Randomised trial of nitric oxide donor versus prostaglandin for cervical ripening before first-trimester termination of pregnancy

BACKGROUND: Vaginal administration of the nitric oxide donor isosorbide mononitrate can induce effective ripening of the human cervix. We investigated whether this drug is associated with fewer side-effects than prostaglandins when used to ripen the cervix before first-trimester surgical termination of pregnancy, and assessed whether the extent of cervical ripening it induces is clinically sufficient. METHODS: 66 primigravid women scheduled for surgical termination were assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg or 80 mg, or the prostaglandin analogue gemeprost 1 mg. The primary measured outcome was onset of new symptoms before termination of pregnancy. FINDINGS: More women remained symptom-free after isosorbide mononitrate than after gemeprost (28/44 [64%] vs 3/22 [14%], p<0.005). Pretreatment with gemeprost resulted in abdominal pain in 73% of women and vaginal bleeding in 32% compared with 3% and 0%, respectively, after isosorbide mononitrate, whereas, more women developed headache after isosorbide mononitrate (27%) than after gemeprost (0%). Cervical resistance and measured intraoperative blood loss were lowest after pretreatment with gemeprost. The measured cervical resistance and intraoperative blood loss with either dose of isosorbide mononitrate did not differ from those in a comparison group of 22 parous women not in the randomised trial. INTERPRETATION: Pretreatment with isosorbide mononitrate to ripen the cervix before first-trimester termination of pregnancy is associated with fewer side-effects than gemeprost treatment and adequately decreases cervical resistance. Isosorbide mononitrate could be used as an alternative to gemeprost for this indication.     

Gender and neurogenic variables in tendon biology and repetitive motion disorders

The incidence of repetitive motion disorders is increasing. Numerous studies have indicated that the incidence in females exceeds that in males. Some of the evidence regarding gender related factors in tendon biology is discussed and new data related to the regulation of gene expression in an animal model of tendon overuse, the determination of sex hormone receptors in tendons, and the influence of pregnancy associated factors on gene expression in four different tendons is provided. Furthermore, because neurogenic mechanisms may contribute to inflammatory conditions, new evidence is provided that supports the concept that neurotransmitters can influence expression of genes that could participate in such inflammation. By increasing our understanding of the regulation of tendon cellular and molecular biology, new approaches to preventing disease development and treatment of existing disease may evolve.     

Mutation of cysteine 111 in Dopa decarboxylase leads to active site perturbation

Cysteine 111 in Dopa decarboxylase (DDC) has been replaced by alanine or serine by site-directed mutagenesis. Compared to the wild-type enzyme, the resultant C111A and C111S mutant enzymes exhibit Kcat values of about 50% and 15%, respectively, at pH 6.8, while the K(m) values remain relatively unaltered for L-3,4-dihydroxyphenylalanine (L-Dopa) and L-5-hydroxytryptophan (L-5-HTP). While a significant decrease of the 280 nm optically active band present in the wild type is observed in mutant DDCs, their visible co-enzyme absorption and CD spectra are similar to those of the wild type. With respect to the wild type, the Cys-111-->Ala mutant displays a reduced affinity for pyridoxal 5'-phosphate (PLP), slower kinetics of reconstitution to holoenzyme, a decreased ability to anchor the external aldimine formed between D-Dopa and the bound co-enzyme, and a decreased efficiency of energy transfer between tryptophan residue(s) and reduced PLP. Values of pKa and pKb for the groups involved in catalysis were determined for the wild-type and the C111A mutant enzymes. The mutant showed a decrease in both pK values by about 1 pH unit, resulting in a shift of the pH of the maximum velocity from 7.2 (wild-type) to 6.2 (mutant). This change in maximum velocity is mirrored by a similar shift in the spectrophotometrically determined pK value of the 420-->390 nm transition of the external aldimine. These results demonstrate that the sulfhydryl group of Cys-111 is catalytically nonessential and provide strong support for previous suggestion that this residue is located at or near the PLP binding site (Dominici P, Maras B, Mei G, Borri Voltattorni C. 1991. Eur J Biochem 201:393-397). Moreover, our findings provide evidence that Cys-111 has a structural role in PLP binding and suggest that this residue is required for maintenance of proper active-site conformation.     

Impact of organizational redesign

Little in-depth objective information is available about the outcomes of restructuring or reengineering. One reason for this is the difficulty of conducting traditional research within the context of dynamic organizational development activities. The authors describe an alternative program evaluation approach that proved successful for assessing and enhancing large-scale organizational change in an acute-care medical center. Sample results are presented and recommendations made for increasing an evaluation's usefulness by tailoring reports to the user.     

Species differentiation by internally transcribed spacer PCR and HhaI digestion of fluconazole-resistant Candida krusei, Candida inconspicua, and Candida norvegensis strains

PCR amplification of the regions containing the internally transcribed spacers and 5.8S rRNA gene of Candida krusei, C. inconspicua, and C. norvegensis yielded fragments of 510, 460, and 500 bp, respectively. HhaI digestion of these fragments yielded species-specific bands. Random amplification of polymorphic DNA with primer R108 showed interspecific discriminatory band patterns. Susceptibilities to fluconazole and amphotericin B were determined.     

Cocaine abuse and HIV-1 infection: epidemiology and neuropathogenesis

The epidemiology of cocaine abuse and potential relationships of cocaine withdrawal to human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) are discussed. Neuroendocrinological changes in HIV-1 infection of the central nervous system (CNS) are discussed with the relevant impact of cocaine abuse. HIV-1 load in the brain tissue of infected substance users is described along with possible associations with neuropathology and HAD. Finally, the molecular epidemiology and sequence heterogeneity of HIV-1 and their implications for neuropathogenesis are summarized. The complex context of addressing cocaine abuse in the setting of HIV-1 infection appears more tractable when decomposed into its components.     

"All fall down": the mechanism of orthostatic hypotension in multiple systems atrophy and Parkinson''s disease

A rare case of rheumatoid vasculitis and responses to a 15-year supervised exercise program. This patient presented with significant impairment in mobility and physical work capacity. His exercise tolerance improved considerably and he benefited emotionally.     

Effect of breeding state, moulting, dehydration, exposure to saturated atmosphere, and arginine vasotocin on cutaneous water permeability in the toad Bufo bufo

Cutaneous water permeability was assessed in hydrated male toads under a variety of conditions, including dehydration and rehydration, and the effects of exogenous arginine vasotocin (AVT) were determined. Cutaneous water permeability (the rate of water uptake by toads in water) was high in toads collected in the breeding pond and declined steeply during the first week, coincident with reduced activity of the cutaneous mucus glands. The slopes of the dose-response curves relating AVT to cutaneous water influx were about the same at the transition from the breeding to the nonbreeding state, but the level of influx was higher in the breeding state. The dose-response relationship in long-term terrestrial-acclimated toads was similar to that in water-acclimated toads. The threshold dose for effect on the cutaneous water permeability was about 1 ng AVT. Dehydration had a substantially greater effect on the cutaneous water permeability than AVT. The ratio between dehydration and AVT responses tended to increase with increasing water transport capacity of the skin. Moulting and acclimation to a saturated atmosphere in fully hydrated toads more than doubled the water permeability and abolished the response to AVT. It is suggested that AVT and other factors increase the cutaneous water permeability by similar mechanisms, such as insertion of water channels in the apical membrane of the epidermal cells. The effect of AVT on the toad skin is interpreted as reflecting the general high potency of neurohypophysial hormones in stimulating the water permeability of membranes of variable permeability.