Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of patients with AIDS and AIDS-related complex (ARC) with zidovudine is limited by major haematological toxicity. In an open study of the use of zidovudine, 10 out of a total of 81 patients developed a severe anaemia within the first 3 months of treatment. In five of these 10 patients the mean cell volume did not increase but remained within the normal range. Bone marrow examination of three of these five showed a pure red-cell aplasia. In all five patients the anaemia resolved on discontinuation of the drug and in three that were re-challenged, the anaemia recurred. Zidovudine-induced anaemia has usually been reported as macrocytic and megaloblastic, but in our experience erythroid aplasia appears to be a major cause of anaemia occurring within the first 3 months of treatment. The earliest sign is anaemia with a stable or only a slight increase in the mean cell volume (MCV).
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PMID:Reversible zidovudine-induced pure red-cell aplasia. 249 34

Opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) require hematotoxic drugs. Neutropenia and anemia are the major hematologic abnormalities attributed to zidovudine (AZT). Concomitant medications associated with an increased frequency of toxicity are trimethoprim-sulfamethoxazole (cotrimoxazole), sulfadiazine, pyrimethamine, ganciclovir. AZT is stopped during initial treatment then reintroduced at full dosage with cotrimoxazole, at reduced dosage with sulfadiazine + pyrimethamine or ganciclovir.
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PMID:[Problems posed by therapeutic combinations of zidovudine during the treatment of opportunistic infections in AIDS]. 262 55

The first placebo-controlled trial of zidovudine in the management of HIV infection involved patients with the acquired immune deficiency syndrome (AIDS) following their first episode of Pneumocystis carinii pneumonia and patients with severe AIDS-related complex (ARC). Zidovudine was shown to increase survival, and the trial was terminated early at the request of an independent review board. In order to obtain more information on the long-term efficacy and tolerance of the drug the study was continued on an open-label basis where all patients were offered zidovudine. Data from this ongoing open-label study are reviewed on a regular basis. Side-effects associated with zidovudine include anaemia and neutropenia both of which are more predominant in patients with more advanced disease. Two basic strategies have been adopted with the aim of improving the therapeutic index of the drug involving (i) dose modification and (ii) combination with other antiviral or immunomodulatory compounds. Although several phase I and II studies are proceeding it is likely that research in this area will continue to expand. AIDS patients with Kaposi's sarcoma (but without a history of AIDS-defining opportunistic infection) were precluded from the original phase II trial described above. The value of zidovudine in the treatment of the sarcoma per se has yet to be established. Trials are currently in progress in this indication evaluating the potential of zidovudine administered either alone or in combination with interferon. Possibly the largest area of research is concerned with defining the role of zidovudine earlier in the course of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Current and future trials with zidovudine. 264 66

Treatment of the acquired immunodeficiency syndrome with 3-azidothymidine (zidovudine; AZT) can induce severe neutropenia and anemia, while platelet counts increase. In order to understand the mechanism by which this favorable effect on platelets is induced, we prospectively studied platelet kinetics and platelet serology in 8 hemophiliacs receiving the drug. All patients underwent a second investigation after 3 months of treatment. Four patients were thrombocytopenic before treatment. Platelet counts increased significantly already after 1 week of treatment (p = 0.03), when only 3 patients remained thrombocytopenic. In these latter patients a further increase of platelet counts was noticed during the following 3 months. Platelet life-span was shortened in all patients at the initial investigation and a significant prolongation was measurable at the second evaluation (p = 0.015). Platelet-associated immunoglobulin G was increased in 3 patients at the first investigation and in 4 patients at the follow-up. Platelet-associated complement (PAC3d) was elevated in all subjects at the first determination. It decreased in 6, but increased in 2 patients thereafter; thus these changes did not become significant (p = 0.078). Immunofluorescence studies revealed antiplatelet antibodies in 7 patients' sera before treatment, and in 5 sera during drug therapy. At both investigations, the antibodies bound to the platelet glycoprotein IIIa as was demonstrated by immunoprecipitation of radiolabeled platelet proteins. We conclude, that AZT treatment improves platelet counts in HIV-infected hemophiliacs primarily by a prolongation of platelet survival without having a significant influence on antiplatelet antibody binding.
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PMID:Effects of 3-azidothymidine on platelet counts, indium-111-labelled platelet kinetics, and antiplatelet antibodies. 267 61

Azidothymidine (AZT) is a useful drug in management of AIDS. Nevertheless, its hematologic toxicity such as anemia and neutropenia present further complications to an already compromised hematopoietic state in patients. We studied the effects of AZT on human and murine bone marrow (BM) colony growth as determined by assays of CFU-E, BFU-E, CFU-GM, and fibroblastoid stromal (CFU-Fb) colonies. Cultures were grown in methylcellulose with growth factors and scored after three- to 14-day incubation. In general, murine marrow cultures were more sensitive to AZT as compared with human marrow. Furthermore, interindividual variation in toxicity to AZT was observed between marrow samples; 1 mumol/L AZT inhibited murine CFU-E, BFU-E, and CFU-GM by 98% to 100%, whereas human marrow was inhibited by 52%, 87%, and 65%, respectively. Lower concentrations of AZT (0.1 mumol/L) inhibited murine erythroid colony growth by 85% to 90%, whereas human growth was inhibited by only 39% to 52%. Myeloid colony inhibition was similar for human and murine systems. CFU-Fb growth was markedly suppressed (75%) by 1 mumol/L AZT. Hemin, at a concentration of 10 mumol/L, overcame some of the inhibitory effects of 1 to 0.1 mumol/L AZT without hindering antiviral activity. Inhibition of human CFU-E growth was completely overcome with hemin, whereas CFU-GM growth was recovered to 66% to 74% of control. A similar but less pronounced effect was observed for BFU-E. Furthermore, hemin does not decrease AZT's effects of HIV antigen content in vitro. We conclude that anemia and neutropenia, occurring as a result of AZT, may not be as pronounced in the presence of hemin. Furthermore, CFU-Fb was significantly reduced in the presence of low concentrations of AZT. This may indicate a major target site for BM toxicity since the stromal microenvironment may be responsible for maintaining short- and long-term hematopoiesis.
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PMID:Microenvironmental toxicity of azidothymidine: partial sparing with hemin. 275 5

Zidovudine was first prescribed for patients from the anti-human immunodeficiency virus (HIV) positive cohort of haemophiliacs in Newcastle in May 1987. Prior to this therapy, seven patients had died of acquired immune deficiency syndrome, and episodes of serious opportunistic infection were common. To date, 22 patients have received zidovudine, seven with or without acyclovir in a prospective Wellcome trial. Of the 22 patients, three were children and one was an adult female. All haemophilic patients were infected around 1982 as a result of factor VIII concentrate contamination with HIV. There have been five deaths, two occurring within 6 weeks of the start of zidovudine therapy. A third death was due to myocardial infarction in week 45. The other two deaths occurred at 41 weeks and 47 weeks in transfusion dependent patients. Only three serious opportunistic infections (pneumocystis pneumonia) have been observed in the remaining patients, one within a week of starting therapy and one in a non-compliant patient at week 24. The latter patients had a further episode of Pneumocystis carinii pneumonia in week 51. The transfusion dependent patients who died presented with anaemia at weeks 5 and 13, and required 48 and 28 units of packed cells respectively. A further patient required a single transfusion at week 7 and at week 43 continues to maintain an acceptable haemoglobin level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Zidovudine: experience at the Newcastle Haemophilia Centre. 278 16

Azidothymidine is a new antiviral drug that acts by competitive inhibition of reverse transcriptase of retroviruses. Azidothymidine is now widely used in treatment of patients with AIDS or ARC; the most important side effects of this drug are anaemia and neutropenia. Recently pigmentary changes of the nails (diffuse pigmentation and longitudinal or transverse bands) provoked by azidothymidine-treatment have also been reported. We describe a such case.
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PMID:[Nail pigmentation caused by azidothymidine]. 280 86

3'-Azido-3'-deoxythymidine (AZT) has attained wide clinical utility in the treatment of acquired immunodeficiency syndrome (AIDS). Unfortunately, associated with AZT use, is the development of severe hematopoietic toxicity as manifested by anemia, neutropenia and overall bone marrow suppression. Interleukin-1 (IL-1), a cytokine, primarily produced by activated macrophages, has been involved in the control of hematopoiesis by acting synergistically with other hematopoietic growth factors, and has been demonstrated to be an effective agent in reducing the myelosuppression associated with the therapy for malignant disease. We report here the ability of recombinant human IL-1 alpha to protect normal murine hematopoietic progenitors (CFU-GM, BFU-E, and CFU-Meg) from the toxic effects of AZT. Following the determination of the LD50 dose for each progenitor, IL-1 was added in co-culture studies (10-1000 units; 0.001-1.0 micrograms/ml protein) with adherent cell depleted marrow. Marrow progenitors expressed differences in AZT sensitivity, e.g., BFU-E, LD50 5 x 10(-9)M; CFU-Meg, LD50 10(-7) M; CFU-GM, 5 x 10(-5) M respectively. IL-1 inhibited AZT induced toxicity. The maximum IL-1 dose effect was observed for CFU-GM and CFU-Meg at 300 units, 0.3 micrograms protein; however BFU-E required a dose of 600 units, 0.6 micrograms/ml protein to reverse the effects of AZT. These results demonstrate marrow progenitors respond differently to AZT and identifies the potential efficacy of IL-1 to minimize the hematopoietic toxicity associated with AZT treatment.
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PMID:Protection of 3'-azido-3'-deoxythymidine induced toxicity to murine hematopoietic progenitors (CFU-GM, BFU-E and CFU-MEG) with interleukin-1. 281 53

The long-term effectiveness of Azidothymidine (AZT, Zidovudine) was evaluated in FIV-seropositive cats with clinical symptoms (n = 9; Group 1) compared with conventional symptomatical therapy (n = 5; Group 2). The oral administration of Azidothymidine at a dosage of 5 mg/kg BW yielded a mean peak plasma concentration of 4.59 microM one hour after application (median: 3.74 microM). Elimination half time was 1.5 h. The permanent oral application of Azidothymidine at a dosage of 5 mg/kg BW TID led to a total recovery from clinical symptoms in six of nine FIV-seropositive cats (Group 1) 4-6 weeks after the onset of therapy. One cat clinically improved with only sporadical recurrence of disease; therapy with Azidothymidine was not effective in two cats. All the FIV-seropositive cats treated symptomatically responded well to antibiotics and immunomodulators within 10-14 days (n = 5; Group 2). Recurrence of clinical symptoms was noticed in three of five patients within 2 years after therapy and one cat died. During the treatment with Azidothymidine hyperproteinemia and abnormal albumin-to-globulin ratio became normal within 6 months in four FIV positive cats (Group 1), whereas hyperproteinemia did not change in Group 2. The following adverse effects were noticed in Group 1: a transient decrease of red blood cell count (RBC), packed cell volume (PCV) and haemoglobin until the 4th week of application of Azidothymidine (5/8), but the haemogram was within the normal range after 3 months. In one cat with hyperglycemia the anaemia remained until the administration of Azidothymidine was terminated. Heinz (Schmauch) bodies in the erythrocytes appeared in two FIV-positive cats 2 weeks after the onset of the therapy.
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PMID:Long-term treatment of diseased, FIV-seropositive field cats with azidothymidine (AZT). 749 72

Lithium is an agent capable of influencing many aspects of blood cell production, in particular, the formation of granulocytes. Because of this property, lithium has been demonstrated to be an effective agent whenever granulocyte production is either faulty or inadequate. The anti-viral drug zidovudine (AZT) has used been extensively in the treatment of acquired immune deficiency syndrome (AIDS). However, its effectiveness is limited because of the myelosuppression and bone marrow toxicity associated with its use. We have previously demonstrated that lithium, when combined with AZT in vitro with normal bone marrow cells or when administered in vivo to mice receiving dose-escalation AZT, reduced the myelosuppression and marrow toxicity of AZT significantly. We report here further studies designed to evaluate the extent of lithium's capacity to modulate AZT toxicity by investigating the ability of lithium to influence blood cell production when administered to normal mice during an initial exposure to AZT. C57BL6 were administered dose-escalation AZT (1.0 mg/ml and 2.5 mg/ml) for a period of 4-weeks in the presence or absence of lithium carbonate (1 mM). This was followed by an additional 4-week period during which mice received only AZT. Animals were analyzed on a weekly basis for their peripheral blood indices. Animals receiving dose-escalation AZT demonstrated anemia, thrombocytopenia, and neutropenia which was dose-related. During the period when animals received combination lithium/AZT, there was significantly less anemia, thrombocytopenia, and neutropenia as compared to the AZT controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lithium and anti-viral drug toxicity: II. Further studies on the ability of lithium to modulate the hematopoietic toxicity associated with the anti-viral drug zidovudine (AZT). 758 37


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