Skip to main content
SpringerLink
Log in

Thalidomide in Human Immunodeficiency Virus (HIV) Patients

A Review of Safety Considerations

  • Review Article
  • Drug Experience
  • Published:
Drug Safety Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Summary

The sedative thalidomide was withdrawn from the market 30 years ago because of its teratogenic and neurotoxic adverse effects. The compound was later discovered to be extremely effective in the treatment of erythema nodosum leprosum, a complication of lepromatous leprosy. This effect is probably due to a direct influence on the immune system, because thalidomide possesses no antibacterial activity. The compound is presently used as an experimental drug in the treatment of a variety of diseases with an autoimmune character, including recurrent aphthosis of nonviral and nonfungal origin in human immunodeficiency virus (HIV) patients. This article reviews the most important chemical and pharmacokinetic properties of thalidomide. The possible mechanisms of the nonsedative effects of thalidomide with respect to the safety of its use in HIV patients are discussed. Because the mechanism of the immunomodulatory effect of thalidomide is unknown, the possibility that the administration of this compound will accelerate the deterioration of the immunological status of HIV patients cannot be excluded. Clinical evidence suggests that thalidomide may aggravate the condition of patients with preexisting peripheral neuropathy. Hypersensitivity reactions to thalidomide may occur more frequently in HIV patients than in other patient groups.

Because of the teratogenic activity of thalidomide, reliable contraception must be provided to female patients of childbearing age. Before the introduction of thalidomide therapy to an HIV patient presenting with oral ulcers, a fungal or viral origin of the lesions should be excluded. Thalidomide should not be used in patients with preexisting HIV-related peripheral polyneuropathy, polyradiculopathy or encephalopathy. In patients experiencing a complete remission, the discontinuation of thalidomide treatment and its reintroduction in the case of a relapse are preferable to maintenance therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alexander IRW. Acute myxoedema. British Medical Journal 2: 1434, 1961

    Google Scholar 

  • Alfonzo RP, Weiss E, Martin JP, Lugo AJR. Liquen plano generalizado con lesión erosiva del pene tratado con talidomida: reporte de un caso y revisión de la literatura. Medicina Cutanea Ibero-Latino Americana 15: 321–326, 1987

    Google Scholar 

  • Alonso AM. Estados reacionais da lepra. Medicina Cutanea Ibero-Latino Americana 3: 199–208, 1975

    PubMed  CAS  Google Scholar 

  • Andrieu JM, Even P, Venet A, Tourani JM, Stern M, et al. Effects of cyclosporin on T-cell subsets in human immunodeficiency disease. Clinical Immunology and Immunopathology 46: 181–198, 1988

    Google Scholar 

  • Aronson IK, Yu R, West DP, Van Den Broek H, Antel J. Thalidomide-induced peripheral neuropathy. Archives of Dermatology 120: 1466–1470, 1984

    PubMed  CAS  Google Scholar 

  • Bach MA, Launois P. Mechanisms of mycobycterium leprae-specific T-cell deficiency in lepromatous leprosy. Biochimie 70: 1013–1018, 1988

    PubMed  CAS  Google Scholar 

  • Bächinger HP. The influence of peptidyl-prolyl cis-trans isomerase in the in vitro folding of type III collagen. Journal of Biological Chemistry 262: 17144–17148, 1987

    PubMed  Google Scholar 

  • Bahmer FA, Zaun H, Luszpinski P. Thalidomide treatment of recurrent erythema multiforme. Acta Dermato-Venerologica 62: 449–450, 1982

    CAS  Google Scholar 

  • Bakay B, Nyhan WL. Binding of thalidomide by macromolecules in the fetal and maternal rat. Journal of Pharmacology and Experimental Therapeutics 161: 348–360, 1968

    PubMed  CAS  Google Scholar 

  • Barba Rubio J, Franco González F. Lupus eritematoso discoide y talidomina: informe preliminar. Dermatologia (Mexico City) 19: 131–139, 1975

    Google Scholar 

  • Barba Rubio J, Franco González F. Lupus eritematoso fijo (su tratamiento con talidomida). Medicina Cutanea Ibero-Latino Americana 5: 279–285, 1977

    PubMed  CAS  Google Scholar 

  • Barnhill RL, McDougall AC. Thalidomide: use and possible mode of action in reactional lepromatous leprosy and in various other conditions. Journal of the American Academy of Dermatology 7: 317–323, 1982

    PubMed  CAS  Google Scholar 

  • Barrett AJ. Graft-versus-host disease: a review. Journal of the Royal Society of Medicine 80: 368–373, 1987

    PubMed  CAS  Google Scholar 

  • Barriere H. Sarcoïdes cutanées: traitement par la thalidomide. Presse Médicale 12: 963, 1983

    CAS  Google Scholar 

  • Beckmann R. Über das Verhalten von Thalidomid im Organismus: 1. Mitteilung: Resorption, Verteilung im Gewebe und Ausscheidung von N-Phthalyl-[14C]-glutaminsäure-imid (Thalidomid-[14C]). Arzneimittel-Forschung 12: 1095–1098, 1962

    PubMed  CAS  Google Scholar 

  • Beckmann R. Über das Verhalten von Thalidomid im Organismus: 2. Mitteilung: biologischer Abbau von N-Phthalyl-D,L-glutaminsäure-imid-[14C](Thalidomid-[14C]). Arzneimittel-Forschung 13: 185–190, 1963

    PubMed  CAS  Google Scholar 

  • Beckmann R, Kampf HH. Zur quantitativen Bestimmung und zum qualitativen Nachweis von N-Phthalyl-glutaminsäure-imid (Thalidomid). Arzneimittel-Forschung 11: 45–47, 1961

    PubMed  CAS  Google Scholar 

  • Behar R, Wiley C, McCutchan JA. Cytomegalovirus polyradiculoneuropathy in acquired immune deficiency syndrome. Neurology 37: 557–561, 1987

    PubMed  CAS  Google Scholar 

  • Bernardo P, Arrizabalaga J, Iribarren JA, Garde C. Eficacia de la talidomida en las úlceras esofágicas inespecíficas en pacientes con síndrome de inmunodeficiencia adquirida. Medicina Clínica 94: 48–49, 1990

    Google Scholar 

  • Birkett DJ. Racemates or enantiomers: regulatory approaches. Clinical and Experimental Pharmacology and Physiology 16: 479–483, 1989

    PubMed  CAS  Google Scholar 

  • Blaschke G, Hess HR, Lüpke NP. Synthese und teratogene Wirkung von N-Hydroxy-thalidomid. Arzneimittel-Forschung 39: 293–294, 1989

    PubMed  CAS  Google Scholar 

  • Blaschke G, Kraft HP, Fickentscher K, Köhler F. Chromatographische Racemattrennung von Thalidomid und teratogene Wirkung der Enantiomere. Arzneimittel-Forschung 29: 1640–1642, 1979

    PubMed  CAS  Google Scholar 

  • Boddingius J. Ultrastructural changes in blood vessels of peripheral nerves in leprosy neuropathy: II. Borderline, borderlinelepromatous and lepromatous leprosy patients. Acta Neuropathologica 40: 21–39, 1977

    PubMed  CAS  Google Scholar 

  • Bowers PW, Powell RJ. Effect of thalidomide on orogenital ulceration. British Medical Journal 287: 799–800, 1983

    PubMed  CAS  Google Scholar 

  • Boylen JB, Horne HH, Johnson WJ. Teratogenic effects of thalidomide and its metabolites on the developing chick embryo. Canadian Journal of Biochemistry 42: 35–42, 1964

    CAS  Google Scholar 

  • Braun AG, Dailey JP. Thalidomide metabolite inhibits tumor cell attachment to concanavalin A coated surfaces. Biochemical and Biophysical Research Communications 98: 1029–1034, 1981

    PubMed  CAS  Google Scholar 

  • Braun AG, Emerson DJ, Nichinson BB. Teratogenic drugs inhibit tumor cell attachment to lectin coated surfaces. Nature 282: 507–509, 1979

    PubMed  CAS  Google Scholar 

  • Braun AG, Harding FA, Weinreb SL. Teratogen metabolism: thalidomide activation is mediated by cytochrome P-450. Toxicology and Applied Pharmacology 82: 175–179, 1986

    PubMed  CAS  Google Scholar 

  • Braun AG, Weinreb SL. Teratogen metabolism: activation of thalidomide and thalidomide analogues to products that inhibit the attachment of cells to concanavalin A coated plastic surfaces. Biochemical Pharmacology 33: 1471–1477, 1984

    PubMed  CAS  Google Scholar 

  • Braun AG, Weinreb SL. Teratogen metabolism: spontaneous decay products of thalidomide and thalidomide analogues are not bioactivated by liver microsomes. Teratogenesis, Carcinogenesis, and Mutagenesis 5: 149–158, 1985

    PubMed  CAS  Google Scholar 

  • Breshnahan TJ. Attempted suicide with thalidomide: a case report. Applied Therapeutics 3: 621–626, 1961

    Google Scholar 

  • Brode E. Experimentelle Untersuchungen mit cyclischen Imiden: III. Beeinflussung der Enzyminduktion durch cyclische Imide. Arzneimittel-Forschung 18: 1051–1052, 1968a

    Google Scholar 

  • Buckley C, Bayoumi AHM, Sarkany I. Pyoderma gangrenosum with severe pharyngeal ulceration. Journal of the Royal Society of Medicine 83: 590–591, 1990

    PubMed  CAS  Google Scholar 

  • Burley DM. Overdosage with thalidomide (‘Distaval’). Medical World 93: 26–28, 1960

    PubMed  CAS  Google Scholar 

  • Burley DM, Dennison TC, Harrison W. Clinical experience with a new sedative drug. Practitioner 183: 57–61, 1959

    PubMed  CAS  Google Scholar 

  • Calnan CD, Meara RH. Actinic prurigo (Hutchinson’s summer prurigo). Clinical and Experimental Dermatology 2: 365–372, 1977

    PubMed  CAS  Google Scholar 

  • Chapon F, Lechevalier B, Da Silva DC, Rivrain Y, Dupuy B, et al. Neuropathies à la thalidomide. Revue Neurologique 141: 719–728, 1985

    PubMed  CAS  Google Scholar 

  • Chavanet P, Lefranc T, Bonnin A, Waldner A, Portier H. Unusual cause of pharyngeal ulcerations in AIDS. Lancet 336: 383–384, 1990

    PubMed  CAS  Google Scholar 

  • Chen TL, Vogelsang GB, Petty BG, Brundrett RB, Noe DA, et al. Plasma pharmacokinetics and urinary excretion of thalidomide after oral dosing in healthy male volunteers. Drug Metabolism and Disposition 17: 402–405, 1989

    PubMed  CAS  Google Scholar 

  • Cicurel L, Schmid BP. Post-implantation embryo culture: validation with selected compounds for teratogenicity testing. Xenobiotica 18: 617–624, 1988

    PubMed  CAS  Google Scholar 

  • Clemmensen OJ, Olsen PZ, Andersen KE. Thalidomide neurotoxicity. Archives of Dermatology 120: 338–341, 1984

    PubMed  CAS  Google Scholar 

  • Connolly GM, Hawkins D, Harcourt-Webster JN, Parsons PA, Husain OAN, et al. Oesophageal symptoms, their causes, treatment, and prognosis in patients with the acquired immunodeficiency syndrome. Gut 30: 1033–1039, 1989

    PubMed  CAS  Google Scholar 

  • Cornea P, Vladutiu A, Marcovici G. The immuno-suppressive effect of thalidomide in experimental tuberculosis in guineapigs. Tubercle 48: 51–53, 1967

    PubMed  CAS  Google Scholar 

  • Couzigou P, Doutre MS, Houdée G, Richard-Molard B, Fleury B, et al. Thalidomide et traitement du syndrome de Behçet. Gastroentérologie Clinique et Biologique 7: 751, 1983

    PubMed  CAS  Google Scholar 

  • Crain E, McIntosh KR, Gordon G, Pestronk A, Drachman DB. The effect of thalidomide on experimental autoimmune myasthenia gravis. Journal of Autoimmunity 2: 197–202, 1989

    PubMed  CAS  Google Scholar 

  • Dalakas MC, Pezeshkpour GH. Neuromuscular diseases associated with human immunodeficiency virus infection. Annals of Neurology 23 (suppl.): s38–S48, 1988

    PubMed  Google Scholar 

  • de Bandt M, Saveuse H, Rouveix E, Dorra M, Burgeois P, et al. Manifestations rhumatologiques observées chez les patients infectés par le virus de l’immuno-déficience humaine. Semaine des Hôpitaux de Paris 65: 1771–1779, 1989

    Google Scholar 

  • De Camp WH. The FDA perspective on the development of stereoisomers. Chirality 1: 2–6, 1989

    PubMed  Google Scholar 

  • Drutz DJ, Gutman RA. Renal manifestations of leprosy: glomerulonephritis, a complication of erythema nodosum leprosum. American Journal of Tropical Medicine and Hygiene 22: 496–502, 1973

    PubMed  CAS  Google Scholar 

  • Dummer JS, Erb S, Breinig MR, Ho M, Rinaldo CR, et al. Infection with human immunodeficiency virus in the Pittsburgh transplant population. Transplantation 47: 134–139, 1989

    PubMed  CAS  Google Scholar 

  • Dwyer JM, Bullock WE, Fields JP. Disturbance of the blood B: T lymphocyte ratio in lepromatous leprosy. New England Journal of Medicine 288: 1036–1039, 1973

    PubMed  CAS  Google Scholar 

  • Eidelberg D, Sotrel A, Vogel H, Walker P, Kleefield J, et al. Progressive polyradiculopathy in acquired immune deficiency syndrome. Neurology 36: 912–916, 1986

    PubMed  CAS  Google Scholar 

  • Eisenbud L, Horowitz I, Kay B. Recurrent aphthous stomatitis of the Behçet type: successful treatment with thalidomide. Oral Surgery, Oral Medicine, Oral Pathology 64: 289–292, 1987

    CAS  Google Scholar 

  • Ellenrieder M, Frankus E, Kruepe W. Immunosuppression durch cyclische Imide bei der Ratte. Klinische Wochenschrift 45: 1159–1160, 1967

    PubMed  CAS  Google Scholar 

  • Emre S, Sumrani N, Hong J. Beneficial effect of thalidomide and ciclosporin combination in heterotopic cardiac transplantation in rats. European Surgical Research 22: 336–339, 1990

    PubMed  CAS  Google Scholar 

  • Eravelly J, Waters MFR. Thalidomide in Weber-Christian disease. Lancet 1: 251, 1977

    PubMed  CAS  Google Scholar 

  • Esser H, Heinzler F. Klinische Erfahrungen mit einem neuen Sedativum und Hypnotikum. Therapie der Gegenwart 95: 374–376, 1956

    PubMed  CAS  Google Scholar 

  • Fabro S, Schumacher H, Smith RL, Williams RT. Teratogenic activity of thalidomide and related compounds. Life Sciences 3: 987–992, 1964

    PubMed  CAS  Google Scholar 

  • Fabro S, Smith RL, Williams RT. The fate of [14C]thalidomide in the pregnant rabbit. Biochemical Journal 104: 565–569, 1967a

    PubMed  CAS  Google Scholar 

  • Fabro S, Smith RL, Williams RT. The fate of the hydrolysis products of thalidomide in the pregnant rabbit. Biochemical Journal 104: 570–574, 1967b

    PubMed  CAS  Google Scholar 

  • Fabro S, Smith RL, Williams RT. Toxicity and teratogenicity of optical isomers of thalidomide. Nature 215: 296, 1967c

    PubMed  CAS  Google Scholar 

  • Faigle JW, Keberle H, Riess W, Schmid K. The metabolic fate of thalidomide. Experientia 18: 389–397, 1962

    CAS  Google Scholar 

  • Ferrara JLM, Deeg HJ. Graft-versus-host disease. New England Journal of Medicine 324: 667–674, 1991

    PubMed  CAS  Google Scholar 

  • Field EO, Gibbs JE, Tucker DF, Hellmann K. Effect of thalidomide on the graft versus host reaction. Nature 211: 1308–1310, 1966

    PubMed  CAS  Google Scholar 

  • Fischer G, Wittmann-Liebold B, Lang K, Kiefhaber T, Schmid FX. Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature 337: 476–478, 1989

    PubMed  CAS  Google Scholar 

  • Florence AL. Is thalidomide to blame? Lancet 2: 1954, 1960

    Google Scholar 

  • Flores O. Prurigo solar de altiplanicie. Resultados preliminares de tratamiento con talidomida en 25 casos. Dermatologia Revista Mexicana 19: 26–39, 1975

    Google Scholar 

  • Fuller GN, Jacobs JM. Cytomembranous inclusions in the peripheral nerves in AIDS. Acta Neuropathologica 79: 336–339, 1989

    PubMed  CAS  Google Scholar 

  • Fullerton PM, Kremer M. Neuropathy after intake of thalidomide (Distaval). British Medical Journal 2: 855–858, 1961

    PubMed  CAS  Google Scholar 

  • Fullerton PM, O’Sullivan DJ. Thalidomide neuropathy: a clinical, electrophysiological, and histological follow-up study. Journal of Neurology, Neurosurgery, and Psychiatry 31: 543–551, 1968

    PubMed  CAS  Google Scholar 

  • Gad SM, Shannon EJ, Krotoski WA, Hastings RC. Thalidomide induces imbalances in T-lymphocyte sub-populations in the circulating blood of healthy males. Leprosy Review 56: 35–39, 1985

    PubMed  CAS  Google Scholar 

  • Gajl-Peczalska KJ, Lim SD, Jacobson RR, Good RA. B lymphocytes in lepromatous leprosy. New England Journal of Medicine 288: 1033–1035, 1973

    PubMed  CAS  Google Scholar 

  • Gelber RH, Drutz DJ, Epstein WV, Fasal P. Clinical correlates of Clq-precipitating substances in the sera of patients with leprosy. American Journal of Tropical Medicine and Hygiene 23: 471–475, 1974

    PubMed  CAS  Google Scholar 

  • Genvo MF, Faure M, Thivolet J. Traitement de l’aphtose par la thalidomide et la colchicine. Dermatologica 168: 182–188, 1984

    PubMed  CAS  Google Scholar 

  • Georghiou PR, Kemp RJ. HIV-associated oesophageal ulcers treated with thalidomide. Medical Journal of Australia 152: 382–383, 1990

    PubMed  CAS  Google Scholar 

  • Gibbels E. Toxische Schäden bei der Thalidomid-Medikation. Fortschritte der Neurologie-Psychiatrie und Ihrer Grenzgebiete 35: 393–411, 1967

    CAS  Google Scholar 

  • Gibbels E. Die Thalidomid-Polyneuritis. Fortschritte der Medizin 86: 1052–1056, 1968

    Google Scholar 

  • Gibbels E. Medikamentös-toxische Polyneuropathien. Aktuelle Neurologie 1: 175–180, 1974

    Google Scholar 

  • Gibbels E, Scheid W, Wieck HH, Kinzel W. Die Thalidomid-Polyneuropathie im Spätstadium: eine klinische Dokumentation. Fortschritte der Neurologie-Psychiatrie und ihrer Grenzgebiete 41: 378–417, 1973

    CAS  Google Scholar 

  • Gimenez S, Bagheri H, Marchou B, Massip P, Lafont J, et al. Bilan d’un suivi de pharmacovigilance de la zidovudine. Therapie 45: 407–409, 1990

    PubMed  CAS  Google Scholar 

  • Gnassia AM, Gnassia RT, Bonvalet D, Puissant A, Goudal H. Histiocytose X avec ‘granulome éosinophile vulvaire’: effet spectaculaire de la thalidomide. Annales de Dermatologie et de Vénéréologie 114: 1387–1389, 1987

    Google Scholar 

  • Goihman-Yahr M, Requena MA, Vallecalle-Suegart E, Convit J. Autoimmune diseases and thalidomide I. Adjuvant disease, experimental allergic encephalomyelitis and experimental allergic neuritis of the guinea pig. International Journal of Leprosy 40: 133–141, 1972

    CAS  Google Scholar 

  • Goihman-Yahr M, Requena MA, Vallecalle-Suegart E, Convit J. Autoimmune diseases and thalidomide II. Adjuvant disease, experimental allergic encephalomyelitis and experimental allergic neuritis of the rat. International Journal of Leprosy 42: 266–275, 1974

    CAS  Google Scholar 

  • Gollop TR, Eigier A, Neto JG. Prenatal diagnosis of thalidomide syndrome. Prenatal Diagnosis 7: 295–298, 1987

    PubMed  CAS  Google Scholar 

  • Gordon GB, Spielberg SP, Blake DA, Balasubramanian V. Thalidomide teratogenesis: evidence for a toxic arene oxide metabolite. Proceedings of the National Academy of Sciences of the United States of America 78: 2545–2548, 1981

    PubMed  CAS  Google Scholar 

  • Gorin I, Vilette B, Gehanno P, Escande JP. Thalidomide in hyperalgic pharyngeal ulceration of AIDS. Lancet 335: 1343, 1990

    PubMed  CAS  Google Scholar 

  • Green JN, Benson BC. The spectrophotometric determination of thalidomide in body fluids. Journal of Pharmacy and Pharmacology 13: 117T–121T, 1961

    CAS  Google Scholar 

  • Grinspan D. Significant response of oral aphthosis to thalidomide treatment. Journal of the American Academy of Dermatology 12: 85–90, 1985

    PubMed  CAS  Google Scholar 

  • Grinspan D, Fernández Blanco G, Agüero S. Treatment of aphtae with thalidomide. Journal of the American Academy of Dermatology 20: 1060–1063, 1989

    PubMed  CAS  Google Scholar 

  • Grosshans E, Illy G. Thalidomide therapy for inflammatory dermatoses. International Journal of Dermatology 23: 598–602, 1984

    PubMed  CAS  Google Scholar 

  • Günzler V. Thalidomide — a therapy for the immunological consequences of HIV infection? Medical Hypotheses 30: 105–109, 1989

    PubMed  Google Scholar 

  • Günzler V, Hanauske-Abel HM, Tschank G, Schulte-Wisser-mann H. Immunological effects of thalidomide: inactivity of the drug and several of its hydrolysis products in mononucleocyte proliferation tests. Arzneimittel-Forschung 36: 1138–1141, 1986

    PubMed  Google Scholar 

  • Gutiárrez-Rodríguez O. Thalidomide: a promising new treatment for rheumatoid arthritis. Arthritis and Rheumatism 27: 1118–1121, 1984

    Google Scholar 

  • Gutiérrez-Rodríguez O, Starusta-Bacal P, Gutiérrez-Montes O. Thalidomide-induced neuropathy in rheumatoid arthritis patients. Arthritis and Rheumatism 31: 145–146, 1988

    PubMed  Google Scholar 

  • Gutiérrez-Rodríguez O, Starusta-Bacal P, Gutiérrez-Montes O. Treatment of refractory rheumatoid arthritis — the thalidomide experience. Journal of Rheumatology 16: 158–163, 1989

    PubMed  Google Scholar 

  • Hafström T. Polyneuropathy after neurosedyn (thalidomide) and its prognosis. Acta Neurologica Scandinavica 43(suppl. 32): 1–41, 1967

    PubMed  Google Scholar 

  • Hague D, Smith RL. Enigmatic properties of (±)-thalidomide; an example of a stable racemic compound. British Journal of Clinical Pharmacology 26: 623P, 1988

    Google Scholar 

  • Hamza MH. Treatment of Behçet’s disease with thalidomide. Clinical Rheumatology 5: 365–371, 1986

    PubMed  CAS  Google Scholar 

  • Hamza M. Behçet’s disease, palmoplantar pustulosis and HLA-B27 treatment with thalidomide. Clinical and Experimental Rheumatology 8: 427, 1990

    PubMed  CAS  Google Scholar 

  • Hamza M, Chaffai M, Ben Ayed H. Le traitement de la maladie de Behçet par la thalidomide. Nouvelle Presse Médicale 11: 1080–1081, 1982

    PubMed  CAS  Google Scholar 

  • Harding MW, Galat A, Uehling DE, Schreiber SL. A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase. Nature 341: 758–760, 1989

    PubMed  CAS  Google Scholar 

  • Harrison RK, Stein RL. Substrate specificities of the peptidyl prolyl cis-trans isomerase activities of cyclophilin and FK-506 binding protein: evidence for the existence of a family of distinct enzymes. Biochemistry 29: 3813–3816, 1990

    PubMed  CAS  Google Scholar 

  • Hasper MF. Chronic cutaneous lupus erythematosus. Thalidomide treatment of 11 patients. Archives of Dermatology 119: 812–815, 1983

    PubMed  CAS  Google Scholar 

  • Hasper MF, Klokke AH. Thalidomide in the treatment of chronic discoid lupus erythematosus. Acta Dermato-Venerologica 62: 321–324, 1982

    CAS  Google Scholar 

  • Hastings RC, Morales MJ, Shannon EJ. Studies on the mechanism of action of thalidomide in leprosy. Pharmacologist 18: 218, 1976

    Google Scholar 

  • Heger W, Klug S, Schmahl HJ, Nau H, Merker HJ, et al. Embryotoxic effects of thalidomide derivatives on the non-human primate Callithrix jacchus; 3. Teratogenic potency of the EM 12 enantiomers. Archives of Toxicology 62: 205–208, 1988

    PubMed  CAS  Google Scholar 

  • Hellmann K, Duke DI, Tucker DF. Prolongation of skin homograft survival by thalidomide. British Medical Journal 2: 687–689, 1965

    PubMed  CAS  Google Scholar 

  • Helm FC, Frankus E, Friderichs E, Graudums I, Flohé L. Comparative teratological investigation of compounds structurally and pharmacologically related to thalidomide. Arzneimittel-Forschung 31: 941–949, 1981

    PubMed  CAS  Google Scholar 

  • Heney D, Lewis IJ, Bailey CC. Thalidomide for chronic graft-versus-host disease in children. Lancet 2: 1317, 1988

    PubMed  CAS  Google Scholar 

  • Hess AD, Tutschka PJ. Effect of cyclosporin A on human lymphocyte responses in vitro I: CsA allows for the expression of alloantigen-activated suppressor cells while preferentially inhibiting the induction of cytolytic effector lymphocytes in MLR. Journal of Immunology 124: 2601–2608, 1980

    CAS  Google Scholar 

  • Hess CW, Hunziker T, Küpfer A, Ludin HP. Thalidomide-induced peripheral neuropathy: a prospective clinical, neurophysiological and pharmacogenetic evaluation. Journal of Neurology 233: 83–89, 1986

    PubMed  CAS  Google Scholar 

  • Hoyer H, Wulff CH, Asboe-Hansen G, Brodthagen H. Behandling af prurigo nodularis Hyde med talidomid. Ugeskrift for Laeger 145: 3243–3245, 1983

    PubMed  CAS  Google Scholar 

  • Hunziker T, Krebs A. Thalidomid in der Dermatologie. Hautarzt 34: 66–72, 1983

    PubMed  CAS  Google Scholar 

  • Jackson AJ, Schumacher HJ. Identification of urinary metabolites of EM12 N-(2′,6′-dioxopiperiden-3′-yl)-phthalimidine, a teratogenic analog of thalidomide in rats and rabbits. Canadian Journal of Pharmaceutical Sciences 15: 21–23, 1980

    CAS  Google Scholar 

  • Jäger G, Fisher H, Klingmüller G. Clinical observations in the treatment of leprosy reaction with cyclic imides. International Journal of Leprosy 39: 589, 1971

    Google Scholar 

  • Jaschonek K, Einsele H, Schmidt H, Lenz HJ, Ehninger G, et al. 8-Methoxypsoralen and ultraviolet A therapy for cutaneous manifestations of graft-versus-host disease. Lancet 1: 599, 1988

    PubMed  CAS  Google Scholar 

  • Jenkins JS, Powell RJ, Allen BR, Littlewood SM, Maurice PDL, et al. Thalidomide in severe orogenital ulceration. Lancet 2: 1424–1426, 1984

    PubMed  CAS  Google Scholar 

  • Jolliffe DS. Leprosy reactional states and their treatment. British Journal of Dermatology 97: 345–352, 1977

    PubMed  CAS  Google Scholar 

  • Jonea MG. Teratogenic effects of proline analogue L-azetidine-2-carboxylic acid in hamster fetuses. Teratology 23: 365–372, 1981

    Google Scholar 

  • Jorizzo JL, Schmalstieg FC, Solomon AR, Cavallo T, Taylor RS, et al. Thalidomide effects in Behçet’s syndrome and pustular vasculitis. Archives of Internal Medicine 146: 878–881, 1986

    PubMed  CAS  Google Scholar 

  • Kahan BD. Cyclosporine. New England Journal of Medicine 321: 1725–1738, 1989

    PubMed  CAS  Google Scholar 

  • Keberle H, Faigle JW, Fritz H, Knüsel F, Loustalot P, et al. Theories on the mechanism of action of thalidomide. In Robson et al. (Eds) Symposium on embryopathic activity of drugs, pp. 210–226, J. and A. Churchill, London, 1965

    Google Scholar 

  • Klüken N, Wente W. Indications for thalidomide therapy for leprosy. Internatonal Journal of Dermatology 13: 20–25, 1974

    Google Scholar 

  • Knop J, Bonsmann G, Happle R, Ludolph A, Matz DR, et al. Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus. British Journal of Dermatology 108: 461–466, 1983

    PubMed  CAS  Google Scholar 

  • Knop J, Happle R, Bonsmann G, Vakilzadeh F, Macher E. Treatment of chronic discoid lupus erythematosus with thalidomide. Archives of Dermatological Research 271: 165–170, 1981

    Google Scholar 

  • Koch H. Die Arenoxid-Hypothese der Thalidomid-Wirkung. Überlegungen zum molekularen Wirkungsmechanismus des ‘klassischen’ Teratogens. Scientia Pharmaceutica 49: 67–99, 1981

    CAS  Google Scholar 

  • Koch HP. Thalidomide and Congeners as anti-inflammatory agents. In Ellis et al. (Eds) Progress in Medicinal Chemistry, Vol. 22, pp. 165–242, 1985

    Google Scholar 

  • Koch H, Schnabel-Arikan F. Thalidomid-Wirkungen. Scientia Pharmaceutica 36: 121–145, 1968

    Google Scholar 

  • Köhnlein E, Lemperle G, Karges I. Verlängerte Überlebenszeit von Homotransplantaten der Haut durch Thalidomid. Bruns’ Beiträge für Klinische Chirurgie 217: 165–170, 1969

    PubMed  Google Scholar 

  • Koransky W, Ullberg S. Autoradiographic investigations of 14C-labelled thalidomide and gluthetimide in pregnant mice. Proceedings of the Society for Experimental Biology and Medicine 116: 512–516, 1964

    PubMed  CAS  Google Scholar 

  • Korngold R, Sprent J. T cell subsets and graft-versus-host disease. Transplantation 44: 335–339, 1987

    PubMed  CAS  Google Scholar 

  • Kreipe U. Missbildungen innerer Organe bei Thalidomidembryopathie. Archiv für Kinderheilkunde 176: 33–61, 1967

    PubMed  CAS  Google Scholar 

  • Krücke W, von Hartrott HH, Schröder JM, Thomas E, Gibbels E, et al. Licht- und elektronenmikroskopische Untersuchungen zum Spätstadium der Thalidomid-Polyneuropathie. Fortschritte der Neurologie — Psychiatrie und ihrer Grenzgebiete 39: 15–50, 1971

    Google Scholar 

  • Kunz W, Keller H, Mückter H. N-Phthalyl-glutaminsäure-imid. Experimentelle Untersuchungen an einem neuen synthetischen Produkt mit sedativen Eigenschaften. Arzneimittel-Forschung 6: 426–430, 1956

    PubMed  CAS  Google Scholar 

  • Kupiec-Weglinski JW, Filho MA, Strom TB, Tilney NL. Sparing of suppressor cells: a critical action of cyclosporine. Transplantation 38: 97–101, 1984

    PubMed  CAS  Google Scholar 

  • Kürkçüoglu N, Atakan N, Eksioglu M. Thalidomide in the treatment of recurrent necrotic mucocutaneous aphthae. British Journal of Dermatology 112: 632, 1985

    PubMed  Google Scholar 

  • Lagueny A, Rommel A, Vignolly B, Taieb A, Vendeaud-Busquet M, et al. Thalidomide neuropathy: an electrophysiologic study. Muscle and Nerve 9: 837–844, 1986

    PubMed  CAS  Google Scholar 

  • Lange DJ, Britton CB, Younger DS, Hays AP. The neuromuscular manifestations of human immunodeficiency virus infections. Archives of Neurology 45: 1084–1088, 1988

    PubMed  CAS  Google Scholar 

  • Larsson H. Treatment of severe colitis in Behçet’s syndrome with thalidomide (CG-217). Journal of Internal Medicine 228: 405–407, 1990

    PubMed  CAS  Google Scholar 

  • Léger JM, Bolgert F, Bouche P, Chaunu MP, Hauw JJ, et al. Système nerveux périphérique et infection par le V.I.H.: 13 cas. Revue Neurologique 144: 789–795, 1988

    PubMed  Google Scholar 

  • Lenz W. Thalidomide and congenital abnormalities. Lancet 1: 45, 1962

    Google Scholar 

  • Lenz W. Discussion in Robson et al. (Eds) Symposium on embryopathic activity of drugs, pp. 182–185, J. and A. Churchill, London, 1965

    Google Scholar 

  • Lenz W. Medizinische Genetik, 4th ed., Georg Thieme, Stuttgart, 1979

    Google Scholar 

  • Lenz W. A short history of thalidomide embryopathy. Teratology 38: 203–215, 1988

    PubMed  CAS  Google Scholar 

  • Leport C, Matheron S, Martin S, Katlama C, Gougerot-Pocidalo MA, et al. Effet de la cyclosporine sur le nombre des lymphocytes circulants et des sous-populations lymphocytaires T au cours du SIDA. Médecine et Maladies Infectieuses 1: 25–29, 1987

    Google Scholar 

  • Lewis HBM, Albert-Recht F, Walker W. Cold haemagglutinin disease treated by thalidomide. British Journal of Haematology 15: 322, 1968

    PubMed  CAS  Google Scholar 

  • Lillicrap DA. Myxoedema after thalidomide (‘Distaval’). British Medical Journal 1: 477, 1962

    Google Scholar 

  • Lim SH, McWhannell A, Vora AJ, Boughton BJ. Successful treatment with thalidomide of acute graft-versus-host disease after bone-marrow transplantation. Lancet 1: 117, 1988

    PubMed  CAS  Google Scholar 

  • Lindahl-Kiessling K, Böök JA. Effects of thalidomide on human leucocyte cultures. Lancet 2: 405, 1963

    Google Scholar 

  • Locker D, Superstine E, Sulman FG. The mechanism of the push and pull principle VIII: endocrine effects of thalidomide and its analogues. Archives Internationales de Pharmacodynamie 194: 39–55, 1971

    CAS  Google Scholar 

  • Londoño F. Thalidomide in the treatment of actinic prurigo. International Journal of Dermatology 12: 326–328, 1973

    PubMed  Google Scholar 

  • Lovell CR, Hawk JLM, Calnan CD, Magnus IA. Thalidomide in actinic prurigo. British Journal of Dermatology 108: 467–471, 1983

    PubMed  CAS  Google Scholar 

  • Ludolph A, Matz DR. Elektrophysiologische Veränderungen bei Thalidomid-Neuropathie unter Behandlung des Lupus erythematodes discoides. Zeitschrift für Elektroenzephalographie, Elektromyographie und verwandte Gebiete 13: 167–170, 1982

    PubMed  CAS  Google Scholar 

  • Lueprasitsakul W, Abend S, Alex S, Reinhardt W, Appel MC, et al. Effect of thalidomide on the incidence of iodine-induced and spontaneous lymphocytic thyroiditis and spontaneous diabetes mellitus in the BB/Wor rat. Acta Endocrinologica 123: 79–83, 1990

    PubMed  CAS  Google Scholar 

  • Mascaro JM, Lecha M, Torras H. Thalidomide in the treatment of recurrent, necrotic, and giant mucocutaneous aphtae and aphthosis. Archives of Dermatology 115: 636–637, 1979

    PubMed  CAS  Google Scholar 

  • Mattila PS, Ullman KS, Fiering S, Emmel EA, McCutcheon M, et al. The actions of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes. EMBO Journal 9: 4425–4433, 1990

    PubMed  CAS  Google Scholar 

  • McBride WG. Thalidomide and congenital abnormalities. Lancet 2: 1358, 1961

    Google Scholar 

  • McCarthy DM, Kanfer EJ, Barrett AJ. Thalidomide for the therapy of graft-versus-host disease following allogeneic bone marrow transplantation. Biomedicine and Pharmacotherapy 43: 693–697, 1989

    CAS  Google Scholar 

  • McCarthy DM, Kanfer E, Taylor J, Barrett AJ. Thalidomide for graft-versus-host disease. Lancet 2: 1135, 1988

    PubMed  CAS  Google Scholar 

  • Merker HJ, Heger W, Sames K, Stürje H, Neubert D. Embryotoxic effects of thalidomide-derivatives in the non-human primate Callithrix jacchus. I. Effects of 3-(l,3-dihydro-l-oxo-2H-isoindol-2-yl)-2,6-dioxopiperidine (EM 12) on skeletal development. Archives of Toxicology 61: 165–179, 1988

    PubMed  CAS  Google Scholar 

  • Miller RG, Parry GJ, Pfaeffl W, Lang W, Lippert R, et al. The spectrum of peripheral neuropathy associated with ARC and AIDS. Muscle and Nerve 11: 857–863, 1988

    PubMed  CAS  Google Scholar 

  • Miller ZB. Inhibition of tissue-culture growth by a soluble thalidomide derivative. Lancet 2: 1068–1069, 1963

    Google Scholar 

  • Moncada B, Baranda ML, González-Amaro R, Urbina R, Loredo CE. Thalidomide — effect on T cell subsets as a possible mechanism of action. International Journal of Leprosy 53: 201–205, 1985

    CAS  Google Scholar 

  • Moran CJ, Ryder G, Turk JL, Waters MFR. Evidence for circulating immune complexes in lepromatous leprosy. Lancet 2: 572–573, 1972

    PubMed  CAS  Google Scholar 

  • Moulin G, Bonnet F, Barrut D, Franc MP. Traitement de la maladie de Jessner et Kanof par la thalidomide. Annales de Dermatologie et de Vénéréologie 110: 611–614, 1983

    PubMed  CAS  Google Scholar 

  • Mouzas GL, Gershon RK. The effect of thalidomide on skin allografts in mice: survival of the grafts. Transplantation 6: 476–478, 1968

    PubMed  CAS  Google Scholar 

  • Munro CS, Cox NH. Pyoderma gangrenosum associated with Behçet’s syndrome — response to thalidomide. Clinical and Experimental Dermatology 13: 408–410, 1988

    PubMed  CAS  Google Scholar 

  • Murdoch JM, Campbell GD. Antithyroid activity of N-phthalyl glutamic acid imide (K17). British Medical Journal 1: 84–85, 1958

    PubMed  CAS  Google Scholar 

  • Murphy GP, Brede HD, Weber HW, van Zyl JJW, Schoonees R, et al. Renal allotransplantation in the baboon with chemical immunosuppression. South African Medical Journal (Suppl.): 26–37, 1968

    Google Scholar 

  • Murphy GP, Mirand EA, Groenewald JH, Schoonees R, Weber HW, et al. Erythropoietin release in renal allografted baboons, with and without immunosuppression. Investigative Urology 7: 271–282, 1970

    PubMed  CAS  Google Scholar 

  • Naafs B, Bakkers EJM, Flinterman J, Faber WR. Thalidomide treatment of subacute cutaneous lupus erythematosus. British Journal of Dermatology 107: 83–86, 1982

    PubMed  CAS  Google Scholar 

  • Naafs B, Faber WR. Thalidomide therapy: an open trial. International Journal of Dermatology 24: 131–134, 1985

    PubMed  CAS  Google Scholar 

  • Neubert D, Krowke R. Effect of thalidomide derivatives on limb development in culture. In Limb Development and Regeneration, part A, pp. 387–397, Alan R. Liss, New York, 1983

    Google Scholar 

  • Newall DR, Tesh JM. Embryo culture as an early screen for teratogenic potential: II. Thalidomide. Food and Chemical Toxicology 24: 635–636, 1986

    CAS  Google Scholar 

  • Newman CGH. Teratogen update: clinical aspects of thalidomide embryopathy — a continuing preoccupation. Teratology 32: 133–144, 1985

    PubMed  CAS  Google Scholar 

  • Nicholls PJ. A note on the absorption and excretion of 14C-labelled thalidomide in pregnant mice. Journal of Pharmacy and Pharmacology 18: 46–48, 1966

    PubMed  CAS  Google Scholar 

  • Nougué J, Nougué M, Bazex J, Hayek PJ, Bidouze H. Survenue d’une hémorragie génitale au cours d’un prurigo nodulaire traité par thalidomide. Annales de Dermatologie et de Vénéréologie 110: 551–552, 1983

    PubMed  Google Scholar 

  • Nowack E. Die sensible Phase bei der Thalidomid-Embryopathie. Humangenetik 1: 516–536, 1965

    PubMed  CAS  Google Scholar 

  • Ockenfels H, Köhler F. Das L-Isomere als teratogenes Prinzip der N-Phthalyl-DL-Glutaminsäure. Experientia 26: 1236–1237, 1970

    PubMed  CAS  Google Scholar 

  • Ockenfels H, Köhler F, Meise W. Teratogene Wirkung und Stereospezifität eines Thalidomid-Metaboliten. Pharmazie 31: 492–493, 1976

    PubMed  CAS  Google Scholar 

  • Oohira A, Nogami H. Limb anomalies produced by 2,2′-dipyridyl in rats. Teratology 18: 63–70, 1978

    PubMed  CAS  Google Scholar 

  • Patey O, Charasz N, Roucayrol AM, Malkin JE, Lafix C. Thalidomide et colite ulcéreuse dans la maladie de Behçet. Gastroentérologie Clinique et Biologique 13: 104–110, 1989

    PubMed  CAS  Google Scholar 

  • Pearson JMH, Vedagiri M. Treatment of moderately severe erythema nodosum leprosum with thalidomide — a double-blind controlled trial. Leprosy Review 40: 111–116, 1969

    PubMed  CAS  Google Scholar 

  • Phillips A, Wainberg MA, Coates R, Klein M, Rachlis A, et al. Cyclosporine-induced deterioration in patients with AIDS. Canadian Medical Association Journal 140: 1456–1460, 1989

    PubMed  CAS  Google Scholar 

  • Powell RJ, Allen BR, Jenkins JS, Steele L, Hunneyball I, et al. Investigation and treatment of orogenital ulceration; studies on a possible mode of action of thalidomide. British Journal of Dermatology 113(suppl. 28): 141–144, 1985

    PubMed  CAS  Google Scholar 

  • Prigent F, Ouazzani W. Sarcoïdose cutanée. Traitement par la thalidomide. Presse Médicale 12: 3007, 1983

    CAS  Google Scholar 

  • Radeff B, Kuffer R, Samson J. Recurrent aphthous ulcer in patient infected with human immunodeficiency virus: successful treatment with thalidomide. Journal of the American Academy of Dermatology 23: 523–525, 1990

    PubMed  CAS  Google Scholar 

  • Ramselaar CG, Boone RM, Kluin-Nelemans HC. Thalidomide in the treatment of neuro-Behçet’s syndrome. British Journal of Dermatology 115: 367–370, 1986

    Google Scholar 

  • Reinherz EL, Parkman R, Rappeport J, Rosen FS, Schlossman SF. Aberrations of suppressor T cells in human graft-versus-host disease. New England Journal of Medicine 300, 1061–1068, 1979

    PubMed  CAS  Google Scholar 

  • Renault JY, Melcion C, Cordier A. Limb bud cell culture for in vitro teratogen screening: validation of an improved assessment method using 51 compounds. Teratogenesis, Carcinogenesis, and Mutagenesis 9: 83–96, 1989

    PubMed  CAS  Google Scholar 

  • Revuz J. Actualité du thalidomide. Annales de Dermatologie et de Vénéréologie 117: 313–321, 1990

    PubMed  CAS  Google Scholar 

  • Revuz J, Guillaume JC, Janier M, Hans P, Marchand C, et al. A double-blind trial of thalidomide in severe aphthous stomatitis. British Journal of Dermatology 121(suppl. 34): 17, 1989

    Google Scholar 

  • Revuz J, Guillaume JC, Janier M, Hans P, Marchand C, et al. Crossover study of thalidomide vs placebo in severe recurrent aphthous stomatitis. Archives of Dermatology 126: 923–927, 1990

    PubMed  CAS  Google Scholar 

  • Ringdén O, Aschan J, Westerberg L. Thalidomide for severe acute graft-versus-host disease. Lancet 2: 568, 1988

    PubMed  Google Scholar 

  • Roath S, Elves MW, Israels MCG. Effect of thalidomide on leucocyte cultures. Lancet 2: 812–813, 1962

    Google Scholar 

  • Roath S, Elves MW, Israels MCG. Effects of thalidomide and its derivatives on human leucocytes cultured in vitro. Lancet 1: 249–250, 1963

    PubMed  CAS  Google Scholar 

  • Rogé J, Testas P. Thalidomide et syndrome de Behçet. Gastroentérologie Clinique et Biologique 8: 196, 1984

    PubMed  Google Scholar 

  • Rojas-Espinosa O, Mendez-Navarrete I, Estrada-Parra S. Presence of C1q-reactive immune complexes in patients with leprosy. Clinical and Experimental Immunology 12: 215–223, 1972

    PubMed  CAS  Google Scholar 

  • Roll R, Bär F. Untersuchungen über die teratogene Wirkung von β-Aminopropionitril bei trächtigen Mäuseweibchen. Arzneimittel-Forschung 18: 806–814, 1968

    PubMed  CAS  Google Scholar 

  • Rustin MHA, Gilkes JJH, Robinson TWE. Pyoderma gangrenosum associated with Behçet’s disease: treatment with thalidomide. Journal of the American Academy of Dermatology 23: 941–944, 1990

    PubMed  CAS  Google Scholar 

  • Salafia A, Kharkar RD. Thalidomide and exfoliative dermatitis. International Journal of Leprosy 56: 625, 1988

    CAS  Google Scholar 

  • Samsoen M, Grosshans E, Basset A. La thalidomide dans le traitement du lupus érythémateux chronique (L.E.C.). Annales de Dermatologie et de Vénéréologie 107: 515–523, 1980

    PubMed  CAS  Google Scholar 

  • Saul A, Flores O, Novales J. Polymorphous light eruption: treatment with thalidomide. Australasian Journal of Dermatology 17: 17–21, 1976

    PubMed  CAS  Google Scholar 

  • Saurat JH, Camenzind M, Helg C, Chapuis B. Thalidomide for graft-versus-host disease after bone marrow transplantation. Lancet 1: 359, 1988

    PubMed  CAS  Google Scholar 

  • Saylan T, Saltik I. Thalidomide in the treatment of Behçet’s syndrome. Archives of Dermatology 118: 536, 1982

    PubMed  CAS  Google Scholar 

  • Schardein JL. In Drugs as teratogens, pp. 145–149, CRC Press, Boca Raton, 1976

    Google Scholar 

  • Schmahl HJ, Heger W, Nau H. The enantiomers of the teratogenic thalidomide analogue EM 12: 2. Chemical stability, stereoselectivity of metabolism and renal excretion in the marmoset monkey. Toxicology Letters 45: 23–33, 1989

    PubMed  CAS  Google Scholar 

  • Schmahl HJ, Nau H, Neubert D. The enantiomers of the teratogenic thalidomide analogue EM 12: 1. Chiral inversion and plasma pharmacokinetics in the marmoset monkey. Archives of Toxicology 62: 200–204, 1988

    PubMed  CAS  Google Scholar 

  • Schnitzler L. Effet bénéfique de la thalidomide dans un cas de pemphigus de Hailey-Hailey. Annales de Dermatologie et de Vénéréologie 111: 285–286, 1984

    PubMed  CAS  Google Scholar 

  • Schübel F, Partsch CJ. Thalidomid-Embryopathien und ihre Einwirkung auf die Zahnanlage. Deutsche zahnärztliche Zeitschrift 20: 1278–1283, 1965

    PubMed  Google Scholar 

  • Schumacher H, Smith RL, Williams RT. The metabolism of thalidomide: the fate of thalidomide and some of its hydrolysis products in various species. British Journal of Pharmacology 25: 338–351, 1965a

    CAS  Google Scholar 

  • Schumacher H, Smith RL, Williams RT. The metabolism of thalidomide: the spontaneous hydrolysis of thalidomide in solution. British Journal of Pharmacology 25: 324–337, 1965b

    CAS  Google Scholar 

  • Schumacher HJ, Wilson JG, Terapane JF, Rosedale SL. Thalidomide: disposition in rhesus monkey and studies of its hydrolysis in tissues of this and other species. Journal of Pharmacology and Experimental Therapeutics 173: 265–269, 1970

    PubMed  CAS  Google Scholar 

  • Scolari F, Harms M, Gilardi S. La thalidomide dans le traitement du lupus érythémateux chronique. Dermatologica 165: 355–362, 1982

    PubMed  CAS  Google Scholar 

  • Shannon EJ, Vadiee AR. Effect of thalidomide on production of interleukin-1. Abstracts of the 89th Annual Meeting of the American Society for Microbiology, p. 132, New Orleans, 14–18 May, 1989

  • Shannon EJ, Vadiee AR, Vaishnavi C. Thalidomide inhibits the synthesis of IL-1β in human monocytes stimulated with endotoxin. Abstracts of the 90th Annual Meeting of the American Society for Microbiology, p. 150, Anaheim, 13–17 May, 1990

  • Shepard TH, Shiota K. Bioactivation of thalidomide by a monkey liver fraction in a rat limb culture system. In Limb development and regeneration, part A, pp. 377–385, Alan R. Liss, New York, 1983

    Google Scholar 

  • Sheskin J. Thalidomide in the treatment of lepra reactions. Clinical Pharmacology and Therapeutics 6: 303–306, 1965

    PubMed  CAS  Google Scholar 

  • Sheskin J. Zur Therapie der Prurigo nodularis Hyde mit Thalidomid. Hautarzt 26: 215, 1975

    PubMed  CAS  Google Scholar 

  • Sheskin J. Study with nine thalidomide derivatives in the lepra reaction. International Journal of Dermatology 17: 82–84, 1978

    PubMed  CAS  Google Scholar 

  • Sheskin J. The treatment of lepra reaction in lepromatous leprosy: Fifteen years’ experience with thalidomide. International Journal of Dermatology 19: 318–322, 1980

    PubMed  CAS  Google Scholar 

  • Sheskin J, Convit J. Results of a double blind study of the influence of thalidomide on the lepra reaction. International Journal of Leprosy 37: 135–146, 1969

    CAS  Google Scholar 

  • Sheskin J, Magora A, Sagher F. Motor conduction velocity studies in patients with leprosy reaction treated with thalidomide and other drugs. International Journal of Leprosy 37, 359–364, 1969

    CAS  Google Scholar 

  • Sheskin J, Sagher F. Trials with thalidomide derivatives in leprosy reactions. Leprosy Review 39: 203–206, 1968a

    PubMed  CAS  Google Scholar 

  • Sheskin J, Sagher F, Dorfman M, von Schrader-Beielstein HW. Unsatisfactory results with thalidomide as a specific treatment for leprosy. Israel Journal of Medical Sciences 4: 901–904, 1968b

    PubMed  CAS  Google Scholar 

  • Sheskin J, Yaar I. Motorische Leitungsgeschwindigkeit der Kubitalnerven bei Patienten mit Leprareaktion: Zusammenfassung einer dreizehnjährigen Beobachtungsreihe während der Thalidomidbehandlung. Hautarzt 30: 376–379, 1979

    PubMed  CAS  Google Scholar 

  • Shiota K, Uwabe C, Yamamoto M, Kazuyoshi A. Susceptibility to cyclophosphamide and thalidomide of fetal rat limb buds grafted in athymic (nude) mice. Toxicology Letters 50: 309–318, 1990

    PubMed  CAS  Google Scholar 

  • Siekierka JJ, Hung SHY, Poe M, Lin CS, Sigal NH. A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. Nature 341: 755–757, 1989

    PubMed  CAS  Google Scholar 

  • Siekierka JJ, Wiederrecht G, Greulich H, Boulton D, Hung SHY, et al. The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase. Journal of Biological Chemistry 265: 21011–21015, 1990

    PubMed  CAS  Google Scholar 

  • Simpson JA. Myxoedema after thalidomide (‘Distaval’). British Medical Journal 1: 55, 1962

    Google Scholar 

  • Sinha AA, Lopez MT, McDevitt HO. Autoimmune diseases: the failure of self tolerance. Science 248: 1380–1388, 1990

    PubMed  CAS  Google Scholar 

  • Smith RL, Fabro S, Schumacher H, Williams RT. Studies on the relationship between the chemical structure and embryotoxic activity of thalidomide and related compounds. In Robson et al. (Eds) Symposium on embryopathic activity of drugs, pp. 194–209, J. and A. Churchill, London, 1965

    Google Scholar 

  • Smith RL, Williams RAD, Williams RT. Phtaloylisoglutamine, a metabolite of thalidomide. Life Sciences 7: 333–336, 1962

    Google Scholar 

  • Snider WD, Simpson DM, Nielsen S, Gold JWM, Metroka CE, et al. Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Annals of Neurology 14: 403–418, 1983

    PubMed  CAS  Google Scholar 

  • So YT, Holtzman DM, Abrams DI, Olney RK. Peripheral neuropathy associated with acquired immunodeficiency syndrome. Archives of Neurology 45: 945–948, 1988

    PubMed  CAS  Google Scholar 

  • Somers GF. Pharmacological properties of thalidomide (α-phthalimido glutarimide), a new sedative hypnotic drug. British Journal of Pharmacology 15: 111–116, 1960

    CAS  Google Scholar 

  • Stahl A. Dysgnathien im Milchgebiss bei Dysmelie: Beitrag zur Thalidomid-Embryopathie. Fortschritte der Kieferorthopädie 27: 447–458, 1966

    PubMed  CAS  Google Scholar 

  • Stahl A. Dysplasien im Bereich des Mundes, der Kiefer und der Zähne bei Dysmelie. Ein Beitrag zur Thalidomid-Embryopathie. Deutsche Zahnärztliche Zeitschrift 22: 356–367, 1967

    PubMed  CAS  Google Scholar 

  • Steinmann B, Bruckner P, Superti-Furga A. Cyclosporin A slows collagen triple-helix formation in vivo: indirect evidence for a physiologic role of peptidyl-prolyl cis-trans-isomerase. Journal of Biological Chemistry 266: 1299–1303, 1991

    PubMed  CAS  Google Scholar 

  • Stephens TD. Proposed mechanisms of action in thalidomide embryopathy. Teratology 38: 229–239, 1988

    PubMed  CAS  Google Scholar 

  • Szer J, Atkinson K, Vowels M, Waters K. Thalidomide in the treatment of refractory chronic graft-versus-host disease after allogeneic bone marrow transplantation. Australian and New Zealand Journal of Medicine 20(Suppl. 1): 390, 1990a

    Google Scholar 

  • Szer J, Atkinson K, Vowels M, Waters K. Thalidomide in the treatment of refractory chronic graft-versus-host disease after allogeneic bone marrow transplantation. Journal of Cellular Biochemistry (Suppl. 14A): 333, 1990b

    Google Scholar 

  • Takahashi N, Hayano T, Suzuki M. Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature 337: 473–475, 1989

    PubMed  CAS  Google Scholar 

  • Tamura F, Vogelsang GB, Reitz BA, Baumgartner WA, Herskowitz A. Combination thalidomide and cyclosporine for cardiac allograft rejection. Transplantation 49: 20–25, 1990

    PubMed  CAS  Google Scholar 

  • Thiele DL, Eigenbrodt ML, Bryde SE, Eigenbrodt EH, Lipsky PE. Intestinal graft-versus-host disease is initiated by donor T cells distinct from classic cytotoxic T lymphocytes. Journal of Clinical Investigation 84: 1947–1956, 1989

    PubMed  CAS  Google Scholar 

  • Toonstra J, Wildschut A, Boer J, Smeenk G, Willemze R, et al. Jessner’s lymphocytic infiltration of the skin: a clinical study of 100 patients. Archives of Dermatology 125: 1525–1530, 1989

    PubMed  CAS  Google Scholar 

  • Torras H, Lecha M, Mascaro JM. La talidomina en el tratamiento de las aftosis y enfermedad de Behçet: experiencia de cuatros años. Medicina Cutanea Ibero-Latino Americana 10: 103–112, 1982

    PubMed  CAS  Google Scholar 

  • Trèves R, Arnaud M, Jacob P, Lubeau M, Tabaraud F, et al. Amélioration spectaculaire des des arthrites de la maladie de Behçet par la thalidomide: à propos d’un cas. Revue du Rhumatisme 51: 585, 1984

    Google Scholar 

  • Tsutsumi S, Gidoh M. Inefficacy of thalidomide on rat adjuvant-induced arthritis and lack of arthrogenicity of Hansen bacilli. Japanese Journal of Leprosy 57: 122–128, 1988

    PubMed  CAS  Google Scholar 

  • Turk JL, Bryceson ADM. Immunological phenomena in leprosy and related diseases. Advances in Immunology 13: 209–266, 1971

    PubMed  CAS  Google Scholar 

  • Ulrich M, de Salas B, Convit J. Thalidomide activity in experimental Artus and anaphylactic reactions. International Journal of Leprosy 39: 131–134, 1971

    CAS  Google Scholar 

  • van den Broek H. Treatment of prurigo nodularis with thalidomide. Archives of Dermatology 116: 571–572, 1980

    PubMed  Google Scholar 

  • Venencie PY, Saurat JH. Pyoderma gangrenosum chez un enfant: traitement par la thalidomide. Annales de Pédiatrie 29: 67–69, 1982

    PubMed  CAS  Google Scholar 

  • Viraben R, Dupre A, Gorguet B. Pure cutaneous histiocytosis resembling sinus histiocytosis. Clinical and Experimental Dermatology 13: 197–199, 1988

    PubMed  CAS  Google Scholar 

  • Vladutiu A. Another chance for thalidomide? Lancet 1: 981–982, 1966

    PubMed  CAS  Google Scholar 

  • Vogelsang GB, Hess AD, Friedman KJ, Santos GW. Therapy of chronic graft-v-host disease in a rat model. Blood 74: 507–511, 1989

    PubMed  CAS  Google Scholar 

  • Vogelsang GB, Hess AD, Gordon G, Brundrette R, Santos GW. Thalidomide induction of bone marrow transplantation tolerance. Transplantation Proceedings 19: 2658–2661, 1987

    PubMed  CAS  Google Scholar 

  • Vogelsang GB, Hess AD, Gordon G, Santos GW. Treatment and prevention of acute graft-versus-host disease with thalidomide in a rat model. Transplantation 41: 644–647, 1986b

    PubMed  CAS  Google Scholar 

  • Vogelsang GB, Hess AD, Santos GW. Thalidomide for treatment of graft-versus-host disease. Bone Marrow Transplantation 3: 393–398, 1988a

    PubMed  CAS  Google Scholar 

  • Vogelsang GB, Taylor S, Gordon G, Hess AD. Thalidomide, a potent agent for the treatment of graft-versus-host disease. Transplantation Proceedings 18: 904–906, 1986a

    CAS  Google Scholar 

  • Vogelsang GB, Wells MC, Santos GW, Chen TL, Hess AD. Combination low-dose thalidomide and cyclosporine prophylaxis for acute graft-versus-host disease in a rat mismatched model. Transplantation Proceedings 20: 226–228, 1988b

    PubMed  CAS  Google Scholar 

  • Waters MFR. An internally controlled double blind trial of thalidomide in severe erythema nodosum leprosum. Leprosy Review 42: 26–42, 1971

    PubMed  CAS  Google Scholar 

  • Waters MFR. Treatment of reactions in leprosy. Leprosy Review 45: 337–341, 1974

    PubMed  CAS  Google Scholar 

  • Waters MFR, Laing ABG, Ambikapathy A, Lennard-Jones JE. Treatment of ulcerative colitis with thalidomide. British Medical Journal 1: 792, 1979

    PubMed  CAS  Google Scholar 

  • Waters MFR, Turk JL, Wemambu SNC. Mechanisms of reactions in leprosy. International Journal of Leprosy 39: 417–428, 1971

    CAS  Google Scholar 

  • Wemambu SNC, Turk JL, Waters MFR, Rees RJW. Erythema nodosum leprosum: a clinical manifestation of the Arthus phenomenon. Lancet 2: 933–935, 1969

    PubMed  CAS  Google Scholar 

  • Williams I, Weller IVD, Malin A, Anderson J, Waters MFR. Thalidomide hypersensitivity in AIDS. Lancet 337: 436–437, 1991

    PubMed  CAS  Google Scholar 

  • Williams RT. Thalidomide: a study of biochemical teratology. Archives of Environmental Health 16: 493–502, 1968

    PubMed  CAS  Google Scholar 

  • Williams RT, Schumacher H, Fabro S, Smith RL. The chemistry and metabolism of thalidomide. In Robson et al. (Eds) Symposium on embryopathic activity of drugs, pp. 167–182, J. and A. Churchill, London, 1965

    Google Scholar 

  • Winkelmann RK, Connolly SM, Doyle JA, Padilha-Goncalves A. Thalidomide treatment of prurigo nodularis. Acta Dermatologica et Venerologica 64: 412–417, 1984

    CAS  Google Scholar 

  • Wood PMD, Proctor SJ. The potential use of thalidomide in the therapy of graft-versus-host disease — a review of clinical and laboratory information. Leukemia Research 14: 395–399, 1990

    PubMed  CAS  Google Scholar 

  • Wuest HM, Fox RR, Crary DD. Relationship between teratogeny and structure in the thalidomide field. Experientia 24: 993–994, 1968

    PubMed  CAS  Google Scholar 

  • Wulff CH, Hoyer H, Asboe-Hansen G, Brodthagen H. Development of polyneuropathy during thalidomide therapy. British Journal of Dermatology 112: 475–480, 1985

    PubMed  CAS  Google Scholar 

  • Yasuda Y, Nishimura H. Thalidomide may inhibit proliferation of mesenchyme in human limb buds. Analytical Cellular Pathology 1: 247–254, 1989

    PubMed  CAS  Google Scholar 

  • Yee GC, Self SG, McGuire TR, Carlin J, Sanders JE, et al. Serum cyclosporine concentration and risk of acute graft-versus-host disease after allogeneic marrow transplantation. New England Journal of Medicine 319: 65–70, 1988

    PubMed  CAS  Google Scholar 

  • Yorke RA, Sutton WS, Kilshaw D, Taylor WH. Neuropathy, hypoglycaemia, and adrenal dysfunction during treatment with thalidomide. British Medical Journal 2: 306–307, 1962

    PubMed  CAS  Google Scholar 

  • Youle M, Clarbour J, Farthing C, Connolly M, Hawkins D, et al. Treatment of resistant aphthous ulceration with thalidomide in patients positive for HIV antibody. British Medical Journal 298: 432, 1989

    PubMed  CAS  Google Scholar 

  • Youle M, Hawkins D, Gazzard B. Thalidomide in hyperalgic pharyngeal ulceration of AIDS. Lancet 335: 1591, 1990

    PubMed  CAS  Google Scholar 

  • Zimmermann B, Riso J, Somogyi H. Effects of L-azetidine-2-car-boxylic acid and β-D-xylosides on lung development in vitro. In Neubert et al. (Eds) Culture techniques: applicability for studies on prenatal differentiation and toxicity, pp. 341–355, Walter de Gruyter, Berlin, New York, 1981

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pharmaceutical Research, Hoechst AG/H 821, Postfach 80 03 20, D-6230, Frankfurt 80, Federal Republic of Germany

    Volkmar Günzler

Authors
  1. Volkmar Günzler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Günzler, V. Thalidomide in Human Immunodeficiency Virus (HIV) Patients. Drug-Safety 7, 116–134 (1992). https://doi.org/10.2165/00002018-199207020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199207020-00004

Keywords

Search

Navigation