Recent Publications by CFE Educators

The Carnegie Foundation for the Advancement of Teaching, which in 1910 helped stimulate the transformation of North American medical education with the publication of the Flexner Report, has a venerated place in the history of American medical education. Within a decade following Flexner's report, a strong scientifically oriented and rigorous form of medical education became well established; its structures and processes have changed relatively little since. However, the forces of change are again challenging medical education, and new calls for reform are emerging. In 2010, the Carnegie Foundation will issue another report, Educating Physicians: A Call for Reform of Medical School and Residency, that calls for (1) standardizing learning outcomes and individualizing the learning process, (2) promoting multiple forms of integration, (3) incorporating habits of inquiry and improvement, and (4) focusing on the progressive formation of the physician's professional identity. The authors, who wrote the 2010 Carnegie report, trace the seeds of these themes in Flexner's work and describe their own conceptions of them, addressing the prior and current challenges to medical education as well as recommendations for achieving excellence. The authors hope that the new report will generate the same excitement about educational innovation and reform of undergraduate and graduate medical education as the Flexner Report did a century ago.

PURPOSE

Adipose tissue derived stem cells can differentiate into muscle and neuron-like cells in vitro. We investigate the usefulness of adipose tissue derived stem cells for overactive bladder in obese hyperlipidemic rats.

MATERIALS AND METHODS

Hyperlipidemia was induced in healthy rats by a high fat diet. The resulting obese hyperlipidemic rats were treated with bladder injection of saline, adipose tissue derived stem cells or tail vein injection of adipose tissue derived stem cells. Bladder function was assessed by 24-hour voiding behavior study and conscious cystometry. Bladder histology was assessed using immunostaining and trichrome staining, followed by image analysis.

RESULTS

Serum total cholesterol and low density lipoprotein were significantly higher in obese hyperlipidemic rats than in normal rats (p 0.01). The micturition interval was shorter in saline treated obese hyperlipidemic rats than in normal rats, obese hyperlipidemic rats that received adipose tissue derived stem cells via the tail vein and obese hyperlipidemic rats that received adipose tissue derived stem cells by bladder injection (mean +/- SEM 143 +/- 28.7 vs 407 +/- 77.9, 281 +/- 43.9 and 368 +/- 66.7 seconds, respectively, p = 0.0084). Bladder wall smooth muscle content was significantly lower in obese hyperlipidemic rats than in normal animals (p = 0.0061) while there was no significant difference between obese hyperlipidemic groups. Nerve content and blood vessel density were lower in controls than in obese hyperlipidemic rats treated with adipose tissue derived stem cells.

CONCLUSIONS

Hyperlipidemia is associated with increased urinary frequency, and decreased bladder blood vessel and nerve density in rats. Adipose tissue derived stem cell treatment ameliorates these adverse effects and holds promise as a potential new therapy for overactive bladder.

PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.