摘要:

A group of 34 homosexual men with acquired immune deficiency syndrome (AIDS) spectrum disorders were assessed for cognitive impairment on a range of neuropsychological tests. There were 17 patients with AIDS, and 17 with AIDS-related complex (ARC). Although none of the patients showed signs of the severe dementing syndrome that has been described in persons with HIV infection, they demonstrated signs of cognitive impairment consistent with organic brain dysfunction. The profile of deficits shown by AIDS and ARC patients could be broadly grouped into disorders of recent and delayed memory and learning, generalized cognitive slowing, and reduced mental flexibility. Considerations of the clinical and neuropathological similarities between subcortical dementing syndromes and HIV-related cognitive impairment suggest that in both processes the pathogenesis of the observed deficits may involve disruption of frontodiencephalic projections.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Seventy-four HIV-infected homosexual males belonging to CDC groups IIB, III, and IVC2 were treated with increasing doses of zidovudine within the Multicentre Canadian AZT Trial. Following a 3 week observation period, consenting volunteers received 600 mg/day for 18 weeks, 900 mg/day for 9 weeks, and 1,200 mg/day for 9 weeks. This was followed by a 6 week washout period after which zidovudine was restarted at 1,200 mg/day for 18 weeks. Patients were followed for a total of 63 weeks. Every 3 weeks they underwent a full clinical and laboratory assessment. For the purpose of this analysis, subjects were divided according to the mean initial platelet value (≥150,000 or <150,000/L) into normals (n = 57) and thrombocytopenics (n = 12), respectively. Analysis of variance was used to compare the mean platelet values at each zidovudine dose. All comparisons were made against baseline values. Zidovudine increased platelet counts in normal and thrombocytopenic subjects. The magnitude of this effect varied depending on the baseline platelet count. Among normals, the platelet count increased from 241,000 ± 45,000/L at baseline to 261,000 ± 51,000/L (p < 0.01) while receiving 600 mg/day of zidovudine. This effect was self-limited, reaching a peak by week 3. The platelet count decreased to baseline values despite increasing the dose of zidovudine to 900 or 1,200 mg/day. The platelet count further decreased to 218,000 ± 43,000/L during the washout phase (washout vs. 1,200 mg, p < 0.01). The platelet count increased to 238,000 ± 50,000/L upon reinstitution of zidovudine at 1,200 mg/day (reinstitution vs. washout; p < 0.01). Among thrombocytopenics, the platelet count increased from 81,000 ± 37,000/L at baseline to 129,000 ± 51,000/L (p < 0.01) while receiving 600 mg/day of zidovudine. This effect reached a peak by week 9 and was sustained for 36 weeks with counts of 117,000 ± 43,000 and 119,000 ± 41,000/L while on 900 and 1,200 mg/day of zidovudine, respectively (900 mg/day vs. baseline, p < 0.01 and 1,200 mg/day vs. baseline, p < 0.01). This effect was not found to be dose related. The platelet count decreased to 101,000 ± 34,000/L during the washout phase (washout vs. 1,200 mg/day, p < 0.07). The platelet count increased once again upon reinstitution of zidovudine at 1,200 mg/day (reinstitution vs. washout p < 0.01). We conclude that zidovudine increases the platelet count in HIV-infected individuals. This effect is drug related but dose independent within the studied dose range. Furthermore, the effect of zidovudine on platelets appears to be more marked and sustained among thrombocytopenic individuals. Based on our findings, HIV-associated thrombocytopenia should be considered a relative indication for zidovudine therapy.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The efficacy of desciclovir, an analog of acyclovir, in eliminating lesions of oral hairy leukoplakia (HL) and suppressing Epstein-Barr virus (EBV) infection was evaluated in a double-blind, placebo-controlled study of 14 patients. Patients were randomized to receive either the active drug, 250 mg three times a day for 14 days, or placebo. In all eight patients receiving desciclovir, lesions of HL were either completely resolved or significantly reduced during the treatment period, whereas lesions in patients receiving placebo showed no change. The histological features of HL were significantly diminished in patients on desciclovir, and cytochemical, in situ hybridization, and ultrastructural studies showed that EBV infection was eliminated or dramatically reduced in the desciclovir group only. Four patients on desciclovir reported side effects, but none required withdrawal from the study. The reappearance of HL in all eight subjects on desciclovir within 1–4 months after therapy was discontinued suggests the need for additional study.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In order to identify the characteristics of the acquired immune deficiency syndrome (AIDS) as it occurs in Mexico, a comparative study of the demographic and pathological findings of the first 58 patients who died of AIDS and were autopsied at two Mexican hospitals, Hospital General de Mexico (HG) and Instituto Nacional de la Nutricion (INN), was performed. The patient population consisted of 52 men and 6 women. Their socioeconomic status (SES) was estimated using the occupational prestige and level of education as indicators. As in the U. S. A., most patients (72%) were male homosexuals/bisexuals (HMS/BSX). However, nine patients (31%) at the HG could not be assigned to any of the currently known risk groups. Comparison of the SES of the two series revealed a significantly higher number of poor patients at HG (81 vs. 17%). For the whole group, the most frequent infections were caused by cytomegalovirus (CMV) (65%), Mycobacterium tuberculosis (28%), Pneumocystis carinii (24%), and Toxoplasma gondii (17%). Kaposi's sarcoma (KS) was found in 41% of the cases. The frequency of toxoplasmosis was higher in poor patients (30 vs. 8%, odds ratio of 5.5, 95% confidence limits of 0.83, 39.34, p = 0.04) while the reverse situation was true for KS (18 vs. 61%, odds ratio of 0.14, 95% confidence limits of 0.04, 0.55, p = 0.001). For KS, this difference persisted when only HMS/BSX patients were compared. In conclusion, dissimilarities observed in the frequency of some AIDS-associated diseases in different institutions appear to be mainly influenced by the SES of the patients.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The tolerance and toxicity of interferon-y (IFN-y) was assessed in a phase I/II study of 21 patients with acquired immune deficiency syndrome (AIDS). A highly purified preparation of human recombinant E. coli-produced IFN-y was given i.v. twice weekly for an 8 week period. Patients were enrolled in the study in groups of four or five; the initial group received an IFN-y dose of 0.03 mg/m2 and subsequent groups received higher IFN-7 doses of 0.3, 1, or 3 mg/m2. Toxicity resulting from IFN-7 was minimal and the therapy was well tolerated even at the maximum dose (3 mg/m2). No patients developed antibodies that neutralized IFN-y. Clinical responses were observed in 3 of 17 patients with Kaposi's sarcoma (KS). A complete clinical response was achieved in one individual and a partial, temporary regression of KS lesions was observed in two other patients. HIV p24 antigen was decreased in plasma samples obtained from six of nine patients with initially detectable HIV protein. These data suggest that IFN-y should be considered as a therapeutic agent, possibly with other antivirals, in the treatment of patients with AIDS.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

This study was undertaken to calculate the in vivo drug interactions between recombinant human interferon-αA/D (rHuIFN-αA/D) and 3′-azido-3′-deoxythymidine (AZT) in a quantitative model for retroviral viremia. When given as single agents, both AZT and rHuIFN-αA/D suppressed virus-induced splenomegaly in a dose-dependent fashion in mice inoculated with Rauscher murine leukemia virus (RLV). However, suppressive doses of single-agent AZT caused anemia after 20 days of therapy. Combining rHuIFN-αA/D with AZT allowed drastic dose reductions for each agent while maintaining ≥93% inhibition of splenomegaly. No clinically significant toxicity was seen. Computer analysis with the isobologram technique and combination index method showed that these combination regimens were highly synergistic. A 20-day course of AZT + rHuIFN-αA/D started 4 h after virus exposure was protective against RLV viremia and disease. After cessation of therapy, the animals were resistant to rechallenge with fully infectious RLV. We conclude that prompt initiation of effective combination therapy after retroviral exposure prevented viremia and disease and led to protective immunity.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Sequence analysis of multiple isolates of the human immunodeficiency virus type 1 (HIV-1) reveals the existence of a conserved open reading frame, designated T, that partially overlaps the tat,rev, andvpucoding sequences. Here we show that in vitro translation of RNA derived from this region of the viral genome yields a 17 kDa fusion protein, the result of a minus one frameshift event in the overlap between thetatand T open reading frames. It is also shown that messenger RNA species accumulate in HIV-1 infection from which the 17 kDa protein can be made. These observations suggest that ribosomal frameshift events may result in the biosynthesis of viral regulatory as well as viral structural proteins.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We have previously reported that immunoconjugates composed of deglycosylated ricin A chain coupled to either recombinant (r) CD4 or two different monoclonal human anti-gp41 antibodies (rCD4-dgA and antigp41-dgA, respectively) are specifically toxic to HIV-infected lines of human T cells (H9) and monocytes (U937). In order to further evaluate these immunoconjugates as potential therapeutic reagents for killing HIV-infected cells, H9 cells infected with five different isolates of HIV were used as target cells in vitro. All three HIV-specific immunoconjugates were toxic to H9 cells infected with each HIV isolate, but were virtually nontoxic to uninfected cells. Chloroquine markedly potentiated the specific toxicity of all three conjugates, particularly the anti-gp41-dgAs. None of the conjugates affected the ability of normal peripheral blood B cells to respond to mitogen or the ability of normal T cells to respond to alloantigens.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A neural network computer program, trained to predict secondary structure of proteins by exposing it to matching sets of primary and secondary structures from a database, was used to analyze the human immunodeficiency virus (HIV) proteins pl7, gpl20, and gp41 from their amino acid sequences. The results are compared to those obtained by the Chou-Fasman analysis. Two α-helical sequences corresponding to the putative fusigenic domain and to the transmembrane domain of gp41 could be predicted, as well as a possible binding site between pl7 and gp41. On the basis of the secondary structure predictions, a three-dimensional model of pl7 was constructed. This model was found to represent a stable conformation by an analysis using an energy-minimization program. The model predicts that pl7 is attached to the membrane only by the acylated N-terminus, in analogy with the N-terminus of the gag protein of other retroviruses and also with the src oncogene protein p60src. The intracellular C-terminal part of gp41 may act as a receptor by electrostatic interaction with pl7.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Sera from 353 cats with naturally occurring feline leukemia virus (FeLV) infection were collected in Boston, Los Angeles, New York City, and Seattle between 1968 and 1988. These sera were retrospectively assayed by enzyme-linked immunosorbent assay for antibodies to feline immunodeficiency virus (FIV). Fifty-one (14.4%) of the FeLV-positive sera had antibodies to FIV, indicating dual oncovirus and lentivirus infections. FIV infections were confirmed by Western blot analysis, antibodies against the 15 and 27 kDa proteins being used as definitive markers. FIV infection was diagnosed in one cat sampled in 1968 and in eight other cats sampled before 1975 in New York City. Illnesses exhibited by coinfected cats were similar to those of cats infected with FeLV only. Two unrelated cats with multicentric fibrosarcomas were found to be simultaneously infected with FIV, FeLV, and feline sarcoma virus. FIV was less contagious than FeLV in 73 cats residing in an exposure household between 1977 and 1980 as determined by evaluation of sera collected sequentially. In this household, 15 resident cats became FeLV infected whereas no cats contracted FIV infection. Comparison of serologic results from 53 cats with leukemia/lymphoma and matched controls confirmed a strong correlation between FeLV viremia and leukemia/lymphoma. A significant correlation between FIV infection and lymphoproliferative malignancies was also found independent of FeLV infection.

ISSN:0894-9255    

出版商:OVID    

年代:1990

数据来源: OVID