Effects of a bezafibrate sustained release formulation on plasma lipoproteins in patients with hypercholesterolemia. Importance of timing of tablet intake for efficacy

The therapeutic effect of a single sustained release tablet of bezafibrate (Cedur retard, 400 mg) in primary hypercholesterolemia type IIa and type IIb was investigated in a placebo-controlled randomised study comparing the efficacy of morning vs. evening intake. The decrease in total cholesterol with the morning intake was 18.5% vs. 16.5% for the evening intake (n.s.). HDL-cholesterol increased more in patients taking bezafibrate retard at morning (29.6% vs. 22.4%, p less than 0.05). Bezafibrate was well tolerated. Animal experiments and precursor studies of cholesterol synthesis in man indicate peak activity of HMG-CoA reductase between 1 a.m. and 3 a.m. The data suggest that with normal eating habits during day time other modes of action of bezafibrate besides HMG-CoA reductase inhibition such as reduction of VLDL-synthesis in the liver and an increased fractional catabolic rate, could contribute to the therapeutic effect.     

Effect of weight reduction on carbohydrate and fatty-acid metabolism in obese, maturity-onset diabetic patients]

In 35 adipose maturity-onset-diabetics (27 women, 8 men, average age 48 years) we examined the influence of a 4--5-week slimming cure on the carbohydrate and fat metabolism. A significant decrease showed the index of ideal weight, volume of adipozytes, fasting free fatty acids concentration, triglyceride content of the liver as well as systolic blood pressure. The decrease of the triglycerides, of cholesterol and of the uric acid level in the serum could not be ascertained statistically. The reduction of weight did not cause an essential change of the basal and stimulated insulin concentrations, whereas the glucose tolerance clearly improved. After an observation period of 36.5 months behaviour of weight and form of therapy are analysed.     

Elimination of lipofundin S during the intravenous fat tolerance test in patients with low, medium, and high fasting triglyceride concentrations

The intravenous fat tolerance test with Lipofundin S (0.5 ml of 20% emulsion/kg body weight) was performed in 22 male nondiabetic patients. According to their fasting triglycerides (TG), the patients were arranged into three groups: low (less than 2.8 mmol/liter), medium (2.8-5.7 mmol/liter), and high (greater than 5.7 mmol/liter) concentrations. Fractional elimination rates of injected Lipofundin S decreased from 11.08 in low TG to 4.57%/min in high TG; they were positively correlated with fasting levels of high-density lipoprotein cholesterol but negatively with those of TG. The same pattern of correlations was observed with fractional catabolic rates of endogenous TG as measured after injection of tritium-labeled glycerol. The intravenous Lipofundin S load effected transient TG and free fatty acid elevations which were delayed in high TG. The elimination mechanisms of injected Lipofundin S and of endogenous TG are compared.     

Instrumented measurements of laxity in patients who have a Gore-Tex anterior cruciate-ligament substitute

Twenty patients who had substitution of the anterior cruciate ligament with a Gore-Tex synthetic ligament were evaluated preoperatively and postoperatively with the University of California at Los Angeles instrumented clinical-testing apparatus, which records anterior-posterior force versus displacement-response curves of the tibia with respect to the femur at 20 degrees of flexion of the knee. The mean age of the patients was thirty-three years (range, nineteen to fifty-four years). The duration of follow-up ranged from twenty-four to forty-four months (mean, thirty-one months). The mean preoperative difference in anterior laxity between the injured knee and the normal knee (4.5 millimeters with neutral rotation of the foot) was unchanged two years after the operation; at that time, all patients had an anterior laxity of the injured knee of more than eight millimeters, and 90 per cent had a difference in anterior laxity of more than two millimeters between sides. The mean values for anterior stiffness at fifty and 100 newtons of anterior force were unchanged after the operation, remaining at 40 to 50 per cent of normal levels. At 200 newtons, or 20.4 kilograms (forty-five pounds) of anterior force, the mean stiffness of the involved knee was 11 to 17 per cent greater than that of the normal knee. Clinically, there were improvements in both subjective and objective knee-rating scores. All but four patients had a reduction of at least one grade in the pivot-shift score; in thirteen, the pivot-shift sign was eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Untersuchungen an 1,3-Thiazinen, 38. Mitt.: Iminiumkohlensäurederivat-Salze, 2. Mitt.: Synthese N-substituierter 2-Chlor-5,6-dihydro-4H-1,3-thiazinium-salze und deren Reaktionen mit primären Aminoverbindungen

Synthesis of N-Substituted 2-Chloro-5,6-dihydro-4H-1,3-thiazinium Salts and Their Reactions with Primary Amino Compounds After a short review of synthesis and reactions of halogeno(organothio)methaniminiumsalts, the reactions of tetrahydro-1,3-thiazine-2-thiones 9 with thionyl chloride or phosgene to yield 2-chloro-5,6-dihydro-4H-1,3-thiazinium chlorides 10 are described. Compounds 10 can be converted to the more stable tetrafluoroborates 13 and hexafluorophosphates 12 , which can be conveniently characterized. Chloroiminium chlorides 10 generated in situ, react with primary amino compounds such as aliphatic or aromatic amines, carboxamides, sulfonamides, diphenylphosphinamide, cyanamide or N-substituted ureas to yield the N,N′-disubstituted 2-iminotetrahydro-1,3-thiazines 17 – 24 .     

Stem fracture incidence in Trapezoidal-28 stainless steel hip arthroplasty

From 1970 to March 1978, 716 forged stainless steel Trapezoidal-28 (T-28) total hip arthroplasties were performed at the authors' institution with a follow-up period from one to 15 years (mean, 64 months). There were 13 (1.8%) stem fractures and one (0.1%) neck fracture. Average time to fracture was 95 months. All fractures occurred in stems implanted before 1976, using early femoral acrylic stem fixation techniques. Stem fracture was related to time of surgery, stem size, patient height, patient weight (for males), and patient age. Survivorship analysis predicted an overall ten-year fracture rate of 4%, and a ten-year rate of 5% for T-28 stems implanted before 1976. There have been no reported fractures in the 204 T-28 stainless steel prostheses implanted since 1976. The mean patient follow-up period for the T-28 stems implanted after 1975 was 52 months, and only 16 patients have been followed for nine years or more. Thus, a longer patient follow-up period is needed in the post-1975 group in order to determine the long-term fracture rate in this group. However, the major difference between this group and the early group is the use of an improved cementation technique, as well as the use of larger prostheses when possible. There was no material or manufacturing change until the introduction of the TR-28 prostheses in 1978.     

Untersuchungen an 1,3-Thiazinen, 20. Mitt. Transacylierende N-Acyltetrahydro-1,3-thiazin-2-thione

On 1,3-Thiazines, XX: Transacylating N-Acyltetrahydro-1,3-thiazine-2-thiones The synthesis of novel N-acyltetrahydro-1,3-thiazine-2-thiones 3 with transacylating activity towards nucleophilic compounds is described.     

Untersuchungen an 1,3-Thiazinen, 19. Mitt. Darstellung von und Cyclisierungsversuche mit N-monosubstituierten S-Prop-2-inyl-thiolurethanen

1,3-Thiazines, XIX: Preparation of N-monosubstituted Prop-2-ynyl Carbonamidothioates and Attempts to Cyclize these Products The preparation of novel N-monosubstituted prop-2-ynyl carbonamidothioates 1 and their aminolysis to N,N'-disubstituted ureas is described. The failure of cyclizing the thioesters to 3,6-dihydro-1,3-thiazin-2-ones 2 is reported.