ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Inconsistent and sometimes disappointing final height outcomes in studies in which exogenous growth hormone (GH) was given to children with short stature resulting from various causes have led to attempts to determine the factors that influence individual responsiveness to GH. Many such factors have been identified, including the genetically determined height potential of the child, the height deficit, current and perinatal auxologic and biologic factors and, importantly, GH treatment modalities. These factors vary among different causes of growth failure and during the course of childhood and treatment. Data from well-defined large cohorts can be entered into multiple regression analyses to derive algorithms describing the variation in growth response during a defined period and the influence of various factors. Pharmacoepidemiologic surveys have been particularly useful in this regard. Algorithms with low-error SD values, which have included the dosage of GH as a variable, can be used to predict the response to a putative GH dosage in a similar cohort or an individual during an equivalent period. A sequential series of such algorithms can be integrated to form a predictive model. Such a model can be used for planning a course of treatment, but the patient data required for entry into the model should be able to be acquired easily if the model is to have widespread utility. The development of such models will allow GH treatment to be better individualized, and optimized for growth and cost outcomes. Growth prediction models will facilitate realistic expectations and will permit stepwise goals to be set and monitored.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Although recombinant human growth hormone (GH) remains the gold standard for treatment of GH-deficient (GHD) children, growth hormone releasing hormone is also approved for this indication. The discovery of the growth hormone releasing peptides (GHRPs) and the highly conserved growth hormone secretagogue (GHS) receptor suggests the existence of an as yet unidentified endogenous ligand involved in the control of GH secretion. Published efficacy data on the use of GH secretagogues (GHRP and GHRP-mimetics) in children with GHD are limited, but suggest that GHSs increase growth velocity compared to pretreatment. However, in these small studies of relatively short duration, growth was less than that seen historically with GH treatment. It is unknown whether, at least in a subset of patients, genetic height potential can be attained with GHS. As the physiologic role of the putative GHS ligand is clarified, any potential therapeutic role for GHS therapy in a subset of children with GHD may become more clear.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

It is now recognized that physical activity is mechanistically linked to anabolic function through the growth hormone→insulin-like growth factor-I axis (GH→IGF-I). Indeed, cross-sectional data from a variety of laboratories demonstrate that fitter adolescents and adults have increased GH pulsatility and/or increased circulating IGF-I levels. But surprisingly, prospective endurance-type exercise training interventions performed in children and adolescents have consistently demonstrated reductions in IGF-I rather than the expected increases. Moreover, the response of GH and IGF-I binding proteins was far more consistent with a systemic catabolic-type, rather than anabolic adaptation. How was it that children and adolescents respond to training with increased muscle mass, improved cardiorespiratory function, and a tendency to gain weight, while their neuroendocrine profile suggested the opposite? The data indicate that an increased level of physical activity simultaneously stimulates both anabolic and catabolic pathways, the latter mediated, perhaps, by certain inflammatory cytokines. In this review, we attempt to identify the mechanisms responsible for the apparent catabolic environment found initially with exercise training. We also highlight new research focused on hormonal mechanisms involved in the paradigm of “growth versus growth plus exercise” that plays an important role in determining the optimal levels of physical activity in both healthy children and those with chronic diseases.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Disorders in water metabolism can be caused by impairment in either vasopressin synthesis or vasopressin action. Recent advances in molecular biological techniques have revealed genetic defects in a variety of genes involved in the osmoregulatory pathway, including vasopressin itself, its renal receptor, and the aquaporin-2 water channel. The molecular pathophysiology of water metabolism and the impact of genetic abnormalities are being clarified.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

McCune-Albright syndrome is a rare disease caused by an activating mutation in the gene for the G protein subunit (GS&agr;) that stimulates cellular cyclic AMP formation. The mutation occurs early during embryogenesis and results in a variable constellation of abnormalities involving bone, skin, endocrine glands, and other tissues. Although traditionally regarded as a disease of children, clinical manifestations may progress into adulthood. Efforts are being made to define the precise mechanisms by which inappropriate GS&agr; activation affects cellular proliferation and differentiated function and to develop more effective means to treat fibrous dysplasia of bone.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Regular physical exercise is important in the prevention and treatment of type 2 diabetes. A single exercise session can influence systemic glucose homeostasis by both increasing glucose uptake into the contracting muscles during exercise, and increasing the sensitivity of muscle glucose uptake to insulin for a prolonged period after the cessation of exercise. The underlying cellular mechanisms responsible for these important effects of a single exercise session are not well understood. Exercise training can also result in changes in skeletal muscle insulin sensitivity, mediated partly by the acute effects of the individual exercise bouts and also by numerous chronic adaptations to the muscle, including increased expression of GLUT4.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Insulin, at physiologic concentrations, increases skeletal muscle blood flow in lean insulin-sensitive subjects. This insulin effect is blunted in states of insulin resistance such as obesity and type 2 diabetes mellitus. Whether insulin-mediated increments in blood flow augment insulin-mediated glucose uptake and whether impaired insulin-mediated vasodilation contributes to decreased rates of insulin-mediated glucose uptake (insulin resistance) are still debated. Recently, positron emission tomography scanning and microdialysis have been applied to answer the question. It has been demonstrated that insulin’s effect on blood flow is mediated through the release of endothelium-derived nitric oxide, the most potent endogenous vasodilator, and that insulin modulates the response to other vasoactive hormones also at the level of the vascular smooth muscle cell. Importantly, nitric oxide is not only a vasodilator but also exhibits a host of anti-atherosclerotic properties. Because impaired insulin-mediated vasodilation in obesity and type 2 diabetes suggested decreased production of nitric oxide, recent research has focused on vascular endothelial function in insulin-resistant states. There is now good evidence for impaired endothelial function and decreased nitric oxide production in obesity and type 2 diabetes. The mechanism(s) by which obesity and type 2 diabetes impair endothelial function have not been fully elucidated but elevated free fatty acid levels as observed in these insulin resistant subjects may account, at least in part, for the vascular dysfunction.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID