PubMed Health⌕ Search

Biomedical subjects

C Marcus

Publications and source records attributed to C Marcus.

At least 73 records · Page 4Linked to original sources
PubMed1997

Increased leptin messenger RNA and serum leptin levels in children with Prader-Willi syndrome and nonsyndromal obesity.

To study the potential role of the ob gene pathway in childhood obesity, we have investigated leptin mRNA levels in s.c. adipose tissue obtained from nonobese prepubertal children (n = 20), obese nonsyndromal children (n = 6), and children with Prader-Willi syndrome (n = 6) by in situ hybridization histochemistry. We have also investigated the fasting serum leptin levels in such children. Compared with nonobese children, leptin mRNA expression was higher both in children with Prader-Willi syndrome and in children with nonsyndromal obesity (p < 0.01). Furthermore, the serum leptin levels were also significantly higher in both children with Prader-Willi syndrome and nonsyndromal obesity compared with the nonobese children (p < 0.001). However, no significant differences in adipose tissue leptin mRNA or serum leptin levels were observed between children with Prader-Willi syndrome and nonsyndromal obese children. As expected both fasting serum leptin levels and leptin mRNA expression levels correlated to body mass index (rs = 0.80 and 0.73, respectively, p < 0.005). No difference in leptin expression between Prader-Willi syndrome and nonsyndromal childhood obesity could be revealed in the present study. However, differences in the hypothalamic response to leptin between the two forms of obesity cannot be excluded.

Adipose Tissue↗
PubMed1997

Circadian cortisol rhythms in healthy boys and girls: relationship with age, growth, body composition, and pubertal development.

To provide basic information on the normal functioning of the hypothalamus-pituitary-adrenal axis in relation to pubertal development, growth (weight and height), body composition, and gender and to obtain reference data for serum cortisol concentrations in children, we investigated the basal circadian rhythm of serum cortisol in a group of 235 healthy children (162 boys and 73 girls). The age range was between 2.2-18.5 yr. Serum cortisol was analyzed from venous blood samples taken at 1400, 1800, 2200, 0200, 0400, 0600, and 1000 h. No evidence was found for differences in temporal placement or level of the circadian cortisol rhythm in relation to age, growth, or body composition. However, we found a broad range of cortisol levels in a healthy population, with individual mean diurnal levels ranging from 100-510 nmol/L. Regardless of high or low mean diurnal cortisol levels, repeated measurements within and between pubertal stages indicated that an individual remains in his or her cortisol range throughout pubertal development. In conclusion, the present study shows that 1) serum cortisol levels do not correlate with either age or gender; 2) there is a large and significant interindividual variability in endogenous mean diurnal cortisol levels; and 3) despite this variability between individuals, there is no correlation between cortisol levels and either body composition or growth rate. This suggests that the variability in cortisol levels is an expression of normal homeostasis rather than pathology.

Adolescent↗
PubMed1997

[Volume rendering technique in 3D vascular imaging].

We used volume rendering technique (VRT) for generating three-dimensional (3D) images of the vasculature from spiral computed tomography (CT) data sets. This paper describes the methods used for volume rendering and focuses on the specific aspects of volume rendering as applied to vascular imaging.

Angiography↗
PubMed1996

Lactate in cord blood and its relationship to pH and catecholamines in spontaneous vaginal deliveries.

The interrelationships between lactate and pH, nonadrenaline (NA), adrenaline (A) and dopamine (DA) were investigated in cord artery (CA) and vein (GV) blood at delivery. Sixty consecutive, spontaneous, vaginal deliveries with fetuses in cephalic presentation were assessed. Median gestational age at delivery was 40 weeks (range, 35-43). There were significant correlations between lactate and pH (P < 0.01), NA (P < 0.01), A (P < 0.05) and arterio-venous NA (P < 0.05) and DA differences (P < 0.01) in CA blood, while no variable correlated significantly to lactate in CV blood. The higher levels both of lactate and of catecholamines in CA blood are probably fetally derived. Dividing the material into high and low lactate subgroups (cut-off level, 75th percentile) showed a high lactate level to be associated with lower pH and higher catecholamine levels in CA blood, though the relationship was only statistically significant for pH. The levels both of catecholamines and of lactate were lower than those reported for cases of fetal distress, and reflect the lower level of fetal stress in the present series of normal deliveries. The low level of fetal stress and the differences in turnover rates between catecholamines and lactate might obscure their causal relationships, vis-a-vis fetal adaptation to extrauterine life during the course of parturition.

Delivery, Obstetric↗
PubMed1996

Avascular necrosis of the femoral head as a complication of chronic myelogenous leukaemia.

A 17-year-old male patient complaining of intense pain in his right hip was found to be suffering from chronic myelogenous leukaemia. Preliminary X-rays and bone scintigraphy did not suggest avascular necrosis of the femoral head. Magnetic resonance imaging (MRI) did, however, reveal leukaemic infiltration of the femoral neck and generalised ischeamia in the femoral head. Further, MRI carried out 4 months later disclosed typical signs of osteonecrosis, despite previous indications of an improvement under chemotherapy. Flattening of the head of the femur appeared in radiographs taken in the 9th month. In the 12th month, recurrence of pain made it necessary to perform a total hip arthroplasty. Anatomo-pathological investigation confirmed both the necrosis and the leukaemic invasion.

Adolescent↗
PubMed1996

Influence of low-dose aprotinin on the inflammatory reaction due to cardiopulmonary bypass in children.

BACKGROUND: The serine protease inhibitor aprotinin inhibits trypsin, kallikrein, and plasmin and enhances the complement hemolytic activity of the first complement component C1. We tested whether low-dose aprotinin influences the inflammatory reaction related to cardiopulmonary bypass. METHODS: In an open, randomized study, 25 children undergoing cardiac operations were investigated prospectively. The treated group comprised 11 patients receiving low-dose aprotinin (20,000 kIU/kg [2.8 mg/kg]), and the control group included 14 patients. Complement activation, cytokine production, and leukocyte stimulation were analyzed before, during, and after cardiopulmonary bypass. RESULTS: In all children, significant C3 conversion and C5a generation, interleukin-6 synthesis, and myeloperoxidase, eosinophil cationic protein, and histamine liberation occurred in relation to cardiopulmonary bypass. This was not influenced by aprotinin treatment. In contrast, neutrophil kinetic studies at the end of cardiopulmonary bypass showed a significantly lower increase in the aprotinin as compared with the control group. CONCLUSIONS: Our results suggest that low-dose aprotinin has little influence on the inflammatory reaction induced by cardiopulmonary bypass. Aprotinin affects neutrophil mobilization but not white blood cell degranulation related to cardiopulmonary bypass, and has no influence on complement activation and interleukin-6 synthesis.

Analysis of Variance↗
PubMed1996

Effect of sodium nitroprusside on complement activation induced by cardiopulmonary bypass: a clinical and experimental study.

Complement activation and leukocyte stimulation were prospectively studied during and after cardiopulmonary bypass in 16 children receiving sodium nitroprusside--a nitrovasodilator releasing nitric oxide--for vasodilation during the cooling and rewarming periods of extracorporeal circulation. Results were compared with those in 29 patients who were not treated with sodium nitroprusside during the operation. Patients treated with sodium nitroprusside had significantly less C3 conversion during cardiopulmonary bypass as measured by the ratio C3d/C3 (p <0.05) and significantly less C5a liberation immediately after cardiopulmonary bypass (p < 0.005) than patients not treated with sodium nitroprusside. C4 was not overtly consumed in our series. Leukocyte count during the rewarming period of cardiopulmonary bypass, but not leukocyte elastase release during cardiopulmonary bypass, was significantly reduced in patients treated with sodium nitroprusside (p <0.05). In vitro experiments were conducted to analyze the effect of sodium nitroprusside on complement hemolytic activity initiated by the classic and the alternate pathways and on zymosan-induced C3 conversion by the activation of the alternate pathway. The in vitro experiments clearly demonstrate inhibition of complement hemolytic activity by sodium nitroprusside in the sera tested. The 50% inhibitory concentration of sodium nitroprusside on the available complement hemolytic activity was less through the alternate pathway than through the classic one (4.2 +/- 0.8 mmol/L and 14.0 +/- 2.88 mmol/L, respectively). The decrease of complement hemolytic activity measured was dose-dependent and was enhanced by the sodium nitroprusside preincubation of the sera tested. This effect was related to the duration of preincubation. Sodium nitroprusside photodegradation (enhancing nitric oxide release) increased the anticomplementary effect of the drug, reducing the 50% inhibitory concentration on complement hemolytic activity to 0.24 to 0.02 mmol/L for the alternate pathway and 2.74 o 0.3 mmol/L for the classic pathway. the zymosan-induced C3 conversion was inhibited by sodium nitroprusside. Nitroglycerin and isosorbide dinitrate (other nitric oxide donors) had in vitro effects on complement hemolytic activity similar to those of nonphotodegraded sodium nitroprusside at similar concentrations (1 mmol/L). Our results suggest that sodium nitroprusside, both in vitro and in vivo, has an inhibiting effect on complement activation initiated by both classic and alternate pathways and that this effect is mediated by nitric oxide release from sodium nitroprusside. This is the first report on the anticomplementary effect of sodium nitroprusside by nitric oxide release.

Cardiopulmonary Bypass↗
PubMed1996

Histamine liberation related to cardiopulmonary bypass in children: possible relation to transient postoperative arrhythmias.

Tumor necrosis factor-alpha production and products of mast cell, basophil, and eosinophil degranulation (prostaglandin D2, histamine, and eosinophil cationic protein) were prospectively studied in 26 children undergoing cardiac operations. The relationship between inflammatory response to cardiopulmonary bypass and transient postoperative arrhythmias was analyzed. Cardiopulmonary bypass was conducted with circulatory arrest and deep hypothermia in 10 patients and with continuous low-flow and moderate hypothermia in 16 patients. Transient postoperative arrhythmias diagnosed on standard or atrial electrocardiograms (or both) were seen in eight of the 26 examined children: accelerated junctional rhythm (n = 3), junctional ectopic tachycardia (n = 3), second-degree atrioventricular block (n = 1), and third-degree atrioventricular block (n = 1). Children with transient postoperative arrhythmias were younger than those without (p < 0.05). Compared with baseline values, there was in all patients a significant release of histamine and eosinophil cationic protein (p < 0.05) related to cardiopulmonary bypass, reaching peak values 4 hours after the operation. In contrast, tumor necrosis factor-alpha production and prostaglandin D2 release were not significant. This suggests that activated basophils but not mast cells are the major sources of histamine liberated during and after cardiopulmonary bypass. Histamine release but not eosinophil cationic protein release correlated with circulatory arrest and deep hypothermia (p < 0.05), suggesting the participation of physicochemical alterations of circulating basophils leading to histamine liberation. Four hours after the operation, patients with transient postoperative arrhythmias had significantly higher blood concentrations of histamine (p < 0.02) and eosinophil cationic protein (p < 0.05) than did those without transient postoperative arrhythmias. On the first postoperative day, four of the eight patients with transient postoperative arrhythmias had persisting elevated histamine levels, whereas in patients without transient postoperative arrhythmias histamine reached baseline values. The multivariate analysis retained histamine release and eosinophil cationic protein variations related to cardiopulmonary bypass for the emerging model to predict transient postoperative arrhythmias. The results of this study show significant histamine release related to cardiopulmonary bypass. Furthermore, they document a possible relationship between circulating histamine and transient postoperative arrhythmias. The latter may therefore be suspected among the consequences of the inflammatory response to cardiopulmonary bypass.

Adolescent↗
PubMed1996

Regulation of glucocorticoid receptor mRNA in nasal mucosa by local administration of fluticasone and budesonide.

The glucocorticoid receptor (GR) is downregulated by glucocorticoids (autoregulation). In contrast, the metallothionein gene (MTIIa) is positively regulated by glucocorticoids, which requires a functional receptor protein. We have investigated the expression of GR and MTIIa mRNA in nasal mucosal biopsy specimens, nasal brush-lavage samples, and peripheral blood lymphocytes from 14 healthy volunteers after local treatment with one of two different glucocorticoids: fluticasone propionate or budesonide. In nasal mucosal biopsy specimens, a significant decrease in GR mRNA occurred with increasing doses of both steroids, whereas a significant and parallel increase in MTIIa mRNA was observed. We found nasal brush-lavage less suitable for studies of GR mRNA and MTIIa mRNA regulation by locally administered glucocorticoids. In mucosal biopsy specimens, but not in peripheral blood lymphocytes, we found a correlation between basal GR mRNA and MTIIa mRNA levels, where low GR mRNA levels were associated with low MTIIa mRNA levels, and vice versa. In conclusion, this study shows that locally administered glucocorticoids significantly affect the expression of specific genes and that there is an interindividual and tissue-specific variation in GR mRNA and MTIIa mRNA expression, which may be used in studies of variations in clinical responses to nasal glucocorticoids.

Administration, Topical↗
PubMed1996

Glucocorticoid resistant syndromes--molecular basis and clinical presentations.

The mechanisms of action of glucocorticoid hormones are mediated via specific intracellular receptor proteins. The glucocorticoid receptor (GR) regulates expression of specific target genes or gene networks by ligand-dependent transcriptional activation, i.e. ligand-dependent activation of the receptor with subsequent dimer formation and DNA binding. There are a number of factors, such as the receptor concentration, receptor associated proteins, receptor alterations and the effects on the gene network including hormonal regulation of transcription, mRNA splicing and translation, that might influence glucocorticoid responsiveness in a normal and healthy population as well as in different diseases. Several categories of glucocorticoid resistance have been described including inherited GR resistance which has been explained in terms of specific mutations and offers an important model for genetic and clinical studies of steroid sensitivity, and relative glucocorticoid resistance, which occurs naturally in the course of cellular differentiation, cell to cell or tissue to tissue, since all cells possess receptors for glucocorticoids but do not show the same response to them. From a clinical point of view, it is also interesting to consider preexisting genetic susceptibility to glucocorticoids, acquired changes in the GR gene structure and organization, including alterations of noncoding sequences, and the importance of mutations, deletions and other changes in the GR gene affecting receptor function. Analysis of mutations within the receptor resulting in relative glucocorticoid resistance, both generalized inherited glucocorticoid resistance (GIGR) and directed mutagenesis, has identified two regions of clustered mutations in the proximity of previously identified affinity labeled residues directly affecting the steroid binding function. Finally, studies of New Words primates and cell lines derived from hematologic malignancies constitute animal and human models for the molecular basis of glucocorticoid resistance where a number of inherited and acquired mutations in the GR gene have been demonstrated.

Animals↗
PubMed1996

Microdialysis for metabolic monitoring in neonates after surgery.

Microdialysis is a new method for continuous metabolic monitoring. We studied the possibility of using microdialysis in neonates treated in a paediatric intensive care unit after surgery. A microdialysis catheter was inserted in the abdominal subcutaneous adipose tissue in 14 neonates for a median of 93 h (range 24-106 h). In four neonates, two microdialysis catheters were used simultaneously. Samples were taken hourly for analysis of glucose, lactate and glycerol. Dialysate and blood concentrations were compared. Serum/whole blood glucose values (n = 68) were in the range 2.1-15.4 mM. The serum glucose levels showed good agreement with the dialysate concentrations of glucose, although these infants were subjected to various forms of stress, drugs and glucose infusions. The whole blood glucose levels were significantly lower than the dialysate levels. The microdialysis concentrations of glucose varied considerably. As almost identical dialysate glucose levels were found when two microdialysis catheters were used simultaneously, the variability probably reflects true changes in blood glucose levels. Our results indicate that microdialysis can be used in neonates.

Anal Canal↗
PubMed1996

Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.

The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.

Adolescent↗
PubMed1995

Evidence for the presence of functional thyrotropin receptor in cardiac muscle.

There is increasing evidence that the membrane-bound thyrotropin receptor (TSHR) may be mediating clinically important direct effects of thyrotropin (TSH) and of TSHR antibodies (TSHRab) in extra-thyroidal tissues. TSHR mRNA has formerly been detected in thyroid, retroorbital muscle and fibroblasts, peripheral lymphocytes and rodent fat. It is well known that thyroid disease may aggravate or induce heart disease, but the pathophysiological role of TSH and TSHRab is not clear. The aim of this study was to investigate if TSHR is present in cardiac muscle. Reverse transcriptase polymerase chain reactions revealed TSHR in human heart and Northern blot on extracted RNA showed a RNA species of 4.4 kb. TSH stimulation of cultured mouse AT-1 cardiomyocytes elevated the levels of intracellular second messenger 3',5'-cyclic AMP. This effect of TSH could be inhibited by TSHR antibodies. In solution hybridization levels of TSHR mRNA in AT-1 cells were 50% of mRNA in crude mouse heart. In conclusion functional TSHR is present in cardiomyocytes.

Analysis of Variance↗
PubMed1995

Metabolic adaptation in IUGR neonates determined with microdialysis--a pilot study.

Subcutaneous microdialysis was used to monitor the immediate metabolic changes with respect to glucose, glycerol and lactate in the extracellular space of adipose tissue among five small-for-gestational-age (SGA) and two appropriate-for-gestational-age (AGA) newborns. There was a good correlation between glucose levels in blood and dialysate (r = 0.97, n = 14). The infants showed rapid rises and falls in dialysate glucose levels that are not seen among older children and adults. The levels of lactate were higher than those reported in blood. Lactate may serve as an alternative source of energy for the neonate. Microdialysis is of potential value in increasing our understanding of metabolic events. It provides a safe on-line means of making continuous measurements in these fragile patients in order to detect periods of hypoglycaemia, at least in infants with a birth weight > 1000 g.

Adipose Tissue↗
PubMed1995

Gestational diabetes mellitus and paradoxical fetal macrosomia--a case report.

Gestational diabetes mellitus (GDM) is associated with an increased rate of fetal macrosomia. We describe the outcome of two pregnancies complicated by GDM occurring 2 years apart in a normal-weight woman. Despite adequate maternal blood glucose control during gestation, both infants were markedly oversized at birth (birth weight and length exceeded normal means by 3 and 2 S.D., respectively). The placental weights were far above normal. At birth, the siblings shared the typical appearance of a diabetes fetopathy. The first one developed transient, the second persistent neonatal hypoglycemia associated with hyperinsulinemia, that needed treatment with diazoxide for 2.5 months. Both infants normalized their growth rates during the following months; their psychomotor development assessed at 2 years and at 9 months of age, respectively, was normal. During the last trimester of the second pregnancy, the plasma concentration of placental lactogen (PL) increased to a very high level (19 micrograms/l). The maternal early insulin response to glucose increased significantly with gestation and was much above that in the non-pregnant state. This rise in insulin response could not compensate for the concomitant decrease in insulin sensitivity as assessed by the minimal model according to Bergman [2]. The pronounced fetal macrosomia described cannot be attributed to GDM only. We speculate that excess activity of lactogenic hormones like PL beside glucose contribute to exaggerated fetal beta-cell function with growth acceleration and neonatal hypoglycemia. This hypothesis is in accordance with in vitro evidence indicating that PL may have an important role in the regulation of the maternal and fetal beta-cell mass and function.

Adult↗
PubMed1995

Anatomo-radiological study of the popliteal artery during knee flexion.

We studied the morphological modifications of the popliteal artery during knee flexion. An anatomical, radiological study consisted of analysis of lateral arteriographs in different degrees in joint flexion followed by dissection to reveal the anatomical structures involved in the morphological adaptation of the popliteal artery to joint movement. In five non-atheromatous volunteers, 15 MRI angiographic sequences were done at the level of the knee in extension and flexion. The arteriographs and angio MRI showed that as joint flexion increased tortuosities appeared in the supra-articular upper popliteal artery while the middle and lower parts of the popliteal artery kept an even curve retracted from the posterior surface of the joint. Dissection seemed to show that this arterial adaptation occurred between two fixed points, one proximal (the adductor canal) and the other distal (the origin of the anterior tibial artery). Angio MRI seems to be a future route for the assessment of the limb vessels. The contrasting behaviour of the different segments of the popliteal artery allows us to understand better the pathophysiology of trauma and malpositions of the popliteal arterial trunk.

Humans↗
PubMed1995

Expression of hsp90 beta messenger ribonucleic acid in patients with familial glucocorticoid resistance--correlation to receptor status.

We have previously shown an increased specific DNA-binding of liganded unactivated glucocorticoid receptor (GR) to the LTR-region of MMTV DNA in a patient with primary cortisol resistance and receptor thermolability indicating a defective interaction of GR with hsp90. In some patients, however, no apparent receptor abnormality was found in spite of a characteristic phenotype. mRNA expression levels of hsp90 beta were analysed in cultured fibroblasts from patients with known receptor defects, such as thermolability, decreased ligand binding affinity and low receptor expression levels, and from patients with a cortisol resistant phenotype but no detected receptor alteration. Fibroblasts from patients with GR defects expressed higher hsp90 beta mRNA levels as compared to patients with no receptor defects or to healthy controls. These data indicate that GR defects are associated with increased hsp90 beta mRNA levels.

Adrenocortical Hyperfunction↗