Biomedical subjects
Publications and source records attributed to G Schlierf.
Neuromuscular syndromes and respiratory insufficiency may be caused by hypophosphataemia. This complication may occur particularly in patients with malnutrition who receive parenteral glucose, as two examples show.
Total starvation is effective for acute weight reduction in obesity. However, in 200 patients, most of whom also had internal diseases, 8% exhibited sometimes severe complications, i.e. reversible cerebral ischemia in 3 hypertensive patients when the blood pressure was lowered to the normal range by natriuresis of fasting; breakdown of water and electrolyte homeostasis with circulatory collapse, vomiting and vertigo; acute crises of paroxysmal nocturnal hemoglobinuria and porphyria respectively and increase of transaminases up to 200 mu/ml, or cardiac arrhythmias. Relative (?) contraindications for total fasting appear to be clinical sings of arteriosclerosis such as vascular bruits, angina pectoris and intermittent claudication. In case of doubt, the method should only be used in hospital.
The therapy of hyperlipidaemias is based on the realisation of few principles of nutrition. Reduction of the weight and energy-controlled permanent nutrition, respectively, has in a distinctly marked degree influence on the majority of the hypertriglyceridaemias. Also mixed hyperlipidaemias as well as hypercholesterolaemias if associated with overweight, show a good reactivity to calorie-restricted forms of diet. Increased bodily motion, also negativation of the energy balance by influencing the consumption of calories is also an excellent measure for the quick decrease of the triglyceride levels. Specific mechanisms increasing the triglyceride concentration can be excluded by a restriction of the sugar and alcohol consumption. Primary hyercholesterolaemias in normal body-weight can be influenced by a decrease and/or changing of the fat consumption in the sense wanted. Since there have been possible comparable decreases of the cholesterol level by forms of diet of different fat content, when the relation of repeatedly unsaturated to saturated fatty acids furthermore exists, here is the possibility for the adaptation to individual habits of nutrition. However, own investigations allow the conclusion that the total addition of fat should lie below 35 kcal %. Whether the coronary risk can be diminished by a nutrition decreasing lipids, was investigated in a number of studies during the last 20 years. Summarzing, a primary prevention by changing the nutrition seems to be possible; chances of success for the secondary prevention - the prophylaxis of the reinfarction - are less well confirmed.
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When testing the effect of a new clofibrate analogue (BM 15.075) on oral anticoagulation and blood clotting in 15 patients for over four weeks it was demonstrated that, depending on the dose of the drug, there was an increase in anticoagulation. The dose of phenprocoumon had to be reduced by 20.6 or 28.7%, respectively, when BM 15.075 was given at a dose of 450 or 600 mg. There was an inhibition of collagen-induced platelet-aggregation. In parallel there was an increase in bleeding time. Fibrinogen concentration was slightly but statistically not significantly decreased. Euglobulin lysis was shortened, especially if previously abnormally long. There was no direct influence on other plasmatic clotting factors.
Acute and chronic effects of three isocaloric diets on plasma lipids and plasma lipoproteins were studied in 10 patients with primary endogenous hypertriglyceridemia (type IV-hyperlipoproteinemia). The diets used contained 20% protein, 50, 37 and 1% fat and 30, 43 and 79% carbohydrates respectively. Cholesterol levels were similar with all diets. Fasting values of plasma triglycerides were lower with the fat-containing diets compared to the high-carbohydrate diet. Diurnal patterns, however, were significantly higher with the former diets in 8 of the 10 patients. Postprandial lipoprotein patterns on fat-containing diets are characterized by chylomicronemia and marked changes of concentration and composition of other lipoprotein classes. If, analogous to diabetic therapy, control of hypertriglyceridemia is meant to imply low all-day levels rather than low fasting levels, a rather low-fat, high-carbohydrate diet seems to be superior in most patients with endogenous hypertriglyceridemia to diets containing more than 35 calorie per cent of fat.
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The effects of different dietary carbohydrates and different dietary fats as well as of differently spaced dietary constituents on 24-h plasma free fatty acids and triglycerides were determined in healthy young males. If, in an isocaloric diet containing 15-20% protein, 37% fat and 43--48% carbohydrates, sucrose is compared with glucose, 24-h plasma triglycerides are significantly higher with the former carbohydrate. When palm oil (mainly 16 : 0 fatty acids) is compared with olive oil (mainly 18 : 1 fatty acids), 24-h triglycerides are significantly higher with the latter. If the carbohydrate component of a mixed meal is removed, alimentary lipemia is considerably greater. Our findings supplement long term studies regarding the effect of different dietary fats and carbohydrates on plasma lipids and allow calculation of "upper normal limits" for 24-h plasma triglycerides and free fatty acid patterns on isocaloric diets of "prudent" composition.
The effect of adrenaline on adenylate cyclase activity in membranes prepared from human abdominal and gluteal adipose tissue was examined. Basal enzyme activity averaged 1.0 mmol cAMP/mg protein/15 min in abdominal tissue and 0.68 nmol cAMP/mg protein/15 min in ghosts from the buttock. Maximally effective concentrations of sodium fluoride (20 mmol/1) induced an eight-fold increase in both membrane preparations. The maximal response to adrenaline (1.0 mmol/1) averaged 170% in ghosts of abdominal tissue compared with 60% in gluteal membranes. The concentrations of adrenaline required to produce half-maximal stimulation were similar in membrane preparations of both regions (about 5 X 10(-5) mol/1).
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We compared direct determination of beta-lipoprotein cholesterol after selective extraction of very-low-density and high-density lipoproteins from serum with poly(ethyleneimine) and a cation-exchange resin with the classical quantitation after lipoprotein fractionation with the ultracentrifuge. At beta-lipoprotein cholesterol concentrations between 1.50 and 5.00 g/liter the correlation is linear (r = 0.95). The precision for the extraction procedure is as good (CV 2.4-2.8%) as for the quantitation by ultracentrifugation (CV 3.2-6.0%). From solutions of isolated lipoproteins, very-low-density lipoproteins are 93% extracted and high-density lipoproteins 60%, but low-density-lipoproteins only 5%. The molecular mechanism of the extraction is supposed to be due to both hydrophobic interaction of long-chain fatty acid residues and ionic interaction of phospholipids located at the surface of very low-density and high-density lipoproteins and the lipophilic polycation.
A two-step procedure for the microdetermination of cholesterol in serum lipoproteins is compared with cholesterol quantitation after density gradient ultracentrifugation. Serum lipoproteins from 10 mul of serum are separated by electrophoresis on agarose and visualized by precipitation with dextran sulfate--CaCl2. The lipoprotein bands are cut off from the plates, the agarose slices are hydrolyzed by gas-liquid chromatography. The comparison between the two procedures reveals satisfactory correlations for beta-and pre-beta-lipoproteins and total serum. There is excellent recovery of cholesterol in fractionated lipoproteins.
The previously described procedure of direct determination of LDL-cholesterol after selective extraction of VLDL and HDL with polycations and a polycation-exchange resin has been improved by using dodecoylated poly(ethyleneimine) instead of poly(ethyleneimine). The acyl derivative has a higher affinity for lipoproteins. Disc-electrophoretic patterns of lipoproteins separated by this procedure correspond to patterns of apolipoproteins in VLDL and HDL, a finding that corroborates the conclusion that the mechanism of the selective binding of certain lipoproteins to lipophilic water-soluble polycations is based on hydrophobic interaction between the polymer and lipids located at the surface of lipoprotein particles. The procedure offers a simple possibility for direct LDL-cholesterol and LDL-triglyceride determination and for the isolation of VLDL and HDL. The mechanism of the reaction has a biochemical correlate in the action of phospholipase A2 on phospholipids.
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The efficacy of a fat-modified, low-cholesterol diet was studied in 38 children and adolescents with familial hypercholesterolemia on an out-patient basis, and the results compared with those achieved with dietary treatment in hospital. On an out-patient basis, a 10% reduction of plasma cholesterol levels was achieved and maintained. However, no patient showed normalization of plasma cholesterol levels. During hospitalisation, the mean plasma cholesterol levels fell by 24%, beta-cholesterol levels by 27%. This resulted in normal plasma lipids in almost half of the patients. Our results demonstrate the efficacy of intensive dietary management in children and adolescents with familial hypercholesterolemia. Long-term results on an out-patient basis could probably be improved by early nutrition education and an improved supply of suitable dietary foods.
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The effect of beta-sitosterol on the lipid and lipoprotein level was evaluated in a randomised double-blind cross-over trial in 24 patients with primary familial type II hyperlipoproteinaemia over a period of 16 weeks. All patients completed the trial, however 10 of them had to be excluded from the evaluation due to fluctuations of their body weight or unreliable drug intake. Sitosterol lowered the total cholesterol level by 12.5% (P less than 0.01) from 9.96 mmol/l (3.69 g/l) to 8.37 mmol/l (3.23 g/l). The LDL-cholesterol level was lowered by 19.5% (P less than 0.05). The sitosterol concentration in plasma was consistently lower than 0.3% of total cholesterol. No side effects or tachyphylaxis was observed in the course of the trial. A return to normal of an increased serum cholesterol level by a combination of a lipid lowering diet and sitosterol monotherapy was only achieved in one patient.
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