PubMed Health⌕ Search

Biomedical subjects

C Marcus

Publications and source records attributed to C Marcus.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1998

Insulin and body fat distribution have no direct effect on plasma leptin levels in obese Caucasian women with and without type 2 diabetes mellitus.

Leptin, a hormone produced by adipose tissue, is potentially involved in the regulation of adiposity. The effects of insulin and body fat distribution on human plasma leptin have not yet been clearly defined. The present study investigated the relationships between plasma leptin and total and regional body fat parameters measured by anthropometry and bienergetic absorptiometry associated or not with computed tomography, taking glucose metabolism into account. A cohort of 51 obese Caucasian women (23 with normal glucose tolerance, 11 with impaired glucose tolerance, and 17 with Type 2 diabetes) was analysed. All non-diabetic subjects had an oral glucose tolerance test together with plasma glucose and insulin measurements. Moreover, a subgroup of 7 diabetic subjects with failure to oral antidiabetic treatment was submitted to about 12 days of intensive subcutaneous insulin therapy. Plasma leptin was essentially dependent on total body fat mass (r = 0.83, p < 0.0001, for the whole population), but not related to adipose tissue distribution. An independent correlation between leptin adjusted on body fat mass and fasting insulinaemia (R = 0.72, p < 0.02) or C-peptide (R = 0.62, p < 0.03) was found significant only in the diabetic group. Insulin treatment was associated with a moderate and transient increase of plasma leptin. The relative variations of plasma leptin levels were strongly negatively correlated with those of free fatty acids. The present data confirm that plasma leptin is not dependent on body fat distribution and suggest an indirect effect of insulin on leptin secretion in clinical conditions.

Adipose Tissue↗
PubMed1998

Right nonrecurrent inferior laryngeal nerve and arteria lusoria: the diagnostic and therapeutic implications of an anatomic anomaly. Review of 17 cases.

The authors report 17 cases of a right non-recurrent inferior laryngeal n. (NRILN) observed during 15 years of practice of thyroid and parathyroid surgery. In their last two cases, the existence of an aberrant right subclavian a., constantly associated with NRILN, was confirmed by MRI angiography. On the basis of the literature and their own experience, the authors review the incidence of this double anomaly, its embryologic explanation and its anatomic and surgical importance. They stress the diagnostic factors and the therapeutic implications, very different in children and adults, of a particular vascular anomaly whose outcome is little understood.

Adult↗
PubMed1997

Effects of reverse transcriptase inhibitor therapy on the HIV-1 viral burden in semen.

HIV-1 infection continues to spread worldwide, primarily through sexual intercourse. Because semen is a major vehicle for transmission of HIV-1, we evaluated the effects of reverse transcriptase inhibitor therapy on the amount of HIV-1 in semen. The semen and blood of 11 HIV-1-infected men (i.e. treatment group) were collected before the initiation of reverse transcriptase inhibitor therapy and then 8 to 18 weeks after initiation of therapy. The semen and blood of another 11 HIV-1-infected men (i.e., longitudinal group), who were not on or had no change in antiretroviral therapy for at least 2 months before study entry, were collected at approximately 2-week intervals for 10 to 26 weeks. In the treatment group, 82% of the seminal plasma HIV-1 RNA levels decreased from baseline after 8 to 18 weeks of therapy (median reduction of 1.01 log10, p = 0.01), and 100% of the blood plasma RNA levels decreased from baseline over the same period (median reduction of 0.92 log10, p = 0.003). Five of these patients were followed for at least 52 weeks and had a median seminal plasma HIV-1 RNA level of 0.66 log10 below baseline at 1 year. All subjects in the treatment group with positive cultures at baseline (50%) had negative cultures or a lower infectious units per ejaculate at the 8- to 18-week follow-up examinations. The HIV-1 RNA levels in blood and semen of the longitudinal group did not change significantly over 10 to 26 weeks. Initiation of reverse transcriptase inhibitor therapy effectively reduces shedding of HIV-1 in semen and may therefore reduce the spread of infection within populations.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The lipolytic effects of thyrotropin and isoprenaline are not affected by growth hormone in infant adipocytes.

The lipolytic effects of growth hormone (GH) in children are not fully clarified. In this study, no lipolytic effect of GH on isolated adipocytes obtained at surgery on healthy infants aged 2-5 months and children 3-6 years was observed. Furthermore, GH did not enhance isoprenaline-induced lipolysis, as in adults. The TSH-induced lipolysis which is prominent in neonatal adipocytes was not affected by incubation of adipocytes with GH. Assuming that GH alters adipocyte metabolism primarily by increasing the sensitivity, but not the maximum response, of the beta 2-adrenergic receptor population, it follows that GH, in this sense, should be a less important co-actor in children where beta 2-adrenergic receptors are more abundant.

Adipocytes↗
PubMed1997

Dental maturity in children of short stature, with or without growth hormone deficiency.

The aim of this investigation was to study dental maturity in healthy prepubertal children of short stature (height<-2 SD), with or without growth hormone (GH) deficiency, compared to healthy controls. The GH-deficient group (GH level<10.0 microg/l) included 29 children (11 female, 18 male) with a mean age of 10.2+/-2.2 years. The GH non-deficient group consisted of 17 children (5 female, 12 male) with a mean age of 8.5+/-2.1 years. All the children were evaluated for serum concentrations of IGF-1, alkaline phosphatase (ALP), triiodthyronin (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and fasting plasma insulin; height and bone age were also recorded. Dental maturity was determined from panoramic radiographs. The mean difference between the dental and chronological ages was -0.67+/-0.89 years in the GH-deficient group compared to 0.23+/-1.07 years in their controls: in the GH non-deficient group the difference was -0.95+/-0.82 years compared to controls 0.16+/-1.06 years in their controls. Compared to chronological age, both bone and dental age were lower in the GH-deficient and GH non-deficient groups. It is concluded that children of short stature, both GH-deficient and GH non-deficient. exhibit a delayed dental age compared to their chronological age- and sex-matched controls. A multiple stepwise regression analysis showed that the sitting height and GH level were the only significant factors associated with dental maturity.

Age Determination by Skeleton↗
PubMed1997

Diagnosis of hypoglycaemia: effects of blood sample handling and evaluation of a glucose photometer in the low glucose range.

Hypoglycaemia is a dangerous condition. Rapid and reliable blood glucose measurements are necessary for the initiation of treatment to reduce the risk of neurological sequelae. The aim of this study was to compare a bedside glucose photometer (HemoCue) with three methods of handling blood glucose measurements in a routine chemistry laboratory and to estimate the reliability of glucose measurements in the low glucose range during controlled hypoglycaemia. Nine children underwent an arginine-insulin tolerance test as part of a growth hormone deficiency investigation. Only blood samples below 4.0 mmol l-1 were included (n = 35). Significant (0.3-1.0 mmol l-1) differences in blood glucose measurements were found, depending on the handling of the blood sample. The differences seem primarily to be due to glycolysis which occurred in spite of the addition of the glycolysis inhibitor NaF to the blood samples. Immediate centrifugation and analysis of the supernatant or immediate analysis with the HemoCue results in higher, and presumably more correct, values than routine procedures and permits a more accurate diagnosis of hypoglycaemia.

Arginine↗
PubMed1997

Treatment of adrenoleukodystrophy with bone marrow transplantation.

Three children with adrenoleukodystrophy (ALD) underwent allogeneic bone marrow transplantation (BMT) between 1992 and 1993. The first boy had attention deficits, marked neuropsychological deficits and widespread demyelination in the frontal lobes on MRI before transplantation. Four years later he has mentally deteriorated and the demyelination on MRI has progressed. The second boy had no symptoms but had white matter lesions on MRI when diagnosed. He was regularly followed with MRI and neuropsychological investigations until BMT 18 months later. A progress of the lesions was noted on the initial MRI investigations, and 4 months before BMT a worsening of deficits in attention and kinaesthetic praxis could be observed. He rapidly deteriorated after the transplantation and died 18 months later. Both PCR and in situ hybridization confirmed the presence of donor cells in the brain. The third boy had no symptoms but white matter lesions on MRI when diagnosed. The neuropsychological tests remained normal but a slight progress was observed on MRI just before transplantation. This boy is still healthy 3.5 years after BMT. BMT as treatment for ALD has to be considered very early, even if a child without symptoms but signs of demyelination on MRI, if a suitable donor is available.

Bone Marrow Transplantation↗
PubMed1997

Antilipolytic effect of insulin and insulin receptor messenger RNA expression in adipocytes of infants, children, and adults.

Human adipose tissue exhibits marked age-dependent differences in morphology and regulation of lipolysis. The mechanism behind this phenomenon is poorly characterized. The aim of the present investigation was to evaluate the antilipolytic effect of insulin and the expression of insulin receptor mRNA in human adipose tissue during development. To study the antilipolytic effect of insulin, lipolysis was induced with submaximal effective concentrations of isoprenaline or forskolin in adipocytes from five infants below 2 mo of age, five infants above 2 mo of age, six children, and five adults. Isoprenaline was equally effective in stimulating lipolysis in all age groups, whereas forskolin was significantly more effective in adipocytes isolated from adults than from infants and children. Increasing the concentration of insulin during the incubation allowed construction of dose-response curves of insulin inhibition of lipolysis. Maximal inhibition was observed with 30 microU/mL of insulin in the presence of either isoprenaline or forskolin. No differences in the maximal antilipolytic effect of insulin or in the insulin sensitivity expressed as ED50 were observed. Furthermore, the expression of insulin receptor mRNA in adipocytes did not differ from six infants, five children, and six adults as determined with a solution hybridization RNase protection assay. Thus, age-dependent variations in the regulation of lipolysis do not appear to be accompanied by variations in insulin action and insulin receptor gene expression in isolated adipocytes.

Adipocytes↗