Mastocytosis and systemic sclerosis: a clinical association.

BACKGROUND: Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vascular alterations and autoimmune activation leading to widespread organ fibrosis. At the early stage of disease when organ involvement and extent of disease are emerging, mast cells may have some role, as implied by both symptoms and histologic evidence. CASE PRESENTATION: A female patient diagnosed with cutaneous mastocytosis experienced the onset of systemic sclerosis after 15 years followed by the switch of mastocytosis to the systemic phenotype. A literature review on the evidences related to mast-cells activation in systemic sclerosis is presented below. CONCLUSIONS: For clinicians, more attention must be paid to the potential association between systemic sclerosis and cancer. This case suggests that a proliferative disease in the mast cell compartment-though representing a rare association-may not be completely unexpected in SSc and perhaps excess mast cell activity can serve a pathogenic role in promoting fibrotic disease.

Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients.

The ultimate goal is to identify and target modifiable risk factors that will reduce major cardiovascular events in African American lupus patients. As a first step toward achieving this goal, this study was designed to explore risk factor models of preclinical atherosclerosis in a predominantly African American group of patients with systemic lupus erythematosus (SLE) using variables historically associated with endothelial function in nonlupus populations. Fifty-one subjects with SLE but without a history of clinical cardiovascular events were enrolled. At entry, a Framingham risk factor history and medication list were recorded. Sera and plasma samples were analyzed for lipids, lupus activity markers and total 25-hydroxyvitamin D (25 OH)D) levels. Carotid ultrasound measurements were performed to determine total plaque area (TPA) in both carotids. Cases had TPA values above age-matched controls from a vascular prevention clinic population. Logistic regression and machine learning analyses were performed to create predictive models. 25(OH)D levels were significantly lower, and SLE disease duration was significantly higher in cases. 25(OH)D levels inversely correlated with age-adjusted TPA. Angiotensin-converting enzyme (ACE) inhibitor nonuse associated with case status. Logistic regression models containing ACE inhibitor use, 25(OH)D levels and low-density lipoprotein levels had a diagnostic accuracy of 84% for predicting accelerated atherosclerosis. Similar results were obtained with machine learning models, but hydroxychlo-roquine use associated with controls in these models. This is the first study to demonstrate an association between atherosclerotic burden and 25(OH)D insufficiency or ACE inhibitor nonuse in lupus patients. These findings provide strong rationale for the study of ACE inhibitors and vitamin D replenishment as preventive therapies in this high-risk population.

Deficits in reproduction and pro-gonadotropin-releasing hormone processing in male Cpefat mice.

Cpe(fat/fat) mice are obese, diabetic, and infertile. These animals have a point mutation in carboxypeptidase E (CPE), an exopeptidase that removes C-terminal basic amino acids from peptide intermediates. The mutation renders the enzyme unstable, and it is rapidly degraded. Although the infertility of Cpe(fat/fat) mice has not been systematically investigated, it is thought to be due to a deficit in GnRH processing. We have evaluated this hypothesis and found hypothalamic GnRH levels to be reduced by 65-78% and concentrations of pro-GnRH and C-terminal-extended intermediates to be high. Basal serum gonadotropin contents are similar among wild-type, heterozygous, and homozygous mice. Testis morphology and function are abnormal in older obese Cpe(fat/fat) mice. Matings between homozygous mutants yield a 5% pregnancy rate. By comparison, when 50-d-old Cpe(fat/fat) males are paired with heterozygous females, rates increase to 43%, and they rapidly decrease to negligible levels by 120 d. As fertility declines without accompanying changes in the hypothalamic-pituitary-gonadal axis and before obesity is evident, reproduction is more complex than originally thought. This suspicion is confirmed in 90-d-old Cpe(fat/fat) males, who readily interact with females, but rarely mount and fail to show intromission or ejaculation behaviors. Together, these findings show that CPE is a key enzyme for pro-GnRH processing in vivo; however, the reproductive deficits in Cpe(fat/fat) males appear to be due primarily to abnormal sexual behavior.

The role of medical students in curriculum committees.

BACKGROUND: Medical students often play a role in local curricular issues by assessing the curriculum and bringing consumers' perspectives to curricular committees. PURPOSE: To identify the formal roles that medical students play on curriculum committees. METHODS: Mail survey to associate deans of medical education at all U.S. medical schools (N = 144). RESULTS: A total of 109 surveys were returned (response rate = 75.7%). Students had formal roles on the curricular committees at 100% of the respondent institutions. The majority of medical schools allow peers to elect their representatives to the committee (53.2%). Students have a right to vote on curricular changes at 86% of the respondent institutions. The vast majority of respondents (97.2%) felt that medical students were important in initiating curricular change. CONCLUSIONS: Medical students play an active role on curriculum committees at U.S. medical schools. Further research is needed to fully elucidate these specific roles.