Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism

OBJECTIVES: To identify infants with hyperinsulinism caused by defects of the beta-cell adenosine triphosphate-dependent potassium channel complex and to distinguish focal and diffuse forms of hyperinsulinism caused by these mutations. STUDY DESIGN: The acute insulin response to intravenous calcium stimulation (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinism caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patients with focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year-old with insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective glutamate dehydrogenase (6 months to 28 years), 4 SUR1(+/-) heterozygotes with no symptoms, and 9 normal adults. Three infants with congenital focal disease, 1 with diffuse hyperinsulinism, and the child with insulinoma underwent selective pancreatic intra-arterial calcium stimulation with hepatic venous sampling. RESULTS: Children with diffuse SUR1(-/-) disease and infants with congenital focal hyperinsulinism responded to CaAIR, whereas the normal control group, patients with hyperinsulinism/hyperammonemia syndrome, and SUR1(+/-) carriers did not. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling revealed selective, significant step-ups in insulin secretion that correlated anatomically with the location of solitary lesions confirmed surgically in 2 of 3 infants with congenital focal disease and in the child with insulinoma. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling demonstrated markedly elevated baseline insulin levels throughout the pancreas of the infant with diffuse hyperinsulinism. CONCLUSIONS: The intravenous CaAIR is a safe and simple test for identifying infants with diffuse SUR1(-/-) hyperinsulinism or with focal congenital hyperinsulinism. Preoperative selective arterial calcium stimulation of the pancreas with hepatic venous sampling can localize focal lesions causing hyperinsulinism in children. The combination of these calcium stimulation tests may help distinguish focal lesions suitable for cure by local surgical resection.     

Pericardial Effusion in the Emergency Department

We report the first child presenting to the emergency department with undiagnosed myxedema in whom incidental detection of pericardial effusion led to diagnosis. Moreover, this patient presented with the highest serum thyrotropin concentration reported to date, a phenomenon that caused the hook effect during laboratory analysis. We discuss key elements of the recognition and management of hypothyroidism in the pediatric population and emphasize the importance of annual screening for hypothyroidism in all patients with Down syndrome.     

The hepatic alpha 1-adrenergic receptor

Since the relatively recent advent of radioligand binding techniques, it has been possible to directly identify and characterize hepatic adrenergic receptors as well as study their physiological regulation. While it is now clear that alpha 1-adrenergic receptors constitute the major population of hepatic adrenergic receptors and are primarily responsible for the actions of catecholamines in liver, relatively little is known about the molecular mechanisms underlying alpha 1-responses. Recent results suggest that guanine nucleotides may be implicated in the transmission of the hormonal signal from the hepatic alpha 1-receptor to its effectors in a manner analogous to that described for adenylate cyclase-linked receptors. The lack of an easily measurable proximal membrane response for the alpha 1-receptor has been a severe handicap in our understanding of the mechanism of transmission of the hormonal signal. It is likely that until such a response is defined, alpha 1-adrenergic research will continue to lag behind research on the beta-adrenergic receptor.     

Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone

Ameloblastoma, a tumor located in bone, when neglected, can perforate the bone and, ultimately, spread into the soft tissues. To expand in the bone, ameloblastoma must have a mechanism of resorbing the surrounding bone. However, the mechanism for bone resorption is poorly understood. In the present study, we found that RANKL and TNFalpha were expressed and secreted by ameloblastoma cells, and was proven to induce osteoclastogenesis. Our present results also showed that phosphorylation of p38, SAPK, p44/42 and Akt were upregulated under treatment of 10xCM (concentrated conditioned media of AM-1 cells). We also noticed formation of resorption lacunae on dentin slice by 10xCM-induced osteoclast-like MNCs. These results suggested that ameloblastoma by secreting RANKL and TNFalpha could induce osteoclastogenesis.     

Surgery for pseudarthrosis of humeral shaft fractures: a retrospective series of 21 cases

INTRODUCTION: The morbidity of surgery for non-union of the humerus is not insignificant: the aims of this retrospective study were to study the results of these rather difficult procedures and to make some logical suggestions regarding surgical technique. PATIENTS AND METHODS: Between 1996 and 2000, 21 patients had a surgical procedure for non-union of the humeral shaft. At follow-up, the mean age was 40 years. The causes of the initial trauma were: 12 road accidents, seven standing height falls, one fall from a window, one farm machine accident. The commonest fracture site was the middle third. In 17 procedures, we performed plate osteosyntesis. Three patients were treated by external fixator because of infection. In one patient we used a nail. For the follow-up evaluation, we used the score of the Western Orthopaedic Society. RESULTS: According to the "WOS" score evaluation, we noted: ten very good results, five good results, three poor results and one bad result. The bad result corresponded to the patient in whom consolidation was not obtained. DISCUSSION AND CONCLUSION: Management of non-union of the humerus should be by immediate surgery. The best treatment of non-union of the humerus is its prevention by correct management of the initial fracture.     

Rapidly exchangeable pool study of zinc in free-living or institutionalized elderly women

OBJECTIVE: We evaluated the effect of age and institutionalization on zinc metabolism by using a stable isotope technique. METHODS: This was a randomized case-control study. Three groups were recruited: nine young women (group 1, ages 36+/-1 y) as controls, nine free-living elderly women (group 2, ages 72+/-2 y), and nine institutionalized women (group 3, ages 73+/-2 y). Only women were recruited to obtain homogeneous groups. The study was set in a Valence hospital (France) in the geriatric department (headed by Dr. Ferry). The experimental design of the study was reviewed and approved by the local ethical committee, and all participants signed a consent form. No subject dropped out of the study. A zinc stable isotope label (0.73 mg of (70)Zn) was injected intravenously into patients and measured by inductively coupled plasma mass spectrometry. RESULTS: Decay curves of the plasma (70)Zn followed a one-compartment kinetic leading to the determination of one pool. The size of this pool suggested that it corresponded to the liver compartment. The size of this pool was significantly smaller in elderly people. (70)Zn plasma resident time was significantly longer in elderly individuals, and shorter in institutionalized than in free-living elderly subjects. CONCLUSION: These data suggest that the zinc metabolism of elderly women is related to lifestyle or its consequences and to age. Moreover, we have demonstrated that kinetic studies using stable isotopes of zinc can provide novel information on exchangeable zinc pools in clinical situations.