A randomised placebo controlled trial of oral misoprostol in the third stage of labour

OBJECTIVE: To compare oral misoprostol 400 microg with placebo in the routine management of the third stage of labour. DESIGN: A double-blind placebo controlled trial. Setting The labour ward of an academic hospital in Johannesburg, South Africa with 7000 deliveries per annum. PARTICIPANTS: Low-risk women expected to deliver vaginally. METHODS: Women in labour were randomly allocated to receive either misoprostol 400 microg orally or placebo after the birth. Conventional oxytocics were given immediately if blood loss was thought to be more than usual. Postpartum blood loss in the first hour was measured by collection in a special flat plastic bedpan. Side effects were recorded. MAIN OUTCOME MEASURES: Measured blood loss > or = 1000 ml within the first hour after birth. Use of additional oxytocics. RESULTS: The groups were well matched. Measured blood loss > or = 1000 ml occurred in 15/250 (6%) after misoprostol and 23/250 (9%) after placebo (relative risk 0.65; 95% confidence interval 0.35-1.22). The difference may have been reduced by the greater use of conventional oxytocics in the placebo group, which was statistically significant for intravenous oxytocin infusion (2.8% vs 8.4%, relative risk 0.33, 95% confidence interval 0.14-0.77). Shivering was more common in the misoprostol group (19% vs 5%, relative risk 3.69; 95% confidence interval 2.05-6.64). CONCLUSIONS: Shivering has been shown in this study to be a specific side effect of misoprostol administered orally in the puerperium. No serious side effects were noted. Misoprostol shows promise as a method of preventing postpartum haemorrhage. Because of the potential benefits for childbearing women, particularly those in developing countries, further research to determine its effects with greater certainty should be expedited.     

Exochelin genes in Mycobacterium smegmatis: identification of an ABC transporter and two non-ribosomal peptide synthetase genes

Many strains of mycobacteria produce two ferric chelating substances that are termed exochelin (an excreted product) and mycobactin (a cell-associated product). These agents may function as iron acquisition siderophores. To examine the genetics of the iron acquisition system in mycobacteria, ultraviolet (UV) and transposon (Tn611) mutagenesis techniques were used to generate exochelin-deficient mutants of Mycobacterium smegmatis strains ATCC 607 and LR222 respectively. Mutants were identified on CAS siderophore detection agar plates. Comparisons of the amounts of CAS-reactive material excreted by the possible mutant strains with that of the wild-type strains verified that seven UV mutant strains and two confirmed transposition mutant strains were deficient in exochelin production. Cell-associated mycobactin production in the mutants appeared to be normal. From the two transposon mutants, the mutated gene regions were cloned and identified by colony hybridization with an IS6100 probe, and the DNA regions flanking the transposon insertion sites were then used as probes to clone the wild-type loci from M. smegmatis LR222 genomic DNA. Complementation assays showed that an 8 kb PstI fragment and a 4.8 kb PstI/SacI subclone of this fragment complemented one transposon mutant (LUN2) and one UV mutant (R92). A 10.1 kb SacI fragment restored exochelin production to the other transposon mutant (LUN1). The nucleotide sequence of the 15.3 kb DNA region that spanned the two transposon insertion sites overlapped the 5' region of the previously reported exochelin biosynthetic gene fxbA and contained three open reading frames that were transcribed in the opposite orientation to fxbA. The corresponding genes were designated exiT, fxbB and fxbC. The deduced amino acid sequence of ExiT suggested that it was a member of the ABC transporter superfamily, while FxbB and FxbC displayed significant homology with many enzymes (including pristinamycin I synthetase) that catalyse non-ribosomal peptide synthesis. We propose that the peptide backbone of the siderophore exochelin is synthesized in part by enzymes resembling non-ribosomal peptide synthetases and that the ABC transporter ExiT is responsible for exochelin excretion.     

Development of novel, potent, and selective dopamine reuptake inhibitors through alteration of the piperazine ring of 1-[2-(diphenylmethoxy)ethyl]-and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909)

The design, synthesis, and biological evaluation of compounds related to the dopamine (DA) uptake inhibitors: 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (1) and 1-[2-[bis-(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (2) (GBR 12395 and GBR 12909, respectively), directed toward the development and identification of new ligands interacting with high potency and selectivity at the dopamine transporter (DAT) is reported. The substitution of the piperazine ring in the GBR structure with other diamine moieties resulted in the retention of the high affinity of new ligands for the DAT. Some of the modified GBR analogs (e.g. 8, 10, (-)-49, or (-)-50) displayed substantially higher selectivity (4736- to 693-fold) for the dopamine (DA) versus the serotonin (5HT) reuptake site than the parent compounds. The bis(p-fluoro) substitution in the (diphenylmethoxy)ethyl fragment slightly increased the affinity of the ligands at the DA reuptake site but reduced their selectivity at this site (e.g. 9 and 8, 11 and 10, or 17 and 16, respectively). Congeners, such as the series of monosubstituted and symmetrically disubstituted piperazines and trans-2,5-dimethylpiperazines, which lack the (diphenylmethoxy)ethyl substituent lost the affinity for the DAT yet exhibited very high potency for binding to the sigma receptors (e.g.28). The chiral pyrrolidine derivatives of 1, (-)-49, and (+)-49, exhibited an enantioselectivity ratio of 181 and 146 for the inhibition of DA reuptake and binding to the DAT, respectively.     

The Aleutian Enterprise sinking and posttraumatic stress disorder: Misdiagnosis in clinical and forensic settings.

This study examines the vulnerability of clinicians to overdiagnose posttraumatic stress disorder (PTSD) when survivors of a traumatic event are involved in litigation. 19 of 22 survivors of a marine disaster were seen by mental health professionals while pursuing personal injury claims and received a PTSD diagnosis that was maintained for more than 6 mo. This yielded an incidence rate for chronic PTSD of no less than 86%, a rate in excess of any previously reported in the literature for any type of trauma. The extraordinary incidence rate appeared to be explained, in part, by crew members' reports of attorney advice and symptom sharing. Clinicians are cautioned not to rely on client's self-reports and to consider postincident factors that may influence these reports when clients are involved in litigation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic basis of neurological tumours

Neurological tumours are common neoplasms of both adults and children. Recent studies have begun to delineate the genetic abnormalities that underlie such tumours, and have implicated two classes of genes, oncogenes and tumour suppressor genes. Most investigations have focused on those astrocytomas that affect the cerebral hemispheres of adults, since these are the most common and malignant brain tumours. The high-grade astrocytomas that affect adults, such as glioblastoma multiforme, often have amplification of the epidermal growth factor receptor (EGFR) oncogene and loss of a variety of chromosomal loci that probably harbour tumour suppressor genes. Of the various tumour suppressor gene loci, the p53 gene on chromosome 17p has been studied most closely and has been shown to be mutated in both low- and high-grade astrocytomas. These genetic alterations may provide a means for subdividing astrocytomas into diagnostic categories. For instance, p53 gene mutations occur more commonly in glioblastomas from young adults and women, while EGFR gene amplification is more common in glioblastomas from older adults and men. For the other primary CNS tumours, genetic studies remain in their infancy. The neurocutaneous syndromes, such as neurofibromatosis types 1 and 2, have provided unique insights into neurological oncogenesis. The NF1 gene on chromosomes 17q and its product, neurofibromin, may be important in the formation of neurofibrosarcomas, while the NF2 gene on chromosome 22q and its product, merlin, are probably involved in the formation of schwannomas and other nervous system tumours. The further characterization of these and other neurological tumour genes will undoubtedly illuminate many other areas in neurooncology.     

Predicting external sulphur requirement of alfalfa from sulphate sorption isotherm of Tanzanian soils

For Tanzanian soils dominant in hydrous oxides of iron and amorphous ferri-alumino silicate, a 48-hour (hr) mixing period with the sulphate (SO₄) solution was adequate for a near-equilibrium condition. Although differing in their SO₄ sorption capacity, all the soils sorbed SO₄ at or beyond 1µg ml^–1 sulphur (S) concentration in the supernatant. Hydroxyl (OH) ions were displaced during SO₄ sorption as indicated by a significant positive correlation between the amount of sorbed SO₄ and the difference in pH values determined in 0.1N K₂ SO₄ and 0.1N KCl, i.e. the dpH values.In a greenhouse experiment, alfalfa was grown on eight soils at six adjusted S concentrations. Sulphur deficiency symptoms appeared in the control pots of those soils which were low in native sorbed SO₄, SO₄ sorption capacity and initial soil solution S concentration. Sulphur fertilization increased dry matter (DM) yield as well as response to applied S. The external S concentration, i.e. adjusted S concentration required for 95% of the maximum DM yield, ranged from 0.8 to 8.2µg S ml^–1 with values less than 2.0 on most of the soils. The external S concentration decreased hyperbolically as the SO₄ sorption capacity of the soils increased. The total amount of fertilizer S required to obtain the external S concentration in solution, and at the same time satisfy the SO₄ sorption capacity of the soil at the external S concentration (determined from the sorption isotherm) was defined as the external S requirement for the specified yield level of alfalfa. The external S requirement for 95% of the maximum yield of alfalfa varied from soil to soil due to differences in their capacity and intensity for S nutrition.Part of a thesis by the senior author for the MSc (Agric) degree of the University of Dar es Salaam     

The relationship of structure to properties in surfactants

Changes in the various structural units present in surfactants strongly affect the interfacial properties shown by these materials. Such properties as surface tension reduction, micelle formation, wetting, foaming and defoaming, detergency, and dispersion of solids all show marked changes with variations in both the hydrophilic and hydrophobic portions of the surfactant molecule, reflecting the processes occurring on a molecular level. Changes in these properties caused by such factors as the length and nature of the hydrophobic group, branching or unsaturation in the hydrophobic group, the nature of the hydrophilic group and its position in the molecule, and the presence or absence of an ionic charge are described and explained in terms of the molecular processes involved. Presented at the AOCS Short Course, “Update on Detergents and Raw Materials,” Lake Placid, New York, June 1971.     

Relationship of structure to properties of surfactants. 16. Linear decyldiphenylether sulfonates

The properties of some well-characterized sodium linear decyldiphenylether (C₁₀DPE)sulfonates have been studied. Among the properties investigated are dynamic and equilibrium surface tension, critical micelle concentration (CMC), area per molecule at the aqueous solution/air interface, wetting time by the Draves technique, foaming by the Ross-Miles method, solubilization, and hydrotropy. The decyldiphenylether moiety appears to be equivalent to a terminally substituted straight alkyl chain of 16 carbon atoms. The trialkyl- and dialkyl-mono-sulfonates have solubilities of < 0.01 g/dm³ in water, but are readily soluble in hexane. The didecyldiphenyl ether disulfonate (DADS) has a very low CMC value (1.0 × 10⁻⁵ mol dm⁻³) in aqueous 0.1 N Na⁺ solution (NaCl), characteristic of surfactants with two hydrophilic and two hydrophobic groups. It also has a much larger area per molecule at the aqueous solution/air interface than the monodecyldiphenyl-ether monosulfonate (MAMS) and a much higher surface tension at the CMC. MAMS has a much lower surface tension at a surface age of 1 second (γ_1s) than either DADS or the monodecyldiphenylether disulfonate (MADS). In agreement with γ_1s and γ_eq values, wetting times increase in the order: MAMS < DADS < MADS and initial foam heights decrease in the order: MAMS > DADS > MADS. Solubilization for three water-insoluble surfactants decreases in the order: DADS > MAMS > MADS, while hydrotropy is most pronounced with the disulfonates.     

Long latency postural reflexes are under supraspinal dopaminergic control

Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.     

Evidence that the modulation of membrane-associated protein kinase C activity by an endogenous inhibitor plays a role in N1E-115 murine neuroblastoma cell differentiation

Murine neuroblastoma cells, N1E-115, were induced to differentiate into neuron-like cells by serum deprivation for 18 h. As previous studies have shown that the suppression of protein kinase C (PKC) activity by selective inhibitors or neutralizing antibodies induces neuroblastoma cells to differentiate, we tested the hypothesis that serum deprivation may cause a rapid loss in membrane PKC activity that occurs well before the morphological changes that are characteristic of cell differentiation. A significant reduction in particulate (membrane) PKC activity was indeed observed within 3 h of serum withdrawal when enzyme activity was measured in intact native membranes by the recently described in vitro "direct" assay. This rapid reduction in enzyme activity was confirmed by the decreased phosphorylation of the MARCKS protein, an endogenous PKC-selective substrate, in intact cells. The decrease in membrane PKC activity occurred without any loss in the amount of membrane-associated enzyme, suggesting that some factor(s) resident in neuroblastoma membranes was suppressing PKC activity. Indeed, results indicate the presence of an endogenous inhibitor of PKC tightly associated with neuroblastoma membranes. This inhibitory activity increased in the membranes of cells subjected to serum deprivation, raising the possibility that it was likely responsible for the decline in membrane PKC activity in differentiating N1E-115 cells. Preliminary characterization indicated that the inhibitory activity is a protein and is localized mainly in the membrane fraction. Thus, these results demonstrate directly that endogenous inhibitor can regulate membrane-associated PKC activity in cells and thereby modulate PKC-related neuronal functions.