Cholangiopathy associated with Microsporidia infection of the common bile duct mucosa in a patient with HIV infection.
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Biomedical subjects
Publications and source records attributed to W Rozenbaum.
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Three patients who were seropositive for human immunodeficiency virus underwent surgery for infected aneurysm of the abdominal aorta. Fever and abdominal pain were the principal presenting clinical features. None of the patients had any opportunistic infections or endocarditis. In two cases, a ruptured aneurysm was demonstrated radiographically. In the remaining case, sonograms were diagnostic. The organisms responsible were salmonella, Hemophilus influenzae, and Mycobacterium tuberculosis. In two cases, the infectious origin was evidenced by bacteriologic examination of the aortic wall, which revealed the presence of Salmonella enteritidis and Koch's bacillus. Although Hemophilus influenzae was not found in the aortic wall of the remaining case, the infectious origin of the aneurysm was established because preoperative blood cultures were positive for this pathogen, and pathohistologic examination of the specimen showed destruction associated with leukocyte infiltration of the aneurysmal wall. An in situ prosthetic graft replacement protected by omentum was performed in all three cases. Antibiotic therapy was continued for several weeks. All patients are well with follow-up ranging from 10 to 21 months. Infectious aneurysm associated with human immunodeficiency virus seropositivity results in bacterial infestation of an atheromatous aorta. Infected phenomena are promoted by cellular immunodeficiency. Surgery was justified in these cases because of the immediate threat of rupture.
Anti-p25 antibodies were evaluated by cross-sectional analysis of sera from 130 human immunodeficiency virus type 1-infected patients and in a longitudinal study of 56 patients by retrospective analysis of sequentially collected sera. High and stable antibody levels were found in Centers for Disease Control stage II or III patients, 78% of whom had levels greater than 10 arbitrary units/mL. Patients with AIDS-related complex displayed heterogeneous levels. Patients with AIDS had the lowest values: less than or equal to 10 units/mL in 96% of cases. In patients whose CD4+ cell counts eventually fell below 200/mm3 or who developed AIDS (or both), antibodies were initially less than 40 units/mL and/or they declined with a rate greater than 1 log unit/5 years, beginning at least 4 years before the index symptom. Because the only point at which CD4+ cell counts significantly differed between progressors and nonprogressors was 1 year before the disease, both initial anti-p25 values and antibody decline seemed to be better long-term prognostic markers than CD4+ cell counts.
The serum levels of cortisol, progesterone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione (delta 4), testosterone (T), estrone, and estradiol of HIV+ men and HIV- men were determined by radioimmunoassay. The cortisol, 17 alpha-hydroxyprogesterone, and estrone levels of all HIV+ subjects were 35-55% (p less than 0.01), 25-90% (p less than 0.01), and 30-50% (p less than 0.01) higher, respectively, than those of controls. Androgen levels were very high in Centers for Disease Control (CDC) groups II and III of HIV infection (DHEA, 85%, p less than 0.01; delta 4, 60%, p less than 0.01; T, 30%, p less than 0.05), but much lower in group IVC1 and IVC2. The estradiol levels were significantly elevated only in group IVD (50%, p less than 0.01) and group IVC2 (25%, NS). These results indicate that serum hormone levels are correlated with HIV infection group. The changes in steroid hormone concentrations during the development of HIV infection may have important implications for the immune response of patients. The high cortisol and estrone levels of all groups, the elevated androgen levels in asymptomatic groups, and the low androgens in AIDS patients may form part of the complex network of immunomodulatory factors.
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96 AIDS patients with fever and either acid-fast bacilli on microscopic examination of bacteriological samples or mycobacteria isolated by culture were treated with a daily 4-drug combination of 7-10 mg/kg rifabutin, 5 mg/kg isoniazid, 20 mg/kg ethambutol and 100 mg clofazimine. 46 patients were excluded from efficacy assessment: 13 died before or within the first days of treatment, 5 had negative initial cultures, 14 had initial cultures positive for M. tuberculosis, 4 for M. kansasii, 1 for M. flavescens, 1 for M. gordonae, 7 were lost to follow-up and 1 received no rifabutin. In the 50 remaining patients, 31 had disseminated disease due to M. avium intracellulare complex (MAIC) and 19 had apparently localised disease, due to MAIC in 15 cases and to M. xenopi in 4 cases. Side-effects led to withdrawal of isoniazid in 1 case (hepatic enzymes increased) and rifabutin in another (thrombocytopenia). After 1 month of treatment, fever decreased from 38.4 +/- 0.6 degrees C to 37.7 +/- 0.5 degrees C (p less than 0.01) and patients stopped losing weight. After 3 months treatment, only 37 patients were alive and still under treatment. Cultures became negative in 16 of 23 patients with available bacteriological data (9 of 14 patients with disseminated disease and 7 of 9 patients with localised disease), relapse occurred before death in 4 patients. 34 patients died before treatment was completed. Death was considered to be related to mycobacterial infection in 5 cases. We conclude that the 4-drug combination is safe and, in some cases, it appears to be effective.
Forty-four patients with acquired immune deficiency syndrome with cytomegalovirus (CMV) retinitis (64 eyes) intolerant of or refusing systemic antiviral therapy received 710 intravitreal injections of ganciclovir at the dosage of 400 micrograms per injection. The patients were followed for a mean period of 9 weeks. Induction therapy consisted of two injections a week until healing. Maintenance therapy consisted of one injection a week until relapse. All but 1 of 53 induction courses led to cicatrization, after a mean of 6.6 injections. In 54 maintenance courses, the 8-week relapse rate was 53%. During intravitreal therapy, involvement of the fellow eye occurred in 11% of the patients and CMV infection developed in a nonocular site in 16% of the patients. Five retinal detachments and two intravitreal hemorrhages occurred. No endophthalmitis or cataract was noted. Intravitreal ganciclovir appears to be a safe and effective alternative in patients intolerant of intravenous anti-CMV drugs.
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Studying the mechanisms of the impaired T-cell colony growth from HIV-infected subjects, we have demonstrated that depletion of adherent cells from some patients' peripheral blood mononuclear cells enhanced the plating efficiency of T colony-forming cells. We report here that media conditioned by patients' cells but not normal adherent cells could inhibit the expression of the interleukin-2 receptor alpha (IL-2R alpha) chain but not the IL-2R beta chain in a dose-dependent manner. This inhibitory activity was produced by macrophage-monocyte cells since they displayed the My9+ My7+ OKM1+ phenotype and since adherent cell depletion by complement-mediated cytotoxicity with the My9 monoclonal antibody completely abrogated production of the inhibitory activity. A similar inhibitory activity, which could not be recognized by anti-p24 or anti-gp 120 monoclonal antibody or purified human anti-HIV immun]gobulin G in Western blot assays, could also be detected in culture supernatants of in vitro HIV-infected normal adherent and U937 leukemic cells. Production of IL-2R alpha chain inhibitory activity was associated with a decreased mitogen-induced expression of IL-2R alpha chain on patients' PBMC in 8 of 10 studied cases. Its production could be detected in 82, 58, and 91% of media conditioned by adherent cells from stage II, III, and IV patients, respectively. The amount of IL-2R alpha chain inhibitor released by patients' adherent cells increased during the deterioration of the patients' clinical status, and zidovudine treatment completely abrogated its production in all patients. These findings strongly suggest that production of IL-2R alpha chain inhibitory activity is involved in the pathophysiology of the impaired T-cell responses during HIV infection and could be of clinical relevance during the patients' follow-up.
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One hundred and twenty patients suffering from an AIDS-related Kaposi's sarcoma treated by 18 million units of recombinant alpha-2A-interferon daily were followed prospectively for a period of between one and six years. An overall complete response was observed in 35% of these patients; the figure was significantly higher in those who did not have a visceral localization or opportunistic infections. Total lymphocyte count, CD4 lymphocyte count, and CD4/CD8 ratio were significantly higher, and beta-2-microglobuline significantly lower, in the responders than in the non-responders. A multivariate analysis showed that localization of KS and CD4 count had independent predictive value, with an odds ratio of 35 for patients who had more than 300 CD4 cells at the onset of treatment versus those with less than 150. Patients whose initially negative p24 antigenemia remained negative during treatment had the highest frequency of complete response. Among patients with initially positive p24 antigenemia, those whose percentage decrease in antigenemia levels was greatest had a higher frequency of complete response. The cumulative probability of survival in responders was 62% at four years. These results demonstrate an anti-tumoral and anti-viral effect and prolonged survival in a group of patients whose initial immune parameters were relatively well preserved. However, these results do not permit us to conclude whether these well-responding patients were treated at the onset of illness, or whether their illness was naturally less evolutive.
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AIDS-related Kaposi's sarcoma (KS) has a better prognosis than other presentations of AIDS. It is more frequent among homo-bisexual men than in other risk groups. This has raised the possibility of specific etiological agent(s) or co-factor(s) which induce its development. However, this suggestion is confusing since it implies that exposure to such agent(s) or co-factor(s) would result in an improved prognosis. Recent virological studies indicate that the HIV itself could be responsible for the induction or growth of KS. Since HIV antigenemia and the immunosuppression are lower among KS cases than among those with opportunistic infections (OI), we could expect a lower level of exposure to AIDS-related factors in KS cases as compared to OI cases. To investigate this possibility, we compared 25 cases with Kaposi's sarcoma alone (KS) with 25 cases having OI without KS, among homo-bisexual men. The KS cases were more likely than OI cases to have a higher educational level. They were less likely to have inhaled nitrites, to have had repeated syphilis and repeated gonorrhoea, and to be promiscuous. In the multivariate analysis, the factors which best discriminated the groups were nitrite inhalations, history of repeated syphilis, and anonymous promiscuity ("one-night stands"). Our study does not support the hypothesized association between nitrite inhalations and Kaposi's sarcoma. We found that cases with opportunistic infections - that is, with a poor prognosis - had been exposed to AIDS-related risk factors (e.g. history of venereal diseases, nitrite inhalations, promiscuity) at higher levels than cases with Kaposi's sarcoma alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytomegalovirus (CMV) retinitis is the major cause of visual loss in acquired immune deficiency syndrome (AIDS). Thirty-one patients with active CMV retinitis were treated with the new antiviral drug, Foscarnet (trisodium phosphonoformate). After a 3-week course of induction therapy, the retinitis improved in 29 of 31 patients (93.5%). Complete resolution of the retinitis was seen in 19 cases (61.3%). Ten patients had partial resolution (32.2%) and two (6.5%) failed to respond. After induction therapy, six patients were put on a low-dose maintenance regimen. All patients without maintenance therapy relapsed within 3 weeks after discontinuation of Foscarnet. The rate of relapse on maintenance therapy was 50% (3/6) within the first 5 weeks. The three other patients of Foscarnet maintenance did not relapse after a follow-up period of 12 weeks. In contrast to ganciclovir, Foscarnet did not induce neutropenia but it produced kidney toxicity that led to reversible renal insufficiency in three cases. Thus, Foscarnet appears to be a useful alternative to ganciclovir, particularly when combined with bone marrow toxic drugs, such as zidovudine (azidothymidine).
A randomized study of 12 treated patients and seven controls was conducted in order to evaluate HPA-23 anti-HIV activity in HIV-infected patients. The antiviral activity was assessed by determining HIV p24 antigenemia. A persistence or even increase in antigenemia was shown in treated patients and thrombocytopenia was observed in nine out of the 12 patients. This suggests that HPA-23 should not be used in anti-HIV therapy.
The gamma/delta T cell receptor is expressed on 1-15% of normal human peripheral blood lymphocytes (PBL). This subpopulation is recognized by anti-TcR-delta 1 MoAb which is functionally defined as a pan-delta MoAb. Two other antibodies, anti-Ti-gamma A and anti-delta-TcS1 are directed at variable determinants of either the gamma or the delta chain, respectively. In normal individuals anti-Ti-gamma A characterizes two thirds of the TcR-delta 1+ subpopulation whereas anti-delta TcS1 reacts with most of the delta-TcR1+, Ti-gamma A- cells. In the present study, we have used these three MoAbs to characterize the TcR gamma/delta+ peripheral lymphocytes during HIV infection. Fifty patients at three distinct clinical stages (SPC/PGL, ARC, AIDS) of the infection have been studied. The Ti-gamma A+ subset in the whole group accounted for 3.45% of PBL and did not differ from controls; it was also unchanged when the three groups were analysed separately. The Ti-gamma A+ circulating cells were in a resting state as assessed by the absence of surface-expressed activation markers. In contrast, in some patients the proportion of circulating TcR-delta 1+, Ti-gamma A-, delta TcS1+ cells was increased (4.75%) leading to an inversion of the Ti-gamma A/delta-TcS1 ratio. Altogether, those data suggest a conservation of the Ti-gamma A+ subset during HIV infection, contrasting with an increase of the delta-TcS1+, Ti-gamma A- fraction in some cases.
Zidovudine (AZT) is of some benefit for selected patients with AIDS-related complex (ARC) or AIDS treated for up to 24 weeks. The activity and toxicity of oral AZT, 200 mg 4-hourly when possible, was evaluated in 365 consecutive patients with ARC (80) or AIDS (285) followed up for a mean of 31 weeks (range 2-52). A transient increase in body weight, Karnofsky index, and CD4 cell count was observed during the first months of therapy. However, by 6 months, these values had returned to their pretreatment levels and several opportunistic infections, malignancies, and deaths occurred. These disappointing results were partly related to the haematological toxicity of the drug, which led to interruption of treatment in many patients. Thus the benefits of AZT are limited to a few months for ARC and AIDS patients. At least for the most severely affected patients, reduced dosage of AZT may increase the therapeutic index.
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