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 drug zidovudine (AZT), a synthetic thymidine analogue, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has induced haematopoietic toxicity manifested by anaemia, neutropenia, frequent thrombocytopenia, and overall bone-marrow suppression. The monovalent cation lithium has been shown to be an effective agent capable of modulating several aspects of haematopoiesis such as the induction of neutrophilia, thrombopoiesis, and protection against suppression of haematopoietic progenitor stem cells following exposure to anticancer drugs and/or radiation in the treatment of malignant disease. We here report the results of studies designed to evaluate the effectiveness of lithium in reversing and/or protecting against either murine or human bone marrow derived haematopoietic progenitors, i.e. (CFU-GM, CFU-Meg, and BFU-E) when co-cultured in the presence of zidovudine in vitro. Lithium chloride (LiCl) reversed zidovudine toxicity to either murine or human derived CFU-GM and CFU-Meg that was optimal at a concentration of 1 mM (P less than 0.05). However, the addition of lithium failed to influence zidovudine toxicity toward either murine or human BFU-E. In summary, these results support the scant clinical studies that have described the presence of neutrophilia and/or thrombopoiesis in zidovudine-treated AIDS patients receiving lithium. In addition, these data further confirm the need for more detailed evaluation of lithium as an adjuvant agent to reduce the haematopoietic toxicity associated with the use of antiviral therapy in HIV-infected patients.
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PMID:Effective modulation of the haematopoietic toxicity associated with zidovudine exposure to murine and human haematopoietic progenitor stem cells in vitro with lithium chloride. 131 88

Retroviruses of the nervous system cause HTLV-1-associated myelopathy and HIV-associated diseases. The treatment of HTLV-1 disease is essentially conservative; there is no effective drug treatment and therefore patients should be simply supported and reassured. If appropriate, other members of the family should be tested for HTLV-1 disease and counselled. The effects of HIV on the nervous system are much more complex. Therapy must take account of the diverse complications of HIV disease. Patients are probably best managed in specialized clinics which can cope with the different manifestations of the disease. Zidovudine (AZT) is the only effective anti-HIV drug that is licensed. It is indicated in complicated seroconversion disease and for any manifestation of HIV progression including AIDS dementia complex. Management of severe neurological disease depends critically on the ability to diagnose and treat CNS-specific opportunistic infections. Whether zidovudine is indicated for early asymptomatic disease when CD4 counts are below 500 microliters-1 is controversial. The main problems of zidovudine are reversible anaemia which results in about 30% of patients not tolerating long-term use, and the development of drug resistance which may be associated with clinical failure of the drug. Other, new and experimental drug treatments are discussed but none of them has as yet shown any convincing evidence of efficacy. Future improvements in treatment appear to depend on the development of effective multiple drug regimens (concurrently or sequentially) which will overcome the challenge of drug resistance.
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PMID:Therapeutic aspects of retroviral disease. 134 52

Twenty-four perinatally HIV infected children received early treatment as soon as the diagnosis of viral contamination was established. In 13 cases (group 1), this diagnosis was based on a viremia and/or antigenemia during the first 6 months of life. In 11 cases (group 2), children were more than 15 months-old and had a positive HIV antibody test. Therapy included azidothymidine (AZT, 400 mg/m2/d) and the prevention of secondary infectious complications with intravenous immunoglobulin and cotrimoxazole. With a median follow-up of 26 months, we reported no case of severe secondary infection and no case of encephalopathy. Hematological side effects of AZT were rarely observed. Only one patient developed anemia. In all other cases, the only hematological abnormality was macrocytosis of red blood cells. Before treatment, the mean value of T4 cells age-adjusted count was 96, 86 and 91%, respectively, for groups 1, 2 and the entire study group. At the time of analysis, these values were 64, 62 and 63% respectively. This decrease was statistically significant for group 1 and for the entire study group, but did not reach statistical significance for group 2. These data show that AZT is probably insufficient as a long-term therapy for HIV infected children. Other therapeutic approaches need to be developed in the future, notably the combination of anti-retroviral drugs.
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PMID:[HIV infection in the child after materno-fetal transmission: early treatment with azidothymidine and prevention of secondary infectious complications]. 136 53

Great strides have been made in the therapy of human immunodeficiency virus (HIV) infection. Currently approved drugs include zidovudine and didanosine. A third drug, dideoxycytidine (zalcitibine), has recently been filed for approval with the Food and Drug Administration. All these drugs work through inhibition of the reverse transcriptase enzyme. Zidovudine is the only drug that has shown clinical efficacy against HIV. Treatment of patients with advanced HIV disease (i.e., acquired immune deficiency syndrome [AIDS] or symptomatic infection with < 200 CD4+ lymphocytes per mm3), results in a prolongation and improved quality of life. Zidovudine is the only antiretroviral agent approved for the treatment of asymptomatic patients. Early intervention with zidovudine has been shown to delay progression to AIDS when patients' CD4+ lymphocyte counts decline to less than 500/mm3, irrespective of clinical signs or symptoms of HIV infection. Didanosine is currently indicated for the treatment of patients with advanced HIV disease who are intolerant to or failing zidovudine therapy. The major toxicity of zidovudine is bone marrow suppression with anemia and granulocytopenia (which occurs in from 1% to 45% of patients, depending on the clinical stage of disease and the dose of the drug). Didanosine and zalcitibine have both been associated with a severe peripheral neuropathy, which is generally reversible on cessation of the drug. In addition, didanosine has been implicated as a cause of pancreatitis that has been fatal in a small percentage of cases. The toxicities of didanosine and zalcitibine range from 1% to 10%, depending on dose, duration of therapy, and the presence of underlying HIV-related peripheral neuropathy or a previous history of pancreatitis. The clinical hallmark of HIV infection is the development of opportunistic infections and malignancies, which are a consequence of the profound immunodeficiency. The risk of an opportunistic infection increases significantly as the T-helper lymphocyte count declines to less than 20%, or 200 to 250/mm3. The spectrum of opportunistic infections ranges from viruses to protozoa. Patients with advanced HIV disease are also at increased risk of infection with nonopportunistic, community-acquired pathogens. Primary and secondary prophylaxis against the most common AIDS-defining opportunistic infection, Pneumocystis carinii pneumonia, is now recommended. Studies are currently underway to determine the efficacy of prophylaxis against other opportunistic pathogens. Treatment of opportunistic infections associated with AIDS has improved significantly over the past 5 years as new drugs and combination regimens of antimicrobials have been developed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:AIDS: Part II. 139 36

It is proposed that the new American and European AIDS epidemics are caused by recreational and anti-HIV drugs rather than by human immunodeficiency virus (HIV). Chronologically, the AIDS epidemic in the 1980s followed a massive escalation in the consumption of recreational drugs that started in the 1960s and 70s. Epidemiologically, both epidemics derive about 80% of their victims from the same groups of 20-44 year-olds, of which 90% are males. In America 32% of these are intravenous drug users and their children, about 60% are male homosexuals who are long-term users of oral aphrodisiac drugs and an unknown percentage are prescribed the cytotoxic DNA chain terminator AZT, as inhibitor of HIV. Direct evidence indicates that these drugs are necessary for HIV-positives and sufficient for HIV-negatives to develop AIDS diseases. The drug-AIDS hypothesis predicts correctly that: (i) AIDS is new in the US, because the drug epidemic is new, while the HIV epidemic is old--fixed at a constant 1 million Americans since 1985; (ii) despite an increase in venereal diseases, AIDS remains restricted to long-term drug users and small groups with clinical deficiencies; (iii) over 72% of AIDS occurs in 20-44 year-old males, because they make up over 80% of hard psychoactive drug use; (iv) distinct AIDS diseases correlate with the use of distinct drugs, eg Kaposi's sarcoma with nitrite inhalants, tuberculosis with intravenous drugs, and leukopenia, anemia, and nausea with AZT; (v) AIDS diseases are only acquired after long-term drug consumption, rather than after single contacts as the virus-hypothesis predicts. The drug hypothesis can be tested epidemiologically and experimentally in animals. It predicts that most AIDS can be prevented by stopping the consumption of drugs, and provides a rational basis for therapy.
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PMID:The role of drugs in the origin of AIDS. 142 Oct 32

Haematologic toxicity is the most common adverse effect related to long-term administration of zidovudine (AZT). We evaluated the kinetics of modifications of some haematologic parameters of erythroid series in 65 patients with HIV infection treated with AZT for a mean duration of 7.6 +/- 4.7 months (13 of them with a previous diagnosis of AIDS, 34 with ARC, 18 asymptomatic or with LAS/PGL), in order to correlate the observation and the evolution of these laboratory changes with the onset of severe anaemia. The development of macrocytosis occurs in a large majority of AZT-treated subjects, in spite of folate and vitamin B12 supplementation; the monitoring of erythrocytes distribution according to cellular volume and cellular haemoglobin concentration makes it possible to early recognize the occurrence of modification in erythropoiesis. There is no correlation between an elevated mean corpuscular volume and the development of severe anaemia (Hb less than or equal to 9 g/dl) in an individual patient; a fall in the reticulocyte count appears to be the earliest peripheral blood sign of the development of bone marrow toxicity.
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PMID:[Monitoring of several hematological parameters of the erythroid series in patients with HIV infection treated with zidovudine]. 149 88

Zidovudine, a nucleoside analog, was the first agent proved to be effective in the management of human immunodeficiency virus type 1 (HIV-1) infection. After demonstration of zidovudine's in-vitro activity against HIV-1 in 1985, the drug was rapidly evaluated in phase I and phase II clinical trials and was found to be effective in decreasing both mortality and the incidence of opportunistic infections in patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex; the drug was also found to have a substantial but tolerable toxicity profile. Since the licensure of zidovudine in 1987, an intensive clinical research effort has established the drug's efficacy in the prevention of disease progression in asymptomatic and mildly symptomatic HIV-infected persons and has established the success of lower-dose therapy in patients at all stages of disease. The current recommendation is to use zidovudine at a dose of 500 to 600 mg/d in both symptomatic and asymptomatic persons with CD4 counts of less than 500/mm3. The major toxicities of anemia and neutropenia are less frequent at the lower doses presently used and can be managed by dose reduction or by use of hematopoietic growth factors. The inexorable disease progression seen despite zidovudine therapy and the isolation of clinical strains of HIV-1 resistant to zidovudine in vitro highlight the limitations of prolonged monotherapy with this agent. Although alternative dideoxynucleoside agents (for example, didanosine [dideoxyinosine and zalcitabine dideoxycytidine]) are available for the management of HIV-infected persons, zidovudine remains the cornerstone of antiretroviral therapy. Current research efforts are directed at elucidating the clinical relevance of zidovudine resistance and studying regimens in which zidovudine is used in combination with other agents. This latter approach holds great promise for improving efficacy, limiting toxicity, and perhaps preventing the emergence of viral resistance. For the forseeable future, zidovudine will continue to play a role in the development and in our understanding of antiretroviral therapy.
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PMID:Zidovudine: five years later. 844 32

Thirty-five children diagnosed of AIDS were studied in order to evaluate toxicity and efficacy of oral Zidovudine treatment (AZT), as well as to analyze the clinical, biochemical, immunological and virological evolution of HIV infection throughout the treatment. Patients (19 males and 16 females) were studied from April 1988 to May 1990 with a mean follow-up time of 13.5 months (SD = 6.7 months). The mean age of the group was 4.68 years. The means of acquisition of this disease was 71.45 vertical and 28.6% via hemo-derivatives. Tolerance has been good with the main toxicity being hematological (28.5% anemia and/or neutropenia), 23% of which required blood supplements. The presence of neurological involvement and thrombopenia were observed in the incidence of greater toxicity. No influence on weight during AXT treatment was observed and hepatosplenomegalia and adenopathies were not modified. Bacterial and opportunistic infections were observed in 97.1% and 20% of patients, respectively. Neurological evolution was irregular and the improvement observed in some patients was mild and transitory. Three patients died during the follow-up from intercurrent infectious process. A progressive increase in MCV and a tendency towards leucopenia and lymphopenia (mainly in hemo-derivative infected patients) was observed. Neither significant immunological nor virological changes were observed during the treatment (except the tendency to diminish basal hypergammaglobulinemia). The results of this study were compared to other pediatric series treated with AZT.
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PMID:[Long-term follow-up study of 35 children with ADS treated with zidovudine (AZT)]. 157 12

Zidovudine is now used extensively in an effort to control infection with the human immunodeficiency virus (HIV). The drug is associated with major hematologic toxicity, especially anemia and granulocytopenia. Conservative management of hematologic toxicity includes dosage reduction or cessation of therapy, diagnosis and treatment of chronic debilitating diseases, and supportive care, such as blood transfusions. New investigational agents, including hematopoietic growth factors, are being studied to combat the toxicities associated with zidovudine. The efficacy of these agents has yet to be established. Recent advances in drug efficacy at reduced dosage and in combination therapy promise to permit use of zidovudine with markedly reduced toxicity.
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PMID:Hematologic toxicity of zidovudine in HIV-infected patients. 169 80

Fifteen children (11 males and four females), on oral Zidovudine (AZT) for symptomatic HIV infection were studied retrospectively. Twelve acquired HIV via blood products, two from vertical transmission (maternal intravenous needle sharing) and one through breast feeding. Their mean age at the start of therapy was 8.6 years (s.d. 4.4 years, range 1.8-15.3 years). The main indications for therapy were failure to thrive (FTT) in 10, recurrent respiratory tract infections (RRTI) in eight, and developmental delay (DD) in one, with overlapping indications being Pneumocystis carinii pneumonia (PCP) in one and pulmonary lymphoid hyperplasia (PLH) in two. The mean commencement dose was 24 mg/kg per day orally in 3-6 divided doses (range 16-35 mg/kg per day). The duration of therapy was 2 weeks-2 1/2 years. Significant improvement in growth was observed by 2 months; at 6 months, growth was sustained in these otherwise ill children, with only two falling below pretreatment weight. Decrease in the frequency of RRTI based on subjective reports of the attending clinicians was observed in seven of the eight evaluable children still on therapy. Improvement in PCP and PLH occurred in two children and modest improvement was subjectively reported in PLH in one while still early in the course of therapy. Overall, AZT was well tolerated. Dose modifications were for neutropenia in three (of which only two were drug related), rapidly falling neutrophil count in one, anaemia in two (with concurrent history of chronic gastrointestinal tract blood loss in one), severe GIT irritation in one and transient sedation in one. Seven opportunistic infections were reported (three in the same patient) of which two occurred following cessation of therapy, one after only 2 weeks of therapy, and one had not been on primary prophylactic therapy. Three deaths occurred, one associated with opportunistic infections and two while off therapy (one respiratory failure, one PCP).
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PMID:Zidovudine (AZT) therapy in children with HIV infection: the Australian experience. 170 96


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