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Biomedical subjects

M Kohlmeier

Publications and source records attributed to M Kohlmeier.

At least 37 records · Page 2Linked to original sources

Treatment of coronary heart disease by diet and exercise: fasting and diurnal lipoproteins.

The effects of a combined exercise and low-fat dietary regimen were studied in 11 patients with angiographically documented coronary heart disease (cholesterol 233 mg/dl, triglycerides 158 mg/dl) and 13 comparable patients (cholesterol 224 mg/dl, triglycerides 174 mg/dl) on usual care. During one year, fasting serum lipoproteins were lowered to "ideal" levels in the intervention group (cholesterol 191 mg/dl, triglycerides 100 mg/dl, LDL-cholesterol 121 mg/dl). There was no change of triglycerides and cholesterol on usual care while LDL-cholesterol rose significantly. Neither regimen had any effect on HDL-cholesterol. Diurnal triglycerides as a presumptive measure of IDL in the intervention group were diminished by 39%. The study demonstrates the feasibility of a diet and exercise regimen to normalize mildly elevated plasma lipid levels and thus to possibly affect the course of coronary heart disease without drugs.

Cholesterol↗

Benzbromarone disposition and uricosuric action; evidence for hydroxilation instead of debromination to benzarone.

Benzbromarone is one of the main uricosuric drugs currently used. We determined plasma concentrations of benzbromarone, bromobenzarone, and benzarone and 24 hour uric acid excretion in ten healthy individuals following fasting application of two different non-micronised benzbromarone brands. In addition we explored the influence of adjusting urinary pH to near neutral values and of concomitant food intake. Benzbromarone was more rapidly absorbed from the test preparation than from the reference preparation; the extent of systemic availability did not differ significantly. Urinary pH adjustment had no clearcut effect, whereas food intake retarded drug absorption (even though not significant because of the variability of the data). Binding of benzbromarone to plasma proteins exceeded 99%. Bromobenzarone and benzarone were not detectable and are unlikely to be major metabolites of benzbromarone. Instead we found two other compounds suggestive of metabolites, one of them being monohydroxilated benzbromarone. The plasma concentrations of the parent compound in one subject exceeded those of the rest of the group, possibly indicating genetic differences in drug metabolism. The uricosuric effect was not related to benzbromarone plasma concentrations.

Adult↗

Plasma-triglycerides and exercise: a delicate balance.

Alimentary lipemia was studied in 12 healthy young men with and without exercise. Three sets of experiments were performed. While continuous exercise of 90 min duration significantly reduced postprandial triglycerides by 26% (study I), this effect could not be observed when exercise was interrupted for 5 min after each 25 min (study II). Plasma free fatty acid concentrations, in the latter experiment, were significantly higher (by 311%) than during rest. When, in a third experiment continuous exercise was compared with intermittent physical activity, the latter condition significantly increased postprandial triglyceridemia, most probably due to precipitous rises of free fatty acids on each interruption of ergometry. It is concluded that in the third experiment the balance between triglyceride removal and triglyceride synthesis was shifted toward the latter. Whether exercise lowers, leaves unaltered, or raises plasma triglyceride levels may depend on subtle changes of experimental design.

Adult↗

Metabolic changes in healthy men using fat-modified diets. I. Disposition of serum cholesterol.

The effect of typical fat-modified diets on serum lipids, lipoproteins and apolipoproteins, on the intravenous fat-tolerance test and on fecal sterol excretion were observed in a group of men living at home and compared to that of their normal diets. Two 4-week-long diet periods alternated with four periods of 6 weeks' duration during which the men followed their normal dietary habits and accustomed life-styles. According to a randomized cross-over design sunflower oil and corn oil were used as the main fat sources for the fat-modified diets. Both diets lowered total cholesterol considerably acting mainly on LDL cholesterol, without affecting plasma triglycerides significantly. Apolipoprotein A-I and A-II concentrations in serum remained constant, and clearance of triglyceride-rich lipoproteins, as measured by an intravenous fat-tolerance test (Intralipid test), was not significantly affected. While changes of all measured parameters pointed in the same direction, serum total and LDL cholesterol levels were significantly lower with corn oil than with the sunflower oil. Excretion of endogenous sterols (fecal sterol balance) was higher with the fat-modified than with the normal diet. This increase in sterol excretion closely corresponded to the extent of serum cholesterol lowering.

Adult↗

Metabolic changes in healthy men using fat-modified diets. II. Composition of biliary lipids.

The composition of fasting gallbladder bile was investigated in a group of 14 healthy men both on their normal diets and on a low cholesterol diet containing less saturated and more polyunsaturated fat given twice for 4 weeks. These dietary changes caused a 21.6% reduction of total serum cholesterol levels. With the use of the fat-modified diet lithogenic indices of fasting gallbladder bile were not significantly changed despite increased relative concentrations of bile acids and decreased relative concentrations of phospholipids and cholesterol in bile. Thus, the experiment provided no evidence for an increased cholelithiasis risk in healthy men ingesting 'prudent diets'.

Adult↗

Low-fat diet and regular, supervised physical exercise in patients with symptomatic coronary artery disease: reduction of stress-induced myocardial ischemia.

The effects of physical exercise and normalization of serum lipoproteins on stress-induced myocardial ischemia were studied in 18 patients with coronary artery disease, stable angina pectoris, and mild hypercholesterolemia (total serum cholesterol 242 +/- 32 mg/dl). These patients underwent a combined regimen of low-fat/low-cholesterol diet and regular, supervised physical exercise at high intensity for 12 months. At 1 year serum lipoproteins has been lowered to ideal levels (serum cholesterol 202 +/- 31 mg/dl, low-density lipoproteins 130 +/- 30 mg/dl, very low-density lipoproteins 22 +/- 15 mg/dl, serum triglycerides 105 [69 to 304] mg/dl) and physical work capacity was improved by 21% (p less than .01). No significant effect was noted on high-density lipoproteins, probably as a result of the low-fat/high-carbohydrate diet. Stress-induced myocardial ischemia, as assessed by thallium-201 scintigraphy, was decreased by 54% (p less than .05) despite higher myocardial oxygen consumption. Eighteen patients matched for age and severity of coronary artery disease served as a control group and "usual medical care" was rendered by their private physicians. No significant changes with respect to serum lipoproteins, physical work capacity, maximal rate-pressure product, or stress-induced myocardial ischemia were observed in this group. These data indicate that regular physical exercise at high intensity, lowered body weight, and normalization of serum lipoproteins may alleviate compromised myocardial perfusion during stress.

Body Weight↗

Mitigation of alimentary lipemia by postprandial exercise--phenomena and mechanisms.

The effects of a single bout of exercise at 40% of maximum aerobic capacity with regard to alimentary lipemia and postprandial lipoproteins was studied in a cross-over design in 12 young healthy male volunteers. In addition to lipids and lipoproteins, lipoprotein lipase, free glycerol, free fatty acids, plasma insulin, and C-peptide concentrations were quantitated. Postprandial exercise reduced alimentary lipemia by 34% while lipoprotein lipase activity rose by 42%. The postprandial fall of high-density lipoprotein (HDL)3 was abolished and the rise of HDL2 accentuated. Free glycerol and free fatty acid concentrations were higher following the meal plus exercise regimen compared to the meal alone. It is concluded that at least part of the chronic effect of exercise may come from additive effects such as observed from individual bouts of muscular activity.

Adult↗

Clinical and metabolic effects of gestodene and levonorgestrel.

The new low-dose combination oral contraceptive (OC) containing 75 micrograms of the new progestogen gestodene (GTD) plus 30 micrograms ethinyl estradiol (EE) was clinically tested and compared with a levonorgestrel (LNG) combined pill (150 micrograms LNG plus 30 micrograms EE). In a randomized clinical comparative study (A), 176 women were treated with the GTD-containing pill and 185 with the LNG-containing pill for six cycles. This study was followed by a second multicenter study (B) covering 707 patients taking the GTD-containing pill for up to 24 cycles (total, 9,947 cycles). In a third study (C), metabolic effects were assessed using a randomly organized baseline control trial (pretreatment/treatment cycles); 30 patients received the GTD-containing pill and 30 received the LNG-containing pill. Carbohydrate metabolism, lipid metabolism, and blood clotting were investigated, and an interim analysis was performed after six OC cycles. No pregnancies and no severe side effects occurred in any of the studies. Intermenstrual bleeding decreased as usual during treatment. In the total number of gestodene cycles in studies A and B, there was a 6.9% incidence of spotting, a 0.8% incidence of breakthrough bleeding, and a 0.7% incidence of both spotting and breakthrough bleeding in studies A and B patients taking gestodene. Amenorrhea occurred in 0.6% of cycles. Body weight remained unchanged (+/- 2 kg) after 24 cycles in 80.5% of study B patients taking gestodene. Blood pressure remained normal in about 95% of all study B patients; a normalization was observed in greater than 60% of patients with previously elevated blood pressure. No clinically relevant changes in carbohydrate metabolism, lipid metabolism, or blood clotting were observed in study C. The new GTD-containing low-dose combination pill proved to be a safe and reliable contraceptive agent.

Adolescent↗

[Composition of gallbladder and bile duct calculi].

The composition of gallbladder and bile duct stones removed at the time of cholecystectomy was analysed in a consecutive series of 45 patients. The type of stones at the two sites was similar in all but two patients. Cholesterol content differed by more than 20% in only six patients. Cholesterol stones were found in the gallbladder of 33 patients, in the bile duct of 36 patients (73 and 80%, respectively); mixed stones in eight and five patients, respectively (18 and 11%); brown-pigment stones in three patients each (7%); black-pigment stones in one patient each (2%). Bile duct stones overlooked during cholecystectomy are thus suitable for litholysis, e.g. by irrigation with monooctanoin, in the majority of cases.

Bile Duct Diseases↗

Influence of bezafibrate on plasma lipoproteins, biliary lipids and fecal sterols in healthy men.

The effect of a 4-week treatment with 600 mg/day of bezafibrate in addition to a low-cholesterol, fat-modified diet on plasma lipids and lipoproteins and on biliary lipids and fecal sterols was investigated in 12 healthy men aged 25-39, and compared to the effect of the diet plus placebo, using a double-blind crossover design. The comparison of placebo and treatment values indicated that bezafibrate, beyond the effect of the diet, significantly lowered concentrations of circulating triglycerides (-25.5%), total cholesterol (-25.8%), LDL cholesterol (-19.5%), and apolipoprotein B (-19.9%), and increased apolipoprotein A-II concentrations in serum (+15.0%). There was a tendency towards lower biliary bile acid and cholesterol secretion rates with bezafibrate; lithogenic indices in fasting and stimulated bile were similar with the drug and placebo. Fecal bile acid excretion rate with diet plus bezafibrate was significantly less than with diet plus placebo. The data obtained are in accord with the hypothesis that bezafibrate exerts its effects on cholesterol and bile acid metabolism predominantly by decreasing VLDL secretion, possibly through an enhancement of fatty acid beta-oxidation in the liver.

Adult↗

Direct enzymic measurement of glycerides in serum and in lipoprotein fractions.

A simple two-step procedure is now available for directly measuring triglycerides in whole serum and in lipoprotein fractions. I tested the performance of the assay, using pooled serum stored frozen, freshly prepared lipoprotein fractions, and pure glyceride standards. A parabolic concentration-response curve ensured linearity well beyond total glycerol concentrations of 10 mmol/L, but gave rise to misleading results for massively lipemic samples. Within-day CVs averaged 2.2% for the stored-frozen serum pools; mean day-to-day variation was 2.4%. Analytical recoveries of triglycerides, after lipoprotein fractionation, ranged between 101.9 and 103.7%. Aqueous glyceride standards gave results equivalent to between 95 and 105% of their glycerol content.

Glycerol↗

[Long-term therapy of familial hypercholesterolemia in young patients with colestipol: availability of minerals and vitamins].

Longterm treatment for 5 years of young patients with familial hypercholesterolemia was accompanied by monitoring of plasma levels of calcium, iron, sodium, parathyroid hormone and water- and fat soluble vitamins, since interference of the ion exchange resin with absorption of numerous substances as well as abnormal plasma levels of some of the above had been described in several studies. Treatment was effective in the group with good compliance (lowering of plasma cholesterol at the end of 5 years by 19% and, compared to the control group, by 23%). Adverse drug effects with respect to the above parameters were not found. Plasma levels of carotinoides and vitamin E were elevated in the patients according to elevated concentrations of lipoproteins which are carriers of these vitamins.

Adolescent↗

Effects of Acipimox on plasma lipids and biliary lipids in healthy subjects.

The effects of Acipimox (5-methylpyracine-2-carboxylic acid-4-oxide, 3 X 250 mg/day) on plasma lipids, lipoproteins, and biliary lipids were studied in 14 healthy male volunteers using a double blind cross-over design. There was a significant (P less than 0.05) rise of HDL-cholesterol by 9.8%, while effects on other lipids and lipoproteins were small and insignificant (total cholesterol minus 6.5%, LDL-cholesterol minus 11.8%, free cholesterol minus 4.2%, total triglycerides plus 13.5% and phospholipids plus 3.9%). There was a significant rise of the HDL-cholesterol/LDL-cholesterol ratio by 23.6% (P less than 0.02) and of the HDL-cholesterol/total cholesterol ratio by 16% (P less than 0.05). Apolipoproteins AI, AII, and B were not significantly affected. The ratio of HDL-cholesterol/Apo AI increased significantly (P less than 0.05), and the ratio of HDL-cholesterol/Apo AII rose from 1.22 to 1.32 (P less than 0.05), while the ratio LDL-cholesterol/Apo B fell from 1.96 to 1.73. The composition of HDL and LDL, therefore, must have been altered by Acipimox. The relative cholesterol concentration in bile was significantly (P less than 0.05) increased by treatment with Acipimox, while bile acids and phospholipids were not significantly affected. The lithogenic index rose significantly by 15.1% (P less than 0.02) as calculated according to Admirand and Small, while calculations according to Hegard and Dam yielded a slight insignificant rise (P less than 0.1). The findings suggest that treatment with Acipimox might be associated with an increased risk of cholelithiasis. However, only long-term epidemiologic studies can ultimately demonstrate whether or not Acipimox increases the risk of gallstone formation.

Adult↗

Influences of "normal" and "prudent" diets on biliary and serum lipids in healthy women.

The differential effect of two diets, taken in synchrony with the menstrual cycles for 2 wk each, on serum and bile lipids was investigated in young healthy women. The "normal" diet was high in cholesterol and total fat, and low in polyunsaturated fat and fiber; the "prudent" diet contained a high proportion of polyunsaturated fat and fiber, but was low in cholesterol and total fat; there was little difference in energy content. Both in whole serum and in low-density lipoprotein the concentrations of cholesterol and apolipoprotein B were almost 30% lower with the "prudent" than with the "normal" diet; HDL-cholesterol was 16.3% lower. Triglycerides were increased, only in the very-low-density lipoproteins while cholesterol and apolipoprotein B did not change much in this fraction. The risk to acquire cholesterol gallstones was not less with the use of the "prudent" diet as originally expected. While using the "prudent" diet five of the women had slightly higher lithogenic indices, in two there were much higher values (greater than 25%), and only in three the lithogenic index was unchanged or slightly lower than with the "normal" diet.

Adult↗

Determination of serum triglycerides by an accurate enzymatic method not affected by free glycerol.

In this automated single-run enzymatic procedure for specific determination of triglycerides in serum, free glycerol is removed from the reaction mixture by pre-incubation with glycerol phosphate oxidase and peroxidase. The subsequent addition of lipase and the chromogen, 4-aminoantipyrine, results in the formation of color proportional to the amount of triglycerides in serum. Standards containing triolein in aqueous detergent are used to calibrate the method. For serum pools from the Centers for Disease Control with target values of 0.74, 1.41, and 2.63 mmol/L, the method produced biases of +0.01, -0.05, and 0.00 mmol/L, respectively (mean: -0.01 mmol/L or -0.4%). The mean coefficient of variation was 1.4% within and 2.5% between days; the combined CV, 2.9%. Ninety 6-microL serum samples can be analyzed per hour. The method is more accurate and precise than one based on an NADH-coupled enzyme system with separate addition of lipase.

Ampyrone↗

Simple method for preparing and quantifying very-low-density lipoprotein.

A micromethod is described for isolating and quantifying human very-low-density lipoprotein (VLDL) from 0.1 mL of human serum, by which more than 100 samples can be processed in half a day with a standard ultracentrifuge. Replicate analysis of 10 normal and hyperlipemic samples gave median coefficients of variation of 11.7% for VLDL cholesterol, 5.1% for VLDL triglycerides. Results obtained by micro-ultracentrifugation and enzymic cholesterol measurement agreed closely with those measured with an electrophoretic method (Pearson's r = 0.98). Compared with the established method, on the other hand, lower values were found for both VLDL cholesterol (r = 0.89) and triglycerides (r = 0.97).

Cholesterol↗

Effect of prolonged exercise on serum lipids and lipoproteins.

It has been shown that physical exercise lowers serum triglyceride levels and may increase high density lipoprotein-cholesterol levels. Understanding of the mechanisms responsible for these beneficial adaptations is still incomplete. Twenty-six men, who played soccer continuously for 64 hours to establish a world's record, were monitored for acute changes in lipid metabolism. Food intake was determined before and during the exercise period. Blood specimens were taken before and repeatedly during the match for the measurement of triglycerides (TG), total cholesterol (CH), glycerol, apolipoprotein A-I (apoA-I), and cholesterol in various lipoprotein fractions (quantitative lipoprotein electrophoresis). During exercise TG levels decreased from 116 +/- 26 to 66 +/- 13 mg/dL and CH from 180 +/- 22 to 135 +/- 25 mg/dL. Both TG and glycerol showed an initial increase followed by a continuous decrease. Alpha-CH increased by 19% whereas beta-CH and pre-beta-CH decreased markedly (39% and 78%, respectively). In contrast to alpha-CH, apo A-1 fell only slightly by 10%. These results indicate that the effect of chronic exercise on lipids and lipoproteins can be mimicked by acute prolonged exercise. Similar mechanisms may be involved in these adaptations. Moreover, the extreme length of physical exertion substantially lowered CH.

Adult↗