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Biomedical subjects

W G Powderly

Publications and source records attributed to W G Powderly.

At least 55 records · Page 3Linked to original sources
PubMed1998

Increased plasma gln and Leu Ra and inappropriately low muscle protein synthesis rate in AIDS wasting.

Muscle protein wasting occurs in human immunodeficiency virus (HIV)-infected individuals and is often the initial indication of acquired immunodeficiency syndrome (AIDS). Little is known about the alterations in muscle protein metabolism that occur with HIV infection. Nine subjects with AIDS wasting (CD4 < 200/mm3), chronic stable opportunistic infections (OI), and >/=10% weight loss, fourteen HIV-infected men and one woman (CD4 > 200/mm3) without wasting or OI (asymptomatic), and six HIV-seronegative lean men (control) received a constant intravenous infusion of [1-13C]leucine (Leu) and [2-15N]glutamine (Gln). Plasma Leu and Gln rate of appearance (Ra), whole body Leu turnover, disposal and oxidation rates, and [13C]Leu incorporation rate into mixed muscle protein were assessed. Total body muscle mass/fat-free mass was greater in controls (53%) than in AIDS wasting (43%; P = 0.04). Fasting whole body proteolysis and synthesis rates were increased above control in the HIV+ asymptomatic group and in the AIDS-wasting group (P = 0. 009). Whole body Leu oxidation rate was greater in the HIV+ asymptomatic group than in the control and AIDS-wasting groups (P < 0.05). Fasting mixed muscle protein synthesis rate was increased in the asymptomatic subjects (0.048%/h; P = 0.01) but was similar in AIDS-wasting and control subjects (0.035 vs. 0.037%/h). Plasma Gln Ra was increased in AIDS-wasting subjects but was similar in control and HIV+ asymptomatic subjects (P < 0.001). These findings suggest that AIDS wasting results from 1) a preferential reduction in muscle protein, 2) a failure to sustain an elevated rate of mixed muscle protein synthesis while whole body protein synthesis is increased, and 3) a significant increase in Gln release into the circulation, probably from muscle. Several interesting explanations for the increased Gln Ra in AIDS wasting exist.

CD4 Lymphocyte Count↗
PubMed1997

Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group.

BACKGROUND: Treatment with low-dose amphotericin B (0.4 mg per kilogram of body weight per day) or oral azole therapy in patients with the acquired immunodeficiency syndrome (AIDS) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization. METHODS: In a double-blind multicenter trial we randomly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B (0.7 mg per kilogram per day) with or without flucytosine (100 mg per kilogram per day) for two weeks (step one), followed by eight weeks of treatment with itraconazole (400 mg per day) or fluconazole (400 mg per day) (step two). Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinically stable at 2 weeks and asymptomatic at 10 weeks. RESULTS: At two weeks, the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone (P=0.06). Elevated intracranial pressure was associated with death in 13 of 14 patients during step one. The clinical outcome did not differ significantly between the two groups. Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks (95 percent confidence interval for the difference in percentages, -100 to 21). The proportion of patients who had clinical responses was similar with fluconazole (68 percent) and itraconazole (70 percent). Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks, with no significant difference between the groups. In a multivariate analysis, the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization. CONCLUSIONS: For the initial treatment of AIDS-associated cryptococcal meningitis, the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks, as compared with regimens used in previous studies. Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole.

AIDS-Related Opportunistic Infections↗
PubMed1997

Molecular epidemiology of mucosal candidiasis in HIV-positive women.

Mucosal candidiasis is a common complication of HIV infection and HIV-positive women may develop both oropharyngeal and vaginal disease. Colonization with Candida albicans and related species at either site is a common preceding event in asymptomatic women. To examine the molecular epidemiology of colonizing yeast strains in HIV-positive women, concurrent oropharyngeal and vaginal cultures were obtained from 32 women (mean CD4 count 392 cells/mm3, range 0-1319). Positive oropharyngeal cultures were obtained in 18 (56%) and positive vaginal cultures in 10 (31%). Candida species were isolated from both sites simultaneously in nine (28%) women. All strains were evaluated for restriction fragment length polymorphisms (RFLPs) at the ribosomal DNA locus (using a heterologous 8.4-kb NotI probe from H. capsulatum) and with a C. albicans-specific repetitive DNA probe. Isolates were grouped into three classes by the NotI probe and then members of each class were evaluated with the C. albicans-specific probe. Isolates were subsequently evaluated by random amplified polymorphic DNA (RAPD) PCR with four arbitrary primers to detect strain-specific differences. All isolates tested were unique and could be discriminated by RFLP or RAPD PCR. Vaginal and oropharyngeal isolates from the same individual in all nine cases were dissimilar, suggesting that the dominant strain of Candida colonizing different body sites is different. These findings suggest that the epidemiology of Candida infection in HIV disease is complex, that the development of oropharyngeal and vaginal disease may be disassociated, and that HIV-positive patients are each infected by their own unique strains of Candida.

AIDS-Related Opportunistic Infections↗
PubMed1997

Serum leptin concentrations in human immunodeficiency virus-infected men with low adiposity.

The product of the obese gene (ob) is the protein leptin, which is synthesized in and secreted from adipocytes. Fasting serum leptin concentrations are closely related to body fat content and are higher in obese than in normal-weight individuals. Leptin may contribute to body weight regulation. Overproduction of leptin in certain pathologic conditions such as acquired immunodeficiency syndrome (AIDS) might in principle contribute to the low body fat content associated with body wasting. We measured fasting serum leptin levels by radioimmunoassay in individuals infected with the human immunodeficiency virus (HIV) and in a group of healthy lean men to determine whether HIV infection increases leptin levels. Thirteen HIV-infected men aged 26 to 50 years with a body mass index (BMI) of 15 to 26 kg/m2 and 4 to 24 kg body fat (7% to 29% body fat) had serum leptin levels (3.4 +/- 1.6 ng/mL) that were not elevated compared with the levels in 17 healthy men (4.0 +/- 1.4 ng/mL) matched for age (23 to 47 years), BMI (18 to 26 kg/m2), and body fat (5 to 21 kg; 9% to 28%). In both groups of men, serum leptin concentrations were correlated with percent body fat and body fat content (P < .001), and these relationships were not different between the two groups. In both groups, leptin concentrations were not correlated with lean body mass (P > or = .24). Energy intake in the HIV-infected men, assessed from 3-day intake records, was within the normal range. These findings extend the hypothesis that circulating leptin concentrations directly reflect adipose tissue mass, even in HIV-infected men with low body fat content. These findings do not support the hypothesis that HIV infection is associated with high circulating leptin concentrations, and suggest that low leptin levels do not stimulate food intake in HIV-infected individuals.

Adult↗
PubMed1997

Cryptococcosis.

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AIDS-Related Opportunistic Infections↗
PubMed1997

Aspergillosis.

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Amphotericin B↗
PubMed1997

Penicilliosis.

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Acquired Immunodeficiency Syndrome↗
PubMed1996

Patterns of opportunistic infections in patients with HIV infection.

The pattern of the development of opportunistic infections (OIs) in HIV-infected patients was evaluated, based on a cohort of 1,530 patients enrolled in two AIDS Clinical Trials Group anti-retroviral studies. We quantified the increase in risk of OIs associated with the occurrence of a previous OI. This assessment was based on the observed event rates of the more common AIDS-defining OIs: Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), cytomegalovirus (CMV), and a systemic mycosis. Additionally, for each OI, we assessed the relative risks associated with a history of prior OIs, changes in CD4 levels, and baseline prognostic factors. We found that the occurrence of each of these OIs increased the risk of subsequent OIs, even after adjusting for the CD4 count. Specifically, the occurrence of PCP significantly increased the risk of MAC and CMV, and somewhat increased the risk of systemic mycoses. Diagnosis with MAC was associated with an increased risk of subsequent CMV, whereas the occurrence of CMV increased the risk of MAC. Finally, once patients were diagnosed with a systemic mycosis, they were at a somewhat increased risk of subsequently developing MAC or CMV. Although current practice for determining the timing and initiation of prophylactic therapies relies chiefly on CD4 count, the occurrence of specific AIDS-defining OIs in patients with HIV infection should also be taken into account in making decisions regarding prophylaxis strategies.

AIDS-Related Opportunistic Infections↗
PubMed1996

A phase II study of recombinant human interferon-alpha 2a and zidovudine in patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group.

To assess safety, antitumor response, and immunological and virological activity of interferon-alpha 2a and zidovudine combination therapy in patients with AIDS-related Kaposi's sarcoma, we conducted an open-label, Phase II, multicenter study. Sixty-three patients with biopsy-proven Kaposi's sarcoma and no previous interferon-alpha therapy received zidovudine 600 mg/day and interferon-alpha 2a 18 x 10(6) U/day. The median duration of follow-up was 49 weeks. Of 62 evaluable patients, 25 (40%; 95% confidence interval, 0.28-0.52) showed a complete (26%) or partial (15%) antitumor response. Eight of 30 patients (27%) with < 100 CD4 cells/mm3 and 17 of 32 patients (53%) with > or = 100 CD4 cells/mm3 had a response. The median time to response was 36 weeks. Of the 25 patients with a response, four developed tumor progression. The median duration of response was 22.4 weeks. Eight patients (13%) developed another AIDS-defining event and 13 (21%) died. The major toxicities included anemia (16%), neutropenia (27%), elevated serum transaminases (16%), weight loss (16%), malaise (14%), fatigue (14%), fever (10%), and headache (6%). Therapy with intermediate-dose interferon-alpha 2a and zidovudine resulted in tumor regression in patients with AIDS-related Kaposi's sarcoma who had a wide range of CD4 cell counts; this therapy was relatively well tolerated.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Recent advances in the management of cryptococcal meningitis in patients with AIDS.

The optimum regimen for the treatment of cryptococcal meningitis in patients with AIDS is still not totally clear. The triazoles fluconazole and itraconazole are associated with response rates of 50%-60%. Amphotericin B appears to be associated with a more rapid clearance of organisms, and there are some data suggesting that initial therapy with amphotericin B is preferable to that with triazoles; however, this finding has not been definitively shown in large comparative trials. Results of a recently completed large trial suggested that initial treatment with amphotericin B followed by triazole therapy is associated with an acute mortality rate (approximately 6%) that is substantially less than that in previous studies. Relapse is common (20%-60% of cases) if the patient does not receive chronic suppressive therapy. The drug of choice for maintenance therapy is fluconazole (200 mg/d). A recent trial showed that fluconazole was superior to itraconazole (200 mg/d) as suppressive therapy. Prophylactic use of fluconazole (200 mg/d) significantly decreases the incidence of cryptococcosis and mucosal candidiasis, especially in patients with CD4 cell counts of < 50/mm3. However, because of the lack of a survival benefit and the risk of the selection effect on fluconazole-resistant Candida, it is difficult to make the recommendation of routine prophylaxis with fluconazole for all patients with AIDS; the decision to use prophylaxis should be based on more selective criteria.

AIDS-Related Opportunistic Infections↗
PubMed1996

Cryptococcosis.

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AIDS-Related Opportunistic Infections↗
PubMed1996

Candidiasis.

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AIDS-Related Opportunistic Infections↗