[Cholestatic jaundice during lovastatin medication]. / Cholestatischer Ikterus während Lovastatin-Einnahme.

A 48-year-old man had type IIb hyperlipoproteinaemia which could not be satisfactorily treated with diet alone (total cholesterol 351 mg/dl, HDL cholesterol 36 mg/dl, triglycerides 480 mg/dl). Treatment with lovastatin (an HMG-CoA reductase inhibitor) was then started at a dosage of 20 mg daily. After two months on the drug cholestatic jaundice developed (total bilirubin 6.15 mg/dl). The jaundice and abnormal biochemical findings regressed within two weeks of discontinuing lovastatin. All other possible causes of jaundice were excluded. These observations indicate that, in addition to hepatocellular damage, lovastatin may in rare instances also exert a cholestatic effect.

Decrease in LDL and increase in HDL concentrations in type II hyperlipoproteinaemic patients on low-dose combination therapy of cholestyramine and Complamin.

A low-dose combination of Complamin retard (1 g t.i.d.) and cholestyramine (4 g b.i.d.) was compared with each agent alone in 2 serial open trials without dietary restriction using type IIa and IIb hyperlipoproteinaemic patients. Complamin alone produced decreases in LDL and VLDL cholesterol concentrations (up to 20%) whereas cholestyramine alone produced only a modest reduction in LDL (up to 15%). The combination produced marked, progressive reductions in total cholesterol (up to 35%) and LDL (up to 40%); reductions in VLDL (up to 45%), total triglyceride (up to 60%) and free fatty acids (up to 60%) were found only in type IIb patients. The average increase in HDL-cholesterol from the 2 studies for combination therapy was 35%. No side-effects were reported or measured and compliance was excellent. The results demonstrate the potential of a method of achieving beneficial actions on lipoprotein levels with a well-tolerated therapy.

Serum profile of non-esterified fatty acids (NEFA) in patients with hyperlipoproteinemia under xantinol--nicotinate (XN) medication.

The effect of 50 mg/kg body weight Xantinol-nicotinate (XN) on serum lipids and on non-esterified fatty acids (NEFA) was tested in 94 out-patients with hyperlipoproteinemia Types IIa, IIb, IV and V. The lipids were measured before treatment, during a 3-week period of drug administration and 10 days after rejection. In each group of hyperlipoproteinemic patients the lipid lowering effect of XN was accompanied by a constant fall in serum NEFA levels. The time dependent course of NEFA showed that the higher the initial level, the longer the time span required to achieve the lowest values. In the context of the partially conflicting data on the hypolipidemic action of nicotinic acid and its derivatives, it is suggested that the constant decrease in NEFA induced by XN treatment might contribute significantly to the lipid lowering effect of this drug.

Spontaneous rupture of the Achilles tendon - a sign of hyperlipoproteinaemia (HLP) type II.

In biopsies from spontaneously ruptured Achilles tendons a serum lipid and lipoprotein analysis was performed in fifty nine patients. In nine males considerable histological signs of lipid deposition were detectable. The tendon fibers were found to be partly desintegrated. Only in these cases LDL-cholesterol values were found to exceed the normal range indicative of type II hyperlipoproteinaemia (HLP). None of the fifty remaining patients presented biochemical or clinical signs of disorders of lipid metabolism. The observations demonstrate that a spontaneous rupture of Achilles tendom may indicate a primary type II HLP.

Efficacy of hypolipidemic treatment in inhibition of experimental atherosclerosis: the effect of nicotinic acid and related compounds.

The hypolipidemic and antiatherogenic effects of different nicotinic acid derivatives were studied. Five rabbit groups maintained on an atherogenic diet were given simultaneously various nicotinic acid derivatives (50 mg/kg body weight/day): nicotinic acid, Xantinol-nicotinate, beta-pyridylcarbinol or Pirozadil (bis-3,4,5-trimethoxybenzoate, 2,6-pyridindiyldimethylene). All 4 compounds showed a clear hypocholesterolemic and antiatherogenic effect, as measured by serum cholesterol, and by planimetric evaluation of the aortic lesions in terms of percent surface area affected in the aortas and coronary lumen. The simultaneously observed elevation of the HDL/LDL cholesterol ratio of the aortic tissue possibly indicates an antiatherogenic effect of these changes.

[Therapy of hyperlipoproteinemia type II with Xantinol-nicotinate (author's transl)]. / Therapie der Hyperlipoproteinämie Typ IIa und Typ IIb mit Xantinolnicotinat.

In 61 out-patients with hyperlipoproteinemia type II the action of 50 mg Xantinol-nicotinate per kg body weight on lipids of plasma and lipoproteins was investigated in a three week trial. The results of six patients had been discharged: two patients failed to attend the follow-up examinations, in four patients a lipid lowering effect could not be demonstrated. 40 Type IIa patients and 15 Type IIb patients were examined. In this two groups cholesterol, phospholipids and triglycerides of plasma were significantly lowered. In Type IIa hyperlipoproteinemia mainly the LDL lipids and in Type IIb additionally the VLDL lipids decreased. In Type IIb patients the decrease of lipids were more rapid than in Type IIa patients. This effect is interpreted by the short half life of VLDL. Withdrawel of the drug resulted in an increase of the lipids to the mean values of the untreated patients within ten days.

[Xantinol-nicotinate in primary type-V hyperlipoproteinaemia (author's transl)]. / Xantinol-nicotinat bei primärer Typ-V-Hyperlipoproteinämie. Wirkung auf Lipide und Serumlipoproteine

The effect of xantinol-nicotinate (50 mg/kg body-weight) on serum lipids and lipoproteins was tested in 16 out-patients with primary type V hyperlipoproteinaemia. The lipids and lipoproteins were measured before treatment, during a three-week period of drug administration and ten days after it had been stopped. There were no side effects such as flushing or gastritis, and no notable reduction of weight. Each serum-lipid fraction (triglycerides, nonesterified fatty acids, phospholipids, ester-cholesterol and free cholesterol) decreased significantly, regaining the initial values ten days after the drug had been stopped. While chylomicrons and very low-density lipoproteins (VLDL) decreased, there was a significant increase in low-density lipoproteins (LDL). High-density lipoproteins were not significantly changed. The decrease in chylomicrons and the significant decrease in VLDL with xantinol-nicotinate was opposite to that seen with dietary treatment. In none of the patients did LDL increase to abnormally high levels.

[Corneal arcus and hyperlipoproteinemia (author's transl)]. / Arcus lipoides corneae und Hyperlipoproteinämie

In 60 patients with corneal arcus the incidence of hyperlipoproteinemia was examined by serum lipid and lipoprotein analysis. An elevation of the serum lipid, or lipoprotein contents was found in every patient. 52 patients showed a primary type II hyperlipoproteinemia, three had a type IV, and one a type V pattern. In three cases hyperlipoproteinemia was found to be secondary to a severe cholestasis. The results show that the occurrence of corneal arcus in nearly every subject under 50 years of age and in most subjects over 50 years of age is highly suggestive of the presence of type II hyperlipoproteinemia. Until atherosclerotic complications appear, the course of the type II hyperlipoproteinemia is lingering and shows poor symptoms. Therefore, corneal arcus is of special importance for the early detection of this type of hyperlipoproteinemia.

Interaction of pentobarbital, diphenylhydantoin and digitoxin with ethanol in the isolated perfused guinea-pig liver.

In the isolated guinea-pig liver the interactions of ethanol with the metabolism of three drugs (14C-pentobarbital, 14C-diphenylhydantoin, and 2H-digitoxin) has been investigated. The disappearance of ethanol could be described by zero-order kinetics and was not influenced by the three drugs. In the case of 14C-pentobarbital and 14C-diphenylhydantoin after a short period of distribution disappearance of radioactivity was faster under the influence of ethanol, whereas radioactivity in liver tissue was increased. The radioactivity accumulated in the liver tissue predominantly represented the unchanged drugs suggesting that the inhibition of drug metabolism by ethanol was the cause of the altered distribution. In the case of 3H-digitoxin ethanol did neither significantly influence the distribution of radioactivity nor the pronounced biliary excretion. However there exists some evidence for a minor inhibition of 3H-digitoxin's metabolism by ethanol.

[Lipid constellation in low density lipoproteins of primary type II hyperlipoproteinemia (author's transl)]. / Lipidkonstellation in der Betalipoproteinfraktion der primären typ II-hyperlipoproteinämie

The lipid composition of purified low density lipoproteins (LDL) was investigated in normal subjects and in type II a and b hyperlipoproteinemia. A significant increase of ester cholesterol in LDL of type II a patients and a decrease of phospholipids in LDL of type II b patients as compared with normal controls, were encountered. The results are compared with other reports from the literature and discussed with regard to the disturbance of LDL metabolism in type II hyperlipoproteinemia.