The enteroinsular axis during hospitalization in newborn foals.

The enteroinsular axis (EIA) is an energy regulatory system that modulates insulin secretion through the release of enteroendocrine factors (incretins). Despite the importance of energy homeostasis in the equine neonate, information on the EIA in hospitalized foals is lacking. The goals of this study were to measure serum insulin and plasma incretin (glucose-dependent insulinotropic polypeptide [GIP], glucagon-like peptide-1 [GLP-1] and glucagon-like peptide-2 [GLP-2]) concentrations, to determine the insulin and incretin association, as well as their link to disease severity and outcome in hospitalized foals. A total of 102 newborn foals ≤72 h old were classified into hospitalized (n = 88) and healthy groups (n = 14). Hospitalized foals included septic (n = 55) and sick non-septic (SNS; n = 33) foals based on sepsis scores. Blood samples were collected over 72 h to measure serum insulin and plasma GIP, GLP-1 and GLP-2 concentrations using immunoassays. Data were analyzed by nonparametric methods and univariate logistic regression. At admission, serum glucose and insulin and plasma GIP were significantly lower in hospitalized and septic compared to healthy foals (P < 0.01), while plasma GLP-1 and GLP-2 concentrations were higher in hospitalized and septic foals than healthy and SNS foals, and decreased over time in septic foals (P < 0.05). As a percent of admission values, GLP-1 and GLP-2 concentrations dropped faster in healthy compared to hospitalized foals. Serum insulin concentrations were lower in hospitalized and septic non-survivors than survivors at admission (P < 0.01). Hospitalized foals with serum insulin < 5.8 µIU/mL, plasma GLP-1 >68.5 pM, and plasma GLP-2 >9 ng/mL within 24 h of admission were more likely to die (OR = 4.2; 95% CI = 1.1-16.1; OR = 13.5, 95% CI = 1.4-123.7; OR = 12.5, 95% CI = 1.6-97.6, respectively; P < 0.05). Low GIP together with increased GLP-1 and GLP-2 concentrations indicates that different mechanisms may be contributing to reduced insulin secretion in critically ill foals, including impaired intestinal production (GIP, proximal intestine) and pancreatic endocrine resistance to enhanced incretin secretion (GLP-1, GLP-2; distal intestine). These imbalances could contribute to energy dysregulation in the critically ill equine neonate.

Cardiovascular images: vascular hamartoma of the mitral valve in a horse.

An 8-month-old Hanoverian gelding was presented with a history of cardiac murmurs that were not apparent as a foal nor reported at the time of castration. Major echocardiographic findings included mitral valvular thickening, functional stenosis, and mitral regurgitation of sufficient severity to cause diastolic and systolic cardiac murmurs, left-sided volume overload, and pulmonary hypertension. Due to the hemodynamic severity of the lesion and poor prognosis for future performance and longevity, euthanasia was elected. On gross postmortem examination, there was focal fibrous epicarditis affecting the heart base, and the left atrium was moderately dilated. The mitral valve surface was irregular and contained several nodules along the atrial face of the cusp. Histologically, this lesion was diagnosed as a vascular hamartoma, which is rarely reported in veterinary species and has not been described in heart valves. This benign proliferative lesion, and concurrent valvular dysfunction, was associated with an unusual manifestation of clinically evident disease and should be differentiated from common incidental valvular lesions such as hematocysts.

Occurrence risk for congenital heart defects in relatives of patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect.

BACKGROUND: Knowledge of the risk of occurrence of congenital heart defects in offspring of individuals with a congenital heart defect is important for genetic counseling and understanding the etiology of congenital heart diseases. METHODS AND RESULTS: A portion of the questionnaire mailed to all patients in the Second Natural History Study of Congenital Heart Defects (NHS-2) addressed marital status, pregnancy, miscarriage, and presence or absence of congenital heart defects or other congenital malformations in first-degree relatives. Offspring were not examined as a part of the study. For male probands with aortic stenosis (AS), three of 251 offspring had congenital heart disease, whereas one of 72 offspring of female probands with AS had congenital heart disease. For patients with pulmonary stenosis (PS), three of 176 offspring of male probands had congenital heart disease, whereas eight of 205 offspring of female probands had congenital heart disease. For male probands with ventricular septal defect (VSD), 10 of 334 offspring had congenital heart defects, and 11 of 384 offspring of female probands with VSD had offspring with congenital heart defects. The prevalence rate for noncardiac congenital anomalies in offspring of probands was 2%. CONCLUSIONS: Based on known congenital heart defects in offspring of probands in the NHS-2, occurrence rates of congenital heart disease in children of subjects with AS, PS, and VSD were 1.2% (confidence interval [CI], 0.34-3.1%), 2.8% (CI, 1.4-5.1%), and 2.9% (CI, 1.8-4.4%), respectively.

Second natural history study of congenital heart defects. Materials and methods.

Results of the location and recruitment efforts and comparisons of responses from patients who cooperated at different levels in the Second Natural History Study of Congenital Heart Defects are included because they influenced the choice of analytic methods and are essential to the generalizability of the results to the entire study cohort. Included are examination and data collection protocols (e.g., protocol definitions, test procedures, and data editing), statistical methods (e.g., box plots, survival curves, multivariable models, and rate adjustment), participation results (e.g., proportional odds analysis, mortality, location, recruitment, and full participants, including comparison of questionnaire responses and comparison of questionnaire response and physician history), and a discussion.

Natural History Study of Congenital Heart Defects.

A strategy designed to locate and recruit individuals who were part of a study in the 1960s of congenital aortic stenosis, pulmonary stenosis, and ventricular septal defect for purposes of a follow-up examination is presented. These individuals are now adults living throughout the United States and some foreign countries. The present study, referred to as NHS-2, is designed to bring the survivors back to one of six clinical centers for medical evaluation to study the long-term results of medical and surgical treatment of such patients.

Factor VIII-von Willebrand factor in giant cell arteritis and polymyalgia rheumatica.

Levels of three factor VIII-von Willebrand factor components (von Willebrand antigen, ristocetin cofactor, and factor VIII coagulant) were higher in specimens of plasma from 27 patients with giant cell arteritis and 18 patients with polymyalgia rheumatica than in specimens from 21 normal control subjects. Values in patients with active giant cell arteritis were higher than those in patients with either inactive giant cell arteritis or active polymyalgia rheumatica. Levels of factor VIII-von Willebrand factor components tended to decline gradually after disease activity had been suppressed by corticosteroid therapy and therefore may be indicators of vascular damage. These levels, however, did not revert to normal rapidly in response to corticosteroid therapy as did the patients' symptoms and the usual laboratory measurements indicative of inflammation; thus, measurements of these components are unlikely to be useful in day-to-day management of these diseases. Electrophoretic analysis suggested that the elevated values are due to increased amounts of normal factor VIII-von Willebrand factor rather than to the presence of an abnormal molecule.