Medical teaching in ambulatory care (second edition). Warren Rubenstein, Yves Talbot. (148 pages, US$36.80.) Springer Publishing Company, 2003. ISBN 0-8261-7691-7

This slim, readable book sets out to help clinicians teach medicalstudents and post-graduate trainees in ‘ambulatory care’(family practice or out-patients). It follows the teaching careerof a hypothetical doctor (Dr ZZ Smith) who enjoyed teachingwhile in     

Inhibition and induction of cytochrome P450 2B1 in rat liver by promazine and chlorpromazine.

Phenothiazine tranquilizers have been associated with pharmacokinetic drug interactions in man. In this study the in vivo and in vitro effects of the clinically important phenothiazines promazine (PZ) and chlorpromazine (CPZ) on drug oxidations catalysed by specific cytochrome P450 (P450) enzymes were investigated in the rat. In vitro, the two drugs were relatively ineffective inhibitors of constitutive P450 activities, but were inhibitory toward the principal phenobarbital-inducible P450 2B1 and, to a lesser extent, P450 1A1. Administration of PZ and CPZ to male rats did not markedly influence the total microsomal P450 content of the liver. However, the quantitatively important male-specific P450 2C11 was down-regulated by CPZ and concomitant induction of P450 2B1 and associated 7-pentylresorufin O-depentylase activity were noted. A small increase in the activity of microsomal 7-ethylresorufin O-deethylase was also observed following administration of both drugs to rats, suggesting induction of P450 1A1/2. Considered together, it is apparent that the two phenothiazines are preferential inhibitors and inducers of P450 2B1 in rat liver. Drug interactions in humans involving phenothiazines may reflect a combined effect of induction and inhibition processes as well as down-regulation of other P450s, such as that produced by CPZ on P450 2C11.     

Ensuring NCLEX-RN success for first-time test-takers.

A major indicator of baccalaureate nursing program effectiveness is the pass rate on the National Council Licensure Examinations, Registered Nurse (NCLEX-RN) among first-time candidates. This article highlights the scope, instructional methods, and outcomes of the remediation program at Georgetown University School of Nursing & Health Studies (GU-NHS). With implementation of the multifaceted program, the NCLEX-RN pass rate for first-time takers at GU-NHS has been consistently above the national mean among all first-time candidates. Although it is impossible to determine which strategy made the greatest contribution to the success of the program, the cumulative effect is impressive and indicates the students are prepared for the challenge of the examination and contemporary nursing practice.     

Estimated distributions for total body surface area of men and women in the United States.

For the U.S. population in the age range 18 to 74 years, we estimated distributions for total body surface area for men and women using Monte Carlo simulations based on estimated bivariate distributions for height and weight. Surface area is well fit by individual lognormal distributions for men and women. These distributions are appropriate for use in public health risk assessments. We also examined the effect of the correlation between height and weight on the surface area distributions.     

Crosslinking of extracellular matrix proteins: a preliminary report on a possible mechanism of argon laser welding

In order to elucidate the biochemical mechanism of laser welding of tissues, we have compared protein profiles from argon laser-treated specimens with controls. Extracellular matrix components from untreated and laser-welded skin and blood vessels were extracted with guanidine hydrochloride and separated by SDS polyacrylamide gel electrophoresis. When compared with matched, untreated tissues, protein electrophoretic profiles from laser-treated samples showed several changes. In both tissue types, argon laser treatment decreased the concentration of a 235 kd protein that migrates between the alpha and beta chains of type I collagen. Laser-treated blood vessels showed significantly more low molecular weight protein at the dye front than in control tissue, whereas significantly more high molecular weight protein appeared in laser-treated skin samples when compared with untreated tissue. These results suggest that the argon laser may either degrade or crosslink proteins in vivo. Laser-induced protein crosslinks may be the biochemical basis of argon laser welding.     

Reproducibility of cardiac output measurement by cross sectional and Doppler echocardiography.

The variability of Doppler echocardiographic estimation of cardiac output at the aortic orifice was investigated in eight healthy subjects. Cross sectional echocardiograms of the aortic orifice and aortic Doppler velocities were recorded and measured by four echocardiographers. Between subject variability was significantly larger than within subject variability for all variables. Variability owing to different echocardiographers and different measurement times was small compared with total variability. Coefficients of variation for aortic annular diameter, aortic velocity integral, and heart rate were 4.1%, 6.4%, and 5.0% respectively. The coefficient of variation for cardiac output was 8.8% and the 95% confidence interval for measurement of cardiac output by the Doppler method was 4.45 to 6.35 l/min. One echocardiographer reanalysed all the recordings and the results showed that recording the echocardiograms introduces a significantly larger source of error than measuring them. Thus serial measurements of cardiac output by the Doppler method can be performed with acceptable reproducibility; this indicates that the technique can be accurately applied in clinical practice.     

Biological profile of the metabolites and potential metabolites of the anticonvulsant remacemide.

Remacemide hydrochloride ((+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)- acetamide hydrochloride or FPL 1292AA) is a novel compound undergoing clinical trials for patients with generalized tonic/clonic and complex partial epilepsy. Remacemide exhibits efficacy against maximal electroconvulsive shock (MES) in rodents and seizures elicited by N-methyl-D,L-aspartate (NMDLA) in mice. Using rat synaptic membrane fractions, remacemide was shown to possess relatively weak noncompetitive binding to the ionic channel site of the NMDA (N-methyl-D-aspartic acid) receptor complex. With the hypothesis that activity against NMDLA-elicited seizures might be reflected by transformation to a more active metabolic species, the aim of the present study was to evaluate potential pharmacological effects of the 9 identified metabolites of remacemide which were all found in human and dog urine. Moreover, specific entities were recognized in plasma (including the rat's), as well as dog and rat cerebrospinal fluid. Five putative metabolites were also examined. A major route of metabolic transformation of remacemide in rats yields the formation of a pharmacologically active more potent desglycine derivative, namely FPL 12495 (+/-). Potency over the parent compound is revealed in the MES test in mice and rats, the NMDA-induced convulsions/mortality test in mice, and especially involving in vitro displacement of MK801 binding to the channel subsite of the NMDA receptor. The S isomer (FPL 12859) of this desglycinate is even more potent, while the R isomer is less potent than the corresponding racemate. Unlike the non-competitive NMDA antagonist, MK801, these desglycinates did not prevent kindled seizures. Three other identified metabolites show efficacy in the mouse and rat in vivo tests, namely the N-hydroxy-desglycinate (FPL 15053) and the p-hydroxy-desglycinates (FPL 14331 and FPL 14465). FPL 15053 exhibited modest activity in all tests. The only in vivo activity exhibited by the 2 p-hydroxy-desglycinates was evidenced in the MES test following i.p. and i.v. dosing. However, FPL 14331 was active in the MK801 binding assay. An oxoacetate metabolite, PFL 15455, failed to demonstrate any biological activity. Of potential metabolites tested 2 beta-hydroxy-desglycinates (FPL 14991 and FPL 14981) displayed modest activity in the MES test, however, only FPL 14981 prevented NMDLA-induced convulsions/mortality in mice and was 2-fold more active regarding MK801 binding. The hydroxy-methyl derivative of remacemide (FPL 13592) and its desglycinate (FPL 15112) prevented MES-induced convulsions only after i.v. administration; only the desglycine derivative displaced MK801 binding.(ABSTRACT TRUNCATED AT 400 WORDS)