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Biomedical subjects

C Marcus

Publications and source records attributed to C Marcus.

At least 19 recordsLinked to original sources

Orlistat treatment in obese prepubertal children: a pilot study.

AIM: This study investigated orlistat treatment in obese prepubertal children with regard to tolerance, safety and psychological well-being. METHODS: 11 healthy, severely obese prepubertal children (age 8.3-12.3 y, body mass index standard deviation score 5.3-9.2) were recruited for a 12 wk open treatment. Before, during and after treatment, the participants were investigated by psychological evaluation, blood chemistry, and parameters reflecting obesity and fat mass. RESULTS: The participants were able to comply with the treatment, as indicated by pill counts and self reports, and expressed a desire to continue the treatment after the study period. Gastrointestinal side effects were mild and tolerable. No negative effects on psychological or physical well-being were detected, and the psychological evaluation demonstrated increased avoidance of fattening food, body shape preoccupation and oral control (p = 0.011). The median weight loss was 4.0 kg (range -12.7 to +2.5 kg, p = 0.016) and was highly correlated to decreased fat mass (regression coefficient 0.953, p < 0.01). CONCLUSION: This pilot study indicates that obese prepubertal children were able to reduce their fat intake to avoid gastrointestinal side effects. Thus, orlistat may be suitable as a component in behaviour-modification programmes for obese children, and the results prompt a placebo-controlled investigation of its effectiveness in promoting weight loss.

Absorptiometry, Photon↗

[Retromuscular prosthetic repair: experience from France].

Large incisional hernias cannot be cured without prosthetic material. A large pore size prosthetic tissue seems to be the best alternative, since connective invasion of the mesh provides a very strong fixation of the prosthesis. In our view, the mesh should be placed in the rectus sheath, in a position we have described as "retromuscular prefascial". With this technique, a good result can be achieved in 98% of very large incisional hernias.

Abdominal Muscles↗

In vitro effects of leptin on human adipocyte metabolism.

OBJECTIVE: Leptin receptors are expressed in adipocytes, suggesting potential autocrine/paracrine effects. Studies on the direct effects of leptin on adipose tissue metabolism in different species have yielded controversial data. To assess the in vitro effects of leptin on human adipocyte metabolism: lipolysis, the insulin-induced inhibition of lipolysis and lipogenesis were studied in adipocytes obtained from infants and adults. METHODS: Lipolysis was studied by incubating adipocytes with increasing concentrations of leptin or isoprenaline. Glycerol in the incubation medium was measured as an indicator of lipolysis. For the lipogenesis and insulin-induced inhibition of lipolysis experiments, the cells were preincubated with 0, 25, or 250 ng/ml of leptin for 2 h. RESULTS: Leptin did not stimulate lipolysis in human adipocytes, either in children or adults. Preincubation with leptin did not affect the insulin-induced inhibition of lipolysis, but decreased the insulin-induced lipogenesis (p < 0.05). CONCLUSIONS: This study shows that leptin has no direct lipolytic effect in human adipocytes. The lack of effect on the insulin-induced inhibition of lipolysis and the negative effect on lipogenesis indicates that the effect of leptin is not at the proximal insulin-signalling pathway but further downstream.

Adipocytes↗

[Persistent sciatic artery: findings using spiral-CT].

Persistent sciatic artery (PSA), a rare anatomical anomaly, results from lack of regression of the embryonic dorsal axial artery combined with a poorly developed superficial femoral artery. The authors report the case of a 68-year old man presenting with subacute ischemia of the right lower limb. Arteriography showed complete bilateral persistent sciatic arteries. CT scan with 3D reconstructions was helpful to demonstrate the PSA descending along the back of the thigh and to exclude an aneurysmal complication.

Aged↗

Upregulation of uncoupling protein homologues in skeletal muscle but not adipose tissue in posttraumatic insulin resistance.

Metabolic alterations after surgical stress include peripheral insulin resistance and increased utilization of fat as a fuel substrate. An up-regulation of skeletal muscle uncoupling proteins (UCPs) has been associated with physiologic states of insulin resistance and enhanced fat metabolism in rodents. We examined whether posttraumatic insulin resistance induced the UCPs in gastrocnemius and soleus muscle and white adipose tissue in an experimental model of surgical trauma. Insulin sensitivity was significantly reduced in isolated soleus muscles but unchanged in adipocytes after trauma. In traumatized rats, mRNA and protein contents of UCP2 and UCP3 and were significantly increased in both muscle types. UCP2 protein content in adipose tissue was unaltered by surgical stress. Circulating NEFAs and glycerol were reduced after surgical trauma. We hypothesize that the changes in UCP2 and UCP3 gene and protein expression are involved in the regulation of substrate utilization in posttraumatic insulin resistance.

Adipocytes↗

Development and validation of a self-completed HIV symptom index.

Traditional, open-ended provider questions regarding patient symptoms are insensitive. Better methods are needed to measure symptoms for clinical management, patient-oriented research, and adverse drug-event reporting. Our objective was to develop and initially validate a brief, self-reported HIV symptom index tailored to patients exposed to multidrug antiretroviral therapies and protease inhibitors, and to compare the new index to existing symptom measures. The research design was a multistage design including quantitative review of existing literature, qualitative and quantitative analyses of pilot data, and quantitative analyses of a prospective sample. Statistical analyses include frequencies, chi-square tests for significance, linear and logistic regression. The subjects were from a multisite convenience sample (n = 73) within the AIDS Clinical Trials Group and a prospective sample from the Cleveland Veterans Affairs Medical Center (n = 115). Measures were patient-reported symptoms and health-related quality of life, physician-assessed disease severity, CD4 cell count, and HIV-1 RNA viral quantification. A 20-item, self-completed HIV symptom index was developed based upon prior reports of symptom frequency and bother and expert opinion. When compared with prior measures the index included more frequent and bothersome symptoms, yet was easier to use (self-report rather than provider interview). The index required less than 5 minutes to complete, achieved excellent completion rates, and was thought comprehensive and comprehensible in a convenience sample. It was further tested in a prospective sample of patients and demonstrated strong associations with physical and mental health summary scores and with disease severity. These associations were independent of CD4 cell count and HIV-1 RNA viral quantification. This 20-item HIV symptom index has demonstrated construct validity, and offers a simple and rational approach to measuring HIV symptoms for clinical management, patient-oriented research, and adverse drug reporting.

Antiretroviral Therapy, Highly Active↗

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↗