PubMed Health⌕ Search

Biomedical subjects

A L Carrel

Publications and source records attributed to A L Carrel.

12 recordsLinked to original sources
PubMed2001

Prader-Willi syndrome: how does growth hormone affect body composition and physical function?

Children with Prader-Willi syndrome (PWS) display diminished growth, reduced muscle mass (lean body mass), and increased adipose tissue-body composition abnormalities resembling those seen in growth hormone (GH) deficiency. Diminished GH responses to various provocative agents, low insulin-like growth factor-I levels, and the presence of other hypothalamic dysfunction support the presence of true GH deficiency (GHD) in many children with PWS. GH treatment in these children decreases body fat, and increases linear growth, muscle mass, fat utilization and energy expenditure. Strength and agility are also improved. These improvements are most dramatic during the first year of GH therapy, and prolonged treatment still does not 'normalize' these parameters. The metabolic effects, including changes in physical strength and agility, may be the most important features for this particular pediatric population. These observations support a contribution of GHD to disabilities of children with PWS, and a clinically significant benefit of GH treatment.

Body Composition↗
PubMed2000

Sustained benefit after 2 years of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome.

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a growth hormone (GH)-deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. Although recent studies have demonstrated short-term benefits of treatment with GH, a critical question is whether beneficial changes persist or wane with prolonged therapy. OBJECTIVES AND METHODS: Effects of 24 months of GH treatment (1 mg/m(2)/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure, and fat utilization were assessed in 35 children with PWS. Percent body fat, lean muscle mass, and bone mineral density were measured by dual-energy x-ray absorptiometry. Indirect calorimetry was used to determine resting energy expenditure and to calculate the respiratory quotient. RESULTS: Compared with baseline evaluations, increased height velocity (SD score -1.1 +/- 2.5 to 2.2 +/- 2.3; P <. 001), reduced percent body fat (46.4% +/- 8.4% to 40.3% +/- 10.0%, P <.001), and improved respiratory muscle function and physical strength and agility (sit-ups, weight-lifts, running speed, and broad jump; P <.01) were observed after 24 months of GH treatment. A decline in respiratory quotient (0.81 +/- 0.07 to 0.75 +/- 0.06; P <. 01) and a trend toward increased resting energy expenditure were also observed. Changes in response to GH occurred predominantly during the initial 12 months of GH therapy. CONCLUSIONS: Children with PWS had sustained increases in lean body mass, decreases in percent body fat, improvements in physical strength and agility, and increased fat oxidation after 24 months of GH therapy. However, between 12 and 24 months, the growth rate slowed. Consequently, encouraging initial results require even more prolonged study to draw conclusions regarding the long-term value of GH therapy in changing body composition in children with PWS.

Adipose Tissue↗
PubMed2000

Effects of growth hormone on body composition and bone metabolism.

Physiologic effects of growth hormone (GH) extend beyond the stimulation of linear growth during childhood and adolescence. These effects include building and sustaining lean body mass, facilitating the utilization of fat mass for energy needs, and maintaining bone mineral density. These nongrowth effects of GH appear to be important throughout life. Children and adults with severe GHD demonstrate marked reductions in lean body mass, increases in percent body fat, and subnormal bone mineral density. Replacement of GH attenuates these abnormalities, though it remains unknown whether it does so completely. Children with body composition abnormalities resembling the GHD state (e.g., Prader-Willi syndrome) also appear to respond favorably to administration of GH treatment, and demonstrate concomitant improvements in strength and agility. Long-term body composition benefits of GH supplementation in these and other non-GHD individuals remain unproven.

Adolescent↗
PubMed2000

Effects of growth hormone on adipose tissue.

Physiological effects of growth hormone (GH) extend beyond the stimulation of linear growth. These include important metabolic effects upon adipose tissue. GH affects both proliferation and differentiation of preadipocytes, although this varies between clonal cell lines and preadipocyte cultures. Both preadipocytes and mature adipocytes possess specific GH receptors. GH may mediate its actions via these receptors, but some effects are indirectly mediated through the GH-mediated secretion of insulin-like growth factor-I (IGF-I) within adipose tissue. GH promotes lipolysis via inhibition of lipoprotein lipase, which hydrolyzes triglycerides in the circulation to make them available for triglyceride accumulation in adipose tissue. GH also stimulates hormone sensitive lipase (HSL), the rate-limiting step for release of stored triglyceride in adipocytes (lipolysis). As GH becomes utilized for various "non-growth" concerns (see Figure 1), awareness of the metabolic effects on adipocytes is important to understand the clinical effects seen with GH therapy.

Adipose Tissue↗
PubMed1999

Glucocorticosteroid therapy in childhood acute lymphoblastic leukemia.

Treatment of childhood acute lymphoblastic leukemia has included glucocorticosteroids for almost 50 years. Glucocorticoids are the subject of renewed interest. In one randomized trial, deferral of glucocorticosteroids from the initial month of induction therapy to the second month of therapy decreased event free survival despite preservation of remission induction rate. Dexamethasone in induction and maintenance provides a better event free survival than prednisone for standard risk patients in an isotoxic comparison even though all patients received dexamethasone in Delayed Intensification (protocol II). In a third report, patients with prior glucocorticosteroid therapy who achieved remission with subsequent multiagent therapy had a relapse rate similar to that of patients in second remission after failure of multiagent therapy. In vitro and in vivo response of leukemic cells to glucocorticosteroids is highly predictive of outcome. At relapse, loss of in vitro sensitivity to glucocorticosteroids is common and out of proportion to the loss of sensitivity to other agents. Glucocorticoid induced cell kill does not require p53 function. Investigation of leukemic cell lines finds that glucocorticosteroid resistance is most commonly linked to altered receptor number or function. Not all ligands are equivalent. Cortivazol, a pyrazolosteroid, may bind to altered receptor in some cases and induce apoptosis in dexamethasone resistant leukemic cells. Host response to exogenous glucocorticosteroid also varies. Associations between host sensitivity, disease sensitivity, and glucocorticosteroid side effects like avascular necrosis of bone remain to be investigated.

Antineoplastic Agents↗
PubMed1999

Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: A controlled study.

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition and diminished energy expenditure resembling a growth hormone deficient state. Hypothalamic dysfunction in PWS often includes decreased growth hormone (GH) secretion, suggesting a possible therapeutic role for exogenous GH treatment. OBJECTIVES AND METHODS: After 6 months of observation to determine baseline growth rate, and with the use of a 12-month randomized controlled study design, the effects of GH treatment (1 mg/m2/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 54 children with PWS (n = 35 treatment and n = 19 control). Percent body fat and bone mineral density were measured by dual x-ray absorptiometry. Indirect calorimetry was used to determine REE and to calculate respiratory quotients. RESULTS: Stimulated levels of GH in response to clonidine testing were low in all patients (peak, 2.0 ng/mL). After 12 months, GH-treated subjects showed significantly increased height velocity Z scores (mean, 1.0 1.7 to 4.6 2.9; P <.001), decreased percent body fat (mean, 46.3% 8.4% to 38.3% 10.7%; P <.001), and improved respiratory muscle function, physical strength, and agility (sit-ups, weight-lifts, running speed, and coordination). A significant decline in respiratory quotients occurred during GH therapy (0.81 to 0.77, P <.001), but total REE did not change. CONCLUSIONS: GH treatment of children with PWS accelerated growth, decreased percent body fat, and increased fat oxidation but did not significantly increase total REE. Improvements in respiratory muscle strength, physical strength, and agility also occurred, suggesting that GH treatment may have value in reducing some physical disabilities experienced by children with PWS.

Adipose Tissue↗
PubMed1999

Assessment of SNRPN expression as a molecular tool in the diagnosis of Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is associated with lesions of the paternal chromosome 15q11- 13. Recently, loss of expression of a paternally expressed gene in this region, SNRPN, has been proposed as a molecular hallmark of PWS. The goal of this study was to determine the diagnostic accuracy of SNRPN expression in a well-characterized cohort of PWS patients. METHODS: SNRPN expression was analyzed by reverse transcription coupled to polymerase chain reaction (RT-PCR). RNA was isolated from peripheral blood leukocytes and subjected to multiplex RT-PCR in which expression of SNRPN and a constituitively expressed internal control gene were analyzed. The amplified products were electrophoresed in agarose gels and visualized by ethidium bromide staining. RESULTS: Multiplex RT-PCR was applied to RNAs isolated from 30 normal control subjects and 30 well- characterized PWS patients. All control patients expressed the SNRPN and internal control genes. In contrast, all 30 PWS patients demonstrated loss of SNRPN expression, with integrity of RNA being demonstrated by the presence of internal control gene expression. CONCLUSIONS: Loss of SNRPN expression appears to be a consistent finding in PWS. Expression analysis of SNRPN offers a novel approach for the diagnostic evaluation of PWS that is robust and can be performed in a single day.

Adolescent↗
PubMed1999

Physical effects of growth hormone treatment in children with Prader-Willi syndrome.

A randomized, controlled study of 54 children (age, 4-16 years) with Prader-Willi syndrome was conducted to assess the potential beneficial effects of growth hormone (GH) treatment. After observation for 6 months, the children were randomized to receive GH at a dose of 3 IU/m2/day (1 mg/m2/day) (n = 35) or no intervention (n = 19). The effects of GH treatment on linear growth, body composition, muscle strength, pulmonary function and resting energy expenditure were assessed. The levels of GH secreted in response to clonidine stimulation were universally low, and mean (+/- SD) insulin-like growth factor I SDS was -1.2 +/- 0.8 pretreatment. In children treated for 1 year, mean height velocity SDS significantly increased from -1.0 +/- 2.5 to 4.6 +/- 2.9 (p < 0.0001), mean percentage body fat decreased from 46.3 +/- 8.4% to 38.4 +/- 10.7% (p < 0.001), mean lean body mass increased from 20.5 +/- 6.3 kg to 25.6 +/- 4.3 kg (p < 0.01) and respiratory muscle function and physical strength improved. Mean respiratory quotients significantly decreased from 0.81 to 0.77 (p < 0.001); however, resting energy expenditure did not change. Therefore, GH therapy appears to reduce some of the physical disabilities experienced by children with Prader-Willi syndrome.

Adolescent↗
PubMed1999

Persistent infantile hypothyroidism attributable to thyroxine-binding globulin deficiency.

An infant diagnosed with thyroid-binding globulin (TBG) deficiency after newborn screening demonstrated persistent elevation of thyroid-stimulating hormone (TSH) and abnormally low free thyroxine (fT4) levels. Treatment with thyroxine (T4) normalized fT4 and TSH levels during the first 5 years of life, but withdrawal of T4 supplementation at that time was associated with return of hyperthyrotropinemic hypothyroidism. To our knowledge, this patient is the first reported case of TBG deficiency-associated hypothyroidism. In rare instances, TBG deficiency may lead to hypothyroidism requiring hormone supplementation.

Humans↗
PubMedDate not supplied

Sustained benefits of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome are dose-dependent.

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a growth hormone (GH) deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. While recent studies have demonstrated short-term benefits of treatment with GH, a critical question is whether beneficial changes persist or wane with prolonged therapy, and whether these effects on body composition are dose-dependent as seen in adult GH deficiency. OBJECTIVES AND METHODS: After 24 months of GH theapy at a dose of 1 mg/m2/day ("standard dose"), the effects of 12 additional months of GH treatment at varying doses (0.3-1.5 mg/m2/day) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 46 children with PWS. Percent body fat, lean muscle mass, and bone mineral density (BMD) were measured by dual X-ray absorptiometry (DXA). Indirect calorimetry was used to determine REE and to calculate respiratory quotient (RQ). RESULTS: During months 24-36 of GH therapy, further changes in body composition (decrease in fat mass, and increase in lean body mass), growth velocity, and REE occurred with standard and higher-dose GH therapy (1.5 mg/m2/day), but not with lower dose GH (0.3 mg/m2/day). Prior improvements in BMD, and strength and agility, which occurred during the initial 24 months, were sustained during the additional 12 months (to 36 months) regardless of dose. CONCLUSIONS: Salutary and sustained GH-induced changes in growth, body composition, and physical function in children with PWS require GH doses of >0.3 mg/m2/day. Conversely, BMD increased during the additional 12 months of therapy regardless of GH dose. Lower doses of GH, effective in improving body composition in adults with GHD, do not appear to be effective in children with PWS.

Absorptiometry, Photon↗