Preparing fourth-year medical students to teach during internship

Interns are expected to teach medical students, yet there is little formal training in medical school to prepare them for this role. To enhance the teaching skills of our graduating students we initiated a 4-hour "teaching to teach" course as part of the end of the fourth-year curriculum. Course evaluations demonstrate that students strongly support this program (overall ratings 2000 to 2005: mean=4.4 [scale 1 to 5], n=224). When 2004 course participants were surveyed during the last month of their internship, 84%"agree" or "strongly agree" with the statement: "The teaching to teach course helped prepare me for my role as a teacher during internship" (2005: mean 4.2 [scale 1 to 5], n=45, response rate 60%). A course preparing fourth-year students to teach during internship is both feasible and reproducible, with a minimal commitment of faculty and resident time. Participants identify it as an important addition to their education and as useful during internship.     

Efficacy of add-on aldosterone receptor blocker in uncontrolled hypertension

BACKGROUND: Uncontrolled hypertension (UH) may be caused by hyperaldosteronism, and some experts recommend the routine use of aldosterone antagonists in this condition. The purpose of this study was to evaluate the efficacy of this approach and to characterize those who respond effectively to an add-on aldosterone antagonist. METHODS: We retrospectively analyzed the effectiveness of spironolactone, an aldosterone antagonist, used as add-on therapy, compared with a standard add-on treatment, in patients referred to a hypertension clinic with UH despite the use of two or more antihypertensive drugs. RESULTS: A total of 340 patients (186 male) with an average age of 63 +/- 14 years were followed for at least 3 months. Of the patients, 42 received add-on spironolactone and 298 received an additional antihypertensive drug other than spironolactone. Baseline characteristics were similar in both groups. Blood pressure (BP) decreased significantly in both groups. In patients who received spironolactone, BP decreased by 23.2/12.5 mm Hg from 165 +/- 27/94 +/- 15 to 142 +/- 25/81 +/- 9 mm Hg, whereas in patients who received other add-on therapy BP decreased by 7.6/5.8 mm Hg from 160 +/- 24/91 +/- 12 to 152 +/- 20/85 +/- 11 mm Hg (P < .05). Patients who received spironolactone had lower serum potassium levels than those who did not receive spironolactone 3.8 +/- 0.4 v 4.5 +/- 0.5 mmol/L respectively (P < .001). Potassium levels <4 mmol/L were associated with a greater reduction in BP. CONCLUSIONS: Add-on spironolactone is a highly effective add-on treatment in UH, mainly in patients with low serum potassium levels. Further studies assessing serum potassium as a marker for treatment approach are needed to establish the role of aldosterone antagonists in the management of UH.     

Coincidental outbreak of methicillin-resistant Staphylococcus aureus in a hematopoietic stem cell transplantation unit

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common nosocomial pathogens among hospital-acquired infections, and immunocompromised patients are highly susceptive to infection. The molecular typing of isolated strains is a common method for tracing an outbreak of MRSA, but experience with this approach is still limited in the hematopoietic stem cell transplantation (HSCT) ward. METHODS: We experienced 6 cases of MRSA infection/colonization in our 26-bed HSCT ward during a 4-week period. This unusual outbreak strongly suggested that the same MRSA strain was involved despite strict isolation and aseptic patient care. Clarification of the transmission pattern was critical, and we applied pulsed-field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP) assays for evaluation. RESULTS AND CONCLUSION: In four of the six cases, the pattern of bands examined by PFGE and AFLP analyses supported the idea that direct person-to-person transmission was very unlikely and the outbreak was coincidental. This experience highlights the clinical value of molecular typing methods for the clinical epidemiological assessment of MRSA outbreak.     

Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism

It is rare that coloboma, heart anomalies, choanal atresia, retarded growth and development, and genital and ear anomalies (CHARGE) syndrome patients have DiGeorge sequence showing severe immunodeficiency due to the defect of the thymus. Although the only treatment to achieve immunological recovery for these patients in countries where thymic transplantation is not ethically approved would be hematopoietic cell transplantation, long-term survival has not been obtained in most patients. On the other hand, it is still not clarified whether hypoparathyroidism is one of the manifestations of CHARGE syndrome. We observed a CHARGE syndrome patient with chromodomain helicase DNA-binding protein 7 mutation showing DiGeorge sequence including the defect of T cells accompanied with the aplasia of the thymus, severe hypoparathyroidism, and conotruncal cardiac anomaly. He received unrelated cord blood transplantation without conditioning at 4 months of age. Recovery of T cell number and of proliferative response against mitogens was achieved by peripheral expansion of mature T cells in cord blood without thymic output. Although he is still suffering from severe hypoparathyroidism, he is alive without serious infections for 10 months.     

Are language and social communication intact in children with congenital visual impairment at school age?

Background: Development of children with congenital visual impairment (VI) has been associated with vulnerable socio‐communicative outcomes often bearing striking similarities to those of sighted children with autism. 1 To date, very little is known about language and social communication in children with VI of normal intelligence. Methods: We examined the presentation of language and social communication of 15 children with VI and normal‐range verbal intelligence, age 6–12 years, using a standardised language assessment and parental reports of everyday social and communicative behaviours. Their profiles were compared to those of typically developing sighted children of similar age and verbal ability. Results: Compared to their sighted peers, and relative to their own good and potentially superior structural language skills, children with VI showed significantly poorer use of language for social purposes. Pragmatic language weaknesses were a part of a broader socio‐communicative profile of difficulties, present in a substantial proportion of these children and consistent with the pattern found in sighted children with autism. Conclusions: There are ongoing socio‐communicative and pragmatic language difficulties in children with congenital VI at school age, despite their good intellectual abilities and advanced linguistic skills. Further research is required to unpack the underlying causes and factors maintaining this vulnerability in such children.     

Massive rotator cuff tears repaired on top of humeral head by McLaughlin's procedure

The clinical and radiographic outcomes of McLaughlin's procedure for massive rotator cuff tears were investigated in 25 shoulders, in which the cuff tears were so severe that the tendons were sutured on the top of the humeral head. The mean age at surgery was 62.2 years (range, 39-74 years). The mean follow-up period was 50 months (range, 24-80 months). The University of California, Los Angeles score significantly improved from 10.9 to 31.8 points postoperatively; the postoperative result was classified as excellent in 11 shoulders, good in 11, and poor in 3. Osteoarthritis progressed postoperatively in 7 shoulders (28%), and upper migration of the humeral head progressed in 6 (24%), although both progression rates were no higher than those for other common procedures. When torn tendons reach over the top of the humeral head with the arm at the side in patients with massive tears that are not reparable to the greater tuberosity, satisfactory clinical outcomes can be expected.     

Buserelin acetate microparticle dispersion effects drug release and plasma E(1) levels

We investigated the effect of different dispersion methods on release behavior and efficacy onset following microparticle administration of buserelin acetate (BA) sustained-release injection. In this in vitro release study, the initial dispersion of BA increased with increased stirring speed (p<0.01). Stability of BA was studied over 7 days after BA release. The initial BA release rate was higher (p<0.01) after a 1-min vibration dispersion method (VDM) using a test tube mixer (2000 rpm) compared with the standard dispersion method (SDM) by hand. Without shaking, powder aggregation was observed, and BA release was lower than in either the SDM or VDM methods. In this study using 4-week-old Sprague-Dawley female rats, the initial plasma estrone (E(1)) concentrations were lower (p<0.05) in the VDM method than in the SDM method. Observations by optical microscope and scanning microscope showed no change in microparticle shape or distribution of size induced by SDM, VDM or the ultrasonication dispersion method. These results suggest that different dispersion methods do not change the shape and distribution of microparticle size, but clearly change the BA release rate and the transition in plasma E(1) concentrations that can affect drug efficacy.     

Functional neuroimaging evidence for high cognitive effort on the Word Memory Test in the absence of external incentives

PRIMARY OBJECTIVE: This study presents data from a functional neuroimaging experiment which brings into question whether poor performance on the Word Memory Test (WMT) can be construed as straightforward evidence for 'poor effort' in the context of cognitive assessment, as asserted in a recent report in this journal. METHODS AND PROCEDURES: Functional magnetic resonance image (fMRI) data were acquired from four participants without brain injury who engaged in the delayed recognition (DR) portion of Green's WMT protocol. OUTCOMES AND RESULTS: Compared to a simple perceptual identification control task, this study found a highly reliable activation pattern across all participants which was restricted almost exclusively to cortical areas most commonly associated with task difficulty, memory load, concentration and other forms of cognitive effort These areas include dorsolateral prefrontal cortex, anterior insula, superior parietal cortex and the dorsal anterior cingulate. CONCLUSIONS: These findings demonstrate that the WMT activates numerous cortical regions that are critical for cognitive effort. Given the extensive neural network necessary to perform the WMT, this study raises important questions about what WMT 'failure' truly means in patients with traumatic brain injury, who have increased likelihood of disruption within this neural network of vision, language, attention, effort and working memory.     

Progress in QSAR toxicity screening of pharmaceutical impurities and other FDA regulated products

Active ingredients in pharmaceutical products undergo extensive testing to ensure their safety before being made available to the American public. A consideration during the regulatory review process is the safety of pharmaceutical contaminants and degradents which may be present in the drug product at low levels. Several published guidances are available that outline the criteria for further testing of these impurities to assess their toxic potential, where further testing is in the form of a battery of toxicology assays and the identification of known structural alerts. However, recent advances in the development of computational methods have made available additional resources for safety assessment such as structure similarity searching and quantitative structure-activity relationship (QSAR) models. These methods offer a rapid and cost-effective first-pass screening capability to assess toxicity when conventional toxicology data are limited or lacking, with the potential to identify compounds that would be appropriate for further testing. This article discusses some of the considerations when using computational toxicology methods for regulatory decision support and gives examples of how the technology is currently being applied at the US Food and Drug Administration.