Could a simple antenatal package combining micronutritional supplementation with presumptive treatment of infection prevent maternal deaths in sub-Saharan Africa?

Background

For women who have a caesarean section in their preceding pregnancy, two care policies for birth are considered standard: planned vaginal birth and planned elective repeat caesarean. Currently available information about the benefits and harms of both forms of care are derived from retrospective and prospective cohort studies. There have been no randomised trials, and recognising the deficiencies in the literature, there have been calls for methodologically rigorous studies to assess maternal and infant health outcomes associated with both care policies. The aims of our study are to assess in women with a previous caesarean birth, who are eligible in the subsequent pregnancy for a vaginal birth, whether a policy of planned vaginal birth after caesarean compared with a policy of planned repeat caesarean affects the risk of serious complications for the woman and her infant.

Methods/Design

Design: Multicentred patient preference study and a randomised clinical trial. Inclusion Criteria: Women with a single prior caesarean presenting in their next pregnancy with a single, live fetus in cephalic presentation, who have reached 37 weeks gestation, and who do not have a contraindication to a planned VBAC. Trial Entry & Randomisation: Eligible women will be given an information sheet during pregnancy, and will be recruited to the study from 37 weeks gestation after an obstetrician has confirmed eligibility for a planned vaginal birth. Written informed consent will be obtained. Women who consent to the patient preference study will be allocated their preference for either planned VBAC or planned, elective repeat caesarean. Women who consent to the randomised trial will be randomly allocated to either the planned vaginal birth after caesarean or planned elective repeat caesarean group. Treatment Groups: Women in the planned vaginal birth group will await spontaneous onset of labour whilst appropriate. Women in the elective repeat caesarean group will have this scheduled for between 38 and 40 weeks. Primary Study Outcome: Serious adverse infant outcome (death or serious morbidity). Sample Size: 2314 women in the patient preference study to show a difference in adverse neonatal outcome from 1.6% to 3.6% (p = 0.05, 80% power).

Clinical Trial Registration

ISCTRN5397431     

Outcome of frozen embryo replacement cycles following elective cryopreservation of all embryos in women at risk of developing ovarian hyperstimulation syndrome

Aim: Our aim was to compare the outcome in subsequent frozen embryo replacement cycles in four groups of patients who had elective cryopreservation of all their embryos because they were considered to be at increased risk of developing severe ovarian hyperstimulation syndrome. Design: Sixty-two (91%) of 68 IVF cycles (68 patients) in which elective cryopreservation of all embryos was performed were analyzed. All patients continued on the GnRH agonist, buserelin, after oocyte recovery until the onset of vaginal bleeding. Frozen embryo replacement occurred in a hormone replacement cycle that started either on day 3 of the withdrawal bleed (group I;N=15) or after serum estradiol levels had fallen to <100 pmol/L (group II;N=16). The other patients commenced a frozen embryo replacement cycle several months later in either a hormone replacement (group III;N=15) or a natural (group IV;N=16) cycle. Results: Two patients developed severe ovarian hyperstimulation syndrome. There were no significant differences among the four groups regarding demographic variables, the dose of hMG used, and the clinical outcome. There was a higher but not significantly different clinical pregnancy rate in group I (26.7%), compared to group II (12.5%), group III (13.3%), and group IV (18.8%). Conclusions: Several options exist for the timing and protocol used for frozen embryo replacement in patients who had elective cryopreservation for the prevention of ovarian hyperstimulation syndrome, none of which was found to be clearly superior in this observational report.Presented at the 1994 Annual Conference of the American Fertility Society.     

Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19

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Otoconin-90, the mammalian otoconial matrix protein, contains two domains of homology to secretory phospholipase A2

The ability to sense orientation relative to gravity requires dense particles, called otoconia, which are localized in the vestibular macular organs. In mammals, otoconia are composed of proteins (otoconins) and calcium carbonate crystals in a calcite lattice. Little is known about the mechanisms that regulate otoconial biosynthesis. To begin to elucidate these mechanisms, we have partially sequenced and cloned the major protein component of murine otoconia, otoconin-90 (OC90). The amino acid sequence identified an orphan chimeric human cDNA. Because of its similarity to secretory phospholipase A₂ (sPLA₂), this gene was referred to as PLA₂-like (PLA2L) and enabled the identification of human Oc90. Partial murine cDNA and genomic clones were isolated and shown to be specifically expressed in the developing mouse otocyst. The mature mouse OC90 is composed of 453 residues and contains two domains homologous to sPLA₂. The cloning of Oc90 will allow an examination of the role of this protein in otoconial biosynthesis and in diseases that affect the vestibular system.     

Influence of electrode misplacement on the electrocardiographic signs of inferior myocardial ischemia

Electrocardiographic (ECG) artifacts resulting from misplacements of electrodes are frequent, difficult to detect, and can become of clinical importance. We investigated 2 healthy volunteers and 3 patients with ECG signs of inferior myocardial scars. We exchanged the peripheral electrodes in a defined manner and investigated the resulting ECG for morphology and possible diagnostic errors. In the volunteers, ECG signs of inferior ischemia could be produced. In the patients with ischemic heart disease, normal ECG without signs of ischemia resulted by placing the electrode of the left leg to the left arm. The automatic ECG analyzer was not helpful in detecting artifacts by misplaced electrodes. A very low amplitude of the QRS complex in lead I, II, or III was pathognomonic for electrode misplacement in half of the cases. ECG artifacts must also be suspected when abnormal QRS- or P-axis occur or when QRS morphology does not match with the clinical presentation of the patient.     

Age-dependent contribution of Rho kinase in carbachol-induced contraction of human detrusor smooth muscle in vitro

Aim： Activation of muscarinic receptors on the detrusor smooth muscle is followed by contraction, which involves both myosin light chain kinase （MLCK） and Rho kinase （ROCK）. The aim of this study was to determine the relative contributions of MLCK and ROCK to carbachol-induced contraction of human detrusor smooth muscle in vitro.
Methods： Detrusor smooth muscle strips were prepared from the macroscopically unaffected bladder wall of patients underwent cystectomy. The strips were fixed in an organ bath, and carbachol or KCl-induced isometric contractions were measured by force transducers.

Results： Addition of carbachol （0.4-4 μmol/L） into the bath induced concentration-dependent contractions of detrusor specimens, which was completely abolished by atropine （1 μmol/L）. Pre-incubation of detrusor specimens with either the MLCK inhibitor ML-9 or the ROCK inhibitors HA1100 and Y-27632 （each at 10 μmol/L） significantly blocked carbachol-induced contractions as compared to the time-control experiments. Moreover, MLCK and ROCK inhibition were equally effective in reducing carbachol-induced contractions. The residual carbachol-induced contractions in the presence of both MLCK and ROCK inhibitors were significantly smaller than the contractions obtained when only one enzyme （either MLCK or ROCK） was inhibited, suggesting an additive effect of the two kinases. Interestingly, ROCK-mediated carbachol-induced contractions were positively correlated to the age of patients （r=0.52, P〈0.05）.

Conclusion： Both MLCK and ROCK contribute to carbachol-induced contractions of human detrusor smooth muscle. ROCK inhibitors may be a new pharmacological approach to modulate human bladder hyperactivity.     

International variation in histologic grading is large,and persistent feedback does not improve reproducibility

Histologic grading systems are used to guide diagnosis, therapy, and audit on an international basis. The reproducibility of grading systems is usually tested within small groups of pathologists who have previously worked or trained together. This may underestimate the international variation of scoring systems. We therefore evaluated the reproducibility of an established system, the Banff classification of renal allograft pathology, throughout Europe. We also sought to improve reproducibility by providing individual feedback after each of 14 small groups of cases. Kappa values for all features studied were lower than any previously published, confirming that international variation is greater than interobserver variation as previously assessed. A prolonged attempt to improve reproducibility, using numeric or graphical feedback, failed to produce any detectable improvement. We then asked participants to grade selected photographs, to eliminate variation induced by pathologists viewing different areas of the slide. This produced improved kappa values only for some features. Improvement was influenced by the nature of the grade definitions. Definitions based on "area affected" by a process were not improved. The results indicate the danger of basing decisions on grading systems that may be applied very differently in different institutions.     

Dantrolene: effects on abnormal intracellular Ca(2+) handling and inotropy in postinfarcted rat myocardium

The present study was designed to investigate the effects of dantrolene on intracellular Ca(2+) ([Ca(2+)](i)) handling and inotropy in rat infarcted myocardium. Dantrolene-treated rats with myocardial infarction were placed into two different dosage groups. The infarcted control group received placebo only. Isometric contractility and intracellular Ca(2+) transients were recorded simultaneously in isolated papillary muscles. Diastolic [Ca(2+)](i) was significantly lower in muscle preparations from infarcted rats receiving dantrolene compared to the placebo control group. Additionally, treatment with dantrolene in infarcted rats significantly improved the inotropic response to 10(-4) M isoproterenol. The protein levels of the sarcoplasmic reticulum Ca(2+) ATPase were increased in infarcted rat hearts with dantrolene treatment. We conclude that dantrolene improved the inotropic response to beta-adrenoceptor stimulation in rat postinfarcted myocardium, which is related to improved intracellular Ca(2+) handling, and lowered diastolic Ca(2+) concentration.     

Nebivolol and metoprolol for treating migraine: an advance on beta-blocker treatment?

OBJECTIVE: To evaluate the efficacy of oral treatment with nebivolol and metoprolol in the prophylaxis of migraine attacks. BACKGROUND: Beta-blockers such as propranolol and metoprolol are known to be effective in preventing migraine attacks. Following earlier observations of successful use of nebivolol in a few hypertensive patients with concomitant migraine, we conducted a prospective study to ascertain whether nebivolol would be effective and better tolerated, in a methodologically strict, randomized and double-blind setting. DESIGN AND METHODS: Randomized, double-blind study in 30 patients with confirmed migraine diagnosis, a minimum 1-year history, onset prior to 50 years of age, written records of attacks for the previous 3 months, and minimum 2 attacks per month. Primary endpoint was frequency of attacks (prevention of migraine attacks) in the final 4 weeks of a 14-week treatment on full dose of metoprolol and nebivolol. Secondary endpoints were time to therapeutic effect, duration of attacks, intensity of headache, consumption of analgesics, evaluation of accompanying symptoms, migraine disability assessment, clinical global impression, quality of life, and responder rates. The statistical analysis was prospectively planned and conducted for all randomized patients. RESULTS: Both metoprolol and nebivolol where similarly effective regarding the main endpoint (prevention of migraine attacks) as well as the secondary ones, and both had a fast onset of action, typically within 4 weeks from starting therapy, with responder rates increasing relatively little over time after the first 4 weeks. Use of acute pain medication decreased on both drugs, as well as accompanying symptoms. Both patients' and physicians' evaluations of disability and disease status were similarly favorable to the 2 treatments. Regarding safety, nebivolol was considerably better tolerated than metoprolol in terms of all reported events, treatment-related events, and event severity. CONCLUSIONS: Our results suggest that nebivolol is as effective as metoprolol in the prophylaxis of migraine attacks, with the advantages of being better tolerated and not requiring up-titration to achieve therapeutic levels. Further and larger trials should be conducted on nebivolol in the prevention of migraine attacks as it may provide an improvement in current migraine prophylaxis with beta-blockers.