Type III hyperlipoproteinaemia: the turnover rate of plasma triglycerides and the response to clofibrate.
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Biomedical subjects
Publications and source records attributed to A van't Laar.
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Cardiac output measurements were performed during 50 exercise tests in 16 normal subjects employing the indirect Fick principle for CO2. During sub-maximal steady state exercise the plateau CO2 tension (PplatCO2) was estimated with a rebreathing procedure. The mixed venous CO2 tension (PvCO2) was calculated by subtracting the alveolocapillary CO2 tension difference from the PplatCO2. Compared with data from the literature the most valid calculation of the cardiac output was obtained by using the PvCO2. Cardiac output values, calculated via the PplatCO2 turned out to be too low. The reproducibility was tested by repitition of 18 exercise tests at least after 5 days. The relative standard error of a single observation was 4.1% for the cardiac output, which was found to be as good as that of invasive measurements.
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We studied polyethylene glycol 6000 precipitation of lipoproteins other than high-density lipoproteins, before cholesterol is estimated in the supernate. Other lipoproteins in the supernatant fractions were detected by using rocket immunoelectrophoresis. A polyethylene glycol concentration of 75 g/L in the final mixture appeared to be optimal, and results agreed with those obtained by ultracentrifugation. Differences in serum pH, use of polyethylene glycol from different suppliers, or the presence of ethylenediaminetetraacetate resulted in values that differed significantly (by 40 to 60 mumol/L) from the reference values. Polyethylene glycol did not interfere in four different methods for determination of cholesterol. In combination with an enzymic cholesterol method, the polyethylene glycol method appeared to be very precise, even when lipemic sera (triglycerides up to 5.5 mmol/L) were analyzed that had diminished high-density lipoprotein cholesterol values. We consider this method a method of choice, especially when lipemic sera are tested and enzymic cholesterol analysis is used.
A double-blind cross-over trial of the non-selective beta-blocker propranolol and the beta1-selective blocker metoprolol was carried out in 8 hypertensive patients. At the end of each 4-week period of treatment haemodynamic and respiratory indices and perceived exertion were studied during moderate exercise. Both beta-blockers resulted in reduced heart rate, cardiac output, and blood pressure, whereas the stroke volume increased. Total peripheral resistance did not change. During exercise the expiratory peak flow rate equally increased in every period. However, the peak flow rate at rest, as well as during exercise, was reduced by propranolol, while metoprolol had no such influence. Neither of the beta-blockers changed O2 consumption, CO2 production, tidal volume, or respiratory rate. Moreover, they did not influence perceived exertion. These results suggest that the arteriolar and bronchiolar beta2-receptors do not play a major role in the alteration of circulation and ventilation during exercise. As far as their practical use as antihypertensive agents is concerned, this study shows no advantage in the use of either of these beta-blockers.
In the oral glucose tolerance test (OGTT), divergent doses of glucose remain in use by virtue of the prevailing conviction that the size of the loading dose hardly affects the outcome of the test. We compared the results of OGTTs with 100-gm. and 50-gm. loads in 85 patients, who were selected for slightly impaired glucose tolerance (plasma glucose at 120 minutes after 100 gm. of glucose was between 130 and 200 mg./dl.) The mean between-load difference in this group appeared to be nearly three times as great (54 mg./dl. at 120 minutes) as reported in the literature for normal subjects. The small impact of the dose in normal subjects could be confirmed in a group of 22 controls. As subjects with normal and with slightly impaired glucose tolerance react divergently to a change in the glucose dose, tests with different loads are not comparable and select different populations. The results can therefore also not be converted to one another by conversion formulas. The finding might be explained by the delay of the additional rise of the plasma insulin in patients after the higher load.
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Early insulin responses were measured after a high dose (50 g/1.73 m2) of rapidly injected glucose in 31 subjects who had repeatedly shown "lag-storage" curves in the OGTT, in 24 controls and in 19 mild maturity-onset diabetics. Division between controls and diabetics was virtually complete, when the insulin responses were expressed as "insulinogenic index" (delta insulin/delta glucose). Twenty out of 31 patients with lag curves showed normal early insulin responses and 11 patients showed diabetic responses. In patients with lag curves, presence of obesity, and absence of family history of diabetes were associated with normal insulin responses. It is concluded that the finding of a lag curve is of little consequence in obese persons but, when in conjunction with a genetic background of diabetes, is suggestive of diabetes.
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A comparative study of the effects of cholestyramine and neomycin has been carried out in 35 patients with severe type II hyperlipoproteinaemia. Both agents were administered during a period of 18 weeks, the daily dosages being 12, 16 or 20 g cholestyramine and 1, 1.5 or 2 g neomycin. The mean decrease in cholesterol concentration was 22% with cholestyramine and 23% with neomycin. There was no difference in effect between the two agents and between the doses used. No significant influence on triglyceride concentration and on body weight was observed. No signs of deficiencies in fat-soluble vitamins were found. Anticoagulant requirements increased during cholestyramine medication. No signs of hyperchloraemic acidosis were observed during treatment with colestyramine. Cholestyramine was tolerated less well than neomycin: it had to be discontinued in 8 cases. Neomycin was not tolerated by 3 patients. The majority of the patients preferred neomycin.
The effects of chlorthalidone, spironolactone and propranolol in reducing blood pressure were compared in the same 11 normoreninemic hypertensive patients. All three drugs decreased the blood pressure significantly and no agent had a superior blood pressure-lowering effect. The blood pressure did not normalize. The data suggest that no one variable--volume factors, relative hyperactivity of the renin-aldosterone system or beta-adrenergic hyperactivity--is the prime mover in normoreninemic hypertension. Long-term treatment with chlorthalidone resulted in slight hyperreninism (26.3 +/- 4.9 ng-ml-1-3 hours-1) (mean +/- standard error) with concomitant changes in plasma aldosterone (23.0 +/- 3.2 ng-100 ml-1). The body weight decreased significantly (--1.8 kg, P less than 0.005). Plasma potassium concentrations were low (3.2 +/- 0.1 mEq-liter -1). Creatinine clearance was unimpaired (117 +/- 6 ml-min-1). Treatment with spironolactone resulted in more marked hyperreninism (47.0 +/- 14.3 ng-ml-1-3 hours-1) and hyperaldosteronism (61.9 +/-11.8 ng-100 ml-1). The body weight decreased significantly (--1.9 kg, P less than 0.004). Significant hyperkalemia occurred (4.4 +/- 0.1 mEq-liter-1). The glomerular filtration rate decreased significantly to 93 +/- 3 ml-min-1 (P less than 0.004). Treatment with propranolol resulted in marked suppression of the plasma renin activity (1.8 +/- 0.2 ng-ml-1-3 hours-1) and plasma aldosterone levels (8.9 +/- 1.3 ng-100 ml-1). A significant increase in body weight occurred (+2.3 kg, P less than 0.013). The plasma potassium concentration increased to a level not significantly different from the value found after treatment with spironolactone (4.2 +/- 0.1 mEq-liter-1). The creatinine clearance decreased significantly to 99 +/- 5 ml-min-1 (P less than 0.008). Hyperreninemia (by spironolactone and chlorthalidone), effective hyperaldosteronism (by chlorthalidone) and volume retention (by propranolol) are considered to represent expressions of mechanisms counteracting the depressor effects of these different pharmacologic maneuvers, leading to the maintenance of supranormal blood pressure.
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The efficacy of semisynthetic human insulin (HI) and monocomponent porcine insulin (PI) in treatment of diabetic ketoacidosis (DKA) was compared in 10 (PI) and 11 (HI) patients in a double-blind randomized study. Insulin (8 U/h i.v.), fluid replacement (0.65% NaCl and 5% glucose), and KCl supplements were administered according to a fixed protocol. Glucose, potassium, sodium, creatinine, calcium, phosphate, and free-insulin concentrations were never significantly different during the study. At the start, mean +/- SD of pH was 7.10 +/- 0.14 in the HI group and 7.10 +/- 0.12 in the PI group. The time to reach arbitrary values for pH, bicarbonate, base excess, and beta-hydroxybutyrate was shorter during HI treatment, but the differences were not statistically significant. During HI treatment, the arbitrary value of 1.0 mM of acetoacetate was reached faster than during PI treatment (5.2 +/- 2.6 and 8.4 +/- 0.9 h, respectively; P less than .05). The concentration of acetoacetate was significantly different between the two groups after 6 and 7 h of insulin treatment (6 h: HI 0.82 +/- 0.50 mM and PI 2.19 +/- 1.65 mM, P less than .05; 7 h: HI 0.51 +/- 0.40 mM and PI 1.74 +/- 1.54 mM, P = .05). We conclude that recovery from DKA during treatment with HI might be slightly faster than during treatment with PI. If this difference is real, it does not seem clinically important.