PubMed Health⌕ Search

Biomedical subjects

W Rozenbaum

Publications and source records attributed to W Rozenbaum.

At least 73 records · Page 4Linked to original sources

Differences in androgens of HIV positive patients with and without Kaposi sarcoma.

AIM: Since most forms of Kaposi sarcoma are much more common in men than in women, the aim of this study was to examine serum concentrations of sex steroids in HIV positive men with and without Kaposi sarcoma. METHODS: Blood samples from 34 HIV positive men without Kaposi sarcoma (KS-) and 28 with Kaposi sarcoma (KS+) and from 35 HIV negative men (controls) were analysed for adrenal and gonadal steroids. Further analysis was done in subgroups classified by CD4 lymphocyte counts. RESULTS: KS+ patients had significantly higher serum dehydroepiandrosterone (DHEA) and testosterone concentrations than the KS- patients, and their DHEA, DHEA sulphate, testosterone, and androstenedione values were higher than in the controls. The KS+ patients with more than 500 CD4 lymphocytes per mm3 had significantly higher serum DHEA, DHEA sulphate, and testosterone than the KS- patients with the same CD4 counts; those with 500-200 CD4 cells/mm3 had higher serum DHEA and testosterone than the equivalent KS- men; and those with < 200 CD4 cells/mm3 had raised DHEA only compared with KS- men. Both KS+ and KS- men had higher serum progesterone and oestradiol than the controls. Glucocorticoids were not significantly altered. CONCLUSIONS: The high androgen levels in KS+ patients, particularly in the early stages of the disease (> 500 CD4 cells/mm3), may affect the immune system by inducing an abnormal cytokine profile, or by increasing T8 proliferation and activation, or both. This raises the question of the relationship between androgens and Kaposi sarcoma.

Adult↗

Autocrine interferon-beta synthesis for gene therapy of HIV infection: increased resistance to HIV-1 in lymphocytes from healthy and HIV-infected individuals.

OBJECTIVE: To explore the possibility of gene therapy of HIV infection based on the multiple antiretroviral activities of interferon (IFN)-beta. DESIGN: We introduced into HIV target cells an IFN-beta gene placed under an expression control ensuring a low and constitutive expression, sufficient to confer a permanent antiviral state without impeding normal cell function. METHODS: We transformed, with an efficacy ranging from 20-55%, peripheral blood lymphocytes (PBL) derived from healthy, seronegative donors, and from asymptomatic HIV-infected individuals by the HMB-KbHuIFN beta retroviral vector carrying the human IFN-beta coding sequence driven by a fragment of the murine H-2Kb gene promoter. RESULTS: The replication rate of the IFN-beta-expressing cells was no different from that of untransformed controls during the 21-day period of in vitro observation. When IFN-beta-transformed, purified CD4+ lymphocytes from healthy donors were HIV-1LAI-infected, virus replication was inhibited and most of the cells survived, in contrast to untransformed CD4+ cells which were all destroyed 12 days after infection. Protection of CD4+ cells from the same donors was also observed in suspensions of IFN-beta-transformed total PBL that were infected with HIV-1LAI. In IFN-beta-transformed PBL from four HIV-infected donors, endogenous HIV replication was decreased and 28-69% of the CD4+ cells survived at the end of the 21 days in culture. In the untransformed control PBL suspensions, all CD4+ cells were destroyed. In long-term experiments, HIV-infected, IFN-beta-transformed cell populations of the lymphocytic CEM and the promonocytic U937 line were kept in culture for 60 days, during which time they remained resistant to HIV infection. CONCLUSION: These results indicate that further exploration of autocrine IFN-beta production for somatic cell gene therapy of HIV infection is warranted.

Antiviral Agents↗

Intestinal histoplasmosis in AIDS patients: report of three cases observed in France and review of the literature.

We report three cases of colonic histoplasmosis observed in a non-endemic area in patients with AIDS. The patients presented with fever, abdominal pain and an abdominal mass in the right lower quadrant. Diagnosis was obtained using Gomori-Crocott staining of endoscopic or surgical biopsies. One patient died without specific treatment and two patients had a complete remission when treated with intravenous amphotericin B but suffered a relapse when given oral itraconazole. Thus, physicians in areas where intestinal histoplasmosis is not endemic should be aware of the condition. Diagnosis can easily be obtained using Gomori-Crocott staining of colonoscopic biopsies; this should avoid unnecessary laparotomies and allow specific treatment to be instituted rapidly.

AIDS-Related Opportunistic Infections↗

Etiology and management of toxic megacolon in patients with human immunodeficiency virus infection.

We report six cases of toxic megacolon in patients with human immunodeficiency virus (HIV). One case, at an early stage of HIV infection, mimicked a severe attack of Crohn's disease, with a negative search for infectious agents. Subtotal colectomy was successfully performed with an uneventful postoperative course. The five other cases concerned patients with acquired immunodeficiency syndrome at a late stage of immunodeficiency. They were related to Clostridium difficile or cytomegalovirus (CMV) intestinal infection in two and three patients, respectively. One case of CMV colitis presented macroscopically and histologically as pseudomembranous colitis. Emergency subtotal colectomy, performed in the first four patients with acquired immunodeficiency syndrome was followed by a fatal postoperative outcome. The last patient treated conservatively by colonoscopic decompression, in association with anti-CMV therapy, had a favorable short-term outcome. From the experience of our series and data from the literature, we discuss the best diagnostic and therapeutic approach to toxic megacolon in patients with HIV.

Adult↗

Results of chemotherapy in 30 AIDS patients with symptomatic pulmonary Kaposi's sarcoma.

BACKGROUND: The aim of this study was to report the effects of a three-drug chemotherapy regimen in patients with symptomatic AIDS-related pulmonary Kaposi's sarcoma and to analyse prognostic factors for survival. METHODS: Thirty consecutive HIV seropositive patients with respiratory symptoms and proven pulmonary Kaposi's sarcoma were treated with the same therapeutic regimen comprising adriamycin (30 mg/m2), bleomycin (10 mg/m2), and vincristine (2 mg) administered intravenously once every four weeks. RESULTS: Two patients died during the first course of chemotherapy. In the other 28 cases dyspnoea improved and Pao2 rose despite minimal (n = 17) or no (n = 11) improvement in the chest radiographic appearance. The median survival from the beginning of chemotherapy was 6.5 months. Poor prognostic factors for survival were: (1) absence of cutaneous Kaposi's sarcoma; (2) previous opportunistic infection; (3) CD4 cell count < 100/microliters; (4) leucocytes < 3500/microliters; (5) haemoglobin < 10 g/dl; and (6) absence of radiological response. Of the 28 patients 24 experienced at least one episode of neutropenia which was associated with bacterial infection in 16 cases. CONCLUSIONS: Chemotherapy may improve respiratory impairment in patients with extensive pulmonary Kaposi's sarcoma but the outcome remains poor. The efficacy of chemotherapy may be limited by neutropenia.

Acquired Immunodeficiency Syndrome↗

[Plurifocal alveolar pneumonia in a patient with AIDS: disseminated Mycobacterium avium intracellulare infection with difficult diagnosis].

In patients with the acquired immunodeficiency syndrome (AIDS), manifestations of generalized Mycobacterium avium intracellulare infection are non-specific and pneumopathy is rarely encountered. We report a case of a patient with AIDS who had clinical and radiological manifestations of multifocal alveolar pneumopathy which was found on autopsy to be due to disseminated Mycobacterium avium intracellulare.

Acquired Immunodeficiency Syndrome↗

[Opportunistic infections in AIDS: the benefits of an "umbrella strategy." From an interview with Professor Willy Rozenbaum].

Availability to practitioners of a treatment for infections by atypical mycobacteria by Ansatipine should produce a reduction or delay in the frequency of opportunistic infections in AIDS, which are a heavy burden on the future of the patients and seriously after their quality of life. Today, the practice of prescribing Ansatipine increase the prophylactic strategy for opportunistic infections in AIDS, or the "Umbrella strategy". This can only improve the possible therapies for practitioners who are faced with the complexity of the disease and bring real benefit to the patients. Distribution of Ansatipine to town pharmacies is a new step in this direction.

AIDS-Related Opportunistic Infections↗

The efficacy and safety of zidovudine alone or as cotherapy with acyclovir for the treatment of patients with AIDS and AIDS-related complex: a double-blind randomized trial. European-Australian Collaborative Group.

OBJECTIVE: To evaluate the efficacy and safety of zidovudine (ZDV) at a maintenance dose of 250 mg every 6 h alone or as cotherapy with acyclovir (ACV; 800 mg every 6 h) as treatment for AIDS and AIDS-related complex (ARC). DESIGN: Double-blind, randomized, placebo-controlled clinical trial of up to 1 year's therapy. SETTING: Teaching hospital ambulatory clinics in eight European countries and Australia. SUBJECTS: A total of 131 patients with AIDS and 134 with ARC were enrolled and followed from 1986 to 1988. MAIN OUTCOME MEASURES: Time to development of AIDS-defining opportunistic infections and AIDS-associated neoplasms, survival assessed at 1 year after entry, performance status, body weight, CD4+ cell counts. RESULTS: During the study period, 46 (36%) ZDV recipients and 37 (27%) cotherapy recipients developed opportunistic infections. The probability of an ARC patient progressing to AIDS (1982 Centers for Disease Control criteria) was 0.18 and 0.15 [95% confidence interval (CI) for difference, -0.17 to 0.11] for the ZDV alone and cotherapy recipients, respectively. After excluding patients who experienced an opportunistic infection during the first 4 weeks of therapy, the probability was 0.13 and 0.099 (95% CI for difference, -0.16 to 0.10) for the ZDV and cotherapy recipients, respectively. Thirty-six patients treated with single-agent therapy [28 (41%) AIDS and eight (12%) ARC patients] and 15 cotherapy recipients [13 (21%) AIDS and two (3%) ARC patients] died during the study. There was a significant difference in time to death between the cotherapy and ZDV alone groups for both AIDS (P = 0.014) and ARC (P = 0.045) patients, with cotherapy patients surviving longer. Infections related to herpesviruses, but not cytomegalovirus, were reduced in patients receiving ACV therapy. CD4+ cell counts in both arms generally increased initially and then declined. Forty-six per cent of patients in the ZDV group (59% of AIDS and 31% of ARC patients) and 52% of patients in the cotherapy group (69% of AIDS and 34% of ARC patients) experienced bone-marrow suppression. Red cell transfusions were administered to 33% of ZDV alone recipients and 34% of cotherapy recipients. CONCLUSION: These data show that the addition of high-dose ACV cotherapy to ZDV for patients with AIDS and advanced ARC results in a statistically significant improvement in survival with minimal increase in the risk of toxicity.

AIDS-Related Complex↗

Diversity of the V3 region of HIV in Paris, France.

OBJECTIVE: To carry out, within France, a large-scale molecular epidemiological investigation on the principal neutralizing determinant of HIV-1, located in the third variable region (V3) of the envelope protein. Such investigations are of the utmost importance in the identification and monitoring of the distribution and spread of different viral strains internationally. DESIGN: Using polymerase chain reaction (PCR), we examined the genetic variation of the V3 region sequences of 28 HIV-infected patients from Paris, France. RESULTS: Comparison of the Parisian V3 loop sequences with other published data indicates that the range of diversity in France is included within that of a large group that contains sequences from North America, the rest of Europe, Japan, India and Africa. Variability appears to be lower in the V3 loop than in its flanking regions. Five out of the six putative N-linked glycosylation sites show preferential alterations to charged amino acids. We report two motifs at the tip of the loop that have not been described previously. CONCLUSIONS: The structural homogeneity and the wide geographic representation of the major V3 group suggests that a common strategy could be applied to a large proportion of isolates in the development of a broad-spectrum HIV vaccine.

Acquired Immunodeficiency Syndrome↗

[Predictive value of the assay of serum anti-p25 antibodies in patients with human immunodeficiency virus (HIV-1) infection].

To assess whether monitoring of antibodies (Ab) directed against the HIV-1 p25 core protein may be used as a predictive marker in the biological monitoring of HIV-infected patients, a study was performed on a transversal cohort of 68 CDC stage II-III, and 36 ARC and 26 AIDS stage IV patients, 37 of whom were being treated with anti-retroviral therapy. A second cohort included 56 patients followed for 3-7 years: 15 stage II-III, 11 ARC and 30 AIDS patients (opportunistic infections: 14; Kaposi's sarcoma: 11; non-Hodgkin's lymphoma: 5). p25 antigenemia and CD4+ blood lymphocyte counts were determined in parallel. Stage II-III patients usually had high and stable anti-p25 Ab levels, ARC patients exhibited more heterogeneous Ab values, while those with AIDS had very low values. No significant difference was observed in the serum anti-p25 levels of patients treated or not with anti-retroviral therapy. In patients whose CD4(+)-cell counts were going to fall below 200/mm3 and/or who were going to progress towards AIDS, the Ab levels started to decrease at a rate of > 1 log U/ml (expressed in arbitrary units/ml) per 5 years at least 2 to 4 years, respectively, before the appearance of the index symptom, despite the fact that the CD4(+)-cell count only differed significantly between progressors and non-progressors one year before the appearance of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus and infected aneurysm of the abdominal aorta: report of three cases.

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.

Acquired Immunodeficiency Syndrome↗

Monitoring of antibodies against human immunodeficiency virus type 1 p25 core protein as prognostic marker.

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.

Adult↗

Evidence for changes in adrenal and testicular steroids during HIV infection.

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.

17-alpha-Hydroxyprogesterone↗