Sociodemographic factors and obesity in preadolescent black and white girls: NHLBI's Growth and Health Study.

The association of sociodemographic and family composition data with obesity was studied in 1213 black and 1166 white girls, ages 9 and 10, enrolled in the National Heart, Lung, and Blood Institute''s Growth and Health Study. Obesity was defined as body mass index at or greater than age- and sex-specific 85th percentile as outlined in the Second National Health and Nutrition Examination Survey. The prevalence of obesity was higher for pubertal girls than for prepubertal girls and for girls with older mothers/female guardians. As odds ratio of 1.14 was observed for each 5-year increase in maternal age. Obesity was less common for girls with more siblings; the odds for obesity decreased by 14% for each additional sibling in the household. In blacks, the prevalence of obesity was not related to parental employment or to parental education. In whites, the odds of obesity were higher for girls with no employed parent/guardian in the household and for girls with parents or guardians with lower levels of educational attainment. Examining the associations between sociodemographic factors and risk of childhood obesity provides important clues for understanding racial differences in obesity, a major risk factor for coronary heart disease.     

Ca2+-dependent and Ca2+-independent glutamate release, energy status and cytosolic free Ca2+ concentration in isolated nerve terminals following metabolic inhibition: possible relevance to hypoglycaemia and anoxia

Hypoglycaemia and anoxia both cause massive release of glutamate from the brain in vivo, and the nature of this release was investigated using guinea-pig cerebral-cortical synaptosomes and iodoacetate and rotenone to simulate the energetic consequences of these conditions. Glutamate release (by continuous fluorimetry), cytoplasmic free Ca2+ (by fura-2), membrane potentials, ATP, ADP and creatine phosphate were determined in parallel, following the addition of iodoacetate or rotenone, alone or in combination. Ca2+-dependent glutamate release had a high energy requirement which could only be satisfied by aerobic glycolysis. Respiration using endogenous substrates, or anaerobic glycolysis following rotenone, caused a progressive inhibition of Ca2+-dependent release, correlating with a decline in the total ATP/ADP ratio and creatine phosphate. With rotenone, an increase in Ca2+-independent glutamate release was observed, correlating with a decline in plasma membrane potential. Only a slight increase in free Ca2+ was seen. Rotenone plus iodoacetate caused an almost immediate collapse of ATP/ADP ratio and a parallel loss of Ca2+-dependent glutamate release before free Ca2+ had risen to a level sufficient for exocytosis. In contrast, Ca2+-independent glutamate release increased. The Ca2+-dependent release of L-glutamate had the characteristics of an exocytotic transmitter release mechanism, being energy-dependent and triggered by elevated cytoplasmic free Ca2+ concentration. A distinct Ca2+-independent release of cytoplasmic glutamate occurred by reversal of the Na+-coupled uptake carrier, which was accelerated by a decline in the Na+ gradient. It is concluded that the Ca2+-independent release of cytoplasmic glutamate may make the major contribution to the excitotoxic release of glutamate in hypoglycaemic and anoxic conditions.     

Peptide expression is altered when afferent nerves reinnervate inappropriate tissue

Neuropeptides are found in specific subpopulations of primary afferent neurones. Peptide expression can be altered following axotomy or under the influence of nerve growth factor. Here we have examined the consequence of altering the peripheral target of afferent neurones. Many unmyelinated afferents from skin contain substance P-like immunoreactivity (SPLI) whilst those from muscle do not. We have found that fibres will innervate inappropriate tissue types. We have therefore cut and cross-anastomosed a skin and muscle hindlimb nerve in the rat and 10-12 weeks later analysed the regenerated nerves immunocytochemically for SPLI. Muscle afferents inappropriately reinnervating skin were found to contain many SPLI fibres in contrast to control nerves resutured to their own distal stumps. Conversely, skin afferents made to innervate muscle showed reduced levels of peptide staining. These results demonstrate the plasticity of peptide expression and suggest that factors in peripheral tissue or perhaps distal nerve sheaths exert a trophic influence on nervous system function.     

Effect of compounds which disrupt proton gradients on secretion of neurosecretory proteins from PC12 pheochromocytoma cells

Treatment of PC12 cells with chroquine (10-50 microM) obliterated the low intragranular pH, as detected by Acridine Orange fluorescence, and depleted the cells of dopamine and norepinephrine. However, these concentrations of chloroquine did not prevent the release of the newly synthesized proteins which normally undergo stimulus-coupled secretion with the catecholamines. Higher concentrations of chloroquine (200 microM) and ammonium chloride (10 and 25 mM) inhibited the release of most of these proteins. This inhibition did not result from alterations in protein synthesis, since the profile of proteins synthesized was not substantially altered. Nor did the inhibition result from degradation of the neurosecretory proteins, since prelabeled proteins were capable of undergoing stimulated secretion from chloroquine-treated cells, as from normal cells. The findings indicated that the inhibition was at the step of packaging of the proteins into the neurosecretory granules. While release of the major secretory proteins, including chromogranin B, was inhibited with 200 microM chloroquine, chromogranin A was secreted upon stimulation of these cells. The results of this study indicate that an acidic intragranular pH is not a requirement for the packaging and secretion of neurosecretory proteins. Higher concentrations of chloroquine had a differential effect on the regulated secretion of different neurosecretory proteins.     

Focal and segmental glomerulosclerosis. Immunohistologic study of 20 renal biopsy specimens

To evaluate the deposition of immunoglobulins and complement and their relationship to sclerotic and nonsclerotic glomerular segments, immunoperoxidase without periodic acid-Schiff counterstain (IMP) and with periodic acid-Schiff counterstain (IMPAS) for IgG, IgA, IgM, and C3 was performed on cryostat-frozen sections using the direct method, along with routine light microscopy and electron microscopy, in a series of 20 renal biopsy specimens from 20 patients with the final diagnosis of focal and segmental glomerulosclerosis. Neither diffuse mesangial nor diffuse glomerular basement membrane deposits were detected by IMP, IMPAS, or electron microscopy. In 18 biopsy specimens, IMPAS demonstrated focal and segmental granular to globular deposits of IgM and/or C3 in sclerotic glomerular segments. In eight biopsy specimens, small granular deposits of IgM and/or C3 deposits were identified in optically normal glomeruli, suggesting that these deposits may precede segmental sclerosis.     

Oxygen exchange and vascular resistance in the totally perfused rainbow trout

A whole trout preparation (Salmo gairdneri) externally ventilated with water and internally perfused with artificial medium via a cardiac pump is discribed for the study of O2 exchange and vascular resistance. As cardiac output (Q) was raised, ventral and dorsal aortic pressures increased while branchial (Rg) and systemic (Rs) vascular resistances fell, reflecting considerable passive distensibility. Arterial oxygenation was negative at low Qs due to significant internal O2 demand by the gill tissue, but increased to zero or positive values at intermediate Qs, and eventually declined at high Qs because of transit time limitation. O2 uptake from the ventilatory flow rose with increasing Q. Epinephrine (10(-5) M) decreased Rg, increased Rs, and enhanced arterial oxygenation. Artificial elevation of dorsal aortic pressure decreased Rg but did not affect arterial oxygenation. A 10-fold elevation of ventilatory flow increased arterial oxygenation but did not alter Rg or Rs. Endogenous metabolism of branchial tissue accounted for 11.7% of resting O2 uptake in vivo, and comprised an internal component taking O2 from perfusion flow and an external component drawing O2 from ventilatory flow.     

Diagnosis-related group prospective payment. Effects on medical quality assurance.

The new system for hospital reimbursement, called "reimbursement by diagnosis-related group" (DRG), offers a unique opportunity for the development of novel approaches to quality assurance. Groups of medically similar patients with stable patterns of resource use have been defined. These groups form the basis of the new payment system. Patients whose care deviates from the norm of resource consumption for their group, so-called outliers, will need to be reviewed by the hospital's administrative and medical staff. Such outliers are likely to constitute different types of patients than those in their assigned group: (1) patients whose medical complexity precludes grouping because of limitations in the abstracted clinical data; (2) patients whose medical care deviated because of complications of therapy or inappropriate diagnostic and/or therapeutic interventions; (3) patients whose medical course is so unique that they would never fit any classification system. The DRG-based reimbursement system, then, will compel hospitals to review the care of these outliers. The rigorous examination of these patients and their care, although just a first step, should be a major boon to quality of care evaluations.