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.     

Cytochemical characteristics of neurons in the trigeminal mesencephalic nucleus of hatchling chicks

The goal of the present study was to identify cytochemical markers characteristic of muscle afferents in hatchling chicks. To this end, we stained neurons in the trigeminal mesencephalic nucleus with a variety of markers that label subsets of neurons in avian dorsal root ganglia. We found that trigeminal mesencephalic neurons are surprisingly heterogeneous in their cytochemical make-up, expressing, to varying degrees, substance P, cholecystokinin, carbonic anhydrase, calbindin D-28k, parvalbumin, and S-100β. Calbindin D28k and S-100β appeared to be expressed equally in medial and lateral divisions of the trigeminal mesencephalic nucleus. In contrast, substance P- and cholecystokinin-immunoreactive neurons were more abundant in the medial division, whereas carbonic anhydrase activity and parvalbumin immunoreactivity were stronger in the lateral division. We were unable to detect met-enkephalin, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal peptide, somatostatin, γ-aminobutyric acid, or tyrosine hydroxylase in the trigeminal mesencephalic nucleus. Moreover, these neurons did not appear to bind the lectin Dolichos biflorus agglutinin. The heterogeneity of expression of markers among trigeminal mesencephalic nucleus neurons, especially between neurons in the medial and lateral divisions, suggests that these neurons are functionally diverse.     

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.     

Morphine place conditioning is differentially affected by CCKA and CCKB receptor antagonists.

In the present study we have examined the interaction between the selective cholecystokinin (CCK)A and CCKB receptor antagonists, devazepide and L365-260 on morphine conditioned place preference (CPP). Using an unbiased procedure, morphine (1.5 mg/kg) produced a reliable CPP which was observed irrespective of the conditioning compartment type. Pretreatment with devazepide (0.001-0.01 mg/kg s.c.) produced a dose related attenuation of this response. At higher doses (0.1-1 mg/kg) this antagonism became variable and dependent on the training compartment with blockade only observed when conditioning was to the white/rough textured environment. This profile has also been reported for the serotonin (5-HT)3 receptor antagonist ondansetron. The CCKB antagonist L365-260 (0.000001-0.01 mg/kg) failed to antagonize the morphine CPP, if anything a mild potentiation was observed. To study this further we examined the interaction between L365-260 (0.01 mg/kg) and a subthreshold dose of morphine (0.3 mg/kg). At these doses neither drug elicited CPP, however when co-administered a significant CPP was recorded. Finally, L365-260 at 1 mg/kg induced a mild but significant CPP when administered alone. These results suggest a differential role of CCK receptor subtypes on reward-related behaviour and complement previous studies suggesting bimodal effects of CCK systems on mesolimbic dopamine function.     

Evaluation of non-invasive blood pressure measurement by the Finapres method at rest and during dynamic exercise in subjects with cardiovascular insufficiency

The accuracy and precision of the Finapres in recording rest and exercise blood pressure compared with the intra-arterial (aortic and brachial) and random-zero sphygmomanometer methods was assessed in 84 ischaemic patients in three different studies. Firstly, comparison at rest with the aortic intraarterial pressure in 50 ischaemic patients demonstrated that the Finapres systolic (136.5 ± 21.1 vs. 129.3 ± 19.0 mmHg;p < 0.001) and mean (92.4 ± 13.4 vs. 90.7 ± 11.4 mmHg;p < 0.001) arterial pressures were higher and diastolic pressures lower (70.4 ± 11.5 vs. 71.5 ± 9.8 mmHg;p < 0.001). The reproducibility of the Finapres and invasive method was similar for systolic (4.6% vs. 4.0%), diastolic (2.8% vs. 2.7%) and mean (3.3% vs. 3.0%) blood pressures. Second, in seven subjects studied twice at rest and during 4 min supine bicycle exercise, the exercise increase in blood pressure was greater on the Finapres compared with the brachial intra-arterial pressure (systolic +10.2 ± 6.3 vs. +3.6 ± 9.8 mmHg; diastolic +9.6 ± 11.1 vs. +0.2 ± 2.1 mmHg;p = 0.02 for each); however, at steady-state the peak/trough differences in pressure between the methods were similar. Thirdly, compared under rest conditions, to random zero sphygmomanometer (RZO), the Finapres systolic pressure was higher (6.8 ± 3.5 mmHg) and diastolic pressure lower (–6.0 ± 1.9 mmHg). During upright bicycle exercise, the difference between the Finapres and RZO in systolic blood pressure increased at each level of exercise (+14.3 ± 4.2, +17.9 ± 4.0 and +22.2 ± 4.1 mmHg respectively at each exercise stage:p < 0.01). For RZO, diastolic blood pressure fell as exercise workload increased whereas Finapres diastolic blood pressure increased on exercise (3.1 ± 2.6, 7.0 ± 2.1 and 8.1 ± 2.0 mmHg respectively:p < 0.01). Thus there were systematic differences between the values recorded by the Finapres and proximal blood pressure methods and limited agreement in the rest to exercise increments related to light exercise. Calibration of the Finapres values in terms of the other methods is limited by the variable relationship to these related changes in arterial distensibility.