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Biomedical subjects

J M Nuoffer

Publications and source records attributed to J M Nuoffer.

13 recordsLinked to original sources

[Hypoglycaemia--diagnosis and therapy in emergencies].

Hypoglycaemia defined as blood sugar below 2.5 mmol/L, is always an important medical emergency. The primary therapy is simple and consists of iv glucose. The occurrence of hypoglycaemia is directly connected to fuel balance, determined by the availability of glucose, free fatty acids and ketone bodies. An intact fuel balance and maintenance of normal blood sugar concentration is dependent upon: (1) an adequate caloric and qualitative dietary intake; (2) afunctionally intact hepatic glucogenolytic and gluconeogenic enzyme system; (3) an adequate supply of endogenous gluconeogenic substrates (lactate, amino acids and glycerol) (4) an adequate energy supply provided by the beta-oxidation of fatty acids to synthesize glucose and ketone bodies and (5) a normal endocrine system (insulin, glucagon, catecholamines and growth hormone) for integrating and modulating these processes. Disturbances in each of these factors may lead to hypoglycaemia. Glucose, like oxygen, is of essential and fundamental importance for the brain metabolism. The major contribution of the brain to the basal metabolic rate (70% in neonates versus 20% in adults) is an important factor contributing to the frequency and severity of a hypoglycaemic syndrome in the paediatric age. If hypoglycaemia is suspected, blood should be obtained prior to treatment for serum glucose determination and an extra tube (5 ml) serum should be obtained and refrigerated for further investigations. The first voided urine has to be tested for ketones using a dipstick and also refrigerated for further investigations. Basic laboratory investigations, anamnestic informations and clinical findings allow rapid tentative diagnosis and determine the specialized investigations out of the refrigerated material. A rapid definitive diagnosis is important for the specific treatment and to avoid recurrent and prolonged hypoglycaemia.

Blood Glucose↗

Regulation of human GH receptor gene transcription by 20 and 22 kDa GH in a human hepatoma cell line.

The human GH gene is 1.7 kilobase pairs (kb) in length and is composed of five exons and four introns. This gene is expressed in the pituitary gland and encodes a 22 kDa protein. In addition to this predominant (75%) form, 5-10% of pituitary GH is present as a 20 kDa protein that has an amino acid (aa) sequence identical to the 22 kDa form except for a 15 aa internal deletion of residues 32-46 as a result of an alternative splicing event. Because it has been reported that non-22-kDa GH isoforms might be partly responsible for short stature and growth retardation in children, the aim of this study was to compare the impact of both 22 kDa and 20 kDa GH on GH receptor gene (GH receptor/GH binding protein (GHR/GHBP)) expression. Various concentrations of 20 kDa and 22 kDa GH (0, 2, 5, 12.5, 25, 50 and 150 ng/ml) were added to human hepatoma (HuH7) cells cultured in serum-free hormonally defined medium for 0, 1 and 2 h. Thereafter GHR/GHBP mRNA expression was measured by quantitative PCR. Addition of either 20 kDa or 22 kDa GH, at low or normal physiological concentrations (0, 2, 5, 12.5, 25 or 50 ng/ml) induced a dose-dependent increase in GHR/GHBP expression. However, a supraphysiological concentration of 20 kDa GH (150 ng/ml) resulted in a significantly lower (P<0.05) downregulation of GHR/GHBP gene transcription compared with the downregulation achieved by this concentration of 22 kDa GH. This difference might be explained by a decreased ability to form a 1 : 1 complex with GHR and/or GHBP, which normally occurs at high concentrations of GH. Nuclear run-on experiments and GHBP determinations confirmed the changes in GHR/GHBP mRNA levels. In conclusion, we report that both 20 kDa and 22 kDa GH, in low and normal physiological concentrations, have the same effect on regulation of GHR/GHBP gene transcription in a human hepatoma cell line. At a supraphysiological concentration of 150 ng/ml, however, 20 kDa GH has a less self-inhibitory effect than the 22 kDa form.

Carcinoma, Hepatocellular↗

Evidence of carotid artery wall hypertrophy in homozygous homocystinuria.

BACKGROUND: We aimed to determine whether intima-media thickness (IMT) was increased in the carotid artery of subjects with homocystinuria to better understand the in vivo contribution of homocysteine to early atherogenesis. METHODS AND RESULTS: We investigated ultrasonographically the right common carotid artery in 14 subjects with homozygous homocystinuria aged 3 to 34 years (mean, 13 years) and in 15 of their heterozygous parents aged 32 to 47 years (mean, 41 years) by comparison with 2 control groups of 15 healthy subjects of the same age. Far-wall IMT and lumen diameter were measured with a computerized program, and the cross-sectional area of the intima-media complex (CSA-IMC) was calculated from IMT and diameter. Comparison with their respective controls, adjusted for body surface area or height, showed that homozygotes had greater IMT (P<0.001) and CSA-IMC (P<0.05) and smaller diameter (P<0.05), whereas heterozygotes had values similar to their controls. Multivariate analysis of the arterial parameters with age, body surface area (or height), and plasma total homocysteine in the homozygous and heterozygous groups combined showed that IMT was related to age (P<0.05) and homocysteine (P<0.01), diameter was related to body surface area (P<0.001) or height (P<0.05), and CSA-IMC was related to age (P<0.05), body surface area (P<0.05) (but not height), and homocysteine (P<0.05). CONCLUSIONS: Homozygous homocystinuria was associated with common carotid wall hypertrophy, whereas heterozygous disease was not. Such hypertrophy may reflect a smooth muscle proliferation induced by hyperhomocysteinemia and represent a promising target for testing vascular effects of therapeutic measures to lower homocysteine.

Adolescent↗

Weekly versus biweekly lipid removal and effect of statins in severe hypercholesterolemia.

Lipid removal using a continuous-flow extracorporeal system is of proven efficacy in severe hypercholesterolemia. Because of the inconveniences and expenses of extracorporeal removal of lipids, the effects of two treatment intervals (weekly versus biweekly) were assessed in two adolescents with circulating cholesterol higher than 20.0 mmol/L. In both patients, circulating levels were largely lower on a weekly lipid removal interval when compared with a biweekly interval. A rapid reaccumulation of cholesterol was noted after lipid removal. Treatment with simvastatin decreased the rapid reappearance of total cholesterol noted during the first 2 days after lipid removal but without any major effect on the subsequent reaccumulation of cholesterol. Aggressive treatment of severe hypercholesterolemia with statins and especially with extracorporeal lipid removal is now possible and of proven efficacy. The minimal practical lipid removal treatment interval should be used.

Adolescent↗

Circulating ionized and total magnesium in end-stage kidney disease.

BACKGROUND: Circulating magnesium exists in the ionized state and in the undissociated form, either bound to albumin, or complexed to various anions. Until recently, only the measurement of total plasma magnesium has been possible. Now circulating ionized magnesium can be assessed as well. METHODS: Total and ionized plasma magnesium were determined in 43 patients on maintenance hemodialysis (dialysate composition: calcium 1.75 mmol/l, magnesium 0.75 mmol/l) before a dialysis session and in a group of 23 healthy subjects. RESULTS: The total (1.16 [1.03-1.31] versus 0.81 [0.78-0.89] mmol/l; median and interquartile range) and the ionized (0.71 [0.66-0.78] versus 0.54 [0.53-0.59] mmol/l) plasma magnesium levels were significantly higher (p < 0.01) and the ionized plasma magnesium fraction lower (0.61 [0.58-0.65] versus 0.67 [0.64-0.70]; p < 0.02) in patients than in controls. CONCLUSION: The determination of circulating ionized magnesium using selective electrodes is an attractive method to evaluate extracellular magnesium in kidney disease.

Adolescent↗

Regulation of human growth hormone receptor gene transcription by human growth hormone binding protein.

The hypothesis that growth hormone binding protein (GHBP) has an effect on its own on the regulation of the GH-receptor/GHBP transcription was tested. Three different forms of human GHBP (recombinant non-glycosylated GHBP, recombinant glycosylated GHBP and GHBP purified and extracted from serum) were added in different concentrations determined by LIFA [0 pmol/l; 50 pmol/l (low level), 200 pmol/l (average level) and 500 pmol/l (high level in circulation)] to a human hepatoma cell line (HuH7 cells) cultured in a serum free hormonally-defined medium. Following the incubation with GHBP for 0, 1 and 2 h, GH-receptor expression was quantitatively assessed by using polymerase chain reaction amplification. Treatment with a GHBP concentration of 50 pmol/l resulted in a significant increase of GH-receptor mRNA molecules given as number of molecules x 10(6)/microg total RNA. In contrast, the concentration of 500 pmol/l presented a significant decrease of GH-receptor mRNA molecules, whereas 200 pmol/l GHBP produced a GH-receptor gene expression which was in between the values of the experiments with 50 and 500 pmol/l of GHBP added. Furthermore, the three different forms of human GHBP used provided similar data and, therefore, did not effect in any variation of GH-receptor expression. In addition, nuclear run-on experiments confirmed the changes in GH-receptor expression; and cycloheximide (10 microg/ml) did not alter the transcription indicating that the up and down regulating effects of GHBP on the GH-receptor/GHBP gene transcription was dependent, at least partly, on pre-existing factors and does not require protein synthesis. In conclusion, we present data showing that GHBP on its own has an effect on GH-receptor gene expression.

Animals↗

Treatment with low-dose diazoxide in two growth-retarded prepubertal girls with glycogen storage disease type Ia resulted in catch-up growth.

Two originally prepubertal girls suffering from glycogen storage disease type Ia and short stature were treated with low-dose diazoxide (3-4.8 mg/kg per day) for 7 and 4 years, respectively. Both showed an impressive catch-up growth following this treatment. This appeared to be due to prolongation of normoglycaemia after meals and reduction of fasting lactic acidosis by diazoxide.

Acidosis, Lactic↗

[Eating behavior, diabetes and weight control in girls with insulin-dependent diabetes mellitus (type 1)].

The object of the study was, first, to investigate whether girls suffering from insulin-dependent diabetes mellitus (IDDM) are more overweight than an age- and puberty-matched control group and, second, to study the impact of diet, calorie intake and pubertal stage on body mass index (BMI), body weight and fat content. We studied 43 girls with IDDM and controls, divided into two age groups: group 1 (n = 21; 10-13 years) and group 2 (n = 22; > 13 years, 13.1-20.7 years). Overweight was assessed by BMI, relative weight and body fat from skinfold thickness. Food consumption data were collected over a one week food and drink protocol. The diabetic girls, particularly those after puberty, were more overweight than the controls. Although the calorie intake was increased compared with their peers, the proportions of energy derived from protein, fat and carbohydrate were as recommended by the American and Swiss Diabetes Association. Most importantly, the recommended proportion of saturated fatty acids (< 10%) was not achieved by either the diabetic patients or the control girls. Insulin dose/unit body weight correlated with BMI and fat content. Therefore, the increased insulin dose may be responsible for the relatively increased energy intake and, in addition, increased intake of saturated fatty acid which has been related to poor metabolic control and obesity. The food intake of the control girls was identical to that reported in adults by the Swiss Government in 1991 in the Third Report on Food Consumption.

Adipose Tissue↗

Chondrodysplasia punctata with a mild clinical course.

We report a 7-year-old patient with chondrodysplasia punctata but without rhizomelia. He was born with typical clinical and radiological symptoms of this disease. He developed slowly with considerable psychomotor retardation but improved later, gaining some speech and psychosocial contacts. Joint contractures and bilateral cataracts are still major problems. De novo plasmalogen synthesis in fibroblasts was greatly reduced and DHAP-AT activity was at the lower limit of controls. Peroxisomal thiolase was present in its precursor form only. Membrane fluidity (measured by TMA-DPH fluorescence anisotropy) was increased in erythrocyte ghosts and in lymphocytes. Plasma phytanic acid concentration was elevated 5-fold. The patient represents a mild clinical course of chondrodysplasia punctata, resembling Conradi-Hünermann syndrome, but biochemically he has the typical peroxisomal dysfunction of rhizomelic chondrodysplasia punctata except for a high residual activity of DHAP-AT.

Acetyl-CoA C-Acetyltransferase↗

Familial neonatal SIDS revealing carnitine-acylcarnitine translocase deficiency.

UNLABELLED: A patient with a severe phenotype of carnitine-acylcarnitine translocase deficiency (CATR)(McKusick 212138) is reported. Prior to birth, a defect in beta-oxidation was suspected because of neonatal death of six siblings. Dietary treatment during neonatal adaptation and the subsequent six months of life and a trial of carnitine supplementation are reported. The rapidity with which long chain fatty acid metabolites can accumulate and induce secondary carnitine deficiency within a few hours after birth in an infant with CATR is noteworthy. CONCLUSION: High rates of glucose suppressed neonatal lipolysis in this infant, but did not seem sufficient to avoid secondary carnitine deficiency as in severe forms of CATR. Therefore simultaneous use of insulin and glucose may be necessary to control neonatal lipolysis. Carnitine supplementation and the possible adverse effects of MCT systematically administrated, should be further assessed in patients with CATR.

Carnitine↗