摘要:

Summary:Transgenic Mov-14 mice, which carry the provirus of Moloney murine leukemia virus (Mo-MuLV) in the germ line and begin to produce infectious virus on embryonic day 14, were used to evaluate the ability of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) to cross the placenta and protect embryos from viremia. We have used the Mov-14 model previously to demonstrate the antiviral efficacy and lack of teratogenicity of transplacental therapy with 3′-azido-3′-deoxythymidine (zidovudine, ZDV). PMEA was administered to pregnant females by daily intraperitoneal injection or by osmotic pump. In contrast to ZDV, PMEA was either noneffective in preventing viremia in the offspring or embryotoxic, depending on the dose. The specific toxic effects seen were resorption of pregnancy, low birth weight, and neonatal death. Histopathological analysis of neonatal mice exposed to PMEA showed severe lymphoid depletion of the thymus. We conclude that PMEA therapy is contraindicated for use during pregnancy.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:To assess the response and toxicity of liquid nitrogen cryotherapy for cutaneous lesions of Kaposi's sarcoma (KS) associated with AIDS, we evaluated 20 subjects with biopsy-proven KS in a phase II clinical trial. Subjects had two to four cutaneous KS indicator lesions treated with liquid nitrogen cyrotherapy. Treatment was repeated at 3 week intervals, allowing adequate healing time. On average, subjects received three treatments per lesion with a mean follow-up time of 11 weeks (range of 6–25 weeks). One treatment consisted of two freeze-thaw cycles, with thaw times ranging from 11 to 60 s per cycle. A complete response was observed in 80% of treated KS lesions and lasted a minimum of 6 weeks following the completion of therapy. Greater than 50% cosmetic improvement of KS was observed. Histopathology of treated lesions correlated poorly with cosmetic improvement. Response was not predicted by tolerance to zidovudine therapy, CD4+cell count, presence of B symptoms, or previous chemotherapy. Subjects without prior history of opportunistic infection (OI) were more likely to have a better response than those with a prior history of OI. Subjects tolerated cryotherapy well. Blistering occurred frequently, but local pain was limited and relieved by acetaminophen. Secondary infection did not occur. Based on this study, we recommend cryotherapy to subjects with cutaneous KS lesions. Liquid nitrogen cryotherapy is easily applied as a primary therapy, and may also have a role in the treatment of cutaneous KS lesions that respond slowly or show incomplete cosmetic improvement with systemic therapies.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:To define the natural variability of human immunodeficiency virus p24 antigen (HIV Ag) over time in untreated HIV-infected patients, we analyzed the percentage change of serum HIV Ag in 40 antigenemic ARC/AIDS subjects receiving placebo in a 24 week clinical trial. When grouped by month of observation, no differences in HIV Ag change were seen among all five 1 month observation periods (p> 0.4). After all 105 monthly changes (medialn of 3 per subject) were pooled, the mean monthly HIV Ag change was 0% change (standard deviation: 77% increase, 44% decrease). Furthermore, HIV Ag changes did not differ among all lengths of observation (from 1 to 5 months using all possible pairwise combinations of HIV Ag levels,p> 0.4). CD4 T-cell changes over the whole study did not correlate with HIV Ag changes over the same period. Knowledge of this broad HIV Ag variability should be useful in calculating sample size and in choosing categorical responses unlikely to occur spontaneously in clinical trials of antiviral agents where HIV Ag changes are used as surrogate markers of efficacy.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:Nucleoside-induced neuropathy characteristically appears as a painful, symmetric, distal polyneuropathy. To evaluate the neurotoxic potential of zidovudine (ZDV, or azidothymidine), in persons with little confounding human immunodeficiency virus (HIV) neuropathy, we evaluated peripheral nerve function in persons completing placebo-controlled studies of ZDV in early HIV disease. Participants had been receiving placebo or ZDV at doses of 800–1,200 mg daily for a median 52 weeks at the time of evaluation. Neuropathic symptoms and abnormalities of motor and sensory function were present in fewer than 10% of both treatment groups. Depressed reflexes were found in 19% of the ZDV group and 18% of the placebo group. Quantitative sensory testing for vibration was abnormal in fewer than 10% of participants and the absolute scores favored the ZDV group. We thus found a low prevalence of peripheral nerve abnormalities and no evidence of ZDV neurotoxicity in this population.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:We evaluated the intensity of medical care for 30 consecutive AIDS patients at one hospital, using methodology based on the Delay Tool of Selker et al. Of 25 AIDS patients who survived hospitalization, 15 had at least one delay day in the hospital. Major factors associated with care that could have been provided at an alternative site included difficulty with skilled nursing facility placement in 20% of the patients, difficulty coordinating out-of-hospital care in 28%, and scheduling of outpatient surgical procedures in 12%. For the 15 patients who could have received some of their care at a lower intensity setting, a median of 7 hospital days could have been potentially saved with better coordination of outpatient care and increased availability of skilled nursing facilities. The five patients who died in hospital also used large amounts of resources and had long lengths of stay. Prior studies of non-AIDS patients revealed similar results, suggesting that, for reasons of quality of care, quality of life, and economics, policy-makers must develop managed care programs, skilled nursing facilities that accept AIDS patients, inpatient psychiatry facilities, and increased hospice availability.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:Nontreponemal testing is a valuable tool in screening for syphilis. False-positive reactions are uncommon and are usually at a titer <1:8. We describe eight intravenous substance abusers and/or HIV-positive patients with high-titer (≥1:16) nontreponemal and negative treponemal serologies in whom the diagnosis of syphilis is unproven and possibly false.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:The study objective was to describe the pharmacokinetics of azidothymidine (AZT) in a large population of early, asymptomatic human immunodeficiency virus (HlV)-infected individuals. The study design was a multicenter, prospective, descriptive single-dose pharmacokinetic study. Each of 66 fasting, male, HIV-infected homosexuals older than 18 years of age and in CDC classifications II, III, and IVC2 received a single 400-mg oral dose of AZT with subsequent pharmacokinetic measurements performed during an 8-h period for AZT and its major metabolite, glucuronylazidothymidine (GAZT). Results were obtained in 65 patients (36 smokers, 29 nonsmokers), of whom 3 were noted to have hepatic dysfunction. In those with normal hepatic function, the following parameters were described: AZT, area under the curve (AUC) ± SD, 9.9 ± 5.7 μ.M.h, maximum concentration (Cmax) ± SD, 7.3 ± 4.7 μ.M; time to maximum concentration (Tmax) ± SD, 0.93 ± 0.42 h, and half-life (t1/2) ± SD, 1.0 ± 0.8 h. Corresponding values for GAZT were: AUC ± SD 35.7 ± 10.3 μM.h, Cmax± SD 21.3 ± 7.3 μ.M,Tmax± SD 1.2 ± 0.50 h,t1/2± SD 0.98 ± 0.62 h, No significant differences were found in comparisons of study site, CDC classification of disease, smokers versus nonsmokers, and in patients with hepatic dysfunction, although a higher AUC and earlier Cmaxfor AZT was noted in the latter group. It is concluded that AZT pharmacokinetics are similar in patients with early asymptomtic HIV disease when compared with previous reports in patients with later disease. This study finds no difference in pharmacokinetics of AZT in smokers versus nonsmokers and suggests a trend to a decreased presystemic elimination in patients with hepatic dysfunction.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:We investigated whether elevated serum levels of β2-microglobulin and neopterin were related to the abnormal in vivo production of interferon described in patients with human immunodeficiency virus (HIV) infection, and whether these factors might add to measurements of CD4+T cells in predicting survival and tumor regression in patients with Kaposi sarcoma associated with AIDS. β2-Microglobulin and neopterin levels were strongly correlated (r= 0.82), and were each significantly higher in patients with detectable serum interferon-α activity. Inverse correlations were observed between prognosis and levels of these serum products. Prediction by CD4+T-cell count of tumor regression after treatment with interferon-α and zidovudine was improved by each of two factors: (a) the presence or absence of endogenous interferon-α activity, and (b) a combined variable reflecting relative levels of the interferon-inducible products, β2-microglobulin and neopterin. The level of β2-micro-globulin was the single best predictor of survival. When β2-microglobulin was not considered, the endogenous interferon-α variable was the best predictor of survival, and the prediction was enhanced by addition of the combined variable, or the neopterin value alone. We conclude that serologie markers, which directly or indirectly reflect activation of the endogenous interferon system, may be valuable adjuncts to CD4+T-cell counts in assessing prognosis and selecting and evaluating treatments for patients with Kaposi sarcoma and AIDS.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:Research data describing the prevalence and patterns of behaviors that place persons at increased risk of HIV infection are extremely limited. The scarcity of data has constrained potential applications of surveillance data, research on specific high-risk behaviors, and epidemiological studies. This article critically reviews available research for four population groups: intravenous drug users, homosexual males, and sexually active adolescents and adults. The fallacies inherent in estimating risk group size underscore the need for population-based research that can provide detailed data on sexual and drug use behaviors.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:Exchange of syringes and needles has for the last 3 years been offered to injecting drug users as part of an HIV prevention project in a small university town in south Sweden. The program at the local hospital has been visited by 979 drug users, of which 182 have participated on a more regular basis. The typical participant is a 30-year-old male who has injected amphetamine or heroin for at least 10 years. The seroprevalence for HIV among drug users in south Sweden has been maintained at approximately 1% in contrast to up to 60% in subpopulations from other Scandinavian regions with a comparable drug problem. No project participant has become HIV infected during the study period and a reduction in risk behavior has been noted among local drug injectors. The HIV prevention project has attracted many individuals with no previous contact with drug rehabilitation programs; for a number of drug users, the syringe exchange has served as an introduction to such treatment efforts.

ISSN:0894-9255    

出版商:OVID    

年代:1991

数据来源: OVID