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Biomedical subjects

C Marcus

Publications and source records attributed to C Marcus.

At least 37 records · Page 2Linked to original sources
PubMed2000

Islet cell antibody frequency differs from that of glutamic acid decarboxylase antibodies/IA2 antibodies after diagnosis of diabetes.

The combination of glutamic acid decarboxylase (GAD) 65 antibodies (GADA) and protein tyrosine phosphatase-like protein IA2 antibodies (IA2-ab), measured by radioligand binding assays, has been suggested to replace islet cell antibodies (ICA), measured by indirect immunofluorescence, as a marker for autoimmune type I diabetes. The aim of this study was to compare the frequency of ICA and GADA and/or IA2-ab not only at, but also after the diagnosis of diabetes. ICA, GADA and IA2-ab were therefore assessed at and up to 11 y after the diagnosis of diabetes in 86 children (1-15-y-old). At diagnosis, ICA were found in 74 (86%) and GADA and/or IA2-ab in 79 (92%) of the diabetic children. Hence, there was no major difference in frequency between ICA and GADA and/or IA2-ab at diagnosis of diabetes. At follow-up, however, ICA were less frequent than GADA and/or IA2-ab; 1-3 y after diagnosis ICA were found in 12 (44%) and GADA and/or IA2-ab in 24 (89%) of 27 children (p=0.001); 4-6 y after diagnosis ICA were found in 7 (24%) and GADA and/or IA2-ab in 27 (93%) of 29 children (p < 0.0001); 7-11 y after diagnosis ICA were found in 4 (13%) and GADA and/or IA2-ab in 21 (70%) of 30 children (p < 0.0001). We conclude that the frequency of ICA does not always correspond to that of GADA and/or IA2-ab. Many years after diagnosis of diabetes, measurements of GADA and IA2-ab, but not ICA, detect autoimmunity in high frequency.

Adolescent↗
PubMed2000

Growth hormone and adipocyte function in obesity.

In obesity, growth hormone (GH) secretion is impaired which is considered a consequence rather than a cause of obesity. GH regulates the expression of GH receptor and the synthesis of insulin-like growth factor I (IGF-I) in adipocytes. Although GH hyposecretion in obesity may decrease the generation of IGF-I in each adipocyte, increased amounts of IGF-I and GH-binding protein could be secreted from the excessively enlarged amounts of adipose tissue. This may contribute to the normal/high serum-IGF-I and high GH-binding protein levels in obesity. Hyperinsulinemia and increased GH receptor activity may also affect the GH-IGF-I axis. Favorable effects of GH treatment have been observed in obese children and adults. GH treatment decreases adiposity, reduces triglyceride accumulation by inhibiting lipoprotein lipase and enhances lipolysis both via increased hormone-sensitive lipase activity and via induction of beta adrenoreceptors. GH treatment also has a favorable effect on obesity-associated dyslipidemia, but the effects on insulin sensitivity have been conflicting.

Adipocytes↗
PubMed2000

Effects of growth hormone treatment in obese prepubertal boys.

Childhood obesity is associated with several abnormalities of the GH axis, including decreased spontaneous secretion, decreased response to exogenous secretagogues, and altered pulsatile pattern of secretion. In adults, GH treatment reduces abdominal obesity and improves insulin sensitivity, as well as blood lipid profiles. Whether GH has similar effects in obese children has not been investigated previously. In this study, seven prepubertal severely obese boys aged 10-12 yr were treated with GH for 6 months and followed for an additional 6 months. No diet or exercise modifications were initiated. Body fat percentage decreased from 51.3% to 46.1% after treatment (P = 0.03). Frequently sampled iv glucose tolerance tests revealed an increased responsivity of the acute insulin secretion (P = 0.04) and a nonsignificant trend toward improved insulin sensitivity. In isolated adipocytes, the maximum isoprenaline- and terbutaline-induced lipolysis were increased approximately 2.5-fold (P = 0.02). The sensitivity of the adipocytes to isoprenaline was unchanged, whereas the sensitivity to terbutaline was increased (P = 0.04). No effect was observed on basal or insulin-stimulated lipogenesis. In conclusion, GH treatment for 6 months of obese prepubertal boys reduces body fat, possibly, via stimulation of catecholamine-induced lipolysis, without negative effects on glucose homeostasis.

Adipocytes↗
PubMed1999

False-negative abdominal CT scan in a cocaine body stuffer.

Computed tomography (CT) imaging has been touted as one of the best techniques to detect body packets in body packers and stuffers. The majority of experience has been with body packers. We describe a case of a body stuffer who presented with abdominal pain after ingesting a large packet containing multiple small packets, with a falsely negative abdominal CT scan without contrast. This case raises questions regarding the best method of detection of body packets in body stuffers.

Abdominal Pain↗
PubMed1999

Dental maturity in children of short stature--a two-year longitudinal study of growth hormone substitution.

The aim of this investigation was to present the 2-year follow-up results of a longitudinal study examining the influence of growth hormone (GH) substitution on dental maturity in healthy children of short stature (height <2 SD). At baseline, the children were divided into a GH-deficient group and a GH non-deficient group, and comparisons were made with healthy controls (height between -2 SD and 2 SD) and between the short stature groups. The GH-substituted group included 24 children (8 F, 16 M) with a mean chronological age of 12.20 +/- 2.40 years, whereas the GH non-substituted group included 19 children (5 F, 14 M) with a mean chronological age of 11.00 +/- 2.40 years. The corresponding age- and sex-matched control groups constituted 48 and 36 children, respectively. The mean dental age in the GH-substituted group was 11.60 +/- 2.70 years, compared to their healthy controls 12.40 +/- 2.60 years (P< 0.05). The dental age for the GH non-substituted children was 10.20 +/- 2.60 years compared to their controls 11.90 +/- 2.60 years (P< 0.001). GH-substituted children show an acceleration in their dental maturity in contrast to controls, whereas in non-substituted children the acceleration is less pronounced.

Adolescent↗
PubMed1999

Prevalence of coeliac disease in Turner syndrome.

This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty-seven children and adolescents with Turner syndrome were screened for IgA-antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA), 5% (4/87) being found to be EMA-positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA- or EMA-positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA-positive patients, but only one of the seven AGA-positive patients). The results suggest EMA-positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome.

Adolescent↗
PubMed1999

Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens.

This paper reports results from an ongoing, randomized, multicentre national trial. The aim is to elucidate whether a dose of growth hormone (GH) of 0.2 IU/kg (0.07 mg/kg), given either as once-daily or twice-daily injections during puberty, is more effective than a once-daily dose of 0.1 IU/kg/day (0.03 mg/kg/day) in improving final height in children with GH deficiency (GHD). The twice-daily regimen comes closer to the spontaneous GH secretion pattern in puberty. Ninety-two children with GHD who had been receiving GH therapy for at least 1 year, and with spontaneous puberty or who were prepubertal and due to be started on replacement therapy to induce puberty, were randomly assigned to receive GH as follows: group A, 0.1 IU/kg/day (0.03 mg/kg/day), administered once daily; group B, 0.2 IU/kg/day (0.07 mg/kg/day), administered once daily; and group C, 0.2 IU/kg/day (0.07 mg/kg/day), divided into two equal injections given at 12-hour intervals. Pubertal height gain was 0.7, 0.7 and 1.3 SDS for groups A, B and C, respectively. The gain in height during puberty was thus most marked in group C. Mean final height, when corrected for parental height, was between 0 and 1 SDS in all treatment groups. All but seven children reached a final height within +/- 2 SD of the general population. There was a wide range of final heights in all three treatment groups. This variation in response suggests the need to individualize treatment in order to achieve an appropriate final height for most individuals.

Adolescent↗
PubMed1999

Insulin induced hypoglycaemia: comparison of glucose and glycerol concentrations in plasma and microdialysate from subcutaneous adipose tissue.

AIMS: To investigate the dynamics between plasma and dialysate glucose during hypoglycaemia in children. STUDY DESIGN: Six children in prepuberty or early puberty were investigated by multiple blood sampling and microdialysis of subcutaneous adipose tissue during a standard arginine-insulin tolerance test. Glucose and glycerol, as an index of lipolysis, were measured in samples from both compartments. Plasma concentrations of insulin and the main counterregulatory hormones were also measured. RESULTS: Plasma and dialysate glucose concentrations were very similar at baseline and increased in concert after infusion of arginine, probably in response to glucagon release. After insulin injection, glucose in both plasma and dialysate fell in parallel. The subsequent hypoglycaemic stress response induced a rapid rebound in the plasma concentration with a mean (SD) delay in the dialysate of 16 (3) minutes. Plasma glycerol was approximately fivefold lower than in the dialysate and did not fluctuate significantly. Dialysate glycerol decreased with arginine infusion and reached a nadir immediately following insulin administration. Subsequently, the antilipolytic effect of insulin was overcome by the hypoglycaemic stress response, and lipolysis prevailed in spite of hyperinsulinaemia. CONCLUSION: After rapidly induced hypoglycaemia, rebound of interstitial glucose concentrations is significantly delayed compared with plasma concentrations, and the antilipolytic effect of hyperinsulinaemia is opposed possibly by the hypoglycaemic stress response.

Adipose Tissue↗
PubMed1999

Growth hormone treatment downregulates serum leptin levels in children independent of changes in body mass index.

The changes in serum leptin levels during growth hormone (GH) treatment were studied in 27 children, 17 with GH deficiency (GHD), 10 with idiopathic short stature (ISS), and 9 with Prader-Willi syndrome (PWS). Within 1 month of GH treatment, serum leptin levels decreased by 40% in the GHD children (p < 0.01). There was no significant change in serum leptin level in the children with ISS. In children with PWS, the mean serum leptin level decreased by almost 60% after 3 months of treatment (p < 0.001). Thereafter, no further decline was observed in any of the 3 groups. Changes in body composition became evident first after the 3 months of treatment. In the GHD children, the BMI was unchanged while the mean body fat percentage was 2.7% lower after 1 year of GH treatment (p < 0.05). In the ISS children, neither BMI nor body fat percentage were significantly changed during treatment. The PWS children exhibited a significant decrease in BMI after 6 months of GH treatment without any further change during the remaining period of treatment. In this group, the mean body fat percentage decreased from 42 +/- 2.4 to 28 +/- 2.2% after treatment (p < 0.001). The finding that the fall in leptin occurs before changes in body composition become detectable suggests a direct effect of GH on leptin production, metabolism, or clearance.

Body Composition↗
PubMed1999

Failure of cortisone acetate treatment in congenital adrenal hyperplasia because of defective 11beta-hydroxysteroid dehydrogenase reductase activity.

Congenital adrenal hyperplasia in children is often treated with cortisone acetate and fludrocortisone. It is known that certain patients with congenital adrenal hyperplasia require very high substitution doses of cortisone acetate, and a few patients do not respond to this treatment at all. A patient with 21-hydroxylase deficiency, for whom elevated pregnanetriol (P3) levels in urine were not suppressed during treatment with cortisone acetate (65 mg/m2 x day), was examined. The activation of cortisone to cortisol was assessed by measuring urinary metabolites of cortisone and cortisol. The patient's inability to respond to treatment with cortisone acetate was found to be caused by a low conversion of cortisone to cortisol, assumed to be secondary to low 11beta-hydroxysteroid dehydrogenase activity (11-oxoreductase deficiency). All exons and exon/intron junctions of the 11beta-hydroxysteroid dehydrogenase type1 gene (HSD11L) were sequenced without finding any mutations, but a genetic lesion in the promoter or other regulatory regions cannot be ruled out. The deficient 11-oxoreductase activity seems to have been congenital, in this case, but can possibly be attributable to a down-regulation of the enzyme activity. The results support the use of hydrocortisone, rather than cortisone acetate, for substitution therapy in adrenal insufficiency.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Pathophysiological and genetic characterization of the major diabetes locus in GK rats.

Genetic studies of the type 2 diabetes-like GK rat have revealed several susceptibility loci for the compound diabetes phenotype. Congenic strains were established for Niddm1, the major quantitative trait locus (QTL) for postprandial glucose levels, by transfer of GK alleles onto the genome of the normoglycemic F344 rat. Despite the polygenic nature of diabetes in GK, the locus-specific diabetes phenotype was retained in the congenic strain Niddmla, containing a GK-derived genomic fragment of 52 cM from the Niddm1 locus. Furthermore, Niddm1 was divided into two non-overlapping loci, physically separated in the two congenic strains Niddmlb and Niddm1i with distinct metabolic phenotypes. Both strains displayed postprandial hyperglycemia and reduced insulin action in isolated adipose cells. Furthermore, Niddm1i already exhibits a pronounced in vivo insulin secretion defect at 65 days, while Niddm1b develops a relative insulin secretory defect at 95 days. This suggests that Niddm1i impairs mechanisms common to insulin secretion in pancreatic B-cells and insulin action in adipocytes. Niddm1b rats show signs of increasing insulin resistance with age associated with obesity, hyperinsulinemia, and dyslipidemia. Moreover, the data indicated nonallelic interaction (epistasis) between Niddm1b and Niddm1i on the postprandial glucose levels. These data emphasize the pathophysiological complexity of diabetes, even within an apparently single QTL, and demonstrate the potential of the GK model in transforming the multifactorial diabetes phenotype into single traits, suitable for positional cloning.

Adipose Tissue↗
PubMed1999

Growth hormone treatment of patients with Prader-Willi syndrome. Swedish Growth Hormone Advisory Group.

Several studies have now been published on the effect of one or several years of growth hormone treatment on growth and body composition of children with Prader-Willi syndrome. The majority of the patients have responded with greatly increased growth rate, decreased body fat and increased muscle volume. Many of these children seem to have a functional growth hormone deficiency, probably secondary to their hypothalamic dysfunction. Further studies are needed to establish the long-term effect of this treatment on somatic and psychological well-being.

Body Composition↗
PubMed1998

Intravascular and total body platelet equilibrium in healthy volunteers and in thrombocytopenic patients transfused with single donor platelets.

Instrument platelet counts used in corrected count increment (CCI) and percent platelet recovery (PPR) formulas presume the transfused platelets are in equilibrium during the first hour after platelet transfusion. The timing of the pre-transfusion count affects CCI results, and we postulate that timing of CCI post transfusion affects CCI results. Platelet equilibrium using indium-111 platelet transfusions has not been reported. Platelet redistribution was studied in 16 healthy volunteers and 12 thrombocytopenic patients by generally infusing less than 72-hr stored single-donor platelets along with an aliquot of indium-111-labeled platelets by intravenous push. Counts were measured at 10, 15, 20, 60, and 120 min, and 24, 48, 72 hr along with continuous body scanning for 2 hr in healthy volunteers, and static organ scanning in patients and volunteers. Results indicated transfused platelets do not reach intravascular equilibrium for 60 min post-infusion and that the 10-min count cannot detect platelet refractoriness. However, total body equilibrium varies considerably between normal volunteers and thrombocytopenic patients. It is recommended to continue with the 1-hr post transfusion count.

Antigens, Human Platelet↗
PubMed1998

Presence of thyrotropin receptor in infant adipocytes.

In healthy infants, the levels of TSH are known to peak at 50-100 times adult values during the first days of life. In studies of isolated human infant adipocytes, we have earlier shown that bovine TSH (bTSH) has a strong lipolytic effect, accompanied by a blunted response of adipocytes to catecholamines. In this study, we used human recombinant TSH (hTSH), and incubation of adipocytes with hTSH induced a lipolytic response similar to that obtained with the beta-adrenergic receptor agonist isoprenaline in adipocytes isolated from three infants. The lipolytic effect of hTSH was completely blocked by inhibitory TSH receptor (TSHR) antibodies. The TSHR mediates the effects of TSH in the thyroid, and it has been detected in some extrathyroid tissues, but not in isolated human adipocytes or childhood adipose tissue. In this study, we found TSHR RNA in infant and adult adipose tissues and isolated adipocytes with reverse transcriptase-PCR. The sequence of the amplified PCR product agreed with the published sequence. Northern blot hybridization on RNA prepared from infant adipose tissue showed a transcript of the expected size, and the expression of TSHR seemed higher in infant than in adult adipose tissue. In conclusion, this study indicates that TSH plays an active role in the metabolic adaptation after birth.

Adipocytes↗
PubMed1998

Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome.

OBJECTIVE: To study the effect of growth hormone (GH) treatment (2-4 months) on insulin action in adipocytes isolated from children with Prader-Willi syndrome (PWS), in whom GH deficiency appears to be a primary defect. We investigated the complex effects of GH on carbohydrate metabolism, as part of a current clinical trial of GH treatment in children with PWS. METHODS: Biopsies of subcutaneous abdominal adipose tissue were obtained from 12 children with PWS before and after 2-4 months of GH treatment. Lipogenesis was determined by the incorporation of radiolabelled glucose into lipids in isolated adipocytes, and glycerol release to the incubation medium was used as an index of lipolysis. GLUT4 RNA was measured by solution hybridization. RESULTS: With low glucose concentrations, at which glucose transport is rate-limiting, maximal insulin-induced lipogenesis was increased by 120% after GH treatment (P < 0.05), but the sensitivity to insulin (half-maximum effective hormone concentration) was unchanged. This was not accompanied by a significant change in the RNA expression of GLUT4. Neither responsiveness (maximum effect) nor sensitivity of insulin-induced inhibition of lipolysis was affected by GH treatment. CONCLUSIONS: GH treatment of children with PWS results in an upregulation of insulin-induced lipogenesis in isolated adipocytes, with no effect on insulin-induced inhibition of lipolysis. The data suggest that the site of the effect of GH on lipogenesis is distal to the insulin hormone-receptor interaction, but does not involve altered GLUT4 expression.

Adipocytes↗
PubMed1998

Variations in glucocorticoid levels within the physiological range affect plasma leptin levels.

OBJECTIVE: Leptin, the obese gene product, is thought to regulate body fat through its action on hypothalamic receptors that influence satiety. The hormonal regulation of leptin is important, since it might affect adiposity. Leptin regulation in man is poorly understood. We studied the relation between endogenous cortisol and leptin levels as well as the acute and chronic effects of a low dose of dexamethasone (DEX) on plasma leptin levels in healthy male volunteers. SUBJECTS AND EXPERIMENTAL PROTOCOL: The correlation between basal plasma levels of leptin and cortisol and the chronic effect of DEX treatment were studied in 12 subjects. Plasma leptin and cortisol levels were determined every other hour for 24 h, before and after 2 weeks of oral administration of 0.1 mg DEX twice daily. The acute effect was studied in 20 subjects, who received 1 mg DEX at 2300 h. Fasting blood samples were taken at 0800 h on the same day (i.e. before DEX) and on the day after. RESULTS: Under basal conditions, we found a correlation between mean plasma levels of leptin and cortisol (r = 0.7, P<0.02). Mean plasma leptin levels had increased by 50% after 2 weeks of DEX treatment (P<0.05). The circadian rhythm of leptin was preserved, but the night peak occurred 2.5 h earlier (P<0.05). Fasting plasma leptin levels were 20% higher 9 h after 1 mg DEX orally than at the same time on the day before (P<0.002). CONCLUSION: Physiological variations in cortisol are involved in the regulation of leptin.

Adult↗