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Biomedical subjects

H H Ditschuneit

Publications and source records attributed to H H Ditschuneit.

At least 37 records · Page 2Linked to original sources

Blood rheology after LDL apheresis using dextran sulfate cellulose absorption--a case report.

The authors describe a thirty-eight-year-old woman with familial hypercholesterolemia treated by dextran sulfate cellulose adsorption apheresis. This technique and the selective extracorporeal LDL cholesterol elimination by immunoabsorption or heparin-induced precipitation not only dramatically decrease blood lipids but also result in a marked improvement in the rheologic profile. It is suggested that the amelioration of blood rheology by LDL apheresis may represent the cause for the early clinical improvement felt by most patients with severe coronary heart disease and hypercholesterolemia.

Adsorption↗

Lovastatin alters blood rheology in primary hyperlipoproteinemia: dependence on lipoprotein(a)?

As part of a randomized, single-blind, comparative study evaluating the efficacy of lovastatin and bezafibrate retard in the treatment of primary hypercholesterolemia, hemorheologic parameters (whole blood viscosity, hematocrit, plasma viscosity, red blood cell aggregation and deformability, and fibrinogen) were studied in 35 patients. Whole blood viscosity and plasma viscosity improved significantly after 3 months of treatment with lovastatin, whereas other hemorheologic variables remained unchanged. Stratifying 24 patients by their lipoprotein Lp(a) levels showed that in those with low Lp(a) (less than or equal to 25 mg/dL) high-density lipoprotein cholesterol increased and red blood cell aggregation as well as deformability decreased considerably, whereas in the group with high Lp(a) levels (greater than 25 mg/dL), the opposite behavior was observed. Treatment of primary hypercholesterolemia with lovastatin may not only reduce the risk for atherosclerotic complications by its pronounced decrease of low-density lipoprotein cholesterol, but also may favorably alter blood rheology, and may decrease insudation of plasmatic components into the arterial wall and improve tissue perfusion, in particular on the microcirculatory level. The possible relevance of Lp(a) levels for the hemorheologic effects of lovastatin remains to be elucidated.

Bezafibrate↗

Postprandial lipoprotein metabolism in obese patients with moderate hypertriglyceridaemia: effects of gemfibrozil.

After an oral fat load of 1 g/kg body weight in 10 obese females with hyperlipoproteinaemia type IV, serum triglycerides concentrations were maximal at 4 h with a slight decline at 6 h, whereas serum cholesterol concentrations rose slightly at 4 h and 6 h. After 6 h, concentrations of triglycerides and cholesterol were significantly increased in chylomicrons and very low-density lipoprotein (VLDL), whereas cholesterol concentrations were decreased in high-density lipoprotein 2 (HDL2) plus HDL3. After oral treatment with 450 mg gemfibrozil twice daily for 28 days, triglyceride concentrations were reduced in serum, chylomicrons, VLDL and low-density lipoprotein, and total cholesterol concentrations were reduced in serum, chylomicrons and VLDL, and increased in HDL2 plus HDL3. At 6 h after a fat load following 28 days' gemfibrozil treatment, triglyceride and cholesterol concentrations were reduced in serum, chylomicrons and VLDL when compared with pretreatment results. It is concluded that gemfibrozil is effective in lowering triglycerides and cholesterol, particularly in triglyceride-rich particles, and raising the cholesterol content of HDL2 plus HDL3. After an oral fat load gemfibrozil inhibits the increase in serum cholesterol and partly prevents postprandial hypertriglyceridaemia.

Adult↗

[LDL cholesterol apheresis by adsorption to dextran sulfate].

Extracorporeal LDL cholesterol elimination may be the sole successful treatment in familial hypercholesterolemia. By treatment of 41 plasma both total cholesterol and LDL cholesterol were lowered by 69 +/- 1% and 78 +/- 1%, respectively. HDL cholesterol was decreased by 24 +/- 3%. This could be explained both by hemodilution (hematocrit was decreased by 9.3 +/- 2.8%) and unspecific adsorption of various plasma proteins (-15.3 +/- 3.7 g/l, i.e. -22 +/- 4%). Protein electrophoresis showed different affinities of the protein fractions. These data suggest that LDL apheresis by dextran sulfate is an effective method for the elimination of LDL cholesterol. However, other proteins besides apolipoprotein B are adsorbed to dextran sulfate.

Adsorption↗

[Pravastatin, cholestyramine and gemfibrozil in long-term therapy of primary hypercholesterolemia. An open randomized comparative study].

In this open controlled clinical trial the lipid-lowering effect, the tolerance and clinical safety of the new hydrophilic HMG-CoA reductase inhibitor pravastatin and cholestyramine were compared in the treatment of 45 patients with primary hypercholesterolaemia over a period of 16 weeks. Following a dietary lead-in of six weeks, patients were randomized at a ratio of 3:2 to receive either pravastatin 10 mg b.i.d. or cholestyramine 8 g b.i.d. The dose of pravastatin was increased to 40 mg per day after eight weeks of treatment and after 16 weeks cholestyramine 8 g b.i.d. was added. Two thirds of the patients in the cholestyramine group were switched to gemfibrocil 900 mg. At the end of the 48 week treatment period the mean reduction rates of total cholesterol, LDL-cholesterol and triglycerides for the pravastatin combination compared to cholestyramine (in brackets values for gemfibrocil) were -30, -35 and -17% versus -17 (-19), -25 (-22) and +27 (-24)%. Pravastatin lead to an increase of the HDL concentration of approximately 8%, gemfibrocil to approximately 13%, whilst cholestyramine alone did not change this lipid fraction. The reduction of total cholesterol and LDL-cholesterol was associated with a decrease in the apolipoprotein B concentration. However, the apolipoprotein AI and AII levels remained unchanged. Due to the absence of clinically relevant side effects and laboratory abnormalities coupled with the excellent compliance in this study, pravastatin proved to be a convincing therapeutic alternative to cholestyramine and gemfibrocil. The combination therapy of pravastatin and cholestyramine offers a potentially highly efficacious and safe therapeutic regimen for the future.

Adult↗

Inhibition of HMG-CoA reductase in mononuclear cells during gemfibrozil treatment.

The effect of gemfibrozil treatment (900 mg/day) on serum levels of total cholesterol, HDL-cholesterol, triglyceride, apoproteins A-I, A-II and B as well as HMG-CoA reductase in mononuclear cells was studied in patients with hyperlipoproteinemia types IIa and IIb. After 4 weeks of treatment gemfibrozil reduced total serum cholesterol (IIa: -17%, IIb: -26%), triglyceride (IIa: -39%, IIb: -47%) and apoprotein B (IIa: -22%, IIb: -15%). HDL cholesterol was increased by 20-22% and apoproteins A-I and A-II by 4-11%. Concomitantly, HMG-CoA reductase activity in freshly isolated mononuclear cells was suppressed by 78% in type IIa and 51% in type IIb patients. Continuation of treatment for up to 16 weeks prompted a further decline to 8 and 5% of the initial values, respectively. However, gemfibrozil failed to affect HMG-CoA reductase directly in homogenized or cultured mononuclear cells and did not further promote the suppressive action of LDL when added to the culture medium. Similarly, preincubation with the drug did not significantly modulate the binding or degradation of LDL in the cultured cells. However, LDL from patients with hyperlipoproteinemia types IIa and IIb exhibited enhanced binding and more potent HMG-CoA reductase suppression when isolated after compared to before gemfibrozil treatment. It is suggested that the HMG-CoA reductase inhibition observed in mononuclear cells during gemfibrozil treatment is due to changes in LDL structure affecting LDL receptor binding rather than direct effects of the drug on cellular cholesterol metabolism.

Adult↗

Comparison of different HMG-CoA reductase inhibitors.

The HMG-CoA reductase inhibitors have been shown to cause marked reduction of cholesterol and offer a new and effective approach to treatment of hyperlipoproteinemia. Three agents, pravastatin (P), lovastatin (L) and simvastatin (S), have been studied with reference to long-term lipid-lowering effect, tolerance and clinical safety. Following a dietary lead-in period of at least 6 weeks in every case, patients with primary hypercholesterolemia were enrolled from participants of short-term controlled studies which after completion were extended as open studies. Treatment was administered over 6 months with 20 mg S (84 patients), L (42 patients) or P (23 patients) twice daily. Total cholesterol was decreased with S by 30.2% of basal, with L by 25.5%, and with P by 28.2%. The decrease in apolipoprotein B was 28.4%, of basal, with S 16.4% and in P 19.2%. Triglycerides were lowered by 19.6% of basal with S by 17.4%, with L, and by 6.4% with HDL-cholesterol increased in the S group by 23% of basal, by 9.7% in the L group, and by 8.0% in the P group. No serious clinical or laboratory abnormalities were observed. In the S group headache (3.6% of patients), abdominal discomfort (2.4%), sleeping disturbances (3.6%), and muscle pain (2.4%) were reported. In the L group headache (7.1%), abdominal discomfort (4.8%), sleep disorders (4.8%), and muscle pain (4.8%) were observed. In the P group one patient complained of abdominal discomfort (8.7%) and one of sleep disorders (8.7%). Increases in CPK were observed in the S group (4.8% of patients) and in the L group (11.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗

Fat distribution, endocrine and metabolic profile in obese women with and without hirsutism.

The relationship between adipose tissue distribution, androgen levels, and metabolic complications of obesity was studied in 20 hirsute and 20 nonhirsute obese premenopausal women. The group of hirsute women showed preferentially an upper body type of obesity as assessed by the waist-to-hip ratio (0.902 + 0.017 v 0.778 +/- 0.015, P less than .01). They had higher serum concentrations of total testosterone (100.4 + 11.7 v 48.8 +/- 4.5 ng/dL, P less than .01) and lower levels of serum sex-hormone-binding globulin (28.1 +/- 3.6 v 44.0 + 4.2 nmol/L, P less than .05) exhibiting an increased androgenic activity as compared to the nonhirsute women. Serum glucose and insulin levels after an oral glucose load were significantly higher in the hirsute women. In addition, the group of hirsute females has significantly higher fasting concentrations of total cholesterol (5.82 +/- 0.28 v 4.75 +/- 0.14 mmol/L, P less than .05) and triglycerides (2.51 +/- 0.38 v 1.14 +/- 0.10 mmol/L, P less than .01). The hirsute group also showed higher systolic (166.7 +/- 5.1 v 142.1 +/- 4.5 mm Hg, P less than .01) and diastolic (100.9 +/- 3.6 v 85.2 +/- 2.5 mm Hg, P less than .01) blood pressure values than the nonhirsute women. Analysis of correlation revealed that an increasing waist-to-hip ratio was accompanied by increasing testosterone levels (r = .39, P less than .05) and by decreasing sex-hormone-binding globulin levels (r = .37, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Endogenous opiates do not influence glucose and lipid metabolism in rat adipocytes.

The effects of the opiates beta-endorphin, dynorphin, met-enkephalin, leu-enkephalin, morphine and of the opiate-antagonist naloxone on glucose metabolism and lipolysis were studied in isolated rat adipocytes. None of the tested substances was found to alter 125I-Insulin binding. The opiates did not influence 2-deoxy-glucose uptake or glucose incorporation into lipids. They also did not exhibit a lipolytic activity. We conclude that the disturbances of glucose homeostasis induced by endogenous opiates are not mediated by an effect on peripheral glucose metabolism.

Adipose Tissue↗

Seasonal variations of glucose and triiodothyronine concentrations in serum of carp (Cyprinus carpio L).

Thyroid hormone and glucose serum concentrations (SC) of carps (Cyprinus carpio L) have been monitored at weekly intervals throughout the year. T4 and rT3 concentrations were always below the limit of detection of the assays applied. T3 and glucose mean SC showed seasonal variations. Highest T3 SC were reached in summer with a peak value in August and lowest values in winter with a maximum in December. Glucose SC have been found to be highest in winter and lowest in summer. Statistical analysis showed a negative correlation between T3 and serum glucose SC (r = -0.77, P less than 0.001). The seasonal dependency of T3 and glucose SC suggest that either temperature, food intake or day-light or both might play a role in the regulation of glucose metabolism as well as of T3 production or metabolism.

Animals↗

[Distribution of adipose tissue and complications of obesity in overweight women with and without hirsutism].

A correlation between the serum androgen levels and the distribution pattern of adipose tissue as well as occurrence of complications of obesity were investigated in 24 obese women with and without hirsutism. The hirsute women (n = 12) displayed higher androgen levels than the women without hirsutism (n = 12) of the same age and weight and possessed a more abdominally pronounced distribution of adipose tissue measured as the quotient of waist and hip circumference (0.87 +/- 0.08 as compared to 0.76 +/- 0.06; P less than 0.05). In addition, the overweight women with hirsutism had higher fasting triglyceride levels as well as higher values of systolic and diastolic blood pressure. Overall, a positive correlation was found between testosterone and the ratio of waist and hip circumference (r = 0.40; P less than 0.05) and the values of diastolic blood pressure (r = 0.51; P less than 0.01). Moreover, the ratio of waist and hip circumference correlated with the systolic blood pressure values (r = 0.61; P less than 0.001), the fasting triglyceride levels (r = 0.42; P less than 0.05) as well as the basal insulin concentration (r = 0.48; P less than 0.05). These results are an indication that raised androgens predispose to accumulation of fat in the abdominal region. In turn, an android distribution of adipose tissue is associated with more frequent metabolic disorders and vascular hypertension.

Adipose Tissue↗

Fenofibrate treatment inhibits HMG-CoA reductase activity in mononuclear cells from hyperlipoproteinemic patients.

The effect of fenofibrate treatment on serum cholesterol levels was studied in relation to the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in mononuclear cells from patients with hyperlipoproteinemia type IIa and IIb. When patients who had received fenofibrate (300 mg/day) for at least 8 weeks were given placebo during a subsequent 2-months period, both serum cholesterol concentration and mononuclear cell HMGR increased significantly in both types IIa and IIb. After reinstitution of fenofibrate treatment both parameters gradually declined and returned close to the initial level after another 28 weeks. It is concluded that a part of the lipid-lowering action of fenofibrate may be due to an inhibition of cholesterol synthesis.

Adult↗

Effect of low-dose somatostatin infusion on pancreatic and gastric endocrine function in lean and obese nondiabetic human subjects.

The present study was designed to compare, in lean and obese nondiabetic subjects, basal and postprandial levels of peripheral venous plasma insulin, glucagon, gastrin, pancreatic polypeptide (PP), glucose, triglycerides, and somatostatin-like immunoreactivity (SLI) during the infusion of synthetic somatostatin-14 or saline. Thirty-five minutes before the ingestion of the test meal, an infusion of synthetic somatostatin-14 was started at a rate of 0.5 ng/kg X min and was increased to 1.0 ng/kg X min 30 min after consumption of the meal and lasted for another 90 min. During the infusion of saline, basal peripheral vein levels of insulin, gastrin, and triglycerides were elevated in obese subjects, whereas basal plasma SLI levels were significantly lower compared with the lean controls. Basal glucagon and PP levels were similar in both groups. After the ingestion of the meal, augmented concentrations of insulin and gastrin were observed in the obese subjects, whereas postprandial SLI and PP levels were reduced. Chromatography of fasting plasma revealed all measurable SLI to be confined to the void volume fractions of a Bio-Gel P-10 column. The rise in SLI after the meal was due to an increase of SLI co-eluting with somatostatin-28 and somatostatin-14. During the infusion of somatostatin, only basal insulin levels were significantly lower in the obese subjects, whereas no change of any basal hormone level was observed in the lean group. During the infusion of somatostatin, SLI levels were elevated by 20-30 pg/ml in both groups compared with the saline controls. During the infusion rate of 0.5 ng/kg X min, only postprandial PP levels were reduced significantly in the obese group, while all the other parameters were unaffected in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Nitrogen balance studies during modified fasting.

Protein or nitrogen depletion may be harmful and deleterious as reports of deaths in obese patients fed by liquid protein diets have shown. The aim of our studies was to determine the protein losses (by urinary nitrogen losses) during treatment of obesity with modified fasting over four weeks under inpatient conditions. Sixty-one patients were treated in our metabolic ward with modified fasting randomized into four groups. The daily diet consisted of 33-50 g protein/day, 1-10 g fat/day and 25-45 g carbohydrates/day thus providing 240 to 450 kcal/day or 1.0 to 1.9 MJ. The mean weight losses ranged between 11.0 +/- 0.7 kg and 13.9 +/- 0.9 kg in 28 days. The acceptability and compliance of the four applied diets were excellent and no severe side effects could be observed. The nitrogen balances could be equilibrated from the third week on. The composition of weight lost during modified fasting was as follows. The percentage of body protein ranged between 3% and 16% and the percentage of adipose tissue between 63% and 79% of the total weight loss. Therefore modified fasting represents a very effective and safe therapy of massive obesity.

Adipose Tissue↗

Binding and biological actions of insulin-like growth factors on human arterial smooth muscle cells.

Insulin-like growth factors (IGF) were isolated from human serum and compared with some biological actions of IGF supplied by Dr. J. Hapf, Zürich. Both factors were potent mitogens. They stimulated DNA-, RNA- and protein synthesis in cultivated human arterial smooth muscle cells. Furthermore, they enhanced the aminoacid transport. Our protein fraction (IGF Ulm) had a more potent biological activity than IGF (Zürich). Specific binding receptors for IGF (Zürich) on human arterial smooth muscle cells could be demonstrated. Specific binding of 125I-IGF (Zürich) was 10%. Half-maximal displacement was achieved by 250 ng/ml of unlabeled IGF (Zürich), by 1.2 micrograms/ml of IGF (Ulm), by 6.3 micrograms/ml of pro-insulin and by 17.8 micrograms/ml of insulin. In separate studies we could demonstrate that sera of normal adults, diabetic, acromegalic and hypophysectomized patients showed different growth-promoting activity in human arterial smooth muscle cells.

Acromegaly↗

[Gastric acid and parotid secretion in obesity [greater than 55%] (author's transl)].

In order to investigate exocrine secretory activity in obesity we studied gastric acid and parotid secretion in 22 massively obese patients (greater than 55% overweight); 15 normal persons were taken as controls. Basal and stimulated secretory values were determined. Basal acid output (BAO) in the obese (4,10 +/- 3,8 mval/h) was higher compared to normal (1,98 +/- 1,59 mval/h); the amylase activity in parotid saliva was reduced in the obese means = 195 U/ml (93,8-406) compared to normal means = 307 U/ml (145-652). These differences were not statistically significant. Maximal acid output (MAO) in the obese was within the normal range 17,6 +/- 8,98 mval/h (norm 16-25) despite it was expected, in a weight related manner, to be in a strongly hypersecretory range.

Adolescent↗

[Nitrogen balance during modified fasting (author's transl)].

Protein-substituted or protein-saving modified fasting (PSMF) is intended to prevent high protein loss during total fasting by use of low-dose substitution. 27 obese in-patients were treated over a period of four weeks with modified fasting. The daily amount of protein substituted was 33 g on an egg-white base (Modifast). As in total fasting the nitrogen balance of the first and second week was negative, balanced in the third week and positive in the fourth. The total balance over 4 weeks was negative with a nitrogen loss of 70.7 g N, equivalent to a protein loss of 442 g (lean body mass). Nitrogen and protein loss in PSMF over 4 weeks was only a third of the loss in total fasting (-183.2 g N equivalent to 1145 g protein). Protein-substituted modified fasting may be used for more than 4 weeks as nitrogen balance is stabilised as from the third week, and remained so until the end of the observation period of 8 weeks.

Adolescent↗