LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder caused by mutations in LMNA, which encodes the nuclear scaffold proteins lamin A and C. In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24. LMNA-linked progerias can be grouped into two classes: (1) the processing-deficient, early onset "typical" progerias (e.g., HGPS), and (2) the processing-proficient "atypical" progeria syndromes (APS) that are later in onset. Here we describe a previously unrecognized progeria syndrome with prominent cutaneous and cardiovascular manifestations belonging to the second class. We suggest the name LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. Affected patients are normal at birth but undergo progressive cutaneous changes in childhood and die in middle age of cardiovascular complications, including accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. In addition, the proband demonstrated cancer susceptibility, a phenotype rarely described for LMNA-based progeria disorders. The LMNA mutation that caused LCPS in this family is a heterozygous c.899A>G (p.D300G) mutation predicted to alter the coiled-coil domain of lamin A/C. In skin fibroblasts isolated from the proband, the processing and levels of lamin A and C are normal. However, nuclear morphology is aberrant and rescued by treatment with farnesyltransferase inhibitors, as is also the case for HGPS and other laminopathies. Our findings advance knowledge of human LMNA progeria syndromes, and raise the possibility that typical and atypical progerias may converge upon a common mechanism to cause premature aging disease.

Current evidence for the use of emerging radiologic technologies for disease screening.

Recent technologic advances in the field of radiology have resulted in the availability of several new tests with potential applications for disease screening. Presently, these tests are being marketed directly to patients as noninvasive means to provide peace of mind that they are disease free. Such assurance is appealing to many individuals, and some are willing to spend up to 1500 dollars to choose from a menu of available diagnostic options. Given that a physician's referral is unnecessary, many healthcare providers are unaware that such testing has taken place until their patients present to them with abnormal test results. In this review, we examine the evidence supporting the use of electron beam computed tomography for coronary artery disease screening, spiral computed tomography of the chest for lung cancer screening, computed tomographic colonography for colon cancer screening, and total-body computed tomography for general screening. Although some of these modalities show promise for the future, there is insufficient evidence to support the use of any of these testing methods for secondary prevention. The potential for harm associated with false-positive test results, false-negative test results, undue anxiety, and radiation exposure exists but requires further study to quantify actual risk.

Training U.S. medical students to care for the chronically ill.

PURPOSE: The growing prevalence of chronic illness has important implications for the training of all physicians. The authors assessed the degree to which undergraduate medical curricula explicitly address chronic care competencies selected through literature and expert review. METHOD: In 2001, trained student assistants interviewed directors of required medical school courses (internal medicine, pediatrics, family practice, and ambulatory care clerkships; longitudinal care; and other relevant courses) at 16 representative U.S. medical schools sampled by geography, curriculum reform activity, and primary care orientation of graduates. Course directors were asked whether chronic care competencies were addressed using specific curricular methods (written objectives, course materials, observational evaluations, written/oral examinations, other required course activities), and to rate the importance (1 = not important; 5 = essential) of each competency for their course and for the overall undergraduate curriculum. RESULTS: All 70 eligible course directors responded. Of 49 chronic care competencies, 29 (59%) received mean importance ratings for a course of >/=3, but only 14 (29%) were addressed using two or more specific curricular methods. Course directors gave highest importance ratings (mean > 3.9) to screening for abuse, awareness of patients' sociocultural perspectives, and protecting patients' confidentiality. They gave lowest importance ratings (mean

Effect of student involvement on patient perceptions of ambulatory care visits: a randomized controlled trial.

OBJECTIVE: To determine if patient satisfaction with ambulatory care visits differs when medical students participate in the visit. DESIGN: Randomized controlled trial. SETTING: Academic general internal medicine practice. PARTICIPANTS: Outpatients randomly assigned to see an attending physician only (N = 66) or an attending physician plus medical student (N = 68). MEASUREMENTS AND MAIN RESULTS: Patient perceptions of the office visit were determined by telephone survey. Overall office visit satisfaction was higher for the "attending physician only" group (61% vs 48% excellent), although this was not statistically significant (P =.16). There was no difference between the study groups for patient ratings of their physician overall (80% vs 85% excellent; P =.44). In subsidiary analyses, patients who rated their attending physician as "excellent" rated the overall office visit significantly higher in the "attending physician only" group (74% vs 55%; P =.04). Among patients in the "attending physician plus medical student" group, 40% indicated that medical student involvement "probably" or "definitely" did not improve their care, and 30% responded that they "probably" or "definitely" did not want to see a student at subsequent office visits. CONCLUSIONS: Although our sample size was small, we found no significant decrement in patient ratings of office visit satisfaction from medical student involvement in a global satisfaction survey. However, a significant number of patients expressed discontent with student involvement in the visit when asked directly. Global assessment of patient satisfaction may lack sensitivity for detection of dissatisfaction. Future research in this area should employ more sensitive measures of patient satisfaction.