endothelin-1 immunoreactivity in plasma is elvated in hiv-1 infected
TRANSCRIPT
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
we in D: Effectiveness of prophylact ic therapy on goiter recurrence in an area wi th low iodine intake - a sonographic fo l low-up study 967
Saal JG -> Spyridopoulos I Sabin Κ -> Haiwachs G Sabol ic I, Brown D: Water t ransport in re
nal tubules is mediated by aquapor ins 698
Sachin id is A -*> Flesch Μ Sadri I Rolinski Β Sagarra Ε -> Fernandez-Real JM Sahota A -> Bye S Salvioni G -> Antonel l i A Sander D, Scholz CW, Eiben P, K l ingel -
höfer J : Postvaccinal plexus neuropathy fo l lowing vaccination against t ick-borne encephal i t is and tetanus in a compet i t ive athlete 399
Sander Ο -> Jablonowski Η Sandmann W -+ Kniemeyer HW Sato Η -+ Mizunashi Κ Schaefer Η -> Feussner G Schäfer-Kört ing Μ, Kört ing HC, Ponce-
P ö s c h l E : Liposomal t ret inoin for uncompl icated acne vulgar is 1086
Schaffner A - • Risti Β Schel lenberg J -> Kienast Κ Scherer G -> Chajek-Shaul Τ Scherer G -»• Einhaus Μ Scherer G -> K i r s c h b a u m e Scherübl Η -> Schneider Τ Schett ler G HabenichtAJR Schewe CK, Schweikart HP, Hammel G,
Spengel FA, Zöl lner N, Zol ler W G : Influence of selective management on the prognosis and the risk of rupture of abdomina l aortic aneurysms 585
Schimr igk Κ -> Jost WH Schi rmacher Ρ -> Wölfel Τ Schlaak J -> Wölfel Τ Schlegel J -> Kienast Κ Schlenker Τ, Raedsch R, DeVries JX,
Schmi tz-Kummer E, Walter-Sack I, Rothe EM, K o m m e r e l l B : Sel f -medicat ion for abdominal discomfort resul t ing in l i fe-threatening consequences 74
Schmidt-Achert Μ -» B e h r T Schmidt-Gayk Η -» Jockenhövel F Schmitt-Gräff A -> Schneider Τ Schmi tz-Kummer Ε -> Schlenker Τ Schmitz U, Ko Y, Becher H, Ludwig M, Vet
ter H, Düsing R: Evidence for card iovas
cular remodel ing in a patient with B a x ter 's syndrome 874
Schmitz U, Ko Y, Seewald S, Düsing R, Vetter Η: Iron-def iciency anemia as the sole manifestat ion of cel iac disease 519
Schnabel A -> Dih lmann W Schnack C -» Capek Μ Schneider Τ, Ul l r ich R, Scherübi Η,
Schmitt-Gräff A, Stein Η, Riecken EO, Zeitz Μ: Intestinal intraepithel ia l Τ cel l der ived lymphoma not associated wi th enteropathy 313
Schneider T, Ul l r ich R, Schmitt-Gräff A, Bergs C, Reiterer L, Dissmann T, Zeitz Μ, Riecken EO: Baci l lary angiomatosis in a German pat ient wi th AIDS 50
Schnitz ler G -»· Herr W Schol lmeyer PJ Dobos GJ Scholz CW -> Sander D Schomburg A -> Buer J Schröder R -> Behrens S Schröder R, B e y e n b u r g s , Weber J, Olek
K, Z ierz S: Myotonic dystrophy and l imb g i rd le muscular dystrophy in one fami ly 409
Schröder R, Urbach H, Zierz S: Cauda equina syndrome with mult ip le lumbar d iver t icu la compl icat ing long-standing ankylosing spondyl i t is 1056
Schüler A -> Buer J Schulz V - • Muley Τ Schupp Μ -> Hafkemeyer Ρ Schuster Η, Humphr ies S: European Work
ing Group on Famil ial Hypercholesterola e m i a : European Workshop on LDL Receptor Defects 898
Schuster HP - * Bodmann KF Schütze F - * L immer J Schuurman H-J: Molecular mechanisms of
t ransplant reject ion 715 Schwart ing A -> Herr W Schweikart HP -> Schewe CK Schweiker t HU - * Danek A Schwindt C -> Kn iemeyer HW Schwörer H, R a m a d o r i G : Treatment of
acute gouty arthr i t is wi th the 5-hydroxy-t ryptamine antagonist ondansetron 811
Seed Μ -> Lindahl G Seed Μ, Ma i l l yF , Val lance D, Doherty E,
Winder A, Talmud P, Humphr ies SE: L i poprotein l ipase activity in patients wi th combined hyper l ip idaemia 100
Seewald S Schmitz U Seibold Η -> Haferkamp Ο Seidel D Windler Ε Seif FJ Iser G Seifr ied Ε -> L immer J Seiberg Ο - • Mül ler MJ Sesto Μ -» Solaj ic-Bozicevic Ν Sexl V, Wagner L, Wiesholzer M, Presterl
E, B a s e W : Treatment of a patient wi th mal ignant mesothe l ioma with interfer-on -a 2 based on in vi tro sensit iv i ty tests 317
Shi loni Ε -> Chajek-Shaul Τ Shionir i Η -> Yasuda G Shirakura Τ -» Kubota Κ Sh i r okoJ -» Kawamor i Τ Sh ish idoT Mizunashi Κ Sieberth H-G Mertens PR
Sieber th HG - * Mrowka C S iekmeier R -> Haak Τ Siffert W -> Düsing R S immonds HA Bye S Sittl R Tschaikowsky Κ Smol le KH Kaufmann Ρ Soergel K H : Colonic fe rmen ta t ion : meta
bol ic and c l in ica l impl icat ions 742 Sola j ic-Bozicev ic N, Stav l jen ic-Rukavina
A, Sesto Μ : Leci th in-cholestero l acy l -t ransferase act iv i ty in pat ients wi th coronary ar tery d isease examined by coronary ang iography 951
S o l e r J -> Fernändez-Real JM Soler J -> Gomez JM Spengel FA -> Schewe CK Spyr idopou los I, Helber U, Voelker W, Hup
pert ΡΕ, Gär tner HV, Saal JG, Hoffmeister H M : Pr imary systemic amylo idos is leading to advanced renal and card iac invo lvement in a 30-year old man 462
Stachan-Kunstyr R -*• Wagner D Stahl RAK, Wolf G, Thaiss F: The possib le
ro le of chemotact ic cytok ines in renal d isease 711
Stark G Decr in is Μ Staszewski S Kamps BS Stauber RE, Hor ina JH, Trauner M, Krejs
GJ, Ratschek M, K l impf inger Μ : Glomeru lonephr i t i s as late mani festat ion of severe α-,-antitrypsin def ic iency 404
Stauch Μ Haferkamp Ο Stav l jen ic-Rukav ina A - * Sola j ic -Bozice
vic Ν Stech C -> Feussner G Stet igen J -> Haug C Stein Η -> Schneider Τ Stein Ο -» Chajek-Shaul Τ Stein Y — Chajek-Shaul Τ Ste l lbr ink HJ -> A lbrecht Η Stel lbr ink HJ, A lbrecht H, Greten Η: Pneu
mococca l parot i t is and cerv ica l lymph node abscesses in an HIV-infected pat ient 1037
Stempf le HU, Krüger T M , Brandl BC, The i -sen Κ, A n g e r m a n n CE: S imul taneous t ransesophagea l echocard iography and atr ia l pac ing : assessment of the funct ional s ign i f icance of coronary ar tery d isease before surg ica l t reatment of an abdomina l aneurysm 206
Storch Μ -> Hafkemeyer Ρ St rasburger CJ K i r s c h b a u m e St rohschneider Τ, Oberhoff Μ, Hanke Η,
Hannekum A, Karsch KR: Effect of chron ic n icot ine de l ivery on the prol i ferat ion rate of endothel ia l and smooth musc le cel ls in exper imen ta l ly induced vascu lar wal l p laques 908
Stühmeier Κ Kn iemeyer HW Sugimachi Κ -> Nagafuchi S Suter PM -> G r e m i n g e r P Syed TA, Lundin S, Cheema KM, Kah-
lon B M M , Cheema R, Ahmad SA, Ah mad Μ : Human leukocyte in ter feron-α in c ream, for the t rea tment of geni ta l war ts in as ian w o m e n : a p lacebo-cont ro l led, doub le-b l ind study 870
Sz iego le i tA Füssle R
χ
Takahashi Η -> Takeda Μ Takaya Κ -> Mizunashi Κ Takeda Μ, Hatano A, Takahashi Η, Tama-
ki M, Komeyama T, Koizumi T, Tsutsui T : ^ -Ad renocep to r s in the human prostatic urethra are different f rom those of the human per ipheral ar ter ies 55
Takeda M, Komeyama T, Koizumi T, Hatano A, Tamaki M, Takahashi H, Tsutsui T, Mizusawa T, Obara K: Endothel in receptors in the human ur inary bladder are different f rom those in the human ureter 213
Takenaka Τ -»· Navar LG Talmud Ρ -+ Seed Μ Tamaki Μ Takeda Μ Tamura J -> Kubota Κ Tanahashi S -»· Kawamor i Τ Tanaka Τ -> Kawamor i Τ Tegtmeyer KF -> Wetterl ing Τ Telenti A : Molecular diagnost ics for infec
t ious d iseases: where do we stand? 415
Terres W -> Engelstein Ε Teuber G -> Höhler Τ Teufelsbauer Η ->· Erlacher L Thaiss F -> Stahl RAK Thei lmann L -+ Arno ld JC Theisen Κ -> Christ Μ Theisen Κ - • Stempfle HU T h i e r y J -> Windler Ε Thoma HA - * Wagner D Tichy Μ -> Mel ichar Β T immer J -> Bauer J Tiran A -> Haiwachs G Tischf ield JA -> Bye S Torsello G ->· Kniemeyer HW Trauner Μ -> Stauber RE Traynor-Kaplan AE -> Dobos GJ Tricker AR -> Einhaus Μ Tröbinger G -> Föger Β Tröster S -> Bodmann KF Tschaikowsky K, Sittl R, Braun GG, Her
ing W, R ü g h e i m e r E : Increased fMet-Leu-Phe receptor expression and a l tered superoxide product ion of neutrophi l granulocytes in septic and postt raumat ic patients 18
Tsutsui Τ Takeda Μ
Uhl W -> Br iegel J Ul lr ich R -> Schneider Τ Ulr ich W -> Pecherstorfer Μ Umemura S -»· Yasuda G Ungi I Nagy I Urbach Η Schröder R Usadel K-H Haak Τ Usman A Bayraktar Μ
Vallance D -> Seed Μ Vetrie D -» Flinter F Vetter Η -» Düsing R Vetter Η Flesch Μ Vetter Η -> Schmitz U Vetter W -> Greminger Ρ Vetter W -> Jeck Τ Vidal-Puig A, Muhoz-Torres M, Jodar-Gi-
meno E, Garcia-Calvente C, Lardel l i P, Ruiz-Requena ME, Escobar-J imenez F: Hyper insul inemia in polycystic ovary
syndrome: re lat ionship to c l in ical and hormonal factors 853
Vi l labona C -» Fernändez-Real JM Vobori l Ζ - * Mel ichar Β Voderholzer U Bauer J Voe lke rW - * Knisei W Voelker W Spyr idopoulos I Voe lke rW -> Wa idne rT VogetsederW, Fil le M, Patscheider S, Die-
r ich MP, A l le rberger F: Molecular ep i demio logy of tuberculos is in Aust r ia 107
Vo lb rach tL - * Malessa R Vorderwink ler K-P, Jakob G, M a i r J , Jud -
m a i e r G , Puschendorf B: Uncoupl ing of atr ial natr iuret ic pept ide and cycl ic guanosine 3 ' ,5 ' -monophosphate product ion in patients wi th l iver c i r rhosis 138
Vorobiev DV -> Gr igor iev AI Voss A de Vries JX Voss A -> Löffler W de Vries JX Löffler W de Vries JX, Voss A, Ittensohn A, Walter-
Sack I, Löffler W, Landthaler R, Zö l lner Ν: Interaction of a l lopur inol and hydrochloroth iaz ide dur ing pro longed oral adminis t rat ion of both drugs in normal subjects. II. Kinet ics of a l lopur ino l , ox-ipur inol , and hydrochloroth iaz ide 1076
Wagenbreth I -> Wagner D Wagner D, Kern WV, Kern Ρ: L iposomal
doxorubic in in AIDS-related Kapos i 's sa rcoma: long-term exper iences 417
Wagner D, Wagenbreth I, Stachan-Kun-styr R, Thoma HA, Hemmer l ing AE, FIik J : Hepatit is Β vaccinat ion of im-munosuppressed heart t ransplant rec ipients with the vaccine Hepa Gene 3 containing pre-S1, pre-S2, and S gene p roducts 350
Wagner DR, Eckert F, Gresser U, Landthaler M, Middeke M, Zöl lner Ν: Deposits of paraprote in in smal l vessels as a cause of skin ulcers in Waldenst rom's macrog lobu l inemia 46
Wagner H-H Ranke C Wagner L Sexl V Wagner R, Bonifacio E, Bingley PJ, Gen-
ovese S, Reinwein D, Bo t tazzoGF: Low interleukin-2 receptor levels in se rum of patients wi th insul in-dependent d iabetes 494
Wagner TOF -» Flüge Τ Wahn V -> Horneff G Wahn V Jablonowski Η WaidnerT, Franzen D, VoelkerW, Ritter Μ,
Borberg Η, Hombach V, Höpp HW, LDL Apheresis Study Group : The effect of LDL apheresis on progression of co ro nary artery d isease in patients wi th fami l ia l hypercholestero lemia. Results of a mult icenter LDL apheresis study 858
Walewska-Zielecka Β -> Habior A Walli A Windler Ε Walter Η -> Baldus Μ Walter-Sack I - • de Vries JX Walter-Sack I -+ Löffler W Walter-Sack I -> Sch lenke rT Wang X, Bacher B, H ö l l t V : Nicot ine- in
duced gene expression of proenkephal -in in bovine chromaff in cel ls 925
Wanitschke R - * H e r r W Wani tschkeR Höhler Τ Wanner C -» Bartens W Ward D -+ Dobos GJ Warncke Κ -+ Einhaus Μ Wascher TC, Hermann J, Brezinschek HP,
Brezinschek R, Wi lders-Truschnig M, Rainer F, Krejs GJ : Cel l- type specif ic response of per ipheral blood lymphocytes to methotrexate in the t reatment of rheumatoid arthr i t is 535
Weber Η Hirschl MM Weber J -> Schröder R Wegener Μ -> Adamek RJ Wehling Μ Christ Μ Wehrmann Τ, Kater W, Mar l inghaus EH,
Peters J , Caspa ryWF: Shock wave t reatment of sal ivary duct s tones: substantial progress with a mini l i thotr ipter 604
Weidinger S Pecherstorfer Μ Weil ler C -> Malessa R Weinerth J H e r r W Weissei Μ Erlacher L Weiss EM Iser G Weisser Β -» Jeck Τ Wenisch C, Etzersdorfer E, Breyer S, Gra-
n i n g e r W : Intravenous te icoplanin does not prevent Clostr id ium diff ici le associ ated d iar rhea 922
Werle Ε Boehme MWJ Wetterl ing T, Tegtmeyer KF: Serum ^ - a n
t i t rypsin and a 2 -macrog lobu l in in Alzhe imer 's and B inswanger 's d isease 196
Wetter S -» Hagendorff A Wiebel Μ -> Muley Τ Wienbeck Μ -* Adamek RJ Wiesholzer Μ -> Sexl V Wilders-Truschnig Μ - • Haiwachs G Wilders-Truschnig Μ Wascher TC Wil lers R -> Jablonowski Η Winder A -»· Seed Μ Windler Ε, Ewers-Grabow U, Thiery J , Wal-
Ii A, Seidel D, Greten H: The prognost ic value of hypocholestero lemia in hosp i ta l ized patients 939
Wintergerst U, Ni in ivaara-Kreuzer Κ, Not-heis G, Auberger K, Brückmann C, Gan-denberger S, Belohradsky BH: Highdose intravenous immunoglobu l ins in the t reatment of adolescent and adult HIV-infected hemophi l iacs 122
Wittig Β -+ Herr W Witt TN -* Danek A Witzke Ο, Kassubek J, Bonmann E, Müsch
E: Cryog lobu l inemia : a compl icat ion of infectious disease 1048
Wizemann V: Hemodia lys is : 70 years 720 Wolf Ε -> Harten Ρ Wölfel Τ, Schi rmacher Ρ, Schiaak J , Knol le
Ρ, Dienes HP, Dippold W, Meyer zum Büschenfelde KH, Gerken G: Sustained e l iminat ion of hepatit is Β virus f rom serum induced in a patient with chron ic hepatit is Β and advanced human immunodef ic iency v i rus infection 1030
Wolff Μ Gross AJ Wolf G Stahl RAK
XI
Wolf Ο, Glaser F, Kuntz C, Lehne r tT : Endorectal u l t rasound and le iomyosarcoma of the rectum 381
Wormsley KG -> Johnston DA Wrenger Ε - * Brunkhorst R
Yasuda G, Z ierer R, Maio A, Shionir i H, Ish i iM, Umemura S Ammon ium urate nephro l i th ias is in a var iant of Bart ter 's syndrome with intact renal tubular funct ion 385
Yu D -> Kel lner Η
Zach R -> Haiwachs G Zach R Kaufmann Ρ
Zalänyi Jr S -> Nagy I Zehetgruber Μ -» Hirschl MM Zei tz Μ -> Schneider Τ Zieg ler R -> Feussner G Ziegler R -+ HabenichtAJR Z ierer R - * Yasuda G Z ierz S -> Maurer I Z ie rz S Ostrowitzki S Z ierz S Schröder R Z ierz S, Mundegar RR, Jerusalem F: Bio
chemical evidence for heterozygosity in muscular carni t ine palmitoyl t ransferase deficiency 77
Z i e r z S : Limited t rypsin proteolysis renders carni t ine palmitoyl t ransferase in
sensit ive to inhibi t ion by malonyl-CoA in patients with muscle carni t ine pa lmi toy l t ransferase def ic iency 957
Z immer-Roth I -> Pecherstorfer Μ Zol ler WG -> Schewe CK Zöl lner Ν -> de Vries JX Zöl lner Ν -> Lö f f le rW Zöl lner Ν - * Schewe CK Zöl lner Ν -> Wagner DR Zöl lner Ν: Anecdotal evidence 815 Zöl lner Ν: Habent sua fata l ibel l i 937
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
References
1. Ehrenreich Η, Anderson RW, Fox C H , Rieckmann P, Hoffmann GS, Travis W D , Coligan JE, Kehr l JH , Fauci AS (1990) Endothelins, peptides wi th potent vasoactive properties, are produced by human macrophages. J Exp Med 172:1741-1748
2. Ehrenreich Η , Anderson RW, Ogino Y, Rieckmann P, Vi tkov ic L , Coligan JE, Fauci AS (1991) Selective autoregu-lat ion of endothelins in pr imary astrocyte cultures: endothel in receptor-mediated potentiation of endothelin-1 secretion. New Biol 3:135-141
3. Ehrenreich Η , Burd PR, Rottem M , Hultner L , Hy l ton JB, Garfield M , Coligan JE, Metcalfe D D , Fauci AS (1992) Endothelins belong to the assortment of mast cell-derived and mast cell-bound cytokines. New Biol 4:147-156
4. Ehrenreich Η , Lange Μ , Near Κ Α , Anneser F, Schoeller L A C , Schmid R, Winkle r PA, Kehr l JH , Schmiedek P, Goebel F D (1992) Longterm moni tor ing of immunoreactive endothelin-1 and endothelin-3 in ventricular cerebrospinal f luid , plasma, and 24 h-urine of patients wi th subarachnoid hemorrhage. Res Exp Med 192:257-268
5. Ehrenreich Η, Rieckmann Ρ, Sinowatz F, Weih Κ Α , A r t h u r L O , Goebel F D , Burd PR, Coligan JE, Clouse K A (1993) Potent st imulation of monocytic endothelin-1 production by H I V - 1 glycoprotein 120. J Immuno l 150:4601-4609
6. Engstrom JW, Lowenstein D H , Bredesen D E (1989) Cerebral infarctions and transient neurologic deficits associated wi th acquired immunodeficiency syndrome. A m J Med 86:528-532
7. Engstrom RE Jr, Hol land G N , Hardy W D , MeiseJman HJ (1990) Haemorheologic abnormalities in patients wi th human immunodeficiency virus infection and ophthalmic mi -crovasculopathy. A m J Ophthalmol 109:153-161
8. Freeman W R , Chen A, Henderly D E , Levine A M , Lu t t ru l l JK , Urrea PT, Ar thu r J, Rasheed S, Cohen JL, Neuberg D (1989) Prevalence and significance of acquired immune deficiency syndrome-related retinal microvasculopathy. A m J Ophthalmol 107:229-235
9. Geier SA, Schielke Ε, Klauss V, Mül le r Α, E i n h ä u p l K M , Goebel F D , Tatsch Κ (1992) Retinal microvasculopathy and reduced cerebral blood flow in patients wi th acquired i m munodeficiency syndrome. A m J Ophthalmol 113:100-101
10. Geier SA, Perro C, Klauss V, Naber D , Kronawi t te r U , Bogner JR, Goebel F D , Lund OE, Hippius Η (1993) H I V - r e -lated microangiopathic syndrome and cognitive functioning. J Acqui r Immune Defic Syndr 6:252-58
11. Hahn AW, Resink TJ, Scott-Burden T, Powell J, D o h i Y, Buhler FR (1990) Stimulation of endothelin m R N A and secretion in rat vascular smooth muscle cells: a novel autocrine function. Cell Regul 1:649-659
12. Hol land G N , Pepose JS, Pettit T H , Gott l ieb MS, Yee R D , Foos R Y (1983) Acquired immune deficiency syndrome. Ocular manifestations. Ophthalmology 90:859-873
13. Kawamura M , Ohgarawa H , Naruse M , Suzuki N , Iwasaki N , Naruse K , H o r i S, Demura H , Omor i Y (1992) Increased plasma endothelin in N I D D M patients w i th retinopathy. Diabetes Care 15:1096-1097
293
14. LaFrance N D , Pearlson G, Schaerf F (1988) SPECT imaging wi th 1-123 isopropyl amphetamine in asymptomatic H I V seropositive persons. Cl in Nucl Med 13:393
15. Lerman A , Click R L , Nar r BJ, Wiesner R H , K r o m R A , Textor SC, Burnett JC (1991) Elevation of plasma endothelin associated wi th systemic hypertension in humans fol lowing or thotopic liver transplantation. Transplantation 51:646-650
16. Masaoka H , Suzuki R, Hira ta Y, Emor i T, Marumo F, H i -rakawa Κ (1989) Raised plasma endothelin in aneurysmal subarachnoid hemorrhage. Lancet 11:1402
17. Pepose JS, Hol land GR^Nester MS , Cochran AJ , Foos R Y (1985) Acquired immune deficiency syndrome. Pathogenetic mechanisms of ocular disease. Ophthalmology 92:472-484
18. Pohl Ρ, Vogl G, Fi l l Η , Roessler Η , Zangerle R, Gerstenbrand F (1988) Single photon emission computed tomogr-pahy in A I D S dementia complex. J Nuc l M e d 29:1382-1386
19. Rolinski B, Sadri I , Bogner J, Held M , Goebel F D (1993) Determination of Endothelin-1 Immunoreactivity in plasma, cerebrospinal fluid and urine. Res Exp Med, in press
20. Salminen K , Tikkanen I , Saijonmaa O, Nieminen Μ , Fyhrquisl F, Frick M H (1989) Modula t ion of coronary tone in acute myocardial infarction by endothelin. Lancet 11:747
21. Stewart DJ, Levy R D , Cernacek P, Langleben D (1991) I n creased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease. A n n Intern Med 114:464-469
22. Toyo-oka T, Aizawa T, Suzuki Ν (1991) Increased plasma level of endothelin-1 and coronary spasm induction in patients wi th vasospastic angina pectoris. Circulat ion 83:476-483
23. Yanagisawa M , Kurihara H , K i m u r a S, Tomobe Y, Kobayashi M , Mi t su i Y, Yasaki Y, Goto K , Masaki Τ (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411-415