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)

Thirty-five children with symptomatic human immunodeficiency virus infection were enrolled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had less than 0.5 10(9) CD4+ lymphocytes per liter (less than 500 cells/mm3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count less than 0.75 10(9)/L (750 cells/mm3] occurred in nine patients. The median neutrophil count fell from 2.50 10(9)/L at entry to 1.72 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.
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PMID:Safety and tolerance of intermittent intravenous and oral zidovudine therapy in human immunodeficiency virus-infected pediatric patients. Pediatric Zidovudine Phase I Study Group. 218 Nov 2

Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]). We conducted a randomized, double-blind, placebo-controlled clinical trial of recombinant human erythropoietin (100 U per kilogram of body weight thrice weekly by intravenous bolus) in 63 patients with AIDS treated with zidovudine (29 in the erythropoietin group and 34 in the placebo group). Reductions in the number of units of red cells transfused and the number of patients given transfusions per month became apparent in the second and third months of the trial. The reductions were observed in patients with endogenous erythropoietin levels less than or equal to 500 IU per liter at base line, but not in patients whose levels were greater than 500 IU per liter at the beginning of the study. Although the hematocrit and hemoglobin level were not used as the primary criteria of efficacy because the patients received transfusions when their physicians decided that they needed them, a significantly higher rate of increase in the hematocrit was observed in the patients treated with recombinant human erythropoietin whose levels of endogenous erythropoietin were less than or equal to 500 IU per liter (0.00353 points per week) than in the patients given placebo (0.00116 points per week). This effect was not seen in patients with higher levels of endogenous erythropoietin. Serious side effects did not occur more often in the group treated with erythropoietin than in the placebo group. We conclude that recombinant human erythropoietin may be useful in patients with AIDS treated with zidovudine, although the indicators for its use remain to be clarified.
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PMID:Recombinant human erythropoietin for patients with AIDS treated with zidovudine. 221 68

Zidovudine (ZDV) is the only approved antiviral for the treatment of human immunodeficiency virus infection (HIV) in the U.S. Although newer antivirals have reached Phase II testing, ZDV is now the accepted therapy against which all other agents will be compared. Zidovudine 1500 mg/d was previously prescribed only to adult HIV-infected patients who had developed AIDS or AIDS-related complex (ARC). However, results obtained from recently completed studies indicate that a lower daily dose (500 mg) appears to be equivalent. In addition, ZDV therapy appears to be beneficial to asymptomatic HIV-infected patients with CD4+ counts less than 500/mm3. The toxicity profile of ZDV, previously obtained from patients receiving 1500 mg/d, consisted of either acute (e.g., fever, rash, headache) or chronic (e.g., anemia, neutropenia, myopathy) adverse effects. ZDV pharmacokinetics are variable within and between the different subpopulations of HIV-infected patients who have been studied. Bioavailability ranges from 50 to 70 percent, and values for half-life, total body clearance, and volume of distribution are 1-2 h, 20-40 mL/min/kg, and 1-2 L/kg, respectively. Drug interactions occur primarily between ZDV and other agents that undergo hepatic glucuronidation (e.g., probenecid, sulfamethoxazole) resulting in decreased ZDV clearance. ZDV is currently measured by HPLC, radioimmunoassay and FPIA; however, the role of therapeutic monitoring is currently under investigation. Studies of ZDV therapy in neonates, pediatric patients, patients with resistant isolates of HIV, and HIV-infected patients receiving combined treatment with other reverse transcriptase inhibitors or immunomodulators are ongoing.
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PMID:Zidovudine update: 1990. 219 18

Zidovudine, the first widely used antiretroviral agent, prevents replication of the human immunodeficiency virus (HIV) by inhibiting reverse transcriptase. Its use in patients with acquired immunodeficiency syndrome slows progression of the disease and prolongs survival. Zidovudine also significantly reduces the rate of progression to AIDS in adults with asymptomatic HIV infection and CD4 T-lymphocyte counts below 500 per mm3. The major toxicity of the drug is bone marrow suppression resulting in anemia or granulocytopenia, or both. Recently, lower doses have been shown to be effective and are associated with less toxicity.
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PMID:Zidovudine for the treatment of HIV infection. 204 38

While anemia and a positive direct anti-globulin test are each frequently observed in the clinical syndrome of human immunodeficiency virus (HIV) infection, autoimmune hemolytic anemia has rarely been reported in this setting. A case of severe warm autoimmune hemolytic anemia (AIHA) with reticulocytopenia in a patient with AIDS-related complex is reported. Laboratory and clinical findings of severe hemolysis were present, including anhaptoglobinemia, microspherocytosis, splenomegaly, and transfusion dependence. Azidothymidine (AZT) therapy may have exacerbated this patient's anemia. Splenectomy produced a delayed but complete remission of the AIHA despite continuation of AZT therapy. Review of other reports of positive direct antiglobulin tests and autoimmune hemolytic anemia in patients with HIV infections suggests that autoantibodies may be a significant cause of anemia in this population and that the frequent lack of reticulocytosis, despite bone marrow erythroid hyperplasia, may lead to the underdiagnosis of AIHA in HIV-infected patients.
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PMID:HIV-associated autoimmune hemolytic anemia: report of a case and review of the literature. 175 45

A therapeutic committee was established in Toulouse Regional University Hospital in order to prescribe zidovudine in patients suffering from AIDS. Using an informatic card, the side effects were evaluated in the 125 patients treated by Zidovudine since the creation of the Committee (from July 1987 to January 1989). Zidovudine was prescribed from May 1987 to June 1988 at the total dose of 1,200 mg daily from June 1988 at 900 mg daily. The most frequent side effects were hematologic: zidovudine used alone (or associated with non hematotoxic drugs) elicited in 21.2% of patients a neutropenia (defined as a number of neutrophils less than 1,000/mm3), in 2.4% anaemia (haemoglobin less than or equal to 9 g/100 ml) and in 4.8% neutropenia associated with anaemia. When zidovudine was administered with hematotoxic drugs, neutropenia, anaemia or the association of both were observed in 12.0%, 3.2% and 2.4% of patients respectively. These hematologic side effects were always regressive after drug cessation. However, it is important to underline the low incidence of hematological side effects on red cells of zidovudine in the present study. This result is unexpected. The other side effects of Zidovudine (used alone) did not led to modification in drug treatment: gastrointestinal disturbances (30.4%), headaches (16.8%), insomnia (13.6%), somnolence (6.4%).... These side effects appeared during the four first months and decreased with the continuation of drug treatment. Their imputation was difficult to define and differentiate to evolution of the disease.
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PMID:[Evaluation of the pharmacovigilance follow-up of zidovudine]. 226 33

The levels of adenosine deaminase (ADA) were determined in the erythrocytes of 10 patients with sexually transmitted HIV-1 infection [five cases with AIDS-related complex (ARC) and five with AIDS] before and after therapy with zidovudine (azidothymidine; AZT). A linear increase in ADA activity was observed during the second and third months of zidovudine treatment, with a final increase of about threefold after 3 months of drug administration. The concentration of adenosine triphosphate (ATP) was significantly lower in the erythrocytes of the same group of patients with respect to healthy controls, and a further decrease was noted after 3 months of zidovudine treatment. The results obtained indicate that treatment of ARC/AIDS subjects with zidovudine induces metabolic changes which could be responsible for the development of anaemia, an adverse effect frequently associated with zidovudine therapy.
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PMID:Enhancement of erythrocytic adenosine deaminase following treatment of AIDS-related complex/AIDS patients with zidovudine. 226 Nov 34

The effect of azidothymidine (Zidovudine, AZT) on pyrimidine (thymidine, deoxyuridine, and thymidine triphosphate) incorporation into DNA in folate- and/or vitamin B12-deficient and normal human bone marrow cells was studied to investigate whether such vitamin deficiency affects susceptibility to AZT-induced hematologic toxicity. Bone marrow cells from 12 patients were studied: 5 had folate and/or vitamin B12 deficiency; 7 controls included 5 with anemia related to chronic disease and 2 with iron deficiency. At 0.2 microM AZT (3 hr, 37 degrees C), the approximate pharmacologic serum trough level, pyrimidine incorporation into DNA was suppressed by 12 to 19% in folate- and/or vitamin B12-deficient cells and by 16 to 23% in normal cells. At 2.0 microM AZT (3 hr, 37 degrees C), the approximate pharmacologic serum peak level, this was suppressed by 15 to 40% in folate- and/or vitamin B12-deficient cells and by 32 to 47% in controls. Deoxyuridine incorporation into DNA was inhibited significantly greater than thymidine at 2.0 microM AZT (3 hr, 37 degrees C) in both groups. Inhibition of deoxyuridine incorporation was not reversed with methyltetrahydrofolate or vitamin B12. There tended to be less striking suppression by AZT of deoxyuridine incorporation into DNA in bone marrow cells from vitamin B12-deficient patients, which was made more striking by adding vitamin B12. This suggests that some of what passes for "AZT damage" to bone marrow cells may in fact be coincident deficiency of vitamin B12. AZT inhibition of DNA synthesis in 3 hr bone marrow cultures is relatively consistent in a variety of hematologic disorders. As approximately two-thirds of AIDS patients appear to be in negative balance with respect to folate and/or vitamin B12, the fact that AZT-induced inhibition of pyrimidine incorporation into DNA is occurring in cells which may be megaloblastic, i.e., in a state of impaired DNA synthesis, suggests that these cells may be more susceptible to AZT toxicity. The data also support the notion that AZT inhibition results predominantly from termination of DNA chain elongation. Whether folate or vitamin B12 supplementation may partially overcome apparent "AZT inhibition" of DNA synthesis (hematologic toxicity) and whether the benefit of such therapy exceeds the risk will require further study.
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PMID:Synergy of inhibition of DNA synthesis in human bone marrow by azidothymidine plus deficiency of folate and/or vitamin B12? 230 78

Although many experimental treatments are being evaluated for the treatment of acquired immunodeficiency syndrome (AIDS) and symptomatic HIV infection (ARC), only zidovudine (AZT) has been shown to prolong the lives of such patients. This article reviews the authors' experience with 101 patients with AIDS (73) or ARC (28) treated with AZT at a public hospital clinic in Los Angeles County. The patients were seen at least monthly for five to 87 weeks (means = 27.6) by nurse practitioners and physicians. Initiation of AZT therapy required a CDC-defined diagnosis of AIDS or an absolute CD4 lymphocyte cell count of 200/mm3 or less. The demographic distribution of the patient population was as follows: Caucasian, 59; Hispanic, 22; and black, 20. The mean age of the population was 37.4 years, and the predominant risk factor was homosexual contact (76 percent). Forty-one patients required modification of their AZT doses secondary to anemia, neutropenia, a combination of anemia and neutropenia, or for personal reasons. Thirty-four of the 41 patients (83 percent) never returned to full dose after reductions. The majority of these patients (81 percent) had AIDS and/or CD4 lymphocyte counts less than 150/mm3. Hematologic toxicity was common; 27 percent required blood transfusions. Of the 101 patients followed from five to 87 weeks, 87 percent were surviving after a mean of 45 weeks of AZT therapy. The article underscores the effectiveness of AZT in prolonging the lives of AIDS and ARC patients.
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PMID:Outcomes of treatment with AZT of patients with AIDS and symptomatic HIV infection. 234 66

Zidovudine was used in an open uncontrolled study for treatment of 145 human immunodeficiency virus (HIV) patients, 102 with acquired immune deficiency syndrome (AIDS) and 43 with symptomatic HIV disease (acquired immune deficiency syndrome related-complex, ARC). The mean period of follow-up was 6 +/- 2.5 months. The median survival time of AIDS patients on zidovudine was 4.5 times longer when compared to a historical zidovudine untreated AIDS group (1657 vs. 370 days). This should be interpreted with reserve regarding improvements in treatment of all aspects of HIV infection and heightened awareness of AIDS which may have led to earlier diagnosis in the zidovudine treated groups. Pneumocystis carinii pneumonia (PCP) was very rarely a cause of death in zidovudine-treated patients (4.8%), while it was responsible for the death in 46.2% of historical controls (P less than 0.001). Extensive Kaposi's sarcoma was equally the cause of death in treated as well as in historical patients. Median T4 cell counts increased on zidovudine reaching a peak at the end of the fourth month of therapy in the ARC group and at the end of the first month in the AIDS group with a subsequent fall. Sixty per cent (53 of 87) patients were p24 viral antigen positive at the start of treatment and 19% of them had a fall of more than 50% in antigen level in three months while 32% became antigen negative within 2.5 months. Survival in patients where the antigen disappeared or in whom there was a major (greater than 50%) fall in antigen level was significantly higher than in those for whom there was no change in antigen level or in whom the antigen was negative at the start of the study (P less than 0.05). Forty-seven of the 145 zidovudine treated patients needed to be transfused because of anaemia. The mortality was significantly higher in this group of patients, particularly in those transfused prior to zidovudine therapy. Neutropenia occurred in four subjects. Platelets rose after the start of zidovudine but subsequently fell to thrombocytopenic levels in eight patients.
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PMID:Zidovudine treatment of patients with acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex: St Stephen's Hospital experience. 249 85


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