RESUMEN
This study sought to better characterize the natural history of AIDS-associated disseminated Mycobacterium avium complex (MAC) infection. Towards that end two retrospective studies were done: a case-control survival study and a MAC respiratory colonization study. Among 137 consecutive patients who had a sterile body site cultured for mycobacteria within 3 months of their first AIDS-defining episode of Pneumocystis carinii pneumonia, median survival was significantly shorter in those with disseminated MAC infection (107 days; 95% confidence interval [CI] 55-179) than those with negative cultures (275 days; 95% CI 230-318; P less than .01), even after controlling for age, absolute lymphocyte count, and hemoglobin concentration. Among 34 patients with AIDS and respiratory MAC colonization, 22 later developed disseminated infection (65% predictive value for subsequent MAC dissemination). Disseminated MAC infection was associated with significantly shorter survival for patients with AIDS, and the presence of MAC in respiratory specimens has substantial predictive value for subsequent disseminated infection.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Infección por Mycobacterium avium-intracellulare/complicaciones , Adulto , Linfocitos T CD4-Positivos , Estudios de Casos y Controles , Humanos , Recuento de Leucocitos , Complejo Mycobacterium avium/aislamiento & purificación , Neumonía por Pneumocystis/complicaciones , Valor Predictivo de las Pruebas , Sistema Respiratorio/microbiología , Estudios RetrospectivosRESUMEN
We studied the natural history of herpes simplex virus (HSV) infection and its association with specific serum antibody in a sample of 68 HIV-infected patients with a first episode of Pneumocystis carinii pneumonia at San Francisco General Hospital in 1986. Seroprevalence was 66 and 77% for HSV-1 and HSV-2 antibody, respectively, by immunoblot assay. Twenty-seven patients had 45 HSV outbreaks diagnosed during 739 patient-months of follow-up. Median frequency of recurrence resulting in a medical visit was once every 6.5 months, and median duration of treated outbreak was 10 days. Fourteen of 48 evaluable patients seropositive for HSV-2 had no outbreak of HSV during a median follow-up of 7.5 months. Our data suggests that neither frequency nor severity of HSV were substantially increased in this group of patients, despite severe immunosuppression caused by HIV. However, validation of these results by a prospective study is required.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Anticuerpos Antivirales/sangre , Herpes Simple/complicaciones , Neumonía por Pneumocystis/complicaciones , Simplexvirus/inmunología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Aciclovir/uso terapéutico , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , VIH-1 , VIH-2 , Herpes Simple/inmunología , Humanos , Immunoblotting , Masculino , Prevalencia , RecurrenciaRESUMEN
Mutagenesis and cytotoxicity were studied in Escherichia coli by iproplatin and carboplatin, two analogs of cisplatin (CDDP) currently undergoing clinical trial. As with CDDP, mutagenesis by these agents was mediated by the umuDC gene product. In contrast to CDDP, however, mismatch repair did not substantially contribute to survival of cells after exposure to these agents since dam-3 E. coli were not more sensitive than wild type E. coli. UvrA- E. coli, however were more sensitive to these analogs demonstrating that as with CDDP, uvr endonuclease-mediated excision contributes to the repair of DNA damage induced by platinum compounds.
Asunto(s)
Antineoplásicos/farmacología , Reparación del ADN/efectos de los fármacos , Escherichia coli/genética , Mutágenos , Mutación , Compuestos Organoplatinos/farmacología , Carboplatino , Escherichia coli/efectos de los fármacos , Genes Bacterianos/efectos de los fármacos , Pruebas de Mutagenicidad , Relación Estructura-ActividadRESUMEN
Because cytotoxicity by an alkylating agent such as N-methyl-N'-nitrosoguanidine is markedly increased in adenine methylase-deficient dam-3 Escherichia coli, it was of interest to assess whether mismatch repair was similarly important in the repair of DNA damage induced by cis-diamminedichloroplatinum(II) (CDDP). The results demonstrate that after exposure to 5-40 microM CDDP, dam-3 E. coli are 2-15-fold more sensitive to the cytotoxic effects of this agent. Further, dam-3 mutL451 E. coli deficient in mismatch repair was as resistant as wild type. trans-Diamminedichloroplatinum(II) treatment did not cause marked increments in cytotoxicity in dam-3 E. coli compared to wild type. The rate of excision of platinum was significantly reduced in dam-3 E. coli compared to wild type, demonstrating that differences in the repair of CDDP-induced DNA damage underlie enhanced cytotoxicity by this agent. Lastly, mutagenesis by CDDP was abrogated in umuDC- E. coli, showing that this gene product mediates mutagenesis by this agent.