Recommendations to achieve rapid therapeutic teicoplanin plasma concentrations in adult hospitalised patients treated for sepsis.

The optimum teicoplanin loading dose and duration of therapy required for rapid attainment of a therapeutic trough plasma concentration (C(min)) (> or = 10mg/L for serious Gram-positive infections and > or = 20mg/L for deep-seated infections) are not known. In this open-label, multicentre, observational study, teicoplanin levels were determined following administration of loading doses of 6 mg/kg every 12h on Day 1 followed by 6 mg/kg once or twice daily to hospitalised patients with suspected or diagnosed Gram-positive infections. C(min) levels for the first 4 days of treatment were collected 15min prior to drug administration. Levels were determined with an Abbott TDx/FLx Analyzer and Seradyn Teicoplanin Innofluor Assay Kit. The two target trough values (> or = 10mg/L and > or = 20mg/L) were only achieved by Day 4 in the once-daily group (n=34; mean 9.55 mg/L, 95% confidence interval (CI) 8.17-10.94 mg/L) and in the twice-daily group (n=40; mean 21.8 mg/L, 95% CI 17.21-26.39 mg/L), respectively. However, the mean C(min) in the twice-daily group was > or = 10mg/L (11.03 mg/L) by Day 2. To achieve rapid therapeutic C(min) concentrations targeted for the majority of serious Gram-positive infections, we recommend teicoplanin loading doses of 6 mg/kg every 12h for 48h followed by once-daily for infections other than infective endocarditis, septic arthritis and osteomyelitis. Regarding the latter infections, higher loading doses might be warranted to reach rapid steady-state concentrations.

Suicide attempts or threats by children and adolescents in Johannesburg.

Current literature on suicide attempts by children and adolescents is reviewed. The records of children and adolescents in the 10-15-year age group who were referred to a child psychiatric unit over the 6-year period 1 January 1977-31 December 1982 were analysed. The results are presented and discussed. Suicide attempts or threats together constituted an average of 10% of the psychiatric referrals in this age group, the figure for 1982 being substantially increased. The peak incidence was among 13-year-olds for both boys and girls. The female: male referral ratio was 2:1. Drug overdosage was the most common method, the commonly employed drugs being analgesics and benzodiazepines. In about 30% of both the boys and girls referred because of taking an overdose, a multiple-drug overdose had been used. Methods other than this were used three times more frequently by boys than by girls. Major predisposing and antecedent factors were family stress (especially divorce), psychiatric illness in the patient or a family member, and school problems. Some 30% had previously made suicide attempts or threats, and at least 7% made further serious suicide attempts after initial treatment. These results suggest a need for further investigations into factors relating to suicide attempts or threats in children and adolescents and their subsequent management.

Activities of some enzymes of pyrimidine and DNA synthesis in a rat transplantable hepatoma and human primary hepatomas, in cell lines derived from these tissues, and in human fetal liver.

Activites of the enzymes DNA polymerase, thymidine kinase, thymidylate kinase, thymidylate synthase, and deoxycytidylate deaminase have been measured in rat and human normal and neoplastic liver, in human fetal liver, and in cell lines derived from human hepatomas and rat transplantable hepatomas. The activities of these enzymes were increased in rat transplantable hepatomas, relative to rat normal or host liver, to a degree corresponding to the rapid growth rate of these tumors. With the exception of thymidine kinase, which did not change, the activities of these enzymes increased in human hepatomas relative to the corresponding host liver (apparently normal liver tissue from the same patient) and to human normal liver. The increases in enzyme activity observed in human hepatomas were small in comparison with those found in the rapidly growing rat hepatomas. The activities of deoxycytidylate deaminase in both human and rat liver tissues were 2 to 3 orders of magnitude higher than those of the other enzymes assayed. Activities of the enzymes of DNA synthesis in a slow-growing cell line derived from a human hepatoma were similar to those in human hepatoma tissues. In the case of rapidly growing cell lines derived from rat and human hepatomas, enzyme activities were higher than those in the corresponding tissues.