeyer D Bäcker A -> Kramer HJ Bajo A -> Laso FJ B a k k e r C J G : Magnet ic resonance angiog­

raphy 85 Baldauf J -> Jurna I Baldi V Antonel l i A B a l d u s M , Möl ler M, Walter H, Brass H,

Q u e i ß e r W : A case of pure red cell ap las ia : fo l low-up on different immuno­suppressive reg imens 1051

Balfour DJK - • Benwel l MEM Banyai Μ -> Capek Μ Barash V Chajek-Shaul Τ Bartens W, Wanner C: L ipoprote in(a) : new

insights into an atherogenic l ipoprotein 558

Bar tmann Ρ -» Jab lonowsk i Η Baschier i L Antonelli A Base W -> Sexl V Bauer J, Hohagen F, EbertT, T immer J,

Ganter U, Kr ieger S, Lis S, Postler E, Voderholzer U, B e r g e r M : lnterleukin-6 serum levels in healthy persons corre­spond to the s leep-wake cycle 315

Bauer Τ -+ Hagendorff A Baumgar tner G - * Pecherstorfer Μ B a y r a k t a r M , Usman A, K o r a y Z : Effect of

the new somatostat in analogue SMS 201-995 on exogenously used in­sul in 669

Becher Η Schmitz U Beger Η -> L immer J Behrens S, Andresen D, Brüggemann T,

Schröder R: Ventr icular f ibr i l lat ion relat­ed to coronary spasm in patients wi thout s igni f icant coronary or other structural heart d isease 307

Behr R Füssle R BehrT, Fischer P, Mül ler-Felber W,

Schmidt-Achert M, Pong ra t zD : Myofi-br i l logenesis in pr imary t issue cultures of adult human skeletal musc le : expres­sion of desmin , t i t in, and nebul in 150

Belohradsky BH -> Wintergerst U Benker G -> Jaspers C Benwel l MEM, Balfour DJK, Khadra LF:

Studies on the inf luence of nicotine infu­sions on mesol imbic dopamine and lo­comotor responses to nicotine 233

Berg Β - • Albrecht Η Berger Μ -> Bauer J Bergmann L -» Kamps BS Berg PA -+ Klein R Bergs C -» Schneider Τ Bernecker Ρ -» Erlacher L Besenthal I -»> Knisei W Beyenburg S -> Schröder R Beyer J -> Kubier A Bingley PJ -»· Wagner R Biscoping J -> Füssle R Bittl Μ -+ Br iegel J Blaustein MP: Endogenous ouaba in : phy­

siological activity and pathophysio logi­cal impl icat ions 706

Bleich Μ -» Greger R Blum HE Offensperger W-B Bobrow Μ Flinter F Bode-Böger S Ranke C Bodmann KF, Tröster S, Clemens R, Schu­

ster HP: Hemodynamic profi le of intra­venous fenoldopam in patients with hy­pertensive cr isis 60

B o e h m e M W J , Werle E, Kommere l l B, Raeth U: Serum levels of adhesion mo­lecules and thrombomodul in as indica­tors of vascular injury in severe Plas­modium fa lc iparum malar ia 598

Bogner C ->· Gawaz Μ Bogner JR -» Lieg! U Bogner JR -> Rolinski Β Böhmer Β Malessa R Bokemeyer D Kramer HJ Bokemeyer D, Fr iedr ichs U, Bäcker A,

Kramer HJ, Meyer-Lehnert H: Cyclospo-rine A enhances total cel l calc ium inde­pendent of Na-K-ATPase in vascular smooth muscle cel ls 992

Böker KHW Mül ler MJ Boldt I -» Brennemann W Bonifacio Ε -> Wagner R Bonmann Ε -> Witzke Ο Borberg Η Waidner Τ Borensztein Ρ -> Pinet F Borräs R -> Laso FJ Bottazzo GF Wagner R Boye Ε -> Flinter F Brandl BC - * Stempfle HU Brass Η Baldus Μ Braun GG -> Tschaikowsky Κ Brech W -» Murer Η Brennemann W, Brensing ΚΑ, Leipner Ν,

Boldt I, K l ingmül ler D: Attempted pro­tection of spermatogenesis f rom i r radia­t ion in patients with seminoma by D-Tryptophan-6 luteinizing hormone re­leasing hormone 838

Brensing KA -> Brennemann W Breyer S -> Wenisch C Brezinschek HP -* Wascher TC Brezinschek R - * Wäscher TC Br iegel J , Kel lermann W, Forst H, Hal ler

M, Bittl M, Hoffmann GE, Büchler Μ, Uhl W, Peter K, Phosphol ipase A 2 Study Group: Low-dose hydrocort isone infu­sion attenuates the systemic in f lamma­tory response syndrome 782

Brockmeyer NH -»· Malessa R Brockmöl ler J -> Drakou l i sN Brodt H-R -> Kamps BS Brown D -> Sabol ic I

IV

Brückmann C -> Wintergerst U Brüggemann Τ Behrens S Brunkhorst R, Wrenger E, Koch K M : Low-

dose predniso lone/ch lorambuci l thera­py in patients wi th severe membranous g lomerulonephr i t is 277

Büchler Μ -> Br iegel J B u e r J , Kirchner Η, Schomburg Α, Schü­

ler A, Manns Μ, Lopez-Hänninen Ε, Duensing S, Po l iwodaH, Atzpodien J : Cytokine-based biotherapy of gastro­intestinal tumors 526

Butruk Ε -> Habior A Butz Κ Hoppe-Seyler F Bye S, Mal lmann R, D u l e y J , S im-

monds HA, Chen J, Tischf ield JA, Sa-h o t a A : Identif ication of a 7-basepair delet ion in the adenine phosphor ibosy l -t ransferase gene as a cause of 2,8-dihy-droxyadenine urol i th iasis 550

Caine Y Chajek-Shaul Τ Calzetti C Pedretti G Campatel l i A -> Antonel l i A Canessa C -> Hor isberger J-D Capek M, Schnack C, Ludvik B, Kautzky-

Wil ler A, Banyai M, Prager R: Effects of Captopril t reatment versus placebo on renal function in type 2 diabet ic patients with microa lbuminur ia : a long-term study 961

Cascorbi I - * Drakoul is Ν Caspary WF -> Wehrmann Τ Castro de S -> Laso FJ Chajek-Shaul T, Scherer G, Barash V, Shi -

loni E, Caine Y, Stein O, Stein Y: Meta­bolic effects of nicotine on human adipose t issue in organ culture 94

Cheema KM -> Syed TA Cheema R - • Syed TA Chen J Bye S Christ M, Klauss V, Pl iml W, Theisen K,

W e h l i n g M : Volumes and N a + / H + an -t iporter activity of lymphocytes in pa­tients with congest ive heart fa i lure 985

Chuman Η -+ Nagafuchi S Cissewski Κ -> Rzepka AH Classen H-G -> Rob PM Clemens R -> Bodmann KF Cocozza S -> De Lorenzo F Co l lazosJ , Mart inez E, Flores M, M a y o J :

Aspergi l lus pneumonia successful ly treated with i t raconazole in a patient with systemic lupus erythematosus 920

Col lazos J : Glycochol ic acid in chronic ac­tive hepatit is and mi ld l iver diseases 36

Collet C - * Lingenfelser Τ Cordero Μ -»· Laso FJ Corvol Ρ Pinet F Creutzig A -> Ranke C

Danek A, Witt TN, Mann K, Schweikert HU, Romalo G, La Spada AR, Fischbeck K H : Decrease in androgen binding and ef­fect of androgen t reatment in a case of X-linked bulbospinal neuronopathy 892

Danos Ρ -> Hagendorff A Danpure CJ : Molecular and cell biology of

pr imary hyperoxalur ia type 1 725 Dec r in i sM, Dode rS , Stark G, Pilger E: A

prospective evaluat ion of sensit ivi ty and

specif ici ty of the ank le/brachia l index in the fo l low-up of superf ic ia l femora l artery occlusions treated by angiop las­ty 592

Dell ing G - * Harten Ρ De Lorenzo F, Mont icel l i A, Cocozza S,

De Simone Β, Rubba Ρ: Extracoronary atherosclerosis and genet ic var iants of apol ipoprote in AI-CIII c luster in myocar­dial infarct ion surv ivors f rom southern Italy 435

Denisl ic M, Meh D: Neurophysio logica l as­sessment of per ipheral neuropathy in pr imary Sjogren's syndrome 822

De Simone Β -> De Lorenzo F Deitmers C -> Hagendorff A DeVries JX -> Sch lenke rT Dieckmann K-P -> Gross AJ Diener H-C -> Malessa R Dienes HP -> Wölfel Τ Dierich MP Vogetseder W Dih lmannW, Schnabel A, Gross WL: The

acquired hyperostosis synd rome : a l i t t le known skeletal d isorder wi th dist inct ive radiological and cl in ical features 4

Dippold W -> Wölfel Τ Dirksen U Horneff G Dissmann Τ -> Schneider Τ Di Vito A -> Antonel l i A Dobmeye rJ -> Feussner G Dobos GJ, Traynor-Kaplan AE, Ward D,

Schol lmeyer PJ: Neutrophi l dysfunct ion in end-stage renal fa i lu re : reduced re­sponse to pr iming by C5a 353

DoderS -> Decrinis Μ Doherty Ε -» Seed Μ Dörr U - • Iser G Drakoul is Ν, Cascorbi I, Brockmöl ler J,

Gross CR, Roots I: Po lymorph isms in the human CYP1A1 gene as suscept ib i l i ­ty factors for lung cancer : exon-7 muta­tion (4889 A to G), and a Τ to C mutat ion in the 3'-f lanking region 240

Drexel Η -> Föger Β Duensing S - • Buer J Duley J Bye S Duque-Reina D Mertens PR Düsing R -> Schmitz U Düsing R, Le ibhammer S, Hoffmann G,

Vetter Η, Siffert W: Hypertonic sal ine in­fusion induces act ivat ion of the lympho­cyte Na + / H + ant iport and cytosol ic a lka-l inization in healthy human subjects 817

Eber tT - * Bauer J Ebert W -> Muley Τ Eckert F -> Wagner DR Eggstein Μ Knisei W Eggstein Μ -» Lingenfelser Τ Eggstein Μ -> Luft D Ehmke Η -»> Ki rchheim HR Ehrenreich Η -> Rolinski Β Ehrenreich Η, Poser W: Dependence on

tramadol 76 Ehrl ich S -> Haak Τ Eiben Ρ -> Sander D Einhaus M, Holz O, Meißner R, Krause T,

Warncke K, Held I, Scherer G, Trick­er AR, Adlkofer F, Rüdiger HW: Determi­nation of DNA single-strand breaks in

lymphocytes of smokers and nonsmok-ers exposed to env i ronmenta l tobacco smoke using the nick t ranslat ion assay 930

Eisele Ε -> L immer J Elia G -+ Pedrett i G Eilbrück D -> L immer J Endo Κ -» Mizunashi Κ Endres HGE, Grüner Ο: Compar ison of

D 2 0 and ethanol di lut ions in total body water measurements in humans 830

Engelhardt D: Steroid biosynthesis in­hibi tors in Cushing's syndrome 481

Engelstein Ε, Terres W, Hofmann D, Han­sen L, Hamm CW: Improved g lobal and regional left vert icular funct ion after an­gioplasty for chronic coronary occlu­sion 442

Ensenauer R, Püttmann Μ, Quintel Μ, Kat-termann R, A u f e n a n g e r J : Compar ison of serum phosphol ipase A 2 , po lymor­phonuclear granulocyte elastase, C-re-act ive protein and serum amylo id A wi th the APACHE II score in the prognosis of mul t ip le in jured patients 843

E r d m e n g e r L -» Jeck Τ Erlacher L, Teufelsbauer Η, Bernecker Ρ,

Pietschmann Ρ, Weissei Μ: Compar ison of serum f luor ide levels after admin is ­trat ion of monof luorophosphate-ca lc ium carbonate or sodium f luor ide : differ­ences in peak serum concentrat ions 1082

Escobar-J imenez F -» Vidal-Puig A Etzersdorfer Ε -> Wenisch C Euler HH -> Harten Ρ European Working Group on Famil ia l Hy-

percholestero laemia -> Schuster Η Evers J , Aboudan F, Lewalter J , Renner Ε:

Hemodia lys is in metacresol poisoning 472

Ewers-Grabow U -> Windler Ε

Fabel Η -> Flüge Τ Faergeman Ο -> Hansen PS Fallahi Ρ -> Antonel l i A Falter Β, Kutzer C, Richter E: B iomoni tor ­

ing of hemoglob in adducts: aromat ic amines and tobacco-specif ic ni t ro-samines 364

Fandrey J -> Gross AJ Fehske W Reichel W Feldges A -> Korte W Ferl inz R -> Kienast Κ Ferl inz R -> Lorenz J Fernandez-Castaner Μ -» Fernandez-Re­

al JM Fernandez Castaner Μ - * Gomez Säez JM Fernandez Real JM -> Gomez Säez J M Fernändez-Real JM, Fernandez-Cas­

taner M, V i l l abonaC, Sagarra E, Go-mez -SäezJM, Soler J : Giant in t rasel lar aneurysm present ing with panhypopi tu­i tar ism and subarachnoid hemor rhage : case report and l i terature rev iew 302

Feussner G, Stech C, D o b m e y e r J , Schae-fer H, Otto G, Ziegler R: Serum amy lo id A protein (SAA): a marker for l iver a l lo­graft reject ion in humans 1007

Fiaccadori F -> Pedretti G Fil le Μ Vogetseder W

ν Finnman U-B Fuxe Κ Fischbeck KH -> Danek A Fischer A, König W: Modulat ion of in v i t ro

Immunoglobul in synthesis of human pe­r ipheral b lood mononuc lear cel ls by nicotine and cot in ine 225

Fischer HP -+ Reichel W Fischer Μ -» Pecherstorfer Μ Fischer Ρ -> Behr Τ F l e s c h M , Sachin id is A, Ko YD, Kraft Κ,

Vetter Η: P lasma l ipids and l ipoprote ins and essent ial hyper tension 944

Flik J Wagner D F l in terF, Boye E, Vetrie D, Harr is A, Bo-

brow Μ: Genetic aspects of renal dys­funct ion: A lpor t 's syndrome 728

F l i se rD , R i t z E : Cl in ical prob lems of d i ­uretic t reatment 708

Flores Μ -» Col lazos J Flüge T, Fabel Η, Wagner TOF, Forss-

m a n n W G : Local izat ion of the bron-chodi lator effect induced by type A natr i ­uretic peptide in asthmatic subjects 772

Flury RF -> Risti Β Föger Β, Drexel Η, Hopferwieser Τ, Mie­

senböck G, Ritsch A, Lechlei tner M, T röb inge rG, Patsch JR: Fenofibrate im­proves postprandia l chy lomicron clear­ance in II Β hyper l ipoprote inemia 294

Fölsch Β -» Haiwachs G Fölsch UR -> Mönig Η Forssmann WG -> Flüge Τ Forst Η -> Br iegel J Franzen D -> Waidner Τ Frei U Kl iem V F r e y F J : 11 ß-Hydroxysteroid dehydroge­

nase: a re levant determinant of g luco-and mineralocor t ico id-act ions 701

Fr iedberg Τ -> Lorenz J Friedrichs U —> Bokemeyer D Fritsch Η -> Ju l ius U Fritsch W -> Ju l ius U Fröl ich J --> Ranke C Fuchs S -* Pinet F Fücker Κ -»> Ju l ius U Fukushima Ν -*• Nagafuchi S FurukawaY -» Mizunashi Κ Füssle R, Biscoping J, Behr R, Sziego-

leit A: Development of resistance by En­terobacter c loacae dur ing therapy of pulmonary infections in intensive care patients 1015

Fuxe K, Rosen L, Lippoldt A, Andbjer B, Hasselrot U, F innman U-B, Agnat i LF : Chronic cont inuous infusion of nicot ine increases the d isappearance of chol ine acetyl t ransferase immunoreact iv i ty in the chol inergic cel l bodies of the media l septal nucleus fo l lowing a part ial uni lat­eral t ransect ion of the f imbr ia fornix 262

Galanski Μ -» Ranke C Gamba G -> Hebert SC Gandenberger S -> Wintergerst U Ganter U -> Bauer J Garcia-Calvente C -» Vidal-Puig A Garcia-Sänchez JE -> Laso FJ Gärtner HV Spyr idopoulos I Gawaz M, Bogner C: Changes in platelet

membrane g lycoprote ins and platelet-

leukocyte interact ion dur ing hemodialy­sis 424

Geier SA -» Rol inski Β Genovese S - * Wagner R Gerdes LU Hansen PS Gerken G -> Wölfel Τ Germain S -+ Pinet F German AIDS Study Group : Survival of pa­

tients receiv ing z idovudine before or af­ter AIDS d iagnos is : results of a German mult icenter study 111

Gerok W Hafkemeyer Ρ Gerok W -»· Offensperger W-B Glaser F - • Wolf Ο Goebel FD -» Liegl U Goebel FD -» Rol inski Β Goebel Y -> Rob PM Gomez JM, A g u i l a r M , Navarro MA, Orto-

l ä J , S o l e r J : Secret ion of growth hor­mone and thyroid-st imulat ing hormone in patients wi th dement ia 489

Gomez-Säez JM -> Fernändez-Real JM Gomez Säez JM, Fernandez Real JM, Fer­

nandez Castaner M, Navarro Moreno MA, Mart inez Matos JA: Study on growth hormone and insul in secret ion in myotonic dystrophy 508

Gonzälez-Bui t rago JM Laso FJ Grabensee Β -> Hol lenbeck Μ Grabitz Κ -» Kniemeyer HW Grajer KH Adorf D Graninger W -> Wenisch C Greger R, Lohrmann E, Bleich M: Tubular

act ions of d iuret ics (overview) 690 Greminger P, Suter PM, Holm D, Kobelt R,

Vetter W: Morn ing versus evening ad­ministrat ion of ni fedipine gastrointest i ­nal therapeut ic system in the manage­ment of essent ial hypertension 864

Gresser U -+ Wagner DR Gressner AM -> Körner Τ Greten Η -> Stel lbr ink HJ Greten Η -> Windler Ε G r i g o r i e v A l , Morukov BV, Vorob ievDV:

Water and electrolyte studies dur ing long-term missions onboard the space stat ions SALYUT and MIR 169

Gross AJ, Wolff M, Fandrey J , Miersch W-D, Dieckmann K-P, Je lkmann W: Preva­lence of paraneoplast ic erythropoiet in product ion by renal cell carc inomas 337

Gross CR -> Drakoul is Ν Gross G -+ Albrecht Η Gross W -* Haak Τ Gross WL -> D ih lmannW Grüner Ο -> Endres HGE Grünert A -» Haug C Grüne S Jeck Τ Gwechenberger Μ ->· Hirschl MM

Haak T, Jungmann E, Kasper-Dahm G, Ehrl ich S, Usadel K H : Elevated endothe­lin 1 levels in cr i t ical i l lness 214

HaakT, MärzW, Jungmann Ε, Hausser S, Siekmeier R, Gross W, Usadel K-Η: Ele­vated endothel in levels in patients with hyper l ipoprote inemia 580

Habenicht AJR, Janßen-Timmen U, Z ieg­ler R, Schett ler G: Lipoproteins and their funct ions 639

Habior Α, Walewska-Zielecka Β, Butruk Ε: Hepatocel lular-cholestat ic l iver injury due to amoxyci l l in-c lavulanic acid com­bination 616

Haferkamp Ο, Seibold Η, Stauch Μ, Klee­berg S, Rödel G: Neutrophi l ic migrat ion through capi l lary l ike mic ropores : inf lu­ence of pu lmonary passage 30

Hafkemeyer P, Schupp Μ, Storch Μ, Ge­rok W, Häussinger D: Excessive iron storage in a patient wi th Wilson's dis­ease 134

Hagendorff A, Deitmers C, Danos P, Wet­ter S, Lassau M, Pizzull i L, Omran H, Bauer T, Hartmann Α, Lüderitz Β: Carot­id artery stenosis and tachyarrhythmi­as : regional cerebral blood f low dur ing high-rate ventr icular pacing after one vessel occlusion in rats 775

Hake U H e r r W H a l b m a y e r W M -> Pecherstorfer Μ Hal ler Μ -> Briegel J Haiwachs G, Tiran A, Reisinger EC, Zach

R, Sabin Κ, Fölsch Β, Lanzer Η, Holz­er Η, Wilders-Truschnig Μ: Serum lev­els of the soluble receptor for tumor ne­crosis factor in patients with renal d is­ease 473

H a m m a r C - H - * Körner Τ Hamm CW -> Engelstein Ε Hammel G -> Schewe CK Hanefeld Μ -> Jul ius U Hanke Η -> Strohschneider Τ Hannekum A -> Strohschneider Τ Hansen L -> Engelstein Ε Hansen PS, Me ine r t zH , Gerdes LU, Klau­

sen IC, Faergeman O: Treatment of pa­tients with fami l ia l defective apol ipo-protein B-100 with pravastatin and gem­f ib roz i l : a two-per iod cross-over study 1065

Harr is A -> Flinter F Harr ison-Bernard LM -> Navar LG Harten P, Euler HH, Wolf E, Dell ing G,

Lö f f l e rH : Disseminated histoplasmosis in a non- immunocompromised host 878

Hart lapp JH Reichel W Hartmann A -> Hagendorff A Hashizume Μ Nagafuchi S Hassel rot U Fuxe Κ Hatano A -> Takeda Μ Haug C, Metzele Α, Stetigen J, Kochs Μ,

Hombach V, Grünert A : Increased brain natr iuret ic peptide and atr ial natr iuret ic peptide p lasma concentrat ions in dialy­sis-dependent chronic renal fai lure and in patients wi th elevated left ventr icular f i l l ing pressure 430

Hauschi ld A -» Mönig Η Hausser S -> Haak Τ Häussinger D -» Hafkemeyer Ρ Hay ID -> Heufelder AE Hebert SC, Gamba G: Molecular c loning

and character izat ion of the renal diuret­ic-sensit ive electroneutral sodium-(po-tassium)-chlor ide cotransporters 692

Hecker Η -> Ranke C Heil ig Β Arnold JC Heimpel Η -» L immer J Helber U Spyr idopoulos I

VI

Held I -»- Einhaus Μ He lmchen U A lbrecht Η Helm EB -> Kamps BS Hemmer l i ng AE -> Wagner D Hengge U - • Malessa R Her ing W ~* Tschaikowsky Κ Hermann J -> Wascher TC Her rW, Schwer t ing A, Wit t ig Β, Wani-

tschke R, Schni tz ler G, Weiner th J , Jo-chum W, Hake U, Meyer z u m Büschen­fe lde K-Η: Enormous hemang iosa rcoma of the heart 372

Heufe lder AE, Hay ID: Ev idence for au ­t o immune mechan isms in the evo lu t ion of invasive f ib rous thyro id i t is (Riedel 's s t ruma) 788

H e y d e n s , Kluthe R, I m m e n h o f e r C : Inter­nat ional Sympos ium on Sod ium and Hy­per tens ion. Results of randomized t r i ­als 800

Hi lbert Ν - * Hol lenbeck Μ Hirschl M M , Gwechenberger Μ, Zehe tg ru -

ber Μ, Weber Η: Severe compl i ca t ions fo l lowing th romboly t ic therapy of an acute th rombos is of a prosthet ic mi t ra l va lve 466

H o e k s t r a J H : Acute gast roenter i t i s in Eu­rope and the use of ora l rehydra t ion therapy 167

Hoffmann G Düsing R Hoffmann GE Br iege l J Hof fmann Κ Adamek RJ Hoffmeister HM -> Spyr idopou los I Hofmann D -> Engelste in Ε Hohagen F -> Bauer J Höhler T, Teuber G, Wani tschke R, Meyer

zum Büschenfe lde K-Η: Indomethac in t reatment in amphote r i c in Β induced nephrogen ic d iabetes ins ip idus 769

Holhorst Κ -» K l iem V Hol lenbeck M, Hi lbert N, Meuse l F, Gra-

b e n s e e B : Increasing sensi t iv i ty and speci f ic i ty of Doppler sonograph ic de­tect ion of renal t ransp lant re ject ion wi th ser ia l invest igat ion techn ique 609

Höllt V -κ Wang Χ Holm D - * Greminger Ρ Holzer Η Haiwachs G Holz Ο ->· Einhaus Μ Hombach V -»· Haug C Hombach V Waidner Τ Hopferwieser Τ -> Föger Β Hoppe-Seyler F, B u t z K : Tumor suppres­

sor genes in mo lecu la r med ic ine 619 Höpp HW Waidner Τ Hor ina JH -> Kaufmann Ρ Hor ina JH -> Stauber RE Hor isberger J-D, Puoti A, Canessa C, Ros-

s ier BC: The ami lo r ide receptor 695 Horneff G, Dirksen U, Wahn V : ln ter feron-γ

for t reatment of severe atopic eczema in two ch i ld ren 400

Houwel ing H: HIV t ransmiss ion in the p ro­v is ion of health care 1

Huer tas-Gonzales JM Perez-Bianco FJ Humphr ies S L indahl G Humphr ies S -» Schuster Η Humphr ies SE Seed Μ Hupper t ΡΕ Spyr idopou los I

I m m e n h o f e r C -> Heyden S

Inscho EW -> Navar LG Irsigler Κ -> Pecherstorfer Μ Iser G, Pfohl M, Dörr U, Weiss EM, Seif FJ :

Ectopic ACTH secret ion due to a bron­chopulmonary carc ino id local ized by so­matostat in receptor sc int igraphy 887

Ishibashi Η -> Nagafuchi S Ishi iM -> Yasuda G Ittel ΤΗ -> Mertens PR Ittensohn A -> de Vries JX Ittensohn A -> Loftier W

Jablonowski H, Sander O, Wi l lers R, Adams O, Bar tmann Ρ, Wahn V: The use of intravenous immunoglobu l ins in symptomat ic HIV infect ion. Results of a randomized study 220

Jakober Β Lingenfelser Τ Jakob G -> Vorderwink ler K-P Jandik Ρ M e l i c h a r B Janßen-Timmen U -> Haben ich tAJR Jaspers C, B e n k e r G , Reinwein D: Treat­

ment of pro lact inoma patients wi th the new non-ergot dopamine agonist rox in-do l : f irst results 451

Jaspersen D -> Körner Τ Jeck Τ, Weisser Β, Mengden Τ, Erd-

menger L, Grüne S, Vetter W: Pr imary a ldosteron ism: di f ference in c l in ical presentat ion and long-term fo l low-up between adenoma and bi lateral hyper­plasia of the adrenal g lands 979

Jelkmann W -*> Gross AJ Jerusalem F ->> Zierz S Jochum W Herr W Jockenhövel F, Lederbogen S, Ulbr icht T,

Schmidt-Gayk H, Krenning EP, Lam­berts SWJ, Reinwein D: The long-acting somatostat in analogue octreot ide a l lev i ­ates symptoms by reducing posttransla-t ional convers ion of prepro-g lucagon to glucagon in a patient wi th mal ignant g lucagonoma, but does not prevent tu­mor growth 127

Jodar-Gimeno Ε -»> Vidal-Puig A Johnston DA, W o r m s l e y K G : Problems

with the interpretat ion of gastr ic pH measurement 12

Jos tWH, Rapp C, König J, S c h i m r i g k K : Are heart rate responses reproducib le in the t i l t-table test? 996

Judmaier G Vorderwink ler K-P Jul ius U, Fritsch H, Fritsch W, Rehak E,

Fücker K, Leonhardt W, Hanefeld M: Im­pact of hormone rep lacement therapy on postprandial l ipoproteins and l ipo­p r o t e i n ^ ) in normol ip idemic post­menopausal women 502

Jungmann Ε -»· Haak Τ Jurna I, Krauß Ρ, Baldauf J : Depression by

nicotine of pain-related nocicept ive ac­tivity in the rat tha lamus and spinal cord 65

Kaboth W Adorf D Kahlon BMM -» Syed TA Kal l inowski Β Arnold JC Kamps BS, Brodt H-R, Staszewski S,

Bergmann L, H e l m E B : AIDS-free sur­vival and overal l surv ival in HIV infec­

t ion : the new CDC classi f icat ion system (1993) for HIV disease and AIDS 283

Kamradik Β Netter Ρ Karsch KR - * Strohschneider Τ Kasper-Dahm G -> Haak Τ Kassubek J Witzke Ο Kater W -» Wehrmann Τ Kat termann R Ensenauer R Kaufmann P, Smol le KH, Horina JH, Zach

R, Krejs G J : Impact of long-term hemo­dialysis on nutr i t ional status in patients with end-stage renal fa i lure 754

Kautzky-Wil ler A -> Capek Μ Kawamor i Τ, TanakaT, Kawase Y, Shi -

roko J, Tanahashi S, Mori H: An α-feto­protein producing pancreat ic cystade-nocarc inoma 377

Kawase Υ Kawamor i Τ Ke l le rmann W Br iegel J Kel lner Η, Yu D: The pathogenesis of HLA-

B27 associated ar thr i t is : lessons f rom the B27 crystal 321

Kern Ρ -» Wagner D Kern WV -> Wagner D Keulers Ρ Mertens PR Khadra LF -> Benwel l MEM Kienast K, Riechelmann Η, Knorst Μ,

Schlegel J , Mül le r -Quernhe im J , Schel­lenberg J, Ferl inz R: An exper imenta l model for the exposure of human ci l iat­ed cel ls to sulfur d ioxide at dif ferent con­centrat ions 215

Kikuchi Μ -> Nagafuchi S K i m u r a T -> Mizunashi Κ K i rchheim HR, E h m k e H : Vasoactive hor­

mones : modulators of renal funct ion 685 688

Kirchner Η -»· Buer J K i r s c h b a u m e , Scherer G, Strasburger

C J : Pituitary and adrenal hormone re­sponses to pharmacolog ica l , physical , and psychological s t imulat ion in habitu­al smokers and nonsmokers 804

Klausen IC -> Hansen PS Klauss V Christ Μ Klauss V -> Rolinski Β Kleeberg S - * Haferkamp Ο Klein R, Berg PA: A comparat ive study on

ant ibodies to nucleol i and 5-hydrox-y t ryptamine in patients wi th f ib romya l ­gia syndrome and t ryptophan- induced eos inophi l ia -myalg ia syndrome 541

Kl iem V, Ringe B, Holhorst K, F r e i U : Kid­ney t ransplantat ion in hepati t is Β sur­face ant igen car r iers 1000

K l i m p f i n g e r M Stauber RE Kl ingelhöfer J Sander D K l ingmül ler D -» Brennemann W Kluthe R - • Heyden S Knappertz VA Kubier A Kn iemeyer HW, Sandmann W, Schw ind tC ,

Grabi tz K, Torsel lo G, Stühmeier Κ: Thrombectomy with ar ter iovenous f istu­la for embol iz ing deep venous th rombo­s is : an al ternat ive therapy for preven­tion of recurrent pu lmonary embol ism 40

Knise lW, Pfohl M, Mül ler M, Besenthal I, d i N i c u o l o A , VoelkerW, Ris lerT, Egg-stein M : Comparat ive long-term exper i ­ence wi th immunoadsorpt ion and dex-

VII

t ran sulfate cel lu lose adsorpt ion for ex­t racorporeal e l iminat ion of low-density l ipoproteins 660

Knol le Ρ - * Wölfel Τ Knorst Μ -> Kienast Κ Kobayashi I -»- Kubota Κ Kobelt R -> Greminger Ρ Koch KM -* Brunkhorst R Kochs Μ -> Haug C Köhler Η -> Adamek RJ K o h l e r S M -> Krämer BK Koizumi Τ Takeda Μ Komeyama Τ Takeda Μ Komlosi Ρ -> Nagy I Kommere l l Β -> Arno ld JC Kommere l l Β Boehme MWJ Kommere l l Β Sch lenke rT König J -> J o s t W H König W Fischer A Konz Κ Luft D Koray Ζ -» Bayraktar Μ Körner Τ, Kropf J , Jaspersen D, Hammar

C-H, G r e s s n e r A M : On the diagnost ic potential of f ibronect in in human bi le f lu­id 316

Korte W, F e l d g e s A : Increased pro throm­bin act ivat ion in a patient with congeni ­tal a f ib r inogenemia is revers ib le by f ibr inogen subst i tut ion 396

Kört ing HC -> Schäfer-Kört ing Μ Κο Υ - * Schmitz U Κο YD Flesch Μ Kraft Κ -» Flesch Μ Krämer BK, Ackermann Μ, K o h l e r S M ,

Riegger G A J : Role of endothel in in hy­pertension 88

Krämer G -> Kubier A Kramer HJ -» Bokemeyer D Kramer HJ, Bäcker A, Bokemeyer D,

Meyer-Lehner t H: Atr ia l natr iuret ic pep­t ide and endothe l in : modulators of renal funct ion 703

Kramer HJ: Mul t ip le scienti f ic publ ica­t ions 555

Krams Μ -> Malessa R Krause Τ -> Einhaus Μ Krauß Ρ - • Jurna I Krejs GJ -> Wascher TC Krejs GJ -> Kaufmann Ρ Krejs GJ Stauber RE Krenning EP -»· Jockenhövel F Kr ieger S -> Bauer J Kropf J -> Körner Τ Krüger TM -> Stempfle HU Kubier A, Rothacher G, Knappertz VA,

Krämer G, Nink M, Beyer J , L e h n e r t H : Intra- and ext racerebra l blood f low changes and f lushing after int ravenous injection of human cor t icot ropin-re leas-ing hormone 331

Kubier W - • N i roomand F Kubota K, T a m u r a J , Kurabayashi H, Shi -

rakuraT, Kobayashi I: Evaluat ion of in­creased serum ferr i t in levels in patients with hyper thyro id ism 26

Kuntz C -» Wolf Ο Kurabayashi Η -» Kubota Κ Kutzer C -> Falter Β

Lamberts SWJ -> Jockenhövel F Landthaler Μ -> Wagner DR

Landthaler R -> d e V r i e s J X Landthaler R -> Löffler W L a n d W : Impact of the reperfusion injury

on acute and chronic reject ion events fo l lowing c l in ical cadaver ic renal trans­plantat ion 719

Lange S Mönig Η Lanzer Η -> Haiwachs G Lardel l i Ρ -+ Vidal-Puig A Laso FJ, Cordero M, Garcia-Sänchez JE:

Esophageal bruce l los is : a new location of Brucel la infection 393

Laso FJ, Madruga I, Borräs R, Bajo A, Gonzälez-Bui t rago J M , Castro de S: Hy­pokalemia in opiate overdose 471

La Spada AR -> Danek A Lassau Μ -> Hagendorff A Läszlö Jr F - • Nagy I LDLApheres i s Study Group -> Wa idnerT Lebeau A - • Rob PM Lechlei tner Μ -> Föger Β Lederbogen S -> Jockenhövel F Lehnert Η -> Kubier A Lehnert Τ -> Wolf Ο Le ibhammer S -> Düsing R Le ipne rN -+ Brennemann W Leonhardt W Jul ius U Lewalter J -> Evers J Liegl U, Bogner JR, Goebel FD: Insulin-de­

pendent diabetes mel l i tus fol lowing pentamid ine therapy in a patient with AIDS 1027

L immer J , El lbrück D, Mül ler H, Eisele E, R i s t J , Schütze F, Beger H, Heim-pel H, Seifr ied Ε: Prospect ive random­ized cl in ical study in general sur­gery compar ing a new low molecular weight hepar in wi th unfract ionated hep­ar in in the prevent ion of thrombosis 913

Lindahl G, Mai l ly F, Humphr ies S, Seed Μ: Apol ipoprote in Ε phenotype and l ipo­p r o t e i n ^ ) in fami l ia l hypercholestero­l e m i a : impl icat ion for l ipoprotein(a) metabol ism 631

L ine tO i , Nef fLL- Intracavernous prosta­glandin E., in erect i le dysfunct ion 139

Lingenfelser T, Pickert A, Pfohl M, Renn W, R a d j a i p o u r M , Col let C, Eggstein M, J a k o b e r B : Hypothalamic-pi tu i tary act i­vat ion does not differ dur ing human and porc ine insul in- induced hypoglycemia in insul in-dependent diabetes mell i tus 56

Lippoldt A -» Fuxe Κ Lis S -» Bauer J Löffler Η Harten Ρ Löffler W ^ de Vries JX Löffler W, Landthaler R, de Vries JX, Wal­

ter-Sack I, I t tensohn A, Voss Α, Zöl lner N: Interact ion of a l lopur inol and hy­drochloroth iaz ide dur ing prolonged oral adminis t rat ion of both drugs in normal subjects. I. Uric acid kinetics 1071

Lohrmann Ε - * Greger R Lopez-Hänninen Ε -> Buer J Lorenz J, Fr iedberg Τ, Paulus R, Oesch F,

Ferl inz R: Oncogene overexpression in non-smal l -cel l lung cancer t issue: prevalence and c l in icopathological s ig­nif icance 156

Lüder i tz Β Hagendorf f A Ludvik Β - * Capek Μ Ludwig Μ Schmi tz U Lu f tD , P a g a l l i e s O B , Konz K, Mann K,

Renn W, Eggstein Μ : Dif ferent ial d iag ­nosis of neuropath ic lesions in d iabet ic and a lcohol ic pat ients 200

Lundin S - • Syed TA Luska G -> Ranke C

Madruga I Laso FJ Magnan i G -> Pedrett i G Mai l l y F -> L indahl G Mai l l y F Seed Μ Maio A -> Yasuda G M a i r J -> Vorderw ink le r K-P Ma lessa R, Diener H-C, O lbr ich tT , Böh­

mer B, B rockmeyer N H : Successful t rea tment of men ingoencepha l i t i s cau­sed by Mycobac te r ium av ium in t race l lu ­l a r in AIDS 850

Ma lessa R, K rams Μ, Hengge U, Wei l ler C, Reinhardt V, Volbracht L, RauhutF , B rockmeyer NH : Elevat ion of in t racra­nial p ressure in acute AIDS-re lated cryptococcal men ing i t i s 1020

Mal i r F - * Me l i char Β Ma l lmann R -> Bye S Mann Κ -> Danek A Mann Κ -> Luft D Manns Μ Buer J Mar l i nghaus EH Wehrmann Τ Mar t inez Matos JA -» Gomez Säez JM Mar t inez Ε -> Col lazos J März W Haak Τ Maure r I, Z ie rz S: Mi tochondr ia l resp i ra to­

ry cha in enzyme act iv i t ies in te t ra logy of Fallot 358

Mayo J Col lazos J Meh D -> Denis l ic Μ Meiner tz Η -> Hansen PS Meißner R -> Einhaus Μ Mel ichar Β, Jand ik Ρ, Tichy Μ, Mal i r F,

M e r g a n c o v a J , V o b o r i l Z : Ur inary zinc excret ion and acute phase response in cancer pat ients 1012

Mengden Τ Jeck Τ Mens ing Η A lb rech t Η M e r g a n c o v a J -+ Me l i char Β Mer tens PR, Duque-Reina D, Ittel ΤΗ, Keu­

lers Ρ, S i e b e r t h H - G : Cont ras t -enhan­ced computed tomography for d e m o n ­strat ion of b i la tera l renal cor t ical necro­sis 499

Metze le A Haug C Meusel F -> Hol lenbeck Μ Meyer -Lehner t Η -+ Bokemeyer D Meyer -Lehner t Η K ramer HJ Meyer zum Büschenfe lde K-Η -> H e r r W Meyer zum Büschenfe lde K-Η -> Höhler Τ Meyer zum Büschenfe lde KH -> Wölfel Τ Middeke Μ -> Wagner DR Miersch W-D - * Gross AJ M i e s e n b ö c k G F ö g e r Β Mizunash i Κ, Sh ish idoT, Furukawa Y, En­

do K, Ota K, K i m u r a T , A b e K : Ery thro-cytosis in pseudohypopara thy ro id i sm type I 341

Mizunash i K, Takaya K, Sato Η, Mor i S, Abe Κ, Furukawa Υ: The t ime course of renal funct ion and bone tu rnover in

VIII

parathyroid cr isis du,me to intratumoral hemorrhage 448

M izusawaT -> Takeda Μ Möl ler Μ -> Baldus Μ Mönig Η, Hauschi ld Α, Lange S, Fölsch

\JR: Suppressed thyroid-st imulat ing hormone secret ion in patients treated with inter leukin-2 and in te r fe ron-a 2 b for metastatic melanoma 975

Monticel l i A -> De Lorenzo F Moreno-Terr ibas G -> Perez-Bianco FJ Mori Η -> Kawamor i Τ Mori S -> Mizunashi Κ Morukov BV -> G r i go r i evA l Mrowka C, Sieberth HG: Circulat ing adhe­

sion molecules ICAM-1, VCAM-1 and E-select in in systemic vascul i t is : marked dif ferences between Wegener 's g ranu­lomatosis and systemic lupus erythe­matosus 762

MuleyT, Wiebel M, Schulz V, Ebe r tW: Elastinolyt ic activity of a lveolar macro­phages in smoking-associated pulmo­nary emphysema 269

Müller-Felber W -> B e h r T Mül ler Η -> L immer J Müller Μ -> Knisei W Müller MJ -> Netter Ρ Müller MJ, Böker KHW, Seiberg Ο: Meta­

bol ism of energy-y ie ld ing substrates in patients with l iver c i r rhosis 568

Mül ler -Quernheim J -> Kienast Κ Mundegar RR -> Z i e r z S Munoz-Torres Μ - * Vidal-Puig A Murer Η, B r e c h W : Editor ial 681 Müsch Ε -> Witzke Ο

Nagafuchi S, Ishibashi H, Anzai K, Ohshi-ma K, Ohno Y, Fukushima N, Hashi-zume M, Sugimachi K, Chuman H, Ki-kuchi M, N ihoY Budd-Chiar i syndrome and Epstein-Barr v i rus (EBV) associated p lasmacytoma in a patient with chronic active EBV infection 883

Nagy I, Pogatsa-Murray G, Z a l a n y i J r S , Komlösi P, L a s z l o J r F , U n g i l : Amani ta poisoning dur ing the second t r imester of pregnancy. A case report and a review of the l i terature 794

N a k a m a H : A study on the efficacy of a screening program for colorectal cancer in a smal l Japanese v i l lage 117

Navar LG. Inscho EW, Harr ison-Bernard LM, TakenakaT: Paracr ine interact ions regulat ing renal microci rculatory func­tion 682

Navarro MA - * Gomez JM Navarro Moreno MA Gomez Säez JM Neff LL L ine tOI Neri C Adorf D Netter P, Mül ler MJ, Neumann A, Kam-

r a d i k B : The inf luence of nicotine on performance, mood, and physiological parameters as related to smoking habit, gender, and suggest ibi l i ty 512

Neumann A -> Netter Ρ Neumann Η.P.Η.: Genetics of hyperten­

s ion : the pheochromocytoma model 729

Neupe r tW: Transport of proteins across mitochondr ia l membranes 251

Neurath G B : Aspects of the oxidat ive me­tabo l ism of nicotine 190

di Nicuolo A -> Knisei W N i h o Y -» Nagafuchi S Ni in ivaara-Kreuzer Κ -> Wintergerst U Nink Μ -+ Kubier A N i roomand F, Kubier W: Hibernat ing, stun­

ning and ischemic precondi t ioning of the myoca rd ium: therapeut ic impl ica­t ions 731

Notheis G -> Wintergerst U

Obara Κ -> Takeda Μ Oberhoff Μ -> Strohschneider Τ Oesch F -> Lorenz J Offensperger W-B, B lum HE, Gerok W:

Molecu lar therapeut ic strategies in hep­atit is Β virus infection 737

Ohno Y -> Nagafuchi S Ohsh ima Κ -> Nagafuchi S O lb r i ch tT -> Jockenhövel F O lb r i ch tT -> Malessa R O lb r i ch tT -> Rzepka AH Olek Κ - • Schröder R Omran Η -> Hagendorff A Ortolä J -> Gomez JM Ostrowi tzk i S, Z i e r z S : Two cases of neu­

ro logical manifestat ions in eos inoph i l ia : var ia t ions of one d isease? 1060

Ota Κ -> Mizunashi Κ Otto G -> Arno ld JC Otto G -+ Feussner G

Pagal l ies OB -> Luft D Patscheider S -> Vogetseder W Patsch JR -> Föger Β Paulus R -> Lorenz J Pecherstor fer Μ, Z immer-Roth I, Weidin­

ger S, Irsigler Κ, Halbmayer WM, Ul­r ich W, Fischer M, Baumgar tner G: High-dose intravenous melphalan in a patient wi th mult ip le myeloma and o l ig­uric renal fa i lure 522

Pedrett i G, E l i a G , Calzett i C, Magnani G, Fiaccador i F: Octreot ide versus terly-pressin in acute var iceal hemorrhage in l iver c i r rhos is . Emergency control and prevent ion of ear ly rebleeding 653

Perez-Bianco FJ, Huertas-Gonzales JM, Moreno-Terr ibas G, Rodr iguez-Cuartero A : Ur inary excret ion of N-acetyl-ß-glu-cosamin idase in sl ight ar ter ia l hyper­tension dur ing pregnancy 799

Peter Κ -> Br iegel J Peters J Wehrmann Τ Pfei lschif ter J : Cytokines and signal t rans­

duct ion 713 Pfohl Μ Iser G Pfohl Μ Knisei W Pfohl Μ -> Lingenfelser Τ Phi l ippe J -> Pinet F Phosphol ipase A 2 Study Group Br ie-

gei J P i cke r tA -» Lingenfelser Τ Pietschmann Ρ - * Er lacher L Pi lger Ε -> Decrinis Μ Pinet F, Germain S, Borensztein P, Fuchs

S, Phi l ippe J, Corvol P: Molecular mech­an isms in renin control 688

Pizzul l i L -> Hagendorff A Pl iml W -> Christ Μ

Pogätsa-Murray G Nagy I Pol iwoda Η -> Buer J Ponce-Pöschl Ε - * Schäfer-Kört ing Μ Pongratz D -»> Behr Τ Poser W -»· Ehrenreich Η Postler Ε -> Bauer J Prager R -> Capek Μ Presterl Ε Sexl V Puoti A -> Hor isberger J-D Puschendorf Β -> Vorderwink ler K-P Püttmann Μ -> Ensenauer R

Queißer W Baldus Μ Quintel Μ -* Ensenauer R

Radjaipour Μ Lingenfelser Τ Raedsch R -» Sch lenke rT Raeth U - Boehme MWJ Rainer F - * Wascher TC Ramador i G -+ Schwörer Η Ranke C, Creutzig A, Luska G, Wagner H-

H, Galanski M, Bode-Böger S, Fröl ich J , Avenar ius H-J, Hecker H, A lexander Κ: Control led tr ial of h igh-versus low-dose aspir in t reatment after percutaneous t rans luminal angioplasty in pat ients wi th per ipheral vascular disease 673

Rapp C -+ Jost WH Ratschek Μ Stauber RE Rauhut F Malessa R Rehak Ε - * Jul ius U Reichel C, Fehske W, Fischer HP, Hart-

l a p p J H : Undif ferentiated (embryonal) sarcoma of the l iver in an adult patient with metastasis of the heart and brain 209

Reinhardt V Malessa R Reinwein D -> Jaspers C Reinwein D -> Jockenhövel F Reinwein D ~> Rzepka AH Reinwein D -> Wagner R Reisinger EC Haiwachs G Reiterer L -> Schneider Τ Renn W Lingenfelser Τ Renn W - • Luft D Renner Ε -> Evers J Richter Ε -> Falter Β Riechelmann Η -»• Kienast Κ Riecken EO -+ Schneider Τ Riegger GAJ -> Krämer BK Ringe Β -> Kl iem V R i s l e rT Knisei W Risti B, Flury RF, Schaffner A : Fatal hema-

tophagic hist iocytosis after granulocyte-macrophage colony-st imulat ing factor and chemotherapy for h igh-grade mal ig ­nant lymphoma 457

R is t J L immer J Ritsch A -> Föger Β Ritter Μ -> Waidner Τ Ritz Ε - * Fliser D Rob PM, Goebel Y, Lebeau A, Classen H-

G: Myocardia l magnes ium deplet ion dur ing cyc lospor ine t reatment, associat­ed with reciprocal ca lc ium over load, can be prevented by plent i ful d ietary magnes ium supply 137

Rödel G -» Haferkamp Ο Rodr iguez-Cuartero A -> Perez-Bianco FJ Rolinski B, Geier SA, Sadri I, Klauss V,

Bogner JR, Ehrenreich H, Goebel FD:

IX

Endothel in-1 immunoreact iv i ty in plas­ma is elevated in HIV-1 infected patients wi th ret inal microangiopathic syn­d rome 288

Romalo G -> Danek A Roots I -> Drakoul is Ν Rose BD: Resistance to diuret ics 722 Rosen L -» Fuxe Κ Rossier BC -> Horisberger J-D Rothacher G -> Kubier A Rothe EM -> Schlenker Τ Rubba Ρ -> De Lorenzo F Rüdiger HW -> Einhaus Μ Rügheimer Ε -> Tschaikowsky Κ Ruiz-Requena ME -* Vidal-Puig A Rzepka AH, Cissewski Κ, Olbr ichtT, Rein­

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Tsutsui Τ Takeda Μ

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XI

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Indexed in Current Contents and Index Medicus

Clin Investig (1994) 72:288-293 © l O C c l !

Original Article Investigator ('} Springer-Verlag 1994

Endothelin-1 immunoreactivity in plasma is elevated in HIV-1 infected patients with retinal microangiopathic syndrome Β. Rolinski 1 , S.A. Geier 2, I . Sadri 1 , V. Klauss 2 , J R . Bogner 1, Η. Ehrenreich 3, F .D. Goebel 1

1 Medizinische Pol ikl inik , Ludwig-Maximi l i ans -Univer s i t ä t , Pettenkoferstrasse 8a, D-80336 M ü n c h e n , Germany 2 Augenklinik, Ludvvig-Maximil ians-Univers i tä t M ü n c h e n , Pettenkoferstrasse 8a, D-80336 M ü n c h e n , Germany 3 K l i n i k für Neurologie und Psychiatrie, Georg-August Univers i tä t , G ö t t i n g e n , Germany

Received: 3 November 1993 / Returned: 3 December 1993 / Accepted: 20 December 1993

Abstract. Endothelin-1 is a recently identified cy­tokine with potent vasoconstrictor activity which is associated with various diseases involving blood vessels. H I V - 1 related retinal microangiopathic syndrome is a frequent finding in patients wi th A I D S or AIDS-related complex, presenting pre­dominantly wi th retinal cotton-wool spots. We in ­vestigated 55 H I V - 1 infected patients by ophthal­moscopy and for endothelin-1 immunoreactivity in plasma and an additional 76 H I V - 1 infected pa­tients only for endothelin-1 levels. For reference values 13 age-matched healthy subjects were stud­ied. In 18 of 55 patients (33%) investigated ophthal-moscopically we found evidence of microangio­pathic syndrome. Overall, the mean endothelin-1 immunoreactivity in plasma of H I V - 1 infected pa­tients was significantly elevated as compared to controls (4.28 ± 3.62 versus 2.72 ± 0.67 fmol/ml, Ρ < 0.0001). H I V - 1 infected patients wi th retinal microangiopathic syndrome had significantly higher plasma levels of endothelin-1 immunoreac­tivity (4.59 + 1.38 fmol /ml) compared to H I V - 1 infected patients without microangiopathic syn­drome (3.18 + 1.64 fmol/ml, Ρ = 0.003). Correla­tion analysis revealed that endothelin-1 immunore­activity in plasma had no significant association with disease progression, CD4 cell count, ß 2 -mi -croglobulin, neopterin, or age. Endothelin-1 i m ­munoreactivity in plasma was correlated exclusive­ly with retinal microangiopathic syndrome in one or both eyes (r = 0.45, Ρ = 0.0006) and with the number of cotton-wool spots (r = 0.50, Ρ = 0.0001). In conlusion, H I V - 1 related retinal microangiopathic syndrome is associated with ele­vated plasma levels of endothelin-1. By virtue of its potent vasoconstrictor activity endothelin-1 may

Abbreviations: A I D S = aquired immunodeficiency syndrome; ET-1 = endothelin-1; H I V = human immunodeficiency virus: I R = immunoreact ivi ty; W R = Walter Reed classification

Correspondence to: B. Rolinski

be involved in the pathogenesis of H I V - 1 related vascular disease.

Key words: H I V - 1 - Endothelins - Endothelin-1 -Cytokine - Retinal microangiopathic syndrome -Vascular disease

Endothelins are a family of potent vasoconstrictor peptides, originally isolated from porcine aortic en­dothelial cells [23]. They have subsequently been found to be produced by a number of other cell types. Since their identification in monocytes/ macrophages and mast cells, they have been con­sidered to be cytokines [1 , 3]. To date three distinct forms (endothelin-1, —2, —3) have been discov­ered, but only endothelin-1 (ET-1) seems to occur in substantial amounts in human plasma. A l ­though data on plasma endothelin concentrations are not unequivocal, elevated levels of ET-1 im­munoreactivity (ET-1 IR) have been detected in various diseases involving blood vessels, especially in myocardial infarction [20], vasospastic angina [22], hypertension [15, 21], subarachnoid hemor­rhage [4, 16], and diabetes mellitus [13]. These ele­vated plasma levels together with the known po­tent and long-lasting vasoconstrictor action may-argue for a role of ET-1 in the pathophysiology of a number of vascular conditions.

Vascular involvement seems to be a frequent phenomenon in H I V - 1 infection. Microangiopathic changes of retinal vessels similar to those seen in other diseases such as diabetes, leukemia, and ma­lignant hypertension are the most frequent ocular finding in patients wi th acquired immunodeficiency syndrome (AIDS). This microangiopathic syn­drome presents in 40-60% of these patients wi th cotton-wool spots or other microvascular lesions such as hemorrhages and Roth's spots [12, 17]. Fur­thermore, clinical and pathological observations

289

point to an involvement of cerebral vessels in hu­man immunodeficiency virus type 1 (HIV-1) related neurological disease [6, 14,18]. Recently we demon­strated a close association of ocular microangio­pathic syndrome and cerebral blood flow using hexamethyl-propylene amine oxime single photon emission computed tomography [9]. In addition, we found a close association between HIV-1-relat­ed ocular microangiopathy and cognitive deficits, especially impairment of short-term memory [10].

I n the present study we investigated ET-1 I R in plasma of H I V - 1 infected patients wi th and without retinal microangiopathic syndrome to elucidate a possible role of endothelins in these vascular dis­turbances in H I V - 1 infection.

Patients and methods

Patients

Fifty-five H I V - 1 infected patients were investigated by ophthalmoscopy and for ET-1 I R in plasma after informed consent. To further study the role of endothelin in H I V - 1 infection we determined ET-1 I R in an additional 76 H I V - 1 infected patients which could not be seen by an ophtalmologist. Blood samples were usually taken wi th the patient in supine position and after a 10-min rest. Patients with hypertension or diabetes mellitus were exclud­ed from the study. Patients suffering from acute opportunistic infections, especially cytomegalo­virus, retinitis were also excluded. Renal function as evaluated by routine laboratory tests was nor­mal in the 131 patients studied. Distr ibution of these patients to risk groups was as follows: 61.8% of the patients were homosexual, 12.2% intra­venous drug users, 9.9% heterosexual, and 2.3% were recipients of blood products. In 13.7% the route of transmission remained unknown. Most of the patients (89.3%) were male. Mean age was 41.2 + 10.2 years. Staging was performed accord­ing to the Walter Reed (WR) classification system, wi th 20.7% of the patients being in W R 1 or 2, 25.0% in W R 3 or 4, and 54.3% in W R 5 or 6. Reference values for ET-1 I R in plasma were ob­tained from 13 healthy volunteers (9 males, 4 fe­males). Mean age of these subjects was 30.0 + 3.3 years.

Ophthalmological investigations

Fundus examination was performed by indirect ophthalmoscopy after dilatation of the pupils. A N i k o n 14 dpt lens was used for posterior pole and peripheral retina examination. Addit ionally, the

outer retinal periphery was examined using a N i k o n 20 dpt lens, and, i f necessary, examination was extended with a Volk 78 dpt lens at the slit lamp. The criterion for the diagnosis of ocular mi ­croangiopathic syndrome was: cotton-wool spots, hemorrhages, or Roth-spots. Patients were classi­fied into three groups: group I , no microangiopath­ic changes; group I I , one eye showing at least one of the described criteria; and group I I I , both eyes showing at least one of the described criteria. As an indicator of the severity of the ocular microangio­pathic syndrome, the number of cotton-wool spots in both eyes was counted.

Extraction procedures and assays

For ET-1 I R determination blood was drawn into EDTA-containing vacutainer tubes (Greiner, Frickenhausen, Germany) without other additives, placed immediately on ice, and centrifuged at 4°C. Plasma was then stored unti l analysis at — 20°C. Sample analysis was performed blinded to the clin­ical and ophthalmoscopic findings. Endothelin was extracted and concentrated from plasma as de­scribed [19]. In brief, 2.5 ml plasma was applied to the preconditioned column (Sepak C I 8 Vac 500 mg, Waters, obtained from Mil l ipore , Esch­born, Germany) and washed wi th 2.5 ml 10% acetic acid and 5 ml ethylacetate. ET-1 was then eluted with 3 ml methanol/0.05 Μ ammonium bi­carbonate (80/20, v/v). The eluate was dried under reduced pressure und reconstituted in radioim­munoassay buffer. Extraction recovery of ET-1 from plasma as determined by the use of a 125 J labeled ET-1 (Amersham, Braunschweig, Ger­many) was 87-92%, independently of the concen­trations tested (1 fmol/ml-100 pmol/ml). The ex­traction procedure reduced the average protein content of plasma (70 g/1) to 50 mg/1 in the eluate and osmolarity from 330 mosm to 10 mosm. Triglycerides and cholesterol were not detectable in the eluate ( < 2 mg/dl). Therefore the sample clean­up described resulted in minimal matrix interfer­ences in the eluate compared to other extraction procedures tested [19]. H P L C analysis of plasma samples spiked wi th pure ET-1 (Serva, Heidelberg, Germany) revealed that ET-1 was stable ( > 95%) throughout the extraction process.

Determination of ET-1 I R in the extracted sam­ples was performed using a radioimmunoassay for ET-1 obtained from N E N / D u p o n t (Dreieich, Ger­many). Performance of the assay was checked by extracting standard curves prepared wi th pure Ε Τ ­Ι from different suppliers spiked in human pool plasma or in radioimmunoassay buffer. Detection

290

l imit of the assay was 0.1 fmol/ml. The level of low­est reliable quantification (defined as Β < Bo —3 SD) was 0.52 fmol/ml. Determination of ET-1 was linear from 1 to 50 fmol/ml. Intra-assay variability for extracted samples was between 9.3% for 1 fmol/ ml added and 8% for 25 fmol/ml added (n = 6 for each concentration). Interassay variability was 13.4% and 11.2%, respectively. A l l determinations of ET-1 I R in plasma were performed in duplicate.

Neopterin in serum was measured by a radioim­munoassay (Henning, Berlin, Germany), and ß 2 -mi -croglobulin by an enzyme-linked immunosorbent assay (Behring, Marburg, Germany). CD4-positive cells were determined by flow cytometry. A l l chem­icals used were of reagent grade or better. For all analytical procedures regarding ET-1 only poly­propylene tubes were used.

Statistical analysis

Statistical calculations were performed using the SPSS software package (SPSS/PC 4.0, Chicago, USA). Tests for statistical significance (two-tailed) were performed wi th Student's t test, χ 2 test, and analysis of variance. Correlations were calculated by Pearson's or Spearman's correlation coefficient. Data are expressed as mean values + standard deviation. In patients investigated repeatedly, only the most recent values were taken for statistical analysis.

Results

Of the 55 patients investigated by ophthalmoscopy 18 (33%) had evidence of microangiopathic syn­drome. In 6 patients only one eye and in 12 patients both eyes were affected. In 2 patients retinal hemor­rhages were observed, but no cotton-wool spots were detectable; in 9 patients 1-3, in 3 patients 4-6, and in 4 patients more than 6 cotton-wool spots were counted. A typical ophthalmoscopic picture in a severly affected patient is shown in Fig. 1.

The mean ET-1 I R in plasma of H I V - 1 infected patients was significantly elevated compared to healthy controls (4.28 + 3.62 versus 2.72 + 0.67 fmol/ml, Ρ < 0.0001). Patients with retinal m i ­croangiopathic syndrome had significantly higher plasma levels of ET-1 I R (4.59 + 1.38 fmol/ml, η = 18) compared to patients without microangio­pathic syndrome (3.18 + 1.64 fmol/ml, η = 37, ρ = 0.003). Analysis of variance revealed a signifi­cant difference in ET-1 I R between patients wi th­out microangiopathic syndrome (3.18 ± 1.64 fmol/ ml) and patients wi th monocular (3.69 +1.52 fmol/ ml , η = 6) or wi th binocular (5.03 + 1.12 fmol/ml,

F i g . 1. H I V - 1 related microangiopathic syndrome of the retina w i th 16 cot ton-wool spots visible on ophthalmoscopy. These feather-edged fluffy white lesions are typically distributed near the optic disc along the major retinal vessels and usually less than one-quarter optic nerve disc diameter in size

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C o n t r o i s No R e t i n a ! M i c r o a n g i o p a t h y

R e t i n a l M i c r o ­a n g i o p a t h y in o n e e y e

( n = 6)

R e t i n a l M i c r o ­a n g i o p a t h y

In b o t h e y e s ( n = 1 2 ) ( n = 1 3 ) ( n = 3 7 )

F i g . 2. ET-1 I R in plasma is elevated in H I V - 1 infected patients w i th retinal microangiopathic syndrome. Scattergram of the val­ues and mean ± standard deviations. ET-1 I R is significantly elevated in H I V - 1 infected patients compared to controls. Ana l ­ysis of variance reveals significant differences in ET-1 I R among patients wi thout microangiopathic syndrome or wi th monocu­lar or wi th binocular involvement (P = 0.0026)

η = 12) microangiopathy (P = 0.0026; Fig. 2). I n addition, we found a significant correlation (Spear­man's correlation coefficient) between ET-1 I R in plasma and microangiopathic syndrome in one or both eyes (r = 0.45, Ρ = 0.0006) and wi th the num­ber of cotton-wool spots (r = 0.50, Ρ = 0.0001).

I n contrast, there was no correlation of ET-1 I R in plasma wi th the risk group, W R stages, C D 4

291

Table 1. Findings in H I V - 1 infected patients in advanced disease states ( W R 5 or 6) wi thout , wi th monocular, and wi th binocular retinal microangiopathic syndrome

N o microangiopathic Microangiopathic Microangiopathic change syndrome in one eye syndrome in both eyes (n = 21) (n = 6) ( n=12)

E T - l I R (fmol/ml) 3.00 ± 1 . 5 5 3.69 ± 1 . 5 2 5.03+1.12 C D 4 (cells/μΐ) 148 + 145 1 4 4 ± 131 49 ± 6 6 Hemoglobin (g/dl) 12.1 ± 2 . 4 11.2 ± 2 . 8 11.4+1.6 / ^ - Mic r og lobu l i n (mg/1) 4.5 ± 1 . 0 4.6 ± 1 . 3 6.4 ± 3 . 1 Neopterin (nmol/1) 32.1 ± 3 4 . 9 31.8 ± 1 9 . 2 70.3 ± 1 0 1 . 7

Analysis of variance revealed a significant increase in ET-1 IR (P = 0.0015) whereas the other parameters were not significantly different between the tree groups

count, ß 2 -microglobul in , neopterin, hemoglobin level, or zidovudine therapy at the time of the study. This was true for the 55 patients investigated by ophtalmoscopy as well as for the total number of patients (n = 131). Furthermore, there was no correlation between ET-1 I R and age or sex either in the healthy or in the H I V - 1 infected subjects.

Correlation analysis revealed a significant (P = 0.027) association of microangiopathic syn­drome and disease progression. I t is therefore im­portant to note that all patients with microangio­pathic syndrome were in advanced disease states, i.e., W R 5 or 6. In contrast, only 21 (56.8%) of the 37 patients without microangiopathic changes were staged W R 5 or 6. Thus patients with mi­croangiopathic syndrome had significantly lower CD4 counts (85 ± 103 versus 206 ± 153 cells/μΐ, Ρ = 0.014) compared to patients without microan­giopathic syndrome. In addition, there was a trend to higher levels of ß 2 -microglobul in (5.8 ± 2.5 ver­sus 4.7 + 4.2 mg/1) and neopterin (58.3 ± 85.6 ver­sus 23.7 + 28.3 nmol/1) in these patients, although these differences were not statistically significant. However, when comparing patients with microan­giopathic syndrome to patients without microan­giopathic syndrome but also in W R stages 5 or 6 (n = 21 ; Table 1) we no longer found significant differences in CD4 counts but still significantly higher ET-1 I R in the former group (4.59 ± 1.38 versus 3.00 ± 1.55 fmol/ml, Ρ = 0.002). Moreover, patients with or without microangiopathic syn­drome showed no significant difference with re­spect to age, hemoglobin level, or zidovudine thera­py at the time of the study (Table 1).

We investigated 21 patients several times over a period of 2-4 months by ophthalmoscopy and for ET-1 I R in plasma. Five of these patients had m i ­croangiopathic syndrome, whereas 16 had no rma l ophthalmoscopic findings. Except for one patient who improved wi th respect to his funduscopic f ind­

ings, all remained unchanged wi th regard to their ophthalmological state. In these patients ET-1 lev­els remained nearly constant over time. Mean ET-1 levels in 11 plasma samples obtained from 5 pa­tients wi th microangiopathic syndrome were 4.51 ± 1.37 fmol/ml as compared to 3.12 + 1.42 fmol/ml in 36 plasma samples from 16 patients wi th normal ophtalmologic findings (P < 0.0001).

Discussion

Our study demonstrates that ET-1 I R in plasma of H I V - 1 infected patients exceeds that of healthy subjects. Moreover, in H I V - 1 infected patients with microangiopathic syndrome of retinal vessels there is a significantly higher level of ET-1 I R in plasma compared to patients in the same disease stage but without microangiopathic changes.

Microangiopathic syndrome of retinal vessels in H I V - 1 infection seems to be a distinct vascular dis­ease [12, 17]. The pathogenetic mechanism underly­ing retinal microangiopathic syndrome in H I V - 1 infection is believed to be related to ischemia, and cotton-wool spots are interpreted as the clinically visible result of ischemic microinfarcts in the super­ficial layer of the retina [12, 17]. Retinal vessels often reflect vascular disease in other organs. In addition to our previous finding that cerebral blood flow is reduced in H I V - 1 infected patients wi th retinal microangiopathy [9], there is a report on a possible connection between proteinuria and retinal microangiopathic syndrome in patients wi th AIDS-related complex [7].

ET-1 apparently acts in a paracrine/autocrine way rather than systemically [2, 11]. Nevertheless, high local levels of this peptide appear to be reflect­ed by increased levels in the peripheral circulation. ET-1 exerts its vasoconstrictor activity predomi­nantly from the the adventitial side of intact vessels.

292

It is therefore of interest that, among other cell types, ET-1 is produced by human monocytes/ macrophages [1]. Monocytes/macrophages are target cells of H I V - 1 , and infection leads to an en­hanced penetration of these cells into perivascular tissue and increased production of cytokines. Monocyte derived cytokines, for example, tumor necrosis factor-α or interleukin-6, have been shown to be mediators of H I V - 1 related tissue damage. Recently we demonstrated enhanced transcription of the ET-1 gene in monocytes isolated from pe­ripheral blood of H I V - 1 seropositive individuals, which cannot be observed in healthy controls [5]. However, no data are yet available on ET-1 plasma levels in H I V - 1 infected patients.

In the present study we found significantly ele­vated levels of circulating ET-1 I R in H I V - 1 infect­ed individuals compared to healthy controls. The source of plasma ET-1 IR in H I V - 1 infection re­mains to be elucidated. Endothelial cells is one pos­sible source of circulating ET-1 . In addition, mono­cytes have been shown to produce high levels of ET-1 upon stimulation in vitro [1]. However, ET-1 I R in plasma did not significantly correlate with ß 2 -microglobul in or neopterin, two other sub­stances produced and released by monocytes upon stimulation.

As in this study, other investigators have shown that microangiopathic syndrome develops predom­inantly in advanced stages of H I V - 1 infection [7, 8]. Interestingly, however, there was a distinct differ­ence in ET-1 I R levels between patients in ad­vanced disease states with and without microan­giopathic syndrome. This suggests that ET-1 eleva­tion is related to vascular disease rather than to advanced disease state in general.

Some of our patients were investigated several times within a few months. Patients with microan­giopathic syndrome had constantly higher ET-1 I R levels than patients with normal ophthalmological findings, suggesting a reliable association between plasma ET-1 I R and microangiopathic syndrome.

In conclusion, the results of our study argue for an involvement of ET-1 in the pathophysiology of H I V - 1 related microangiopathic syndrome. By virtue of its strong vasoconstrictor action it may contribute to ischemic damage in this condition. The availability of endothelin antagonists for clini­cal use in the near future may help to elucidate the functional significance of ET-1 in H I V - 1 related retinal microangiopathic syndrome and may open therapeutic avenues.

Acknowledgements. The authors wish to thank A.Vielhauer and B. Rö t tge r for expert technical assistance and I . Lochner for help

in the data collection. We are indebted to M . Held, U . Kronawi t -ter, M . Liebschwager, P. Sandor, and S. Spä t l ing who cared for the patients. This research was supported by a grant ( F K Z 111-002-89/FVP) from the Bundesministerium für Forschung und Technologic

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