Device-associated infections in a paediatric intensive care unit in Pakistan.

This study assessed the effect of implementation of active infection control and surveillance on the occurrence of device-associated infections (DAIs) in a paediatric intensive care unit (PICU) from 2012 to 2015. There were 1378 patients, equating to 4632 patient-days, on the PICU, and 29 DAI episodes, giving an incidence rate of 2.1% and an incidence density rate of 6.26 per 1000 patient-days. The rates of central-line-associated bloodstream infections, ventilator-associated pneumonia and catheter-related urinary tract infections were 7/1000 central-line-days, 1.17/1000 ventilator-days and 0.24/1000 urinary-catheter-days, respectively. Despite the overall low rate of DAIs in the PICU, there was a relatively high rate of central-line-associated bloodstream infections.

A randomised controlled trial of the closure or non-closure of peritoneum at caesarean section: effect on post-operative pain.

OBJECTIVE: To compare the analgesic requirement in the post-operative period after closure or non-closure of the peritoneum at the caesarean delivery with a standardised anaesthetic and surgical technique. DESIGN: A randomised double-blind controlled trial was performed on 100 women who underwent elective caesarean delivery. MAIN OUTCOME MEASURES: Analgesic requirement assessed by morphine usage via patient controlled analgesia pump over the first 24-hour period after surgery, oral analgesia used during the first four days, postoperative pain assessed by a visual analogue scale and a verbal rating scale, and patient satisfaction assessed by verbal rating scale were the main outcome measures. RESULTS: Pain scores at 24 hours were similar in both groups (43.5 in closure and 40.5 in non-closure) but during the first 24 hours the non-closure group had used significantly less morphine than the closure group (0.64 mg/kg of body weight vs 0.82 mg/kg, P = 0.04). The patients in non-closure group had significantly higher satisfaction scores after 24 hours than the closure group. CONCLUSION: Non-closure of both visceral and parietal peritoneum at the caesarean section produces a significant reduction in the post-operative use of patient controlled analgesia pump morphine and significantly higher patient satisfaction at 24 hours post-operatively.

Ligand-mediated induction of thymidylate synthase occurs by enzyme stabilization. Implications for autoregulation of translation.

Thymidylate synthase (TS) is indispensable in the de novo synthesis of dTMP. As such, it has been an important target at which anti-neoplastic drugs are directed. The fluoropyrimidines 5-fluorouracil and 5-fluoro-2'-deoxyuridine are cytotoxic as a consequence of inhibition of TS by the metabolite 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP). This inhibition occurs through formation of a stable ternary complex among the enzyme, the nucleotide analog, and the co-substrate N5, N10-methylenetetrahydrofolate. Numerous studies have shown that cellular concentrations of TS undergo about a 2-4-fold induction following treatment with TS inhibitors. An extensive body of in vitro studies has led to the proposal that this induction occurs because of relief of the translational repression brought on by the binding of TS to its own mRNA. In the current study, we have tested several predictions of this autoregulatory translation model. In contrast to expectations, we find that fluoropyrimidines do not cause a change in the extent of ribosome binding to TS mRNA. Furthermore, mutations within the mRNA that abolish its ability to bind TS have no effect on the induction. Finally, enzyme turnover measurements show that the induction is associated with an increase in the stability of the TS polypeptide. Our results, in total, indicate that enzyme stabilization, rather than translational derepression, is the primary mechanism of TS induction by fluoropyrimidines and call into question the general applicability of the autoregulatory translation model.