Lyme carditis: An atypical cause of syncope.

ABSTRACT: With the rising prevalence of Lyme disease over the last 2 decades comes an increase in cases of Lyme carditis, a consequence of early disseminated infection. This case report focuses on a young man with a complicated case of Lyme carditis that required advanced therapy.

Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects.

High levels of granulocyte/macrophage-colony-stimulating factor (GM-CSF) autoantibodies are thought to cause pulmonary alveolar proteinosis (PAP), a rare syndrome characterized by myeloid dysfunction resulting in pulmonary surfactant accumulation and respiratory failure. Paradoxically, GM-CSF autoantibodies have been reported to occur rarely in healthy people and routinely in pharmaceutical intravenous immunoglobulin (IVIG) purified from serum pooled from healthy subjects. These findings suggest that either GM-CSF autoantibodies are normally present in healthy people at low levels that are difficult to detect or that serum pooled for IVIG purification may include asymptomatic persons with high levels of GM-CSF autoantibodies. Using several experimental approaches, GM-CSF autoantibodies were detected in all healthy subjects evaluated (n = 72) at low levels sufficient to rheostatically regulate multiple myeloid functions. Serum GM-CSF was more abundant than previously reported, but more than 99% was bound and neutralized by GM-CSF autoantibody. The critical threshold of GM-CSF autoantibodies associated with the development of PAP was determined. Results demonstrate that free serum GM-CSF is tightly maintained at low levels, identify a novel potential mechanism of innate immune regulation, help define the therapeutic window for potential clinical use of GM-CSF autoantibodies to treat inflammatory and autoimmune diseases, and have implications for the pathogenesis of PAP.

GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis.

BACKGROUND: Increased mortality from infection in patients with pulmonary alveolar proteinosis occurs in association with high levels of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). We tested the hypothesis that neutrophil functions are impaired in patients with pulmonary alveolar proteinosis and that GM-CSF autoantibodies cause the dysfunction. METHODS: We studied 12 subjects with pulmonary alveolar proteinosis, 61 healthy control subjects, and 12 control subjects with either cystic fibrosis or end-stage liver disease. We also studied GM-CSF-/- mice and wild-type mice. We evaluated basal neutrophil functions, neutrophil functions after priming by GM-CSF to augment antimicrobial functions, and the effects of highly purified GM-CSF autoantibodies on neutrophil functions in vitro and in vivo. RESULTS: Neutrophils from subjects with pulmonary alveolar proteinosis had normal ultrastructure and differentiation markers but impaired basal functions and antimicrobial functions after GM-CSF priming. GM-CSF-/- mice also had reduced basal neutrophil functions, but functions after GM-CSF priming were unimpaired. The neutrophil dysfunction characteristic of pulmonary alveolar proteinosis was reproduced in a dose-dependent fashion in blood specimens from healthy control subjects after incubation with affinity-purified GM-CSF autoantibodies isolated from patients with pulmonary alveolar proteinosis. The injection of mouse GM-CSF antibodies into wild-type mice also caused neutrophil dysfunction. CONCLUSIONS: The antimicrobial functions of neutrophils are impaired in patients with pulmonary alveolar proteinosis, owing to the presence of GM-CSF autoantibodies. The effects of these autoantibodies show that GM-CSF is an essential regulator of neutrophil functions.

Resident perceptions of the impact of work hour limitations.

BACKGROUND: Mandatory work hour limitations for residents began in July 2003. There has been little evaluation of the impact of the new limitations on Internal Medicine residency training. OBJECTIVE: To assess Internal Medicine residents' perceptions of the impact of work hour limitations on clinical experiences, patient care, resident education, and well-being, and their compliance with the limitations. DESIGN AND PARTICIPANTS: Cross-sectional survey administered to Internal Medicine residents at 1 large U.S. teaching hospital. MEASUREMENTS: Resident perceptions using 5-point Likert scales, and self-reported compliance. Exploratory factor analysis was used to identify underlying domains and develop scales. RESULTS: The survey response rate was 85%. Five domains were identified by factor analysis: 1) clinical experience, 2) patient care and safety, 3) communication, 4) satisfaction with training, and 5) work-rest balance. Residents perceived work hour limitations to have a negative impact on clinical experience (mean scale score 1.84, 1 = negative, 5 = positive), patient care and safety (2.64), and communication domains (1.98). Effects on satisfaction (3.12) and work-rest balance domains (2.95) were more positive. Senior residents perceived more negative effects of work hour limitations than interns. Compliance was difficult; 94% interns and 70% residents reported violating work hour limits. Patient care and teaching duties were the main reasons for work hour violations. CONCLUSIONS: This study suggests that the current work hour limitations may be having unintended negative consequences on residency training. Ongoing monitoring to evaluate the impact of program changes as a result of work hour regulation is crucial to improving residency training.

Residents' perceptions of the effects of work hour limitations at a large teaching hospital.

PURPOSE: To assess residents' perceptions of the impact of resident work hour restrictions on patient care, education, and job satisfaction. METHOD: Four focus groups of internal medicine residents at Barnes-Jewish Hospital at the Washington University School of Medicine were conducted during February and March 2004. Twenty-six housestaff from the first three years of residency participated; all were volunteers. Transcripts were analyzed for major themes. RESULTS: Both residents and interns supported work hour limitations and enjoyed the benefits of working fewer hours. However, they had difficulty complying with the restrictions, particularly if they felt patient care, teaching, or their own education would be compromised. Participants perceived that restricted work hours diminished the continuity of patient care and increased the likelihood of medical errors such as those resulting from delayed follow-up of diagnostic tests. Both interns and residents found it difficult to attend conferences, and residents found fewer opportunities to teach. Effects on job satisfaction were mixed as a result of work hour restrictions. CONCLUSIONS: Residents in the sample favored work hour restrictions but had serious concerns about the effects of the restrictions on patient care and medical education. The findings suggest that imposing rigid work hour restrictions has significant consequences for patient care and medical education and that the most effective ways to balance work hour limitations with the demands of patient care and necessary educational components to train competent physicians have yet to be identified.