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Biomedical subjects

B Hirschel

Publications and source records attributed to B Hirschel.

At least 127 records · Page 7Linked to original sources
PubMed1995

Once-weekly administration of dapsone/pyrimethamine vs. aerosolized pentamidine as combined prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus-infected patients.

To evaluate combined prophylaxis for Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis, 533 patients with symptomatic human immunodeficiency virus infection and/or CD4 lymphocyte counts of < 200/microL were randomized to receive dapsone/pyrimethamine (200/75 mg once weekly) or aerosolized pentamidine (300 mg every 4 weeks). The median CD4 lymphocyte count was 110/microL; 47.5% were seropositive for toxoplasma antibodies. The median duration of follow-up was 483 days. In the intent-to-treat analysis, 12 cases of PCP and 14 of toxoplasmic encephalitis occurred in the dapsone/pyrimethamine group and 13 and 20 cases, respectively, in the aerosolized pentamidine group (adjusted relative risk for toxoplasmosis, 0.56; P = .10). However, only two of the 14 cases of toxoplasmic encephalitis in the dapsone/pyrimethamine group developed during actual treatment. The mortality among the two groups was similar. Dapsone/pyrimethamine was not tolerated by 30% of participants. A subanalysis of 240 matched, tolerant patients yielded a relative risk for toxoplasmosis of 0.21 (P = .014), a result favoring the use of dapsone/pyrimethamine. Dapsone/pyrimethamine was as effective as aerosolized pentamidine as prophylaxis for PCP and significantly reduced the incidence of toxoplasmic encephalitis among those participants who tolerated it.

AIDS-Related Opportunistic Infections↗
PubMed1995

Growth-deficient mycobacteria in patients with AIDS: diagnosis by analysis of DNA amplified from blood or tissue.

Amplification and sequencing of mycobacterial ribosomal RNA genes (16S rDNA) may permit the detection of growth-deficient species (i.e., those exhibiting no growth or those whose growth is delayed for more than 12 weeks). Of blood samples from 26 patients with AIDS and a liver sample from one additional AIDS patient, three samples (two of blood and the one of liver) were positive by polymerase chain reaction only; cultures of these three samples remained negative for more than 12 weeks. Analysis of amplified 16S rDNA from blood revealed a sequence characteristic of Mycobacterium genavense in the first case, in which one of many previous blood cultures had also been positive for M. genavense. The sequences found in the second and third cases were characteristic of Mycobacterium avium. The sample from the second patient was a liver biopsy specimen in which acid-fast bacilli were visualized; the culture of this specimen yielded M. avium after 7 months. The third sample was a blood sample from a patient in whom a relapse of treated M. avium infection was suspected. These results indicate that amplification and sequencing of mycobacterial 16S rDNA may permit early diagnosis and provide a rationale for treatment of infections due to growth-deficient mycobacteria.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Foscarnet decreases human immunodeficiency virus RNA.

Foscarnet inhibits human immunodeficiency virus (HIV) replication in vitro and decreases p24 antigenemia in patients with cytomegalovirus (CMV) retinitis. To evaluate the effect of foscarnet on HIV replication, HIV RNA was quantitated in 17 patients before and during foscarnet therapy. Fifteen patients had CMV retinitis, 1 had CMV encephalitis, and 1 had intractable zoster. A decrease in HIV RNA was observed in 16 of 17 patients. Before the introduction of foscarnet, mean HIV RNA was 5.82 +/- 0.24 log RNA/mL and, after a median of 13 days of therapy, mean HIV RNA was 5.30 +/- 0.27 log RNA/mL (P < .001). Among patients with detectable p24 antigen at baseline, a significant decrease was observed (P = .017). This decrease in HIV RNA demonstrates that foscarnet is a potent antiretroviral drug.

AIDS-Related Opportunistic Infections↗
PubMed1995

HIV-related non-Hodgkin's lymphoma among European AIDS patients. AIDS in Europe Study Group. AIDS in Europe Study Group.

The epidemiology of HIV associated non-Hodgkin's lymphoma (NHL) was investigated in 6550 European patients with AIDS. NHL was diagnosed in 3.5% of all patients at the time of the AIDS diagnosis. Although the probability of being diagnosed with NHL at AIDS diagnosis was significantly higher among intravenous drug users than among homosexual men, and was associated with increasing age, the observed incidences of NHL were more strikingly similar than any differences. The rate of developing NHL after a previous AIDS diagnosis was 2.4 per 100 patient years of follow-up, and remained constant during a 5-year follow-up period. While primary brain lymphomas comprised only 9% of NHL diagnosed at the time of AIDS, they comprised 38% of NHL diagnosed after AIDS (p < 0.001). The prognosis for patients with NHL at AIDS diagnosis was poor with a median survival of 5 months. A diagnosis of primary brain lymphoma was uniformly associated with a poor outcome. It is concluded that the probability of developing NHL in late stage HIV infection is lower than previously anticipated from the results of small studies on patients receiving long-term anti-retroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Cervical lymphadenitis caused by a fastidious mycobacterium closely related to Mycobacterium genavense in an apparently immunocompetent woman: diagnosis by culture-free microbiological methods.

Fastidious mycobacteria usually infect immunocompromised hosts (human immunodeficiency virus-infected or otherwise immunosuppressed patients). We here describe severe lymphadenitis, caused by a fastidious mycobacterium closely related to Mycobacterium genavense, in an apparently immunocompetent woman, whose brother had died from an unidentified mycobacterial infection in 1969. A variety of techniques, including inoculation of nude mice, histopathology, electron microscopy, lipid analysis, ATP measurements, and molecular biology, were used to characterize this mycobacterium. All attempts to culture the etiological agent on many different media failed. The organism multiplied only in congenitally athymic nude mice. Although phenotypically similar to M. genavense, the mycobacterium differs from M. genavense by three nucleotides of the 16S rRNA gene sequence. Various antimycobacterial drugs were administered, including gamma interferon, but multiple relapses occurred. Finally, therapy with a combined regimen of clarithromycin, clofazimine, rifabutin, and ethambutol was curative. To our knowledge, this is the first report of lymphadenitis in an apparently immunocompetent patient, caused by a noncultivable Mycobacterium sp. closely related to M. genavense. This study emphasizes the importance of employing a variety of diagnostic approaches such as the inoculation of laboratory animals, histopathology, electron microscopy, lipid analysis, ATP measurements, and molecular biology to characterize novel microorganisms that cannot be cultured in vitro.

Adenosine Triphosphate↗
PubMed1995

Response of HIV RNA to didanosine as a predictive marker of survival.

OBJECTIVE: To evaluate whether early changes in viraemia in response to didanosine (ddI) predict death and occurrence of new AIDS-defining events. METHODS: Forty-three patients were followed during ddI treatment with sequential determinations of serum viraemia, mutations associated with drug resistance, CD4 counts and clinical evaluation. Patients were stratified into two groups of equal size, responders and nonresponders, using the median of individual changes in viraemia 1 month after initiation of ddI therapy. RESULTS: After 1 month of ddI, mean viraemia decreased by 0.35 log RNA copies/ml of serum (P < 0.001) in the population. A significant difference in survival (median, 14 and 35 months in nonresponders and responders, respectively; log rank, P = 0.004) and in the delay to the occurrence of new AIDS-defining events (median, 8 and 33 months in nonresponders and responders, respectively; log rank, P = 0.018) was observed. After stratification for presence of AIDS before starting ddI, viraemia response at 1 month remained predictive of both overall and AIDS-defining event-free survival (log rank, P = 0.0006 and P = 0.01). After a similar stratification for initial CD4, viraemia response still predicted overall survival (log rank, P = 0.009), but its predictive value for AIDS-defining event-free survival did not reach statistical significance (P = 0.12). High initial levels of HIV RNA, presence of mutation 215 or previous duration of zidovudine therapy were not predictive of survival. CONCLUSIONS: In patients treated with ddI, changes in viraemia at 1 month predict survival independently of initial AIDS diagnosis and initial CD4 counts.

Acquired Immunodeficiency Syndrome↗
PubMed1994

A cohort study of drug users' compliance with zidovudine treatment.

OBJECTIVES: Determine whether patients who have acquired the human immunodeficiency virus through injecting drug use receive less antiviral medication (zidovudine) than comparable patients of other risk groups considering access to, acceptance of, and compliance with treatment. DESIGN: Historical cohort study. SETTING: Human immunodeficiency virus outpatient clinic. PATIENTS: Human immunodeficiency virus-infected subjects eligible for zidovudine treatment between January 1, 1989, and January 1, 1992, comparing injecting drug users (IDUs) with non-IDUs ("others"). MAIN OUTCOME MEASURES: Proposal, acceptance, start of, and compliance with zidovudine treatment. RESULTS: One hundred fifty-one IDUs and 162 other human immunodeficiency virus-positive subjects became eligible for zidovudine treatment between January 1, 1989, and January 1, 1992. Both groups were proposed zidovudine as often, but zidovudine treatment was refused by 14.9% of IDUs compared with 7.1% of others (P = .029). The IDUs needed considerably more time than other subjects to accept zidovudine therapy (median delay between indication and start of zidovudine treatment, 61 days vs 30 days, P = .0001). After accepting, IDUs were as compliant with treatment as others: 81.3% vs 83.2% were good compliers, and rises of mean corpuscular volume of erythrocytes after 3 and 6 months of treatment were similar in both groups. Former drug users and IDUs receiving methadone were started on zidovudine treatment more often and complied better with treatment than active drug users. Absence of housing and presence of psychiatric diagnosis (both more prevalent in IDUs) were associated with less zidovudine treatment and worse compliance. CONCLUSION: Injecting drug users tend to delay the start of zidovudine treatment. However, once they have started, their compliance is no worse than the compliance of patients from other risk groups. These results have important implications for clinical trials, medical care, and public health.

Adult↗
PubMed1994

[Diagnostic aspects and frequency of retrocorneal precipitates in diagnosis of cytomegalovirus retinitis in the HIV+ patient].

Cytomegalovirus retinitis (CMV) is the most common ocular opportunistic infection seen in patients with acquired immune deficiency syndrome. The anterior segment is usually quiet or with minimal aqueous humour flare and cell reaction. Nevertheless, in this prospective study of 30 eyes with CMV retinitis, 22 (73%) had white, small and filamentous keratic precipitates (KPS) which seem to corroborate this inflammation. The positivity of the KPS depends upon the extent of CMV retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Disseminated Mycobacterium genavense infection in two patients with AIDS.

Mycobacterium genavense is a recently defined fastidious organism that has been identified as a cause of disseminated infection in patients with AIDS. We report the cases of two patients who had advanced AIDS and a clinical syndrome of fever, anorexia, abdominal pain, diarrhea, and weight loss. In addition, splenomegaly and lymphadenopathy were prominent in both cases, and in one patient's case radiographic findings were suggestive of splenic abscesses. Mycobacteria isolated from specimens of blood and bone marrow grew in liquid media but not on solid media. The results of DNA probe tests for Mycobacterium tuberculosis and Mycobacterium avium complex were false-positive for both patients. After treatment of the broth cultures to lyse red blood cells, the results of DNA probe tests were negative for these pathogens. Amplification and sequencing of 16S rRNA with use of the polymerase chain reaction indicated that the mycobacterial isolates from both patients had sequences identical to those previously reported for M. genavense. One patient survived 5 months after diagnosis, the other 2 months after diagnosis; only one patient responded (transiently) to antimycobacterial chemotherapy.

AIDS-Related Opportunistic Infections↗
PubMed1994

Single-dose pharmacokinetics of oral fleroxacin in bacteremic patients.

Fleroxacin is a new broad-spectrum quinolone which can be given by the oral route. The present study was designed to assess the influence of bacteremia on the pharmacokinetics of a single oral dose of fleroxacin. Thirteen patients with proven bacteremia (one or more pairs of positive blood cultures, no hypotension) were given a single 400-mg fleroxacin dose orally on two occasions while also receiving standard antibiotic therapy. The first dose was administered 12 to 36 h after the last positive blood culture was drawn (day 1), and a second dose was administered 7 days later (day 7 +/- 2) to compare the pharmacokinetics between the acute and the convalescent phases of the disease. Following each administration of fleroxacin, serial plasma samples were collected for up to 72 h and were analyzed for unchanged drug by a reversed phase high-pressure liquid chromatography technique. There were no significant changes in the following pharmacokinetic parameters (mean standard deviation) the maximum concentration of drug in serum (6.4 +/- 1.5 versus 6.7 +/- 1.9 mg/liter), the minimum concentration of drug in serum, defined as the concentration of drug in serum at 24 h postdose (3.0 +/- 1.7 versus 2.5 +/- 1.2 mg/liter), the time to the maximum concentration of drug in serum (2.3 +/- 1.4 versus 2.0 +/- 1.2 h), and the elimination half-life (19.7 +/- 8.0 versus 17.9 +/- 6.9 h). Fleroxacin clearances were compared for each individual patient. A positive correlation (R2 = 0.787) was found between the values measured on day 1 and day 7. Oral clearance of fleroxacin (CL = CL/F, where F is bioavailability was slightly, but not significantly, reduced during the bacteremic phase (oral clearance, 43.8+/- 23.5 versus 48.5 +/- 17.5 ml/min.). When compared with previous results obtained in healthy young subjects, longer times to the maximum concentration of drug in serum and elimination half-lives and higher areas under the curve were observed. This could be due to the bacteremic state, the old age of the patients (mean, 66 years), and the low renal clearance (mean calculated creatinine clearance, 71.1 ml/min). A single oral dose of 400 mg of fleroxacin provides sufficient levels in serum to cover susceptible microorganisms for at least 24 h in bacteremic patients. Renal function appeared to be the key element that had to be taken into consideration to adapt fleroxacin dosage profiles in our patient population. Bacteremia itself appeared to amplify that phenomenon, but to a much lesser extent than renal function did.

Administration, Oral↗
PubMed1994

Chronic destructive lung disease associated with a novel mycobacterium.

A woman born in 1920 has suffered from a chronic destructive lung disease since 1972, with development of a severe combined restrictive and obstructive ventilatory defect. Large quantities of acid-fast microorganisms have been repeatedly observed in her sputum. Multiple courses of antimycobacterial treatment did not stop the progression of the disease. The mycobacterium involved was first identified as Mycobacterium gordonae, and later as Mycobacterium scrofulaceum. Analysis of part of the amplified gene of the 16S rRNA, however, revealed that its sequence differed from that of any established mycobacterial species, although it was observed once before in a German lymph node isolate, for which the name "Mycobacterium interjectum" has been proposed. Retrospective analysis confirmed the presence of this sequence in frozen samples which had been provided by the patient in 1983, 1985, 1989, 1990, and 1993. Our case confirms the value of amplification and sequencing of mycobacterial 16S rRNA for classifying mycobacteria, and suggests that "Mycobacterium interjectum" may be involved in cases of chronic destructive lung disease.

Aged↗
PubMed1994

[HIV infection--current possibilities in antiviral therapy].

Three drugs are currently available to treat HIV infection: zidovudine, didanosine, and zalcitabine. They resemble the natural nucleosides and inhibit retrotranscriptase, an enzyme which transforms HIV's genomic RNA into DNA. Indications for treatment are symptomatic HIV infection and, in asymptomatic patients, moderate immunodeficiency with a CD4-lymphocyte count below 350/mm3. In patients who have not yet received antiviral treatment, zidovudine remains the drug of choice, in spite of its toxicity for the bone marrow, which is particularly problematic in those with advanced immunodeficiency. Unfortunately, HIV develops resistance to zidovudine, and its efficacy wanes after a few months. When that happens, zidovudine may be replaced by didanosine, which is mainly toxic for the pancreas, or by zalcitabine, which causes peripheral neuropathy. A number of drugs are being developed. Among these, nonnucleoside retrotranscriptase inhibitors are well tolerated, but rapid development of resistance is problematic. Resistance seems less of a problem for inhibitors of the viral protease, but biodispensibility of these drugs is poor.

Antiviral Agents↗