A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects.

OBJECTIVES: We have previously shown that dexamethasone increases serum leptin in fed but not in fasted human subjects. We hypothesized that insulin and/or glucose mediated the effect of food intake. The primary aim of this study was to determine whether the administration of a pulse of insulin with dexamethasone was sufficient to increase serum leptin in vivo in fasted human subjects. Whether the presence of transient hyperglycemia and the dose of insulin were important was tested as a secondary aim. METHODS: Twenty-nine normal subjects were studied. In experiment 1 (meal-like), a pulse of insulin (0.03 U/kg s.c.) and of dexamethasone (2 mg i.v.) was given, and the blood glucose transiently elevated to 50 mg/dl above baseline for the first 2 h. In experiments 2 and 3 (dose-response), the effect of two doses of insulin (0.03 U/kg in experiment 2 and 0.06 U/kg in experiment 3) was tested in combination with dexamethasone, this time without transient hyperglycemia. Nine subjects were studied under fasting conditions, with or without dexamethasone, as a control experiment. RESULTS: A meal-like transient hyperinsulinemia and hyperglycemia, with a pulse of dexamethasone, increased serum leptin levels from baseline by 54+/-21% at 9 h (P=0.038). In the absence of transient hyperglycemia, leptin increased significantly after doses of both insulin and dexamethasone. The effect of insulin was dose-dependent, with a larger increment of serum leptin at 9 h after the highest dose of insulin (75.2+/-15.7% vs 21.3+/-8.5%, P=0.013). Fasting, with or without dexamethasone, resulted in a significant 20% decrease in leptin from morning basal levels. Conversely, the administration of a pulse of insulin and glucose, in the absence of dexamethasone, prevented the drop in serum leptin observed during fasting, regardless of the insulin dose or the serum glucose elevation. CONCLUSIONS: With the permissive effect of dexamethasone, a single pulse of insulin triggered a rise in serum leptin in humans, even in the absence of transient hyperglycemia. A single pulse of insulin with glucose can prevent the drop in serum leptin normally observed during fasting.

Insulin, unlike food intake, does not suppress ghrelin in human subjects.

UNLABELLED: Food intake suppresses plasma levels of the gastric peptide ghrelin in humans. We hypothesize that the food intake- suppression of ghrelin could be secondary to the plasma glucose and insulin changes after a meal. The aim of this study was to compare the effect of the administration of a combined pulse of glucose and insulin to the effect of one meal on plasma ghrelin in human subjects. A secondary aim was to study the effect of an oral glucose load on ghrelin levels. METHODS: Experiment 1 (n = 10) studied plasma glucose, insulin, leptin and ghrelin for 6 hours after a 790 kcal liquid meal. In Experiment 2 (n = 7), a subcutaneous pulse of insulin (Humalog 0.03U/kg) and an I.V. infusion of glucose were administered in order to mimic the plasma changes of glucose and insulin after a meal, and plasma ghrelin levels were monitored for 9 h. The OGTT data was used to study the effect of oral glucose on ghrelin. RESULTS: A mixed liquid meal decreased basal serum ghrelin by 26% at 40 minutes (p = 0.009). A 75 gr oral glucose load suppresses ghrelin by 28% at 30 minutes. Contrary to the meal effect, the parenteral administration of insulin and glucose did not suppress serum ghrelin. CONCLUSION: Unlike food intake, the administration of insulin and glucose does not suppress ghrelin levels. These data suggest that the suppressive effect of food intake or oral glucose on serum ghrelin is unlikely mediated by the changes of plasma insulin and glucose observed after the ingestion.

Avascular necrosis of the talus after McKay clubfoot release for idiopathic congenital clubfoot.

Avascular necrosis of the talus is a serious potential complication of clubfoot surgery. In the few cases described in the literature, the necrosis has involved the entire talus and resulted in progressive fragmentation and collapse. Serial postoperative radiographs of 96 idiopathic clubfeet in 70 patients are reviewed here to determine the incidence of avascular necrosis after McKay soft tissue release. Based on criteria in the literature for making the diagnosis, no cases of avascular necrosis were seen. Growth lines were observed in the cuboids and calcanei of all the feet during the follow-up period. Eight feet failed to develop growth lines in the talus during follow-up. Five of these feet showed flattening of the dome of the talus and three hypoplasia of the talar head and neck at the most recent follow-up. Absence of normal growth lines in the talus after operation seems to predict talar abnormalities.

Staging of bone neoplasms: an orthopedic oncologist's perspective.

The process of staging bone tumors is complex. The goal of staging is to define the type of tumor and its extent. Like staging for other neoplasms, it stratifies patients into groups based on prognosis and established treatment protocols. Staging is a multidisciplinary effort involving orthopedic oncologists, musculoskeletal radiologists, and orthopedic pathologists. The diagnosis is often suggested on clinical examination and review of the radiographs. The biopsy usually confirms the clinical and radiographic impression. However, biopsy is difficult and leads to errors in diagnosis in nearly 20% of cases. These errors may make limb salvage impossible and adversely affect survival. For this reason, staging and especially the biopsy should be done in the institution where definitive treatment is planned.

Management of metastatic lesions of the humerus.

The management of patients with metastatic disease in the humerus requires consideration of many factors. A careful evaluation of the patient's general condition, an understanding of the disease process, an appreciation of the degree of bone destruction, and a working knowledge of available treatment options are required. A multidisciplinary approach is essential to determine the course of treatment that best alleviates pain, preserves function, and optimizes the quality of life remaining in the patient with metastatic disease.