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In 5 intervention studies the beneficial effect of lipid lowering by antilipemic drugs on the course of atherosclerotic lesions has been shown by serial coronary angiography in patients with manifest coronary heart disease. The beneficial effect depended on the level of LDL and HDL cholesterol during drug therapy. This could not only be shown by coronary angiography but also by the frequency of clinical cardial events. The results of these studies indicate that the prognosis of patients with coronary heart disease depends on the LDL and HDL cholesterol concentrations during therapy and not on those before initiating antilipemic drug therapy. Therefore a consequent lipid-lowering therapy is necessary. The best prognosis was observed at LDL cholesterol concentrations lower than 100 mg/dl.

In order to evaluate whether changes in plasma phospholipid composition are rapidly transmitted to the red blood cell membrane (RBCM) under in vivo conditions, the levels of major phospholipids in plasma, low density and high density lipoproteins (LDL and HDL) as well as in RBCM were determined before (pre), directly after (post) and 2 days after (48 h post) LDL apheresis in six patients with severe hypercholesterolaemia. LDL apheresis induced a 30-70% decrease in plasma and LDL cholesterol and total phospholipid levels within 2-3 h. Concomitantly, the percentages of plasma phosphatidylcholine (PC) and the PC/sphingomyelin (SM) ratio were increased compared to initial values. The percentage of plasma lyso PC (LPC) determined before apheresis in the patients was 30% lower with respect to the mean level of LPC in a normolipidaemic control. For LPC of LDL no differences were observed between normolipidaemia and hypercholesterolaemia. LDL apheresis induced a rise by about one third in the percentage of plasma LPC. At 48 h post, plasma LPC levels reapproached pre-apheresis levels, while the percentages of PC and the PC/SM ratio remained elevated. The pattern of changes induced by apheresis in plasma PC, SM and LPC levels was mimicked by changes in RBCM phospholipids. Strong positive relationships were noted for PC, SM and PC/SM as determined at pre, post and 48 h post between plasma and RBCM. In summary, changes in plasma PC, LPC, and PC/SM ratios as induced by LDL apheresis are rapidly transmitted to the RBCM under in vivo conditions, most probably as a result of phospholipid transfer between both compartments.(ABSTRACT TRUNCATED AT 250 WORDS)

The basis of successful treatment of the various forms of hypercholesterolemia is a balanced diet. Initially this includes a general change in lifestyle with a new approach to nutrition, an increase in physical activity and nicotine abstinence. For the individual this implies a diet containing less fat but more unsaturated fatty acids, less salt, less cholesterol, more proteins, more dietary fiber and more complex carbohydrates. Hyperlipidemia triggered by incorrect nutrition or polygenous hypocholesterolemia can usually be successfully treated by means of a fat-modified diet alone. Hypercholesterolemia due to apolipoprotein E polymorphism responds equally well to dietary change. In some cases such dietary modifications can result in a 25% decrease of LDL-cholesterol.

The therapeutic aim in patients with LDL-hypercholesterolemia and coronary heart disease is to reduce LDL-cholesterol levels to around 100 mg/dl. Since such levels are hardly ever reached solely by diet modifications, inevitably the targeted use of cholesterol-lowering drugs is required. Drug therapy of LDL-hypercholesterolemia nowadays includes the following: anion exchange resins, HMG CoA-reductase-inhibitors, fibrates, nicotinic acid and its derivatives, beta-sitosterol and probucol. If cholesterol levels are not sufficiently lowered in response to monotherapy with one of these drugs combined drug therapy should be attempted. Should this likewise prove unsatisfactory then LDL apheresis can be attempted at regular intervals. This regimen usually achieves the desired LDL-cholesterol level even in severe cases.

Effects of alpha-melanocyte-stimulating hormone (alpha-MSH), beta-melanocyte-stimulating hormone (beta-MSH), beta-lipotropin (beta-LPH), and beta-endorphin (beta-EPH) at concentrations from 10(-9) M up to 10(-6) M on human adipose tissue lipoprotein lipase (LPL) were studied in a cell-free system. alpha-MSH and beta-MSH did not exert any effect on LPL; no degradation of these peptides in the incubation medium could be detected by HPLC analysis. beta-LPH and beta-EPH failed to alter enzyme activity. However, HPLC analysis revealed an unspecific rapid degradation of the peptides due to the activity of tissue proteases. Therefore, the protease inhibitors amastatin, antipain, APMSF, and TPCK were tested at concentrations of 10(-5), 10(-4), and 10(-3) M for their efficacy to inhibit degradation. None of the inhibitors was able to substantially reduce proteolysis of beta-LPH, as was the case with amastatin, APMSF, and TPCK for beta-EPH. However, antipain at 10(-4) M preserved at least 20% of the initial peptide concentration from proteolysis up to 150 min. Antipain caused a decrease in lipoprotein lipase activity (LPLA), which was dependent on concentration. The adverse effect of antipain at concentrations of 10(-4) M on LPL was completely abolished by beta-EPH at a concentration of 10(-6) M.

In order to evaluate whether acute changes in fatty acids bound to phospholipids in plasma are transmitted into red blood cell membrane (RBCM) phospholipids, molecular species of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were analyzed after reduction of apo B containing lipoproteins through low density lipoprotein (LDL) apheresis in patients with severe hypercholesterolemia. As compared to the control, increases and decreases in molecular species with arachidonic acid (20:4) and with linoleic acid (18:2), respectively, at sn-2 of plasma diacyl-PC were seen in the patients before the apheresis. Directly after the procedure, the sum of species of plasma and RBCM PC plus PE with 20:4 were reduced. Two days after apheresis major species of plasma diacyl-PC reapproached preapheresis values while, in contrast, the composition of plasma alkenylacyl(plasmalogen)-PE was distinctly altered. In plasmalogen-PE of RBCM similar modifications were induced by the apheresis as in the same subgroup in plasma. In vitro experiments using vesicles with plasmalogen-PE labeled at sn-2 with either [14C]20:4 or a fluorescent pyrenedecanoyl residue indicated fast incorporation of the subgroup into the RBCM. In contrast, diacyl-PE was not taken up by the RBCM. In conclusion, apo B containing lipoproteins are partially responsible for the supply of phospholipids with arachidonic acid to RBCM, in particular by means of the fast incorporation of plasmalogen-PE. The transmission of changes induced by apheresis in plasma into those of the RBCM suggest that erythrocytes play an important role in the homeostasis of fatty acids bound to plasma phospholipids in vivo.

Lipoprotein(a) [Lp(a)] concentrations are known to be stable under various dietary and drug regimens. Little is known about the influence of hyperlipoproteinemia on Lp(a) levels. Therefore, we investigated Lp(a) concentrations and apolipoprotein(a) [apo(a)] polymorphism in 147 patients with hypertriglyceridemia and in 93 patients with hypercholesterolemia and compared them with 404 subjects without hyperlipoproteinemia (controls). Despite a similar apo(a) isoform and phenotype distribution, Lp(a) concentrations differed significantly (P < .0001) between the three groups. The median Lp(a) level in control subjects was 17 mg/dL (mean, 38 mg/dL), compared with 38 mg/dL (mean, 56 mg/dL) in patients with hypercholesterolemia and 9 mg/dL (mean, 21 mg/dL) in those with hypertriglyceridemia. These differences persisted after exclusion of 61 subjects with coronary heart disease. The inverse correlation between the molecular weight of the apo(a) isoforms and the Lp(a) concentration was preserved within each group (P < .001), but for every molecular weight range studied the level of Lp(a) was always higher in patients with hypercholesterolemia and always lower in those with hypertriglyceridemia than in controls. We conclude that hypertriglyceridemia or hypercholesterolemia have profound--but divergent--influences on the concentration of Lp(a).

Beyond cholesterol, inflammatory ether phospholipids such as platelet-activating factor (paf) may play a role in atherogenesis. (1) We detected a paf-like compound ('LA-paf') associated with human serum lipoproteins, mainly in LDL but not with the lipoprotein-poor fraction. (2) LA-paf was also found in washed human platelets, from where it was partially released during platelet aggregation in response to paf (50 nM) or thrombin (1 U). In addition, resident monocyte/macrophage-like U937 cells carried huge amounts of LA-paf (41 ng per 10(7) cells) and metabolized added [3H]paf to a labelled compound co-eluting with the retention time of LA-paf in standard HPLC. (3) Functionally, LA-paf had a comparable potency to synthetic paf, because LA-paf aggregated washed aspirin-treated platelets in a concentration-dependent manner. The specific paf receptor antagonist WEB2086 inhibited the platelet aggregation induced by three distinct LA-paf preparations as compared with synthetic paf with similar inhibitory concentrations (IC50: 35.6 +/- 12.8, 24.0 +/- 4.0, 38.0 +/- 15.8 nM for LA-paf, and 43.6 +/- 6.5 nM for synthetic paf), indicating that LA-paf interacted with paf receptors. (4) However, LA-paf had a distinct retention time using high-pressure liquid chromatography (HPLC) as compared with synthetic paf. LA-paf eluted at 9-15 min and synthetic paf at 21-24 min. In addition, total and non-specific [3H]paf binding to intact washed human platelets was affected differently by the two unlabelled agonists: while LA-paf increased total and non-specific (but not specific) binding in a significant manner (P < 0.002 and P < 0.007) as LDL did (P < 0.006 and P < 0.03), synthetic paf decreased total binding (P < 0.03). Similarly, low-density lipoproteins (LDL) increased significantly the total [3H]paf binding. In contrast, paf did not affect specific [125I]LDL binding to human fibroblasts. Our results show the presence of LA-paf in lipoproteins, washed human platelets and monocyte/macrophage-like cells. As LDL and LA-paf purified from the same LDL particles increased significantly the total [3H]paf binding to intact human platelets, it might modulate platelet adherence to vascular endothelial cells.

Android obesity is associated with metabolic disorders, but the causality of this relationship remains unclear. We investigated the association of body mass index (BMI) and waist-to-hip ratio (WHR) with hormones, glucose tolerance, insulin sensitivity, serum lipoproteins, and the serum activity of hepatic enzymes in 40 healthy premenopausal women (BMI 19.2-46.1, mean 32.6 +/- 1.3 kg/m2; WHR 0.68-1.01, mean 0.82 +/- 0.02). BMI correlated with WHR (r = 0.52, P < 0.01). After correction for WHR, BMI was negatively correlated with high-density lipoprotein cholesterol and positively with total and very low density lipoprotein triglycerides, insulin sensitivity, blood glucose, serum insulin and glucagon. After adjustment for BMI, WHR was significantly associated with high-density lipoprotein cholesterol, total and very low density lipoprotein triglycerides, and the serum activities of hepatic enzymes but not with insulin sensitivity, blood glucose, serum insulin, or glucagon. According to these results, body fat distribution assessed by WHR is related to hypertriglyceridemia and alterations in hepatic function such as a fatty liver. WHR is not primarily related to glucose metabolism in healthy premenopausal women without preexisting metabolic disorders such as glucose intolerance. Therefore the observable association between android obesity and manifest impairment in glucose metabolism may develop secondarily during persisting hyperinsulinemia, which itself is primarily related to obesity. Thus an android body fat distribution may rather be an accompanying feature than a predictor of impaired glucose tolerance and insulin resistance.

To establish whether additional therapy with 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors enhances the low-density lipoprotein (LDL) cholesterol lowering effect of LDL apheresis with immunoadsorption in the treatment of patients with familial heterozygous hypercholesterolemia and coronary artery disease we studied eight patients initially on immunoadsorption therapy alone for 3 years. The adding of HMG CoA reductase inhibitors decreased pretreatment LDL cholesterol from 6.76 +/- 0.98 to 4.97 +/- 0.98 mmol/l and posttreatment LDL cholesterol from 2.33 +/- 0.80 to 1.94 +/- 0.67 mmol/l and increased pre- and posttreatment high-density lipoprotein (HDL) cholesterol by 0.08 and 0.13 mmol/l respectively. The LDL/HDL ratio was reduced from 4.0 to 2.8 (prior to any therapy the ratio was 13.4). The increase in LDL cholesterol between weekly treatments was less steep under the combined therapy. At the same time the treated plasma volume during LDL apheresis could be decreased from 5070 +/- 960 to 4370 +/- 1200 ml. We conclude that in patients with severe familial heterozygous hypercholesterolemia LDL apheresis should be combined with HMG CoA reductase inhibitors.

There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gallstone formation and mitigate biliary pain in gallstone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gallbladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 x 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05 +/- 0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94 +/- 0.27 versus 0.93 +/- 0.32 mg/ml) or total protein (5.8 +/- 0.9 versus 6.4 +/- 1.3 mg/ml), cholesterol saturation (1.3 +/- 0.2 versus 1.5 +/- 0.2), or nucleation time (2.0 +/- 3.0 versus 1.5 +/- 2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9 +/- 0.6 versus 5.6 +/- 1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of the two HMG CoA reductase inhibitors lovastatin and pravastatin in combination with 12-16 g cholestyramine on serum lipids were studied in 18 patients with severe primary hypercholesterolemia. Combined therapy of cholestyramine with lovastatin (80 mg daily) decreased low-density-lipoprotein (LDL) cholesterol by 44% (baseline 7.65 +/- 0.51 mM) and increased high-density-lipoprotein (HDL) cholesterol by 20% (baseline 1.22 +/- 0.12 mM) in 9 patients after 2 years. In 9 other patients with comparable baseline lipid values, cholestyramine plus pravastatin (40 mg daily) reduced LDL cholesterol to a comparable extent after 2 years (-43%, baseline 7.71 +/- 0.44 mM) and increased HDL cholesterol by 18% (baseline 1.06 +/- 0.11 mM). The combination with lovastatin led to a significant reduction in triglycerides level by 25% (baseline 1.63 +/- 0.24 mM), whereas the combination with pravastatin did not change triglycerides level (baseline 1.39 +/- 0.15 mM). Both drug regimens were well tolerated without serious side effects. The effects of both HMG CoA reductase inhibitors after 2 years were comparable to those after short-term intake and after 1-year therapy without loss of efficacy.

Familial hypercholesterolemia is a disorder of lipid metabolism associated with a highly increased risk for cardiovascular disease. Since in such patients even combined drug therapy often fails to decrease low-density lipoprotein (LDL) cholesterol levels sufficiently, extracorporeal LDL elimination has been developed. We treated eight adult patients with LDL immunoadsorption using antibodies against apolipoprotein B without additional lipid-lowering drug therapy for 3 years; this procedure was performed at weekly intervals. By one treatment session, LDL cholesterol and lipoprotein(a) levels were decreased by 55%. Under regular treatment, mean LDL cholesterol levels of 165 mg/dL between two consecutive treatment sessions could be reached, compared with 522 +/- 24 mg/dL before any treatment. As high-density lipoprotein (HDL) cholesterol levels increased under regular treatment, the LDL/HDL cholesterol ratio decreased from 13.4 to 3.4. Positive influences on plasma and whole-blood viscosity as well as on erythrocyte aggregation also seem to be beneficial with regard to retarding atherosclerosis. Very-low-density lipoprotein (VLDL) levels were reduced by approximately 50% after treatment, accompanied by a marked increase of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activity. The effects of LDL apheresis on hemostasis, complement activation transport proteins, and hematological parameters were found to be small. In addition, no side effects amounting to any major clinical relevance occurred in any of the patients. After 3 years of LDL apheresis, a decrease in the frequency of anginal chest pain and ST segment depression on exercise testing and a marked reduction of tendon xanthoma size were observed.

Fundamentals: Cardiovascular risk factors depend decisively on living conditions and nutrition. The aim of the present study was to establish whether the different living conditions in the eastern and western parts of Germany were associated with differences in the frequency and severity of these risk factors., Method: In Leipzig, 15,291 people (9,600 women and 5,691 men), in Nuremberg 8,387 (4,559 women and 3,828 men) were examined either after responding to a public appeal, or in the factory, etc., Results: Clearly elevated cholesterol levels (> 250 mg/dl) were found in 33.8% of the men, and 35.9% of the women in Leipzig, and in 39.1% of the men and 50.7% of the women in Nuremberg. This larger incidence of treatment-requiring hypercholesterolemia in Nuremberg was distributed throughout all age groups up to the age of 60. Hypertension was significantly more common among the 30 to 80-year-old women, and the 20 to 40-year-old and 50 to 80-year-old men in Leipzig. the frequency of cigarette smoking, diabetes mellitus and overweight did not differ significantly between the two cities. In cases with known dyslipoproteinemia, drug treatment was rarely applied, and the therapeutic aim of a cholesterol level < 200 mg/dl, was achieved in only 2-6% of those treated. The most significant difference with respect to cardiovascular risk factors was serum cholesterol. It is possible that a higher ingestion of monounsaturated fatty acids and more physical activity may be responsible for the lower cholesterol levels in Leipzig.

To verify the benefit of nonglucose carbohydrates and fiber in enteral formula diets we studied the postprandial metabolism of eight healthy subjects after the intake of two helpings (25 g carbohydrates each) of five commonly used enteral formulas over 4 h. There were no significant differences in postprandial concentrations of blood glucose among the formulas. The area under the curve of postprandial insulin values, however, was significantly smaller after consumption of the fructose-containing formula (1948 +/- 285 microU min ml-1, P < 0.05) than after fiber-free (3222 +/- 678 microU min ml-1) or two fiber-containing products (2664 +/- 326 microU min ml-1, P < 0.05; and 3040 +/- 708 microU min ml-1, P < 0.05). The insulin area of the xylitol-containing formula (2307 +/- 364 microU min ml-1) was significantly smaller compared to the fiber-free product (P < 0.05). In addition, we found the postprandial increase in triglycerides to be significantly higher after the xylitol-containing formula (from 0.93 +/- 0.14 to 1.25 +/- 0.22 mmol/l) than after the fiber-free product (from 0.82 +/- 0.13 to 0.97 +/- 0.16 mmol/l, P < 0.05) or the two fiber-containing products (from 0.88 +/- 0.16 to 0.96 +/- 0.18 mmol/l, P < 0.05; and from 0.80 +/- 0.08 to 0.95 +/- 0.10 mmol/l, P < 0.05). We conclude that a patient with type II diabetes may benefit from replacing glucose and glucose-equivalent carbohydrates with fructose or xylitol.

Objective: To study the relation between serum lipoprotein levels and the frequency of colorectal adenomas, the benign precursors of colorectal cancer., Design: Cross-sectional., Setting: University hospital in Germany., Patients: The study included 822 of 1124 consecutive patients who underwent colonoscopy at our institution (302 patients were excluded because of malignant disease, chronic inflammatory bowel disease, familial polyposis, partial colectomy, or other chronic diseases). Of the 822 study patients, 194 had colorectal adenoma., Measurements: Serum cholesterol fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein [VLDL]) and presence or absence of adenomas; univariate and logistic regression analyses were carried out to evaluate the association between serum HDL, LDL, and VLDL cholesterol levels and the frequency of colorectal adenoma., Results: Univariate analysis of the total patient group showed that the HDL cholesterol level was inversely related to the frequency of colorectal adenoma (odds ratio, 0.36; 95% Cl, 0.21 to 0.62) and that LDL and VLDL cholesterol levels were positively associated with adenoma frequency (odds ratio, 2.31 [Cl, 1.36 to 3.92] and 1.72 [Cl, 1.03 to 2.86], respectively). Univariate analysis of the subgroup of 89 patients with high-risk adenomas showed an inverse association between such adenomas and HDL cholesterol (odds ratio, 0.37; Cl, 0.18 to 0.76). A logistic regression analysis that included age and body mass index showed an association between lipoprotein levels and the presence of adenomas. The relative strength (in descending order) of these associations was as follows: HDL, LDL, VLDL, and total serum cholesterol. A logistic regression analysis of patients with high-risk adenoma showed a significant association between such adenomas and the HDL cholesterol level., Conclusions: Patients with colorectal adenomas have lower HDL cholesterol levels and higher LDL and VLDL cholesterol levels; these lipoproteins may have prognostic significance for the development of colorectal adenomas.

Basic remarks and aims: Alpha-receptor blockers, central sympathicolytic agents and vasodilators are all drugs that are often used to treat hypertension. On the basis of a study of the literature, the effects of these groups of substances on lipid metabolism are described. Main points discussed: Although the data available are few, vasodilators, in particular dihydralazine and hydralazine appear to have no unfavorable effect on serum lipids. Nor do the centrally acting alpha-receptor agonists, such as methyldopa and clonidine have any unfavorable effect, with the exception of the decrease in the HDL cholesterol observed under methyldopa. The selective alpha-1-receptor blockers, prazosin, doxazosin and urapidil, even have a positive effect of varying degree on lipid metabolism: increase in HDL cholesterol and decrease in triglycerides. Long-term studies over a number of years are, however, lacking. The effect of labetalol, reserpine and guanethidine on lipid metabolism cannot yet be definitively assessed owing to a lack of data.

Aim: Cardio-active substances and ACE-Inhibitors are often employed in patients with metabolic disturbances. The question as to whether they have any effect on the lipid levels therefore needs to be answered., Major Points Studied: The effects of antiarrhythmics, ACE-inhibitors, positively inotropic substances and antianginal substances on lipid metabolism are discussed on the basis of a search through the literature. The wealth of data permit the conclusion that many of the drugs in these substance groups are neutral in terms of metabolism. There are, however, also individual substances that lead to an elevation of lipid levels. Via an improvement in glucose tolerance, ACE-inhibitors can contribute to a lowering of triglyceride concentrations and an increase in the HDL cholesterol levels. For a number of substance groups, the data available still do not suffice to permit a definitive conclusion to be drawn., Conclusion: In the case of treatment with the above-mentioned substance groups, effects on lipid metabolism should be checked wherever this is in doubt. This applies, of course, in particular to patients already suffering from hyperlipoproteinemia.

Epidemiologic studies have identified lipoprotein(a) (Lp(a)) as an independent risk factor for atherosclerosis, mainly for coronary heart disease. Atherosclerosis is the most common cause of death in diabetic patients, but there is little information available concerning the importance of Lp(a) in these patients. We compared the presence or absence of late diabetic complications with Lp(a) serum concentrations in 224 patients (82 IDDM, 142 NIDDM). Lp(a) distribution was skewed as described for non-diabetic patients. Despite highly significant differences for total cholesterol, total triglycerides, HDL-cholesterol, VLDL-cholesterol and VLDL-triglycerides (P < 0.001) and for LDL-cholesterol (P < 0.01) Lp(a) concentrations were similar in NIDDM and IDDM (mean: 27 vs. 30, median: 12 vs. 21 mg/dl, P = 0.10). Diabetic polyneuropathy, autonomic neuropathy, nephropathy, peripheral occlusive disease, diabetic gangrene and coronary heart disease were not associated with raised Lp(a) values. Non-insulin-dependent patients with retinopathy exhibited higher Lp(a) concentrations in serum than those without this complication. This significant association was lost when duration of diabetes was taken into account by logistic regression. We conclude, that other risk factors surpass the significance of Lp(a) in diabetic patients.

Background: Epidemiological and animal studies have suggested that the secondary bile acid deoxycholic acid is cocarcinogenic in colorectal cancer, but this hypothesis was not confirmed by case-control studies investigating fecal bile acids., Methods: Individual serum bile acid concentrations were investigated in 25 men and 25 women with colorectal adenomas and in an equal number of age- and sex-matched controls by gas-liquid chromatography., Results: Deoxycholic acid levels were significantly higher in the sera of men with colorectal adenomas (1.70 +/- 0.59 vs. 1.16 +/- 0.39 mumol/L, P < 0.0005) and in a combined analysis of both sexes (1.47 +/- 0.78 vs. 1.08 +/- 0.39 mumol/L, P < 0.0025). Six- and 12-month follow-up measurements of deoxycholic acid concentrations in a subgroup of 22 men and 17 women showed higher serum levels in men with adenomas, indicating that measurement of deoxycholic acid concentration may be a reliable parameter to investigate its pathogenetic role in colonic neoplasia., Conclusions: The data of this study support the hypothesis that deoxycholic acid may play a role in the pathogenesis of colorectal cancer.

Polyclonal antibodies against human low-density lipoprotein (LDL), covalently coupled to Sepharose CL-4B, are used to remove LDL from the plasma of familial hypercholesterolemic patients. During a single treatment LDL-cholesterol is lowered by more than 60%, and plasma viscosity is decreased by 10%. The usual treatment frequency is once a week. The possible development of human antisheep antibodies was followed for up to 5 years. The ELISA signal rose slightly above baseline reaching a plateau within the first year. Clinically, there have been no signs of column-related adverse reactions. Due to the versatility of immunoapheresis it is also applicable to deplete IgG by coupling antihuman IgG antibodies. These columns might be indicated for patients with high panel reactivity to enable organ transplantation and for patients with autoimmune disease. In vitro tests with plasma from high-panel-reactive dialysis patients have shown that IgG could be depleted by 95% across all subclasses and that panel reactivity could be reduced from 91 to 25%.

Endothelins are made by endothelial cells, macrophages, and vascular smooth muscle cells, among others, and are the most potent endogenous vasoconstrictors yet discovered, with additional growth-promoting properties. A locally increased endothelin production in coronary artery disease or other atherosclerotic diseases may increase circulating endothelin plasma concentrations before symptoms of disease are manifest. We determined endothelin plasma concentrations (1) in 43 patients suffering from coronary artery disease (CAD); (2) in 43 patients with hyperlipoproteinemia without coronary artery disease (HLP); (3) in 29 healthy control subjects (C), by means of a novel extraction procedure and radioimmunoassay followed by chromatographic separation. Plasma concentrations in HLP and C overlapped, but were still significantly different (29 +/- 10 vs 21 +/- 8 fmol/ml, ANOVA and Duncan's test). Significantly increased plasma concentrations were also found in patients with CAD, with the highest levels in a subgroup of 8 patients presenting with unstable angina (43 +/- 12 vs 53 +/- 15 fmol/ml). There were no statistically significant differences between CAD groups with (n = 28) or without hyperlipoproteinemia (n = 15) (42 +/- 14 vs 41 +/- 16 fmol/ml; n.s.). Likewise there was no relationship between endothelin plasma concentration in any of the patients studied and lipid fractions in serum. Increased endothelin plasma concentrations in HLP patients without evidence of coronary artery disease are thus not related to the hyperlipidemic state per se, but may rather indicate presence of an increased vasoconstrictor tonus, pre-clinical or silent atherosclerotic disease.

Unlabelled: BASICS: Drug treatment of the risk factor hypertension has not led to the expected reduction in morbidity and mortality of coronary arterial disease. A negative effect of antihypertensive drugs on the lipid metabolism is under discussion as a possible cause., Main Topics: Both the commonly employed thiazide diuretics and chlorthalidone and the loop diuretics furosemide, piretanide and xipamide lead, to varying extents, to an increase in total and LDL cholesterol as well as triglycerides in subjects with normal metabolism. In addition, some diuretics lower the levels of protective HDL cholesterol. These side effects can be avoided--at least in part--by a combination with such drugs as prazosin, pindolol or captopril, which have a favorable effect on metabolism., Conclusion: It is recommended to carefully monitor serum Lipoproteins during diuretic treatment so that possible adverse changes may be counteracted by appropriate measures.

The composition of red blood cell membrane and plasma phospholipids has been analyzed in patients with hyperlipidemias. In red cells of patients with elevated levels of triacylglycerol-rich lipoproteins, phosphatidylcholine (PC) was raised and sphingomyelin (SM) reduced, resulting in a 20% increase of the membrane PC/SM ratio. In plasma phospholipids of these patients PC and SM levels were also higher and lower, respectively and the plasma PC/SM ratio was elevated by more than 50%. Close positive correlations between plasma and membrane phospholipids were obtained for PC, SM and the PC/SM ratio in normolipidemic and hyperlipidemic donors. Plasmalogen phosphatidylethanolamine (PE), a supposed endogenous protector against lipid oxidation, was reduced by about 20% in red cell membrane lipids in hyperlipidemic patients. Also plasmalogen-PE in plasma tended to be reduced in hyperlipidemic donors. Plasma HDL levels were positively related to the content of plasmalogen PE in the red cell membrane. In conclusion, there are closely related increases in PC/SM ratios in plasma and the red cell membrane in patients with elevated levels of triacylglycerol-rich lipoproteins. It is speculated that decreases in red cell membrane plasmalogen-PE in hyperlipidemic patients could be related to impaired antioxidant protection, possibly as a consequence of reductions in plasma HDL levels.

The molecular species composition of red blood cell diacyl-phosphatidylcholine (PC), diacyl-phosphatidylethanolamine (PE) and alkenylacyl-PE (plasmalogen PE) has been analyzed in normolipidemic and hyperlipidemic donors. In all three phospholipid subclasses the percentages of the species 16:0/20:4 were increased in hyperlipidemic patients. In diacyl-PE, 18:1/20:4 was also elevated. No changes were observed in the other quantitatively important molecular species containing arachidonic acid at sn-2, namely 18:0/20:4. The rise in 16:0/20:4 in diacyl-PC and diacyl-PE of hyperlipidemic donors was accompanied by a fall in molecular species with linoleic acid (18:2) at sn-2 (in particular 18:1/18:2). In alkenylacyl-PE the elevation of 16:0/20:4 was compensated by a decrease in species with docosatetraenoic acid (22:4) at sn-2 in particular by a fall in 16:0/22:4. Among all donors, the percentages of 16:0/20:4 in diacyl-PC and PE were positively associated with plasma total cholesterol levels. The changes in molecular species composition of PC and PE in hyperlipidemia are expected to alter the function of erythrocyte membrane transport proteins and--if present also in other cell types--to affect eicosanoid metabolism.