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Biomedical subjects

A van't Laar

Publications and source records attributed to A van't Laar.

At least 19 recordsLinked to original sources

Why is the measurement of jugular venous pressure discredited?

Every doctor should be able to make a probable diagnosis of congestive heart failure by clinical examination. The most revealing clinical sign is an elevated jugular venous pressure. The measurement of this pressure was introduced by Lewis in 1930 and refined and standardised by Borst and Molhuysen in 1952. Still, this method has fallen into disuse and is thought to be not very sensitive for diagnosing congestive heart failure. A study of the methods described in the literature reveals that variations in technique are responsible for great differences in normal values. It is argued that smaller elevations of jugular venous pressure can only be measured reliably by adhering strictly to the conditions put forward by Borst and Molhuysen. In this way the sensitivity will improve considerably. A plea is made for an intensive training in this method for doctors and medical students.

Blood Pressure Determination↗

The variability of the absorption of subcutaneously injected insulin: effect of injection technique and relation with brittleness.

A comparison has been made of insulin absorption rate and its variability in healthy subjects (n = 12), matched Type 1 diabetic patients (n = 12), and brittle Type 1 diabetic patients (n = 13) after subcutaneous injection with a standardized injection technique. In each individual 8 U of iodinated neutral human soluble insulin were injected twice, at the fat-muscle boundary. Disappearance of radioactivity was measured for 8 h. Differences in absorption rate could not be demonstrated (T50 207 +/- 30 (+/- SD), 224 +/- 73 and 217 +/- 80 min in the three groups, respectively). Intra-individual variance was similar in the three groups (intra-individual SD of T50 14 +/- 9, 10 +/- 6 and 12 +/- 10%, respectively). Injection with the skinfold technique each patient usually employed, did not alter mean absorption rate or its variability significantly (T50 179 +/- 52 min; intra-individual SD 12 +/- 8%). In a group of Type 1 diabetic patients (n = 26) the absorption rate after deep injection was compared with that after superficial injection. No differences were found (T50 207 +/- 66 vs 236 +/- 66 min). In some of these patients (n = 10) plasma free insulin and glucose concentrations were measured. The increase in free insulin concentrations was significantly different only at some time-points, but insulin curves and plasma glucose concentrations did not differ significantly. Thus neither insulin absorption nor its variability differ between healthy subjects and diabetic patients, between deep and superficial subcutaneous injection, or between stable and brittle diabetic patients.

Absorption↗

Low-density lipoprotein catabolism in WHHL rabbits after partial ileal bypass surgery.

The effect of partial ileal bypass surgery (PIB) on lipoprotein concentrations and compositions and on the catabolism of low-density lipoproteins (LDL) was studied in Watanabe heritable hyperlipidemic (WHHL) rabbits. After PIB, total serum cholesterol was 65% lower (6.22 +/- 1.58 vs. 17.24 +/- 3.22 mmol/l) and LDL cholesterol 81% lower (2.02 +/- 0.95 vs. 10.90 +/- 3.60 mmol/l) than in control WHHL rabbits; cholesteryl esters, expressed as percentage of mass, were 55% lower in the very-low and intermediate-density lipoprotein (VLDL + IDL) fractions, and 45% lower in LDL, whereas triacylglycerols were 89% higher in VLDL + IDL and 121% higher in LDL. The fractional catabolic rate (FCR) of LDL protein (apoLDL) from operated animals was 10% higher than that from controls in all animals (0.55 +/- 0.10 vs. 0.50 +/- 0.10 pools/day; P less than 0.01). The FCR of autologous apoLDL in PIB rabbits was 50% higher than that of autologous apoLDL in control rabbits (0.63 +/- 0.05 vs. 0.42 +/- 0.06 pools/day); this was not caused by induction of receptor-mediated clearance of LDL. The production rate of apoLDL after PIB in PIB rabbits was 50% lower compared to control apoLDL in controls (26.0 +/- 6.7 vs. 51.7 +/- 16.4 mg/kg per day). We conclude that PIB lowers LDL cholesterol in WHHL rabbits by a decreased production of LDL, by an increased non-specific clearance of LDL and by compositional changes, which lead to LDL particles containing less cholesterol.

Animals↗

Apo E polymorphism and the removal of remnants of triglyceride-rich lipoproteins in normolipidemic subjects during a carbohydrate-rich diet.

The role of the apo E polymorphism in the removal of remnants of very low density lipoproteins and chylomicrons was studied after a carbohydrate-rich diet in 10 healthy normolipidemic volunteers with different apo E phenotypes during 7 days. The cholesterol concentration in the heparin-sepharose bound part of the VLDL + IDL fraction (d < 1.019 g/ml) was taken as an estimate of the remnant concentration. Before and after carbohydrate-rich diet retinyl palmitate, mixed with cream, was consumed by each subject the evening before the fasting venepuncture to quantify the removal of chylomicron remnants. After the diet there was a comparable mean rise in the three groups in serum and in very low density lipoprotein triglycerides of about 30% and 50%, respectively. The concentration of remnants of very low density lipoproteins increased slightly in all subjects. The concentration of retinyl palmitate in the d < 1.019 g/ml fraction was 20% lower than before this diet in the E-2 homozygous subjects. In the other two groups, however, 25 to 80% higher retinyl palmitate levels were found. It is concluded, that after a carbohydrate-rich diet there is only a slight increase of very low density lipoprotein remnants, independent of the apo E polymorphism. The removal of chylomicron remnants, however, seems to be facilitated in E-2 homozygous subjects, in contrast to a slower removal in the groups with other apo E phenotypes.

Journal Article↗

Some metabolic characteristics of low-density lipoprotein subfractions, LDL-1 and LDL-2: in vitro and in vivo studies.

Two low-density lipoprotein subfractions, LDL-1 and LDL-2, with density ranges of respectively 1.023-1.034 and 1.036-1.041 g/ml, were isolated by aspiration after density gradient ultracentrifugation of human pooled serum. In vitro interactions of both LDL subfractions with the LDL receptor of human cultured fibroblasts, human hepatoma cell line Hep G2 and human hepatocytes were compared. No difference in association (binding and internalization) nor in degradation between LDL-1 and LDL-2 by these cells was found. However, kinetic studies in guinea pigs showed that LDL-2 disappeared faster from the circulation and accumulated to a greater extent in the liver, compared to LDL-1. Thus, we were unable to show a difference in the LDL receptor-mediated uptake of both LDL subfractions by various cells in vitro. The results obtained in vivo suggest that LDL-1 is more atherogenic than LDL-2, because its longer half-life renders the particle more susceptible to uptake by the scavenger LDL receptor on macrophages.

Animals↗

Insulin antibodies do not influence the absorption rate of subcutaneously injected insulin.

The influence of insulin antibodies on absorption rate and plasma free insulin concentrations after subcutaneous injection of insulin, was studied in two groups of insulin-treated diabetic patients, one without insulin antibodies (n = 9) and a second with high plasma concentrations of antibodies (n = 14). Except for antibody concentration there were no differences in clinical variables. During 8 h after the injection of 12 U of iodinated neutral human insulin, residual radioactivity at the injection site, plasma glucose, and free and total insulin were measured. Significant differences in absorption rate of insulin were not found between the groups. Plasma glucose (basal value 16.8 +/- 4.4 SD vs 16.1 +/- 4.2 mmol l-1) and free insulin (basal value 8.3 +/- 1.4 vs 11.4 +/- 2.3 mU l-1, maximum after 90 min 36.9 +/- 19.5 vs 30.5 +/- 18.7 mU l-1) were never significantly different between the groups, nor were areas under the curve for free insulin (191.4 +/- 69.2 vs 170.8 +/- 98.6 mU l-1 h). In the high antibody group a small increase in bound insulin was found.

Adult↗

The influence of intrinsic sympathomimetic activity and beta-1 receptor selectivity on the recovery of finger skin temperature after finger cooling in normotensive subjects.

A double-blind randomized study was designed to investigate differences in the recovery of finger skin temperature after finger cooling during dosing with placebo or one of four beta-blockers: propranolol, atenolol, pindolol, and acebutolol. In 11 normotensive nonsmoking subjects, finger skin temperature was measured with a thermocouple before and 20 minutes after immersion of one hand in a water bath at 16 degrees C. This finger cooling test caused no significant changes in systemic hemodynamics such as arterial blood pressure, heart rate, and forearm blood flow. The recovery of finger skin temperature during propranolol dosing was better than that during pindolol and atenolol dosing. There were no differences between the recoveries of skin temperature during pindolol, atenolol, and acebutolol dosing. Thus we could demonstrate no favorable effect of intrinsic sympathomimetic activity or beta 1-selectivity on the recovery of finger skin temperature after finger cooling.

Acebutolol↗

A study of the hypolipidemic effect of estrogen in type III hyperlipoproteinemia.

Ethinylestradiol (1 microgram/kg/day during 15 days) resulted in a gradual decrease of serum cholesterol, serum triglycerides (TG), very low density lipoprotein (VLDL) cholesterol and VLDL-TG in 2 postmenopausal women and 2 men with type III hyperlipoproteinemia (HLP). The turnover rate of VLDL-TG did not change. These findings contrast with previous observations in normal subjects and patients with type IV HLP. Thus, the catabolism of VLDL and VLDL-remnants increased during treatment with estrogen in type III HLP, probably by direct degradation of VLDL-remnants because in the initial days of treatment no increase of LDL-cholesterol was observed.

Adult↗

Circulatory effects of coffee in relation to the pharmacokinetics of caffeine.

Drinking coffee results in an increase in blood pressure (BP) after an interval of caffeine abstinence. During chronic caffeine intake this pressor response disappears and adaptation to the circulatory effects of caffeine develops. This study was designed to determine whether a pressor response to coffee occurs during chronic caffeine intake if low basal plasma caffeine levels are achieved by a period of caffeine abstinence, defined by individual plasma caffeine half-life. In 8 normotensive subjects, circulatory measurements were studied after ingestion of coffee in 2 strengths, decaffeinated coffee and hot water after a caffeine abstinence of 4.5 times individual caffeine half-life. These measurements were compared to the same protocol without intervention. Coffee of both strengths resulted in a similar increase in BP (diastolic BP +/- 15%). The coffee-induced increase in forearm blood flow and plasma epinephrine levels were less pronounced. Decaffeinated coffee induced a smaller increase of diastolic BP, and after water, no changes were observed. Additionally, a negative correlation was found between the coffee-induced BP increase and basal plasma caffeine level in a group of 30 normotensive subjects (r = -0.71, p less than 0.001). During chronic caffeine intake, subjects with short plasma caffeine half-life are exposed to a pressor response after drinking coffee, despite the phenomenon of adaptation.

Adult↗

Therapeutic efficacy of alpha-adrenoceptor blockade in primary and secondary Raynaud's syndrome.

Twenty patients with primary and 11 with secondary Raynaud's syndrome were treated with the alpha-adrenoceptor blocker phenoxybenzamine (10-20 mg daily). In the secondary group mean age and mean duration of symptoms as well as presence of positive ANA and positive Clq binding test were significantly higher than in the primary group. In both groups a beneficial effect of the medication on finger temperature 12 min after finger cooling and on clinical symptoms was established. Secondary Raynaud's syndrome reacted at least as well as primary syndrome.

Adrenergic alpha-Antagonists↗

Hemodynamic and humoral effects of coffee after beta 1-selective and nonselective beta-blockade.

Several studies report a substantial rise in plasma catecholamines after caffeine. Epinephrine infusion induces a pressor response after nonselective beta-blockade. We studied the hemodynamic and humoral effects of drinking coffee after placebo and after both nonselective (propranolol) and beta 1-selective (metoprolol) blockade in 12 normotensive subjects. After placebo, coffee induced a rise in systolic and diastolic blood pressure and a fall in heart rate, whereas forearm blood flow did not change. Plasma catecholamines, especially epinephrine (+150%), rose and plasma renin activity, fell after drinking coffee. The effects of coffee on blood pressure, forearm blood flow, and all humoral parameters were not altered by pretreatment with propranolol or metoprolol. The fall in heart rate after coffee, however, seemed to be greater during propranolol. We conclude that the rise in plasma epinephrine after coffee was too small to reveal differences in reaction in propranolol- and metoprolol-pretreated subjects.

Adolescent↗

Hemodynamic effects of isometric exercise and mental arithmetic in hypertension treated with selective and nonselective beta-blockade.

Hypertensive patients have an unfavorable pressor response to exogenous epinephrine during nonselective beta-blockade. We studied hemodynamics during epinephrine release induced by handgrip exercise and mental arithmetic to examine the clinical relevance of this phenomenon. Twenty-two hypertensive patients were examined in a double-blind crossover experiment with placebo, propranolol (240 mg daily), placebo-washout, and metoprolol (300 mg daily). Changes induced by stress tests for systolic and diastolic blood pressure, heart rate (HR), and forearm blood flow (FBF) were of the same order on both beta-blockers. Rises in HR and FBF were equally reduced by both drugs. Neither handgrip exercise nor mental arithmetic induced significant differences in reaction during selective and nonselective beta-blockade.

Adolescent↗

Ultracentrifugation in swinging-bucket and fixed-angle rotors evaluated for isolation and determination of high-density lipoprotein subfractions HDL2 and HDL3.

We evaluated the density-gradient ultracentrifugation method in a swinging-bucket rotor (Anal Biochem 111, 149-157, 1981) in a slightly modified version for isolation and determination of high-density lipoprotein (HDL) subfractions. We prestained the serum with Coomassie Brilliant Blue R, which did not change the hydrated densities of the lipoproteins, and after only 2.2 X 10(8) gav . min obtained an equilibrium distribution of the lipoproteins along the gradient. The density distribution of the HDL of 120 sera obtained from apparently healthy persons and from patients with different types of hyperlipoproteinemia was bimodal. The HDL2 could be isolated in the density range 1.072-1.098 kg/L and the HDL3 at 1.100-1.176 kg/L, the latter fraction being more heterogeneous. At a solvent density of 1.100 we obtained similar results for HDL2-and HDL3-cholesterol by ultracentrifugation in two different fixed-angle rotors with tube angles of 15 degrees or 35 degrees. Independent of the rotor and the ultracentrifugation technique, subfractionation at d = 1.100 resulted in more distinct stained entities than ultracentrifugation at d = 1.125. In the swinging-bucket rotor procedure, interference by sinking pre-beta-lipoproteins was minimized because, having hydrated densities between 1.058 and 1.075, they could be removed without aspirating the HDL2. The method is both accurate and precise. For HDL2- and HDL3-cholesterol determined in a thawed frozen serum pool, CVs were 8.8 and 6.3%, respectively (n = 18).

Centrifugation, Density Gradient↗

Influence of contraceptive pill and menstrual cycle on serum lipids and high-density lipoprotein cholesterol concentrations.

The fluctuations of serum lipid and lipoprotein concentrations within one cycle were studied both in women using and not using oral contraceptives. High-density lipoprotein cholesterol decreased significantly from 1.47 mmol/l (57 mg/100 ml) to 1.30 mmol/l (50 mg/100 ml) during one contraceptive cycle in eight women and rose again to the initial value during the pill-free days. The mean concentration of total cholesterol also fell significantly as a result of the decrease of high-density lipoprotein cholesterol and of a not significant decrease of low-density lipoprotein cholesterol. The mean serum triglyceride concentration did not change significantly. The fluctuations in the concentration of serum lipids and lipoproteins in 10 women not using oral contraceptives were smaller than in the women using oral contraceptives and no significant changes in the concentrations were found during one cycle. Thus, high-density lipoprotein cholesterol concentration decreases during each contraceptive cycle. The time of blood sampling during the cycle is, therefore, of vital importance in interpreting the effect of oral contraceptives on high-density lipoprotein cholesterol. In women not using oral contraceptives blood can be sampled on random days during the cycle.

Adult↗

Apolipoprotein C in type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia.

The composition of apolipoprotein C of the very low density lipoproteins (VLDL) was examined in 23 treated Type 2 (non-insulin-dependent) diabetic patients, who had elevated VLDL concentrations. Apolipoprotein C was separated by isoelectric focussing into apolipoprotein C-II which is known as the specific activator of lipoprotein lipase, and three apolipoprotein C-III fragments. A regulatory role has been ascribed to the ratio of apolipoprotein C-II to apolipoprotein C-III in the removal of plasma triglycerides. In our diabetic group, the composition of apolipoprotein C of the VLDL particles was not different from that of a healthy control group. In particular, the above apolipoprotein ratio and the relative amounts of apolipoprotein C-III fragments were normal. Hypertriglyceridaemia in these diabetic subjects does not seem to be related to alterations in the apolipoprotein C composition.

Apolipoprotein C-I↗

Finger temperature after a finger-cooling test: influence of air temperature and smoking.

Skin temperature of one finger was measured before and after immersion of the gloved fingers of both hands in 16 degrees C water for 5 min [room temperature (Ta) 24 or 20 degrees C]. At Ta 24 degrees C, 23 of 25 normal nonsmokers (92%) had finger rewarming to above 24 degrees C in 12 min after cold immersion, at Ta 20 degrees C, only 1 of 12 (8%) had similar rewarming. Among 12 habitual smokers only 4 (33%) rewarmed above 24 degrees C (Ta 24 degrees C) following a 1-h abstinence from smoking, but 8 (67%) did so after a 24-h abstinence. Only 2 of these 8, however, did so in a retest 10 min after smoking a cigarette. The smokers were not tested at Ta 20 degrees C. We conclude that air temperature and cigarette smoking are important determinants of finger rewarming following a finger-cooling test.

Adult↗