Search PubMed⌕ Search

Biomedical subjects

C Marcus

Publications and source records attributed to C Marcus.

At least 37 records · Page 2Linked to original sources

Cerebrospinal fluid and plasma concentrations of leptin, NPY, and alpha-MSH in obese women and their relationship to negative energy balance.

Leptin and its principal mediators, NPY and alpha-MSH are postulated to play a pivotal role in energy balance. To determine the possibility of the disturbance in neuropeptides in human obesity and their consequent changes in response to negative energy balance, we evaluated plasma and cerebrospinal fluid (CSF) leptin, NPY, and alpha-MSH levels in obese women before and after weight loss in comparison with normal control women. Subjects included 16 obese women [mean body mass index (BMI), 35.6 kg/m(2)] before and after weight loss induced by a 2-wk very low caloric diet (800 kcal/d) and 14 normal weight women (mean BMI, 20.4 kg/m(2)). The CSF to plasma leptin ratio in normal weight subjects was 2.3-fold higher than that in obese subjects. After weight loss in obese subjects, plasma leptin levels decreased by 40% and CSF levels decreased by 51%. There was a positive linear correlation between CSF and plasma leptin levels at baseline in obese subjects (r = 0.74, P < 0.05) and a positive logarithmic correlation in normal weight subjects (r = 0.89, P < 0.05) and in obese subjects after weight loss (r = 0.64, P < 0.05). The BMI was negatively correlated with the CSF to plasma leptin ratio (r = -0.86, P < 0.05) in all subjects. Neither the baseline plasma levels nor the baseline CSF levels of NPY were different between normal weight subjects and obese subjects. After weight loss, the CSF NPY level decreased significantly compared with baseline values in obese subjects. The alpha-MSH levels in plasma and CSF did not differ significantly from controls in obese subjects at baseline or after weight loss. Baseline CSF leptin level correlated with neither the baseline CSF NPY level nor the baseline CSF alpha-MSH level. In conclusion, this study demonstrated that the efficiency of brain leptin delivery is reduced in human obesity and central nervous system leptin uptake involves a combination of a saturable and an unsaturable mechanism. CSF NPY and alpha-MSH did not differ from controls in human obesity, and the CSF NPY level decreased significantly whereas alpha-MSH did not differ after weight loss in obese subjects compared with baseline. There was no significant correlation between CSF leptin and CSF NPY or alpha-MSH. This could be the result of leptin resistance present in human obesity and/or the more complex mechanisms involved in modulating appetite and regulating energy balance in human obesity.

Adult↗

Total parenteral nutrition after surgery rapidly increases serum leptin levels.

OBJECTIVE: In humans, leptin is regulated by long-term changes in energy intake. However, short-term regulation of serum leptin by nutrients has been difficult to show. The aim of this study was to investigate whether short periods of fasting and stress sensitise the leptin response to nutrients. SUBJECTS AND EXPERIMENTAL PROTOCOL: Fourteen patients of normal weight undergoing elective open cholecystectomy were randomised into two groups. One group received saline infusion during surgery and for 24 h postoperatively. The other group also received saline during the surgical procedure, but total parenteral nutrition (TPN) was started immediately after surgery. Blood samples were drawn before as well as 2, 4, 8, 16, and 24 h after the start of surgery to determine the serum levels of leptin and other hormones. RESULTS: Postoperative TPN induced a significant rise in serum leptin within 6 h, reaching a more than fourfold increase within 14 h (P<0.001). Serum glucose and insulin levels increased within 2 h. Growth hormone and IGF-1 serum levels also increased significantly in the group receiving TPN. Serum cortisol levels increased postoperatively in both groups, which may explain why no significant reduction in serum leptin was observed in the group receiving saline. Free tri-iodothyronine (T3) decreased in both groups, while catecholamines were similar in the groups. CONCLUSION: During fasting and surgical stress, nutrients rapidly increased the serum leptin levels in humans in a manner similar to that previously reported in rodents. This may be mediated by increases in serum glucose, insulin and cortisol.

Adult↗

Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone levels and CYP21 genotypes in preterm infants.

OBJECTIVE: Neonatal screening for congenital adrenal hyperplasia (CAH) among preterm infants is complicated by the fact that healthy preterm infants have higher levels of 17-hydroxyprogesterone (17-OHP) than term infants, resulting in a higher false-positive rate. Even when gestational age-related cutoff levels after ether extraction were used, the false-positive cases primarily comprised preterm infants. The aim of the study was to optimize the procedure for neonatal screening for CAH in preterm infants. METHODS: The 17-OHP levels in 6200 preterm infants were correlated to the gestational age. We also calculated the number of recalls for different putative cutoff levels of the 17-OHP by direct assay and after extraction in 1275 preterm infants who represented the most elevated cases in a population of approximately 30 000 preterm infants. The CYP21 genotypes and screening levels were determined in the 12 preterm infants with CAH diagnosed since the start of screening. The effect of possible interfering factors such as gestational age, neonatal stress, and prenatal glucocorticoid treatment for pulmonary maturation was studied. RESULTS: The extraction procedure did not significantly improve the sensitivity or specificity of the screening, whereas it delayed the day of recall from 8 to 13 days (median). We could not demonstrate any systematic influence of the studied stress factors or the prenatal glucocorticoid treatment on the 17-OHP screening levels. In the patients with CAH, the 17-OHP levels correlated better with disease severity than with the degree of prematurity. CONCLUSIONS: On the basis of these results, we omitted the extraction step and changed the cutoff levels in the Swedish screening program for preterm infants. We chose to use a cutoff level of 400 nmol/L plasma in infants who were born before week 35 and 150 nmol/L for infants who were born in weeks 35 and 36. For detecting more patients, the cutoff level would have to be much lower, which would result in a number of false-positive tests that we consider to be unacceptably high. It is clear that neonatal screening cannot detect all infants with CAH. Some milder forms of the disease, just like in the past, will have to be diagnosed on the basis of clinical signs and symptoms.

17-alpha-Hydroxyprogesterone↗

Effects of growth hormone treatment on the leptin system and body composition in obese prepubertal boys.

UNLABELLED: Leptin correlates with measures of body fat stores. Growth hormone (GH) treatment may affect leptin levels either directly or indirectly by influencing body composition and circulating insulin level. Here, the effects of GH treatment on the leptin axis and body composition of six severely obese, but otherwise healthy, prepubertal boys were studied. Fasting serum leptin was significantly reduced after only 3 wk of GH treatment. Body fat percentage, but not BMI, decreased significantly (p < 0.05) after 3 mo. The serum leptin concentration per unit fat mass decreased significantly during GH treatment (p < 0.05), suggesting that such treatment might have a direct effect on serum leptin independently of the effects on body composition. Leptin RNA expression in abdominal subcutaneous tissue was not significantly changed by treatment. CONCLUSIONS: The data indicate that GH has an early downregulatory effect on the circulating leptin level independently of the concomitant changes in body composition. Whether GH affects leptin production or metabolism needs further study.

Area Under Curve↗

Functional anatomy of the gastroesophageal junction.

The study of the functional anatomy of the gastroesophageal junction allows for the demonstration of a double mechanism that combats the conflict of pressures that tends to lead to gastroesophageal reflux. On one hand, the LES, an intrinsic structure, is directly related to the muscle fibers of the organ and responds to a neurohormonal physiologic command. On the other hand is an anatomic entity, centered by the crura of the diaphragm, closely related to the movements of respiration. These structures constitute a second, extrinsic sphincter that gives rise to the zone of high pressure in the terminal esophagus. This role is difficult to assess, and its importance is underestimated. The proper functioning of these two mechanisms implies that the gastroesophageal junction remains in place within the diaphragmatic channel of the esophagus. Also important are the postural phenomena associated with the sloping position of the fundus. In patients with gastroesophageal reflux, the decrease of the pressure measured in the terminal esophagus accounts for the occurrence of reflux. Investigators concede that, under the influence of abdominal straining, the gastroesophageal junction tends to ascend into the diaphragmatic channel. The results are twofold: (1) the muscle fibers of the lower esophagus relax, explaining the incompetence of the intrinsic sphincter, and (2) the sphincteric zone is withdrawn from its muscular diaphragmatic environment. Physicians should consider these structures as a whole in approaching the surgical treatment of reflux. The construction of a periesophageal valve has no anatomophysiologic basis. A gastropexy procedure must be added to replace the gastroesophageal junction in its anatomic setting and keep it there. This procedure also allows retightening of the muscle fibers of the esophageal wall, which is essential in long-term surgical correction.

Esophagogastric Junction↗

Surgical anatomy and embryology of the adrenal glands.

Gross anatomy explains the different surgical approaches to adrenalectomy and the difficulties encountered by surgeons during this procedure. Development of the adrenal glands explains the location of the ectopic sites and excess hormone production by adrenal tumors. The choice of a surgical approach is sometimes difficult and is dependent on (1) the morphology of the body; (2) the volume of the tumor, which necessitates immediate vascular control; and (3) the type of disease, which may necessitate a complete exploration of the abdominal cavity.

Adrenal Gland Diseases↗

Measurement of visceral adipose tissue by DXA combined with anthropometry in obese humans.

OBJECTIVE: To get accurate measurements of visceral adipose tissue (VAT) using dual energy X-ray absorptiometry (DXA). DESIGN: DXA and anthropometric data and their combinations were compared to the VAT area calculated from a computed tomography (CT) single scan. SUBJECTS: 71 overweight subjects (44 women, 27 men), age: 16-70 y, BMI: 27-52 kg/m2. MEASUREMENTS: Total body and segmental tissue composition, and new parameters obtained from DXA, in addition to waist and hip circumferences and abdominal sagittal diameter measurements. RESULTS: The ratio measured at the umbilical level (sagittal diameter - subcutaneous fat width) x (transverse internal diameter)/(height) was closely related to VAT (r=0.94 for women and 0.88 for men). It gave the most predictive equation for VAT: y = 79.6x (s.e. 3.9) - 149 cm2 for the whole population (r2=0.86, P<0.0001, root mean square error=38.2 cm2. An independent relationship between lean mass or its index (r=0.52 and 0.72, P<0.001) and VAT was also found in women. CONCLUSION: This study demonstrates the potential usefulness of DXA to supply accurate measurements of VAT in addition to total body composition determination in obese subjects.

Absorptiometry, Photon↗

Age-dependent variations in white adipose tissue glycerol and lactate production after surgery measured by microdialysis in neonates and children.

In previous studies, we observed that lactate concentrations in interstitial white adipose tissue are higher in small infants than in adults. Moreover, no lipolysis following catecholamine challenge has been reported in neonates and small infants. Our aim was to determine with microdialysis whether the above mentioned age-dependent changes could be detected in situ after surgery. A microdialysis catheter was introduced into the abdominal subcutaneous tissue in 13 neonates and 12 children undergoing surgery. Interstitial concentrations of glucose, lactate and glycerol were measured hourly during the first 20 postoperative hours. The concentrations of lactate in interstitial white adipose tissue were consistently higher in neonates compared to older children, with a significant difference during the 9-18 h postoperative period (P < 0.05). A significant difference in the lactate:glucose ratio was observed at 1-2, 8-10, 15 and 18 h postoperatively (P < 0.05). No significant differences were observed between the two groups with respect to glycerol and glucose concentrations. Interstitial lactate concentrations in white adipose tissue were higher in neonates compared with children in the early postoperative period. No age-dependent difference in postoperative lipolysis, measured as interstitial glycerol concentrations, was observed. Thus, an age-dependent difference in interstitial lactate production, but not lipolysis, was detected in the early postoperative period.

Adipose Tissue↗

Eating behavior in Prader-Willi syndrome, normal weight, and obese control groups.

OBJECTIVE: Hyperphagia in Prader-Willi syndrome (PWS) is hypothesized to be due to hypothalamic dysfunction; thus the study of individuals with PWS might illustrate how hypothalamic dysfunction affects eating behavior. The aim of this study was to document the microstructure of the eating behavior in patients with PWS and to compare it with that of members of obese and normal weight control groups of the same age. STUDY DESIGN: Nine subjects with PWS (age, 10 +/- 4 years), 20 normal weight subjects (age, 12 +/- 3 years), and 20 obese subjects (age, 12 +/- 4 years) were served an excess lunch meal (hash) on a hidden scale built into a table and connected to a computer. The plate of food is placed on top of the scale, and when the food is eaten, the change in food weight is registered continuously. An eating curve is displayed online. After the meal, the eating data are fitted to a polynomial, and the computer calculates the amount of food eaten, time of consumption, eating rate (initial and total), and rate of deceleration. RESULTS: Subjects with PWS were found to have a longer duration of eating (P =.04) and a slower initial eating rate (P =. 01) compared with members of both obese and normal weight groups. In subjects with PWS, 56% of the eating curves were non-decelerating (linear or accelerating) compared with 10% of the normal weight group and 30% of the obese group (P =.02). CONCLUSION: The microstructure of the eating behavior in subjects with PWS differs from that of members of obese and normal weight control groups. Thus the eating behavior found in subjects with PWS might be due to decreased satiation rather than increased hunger.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗