Temporal and spatial relations between age specific mortality and ambient air quality in the United States: regression results for counties, 1960-97

Objective: To investigate longitudinal and spatial relations between air pollution and age specific mortality for United States counties (except Alaska) from 1960 to the end of 1997.     

A BPA survey of recently appointed consultants

A postal survey of recently appointed consultant paediatricians was undertaken to determine whether they perceived their training had adequately equipped them for their current job. The response rate was 69% (207/299). After excluding replies from consultants trained outside the UK the analysis was carried out on 167 replies. Trainees held a mean 5.2 posts during general and higher professional training, necessitating a mean 1.8 house moves. Altogether 82% felt moves were beneficial to training but 46% found moves 'very disruptive' to family life. Only 12% of district general hospital and 22% of teaching hospital senior registrars took two research sessions a week. Supervision and training in research was absent or poor for more than 60%; 24% felt major changes and 55% moderate changes were needed to current training. Training in non-clinical skills was particularly in demand and a curriculum for both trainers and trainees with regular appraisals is required. Research at senior registrar level needs review and educational methods improved to achieve better training in a shorter period.     

Otoacoustic emissions as a screening test for hearing impairment in children

Transient evoked otoacoustic emissions (TEOAEs) are low amplitude sound waves produced by the healthy cochlea. They can be recorded with a microphone in the external ear. TEOAEs are abolished by hearing losses of 30 dB or more. The feasibility of using TEOAEs as a screening test for hearing loss in children was studied. TEOAE recordings were attempted in 56 children attending an audiology clinic. Recordings were possible from both ears in 52 children; of these 104 ears, 32 had hearing deficits of 30 dB or more. Hearing status was compared with the results of six TEOAE screening criteria. All criteria had a sensitivity of 1.00. Four standard TEOAE criteria yielded specificities of 0.46-0.58. Two new criteria derived from analysis of limited frequencies from the TEOAE waveform gave specificities of 0.76 and 0.82. It can be concluded that, when appropriate pass/fail criteria are employed, TEOAEs are a feasible screening test in children.     

Induction Of Endothelin-1 Expression By Glucose: An Effect Of Protein Kinase C Activation

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta 2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta 1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.     

Temporal patterns in air pollution and hospital admissions.

A 6-year data set of daily counts of admissions to 79 acute care hospitals in Southern Ontario was analyzed in relation to concurrent measurements of air pollution and weather pooled over the same regions, using progressively more sophisticated statistical techniques. The diagnoses studied included a group of respiratory causes and two control diagnoses: accidents and gastrointestinal causes. The 6-year period (1979-1985) was subdivided into six 2-month "seasons" and the area of study was divided into three subregions. Bivariate correlations were found to be significant more often than expected due to chance for all three admissions variables, but accounting for the temporal variation within the 60-day seasons greatly reduced the significance of the control diagnoses. Twenty-four-hour averages for air quality were found to yield more significant associations than peak hourly concentrations. July-August was the only period not having important within-season temporal trends and also had the lowest daily counts for respiratory admissions. Based on a model which accounted for serial correlation, SO2, ozone, and sulfate aerosol were found to be significant predictors of respiratory admissions during July-August. Using cumulative lags increased the magnitude of the estimated response to about 20% of summer respiratory admissions, but no consistent relationships were found which could identify the "responsible" pollutant(s) with certainty. Average pollutant concentrations were generally within U.S. ambient standards.     

Nonpeptide alphavbeta3 antagonists. Part 11: discovery and preclinical evaluation of potent alphavbeta3 antagonists for the prevention and treatment of osteoporosis

3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)-(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC(50) = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.     

Mirtazapine and its enantiomers differentially modulate acute thermal nociception in rats

The antidepressant mirtazapine is an optically active drug and currently marketed as a racemic compound consisting of its S(+) and R(-)-enantiomers in a 50:50 mixture. As stereochemistry of antidepressants has become increasingly important to consider for the relevance of their analgesic properties, we investigated the effect of (+/-)-mirtazapine and its enantiomers in an animal model of acute thermal nociception. Wistar rats were injected intrathecal with either (+/-)-mirtazapine, R(-)-mirtazapine, S(+)-mirtazapine from 1 to 0.001 mg/kg and vehicle (0.9% NaCl), respectively. The effects on thermal paw withdrawal thresholds were monitored using the Hargreaves test. (+/-)-Mirtazapine exerted pro- and antinociceptive effects in acute thermal nociception, whereas R(-)-mirtazapine showed solely antinociceptive and S(+)-mirtazapine pronociceptive properties. These results clearly demonstrate a differential effect of (+/-)-mirtazapine and its enantiomers on nociception. As R(-)-mirtazapine exerts the antinociceptive activity of the racemic mixture it may be a putative candidate for an enantioselective use as analgesic.     

Open vs Laparoscopic Vertical Banded Gastroplasty: A case control study with 1-year follow-up

Background: Vertical Banded Gastroplasty (VBG) is one of the most common bariatric operations. It can be performed by open or laparoscopic methods. The purpose of this study was to analyze and compare the 1-year results of 40 patients who underwent laparoscopic (20) and open (20). Methods: The initial 20 patients undergoing LaparoscopicVBG and the initial 20 patients in whom an Open VBG were performed in our Institution were comparatively evaluated. Demography, surgical details, complications, and 1-year weight loss were analyzed. Results: Both groups were highly comparable in terms of age, sex and body mass index. Laparoscopic VBG was a more prolonged procedure (median 4 hr) than the open VBG (median 3 hr). On the other hand, hospital stay was significantly shorter in the laparoscopic procedure (median 10 days for the open and 6 days for the laparoscopic). One year weight loss and complications were similar in both groups. Conclusions: Laparoscopic VBG is a safe procedure for the treatment of morbid obesity. This initial series shows comparable results.