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Biomedical subjects

B Hirschel

Publications and source records attributed to B Hirschel.

At least 145 records · Page 8Linked to original sources

Symptomatic primary infection due to human immunodeficiency virus type 1: review of 31 cases.

In this series of 31 patients with acute infection due to human immunodeficiency virus (HIV) type 1, the male-to-female ratio was 3.4:1 and the mean age was 31.3 years. Sexual transmission accounted for 83.9% of cases; 45.2% of the patients were homosexual and 38.7% were heterosexual. The mean duration of symptoms and signs was 21 days (range, 5-60 days). Fever (87.1%) and skin rash (67.7%) were most commonly reported. Physical examination findings were abnormal for 96% of the patients; the oral cavity (76.7%) and the skin (73.3%) were the most frequently involved sites. Thirteen of 25 patients with sexually acquired infection had genital or oral ulcers, whereas five intravenous drug users had none (P = .052). Thrombocytopenia was the most common hematologic abnormality and was detected in 17 of 23 patients tested. P24 antigenemia, an initially negative screening test for HIV antibody, and a low CD4+ lymphocyte count were noted in 23 of 29, 23 of 30, and 14 of 21 tested patients, respectively.

Adult↗

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↗

High levels of circulating RNA in patients with symptomatic HIV-1 infection.

OBJECTIVE: To evaluate the concentration of circulating RNA (viraemia) in patients with symptomatic primary HIV infection and relate it to sero-immunological parameters. METHODS: Semiquantitation of circulating HIV RNA and proviral HIV DNA was performed using the polymerase chain reaction. Circulating HIV RNA concentrations were expressed as virus equivalent (RNA copies/2) per ml serum. RESULTS: The mean CD4+ lymphocyte count for 19 patients with symptomatic primary HIV infection was 583 x 10(6)/l. Fifteen (79%) patients had detectable levels of p24 antigen (median 462 pg/ml). Circulating HIV RNA (median 2.3 x 10(7) virus equivalent/ml serum) and proviral HIV DNA (median 3630 copies/ml blood) were detected in all samples tested. Follow-up data for five patients (200-1600 days) showed a 1-3 log reduction in circulating RNA within 2 months. Later, circulating RNA concentrations were consistently greater than 10(3) virus equivalent/ml serum. Within 10 days no p24 antigen was detectable. Levels of CD4+ cells varied markedly from patient to patient during the follow-up and, in this small group, no evident correlation was observed between circulating RNA levels and CD4+ lymphocyte counts. CONCLUSIONS: High concentrations of circulating RNA (viraemia) were present in 19 patients with symptomatic primary HIV infection. Although a decrease in viraemia was observed during the following 2 months, viraemia persisted in all patients with long-term follow-up. This suggests that active viral replication is a continuous process in HIV-infected patients.

Adult↗

Mycobacterium genavense sp. nov.

Strains of a suggested novel type of mycobacterium have been repeatedly isolated from patients with AIDS. We summarize the results of tests performed to determine enzymatic activities and metabolic properties, the results of fatty acid analyses, and the results of a comparative 16S rRNA sequence determination. We propose formally that this organism represents a new species, Mycobacterium genavense. The type strain is strain 2289, a culture of which has been deposited in the American Type Culture Collection as strain ATCC 51234.

Acquired Immunodeficiency Syndrome↗

Disseminated "Mycobacterium genavense" infection in patients with AIDS.

We describe 18 patients with advanced HIV infection, most of whom had a chronic illness characterised by fever, diarrhoea, and massive loss of weight. Biopsy and necropsy samples revealed abundant acid-fast microorganisms in intestines, liver, spleen, lymph nodes, and many other tissues, which did not grow on solid media, although limited growth was observed in liquid blood cultures. Using primers complementary to bacterial 16S rRNA we amplified DNA sequences from tissue and leucocyte extracts and from blood-culture bottles. The sequences obtained were unique and suggest that the microorganism is a new member of the genus Mycobacterium, for which we propose the name "Mycobacterium genavense". Disseminated infection with "M genavense" should be considered in the differential diagnosis of HIV-infected patients with extreme immunosuppression, wasting, and fever.

Acquired Immunodeficiency Syndrome↗

[Typing and sensitivity of meningococci isolated in Switzerland 1988-1990].

Since 1906 severe infections due to Neisseria meningitidis have been reported in Switzerland. The clinical application of antimicrobial agents reduced the mortality rate due to meningococcal infections from 82% before 1939 to 22% after 1942. However, the annual incidence remained at about 1.5 cases per 100,000 inhabitants. During the years 1988 to 1990, 177 strains isolated in Switzerland have been typed with a dot ELISA using 15 different monoclonal antibodies. The distribution of serogroups was as follows: A (0.6%), B (70.6%), C (22.6%), and W135 (0.6%), while 5.6% could not be assigned to a serogroup. The most common associations of serogroup, serotype and subtype were: B:15:P1.16 (15.3%), B:4:P1.15 (13.6%), and C:2a:P1.2 (9.0%). The susceptibility of 174 strains was determined by an agar-dilution procedure. All strains were susceptible to cefuroxime, ceftriaxone, ciprofloxacin, minocycline and spiramycin. One strain showed reduced sensitivity to penicillin (MIC = 0.25 mg/l), while another strain was resistant to rifampicin, 3% were resistant of erythromycin and 75% to sulfadiazine.

Drug Resistance, Microbial↗

Quantitation of human immunodeficiency virus provirus and circulating virus: relationship with immunologic parameters.

Virologic and seroimmunologic parameters were determined in 56 persons infected with human immunodeficiency virus (HIV). The provirus level varied from 10 to 100,000/10(6) CD4+ lymphocytes, and genomic HIV RNA was detectable in 39 of 56 patients at a relative concentration varying from 10 to greater than 250 copies/mL of serum. Provirus expressed as copies per 10(6) CD4+ lymphocytes and as circulating virus per milliliter of serum increased with disease progression and decrease of CD4+ cell concentration. The mean provirus concentration expressed per milliliter of blood varied little among categories of patients with various levels of CD4+ cells, but there was a progressive increase of circulating HIV genomic RNA. These virologic data suggest that during the course of HIV infection, an increasing proportion of the remaining CD4+ lymphocytes harbor the HIV genome and produce infectious virus. Finally, there was a marked correlation between increased provirus and genomic RNA concentration and three seroimmunologic markers: decrease in CD4+ cell count, p24 antigenemia, and disappearance of antibodies to HIV core antigen.

Base Sequence↗

Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome.

Among 504 cases of AIDS diagnosed between 1983 and 1990, there were 86 patients (17%) with toxoplasma encephalitis (TE). All were symptomatic at the time of diagnosis. General signs such as fever, neck stiffness, or headache were present in 87.2%, and 75.6% had focal signs. The primary means of diagnosis was computerized tomographic scanning, revealing 169 lesions of which 80% were immediately contrast-enhancing. All patients had IgG antibodies against Toxoplasma gondii either before (74 of 75 evaluable patients) or at the time of diagnosis of TE (73 of 75). Elevated antibody titers were present in 44% of evaluable patients, compared to 11% of patients with AIDS and other opportunistic infections. Initial treatment was pyrimethamine plus sulfonamides in 65 patients, and pyrimethamine plus clindamycin in 12 patients, with other combinations or no treatment accounting for the remainder. Life-table analysis of the time to discontinuation of treatment because of suspected side effects suggested that sulfadiazine was significantly more toxic, with 48% of patients experiencing an interruption in treatment after 30 days, than pyrimethamine (12%) or clindamycin (24%). The 30-day mortality rate was 12%, and median survival was 310 days after diagnosis, 530 in patients treated with zidovudine and 190 days in those not so treated. Of 82 evaluable patients, 16 relapsed once and 4 of these more than once. The risk of relapse was 27% 1 year after diagnosis of a first episode of TE.

Acquired Immunodeficiency Syndrome↗

Treatment for cerebral toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with AIDS. The Swiss HIV Cohort Study.

OBJECTIVE: To determine whether long-term maintenance treatment for toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Cohort study. SETTING: Switzerland. PATIENTS: A total of 453 patients with human immunodeficiency virus (HIV) entered the Swiss HIV Cohort Study. Ninety-nine patients with cerebral toxoplasmosis but no previous or simultaneous P. carinii pneumonia were compared with 240 patients with AIDS and other severe opportunistic infections (Centers for Disease Control [CDC] stage IVC1 infection other than toxoplasmosis and P. carinii pneumonia) as well as with 114 patients receiving inhaled pentamidine in a study of primary pneumocystis prophylaxis in patients infected with HIV. MEASUREMENTS: Life-table analysis for P. carinii-free survival. MAIN RESULTS: Six of 99 (6%) patients with toxoplasmosis, 50 of 240 (21%) patients with other severe opportunistic infections, and 8 of 114 (6%) patients receiving inhaled pentamidine developed P. carinii pneumonia. Life-table analysis showed that the incidence of pneumonia was substantially lower in patients with toxoplasmosis compared with that in patients with other severe opportunistic infections and was similar to the incidence in patients receiving pentamidine as prophylaxis. Analysis of the medication records from patients with toxoplasmosis showed that pyrimethamine and sulfonamides were administered 50% of the time; pyrimethamine and clindamycin, 25% of the time; and pyrimethamine alone, 9.9% of the time but that only one of the six patients with toxoplasmosis who developed P. carinii pneumonia received pyrimethamine and sulfonamides in the month before diagnosis. CONCLUSION: Patients with cerebral toxoplasmosis have a low risk for subsequently developing P. carinii pneumonia. This decreased risk is probably the result of chronic suppressive treatment with pyrimethamine and sulfonamides.

Acquired Immunodeficiency Syndrome↗

[Antiretroviral therapy in Switzerland 1991].

Zidovudine (azidothymidine, Retrovir) and ddI (di-deoxy-inosine, Videx) interfere with the multiplication of HIV by incorporation into nascent DNA chains and interruption of the further linking of nucleotides. Zidovudine lowers early mortality in patients with Aids and pneumocystis carinii pneumonia. However, much of the effectiveness of zidovudine is lost later on; the average prolongation of life in treated patients is estimated to be about 1 year. About two thirds of patients with Aids can be treated with zidovudine; in the others, the drug is ineffective or contraindicated. Frequent blood counts are necessary to monitor myelotoxicity, even at relatively low doses of 500 mg/day. In contrast, zidovudine is well tolerated by asymptomatic patients with 200 to 500 CD4 lymphocytes/mm3, in whom it diminishes the incidence of Aids from about 7 to 3% during the first year of treatment, with less than 2% severe anemia or leukopenia. For patients who do not tolerate zidovudine, ddI is an alternative. It is not myelotoxic but can cause neuritis and pancreatitis, especially at doses in excess of 10 mg/kg/day. Although its antiviral effect is excellent both in vitro and in vivo, there is still a lack of firm data on its clinical value, such as the decrease in opportunistic infections and increase in survival.

Acquired Immunodeficiency Syndrome↗