A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action.

Data now exist from which an accurate definition for serotonin toxicity (ST), or serotonin syndrome, has been developed; this has also lead to precise, validated decision rules for diagnosis. The spectrum concept formulates ST as a continuum of serotonergic effects, mediated by the degree of elevation of intrasynaptic serotonin. This progresses from side effects through to toxicity; the concept emphasizes that it is a form of poisoning, not an idiosyncratic reaction. Observations of the degree of ST precipitated by overdoses of different classes of drugs can elucidate mechanisms and potency of drug actions. There is now sufficient pharmacological data on some drugs to enable a prediction of which ones will be at risk of precipitating ST, either by themselves or in combinations with other drugs. This indicates that some antidepressant drugs, presently thought to have serotonergic effects in animals, do not exhibit such effects in humans. Mirtazapine is unable to precipitate serotonin toxicity in overdose or to cause serotonin toxicity when mixed with monoamine oxidase inhibitors, and moclobemide is unable to precipitate serotonin toxicity in overdose. Tricyclic antidepressants (other than clomipramine and imipramine) do not precipitate serotonin toxicity and might not elevate serotonin or have a dual action, as has been assumed.     

Screening for type 2 diabetes mellitus in children and adolescents: attitudes, barriers, and practices among pediatric clinicians.

OBJECTIVE: The American Diabetes Association (ADA) recommends screening children at risk for type 2 diabetes with a fasting plasma glucose test or an oral glucose tolerance test. The purpose of this study was to describe attitudes, barriers, and practices related to type 2 diabetes screening in children among pediatric clinicians. METHODS: Pediatricians, nurse practitioners and physician assistants from a multispecialty, group practice in Eastern Massachusetts completed a mailed survey. To assess screening practice, three vignettes were presented representing pediatric patients with low, moderately high, and high risk for type 2 diabetes. The moderately high-risk and high-risk patients met ADA criteria for screening. ADA-consistent practice was defined as only screening the moderately high-risk and high-risk patients; lower-threshold practice was defined as also screening the low-risk patient; and higher threshold practice was screening only the high-risk patient. RESULTS: Sixty-two of 90 clinicians responded (69%). Based on intent to screen in the 3 vignettes, 21% of respondents reported ADA-consistent screening practice, 39% lower-threshold, and 35% higher-threshold screening practice. Five percent had incomplete or nonclassifiable responses. Many clinicians ordered screening tests other than those recommended by the ADA; few (< or =8% in any vignette) ordered only an ADA-recommended test. Preferences for nonfasting tests were influenced by nonmedical factors such as access to or cost of transportation. Inadequate patient education materials and unclear recommendations for appropriate screening methods were the most frequently reported moderate/strong barriers to screening. CONCLUSIONS: Most respondents reported type 2 diabetes screening practices that differed from current ADA recommendations. Our findings suggest that type 2 diabetes screening tests must be practical for clinicians and patients if they are to be used in pediatric practice. Further study of the benefits and cost-effectiveness of type 2 diabetes screening in children is warranted to clarify the role and optimal methods for screening in pediatric primary care.     

硫酸多糖对体外人脐静脉内皮细胞损伤的保护作用

研究表明,硫酸多糖体外对多聚阳离子和氧自由基损伤的人脐静脉内皮细胞有保护作用。肝素、硫酸软骨素A抗多聚阳离子损伤作用比同浓度低分子肝素和甘糖酯强。肝素、硫酸软骨素A、甘糖酯抗氧自由基损伤作用优于同浓度低分子肝素。结果显示硫酸多糖有保护血管内皮的作用,其作用可能与所带阴离子基团有关。     

Nitrous oxide abuse in perspective.

I present evidence that certain health professionals have a higher liability to drug abuse than does the general population. In view of this, data are presented in which the extremely limited contribution of nitrous oxide to this problem is assessed. I demonstrate on the basis of the limited published data now available that pure nitrous oxide addiction is very rare among health professionals, being the rarest drug of abuse among them. When used by the latter, it is most commonly part of a polydrug abuse pattern, not being a major component of the addiction in these cases. It is clear that nitrous oxide addiction is even less of a problem in the general population. Furthermore, after almost 200 years of use, its very minor addictive potential should by now have clarified itself. It would appear that it is unlikely to become, has never been, nor is it the moment of any real significance as a drug of abuse when compared with the many currently available addictive drugs, which clearly pose a much more serious problem.     

Assessing the validity of childhood blood pressure screening: unbiased estimates of sensitivity, specificity, and predictive values.

Blood pressure measurement in childhood can be considered as a screening test for future blood pressure levels. Evaluating this test involves calculating sensitivities, specificities, and predictive values for a blood pressure measurement at an initial time for predicting underlying true blood pressure at a subsequent time. We demonstrate the use of childhood blood pressure tracking correlations that are corrected for within-person variability to calculate unbiased estimates of these test characteristics. In a cohort of 333 schoolchildren, we measured blood pressure on multiple visits in each of 4 successive years. Using these data for within-person variances and corrected tracking correlations, and U.S. population data for means and total variances, we tabulated positive predictive values, sensitivities, and specificities for the case of predicting a 9-year-old male's true systolic blood pressure 3 years later. For example, if a 9-year-old's average blood pressure from 4 visits is 115 mmHg, the probability of his true blood pressure being greater than 116 mmHg (90th percentile) at age 12 is 0.50. With longer follow-up, the use of predictive values, sensitivities, and specificities that incorporate corrected correlations should allow determination of the accuracy of predicting adult blood pressure from childhood values, and therefore the usefulness of screening children for those at high risk of developing hypertension.