Cyclosporin A (CsA; 50 mg/kg) and Fujimycine (FK506; 5 mg/kg), but not the related macrolide immunosuppressant rapamycin (5 mg/kg), caused a reduction of glomerular filtration rate, degenerative changes of proximal tubular epithelium, and hypertrophy of the juxtaglomerular apparatus in male Wistar rats when given for 10 days. The molecular mechanisms of CsA and FK506 toxicity were investigated. Cyclophilin A and FK506-binding protein, the main intracytoplasmic receptors for CsA and FK506, respectively, were each detected in renal tissue extract. In the kidney, high levels of immunoreactive and enzymatically active calcineurin were found which were inhibited by the immunosuppressants CsA and FK506, but not by rapamycin. Finally, specific immunophilin-drug-calcineurin complexes formed only in the presence of CsA and FK506, but not rapamycin. These results suggest that the nephrotoxic effects of CsA and FK506 is likely mediated through binding to renal immunophilin and inhibiting calcineurin phosphatase.

Animals↗

PubMedDate not supplied

Cimetidine for prophylaxis of aspiration pneumonitis: comparison of intramuscular and oral dosage schedules.

Explore the source record for details and available documents.

Administration, Oral↗

PubMedDate not supplied

Prognostic factors for tumour response and skin damage to combined radiotherapy and hyperthermia in superficial recurrent breast carcinomas.

Prognostic factors for complete tumour response and acute skin damage to combined hyperthermia and radiotherapy were analysed in material of patients with breast cancer, recurrent in previously irradiated areas. Radiotherapy was given daily to a total absorbed dose of 30.0 Gy in 2 weeks or 34.5 Gy in 3 weeks. The first radiotherapy schedule was combined with heat twice weekly, a total of four heat treatments (schedule A). The second radiotherapy schedule was combined with heat either once or twice a week resulting in a total of three (schedule B) or six (schedule C) heat treatments. Heat was induced with microwaves (2450, 915 or 434 MHz) via external applicators and always given after the radiotherapy fraction. The complete response (CR) rate in evaluable patients was 71% (49/69). There was no significant difference in CR rate between the three different hyperthermia schedules. The CR rates were 74% (14/19), 65% (15/23) and 74% (20/27) for schedules A, B and C respectively. The only factor predicting CR, evaluated both uni- and multivariately, was the CRE-value for the present radiotherapy dose (p = 0.02). If only tumours treated with 915 MHz were taken into account, however, then the highest minimum temperature at a given heat session predicted complete response (p = 0.03). This was true also in a multivariate analysis of this subgroup of tumours. A Kaplan-Meier analysis (log rank test) showed no significant difference in duration of CR between the different treatment schedules. Cox's proportional hazards method revealed three significant factors: tumour size (negatively correlated, p = 0.007), the time interval between the diagnosis of the primary tumour and the present treatment (p = 0.02) and the average temperature (0.03). Maximum acute skin reactions in the treatment field were scored according to an ordinal scale of 0-8, modified after WHO 1979. Twenty-six treatment areas (32%) expressed more severe skin damage (score > or = 5) in terms of desquamation with blisters (14%) and necrosis or ulceration (19%). Factors correlated with skin damage were the size of the lesion area (p = 0.011), the highest average maximum temperature during a given heat session (p = 0.03) and the fractionation schedule of hyperthermia (p = 0.05). The extent of previous radiotherapy absorbed dose, previous surgery in the treated area or previous chemotherapy had no significant influence on the acute skin reactions.

Adult↗

PubMedDate not supplied

Cancer risk associated with simian virus 40 contaminated polio vaccine.

BACKGROUND: The presence of SV40 in monkey cell cultures used in the preparation of the polio vaccine from 1955 through 1961 is well documented. Investigations have consistently demonstrated the oncogenic behavior of SV40 in animal models. Early epidemiologic studies were inadequate in demonstrating an increase in cancer incidence associated with contaminated vaccine. Recently, investigators have provided persuasive evidence that SV40 is present in human ependymomas, choroid plexus tumors, bone tumors, and mesotheliomas, however, the etiologic role of the virus in tumorigenesis has not been established. MATERIALS AND METHODS: Using data from SEER, we analyzed the incidence of brain tumors, bone tumors, and mesotheliomas from 1973-1993 and the possible relationship of these tumors with the administration of the SV40 contaminated vaccine. RESULTS: Our analysis indicates increased rates of ependymomas (37%), osteogenic sarcomas (26%), other bone tumors (34%) and mesothelioma (90%) among those in the exposed as compared to the unexposed birth cohort. CONCLUSIONS: These data suggest that there may be an increased incidence of certain cancers among the 98 million persons exposed to contaminated polio vaccine in the U.S.; further investigations are clearly justified.

Age Factors↗