Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0031117 (peripheral neuropathy)
10,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five dose regimens of 2',3'-dideoxycytidine (ddC) were administered, intravenously for 2 weeks then orally for 4 or more weeks, to 20 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). ddC was well absorbed from the gut and crossed the blood-brain barrier. 10 of the 15 patients who received 0.03-0.09 mg/kg every 4 h had increases in their absolute number of T4+ T cells at week 2 (p less than 0.05), though in many these rises were not sustained. 11 of 13 evaluable patients had a fall in their serum human immunodeficiency virus (HIV)p24 antigen by week 2 of therapy (p less than 0.01); in 4 patients the p24 antigen subsequently rose to baseline while in others the decline was sustained. Dose-related toxic effects included cutaneous eruptions, fever, mouth sores, thrombocytopenia, and neutropenia. A reversible painful peripheral neuropathy developed in 10 patients after 6-14 weeks' treatment. These results suggest that ddC has activity against HIV in vivo and has a different toxicity profile from that of zidovudine (AZT). 6 patients with AIDS or ARC were given an alternating regimen of oral AZT (200 mg every 4 h for 7 days) and oral ddC (0.03 mg/kg every 4 h for 7 days). The regimen was well tolerated, and the 5 patients who completed 9 or more weeks of treatment had sustained rises in their T4+ T cells and/or falls in p24 antigen.
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PMID:Phase I studies of 2',3'-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT). 289 81

Zalcitabine (ddC) was the first drug to be approved under the US Food and Drug Administration's (FDA's) accelerated drug approval process. Zalcitabine is a potent nucleoside analogue inhibitor of reverse transcriptase used in the treatment of HIV infection. It is approximately 10-fold more potent than zidovudine (AZT) on a molar basis in vitro. Zalcitabine is well absorbed orally and reaches maximal plasma concentrations within 1 to 2 hours. In humans it is mainly eliminated by renal excretion of unchanged drug, and patients with renal failure may exhibit a prolonged half-life. A variety of clinical trials have evaluated the efficacy of zalcitabine based on improved survival and decreased frequency of opportunistic infections and on a surrogate marker of HIV disease, the CD4 count, or the concentration of an antigen associated with HIV, p24. Alternating zalcitabine therapy with zidovudine therapy was associated with increased CD4+ lymphocyte counts and reduced plasma p24 antigen levels. Zalcitabine can cause peripheral neuropathy (in 17 to 31% of patients), which is dose-related and is completely reversible when the drug is discontinued. Zalcitabine will continue to play a role in chemotherapeutic approaches to HIV.
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PMID:Zalcitabine. Clinical pharmacokinetics and efficacy. 761 75

Data on the biologic effects and safety of stavudine in patients with AIDS and AIDS-related complex represent results of two phase I trials (n = 84), another phase I study of patients with hematologic intolerance to zidovudine (n = 23), and a phase II trial (n = 152). The daily doses of stavudine ranged from 0.1 to 12.0 mg/kg. Increases in CD4 cell count, declines in serum p24 antigen, and weight gain were all related to the dose of stavudine. Doses of < or = 2 mg/kg/day (n = 216) were well-tolerated, with a median duration of therapy of > or = 48 weeks in the phase I studies and > or = 79 weeks in the phase II study. The predominant dose-limiting toxicity was peripheral neuropathy, which was related to both the dose and duration of treatment with stavudine. Elevations of liver enzymes were seen in some patients but appeared to be related to underlying disease rather than treatment. There was no evidence of dose-related hematologic toxicity.
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PMID:Biologic effects and safety of stavudine: overview of phase I and II clinical trials. 786 Oct 15

In a phase I trial of stavudine in AIDS or AIDS-related complex (ARC), antiviral effects and safety were assessed in 41 patients treated with dosages of 0.5-12.0 mg/kg/day. Among evaluable patients, 10% increases in CD4 lymphocyte counts were sustained in 24 (60%) of 40 during treatment; an NAUC response (normalized area under the CD4 cell count-versus-time curve > 1.0) was observed in 31 (91%) of 34 at 10 weeks and in 20 (80%) of 25 at 24 weeks; 15 (83%) of 18 had decreases in p24 antigenemia; and 24 (60%) of 40 gained > or = 2.5 kg body weight. Median CD4 lymphocyte levels remained above baseline for 6 months in patients receiving > 0.5 mg/kg/day. Median serum p24 antigen levels remained below baseline for > or = 1 year in patients with p24 antigen responses. The principal toxicity was peripheral neuropathy, which generally resolved after drug discontinuation but limited the dosage to < or = 2.0 mg/kg/day. Additional trials assessing the effect of stavudine on overall morbidity and mortality are ongoing.
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PMID:Stavudine in patients with AIDS and AIDS-related complex: AIDS clinical trials group 089. 786 Oct 17

2',3'-didehydro-3'-deoxythymidine (d4T) is a pyrimidine analogue and inhibitor of reverse transcriptase with potent in vitro activity against human immunodeficiency virus (HIV). A phase I trial of d4T was conducted in 41 HIV-infected patients, 12 with AIDS and 29 with AIDS-related complex (ARC). Thirty-six patients were evaluatable. The maximum tolerated dose was 2 mg/kg/day. The dose-limiting toxicity was sensory peripheral neuropathy, which occurred in 20 patients (55%). Four patients (11%) developed hepatotoxicity. Five (14%) developed anemia requiring a transfusion but not discontinuation of drug. The mean +/- SE plasma elimination half-life at all dose levels was 1.2 +/- 0.09 h. Increased or stable absolute CD4 counts were seen in most patients. The majority of patients with detectable serum p24 antigen levels had a persistent decrease by 6 months. d4T is a promising drug for patients with AIDS or ARC. This clinical trial is continuing to determine the minimal effective dose.
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PMID:2',3'-didehydro-3'-deoxythymidine (d4T) in patients with AIDS or AIDS-related complex: a phase I trial. 809 63

One hundred fifty-one patients who were positive for antibody to human immunodeficiency virus (HIV) and intolerant of zidovudine received oral didanosine at a dose adjusted by weight to a maximum of 12.5 mg/(kg.d). After 1 year of follow-up, 49 patients were still receiving didanosine; 19 had died during therapy and 23 thereafter. Therapy had been discontinued in 10 cases because of continued deterioration in health and in the remainder because of adverse reactions. Only 11 of 38 patients with positive results in an ELISA for p24 antigen before therapy had a significant reduction in titer. CD4 lymphocyte subset counts were more likely to rise for patients who had only constitutional disease due to HIV than for those with AIDS. Eleven percent of treated patients gained > 2.5 kg. Diarrhea was the commonest side effect, occurring in 60% of cases. Pancreatitis developed in six cases (with two deaths) and asymptomatic hyperamylasemia in 13. Seven patients developed glucose tolerance in the diabetic range. Peripheral neuropathy was documented in 12 instances but was reversible on cessation of therapy in six.
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PMID:Use of didanosine in zidovudine-intolerant patients infected with human immunodeficiency virus. 809 48

To evaluate whether P300 testing might serve as a screening modality for the early detection of HIV-related neuropathology, we tested 26 HIV-infected men (23 without neurologic symptoms, 2 with peripheral neuropathy, 1 with AIDS-associated dementia) and 15 controls. Although they had no overt neurologic symptoms, the P300 latency was delayed or undetectable in 30% of patients without clinically evident neurologic disease. P300 latencies did not correlate with peripheral blood CD4 T-cell count, serum quinolinic acid or p24 antigen levels, or the numbers of activated peripheral blood monocytes. Three individuals with abnormal P300 latencies had been HIV-seropositive for < or = 1 year, suggesting that delayed evoked responses detect early neurologic dysfunction. P300 responses do not predict imminent dementia. In only one previously asymptomatic individual with abnormal P300 waveforms have overt neurologic symptoms developed during a 2-year followup. Extended longitudinal studies will be necessary to define the predictive value of P300 latencies in the development of AIDS-related dementia. However, the sensitivity, quantitative nature, and speed of administration of this test suggest that it may be useful for identification of early neurologic involvement in HIV infection.
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PMID:Auditory P300 abnormalities and leukocyte activation in HIV infection. 829 Mar 2

One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.
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PMID:The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT) 832 44

Didanosine (ddI) is a purine analogue that demonstrates in vitro anti-human immunodeficiency virus (HIV) activity, effects on the surrogate markers CD4+ T-lymphocytes and p24 antigen, and has adequate oral bio-availability. Recently, 500 mg/day of ddI in sachet form demonstrated clinical effectiveness compared with zidovudine (ZDV) for delaying HIV disease progression in patients with AIDS or AIDS related complex (ARC) and less than 300 CD4+ T-lymphocytes, or asymptomatic individuals with less than 200 CD4+ T-lymphocytes. All patients tolerated a minimum of 16 weeks of prior ZDV treatment. ddI treatment was associated with an increase in serum amylase and pancreatitis, however, there was no significant difference in the incidence of pancreatitis between the 500 mg ddI and ZDV groups. There was significantly more hematologic toxicity associated with ZDV and no difference between ddI and ZDV groups with respect to peripheral neuropathy. ddI is presently available in tablet form with 125% the bioavailability of the sachet form of ddI; therefore, the 500-mg sachet formulation corresponds to a 400-mg daily tablet dose of ddI. Future studies of ddI will involve ddI's effects on antiretroviral naive patients and the potential of combining ddI with other agents.
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PMID:New developments in the clinical use of didanosine. 842 1

Stavudine, 2',3'-didehydro-3'-deoxythymidine (D4T), is a potent inhibitor of HIV-1 reverse transcriptase in vitro. In clinical studies, stavudine has excellent oral bioavailability in excess of 80%. The dose-limiting toxicity is peripheral neuropathy, which occurred in 15% of stavudine versus 6% of zidovudine-treated patients for 80 weeks in a randomized, blinded, phase III trial. Stavudine-treated groups have experienced significant increases in mean CD4 cell counts and decreases in both mean serum p24 antigen levels and infectious HIV titers in peripheral blood mononuclear cells. In subjects with prior zidovudine treatment, the duration of these responses is limited; CD4 counts and serum p24 antigen levels return to baseline after approximately 6 months. The effect of stavudine on clinical outcome and survival has not yet been established in comparative trials. Stavudine offers an additional therapeutic option to those individuals who are refractory to or intolerant of other available antiretrovirals.
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PMID:Antiretroviral activity of stavudine (2',3'-didehydro-3'-deoxythymidine, D4T). 854 Jul 43


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