Esophageal IgG4 levels correlate with histopathologic and transcriptomic features in eosinophilic esophagitis.

BACKGROUND: Recent data associate eosinophilic esophagitis (EoE) with IgG4 rather than IgE, but its significance and function have not been determined. Our aims were to measure esophageal IgG4 levels and to determine functional correlations as assessed by histologic and transcriptome analyses. METHODS: This case-control study included pediatric subjects with EoE (≥15 eosinophils/HPF) and non-EoE controls. Protein lysates were analyzed for IgA, IgM, and IgG1-IgG4 using the Luminex 100 system; IgE was quantified by ELISA. Esophageal biopsies were scored using the EoE histology scoring system. Transcripts were probed by the EoE diagnostic panel, designed to examine the expression of 96 esophageal transcripts. RESULTS: Esophageal IgG subclasses, IgA, and IgM, but not IgE, were increased in subjects with EoE relative to controls. The greatest change between groups was seen in IgG4 (4.2 mg/g protein [interquartile range: 1.0-13.1 mg/g protein] vs 0.2 mg/g protein [0.1-0.9]; P < .0001). Tissue IgG4 levels correlated with esophageal eosinophil counts (P = .0006); histologic grade (P = .0011) and stage (P = .0112) scores; and IL4, IL10, IL13, but not TGFB1, expression and had strong associations with a subset of the EoE transcriptome. Esophageal IgG4 transcript expression was increased and correlated with IgG4 protein levels and IL10 expression. CONCLUSION: These findings extend prior studies on IgG4 in adult EoE to the pediatric population and provide deeper understanding of the potential significance and regulation of IgG4, demonstrating that IgG4 is a relevant feature of the disease; is closely related to esophageal eosinophil levels, type 2 immunity and T regulatory cytokines; and is likely produced locally.

Medical evaluation for driver qualification for patients with cardiovascular disorders.

BACKGROUND: Primary care physicians commonly care for patients whose disabilities caused by cardiovascular diseases result in difficulty driving an automobile. Patients often seek their physician's advice as to whether they can continue to drive safely. METHODS: A MEDLINE literature search was performed from 1966 to 2000, using the query terms "automobile driving" and "automobile driving and cardiac." Selected articles were reviewed, as well as additional articles found through review of the references. In some cases articles were found by searching the Internet using the above key words and new query terms guided by the results of the original search. RESULTS AND CONCLUSIONS: The most important factor determining eligibility is whether the patient reports manifestations of cerebral hypoxia. Laboratory procedures are available for patients in whom the decision is difficult. Sometimes a referral to a specialist is needed. Many patients with a known cardiovascular disorder can continue to drive safely. Some conditions require a waiting period before driving can be resumed, while others call for a complete cessation of driving. Several guidelines from the literature are listed that can be helpful to primary care physicians when dealing with questions from their patients on this important topic.

Evaluation of fitness to drive. The physician's role in assessing elderly or demented patients.

The role of physicians in deciding whether a patient should continue to drive is purely advisory. However, physicians have a moral and, in some states, a legal obligation to report patients who are no longer fit to drive. The most authoritative test to predict safe driving in the elderly is an on-road evaluation conducted by the state driver's licensing authority, which has ultimate responsibility for deciding a patient's fitness to drive. Patients with mild dementia are generally considered safe drivers, although specialized testing, such as an on-road test, may be indicated. Those with moderate dementia can be further evaluated by the on-road test, since psychological testing to distinguish moderate from mild dementia is imprecise. Severe dementia is generally considered a contraindication to driving. When a patient is deemed unfit to drive, the physician can provide counseling and support to help ease the transition away from driving.

Community-based faculty: motivation and rewards.

BACKGROUND AND OBJECTIVES: The reasons why practicing physicians precept students in their offices, and the rewards they wish to receive for this work, have not been clearly elucidated. This study determined the reasons for precepting and the rewards expected among a network of preceptors in Milwaukee. METHODS: A questionnaire was mailed to 120 community-based physician preceptors in a required, third-year ambulatory care clerkship. Respondents were asked to identify why they volunteered and what they considered appropriate recognition or reward. RESULTS: The personal satisfaction derived from the student-teacher interaction was, by far, the most important motivator for preceptors (84%). The most preferred rewards for teaching included clinical faculty appointment, CME and bookstore discounts, computer networking, and workshops for improving skills in clinical teaching. CONCLUSIONS: Community-based private physicians who participate in medical student education programs are primarily motivated by the personal satisfaction that they derive from the teaching encounter. An effective preceptor recognition/reward program can be developed using input from the preceptors themselves.

Effect of student and preceptor gender on clinical grades in an ambulatory care clerkship.

BACKGROUND: Although several studies have addressed the effect of student gender on clinical performance evaluation, none has looked at the effect of preceptor gender or the interaction of preceptor gender and student gender. We investigated the possibility of gender effects in an ambulatory care clerkship where the preceptor-student ratio is usually one to one. METHOD: Clinical grades given by preceptors to third-year students after a required one-month ambulatory care medicine clerkship were analyzed by student gender, preceptor gender, and preceptor-student gender pairs. The study was conducted from August 1990 to October 1992 at the Medical College of Wisconsin. A total of 121 preceptors (97 men and 24 women) and 375 students (233 men and 142 women) participated. Analyses of variance were used to detect significant differences. RESULTS: On a scale of 0 to 4, the female students received a higher mean clinical grade than the male students (3.1 versus 3.0, p < .04). Preceptor gender had no effect on clinical grades until student gender was considered. The highest mean grade of 3.3 was given by male preceptors to female students, and the lowest mean grade of 2.9 was given by female preceptors to male students (p < .01). CONCLUSION: The female students received higher clinical grades in the ambulatory care clerkship, especially when the preceptor was male. Perhaps gender interaction should be considered when assigning students to preceptors and evaluating grading practices.

Students' time allocation in a required third-year ambulatory care clerkship.

PURPOSE: To assess time use by students during clinic sessions of an ambulatory care clerkship. METHOD: All 207 third-year students at the Medical College of Wisconsin during 1991-92 were asked to report their time use in eight categories during two clinic sessions of the three-week clinical component of the required clerkship in ambulatory care medicine. Other variables assessed were site of clinical rotation, first versus third week of rotation, and time of year of rotation. The statistical methods used were t-tests and one-way analysis of variance. RESULTS: Of the 207 students, 192 (93%) completed time-allocation reports for the first and third weeks of their rotations. The average time spent per clinic session was four hours. Compared with the students at faculty practice sites, the students at private practice sites spent significantly more time observing and working with preceptors as they saw patients and significantly less time doing solo clinical work (reviewing and writing in charts). During the course of each rotation, the students increased the time they saw patients by themselves and decreased the time they observed preceptors. As the year progressed, later cohorts of students spent less time observing preceptors and more time working by themselves. CONCLUSION: Both within and across rotations, the students eventually spent less time observing and more time working independently. However, the results suggest that preceptors in private practice may not allow students as much autonomy as do faculty preceptors. Further research is needed to determine (1) whether the differences between types of preceptors result in meaningful differences in the quality of education and (2) which activities or mixes of activities contribute most to students' education.

Crystallochemical characteristics of the inorganic phase of human calcific aortic valvar stenosis.

To determine the elemental composition of the mineral deposits found in human calcific aortic valvar stenosis and to verify by x ray diffraction crystal class previously reported by electron diffraction 138 quantitative energy dispersive analyses and x ray diffraction of pooled specimens were performed on samples of aortic valves excised from 12 patients. The principal components of the calcified portions of the valves were 38.15% calcium and 17.68% phosphorus. The weight percentage calcium to phosphorus ratio was 2.16 and an elemental distribution related to the simplest ideal unit cell formulation Ca10(PO4)6(OH)2 was determined as: (Ca0.952Mg0.044Na0.097K0.005)10 (P0.952S0.025C0.023)6O23.96(Cl0.0184O0. 982H)2. The hexagonal unit cell was found to have an a axis of 9.424 A(0.9424 nm); c axis of 6.787 A(0.6787 nm); volume of 522 A3(0.522 nm3); and density of 3.2 g.cm-3. On the bases of the composition, the axial dimensions, and the density the material was classified as the dahllite form of apatite. There was no evidence of crystalline cholesterol. Variations in elemental composition showed no significant correlation with age or sex of the patient; statistically, neither the cusp involved nor the location on the leaflet affected the mineral composition.

The way we teach: anatomy of the coronary artery system.

A simple model to enhance understanding of the three-dimensional anatomy of the human epicardial coronary artery circulation is discussed and potential instructive applications reviewed. The chambers of the heart are visualized as being related to one another as in a pair of opposed hands, which can be rotated to demonstrate the various structures as viewed in different angles of obliquity.

Relationship of angiographic and echographic dimensions in chronic left ventricular dilatation.

Recently discrepancies have been reported between echocardiographic (Echo) % delta D and angiocardiographic (Angio) ejection fraction (EF), particularly in valvular regurgitation. One hundred and twelve patients with varying degrees of LV dilatation were studied in the right anterior oblique position with M-mode Echo. None had localized contraction abnormalities. There were 20 normals, 33 with primary myocardial disease, and 59 with mitral and/or aortic regurgitation. Echo end-diastolic diameter (EDD) and end-systolic diameter (ESD) were consistently smaller than Angio calculated EDD and ESD, and the difference was magnified at larger EDDs (p less than 0.01). The result is a relatively poor correlation of Echo % delta D and Angio EF (r = 0.69), compared to r = 0.98 for Angio % delta D and EF, both from Angio visualization. However, if valvular disease patients are excluded, the correlation improves to 0.82. The mechanisms for these disparities include increased sphericity as the ventricle dilates, and in the case of valvular disease where the EF is better for any degree of dilatation, the echo measurement errors for EDD and ESD are different.

Postoperative pericarditis following thymectomy for myasthenia gravis. A prospective study.

Eight consecutive patients who underwent thymectomy for the treatment of myasthenia gravis were evaluated prospectively for the development of postoperative pericarditis. In four of the eight patients (50 percent) pericarditis developed within 48 hours after thymectomy. All four had a three-component pericardial friction rub, two of the four patients had a new postoperative pericardial effusion by echocardiography, and in two typical ECG diffuse concave ST segment elevation and evolutionary ST and T wave changes developed. In the four patients with postoperative pericarditis, a malignant thymoma adherent to the pericardium was found in two, while two patients had a normal thymus histology with no adherence to the pericardium. Thus, postoperative pericarditis was found in both of the patients with a thymoma and in two of six patients without a thymoma. This study demonstrates that a high incidence of pericarditis occurs following thymectomy for the treatment of myasthenia gravis.

Repolarization variant vs acute pericarditis. A prospective electrocardiographic and echocardiographic evaluation.

Patients with ECG nonischemic ST segment elevation were prospectively studied to determine the accuracy of the initial ECG diagnoses. Evaluations were made of 131 consecutive patients by serial clinical, ECG, and echocardiography to establish a diagnosis. Eighty-six (66 percent) had an initial ECG interpretation of repolarization variant. Only three of the 86 (3 percent) subsequently met clinical criteria for acute pericarditis. Analysis of the mean frontal ST segment vector and PR segment depression revealed no significant differences between the 119 patients with final clinical diagnosis of repolarization variant and the 12 with clinical acute pericarditis. The diagnostic reliability of the initial ECG alone as a means of confirming acute pericarditis is low (9/45, 20 percent) but in the detection of repolarization variant is extremely high (83/86, 97 percent).

Assessment of ventricular function by combined noninvasive measures: factors accounting for methodologic disparities.

We studied the predictive accuracy and disparities among cineventriculographic ejection fraction, pre-ejection period over left ventricular ejection time (PEP/LVET) obtained from the systolic time intervals and the percent shortening of the internal echocardiographic diameter (% delta D) in assessing left ventricular performance in 453 consecutive patients without valvular heart disease. In 308 patients all three tests were normal, and in 78 patients all three tests were abnormal. Overall agreement (predictive accuracy) among ejection fraction (normal greater than or equal to 57), % delta D (normal greater than or equal to 28%) and PEP/LVET (normal less than or equal to 0.42) was 85%. In 67 patients disparities among the tests as measures of global left ventricular performance were found. The major mechanisms accounting for such disparities were: (a) large segmental contraction abnormalities which selectively distort the % delta D and ejection fraction and (b) diminished isovolumic pressure (less than 45 mmHg) which distorts PEP/LVET. When patients with segmental contraction abnormalities and low isovolumic pressure were excluded the agreement between PEP/LVET and ejection fraction was 97%, ejection fraction and % delta D 98% and PEP/LVET and % delta D 97%. The combined uses of systolic time intervals and echocardiogram minimizes error due to segmental contraction abnormalities and isovolumic pressure. If both PEP/LVET and % delta D are concordant the agreement with ejection fraction is 94% for normal and 99% for abnormal left ventricular function.

Cardiac function in Duchenne's muscular dystrophy. Results of 10-year follow-up study and noninvasive tests.

The purposes of this study were to: (1) evaluate the progression of cardiac involvement in Duchenne's muscular dystrophy using systolic time intervals (PEP/LVET); (2) determine if the degree of cardiac involvement bears a relation to the severity of skeletal muscle disease; and (3) describe the M-mode and two-dimensional echocardiographic findings. In 1970, systolic time intervals were studied in 16 patients. During the 10-year interim, two patients were lost to follow-up study, and five patients died. Nine remaining patients were re-studied in 1980 with M-mode and two-dimensional echocardiography as well as systolic time intervals. The PEP/LVET value of these nine patients increased from 0.37 +/- 0.05 (mean +/- SD) in 1970 to 0.47 +/- 0.07 (p less than 0.005) in 1980. Three patients remained ambulatory, and their PEP/LVET value (0.41 +/- 0.04) was significantly better than that of the nonambulatory patients (0.50 +/- 0.07, p less than 0.05). The M-mode echocardiography percentage diameter change was also worse in the nonambulatory group (21 +/- 4 percent versus 34 +/- 7 percent, p less than 0.02). The five patients who were nonambulatory in 1970 died in the intervening 10 years. This study demonstrated that the heart disease of Duchenne's muscular dystrophy is progressive and that the severity of skeletal muscle disease is probably associated with the degree of cardiac dysfunction.