A combination of misoprostol and estradiol for preoperative cervical ripening in postmenopausal women: a randomised controlled trial

Objective  To compare the impact of 1000 μg of self-administered vaginal misoprostol versus self-administered vaginal placebo on preoperative cervical ripening after 2 weeks of pretreatment with estradiol vaginal tablets in postmenopausal women prior to day-care operative hysteroscopy.
Design  Randomised, double-blind, placebo-controlled sequential trial.
Setting  Norwegian university teaching hospital.
Population  Sixty-seven postmenopausal women referred for day-care operative hysteroscopy.
Methods  The women were randomised to receive either 1000 μg of self-administered vaginal misoprostol or self-administered vaginal placebo on the evening before day-care operative hysteroscopy. All women had administered a 25-μg vaginal estradiol tablet daily for 14 days prior to the operation.
Main outcome measures  Primary outcome: preoperative cervical dilatation at hysteroscopy. Secondary outcomes: difference in dilatation at recruitment and before hysteroscopy, number of women who achieved a preoperative cervical dilatation of 5 mm or more, acceptability, complications and adverse effects.
Results  The mean cervical dilatation was 5.7 mm (SD, 1.6 mm) in the misoprostol group and 4.7 mm (SD, 1.5 mm) in the placebo group, the mean difference in cervical dilatation being 1.0 mm (95% CI, 0.2–1.7 mm). Self-administered vaginal misoprostol of 1000 μg at home on the evening before day-care hysteroscopy is safe and highly acceptable, although a small proportion of women experienced lower abdominal pain.
Conclusions  One thousand micrograms of self-administered vaginal misoprostol, 12 hours prior to day-care hysteroscopy, after 14 days of pretreatment with vaginal estradiol, has a significant cervical ripening effect compared with placebo in postmenopausal women.     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.      

Diuretic drugs

This group of drugs is commonly used to treat oedema in conditions ranging from congestive heart failure to raised intracranial pressure, where the aim is to increase urine output and the amount of sodium and other electrolytes excreted in urine. Carol McLoughlin looks at the indications for administering diuretics, describes their modes of action and the possible side-effects.     

Ethics roundtable debate: Child with severe brain damage and an underlying brain tumour

A young person presents with a highly malignant brain tumour with hemiparesis and limited prognosis after resection. She then suffers an iatrogenic cardiac and respiratory arrest that results in profound anoxic encephalopathy. A difference in opinion between the treatment team and the parent is based on a question of futile therapy. Opinions from five intensivists from around the world explore the differences in ethical and legal issues. A Physician-ethicist comments on the various approaches.     

A novel family of hydroxamate-based acylating inhibitors of cyclooxygenase

Aspirin irreversibly inhibits cyclooxygenase (COX) by acetylating a serine residue in the active site. We synthesized a series of novel acylating agents based on our previously reported acetylating compound, O-acetylsalicylhydroxamic acid. One of these, triacetylsalicylhydroxamic acid (TriAcSHA) was more effective than aspirin and O-acetylsalicylhydroxamic acid in inactivating both COX-1 and COX-2. Preincubation of COX-1 with inhibitor for 5 min yielded IC(50) values of 18 microM for TriAcSHA and 60 microM for acetylsalicylic acid. Inhibition was time-dependent, with complete inhibition within 10 min at a concentration of 50 microM. As with aspirin, mutation of the serine 530 of COX-1 to alanine abolished the activity of the TriAcSHA. Mutation of the alanine 119 to a glutamine markedly reduced the sensitivity to TriAcSHA, suggesting that this residue was necessary for the interaction with the enzyme. TriAcSHA was also more effective than aspirin as an inhibitor of platelet aggregation induced by arachidonic acid. The diacetylated phenylhydroxamates N-methyl-O,O-diacetylsalicylhydroxamic acid, N,O-diacetylbenzohydroxamic acid, and 2-methyl-O,N-diacetylbenzohydroxamic acid showed reduced or absent activity against COX-1. In addition, we synthesized a series of triacylsalicylhydroxamic acids with progressively longer acyl groups (three to six carbons). All of the compounds inhibited COX-1 and demonstrated progressively greater COX-1 selectivity with increasing number of carbons. Hence, salicylhydroxamic acid provides a versatile backbone for the generation of a family of acylating inhibitors of cyclooxygenase.     

Effects of positive and negative pressure ventilation on cerebral blood volume of newborn infants

The effects of intermittent positive airway and continuous negative extrathoracic pressure ventilation on cerebral blood volume in preterm infants were studied using near infrared spectroscopy. In 12 infants continuous negative extrathoracic pressure caused a median decrease in cerebral blood volume of 0.14ml/100ml brain (95% confidence intervals (CI) 0.035–0.280) compared with no respiratory support. Oxygenated and deoxygenated haemoglobin also decreased, implying increased venous drainage as the main effect. In 17 infants intermittent positive pressure ventilation also caused a median reduction in cerebral blood volume of 0.06 ml/100 ml brain (95% CI 0.010–0.115) compared with endotracheal positive airway pressure. Deoxygenated haemoglobin increased by 0.07 ml/100 ml brain (95% CI 0.010–0.100) while oxygenated haemoglobin decreased by O.lOml/lOOml brain (95% CI 0.005–0.175). The increase in deoxygenated haemoglobin implies decreased venous drainage and the decrease in oxygenated haemoglobin implies that other factors may also be significant. Heart rate, blood pressure and oxygen saturation were monitored continuously and remained stable.