Assessing the clinical ethical competence of undergraduate medical students

At the University of Newcastle, health law and ethics is taught and assessed in each year of the five-year curriculum. However, the critical question for assessment remains: 'Does teaching ethics have a measurable effect on the clinical activity of medical students who have had such courses?' Those responsible for teaching confront this question each year they sit down to construct their assessment tools. Should they assess what the student knows? Should they assess the student's moral reasoning, that is, what decisions the student makes, and, how these decisions are justified, or should they assess what the student actually does when dealing with patients in the clinical setting, and how he or she does it? From 1982 to 1991, assessment at Newcastle was primarily aimed at determining the quality of the students' ethics knowledge base. This paper describes the strengths and limitations of a purely knowledge-based method of evaluation and why in 1992, we are now attempting to redefine and assess, what we call 'clinical ethical competence' in terms of how students actually apply this knowledge base in a controlled clinical context.     

Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans

This study investigates the possible interactions of antidepressant agents and hallucinogens in humans through structured interviews using a standardized questionnaire. Volunteer subjects recruited through announcements placed on the Internet or other sources were asked to describe the somatic, hallucinatory, and psychological effects of self-administered LSD prior to and during chronic administration of an antidepressant. Twenty-eight out of 32 subjects (88%) who had taken an antidepressant with inhibitory effects on serotonin (5-HT) reuptake (fluoxetine, paroxetine, sertraline, trazodone) for over 3 weeks had a subjective decrease or virtual elimination of their responses to LSD. An additional subject who had taken fluoxetine for only 1 week had an increased response to LSD. These data are in contrast to our previous study that reported increased responses to LSD during chronic administration of tricyclic antidepressants or lithium. Possible mechanisms of action for the effects from serotonergic antidepressants involve 5-HT2 and 5-HT1A receptors, changes in extracellular brain serotonin concentrations, and changes in brain catecholamine systems.     

Concentrations of trypsin inhibitor and immunoglobulins in colostrum of Jersey cows

Colostrum samples from 49 Jersey cows were analyzed for concentrations of trypsin inhibitor, IgG, IgM, IgA, TS, fat, specific gravity, and N fractions. Colostrum (100 ml) was sampled from each cow as soon as possible after parturition. Mean concentrations of IgG, IgM, and IgA were 84.6, 3.4, and 4.5 g/L, respectively. Mean concentration of trypsin inhibitor was 56 mg of trypsin inhibited/dl of colostrum. Concentration of trypsin inhibitor was unaffected by lactation number and averaged 60, 53, and 54 mg of trypsin inhibited/dl of colostrum for cows in first, second, and third or later lactations, respectively. Colostral trypsin inhibitor and IgG were correlated (.54), although correlations between trypsin inhibitor and IgM and IgA were not significant. Trypsin inhibitor in colostrum was also positively correlated with fat, total N, protein N, noncasein N, and TS in colostrum. Variation in concentration of trypsin inhibitor from first-milking colostrum was closely related to colostral IgG concentration and may serve to protect IgG and other proteins from proteolytic degradation in the intestine of the neonatal calf.     

Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery

BACKGROUND: The antineoplastic compound paclitaxel (Taxol) causes an increased assembly of extraordinarily stable microtubules. The present study was designed to characterize the effects of paclitaxel on proliferation and migration of human arterial smooth muscle cells (haSMCs) in vitro and on neointima formation in an in vivo experimental rabbit model. METHODS AND RESULTS: Both monocultures of haSMCs and cocultures with human arterial endothelial cells (haECs) were used. Cell growth after 4, 8, and 14 days was determined in the absence or presence of platelet-derived growth factor-AB (PDGF-AB), basic fibroblast growth factor (bFGF), or thrombin. Nonstop paclitaxel exposure, as well as single-dose applications of paclitaxel for 24 hours or even 20 minutes (0.1 to 10.0 micromol/L), caused a complete and prolonged inhibition of haSMC growth up to day 14, with an IC50 of 2.0 nmol/L. Mitogens or cocultures with stimulating haECs did not significantly attenuate paclitaxel-induced effects. Immunohistochemistry showed characteristic cytoskeletal changes predominantly in the microtubule network. Additionally, in 20 male New Zealand White rabbits, intimal plaques were produced by electrical stimulation. In 10 animals, paclitaxel was locally applied by use of microporous balloons. Histologically, the intima wall area, wall thickness, and degree of stenosis were reduced significantly in paclitaxel-treated animals compared with controls. CONCLUSIONS: Our data show that paclitaxel inhibits haSMC proliferation and migration in a dose-dependent manner in monocultures and cocultures even in the presence of mitogens. Furthermore, paclitaxel prevents neointima formation in rabbits after balloon angioplasty. The long-lasting effect after just several minutes' exposure time makes this lipophilic substance a promising candidate for local antiproliferative therapy of restenosis.     

Differential effect of unfractionated heparin and low molecular weight heparin on intravascular tissue factor pathway inhibitor: evidence for a difference in antithrombotic action

PURPOSE: Successful endovascular repair of an abdominal aortic aneurysm (AAA) requires the creation of a hemostatic seal between the endograft and the underlying aortic wall. A short infrarenal aortic neck may be responsible for incomplete aneurysm exclusion and procedural failure. Sixteen patients who had an endograft positioned completely below the lowest renal artery and 37 patients in whom a porous portion of an endograft attachment system was deliberately placed across the renal arteries were studied to identify if endograft positioning could impact on the occurrence of incomplete aneurysm exclusion. METHODS: Fifty-three patients underwent aortic grafting constructed from a Palmaz balloon expandable stent and an expandable polytetrafluoroethylene (ePTFE) graft implanted in an aorto-ilio-femoral, femoral-femoral configuration. Arteriography, duplex ultrasonography and spiral CT scans were performed in each patient before and after endografting to evaluate for technical success, the presence of endoleaks, and renal artery perfusion. RESULTS: There was no statistically significant difference in patient demography, AAA size, or aortic neck length or diameter between patients who had their endografts placed below or across the renal arteries. However, significantly more proximal aortic endoleaks occurred in those patients with infrarenal endografts (P < or = .05). Median serum creatinine level before and after endografting was not significantly different between the 2 patient subgroups, with the exception of 2 patients who had inadvertent coverage of a single renal orifice by the endograft. Median blood pressure and the requirement for antihypertensive therapy remained the same after transrenal aortic stent grafting. Significant renal artery compromise did not occur after appropriately positioned transrenal stents as shown by means of angiography, CT scanning, and duplex ultrasound scan. Mean follow-up time was 10.3 months (range, 3 to 18 months). Patients who had significant renal artery stenosis (> or =50%) before aortic endografting did not show progression of renal artery stenosis after trans-renal endografting. Two patients with transrenal aortic stent grafts had inadvertent coverage of 1 renal artery by the endograft because of device malpositioning, which resulted in nondialysis dependent renal insufficiency. In addition, evidence of segmental renal artery infarction (<20% of the kidney), which did not result in an apparent change in renal function, was shown by means of follow-up CT scans in 2 patients with transrenal endografts. CONCLUSION: Transrenal aortic endograft fixation using a balloon expandable device in patients with AAAs can result in a significant reduction in the risk of proximal endoleaks. Absolute attention to precise device positioning, coupled with the use of detailed imaging techniques, should reduce the risk of inadvertent renal artery occlusion from malpositioning. Long-term follow-up is essential to determine if there will be late sequelae of transrenal fixation of endografts, which could adversely effect renal perfusion.     

Six-month outcomes for MRI-related vascular depression

A patient with 'spent' polycythaemia vera showed extensive extramedullary haematopoiesis (EMH) in non-haematopoietic tissue clinically resulting in an ischaemic colitis and respiratory symptoms due to lung infiltrates. On laboratory investigation, the EMH also included immature erythroblasts due to acute erythroid leukaemia. It is hypothesised that the abnormal homing of erythroid progenitors might be related to the abnormal expression of antigens, such as CD36.     

Calculated prostate cancer volume greater than 4.0 cm3 identifies patients with localized prostate cancer who have a poor prognosis following radical prostatectomy or external-beam radiation therapy

PURPOSE: Patients with palpable extraprostatic disease (T3) have a poor prostate-specific antigen (PSA) failure-free (bNED) survival rate after radical prostatectomy (RP) or external-beam radiation therapy (RT). This study was performed to validate or refute the prognostic value of the previously defined calculated prostate cancer volume (cV(Ca)). PATIENTS AND METHODS: For patients with clinically localized disease (T1c,2), a Cox regression multivariable analysis was used to assess the ability of the cV(Ca) value to predict time to posttherapy PSA failure following RP or RT. RESULTS: The cV(Ca) value was a significant predictor (P < or = .0005) of time to posttherapy PSA failure in both an RP and RT data set independent of the one used to derive the cV(Ca)-based clinical staging system. In both RP- and RT-managed patients, estimates of 3-year bNED survival were not statistically different for patients with either T1c,2 disease and a cV(Ca) greater than 4.0 cm3 (RP, 27%; RT, 18%) or T3 disease (RP, 37%; RT, 34%). Despite pathologic T2 disease, the 3-year estimate of bNED survival was at most 51% in RP-managed patients with T1c,2 disease and cV(Ca) greater than 4.0 cm3. CONCLUSION: A cV(Ca) greater than 4.0 cm3 identified patients with T1c.2 disease whose bNED survival was poor after RT or RP despite pathologic T2 disease that suggests the presence of occult micrometastatic disease in many of these patients. Prospective randomized trials to evaluate the impact on survival of adjuvant systemic therapy in these high-risk patients are justified.