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 most common hematological abnormality associated with HIV infection is anaemia. The aetiology is multifactorial and may include the HIV virus itself; the anaemia of chronic diseases (ACD); infection with other viruses, mycobacteria and fungi; medications, especially zidovudine; and even B12 deficiency. Erythropoietin insufficiency is present in all anaemic AIDS patients, probably as a result of the mechanism of ACD. The studies, performed in patients with PGL, ARC and AIDS stages of disease demonstrate that rHuEPO is safe, and in dose of 100-200 U/kg b.w. three times a week can alleviate the anemia in AIDS patients taking AZT whose baseline EPO levels are less than 500 mU/ml.
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PMID:[Anemia in AIDS: the problem to avoid. Human recombinant erythropoietin in the treatment of HIV positive patients]. 759 81

The transmission, diagnosis, and clinical manifestations of human immunodeficiency virus (HIV) infection in children up to 13 years of age are reviewed, and maintenance and prophylactic drug therapies for these patients are discussed. HIV can be transmitted from mother to infant in utero, during delivery, or through breast milk. Perinatal transmission accounts for almost 90% of all pediatric HIV infections. HIV infection can be diagnosed with HIV culturing, polymerase chain reaction testing, the enzyme-linked immunosorbent assay, the Western blot antibody assay, or the p24 core-antigen assay. Testing should begin as soon as possible after the at-risk child reaches one month of age. CD4+ lymphocyte counts are also used in diagnosis and monitoring. The median age at diagnosis of AIDS in children with perinatally acquired HIV infection is 12-24 months. Among the many possible clinical features are Pneumocystis carinii pneumonia (PCP), cytomegalovirus infection, failure to thrive, encephalopathy, recurrent bacterial infection, thrush, lymphoid interstitial pneumonitis, lymphadenopathy, pancreatis, hepatitis, anemia, and thrombocytopenia. Zidovudine is considered the drug of choice for initial therapy in HIV-infected children and is indicated for asymptomatic infection, early symptomatic disease, and advanced disease. However, new research is questioning the role of zidovudine monotherapy. Didanosine is the only agent with FDA-approved labeling for use as second-line therapy in children who do not respond to or become resistant to zidovudine. Agents under investigation for pediatric use are zalcitabine, stavudine, lamivudine, and nevirapine. Drug combinations, such as zidovudine plus didanosine, are also being examined. Zidovudine appears to reduce the rate of maternal transmission of HIV. Agents used prophylactically against PCP in children are trimethoprim-sulfamethoxazole, dapsone, and inhaled or i.v. pentamidine. HIV-infected children should also received prophylaxis against recurrent bacterial infections. The standard pediatric immunization schedule is used, but inactivated injectable poliovirus vaccine must be given instead of the live oral vaccine. Zidovudine remains the first-line agent for treating HIV infection in children. Alternatives are available for those who do not respond to zidovudine.
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PMID:Human immunodeficiency virus infection in children. 764 Oct 35

Erythropoietin (EPO) is the primary hormone responsible for the growth and maturation of red blood cells in mammals. In contrast to many other growth factors, the specificity of EPO for mature erythroid cells has lead to its development as a safe and efficacious therapeutic, EPREX. The medical benefits of EPREX have been well established in the treatment of anaemic chronic renal failure patients, anaemic HIV patients treated with AZT, cancer chemotherapy patients, and patients wishing to donate their own blood prior to elective surgery (autologous predonation). Due to the chronic nature of EPO therapy, it would be desirable to have an orally administered 'second generation' molecule. An understanding of the structural basis of the interaction of EPO with its receptor will aid in the design of an oral anaemia drug. In this study, a series of mutations have been generated in a truncated form of the receptor comprising the extracellular region, termed EPO binding protein (EBP). One mutant, in which alanine replaces phenylalanine at position 93 (F93A) has a 500-fold reduction in binding compared to wild-type EBP. A neutralizing anti-EBP antibody binds poorly to the F93A mutant, while a non-neutralizing anti-EBP antibody binds wild-type and F93A equally well. Information from this mutational analysis can be applied to a receptor 3-D model and ultimately used in drug development.
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PMID:Erythropoietin receptor: application in drug development. 764 2

Advances in the development of antiviral drugs have been rapid and dramatic. Since the recognition of HIV-1 as the cause of AIDS in 1984, and improved understanding of retroviral replication and pathogenesis, three antiviral drugs, Zidovudine, Didanosine, and Zalcitabine, have been developed to the point of routine use in humans. There is substantial experience with the former two in children. Despite being unable to cure HIV-1 infection, the benefits of antiretroviral therapy, including extended survival and reductions in opportunistic infections in adults, and improved weight gain and well-being in children, are strong arguments for routine treatment of symptomatic disease. Because these agents may also interfere with human cellular processes and have toxicities including anemia, neutropenia, pancreatitis, and neuropathy, their routine use for the treatment of asymptomatic children requires further controlled study. There are multiple candidate agents being developed for entry into clinical trials. An additional potentially effective strategy is the use of combinations of drugs at the same time or in sequence to maximize the viral targets being attacked, while minimizing toxicity, and to prevent the emergence of a drug-resistant virus.
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PMID:Antiretroviral therapy for children. 783 65

Recently we encountered a case of pulmonary tuberculosis with HIV infection. The patient was 54-years old male. His chief complaints were anemia, emaciation and severe diarrhea. He was admitted to our hospital on September 18, 1992. He had been diagnosed in another clinic as having pulmonary tuberculosis before the admission to our hospital. His chest films taken on admission revealed homogeneous infiltrates with cavitation in right upper lobe. Serial chest X-rays consisted with the findings of post-primary tuberculosis. Sputum smear for acid fast bacilli was positive. From his clinical manifestations and life-history, we had a suspicion that he had infected with HIV. Laboratory findings were as follows: serum albumin level was 1.9 g/dl, CRP was 10.2 mg/dl, serological tests for HIV were positive by EIA, IFA and western blott method, total lymphocyte count was 819/microliters, CD4+ T lymphocyte count was 120/microliter CD4+/CD8+ ratio was 0.2. He was treated with AZT, isoniazid, streptomycin and rifampicin. The disease progressed rapidly and interstitial pneumonia, jaundice and clouding of consciousness appeared at the terminal stage. He expired on October 14, 1992. In this paper, the authors reported a case of pulmonary tuberculosis with HIV infection and also reviewed 5 cases of pulmonary tuberculosis associated with HIV in Japan.
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PMID:[A case of pulmonary tuberculosis with HIV infection--review of 5 cases in Japan]. 783 23

Eleven (50%) of 22 HIV-seropositive patients suffering from congenital coagulation defects and followed at the Hemophilia Center of Padua met the eligibility criteria for zidovudine (AZT) therapy. A 3-year clinical and laboratory follow up is described. Mean length of AZT treatment was 14.3 +/- 11 months. Three patients were enrolled at the latest stages (CDC stage IV) of HIV disease. They showed no clinical improvement after AZT administration and died with AIDS. One CDC stage III patient died from a high-grade non-Hodgkin's lymphoma (NHL) which suddenly developed 3 months after starting AZT. Seven patients began antiretroviral treatment when they were mild or asymptomatic for HIV infection (CDC stage II and III). None developed any sign of HIV disease progression on the basis of CDC criteria. Moreover, AZT administration induced an improvement of the humoral markers related to HIV disease, as CD4 T-lymphocyte count, serum beta 2-microglobulin (B2M) and, although only for few months, neopterin (Np) levels. A mild thrombocytopenia due to HIV infection was detected in 5 patients. In all cases AZT treatment was effective in increasing and/or normalizing the platelet count. Reduced daily dose AZT (600-500 mg/day) appeared to be well tolerated and of minimal toxicity as compared to the higher dose (1200 mg/day). In our study, the zidovudine-induced bone marrow suppression, namely severe anemia or pancytopenia, was the major side-effect limiting tolerance of the higher dose AZT.
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PMID:Report on a 3-year follow-up zidovudine (AZT) treatment in a group of HIV-positive patients with congenital clotting disorders. 795 71

The drug zidovudine (AZT), a synthetic thymidine analog, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has been associated with the development of hematopoietic toxicity manifested by anemia, neutropenia, and on occasion thrombocytopenia. This toxicity has resulted in the development of alternative dideoxynucleoside drugs capable of exerting anti-viral potency while minimizing the risk for inducing organ toxicities. One such dideoxynucleoside drug is 2',3'-dideoxyinosine (ddI). Clinical trials are currently evaluating the effect of combination anti-viral drug treatment such as zidovudine plus ddI. We report here the results of studies designed to evaluate the effect of interleukin-3 (IL-3) on its ability to influence the hematopoietic toxicity associated with zidovudine and ddI following combination with retroviral-infected murine bone marrow cells. Toxicity was evaluated by quantitating several classes of hematopoietic progenitor stem cells such as granulocyte-macrophage (CFU-GM), erythroid (CFU-E and BFU-E) and megakaryocyte (CFU-Meg). Dose-escalation IL-3 provided protection of anti-viral drug induced suppression of progenitor cells when combined in the presence of the ID50 concentration of either zidovudine or ddI; however, when zidovudine and ddI were combined, IL-3 was less effective in providing protection against drug-induced toxicity at any concentration examined. These results indicate that IL-3 is effective in reducing anti-viral drug-induced hematopoietic toxicity associated with single-agent use; however, IL-3 is less effective when such drugs are used in combination.
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PMID:Influence of interleukin-3 (IL-3) on the hematopoietic toxicity associated with combination anti-viral drugs (zidovudine and DDI) in vitro using retrovirus-infected bone marrow cells. 804 75

Infection with human immunodeficiency virus type 1 (HIV-1) primarily involves a subgroup of T-lymphocytic cells, but other cell types are also invaded by the virus, including cell lines within the haematopoietic system. Together with infectious, inflammatory and neoplasic processes, invasion of haematopoietic tissue explains the haematological alterations which are seen during the course of infection with HIV-1. Anaemia develops in the large proportion of patients. Thrombocytopenia frequently occurs during the course of the disease, but may be seen in some patients already at the time of diagnosis, where the condition may be misdiagnosed as "idiopathic" thrombocytopenic purpura. Neutropenia is seen in all disease stages, but is most severe in patients with advanced disease. Bone marrow changes include varying degrees of dysplasia in one or more cell lines, which in some patients may mimic a myelodysplastic syndrome. The number of plasma cells is always increased. In many patients the bone marrow stroma exhibits an increased amount of reticular fibres. HIV-1 infection is associated with an increased risk of non-Hodgkin malignant lymphoma. Acute myelogenous leukaemia and myelomatosis have been described in patients with advanced disease. Treatment of the above mentioned haematological abnormalities aims primarily at reducing replication of HIV-1, thereby diminishing suppression of haematopoiesis by the virus infection, and at controlling the opportunistic infections during the course of the disease. Specific antiviral therapy (AZT) is most successful in correcting thrombocytopenia. The possibility of bone marrow suppression mediated by a toxic drug effect should always be considered in this patient group.
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PMID:[Hematological changes associated with human immunodeficiency virus (HIV-1) infection]. 831 70

12 HIV-infected children were treated with a high dose of zidovudine (800/mg/m2/day) during a mean follow up period of 18 months. After starting treatment with zidovudine there was a subjective improvement and an increase in body weight, and a significant decline in serum HIV-antigenemia (p < 0.01) and serum IgG levels (p < 0.05). Zidovudine was generally well tolerated but there was serious hematological toxicity. In 9 patients (75%) dose reduction was necessary because of severe anemia (3 patients) or leucopenia (6 patients). Because of the high incidence of these side effects the starting dose of zidovudine was reduced to 600 mg/m2/day. These results confirm that zidovudine can safely be used to treat HIV-infected children. The main limitation is serious hematological toxicity which appears to be dose-related.
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PMID:[The treatment of 12 HIV-infected children with zidovudine]. 836 63

This study evaluated the safety, tolerability, and pharmacokinetics of zidovudine administered intravenously and orally to infants born to women infected with the human immunodeficiency virus. Thirty-two symptom-free infants were enrolled before 3 months of age. The pharmacokinetics of zidovudine were evaluated in each infant after single intravenously and orally administered doses of zidovudine on consecutive days, and during long-term oral administration of the drug for 4 to 6 weeks. As new patients were enrolled, doses of zidovudine were progressively increased from 2 to 4 mg/kg. Therapy was continued for up to 12 months in 7 of the infants proved to be infected with human immunodeficiency virus. Zidovudine was generally well tolerated; 20 children (62.5%) had anemia (hemoglobin level < 10.0 gm/dl) during therapy and 9 (28.1%) had neutropenia (neutrophil count < or = 750 cells/mm3); these hematologic abnormalities usually resolved spontaneously. The total body clearance of zidovudine increased significantly with age, from an average of 10.9 ml/min per kilogram in infants < or = 14 days of age to 19.0 ml/min per kilogram in older infants (p < 0.0001). Concurrently, there was a significant decrease in serum half-life from 3.12 hours in infants < or = 14 days to 1.87 hours in older infants (p = 0.0002). Oral absorption was satisfactory and bioavailability decreased significantly with age, from 89% in infants < or = 14 days to 61% in those > 14 days of age (p = 0.0002). Plasma concentrations of zidovudine were calculated to be in excess of 1 mumol/L (0.267 micrograms/ml) for 4.12 +/- 1.86 hours and 2.25 +/- 0.78 hours after oral doses of 2 mg/kg in infants younger than 2 weeks and 3 mg/kg in older infants, respectively. We conclude that zidovudine administered at oral doses of 2 mg/kg every 6 hours to infants aged less than 2 weeks and 3 mg/kg every 6 hours to infants older than 2 weeks resulted in plasma concentrations that are considered virustatic against human immunodeficiency virus. Zidovudine was well tolerated by infants at these doses.
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PMID:Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus. 841 1


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