THE SCIENCES OF CLINICAL PRACTICE

The Robert Wood Johnson Commission on Medical Education focused on evidence that, in the midst of the genetic revolution in medicine, medical students all too often are not engaged by the science component of their education. Medical education is being driven by social as well as these intellectual forces to make fundamental changes. In the USA, the rich array of scientific talent can be used more effectively, and there is a new significance for the behavioural, social, probabilistic, and information sciences. The Report discusses the general changes under way in the USA and includes examples from the eight schools in the Robert Wood Johnson Foundation's Preparing Physicians for the Future: A Program in Medical Education .
Another report explores the reasons why the general changes under way in North American medical education are difficult to bring about. Educating Medical Students is the report of the Assessing Change in Medical Education: The Road to Implementation (ACME-TRI) project of the Association of American Medical Colleges. This project, funded by the Charles E. Culpeper Foundation, explored the recurring problems in medical students' education that have been reported from the 1930s. The ACME-TRI report documents that most medical schools have not solved these recurring problems, summarizes the schools' views of the barriers to solving these problems, and identifies strategies to assist schools in overcoming or minimizing the barriers they have identified.
Together, the Robert Wood Johnson Commission report and the ACME-TRI report provide a context in which to consider the complex issues facing medical education in the 21st century.     

Different effects of intracellular and extracellular TEA on voltage-dependent K currents of acutely isolated hippocampal CA1 neurons.

Tetraethylammonium (TEA) effects on K currents were examined on either side of the membrane of hippocampal CA1 neurons by means of whole-cell voltage-clamp recording and intracellular perfusion. Recording media contained ion channel blockers to allow the selective activation of voltage-dependent K currents which consisted of a rapidly decaying component (A-current) and a delayed component. Voltage protocols were applied to separate the A-current from the delayed component. Results show that 10 mM extracellular TEA suppressed 50 +/- 11% (S.D., n = 4) of the delayed current at different levels of depolarization but had little effect on the A-current. In contrast 10 mM TEA applied by intracellular perfusion suppressed the A-current by 42 +/- 10% (S.D., n = 4) in addition to inhibiting the delayed currently 55 +/- 15% (S.D., n = 4). Both the intracellular and extracellular actions of TEA on K currents showed no voltage- nor time-dependency. The results suggest that voltage-dependent transient current (A-current) is mediated through a separate group of ionic channels distinct from those that sustained the delayed current. Furthermore, the asymmetrical effects of intracellular and extracellular TEA on the transient current are similar to those described for the A-current in molluscan neurons. This observation supports the notion that the structure of the ion channel mediating the A-current is closely conserved across different species.     

Norephedrine (phenylpropanolamine) stimulates oxygen consumption and lactate production in the perfused rat hindlimb

d,l-Norephedrine (phenylpropanolamine) which is both a demethylated analogue and a metabolite of d,l-ephedrine, is a reputed anorectic agent. In the present study the proposed most active isomer of this mixture, l-norephedrine has been assessed as a peripherally acting thermogenic agent in the isolated perfused rat hindlimb. l-Norephedrine produced a dose-dependent increase in oxygen uptake and perfusion pressure and increased lactate production. Whereas propranolol potentiated the increase in oxygen uptake and perfusion pressure produced by l-norephedrine, prazosin significantly and nitroprusside totally inhibited both of these changes. Nitroprusside also completely inhibited the increase in lactate production. We conclude that norephedrine has a hitherto unrecognized peripheral thermogenic activity in the perfused rat hindlimb resulting from its interaction with alpha 1 adrenergic receptors that control vasoconstriction in this tissue.     

Successful pregnancies following remission in childhood acute lymphoblastic leukaemia--case report.

We report two successful pregnancies in a 17-year-old Arab girl who had received modern combination chemotherapy and central nervous system minimal disease therapy for childhood acute lymphoblastic leukaemia at the age of 9.5 years.     

烧伤大鼠血清对血管内皮细胞通透性的影响

加深入阐明严重烧伤早期全身血管通透性增加继而引直民早期损害的发生机制，本实验应用培养于微孔滤膜上的小牛瞌 及皮细胞单层所构成的选择性通透屏障模型，观察了３０％Ⅲ度烧伤大鼠血清对其影响，结果发现，烧伤早期烧伤血清刺激后ＥＣ单层对Ｈａｎｋｓ液或白蛋白液滤过流量、滤过系数均明显增加。     

Clinical evaluation of technetium-99m infecton for the localisation of bacterial infection

The aim of the study was to distinguish infection from inflammation in patients with suspected infection using technetium-99m Infecton. Ninety-nine patients (102 studies) referred for infection evaluation underwent imaging with 400 MBq^99mTc-Infecton at 1 and 4 h. Most patients had appropriate microbiological tests and about half (56) had radiolabelled white cell scans as well. No adverse effects were noted in any patient. The clinical efficacy of^99mTc-Infecton depended in part on whether imaging was undertaken during intibiotic therapy for infection or not. In consultation with the microbiologist, 5–14 days of appropriate and successful antibiotic therapy was considered adequate to classify some results as true-negatives. The figures for sensitivity and specificity of^99mTc-Infecton for active or unsuccessfully treated infection were 83% and 91% respectively. It is concluded that^99mTc-Infecton imaging contributed to the differential diagnosis of inflammation. It is being used as the first imaging modality when bacterial infection is suspected.     

The pharmacokinetics of lignocaine in humans during a computer-controlled infusion.

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.     

大剂量卡铂化疗的药物毒性观察

6例肺癌患者接受了大剂量卡铂并自体骨髓移植治疗 ,卡铂剂量从 5 60～ 1375 mg/ m2 ,5例加用 VP～ 1630 0 mg,1例并用 MMC6mg和 VCR2 mg;主要毒性反应为白细胞、中性粒细胞、血小板减少和脱发 ( WHO毒性反应 ～ 级 )其次是贫血、皮肤粘膜出血、呕吐和可逆性肝功能损害 ,口腔粘膜溃疡及轻度发烧各 2例 ,一过性蛋白尿、室上性心动过速和便秘各 1例 ,尿素氮和肌酐未见升高 ;全部患者骨髓均获解救 ,从自体骨髓回输到骨髓造血功能重建成功平均 2 6.67( 17～ 32 )天     

Risk factors of acute pancreatitis]

A total of 689 operative cases of acute necrotic pancreatitis (ANP) were collected from 42 hospitals all over the country by the ANP Cooperative Study Group in the years of 1987 to 1989. General data, laboratory findings, pathology of the pancreas and the type of surgical treatment were analysed according to the outcome of the patient. The results showed that 37% of the cases were related to cholelithiasis, the highest incidence was in age above 60, and female patients were predominant and with higher mortality. Laboratory findings at admission, WBC greater than 20,000/mm3, Hb greater than 15 g%, blood sugar greater than 200 mg%, serum bilirubin greater than 5 mg%, BUN greater than 20 mg%, and serum calcium less than 7 mg% were related to the markedly elevated mortality rate. Operative findings noted in patients with bloody or cloudy peritoneal fluid, necrotic changes up to 75% of the pancreas, more than 2 areas of extrapancreatic involvements and resection of a large portion of the pancreas was found to be necessary were all related to a higher mortality. And emergency operations performed within 24 hours after the onset of the disease was also related with a highest mortality rate.