Ankle-brachial index and 7-year ischemic stroke incidence: the ARIC study.

BACKGROUND AND PURPOSE: Low ankle-brachial index (ABI), which is the ratio of tibial artery systolic blood pressure to brachial systolic artery pressure, is known to be a measure of lower limb peripheral artery disease as well as a marker for other cardiovascular disease events. The ability of ABI to predict incident ischemic stroke, however, is not established in population-based studies. METHODS: ABI was measured in a cohort of 14 839 black and white men and women aged 45 to 64 years. Stroke incidence was calculated during approximately 7 years of follow-up. RESULTS: A total of 206 incident strokes occurred. Adjusted stroke incidence rates were markedly higher for those in the lowest versus the highest categories of ABI for men, women, blacks, and whites. The proportional hazards regression model, adjusted for age, race, gender, and field center, showed an inverse linear trend between ABI and ischemic stroke incidence (P<0.0001). The lowest group (ABI <0.80) had a hazard ratio of 5.68 (95% CI 2.77 to 11.66). After adjustment for major risk factors in a multivariate model, the hazard ratio in the lowest group was elevated (1.93) but no longer statistically significant (95% CI 0.78 to 4.78). There was, however, still an indication of an overall inverse linear trend between ABI and incident stroke (P=0.03). CONCLUSIONS: Low ABI was strongly associated with increased incidence of ischemic stroke, but the relationship was substantially reduced after adjustment for major cardiovascular risk factors.

Intestinal intussusception and occlusion caused by small bowel polyps in the Peutz-Jeghers syndrome. Management by combined intraoperative enteroscopy and resection through minimal enterostomy: case report.

UNLABELLED: The Peutz-Jeghers syndrome is a hereditary disease that requires frequent endoscopic and surgical intervention, leading to secondary complications such as short bowel syndrome. CASE REPORT: This paper reports on a 15-year-old male patient with a family history of the disease, who underwent surgery for treatment of an intestinal occlusion due to a small intestine intussusception. DISCUSSION: An intra-operative fiberscopic procedure was included for the detection and treatment of numerous polyps distributed along the small intestine. Enterotomy was performed to treat only the larger polyps, therefore limiting the intestinal resection to smaller segments. The postoperative follow-up was uneventful. CONCLUSION: We point out the importance of conservative treatment for patients with this syndrome, especially those who will undergo repeated surgical interventions because of clinical manifestation while they are still young.

Serum leptin and weight gain over 8 years in African American and Caucasian young adults.

OBJECTIVE: There is considerable interest in how to prevent weight gain in adulthood. Leptin, a peptide hormone expressed in adipose tissue, is believed to signal the central nervous system about the level of body fat stores, and thereby may control appetite. Little information exists on whether the serum leptin concentration influences long-term weight changes in the free-living population. RESEARCH METHODS AND PROCEDURES: From an ongoing cohort study of young African American and white adults, we selected a sample of participants (n=492), stratified on sex, race, and weight changes over 8 years. Serum leptin was measured on stored specimens using a radioimmunoassay. Weight change was modeled in relation to baseline leptin concentrations. RESULTS: Cross-sectionally, leptin concentration was associated positively with body mass index, negatively with physical activity level, and was higher in women than men. These variables explained 72% of the variance in serum leptin. Over the 8 years, the sample gained an average of 7.8 kg (standard deviation = 10.8). There was no evidence that 8-year weight change was associated with initial leptin concentration: 8-year weight change was only 0.5 kg less (95% confidence interval =-1.8 to 0.8, p = 0.47) per each 10 ng/ mL increment (approximately one standard deviation) of baseline leptin. In contrast, leptin change correlated highly (r=0.62) with weight change. DISCUSSION: Our data corroborate evidence that adiposity determines leptin levels but do not support the hypothesis that leptin deficiency plays an important role in obesity in the general population.

Mu and delta opioid receptor desensitization in undifferentiated human neuroblastoma SHSY5Y cells.

Both mu and delta opioid receptors are expressed in undifferentiated human neuroblastoma SHSY5Y cells and are negatively coupled to adenylate cyclase. The ability of various mu opioid, delta opioid and alpha-2 adrenergic agonists to inhibit acutely forskolin-stimulated adenylate cyclase activity in undifferentiated SHSY5Y cells after chronic administration with the selective mu opioid agonist [N-MePhe3,D-Pro4]morphiceptin (PLO17) or delta opioid agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE) was assessed. In control cells, both PLO17 and DPDPE inhibited cyclic AMP (cAMP) formation with equal maximal inhibition, i.e., 60 +/- 3 and 66 +/- 2%, having IC50 values of 51.1 +/- 1.3 and 3.7 +/- 1.0 nM, respectively. The inhibition of intracellular cAMP formation by both agonists could be blocked by pertussis toxin pretreatment. After 24 hr of chronic administration of PLO17 (50 nM to 10 microM), a concentration-dependent loss of the ability of mu opioid agonists PLO17 and DAMGO, but not the delta opioid agonists DPDPE, nor alpha-2 adrenergic agonist UK-14304 (5-Bromo-N-(4,5,-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine) to inhibit adenylate cyclase activity was observed. In contrast, chronic administration of DPDPE (0.1 nM to 0.3 microM) resulted in a concentration-dependent reduction in the inhibition of cAMP formation produced by delta opioid agonists DPDPE and DSLET, but not mu opioid, nor alpha-2 adrenergic agonists tested. The observed homologous desensitization was also time-dependent. In addition, antagonist-induced increases in adenylate cyclase activity were observed only after chronic PLO17 administration.2+ Finally, chronic pretreatment of cells with PLO17 (10 microM) resulted in a significant decrease in mu opioid, but not delta opioid receptor, binding, whereas treatment with DPDPE (0.3 microM) resulted in a significant decrease in delta opioid, but not mu opioid receptor binding. Therefore, undifferentiated SHSY5Y cells may provide an excellent model system to study not only the signal transduction mechanisms of mu and/or delta opioid receptors, but also the cellular adaptations of specific opioid receptors.