Salt and hypertension: data from the "Heidelberg Study".

Prevalence of hypertension and "intake" of sodium chloride (as estimated from 24-hr urinary Na-excretion) were measured in a random sample (n = 800) of 20- to 40-year-old Heidelberg men. There was a high (14%) prevalence of hypertension and a high (mean = 11.32 g) NcCl intake; both showed, however, no correlation. The lack of a NaCl/blood pressure correlation in this cross-sectional study might be due to intra- and interindividual variability of both parameters and, possibly, to a "threshold" argument concerning the etiological role of sodium in hypertension.

Sitosterol in juvenile type II hyperlipoproteinemia.

The effect of beta-sitosterol on plasma lipids and lipoproteins was evaluated in a randomized double-blind cross-over trial in 15 children and adolescents with familial hypercholesterolemia over a period of 6 months. Twelve patients completed the study, with good adherence to drug intake. Sitosterol lowered the plasma total choelsterol by 6%, LDL cholesterol by 7% and HDL cholesterol by 15% (P less than 0.05). This insufficient response of total and LDL cholesterol and the marked fall of HDL cholesterol appears to advise against the use of beta-sitosterol granulate in juvenile type II hyperlipoproteinemia.

"Low dose" colestipol in children, adolescents and young adults with familial hypercholesterolemia.

The effect of colestipol on plasma lipids and lipoproteins was studied in children, adolescents and young adults with familial hypercholesterolemia. O.125 g or 0.25 g/kg body weight were given in randomized sequence for period of 4 weeks. Total cholesterol was lowered by 13 and 18% with the smaller and larger dose , respectively, and LDL cholesterol lowered by 15% with the smaller and 12% with the larger dose. HDL cholesterol rose by 18 an 32%. LDL composition before and during the study was abnormal due to a markedly reduced triglyceride content. "Low-dose" colestipol is less effective lowering total plasma and LDL cholesterol than conventional doses but may, due to very few side effects, by advantageously used in cases of familial hypercholesterolemia when plasma cholesterol levels after dietary management are only 15-20% above normal.

Acute dietary effects on diurnal plasma lipids in normal subjects.

The effects of different dietary carbohydrates and different dietary fats as well as of differently spaced dietary constituents on 24-h plasma free fatty acids and triglycerides were determined in healthy young males. If, in an isocaloric diet containing 15-20% protein, 37% fat and 43--48% carbohydrates, sucrose is compared with glucose, 24-h plasma triglycerides are significantly higher with the former carbohydrate. When palm oil (mainly 16 : 0 fatty acids) is compared with olive oil (mainly 18 : 1 fatty acids), 24-h triglycerides are significantly higher with the latter. If the carbohydrate component of a mixed meal is removed, alimentary lipemia is considerably greater. Our findings supplement long term studies regarding the effect of different dietary fats and carbohydrates on plasma lipids and allow calculation of "upper normal limits" for 24-h plasma triglycerides and free fatty acid patterns on isocaloric diets of "prudent" composition.

24-hour patterns of blood sugar, plasma insulin and free fatty acids in patients with primary endogenous hyperlipoproteinemia on isocaloric diets containing 30, 40 and 79 cal% carbohydrates.

10 patients with primary, endogenous hypertriglyceridemia (type IV hyperlipoproteinemia) underwent three different isocaloric dietary regimes of 10 days duration each. The diets contained either 30, 43 or 79% of calories as carbohydrate with 20% of calories from protein. Analyses of insulin, blood sugar and free fatty acids were conducted on the last day of each dietary period, at frequent intervals. There were no differences in either fasting or diurnal blood sugars with the different diets. Insulin levels were positively correlated with the amount of carbohydrate in the diet and there was an inverse correlation between the carbohydrate contents of the diets and circulating free fatty acid levels during waking hours. Since glucose tolerance is maintained, and diurnal plasma lipid levels are lowest with the low fat regime, such diets may be advantageously used for patients with endogenous hypertriglyceridemia.

24-Hour patterns of blood sugar, plasma insulin and free fatty acids in patients with primary endogenous hyperlipoproteinemia on isocaloric diets containing 30, 43 and 79 cal% carbohydrates.

10 patients with primary, endogenous hypertriglyceridemia (type IV hyperlipoproteinemia) underwent three different isocaloric dietary regimes of 10 days duration each. The diets contained either 30, 43 or 79% of calories as carbohydrate with 20% of calories from protein. Analyses of insulin, blood sugar and free fatty acids were conducted on the last day of each dietary period, at frequent intervals. There were no differences in either fasting or diurnal blood sugars with the different diets. Insulin levels were positively correlated with the amount of carbohydrate in the diet and there was an inverse correlation between the carbohydrate contents of the diets and circulating free fatty acid levels during waking hours. Since glucose tolerance is maintained, and diurnal plasma lipid levels are lowest with the low fat regime, such diets may be advantageously used for patients with endogenous hypertriglyceridemia.

Antiepileptic drugs reduce serum uric acid.

Uric acid examination in 554 epileptic out-patients under long-term anticonvulsant medication revealed significantly lower serum concentrations compared to a group of normal controls. In patients taking enzyme-inducing drugs, uric acid levels were found to be lower than in those under valproate sodium. In addition, uric acid concentrations showed a negative correlation with duration of therapy in epileptic males. At this time, we can only speculate on the mechanism involved in the reduction of uric acid by enzyme-inducing anticonvulsants as well as on the possible implication of this finding in the treatment of hyperuricemia.

Diet and high density lipoproteins.

The acute and subacute effects of different diets on serum high density lipoprotein (HDL) cholesterol concentration and/or HDL composition are described. In obese normolipemic, hypercholesterolemic (type II) and hypertriglyceridemic (type IV) patients, low HDL cholesterol values remained low during total starvation for 2 weeks. Prudent diets in patients with type II and IV hyperlipoproteinemia had no significant effects on HDL cholesterol within 3 weeks, whereas in normal individuals, a high carbohydrate diet given for 10 days caused significant decreases in HDL cholesterol with concomitant increases in HDL triglycerides as compared to a high-fat diet. The HDL triglyceride fatty acid composition changed in healthy volunteers during the day, depending on the type of ingested fat. The data demonstrate the possibility of acute manipulations of HDL in normal patients and the difficulties of normalizing low HDL cholesterol levels in patients by dietary means. Additional information on the function of HDL is desirable before the therapeutic manipulation of HDL cholesterol or other constituents of HDL can be evaluated regarding their effectiveness in the prevention of ischemic vascular disease.

Vitamin status in patients on chronic anticonvulsant therapy.

Vitamin levels in blood were estimated in 146 epileptics, aged 20-40 years. Compared to healthy subjects, no higher risk rates of a vitamin deficiency were found in epileptics for vitamins B1, B12, A, C, E and beta-carotene. alpha EGR was elevated only in epileptic females, alpha EGOT in epileptic males, indicating a higher risk of a vitamin B2 and B6 deficiency in these groups. Markedly reduced levels of folate, 25-hydroxy-cholecalciferol, and biotin were found in the epileptics; folate and biotin levels showed a significant negative correlation with the total amount and the average daily dose of anticonvulsants administered.

[Isobaric spinal anaesthesia with bupivacaine and tetracaine (author's transl)]. / Isobare Spinalanaesthesie mit Bupivacain und Tetracain.

4 ml 0.5% solutions of bupivacaine and tetracaine without the addition of a vasoconstrictor, approximately isobaric, were used for spinal anaesthesia on patients in the sitting position. The sensory and motor block due to the two local anesthetics was tested and compared. The mean time on onset of complete analgesia was the same for both local anaesthetics (9 and 11 min), as was also the highest level of analgesia (T10). The duration of maximal extension of analgesia was on an average 45 min longer due to tetracaine (bupivacaine 105 min, tetracaine 150 min). The duration of maximal spread of the blocked sensation of pain, temperature, pressure and touch was similar for each of both local anesthetics. The regression of these sensory qualities, blocked in a dissoaciated manner, took a parallel course. With tetracaine the motor block of the lower extremities developed faster and lasted longer (Bromage 3 for bupivacaine 192 min, for tetracaine 220 min). Motor function and proprioception normalized in a synchronized manner. Isobaric spinal anaesthesia with these two solutions of local anaesthetics was found to be reliable and controllable, especially when administered to the sitting patient. Tetracaine is a good alternative to bupivacaine, currently controversial for intrathecal use.

[Oral contraception and cardiovascular risk (author's transl)]. / Orale Kontrazeption und kardiovaskulares Risiko.

PIP: The 1/3-1/2 of the 30-40 year old Heidelberg women who use the pill may risk a total mortality 40% higher than that of nonusers. Oral contraceptive (OC) use, through still poorly understood mechanisms, remains 1 of the main risk factors for cardiovascular disease in young women, and can enhance other known risk factors. Smoking behavior influences the risk considerably, and in Heidelberg, 49% of the women using OCs were smokers as well. Because of this, medical advice should include recommendations emphasizing the urgency of nonsmoking in OC users, as well as changeover to low dose estrogen pills wherever possible. (author's)^ieng

[A comparison of bezafibrate and clofibrate in type II B and type IV hyperlipoproteinemia]. / Eine vergleichende Studie von Bezafibrat und Clofibrat bei Patienten mit Hyperlipoproteinämie vom Typ IIB und IV.

In 36 patients with primary hyperlipoproteinemia of type II B or IV the effect of bezafibrate, a new derivate of clofibrate, has been compared with the effect of clofibrate. In an open cross-over-study the effect of 1.5 g clofibrate p.d. has been compared with that of 450 mg bezafibrate p.d. for several months. The effect of bezafibrate on plasma triglyceride concentration and plasma cholesterol concentration was more pronounced than that of clofibrate. This difference was statistically significantly only in the concentration of plasma triglycerides of type IV patients. It is obvious that the difference between bezafibrate and clofibrate would have been more pronounced if the dose of bezafibrate had been in the optimal range. Serious side-effects caused by bezafibrate could not be observed.

L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin.

Ascorbic acid has been shown to stimulate endothelial nitric oxide (NO) synthesis in a time- and concentration-dependent fashion without affecting NO synthase (NOS) expression or l-arginine uptake. The present study investigates if the underlying mechanism is related to the NOS cofactor tetrahydrobiopterin. Pretreatment of human umbilical vein endothelial cells with ascorbate (1 microm to 1 mm, 24 h) led to an up to 3-fold increase of intracellular tetrahydrobiopterin levels that was concentration-dependent and saturable at 100 microm. Accordingly, the effect of ascorbic acid on Ca(2+)-dependent formation of citrulline (co-product of NO) and cGMP (product of the NO-activated soluble guanylate cyclase) was abolished when intracellular tetrahydrobiopterin levels were increased by coincubation of endothelial cells with sepiapterin (0.001-100 microm, 24 h). In contrast, ascorbic acid did not modify the pterin affinity of endothelial NOS, which was measured in assays with purified tetrahydrobiopterin-free enzyme. The ascorbate-induced increase of endothelial tetrahydrobiopterin was not due to an enhanced synthesis of the compound. Neither the mRNA expression of the rate-limiting enzyme in tetrahydrobiopterin biosynthesis, GTP cyclohydrolase I, nor the activities of either GTP cyclohydrolase I or 6-pyruvoyl-tetrahydropterin synthase, the second enzyme in the de novo synthesis pathway, were altered by ascorbate. Our data demonstrate that ascorbic acid leads to a chemical stabilization of tetrahydrobiopterin. This was evident as an increase in the half-life of tetrahydrobiopterin in aqueous solution. Furthermore, the increase of tetrahydrobiopterin levels in intact endothelial cells coincubated with cytokines and ascorbate was associated with a decrease of more oxidized biopterin derivatives (7,8-dihydrobiopterin and biopterin) in cells and cell supernatants. The present study suggests that saturated ascorbic acid levels in endothelial cells are necessary to protect tetrahydrobiopterin from oxidation and to provide optimal conditions for cellular NO synthesis.

Biliary cholesterol saturation and weight reduction--effects of fasting and low calorie diet.

The effects of fasting or a 600-cal diet on biliary lipid composition were studied in 20 persons with overweight. With complete fasting for 20 days and a mean weight loss of 650 g/day, biliary cholesterol fell significantly from 10.1 to 6.9 mol% and the 'lithogenic index' from 1.0 to 0.7. Following fasting, the index, in 10 of the 11 patients, was in the normal range below 1.0. With a 600-cal diet, in agreement with findings by other authors, there was no significant change of individual bile lipids or of the lithogenic index. While it has been shown that lithogenicity increases up to 16 h of fasting, it obviously significantly decreases with continued fasting. Fasting, therefore, in addition to manipulation of dietary cholesterol and, possibly, fiber consumption, appears to be an effective method for rapid lowering of biliary cholesterol saturation.

[The effect of bezafibrate on biliary lipids (author's transl)]. / Gallenlipide unter Bezafibrat.

The effect of bezafibrate (3 x 200 mg/day) on biliary lipids was studied in 12 healthy male subjects and in 13 patients with hyperlipidemias. In normal subjects, the lithogenic index, with bezafibrate and placebo administered in a double blind cross-over design, was 1.1 and 0.77 respectively. The difference was not significant. In patients, who have been treated with bezafibrate for 6 months to 3 years the index was 0.76, and 0.64 six weeks after discontinuation of the drug. This difference, too, was not significant. It appears, therefore, that contrary to findings with clofibrate, bezafibrate may not be associated with an increased risk of cholelithiasis. This question, however, can ultimately be answered with certainty only on the basis of long-time epidemiologic evidence.

Blood pressure and adipose tissue linoleic acid.

In a natural, "free-living population" of 650 men, surveyed with the purpose of health assessment within an epidemiological design, a strongly significant negative correlation between the relative linoleic acid composition of adipose tissue and blood pressures was found (P less than 0.001). This correlation remained significant when age and weight were statistically controlled for. Thus, dietary, lipid-lowering linoleic acid seems to effect blood pressures as well in a favorable way.