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Biomedical subjects

P Berchtold

Publications and source records attributed to P Berchtold.

At least 19 recordsLinked to original sources

[High-dose gamma globulin in autoimmune diseases].

The short-term benefit of high-dose intravenous gammaglobulin (IvIgG) in autoimmune diseases is widely accepted in patients with chronic immune thrombocytopenic purpura (ITP). Recent studies reported remission or stabilization of the disease in some patients receiving long-term IvIgG therapy. It has been suggested that this long-term effect may be due to antiidiotypic antibodies in IvIgG down-regulating the immune response in chronic ITP. Because of the high costs and the transient effect in most instances, this treatment should not be used routinely. IvIgG may be considered in severely thrombocytopenic patients with chronic ITP who develop serious bleeding.

Antibodies, Anti-Idiotypic

The effects of the alpha-glucosidase inhibitor BAY g 5421 (Acarbose) on meal-stimulated elevations of circulating glucose, insulin, and triglyceride levels in man.

In blind studies the effects of a new alpha-glucosidase inhibitor (BAY g 5421) were tested in normal weight and overweight male volunteers after oral application of 75, 150, or 300 mg of BAY g 5421 or placebo per os before three standardized main meals of one day. Before and three hours after each meal blood glucose, serum insulin, and serum triglyceride levels were determined. In addition, safety studies were performed. BAY g 5421 induced a statistically significant, in part dose-dependent inhibition of the postprandial increase of blood glucose- and serum insulin levels. The reduction of the postprandial increase of serum triglyceride levels was variable. Routine blood chemistry and hematology tests have revealed no adverse side effects; but the application of the drug was frequently associated with intestinal effects, such as flatulence and diarrhea, which were substrate (carbohydrate) and, in part, dose-dependent.

Administration, Oral

The effects of the alpha-glucosidase inhibitor BAY g 5421 (Acarbose) on postprandial blood glucose, serum insulin, and triglyceride levels: dose-time-response relationships in man.

In a double-blind quadruple cross-over study the effect of a new alpha-glucosidase inhibitor (BAY g 5421) on postprandial blood glucose, serum insulin, and serum triglyceride increases was tested in 24 male healthy volunteers. They received before a standardized breakfast 50, 100, or 200 mg of BAY g 5421 or a placebo per os. The dose-time-response relationships were calculated and the drug tolerance was assessed. There was a statistically significant inhibition of the postprandial increases of the blood glucose, serum insulin, and triglyceride values. Further analysis showed no dose-dependent effect of the drug on the blood glucose values, whereas the serum insulin and triglyceride values were affected in a dose-dependent fashion. The maximal inhibitory effect on the serum insulin levels occurred 69 min after breakfast and on the serum triglyceride levels 104 min after breakfast. One hundred and 200 mg of BAY g 5421 were equally inhibitory-effective on the serum insulin levels, whereas the highest dose used was markedly more effective on serum triglyceride values than lower doses. Based on these results, a dosage of 100--200 mg of BAY g 5421/meal is recommended for clinical trials in metabolic diseases.

Administration, Oral

Effect of physical training on glucose tolerance and on glucose metabolism of skeletal muscle in anaesthetized normal rats.

The effect of physical training on glucose tolerance in vivo and skeletal muscle glucose metabolism in vitro was investigated in normal rats. Treadmill running for 10 days up to 240 min/day led to a decrease of basal and glucose-stimulated plasma insulin levels without major alterations of the IV glucose tolerance (1 g/kg body weight). Swim training of two weeks' duration, i.e. exercise up to 2 X 75 min/day, which did not induce significant changes in body composition, skeletal muscle glycogen levels or citrate synthase activity, resulted in a significant improvement of IV glucose tolerance and substantial reductions of basal and glucose-stimulated plasma insulin levels. Associated with this apparent improvement of insulin sensitivity in vivo, significant increases of the insulin-stimulated glucose uptake (+ 55%) and lactate oxidation + 78%) in vitro were found on perfusion of the isolated hindquarter of swim-trained animals. It is suggested that mild physical training can improve glucose tolerance and insulin sensitivity in normal rats, at least in part, due to an increase of insulin sensitivity of skeletal muscle glucose metabolism.

Anesthesia

Plasma glucagon in diabetes of haemochromatosis: too low or too high?

Glucagon secretion before and during arginine infusions was tested in 11 patients with diabetes associated with haemochromatosis. The results were compared with those obtained in six normal subjects and five patients with haemochromatosis but normal glucose tolerance. The patients with haemochromatosis, regardless of glucose tolerance, exhibited higer level of plasma immunoreactivity for glucagon (antiserum 30-K) suggesting hyperglucagonaemia. However, additional analysis revealed that a considerable amount of this glucagon immunoreactivity was due to cross-reacting material of high molecular weight, the levels of which were significantly higher in patients with idiopathic haemochromatosis. When this was deducted from the total immunoreactivity measured, the resulting values for true glucagon concentrations were similar to those of normal subjects. The data suggest that (1) patients with idiopathic haemochromatosis, whether or not associated with diabetes, exhibit plasma glucagon levels comparable with those of normal subjects; (2) the plasma of the same patients contains significantly more high-molecular-weight substances reacting with glucagon antiserum 30-K than is present in plasma of normal subjects; and (3) 'hyperglucagonaemia' may be erroneously suggested when glucagon is measured with certain antisera reputed to be specific for glucagon.

Arginine

The role of physical exercise and training in the management of diabetes mellitus.

The effects of physical activity on blood glucose homeostasis in diabetes mellitus and the potential benefits of exercise in the treatment of diabetic patients, are reviewed. Mild physical exercise results in a fall of blood glucose levels in controlled diabetic patients; this acute effect of exercise might be used in particular to inhibit the rise of blood glucose seen in insulin-treated diabetics after food intake. In contrast, physical activity will further deteriorate the metabolic situation in decompensated diabetic patients by an increase in blood glucose and a rapid aggravation of ketosis. On the other hand exercise potentiates the blood glucose lowering effect of subcutaneously injected insulin; therefore precautions have to be taken in order to avoid hypoglycemia in insulin-dependent diabetics especially during and after more strenous exercise. In juvenile-type diabetes, physical activity can be used as an efficient therapeutic adjunct only in cooperative, well-instructed patients who are used to check their metabolic situation on a regular basis. Physical training increases the tissues' sensitivity towards (endogenous) insulin. Hence, in addition to the diet, training might represent the most appropriate treatment in maturity onset-type diabetic patients. However, direct evidence for an improvement of glucose tolerance in diabetic patients by physical training is still lacking. In order to formulate detailed, generally applicable recommendations on how to carry out a useful therapeutic program of physical exercise and/or training in diabetic patients, further clinical studies assessing the quantitative effects of physical activity on carbohydrate metabolism are needed.

Animals

Glucagon immunoreactivities and amino acid profile in plasma of duodenopancreatectomized patients.

Glucogon immunoreactivity (IRG) was measured in plasma of duodenopancreatectomized subjects with a nonspecific (K-4023) and a specific (30-K) glucagon antiserum. After an overnight fast, plasma IRG (K-4023) was significantly (P < 0.05) higher in the subjects without pancreas, averaging 782+/-79 (SEM) pgeq/ml, than in the controls (482+/-80 pgeq/ml). IRG (30-K) of 162+/-68 pg/ml did not change during an infusion of arginine (450 mg/kg per 40 min). Insulin deprivation during 3 d in one patient did not restore the IRG response to arginine as reported in depancreatized dogs.Bio-Gel P-30 column chromatography revealed that virtually all IRG (30-K) measured in whole plasma was of different molecular weight than glucagon, and primarily of a mol wt >/= 40,000. Intravenous arginine did not significantly alter the chromatographic pattern of these plasmas. Thus, as postulated by others, duodeno-pancreatectomized humans have virtually no circulating 3,500-dalton glucagon. Hence, the presence of 3,500-dalton glucagon in plasma is not a condition for the diabetic state. It might, nevertheless, when present in normal or excessive amounts, worsen the metabolic state of diabetic patients. Among 14 amino acids measured in plasma of these patients, the concentrations of alanine, serine, ornithine, and arginine were significantly (P < 0.05) elevated to approximately twice that of normal: alanine and serine are both substrates for gluconeogenesis, whereas ornithine and arginine are involved in the formation of urea, the second product of hepatic gluconeogenesis. As the concentrations of branched chain amino acids were not grossly altered, it is hypothesized that this amino acid pattern is a consequence of glucagon deficiency rather than secondary to the diabetic state of these patients.

Adult

[Obesity and cardiovascular risk].

Epidemiological studies on the relationship of obesity, morbidity and mortality revealed the following results: In life insurance studies, excess mortality of obese people was found with more than 30 percent overweight. Mortality was caused by cardiovascular disease and diabetes mellitus. Obesity at issue of the policy in younger age was a greater risk than in the older age group. In prospective studies with long follow-up periods (greater than 16 years) it could be shown that obesity alone was a risk factor for coronary heart disease, the risk being greatest for men and middle aged women. However, the prevalence of accepted risk factors in an obese population is so high that the question whether obesity alone is a risk factor for coronary heart disease is of little interest. The correlations between obesity and risk factors were of minor magnitude; therefore other factors, such as age or HDL-cholesterol, should be considered in the elucidation of the relationship between obesity and coronary heart disease. HDL-cholesterol appears to be a powerful independent protective factor which is diminished in obesity. Despite the fact that studies proving a prolongation of life by treating obesity are not available, the treatment of obesity may be beneficial for the patient by diminishing risk factors.

Adult

Blood amine acid levels in patients with insulin excess (functioning insulinoma) and insulin deficiency (diabetic ketosis).

Blood amino acid concentrations were determined in the postabsorptive state in nine patients with insulin excess (functioning insulinomas), nine juvenile-type diabetics with insulin deficiency (diabetic ketosis due to insulin withdrawal), six juvenile diabetics in moderate metabolic control, and five healthy control subjects. Blood branched-chain amino acid (BCAA) levels were elevated in diabetic ketosis and decreased in patients with insulinomas. Blood concentrations of BCAA were significantly correlated to blood glucose levels, and in diabetics they were also correlated to blood ketone bodies, serum free fatty acids, and glycerol levels. These data indicate an inverse relationship between circulating effective insulin levels and blood BCAA concentrations. It is suggested that blood levels of BCAA might represent an indicator of insulin-dependent alterations of protein metabolism.

Adenoma, Islet Cell

Non-glucoregulatory hormones (T4, T3, rT3, TSH, testosterone) during physical exercise in juvenile type diabetics.

Non-glucoregulatory hormones (T4, T3, rT3, TSH and testosterone) were studied by radioimmunoassay in juvenile-type diabetics in moderate control and in ketosis due to insulin withdrawal and in age matched "normals" during a mild prolonged exercise test. The basal serum hormone levels revealed the following findings: Serum testosterone was markedly lower in diabetics than in normals ( 177 +/- 24 resp. 618 +/- 52 ng/dl). This is in contrast to other studies, but it may reflect decreased testicular function due to an early, clinically not apparent atherosclerotic disease. Serum T3 was significantly lower in diabetics than in normals (110 +/- 16 resp. 145 +/- 19), suggesting an early "low T3-syndrome" in juvenile-type diabetics. However, increased serum rT3 levels were not observed, and serum T4 and TSH were normal. Mild prolonged exercise had no major effects on these nonglucoregulatory hormones. In juvenile-type diabetics the degree of metabolic control had no influence on the response of the mentioned hormones. However, an increased cortisol/testosterone ratio in ketotic diabetics in the basal state with a further increase during exercise was demonstrated, indicating an aggravation of the catabolic state in these patients during exercise.

Adult