Ocular and nasal irritation in operatives in Lancashire cotton and synthetic fibre mills

OBJECTIVES: To document the prevalence of work related ocular (eyeWRI) and nasal (noseWRI) irritation in workers in spinning mills of cotton and synthetic textile fibres and to relate the prevalence of symptoms to atopy, byssinotic symptoms, work history, and measured dust concentrations in the personal breathing zone and work area. METHODS: A cross sectional study of 1048 cotton workers and 404 synthetic fibre workers was performed. A respiratory questionnaire was given to 1452 workers (95% of the total available population). Atopy was judged by skin prick tests to three common allergens. Work area cotton dust sampling (WAdust) was carried out according to EH25 guidelines in nine of the 11 spinning mills included in the study. Personal breathing zone dust concentrations were assessed with the IOM sampler to derive total dust exposure (PTdust) and a concentration calculated after the removal of fly (Pless). RESULTS: 3.7% of all operatives complained of symptoms of byssinosis, 253 (17.5%) complained of eyeWRI and 165 (11%) of noseWRI. These symptoms did not relate to atopy or byssinosis, or correlate univariately with any measure of cotton dust exposure (noseWRI v WAdust r = 0.153, PTdust r = 0.118, eyeWRI v WAdust r = 0.029, PTdust r = 0.052). Both of these symptoms on logistic regression analysis were related to being of white origin (P < 0.001), female sex (P < 0.001), and younger age (P < 0.001). With regression analysis, there was a negative relation between dust concentration and prevalence of symptoms. CONCLUSION: Work related ocular and nasal irritation are the most common symptoms complained of by cotton textile workers. There was no relation between these symptoms and atopy, byssinosis, or dust concentration. It is likely that they relate to as yet unidentified agents unrelated to concentration of cotton dust.     

Dexamethasone protection of rat intestinal epithelial cells against oxidant injury is mediated by induction of heat shock protein 72

Although the therapeutic actions of glucocorticoids are largely attributed to their anti-inflammatory and immunosuppressive effects, they have been implicated in enhancing tissue and cellular protection. In this study, we demonstrate that dexamethasone significantly enhances viability of IEC-18 rat small intestinal cells against oxidant-induced stress in a dose-dependent fashion. This protective action is mediated by induction of hsp72, the major inducible heat shock protein in intestinal epithelial cells. Dexamethasone stimulates a time- and dose-dependent response in hsp72 protein expression that parallels its effects on cell viability. Furthermore, the induction of hsp72 is tissue dependent, as nonintestinal epithelioid HeLa cells show differential induction of hsp72 expression in response to the same dexamethasone treatment. Antisense hsp72 cDNA transfection of IEC-18 cells abolishes the dexamethasone-induced hsp72 response, without significantly affecting constitutive expression of its homologue, hsc73. Dexamethasone treatment also significantly induces hsp72 protein expression in rat intestinal mucosal cells in vivo. These data demonstrate that glucocorticoids protect intestinal epithelial cells against oxidant-induced stress by inducing hsp72.     

Direction of temperature control in the thermal biofeedback treatment of vascular headache

In order to test for the specific therapeutic effects of thermal biofeedback (TBF) for hand warming on vascular headache (HA), 70 patients with chronic vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling, TBF for stabilization of hand temperature, or biofeedback to suppress alpha in the EEG. Patients in each condition initially had high levels of expectation of therapeutic benefit and found the treatment rationales highly credible. Participants in each condition received 12 treatment sessions on a twice-per-week basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and 4 weeks after treatment, HA Index was significantly (p = .003) reduced as was HA medication consumption. There were no differential reductions in HA Index or Medication Index among the four conditions. Global self-reports of improvement gathered at the end of the post-treatment monitoring period also did not differ among the four conditions. We were unable to demonstrate a specific effect of TBF for hand warming on vascular HA activity.     

The treatment of patients with benign prostatic hyperplasia using the selective alpha-blocker alfuzosin

40 patients with benign prostatic hyperplasia (BPH) were treated with the alpha-blocker alfuzosin which was administered per os twice a day in a dose 5 mg. The treatment brought about a decrease of the mean symptom score from 19.6 to 12.2, of quality of life from 5.2 to 2.1, of residual urine from 152 to 82 ml. Mean and maximal urinary flow rates rose by 35 and 45%, respectively. The level of prostate-specific antigen over the treatment course did not change. The findings of the trial evidence for high efficacy of alfuzosin in the treatment of urination disorders in BPH patients.     

Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy

PURPOSE: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and polytherapy. METHODS: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies. RESULTS: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2-4.7]. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6-15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3-18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4-67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1-57.6). Offspring of mothers using > 1,000 mg VPA/day were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed < or =600 mg VPA/day (RR 6.8; 95% CI: 1.4-32.7). No difference in risk of MCA was found between the offspring exposed to 601-1,000 mg/day and < or =600 mg/day. CONCLUSIONS: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population-based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.     

Demonstration of protein-protein interaction specificity by NMR chemical shift mapping

Chemical shift mapping is becoming a popular method for studying protein-protein interactions in solution. The technique is used to identify putative sites of interaction on a protein surface by detecting chemical shift perturbations in simple (1H, 15N)-HSQC NMR spectra of a uniformly labeled protein as a function of added (unlabeled) target protein. The high concentrations required for these experiments raise questions concerning the possibility for non-specific interactions being detected, thereby compromising the information obtained. We demonstrate here that the simple chemical shift mapping approach faithfully reproduces the known functional specificities among pairs of closely related proteins from the phosphoenolpyruvate:sugar phosphotransferase systems of Escherichia coli and Bacillus subtilis.     

Radiofrequency catheter ablation of sustained monomorphic ventricular tachycardia in hypertrophic cardiomyopathy

INTRODUCTION: Incessant monomorphic ventricular tachycardia (VT) with a right bundle branch block morphology and a northwest axis is a rare arrhythmic complication in a patient with hypertrophic cardiomyopathy and apical left ventricular aneurysm. METHODS AND RESULTS: The origin of this VT was localized using the following criteria: the presence of entrainment without fusion, equal intervals from the stimulus to the beginning of the QRS complex and from the electrogram to the QRS complex during VT, and the first postpacing interval identical to the tachycardia cycle length. Radiofrequency energy applied to the septoapical part of the apical left ventricular aneurysm terminated the tachycardia within 2 seconds. CONCLUSION: Using criteria to guide radiofrequency (RF) ablation of VT in patients with coronary artery disease, an incessant monomorphic VT in a patient with hypertrophic cardiomyopathy was successfully ablated.     

Evidence for increased seizure susceptibility in rats exposed to cocaine in utero

The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel cognition enhancer, on adenylate cyclase activity was investigated in cultured neurons of the mouse cerebral cortex. NS-105 (10(-7) and 10(-6) M) inhibited forskolin-stimulated cyclic AMP formation, an action that was dependent on pertussis toxin-sensitive G proteins. Conversely, in pertussis toxin-pretreated neurons, NS-105 (10(-7)-10(-5) M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera toxin. A metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S, 3R-ACPD) produced similar bi-directional actions on the cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105 and 1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS-105 (10(-6) M) and 1S, 3R-ACPD (10(-4) M) significantly enhanced isoproterenol- and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled receptor agonists-stimulated cyclic AMP formation was also produced by quisqualate but not by L(+)-2-amino-4-phosphonobutanoate (L-AP4). The phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10(-4) M) but not by NS-105 (10(-6) M), however, 1S, 3R-ACPD-induced increase in phosphoinositides turnover was attenuated by NS-105. These findings suggest that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis.