Are we complying with NICE guidelines on the use of prostaglandin E2 for induction of labour? A survey of obstetric units in the UK.

To determine whether obstetric units in the UK comply with the recommendations by the National Institute for Clinical Excellence (NICE) on the maximum doses of intravaginal prostaglandin for induction of labour, a cross-sectional telephone survey of all obstetric units in the UK listed on Dr Foster's website was undertaken. The maximum doses recommended by NICE were exceeded by 86.4% (76/88) and 61.1% (55/90) of units that use intravaginal prostaglandin tablet and intravaginal prostaglandin gel, respectively. Units that use prostaglandin tablets were four times more likely to exceed the recommended maximum dose (OR = 4.03, 95% CI, 1.9 - 8.4), six times more likely to use 50% or more of the recommended maximum dose for nulliparous women (OR = 5.9, 95% CI, 3.1 - 11.0), and six times more likely to use 50% or more of the recommended maximum dose for multiparous women (OR = 6.5, 95% CI, 3.0 - 13.9). A majority of obstetric units in the UK exceed the maximum doses of intravaginal prostaglandin recommended by NICE for induction of labour.     

Atenolol and eprosartan: differential effects on central blood pressure and aortic pulse wave velocity

BACKGROUND: Recent data suggest that atenolol may be inferior to other antihypertensive drugs in reducing cardiovascular risk in older individuals with hypertension, despite lowering peripheral blood pressure (BP). We hypothesized that that atenolol fails to reduce central BP as much as other agents. The aim of the present study was to compare the hemodynamic effects of atenolol and eprosartan in a double-blind, randomized, cross-over study. METHODS: After a 2-week placebo run-in, 21 subjects with never-treated hypertension underwent 6 weeks of therapy with atenolol (50 mg) and eprosartan (600 mg). Central BP and augmentation index were assessed using pulse wave analysis, and aortic pulse wave velocity was measured, at baseline and at the end of each treatment. RESULTS: Both drugs reduced peripheral BP to the same degree. However, there was a significantly greater reduction in central systolic BP with eprosartan (means +/- SEM: 16 +/- 3 v 11 +/- 2 mm Hg; P = .03). Despite identical reductions in mean pressure, atenolol reduced aortic pulse wave velocity more than eprosartan (0.8 +/- 0.1 v 0.5 +/- 0.1 m/sec; P = .005). Conversely, augmentation index and N-terminal pro-brain natiuretic peptide levels were reduced significantly after eprosartan (6% +/- 2% and 11 +/- 5 pg/mL, respectively) but were increased after atenolol (7% +/- 2% and 67 +/- 24 pg/mL, respectively). CONCLUSIONS: These data indicate that despite similar effects on peripheral BP and a greater effect on aortic stiffness, atenolol had less impact on central systolic BP than eprosartan because it failed to reduce wave reflection. This provides one potential explanation for the failure of atenolol to improve outcome in older patients with essential hypertension.     

Developing and validating a new nomogram for diagnosing bladder outlet obstruction in women

Objective

To develop and validate a nomogram for assessing bladder outlet obstruction (BOO) in women derived from concurrent P_det.Qmax and Q_max based on radiographic evidence of increased urethral resistance.

Patients and Methods

Retrospective analysis of prospectively acquired video‐urodynamics and clinical data of 185 women (development cohort) was performed. The P_det.Qmax were plotted against Q_max and cluster analysis was performed to determine an axis that best divided the definitively obstructed and unobstructed. Using data from a further 350 women (validation cohort), the sensitivity and specificity of the derived criterion was calculated. Finally, the data from both groups was pooled together and using binary logistic regression analysis, a nomogram was produced.

Results

Of the 535 patients in the two cohorts, (122 [22.8%]) demonstrated radiographic evidence of BOO. Cluster analysis identified the axis that best separates the radiographically obstructed and unobstructed as P_det.Qmax = 2*Q_max. Using the data from the validation cohort, the sensitivity and specificity for this was calculated as 0.94 and 0.93, respectively. A nomogram, representing the probability of BOO for concurrent P_det.Qmax and Q_max measurements was derived by pooling data from both cohorts. Alternatively, a female BOO index (BOOIf) may be calculated mathematically using the formula BOOIf = P_det.Qmax ? 2.2*Q_{max, that is,} BOOIf < 0, <10% probability of obstruction, BOOIf > 5 likely obstructed (50%) and If BOOIf > 18, obstruction almost certain (>90%).

Conclusion

A female BOO nomogram (the SG nomogram) with high sensitivity and specificity is proposed. The nomogram can be used to stratify the degree of BOO or assess response to treatment.     

SULT1C3, an orphan sequence of the human genome,encodes an enzyme activating various promutagens

The human genome contains a sequence that is homologous to genes encoding soluble sulphotransferases (SULTs) based on the nucleotide sequence and possible intron/exon splice sites. The putative coding sequence (termed SULT1C3) was synthesized and integrated into a bacterial expression vector. We used the cDNA-expressed protein for raising an antiserum and studying enzyme activities. No activity was detected with 4-nitrophenol and 1-naphthol, known substrates of all other members of the human SULT1 subfamily. The activity was also negligible with paracetamol, ethanol, 5-hydroxymethylfurfural, 2-hydroxymethylpyrene, 2-(α-hydroxy)ethylpyrene, and corticosterone, compounds for which we have developed sensitive enzyme assays with direct determination of the product by HPLC-UV, HPLC-fluorescence or HPLC-MS/MS. Since diverse sulpho conjugates are chemically reactive – often short-lived and mutagenic – we expressed SULT1C3 in Ames’ Salmonella typhimurium strains TA1538 and TA100, as we had done with many other SULTs previously. The expression level of SULT1C3 protein amounted to 2% of the total cytosolic proteins, which is in the middle range of other SULTs expressed in this model. Using recombinant bacterial tester strains in mutagenicity assays, we observed SULT1C3-mediated activation of several large benzylic alcohols derived from alkylated polycyclic hydrocarbons: 1-hydroxymethylpyrene, both enantiomers of 1-(α-hydroxy)ethylpyrene, 6-hydroxymethylbenzo[a]pyrene and 6-hydroxymethylanthanthrene. 1′-Hydroxysafrole was the smallest molecule activated by SULT1C3 up to date. Our study demonstrates that SULT1C3 has sulphotransferase activity and that it prefers relatively large substrates. The substrates detected were activated to mutagens, which cannot be the regular function of the enzyme. The physiological substrates remain to be identified. Probably, they are relatively large, endogenous or common exogenous, molecules.     

A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine.

BACKGROUND: A previous pilot study of open-label mirtazapine augmentation conducted by the authors in 20 depressed patients yielded a 55% response rate at week 4. A double-blind controlled trial was undertaken to further elucidate the efficacy of this intervention. METHODS: 26 adult outpatients with persistent major depression despite adequate antidepressant monotherapy were randomized to receive 4 weeks of mirtazapine or placebo augmentation. Mirtazapine was begun at 15 mg at bedtime, with possible titration to 30 mg at bedtime per physician's discretion after week 1. RESULTS: Categorical positive response rate at end point was 64% for active drug and 20% for placebo. Remission rates were 45.4% and 13.3% for active drug and placebo groups, respectively, Mirtazapine demonstrated statistically significant superiority to placebo on most major outcome measures, and was associated with improvement in overall functioning and quality of life. There were no significant group differences with regard to emergent side effects, weight change, or serum concentrations of primary antidepressants. CONCLUSIONS: Mirtazapine appears safe and effective for short-term antidepressant augmentation.     

Large Congenital Melanotic Nevi in an Extremity with Neurocutaneous Melanocytosis

Abstract:   A 14-day-old boy presented with a large congenital melanocytic nevus over his left thigh with approximately 17 satellite nevi distributed over the rest of his skin surface. Six weeks later, he developed generalized tonic–clonic seizures and additional satellite nevi became apparent ( n  > 20). A subsequent brain magnetic resonance imaging demonstrated right temporal T1 hyperintense signal abnormality. At 4 months of age the patient underwent a lumbar puncture that was normal without evidence of melanocytes or tumor. Nevertheless, a few days later he underwent resection of his right medial temporal lesion which demonstrated melanocytosis in the temporal lobe as well as melanocytosis in subependymal areas in other parts of the brain and ventricles, confirming the suspected diagnosis of neurocutaneous melanocytosis. Our case supports previous studies that conclude that the number of satellite nevi is a greater predictor of neurocutaneous melanocytosis than is the location of large congenital melanocytic nevus. In our case, cerebrospinal fluid studies were not reliable even in the face of florid neurocutaneous melanocytosis involving the leptomeninges and ventricles.