[Update of lipid lowering therapy]. / Update der lipidsenkenden Therapie.

Dyslipidemia is one of the most important cardiovascular risk factors. Accordingly preventive measures to normalize lipids are of great importance. The indication for a lipid lowering therapy according to current guidelines focuses on the identification of a patient's global risk, i.e. the contribution of all major cardiovascular risk factors. The selection of the lipid lowering therapy should be appropriate for the kind of lipid disorder. This may be a special challenge with respect to target values and safety aspects. Statins in monotherapy are generally considered safe drugs. Higher dosages may be associated with liver toxicity and muscle problems. Lifestyle management should underpin all lipid management strategies.

Risk factor interactions for coronary heart disease.

There is now an increasing awareness of the atherogenicity of the individual lipoprotein subfractions. In addition, the effects of commonly used antihypertensive drugs has been a cause for concern. Thiazides and loop diuretics both increase LDL cholesterol, but indapamide and spironolactone have no apparent effects. Beta-blocker monotherapy may also increase triglycerides whilst post-synaptic alpha-blockers do not affect, or slightly lower triglycerides, total cholesterol, LDL and VLDL levels.

[Cyclosporin A and hyperlipidemia after kidney transplantation. Prospective study]. / Cyclosporin A und Hyperlipidämie nach Nierentransplantation. Eine prospektive Untersuchung.

Hyperlipidemia is common after renal transplantation and has been attributed, at least in part, to corticosteroid therapy. We therefore studied serum lipids in a group of nondiabetic transplant recipients on conventional immunosuppression with azathioprin and prednisone (Aza/P), in comparison with a transplanted group on cyclosporin A monotherapy (CyA) without steroids. Frequency and degree of hyperlipidemia in the two groups showed no significant difference. Atherogenic hypercholesteremia was found as frequently in patients on CyA as in those on Aza/P. Possible factors preventing normalization are discussed.

Long-term cimetidine in children with cystic fibrosis: a randomized double-blind study.

A prospective, randomized double-blind study of 38 children with cystic fibrosis (CF) was designed to evaluate the effectiveness of cimetidine in improving fat absorption and clinical condition. The treatment consisted of cimetidine or placebo, 600 mg/m2 body surface/day, over a 4-mo period. Clinical state, weight, height, skinfold thickness, lung function tests, para-aminobenzoic acid (PABA) peptide test, and plasma lipid and lipoprotein determinations were performed before and after the treatment period. Compared with age-matched healthy children, patients showed decreased cholesterol (150.2 +/- 31.2 mg/dl, mean +/- SD), decreased high density lipoprotein cholesterol (44.1 +/- 11.8 mg/dl), and decreased low density lipoprotein cholesterol (84.1 +/- 25.5 mg/dl) whereas the triglycerides and the very low density lipoprotein triglycerides were slightly elevated (118.2 +/- 33.0 mg/dl and 60.5 +/- 17.5 mg/dl, respectively). Apoprotein B and AI were slightly reduced and Apoprotein AII was in the normal range. After the 4-mo treatment no significant change in clinical condition, weight, or lipoprotein patterns could be detected between the two groups. The total PABA recovery in urine also did not change significantly (36.6 +/- 19.4% of the dosage given before versus 28.7 +/- 12.9% after 4 mo in the cimetidine group). Cimetidine gave rise to bronchoconstriction as shown by an increase in airway resistance (mean increase 14.8%) whereas the placebo group had a decreased Raw with a mean of 8.3%. Patients with CF have a dyslipoproteinemia that was not influenced by cimetidine. We conclude that cimetidine does not improve fat absorption and has, therefore, no place and no benefit in the treatment of children with CF.

Studies on retinal microangiopathy and coronary macroangiopathy in rats with streptozotocin-induced diabetes.

Diabetes mellitus was induced in male rats by streptozotocin injection. After 4, 8 and 12 months, retinal and coronary vessels were prepared and their structure was studied. An age-dependent increase in thickness of the capillary basement membrane of retinal vessels was found both in controls and diabetics. Furthermore, diabetics had an added 20%, disease-related thickening, present after 4 months and thereafter. No significant change in coronary arteries was found. After 8 and 12 months, plasma lipids, triiodothyronin and thyroxin were measured. In diabetics, triglycerides were higher at both time intervals, high density lipoprotein was slightly increased and thyroxin was reduced after 8 months, and triiodothyronin was reduced after both 8 and 12 months. Diabetes of 12 months duration appears insufficient to induce significant arteriosclerotic changes in rats.

Electroimmunoassay and radioimmunoassay for the quantitation of high density apolipoproteins A-I and A-II.

An electroimmunodiffusion assay (EID) for the quantitative determination of the major apolipoproteins of the human high density lipoprotein fraction, apolipoproteins A-I and A-II, was compared with a solid phase radioimmunoassay (RIA), previously described by us. Data obtained by both methods largely depended on the pretreatment of the sera. Pretreatment consisted either of delipidation with an ether/ethanol mixture or tetramethyl urea, or of denaturation by heating the sera to 52 degree C for 3 hours. Delipidation with ether/ethanol produced a decrease of apolipoprotein A-I values in both methods as compared to treatment with tetramethyl urea. In contrast, the ether/ethanol treatment did not alter apolipoprotein A-II values in the RIA, while in the EID this procedure led to an increase of apolipoprotein A-II values. Heating gave an increase of both apolipoproteins A-I and A-II in both assays, but results obtained by EID were difficult to interpret because of the appearance of indistinct or double rockets. Comparable results by both methods were obtained, when sera were pretreated with tetramethyl urea. Handling and reproducibility seemed to be slightly better with the EID than with the RIA.

[Serum lipids in diminished kidney function, during hemodialysis and after kidney transplantation]. / Serumlipide bei eingeschränkter Nierenfunktion, unter Hämodialysebehandlung und nach Nierentransplantation.

Lipids have been investigated in three groups of patients with chronic renal insufficiency. 19 patients were on conservative treatment (no dialysis), 52 patients were on regular hemodialysis, and 27 patients had been transplanted. The results were compared with those obtained from control subjects of the same age and sex. Hyperlipoproteinemia was found in 25% of the uremic patients, 55% of hemodialysis patients, and 85% of transplant recipients. The predominant lipid abnormalities were hyperlipoproteinemia of Type IV in both uremic (5 out of 19) and hemodialysis patients (17 ou of 52). Hyperlipoproteinemia of Type II was mainly observed after transplantation (IIb: 13, IIa: 5 out of 27).

[Changes in serum lipids and lipoproteins in acute hepatitis]. / Veränderungen der Serumlipide und-lipoproteine bei akuter Hepatitis

In 50 patients with acute hepatitis serum lipide and lipoproteins were determined at regular intervals and the results were compared with the usual liver function tests. Australia-antigen was established in 26 patients. During the first three weeks of the disease the most striking finding was a significant increase in the triglycerides, which was most pronounced at the end of the second week. Triglyceride levels usually returned to normal during the fourth week. In the course of the disease, lipoprotein electrophoresis showed marked decrease or absence of alpha- and pre-beta-lipoproteins during the first two weeks. During the third week faint alpha and pre-beta bands recurred in most patients. By the end of the fourth week lipoprotein electrophoretic findings were back to normal. There was general correlation between routine tests of liver function and results of lipid analyses throughout the course of the disease. This typical pattern of serum lipid and lipoprotein changes was found with near-consistency in patients with HAA-positive hepatitis. It was also present in the majority of HAA-negative patients, though in these the characteristic discrepancy between hypertriglyceridemia and simultaneous decrease of the pre-beta-lipoprotein band in eletrophoresis was, on the average, absent.

[Lipoprotein X in hepatobiliary diseases]. / Lipoprotein X bei hepatobiliären Erkrankungen

The diagnostic and prognostic reliability of lipoprotein-X (Lp-X) in demonstrating or ruling out cholestasis has been evaluated in a group of 80 patients with diseases of the liver and/or the biliary tracts, and in 103 subjects with various other diseases. The results of Lp-X detection were compared with the so-called "enzymes indicating cholestasis": alkaline phosphatase, leucine arylamidase, and gamma-glutamyltranspeptidase. Where possible a histologic specimen of the liver was obtained. The correlation between Lp-X and "enzymes indicating cholestasis" was satisfactory in more than 90% of cases. When compared with the histologic findings, Lp-X proved to be more reliable than the enzymes. Despite this fact, Lp-X did not show absolute specifity in the detection of cholestasis as there were several negative results in cases with histologically proven cholestasis. Furthermore, the differentiation of intra- and extrahepatic cholestasis was not possible on the basis of Lp-X. In the control group of 103 patients with other than hepatobiliary diseases, a positive Lp-X result was found in 3 cases. Further investigations in these three patients revealed that primarily unsuspected hepatobiliary disease could not be ruled out. In the follow-up of a hepatobiliary disease the transition of Lp-X to negative indicates a trend towards improvement of cholestasis 1-2 weeks earlier than the enzymes mentioned above.