Biomedical subjects

P Mulder

Publications and source records attributed to P Mulder.

69 records · Page 4Linked to original sources

PubMed1989

Long-term effect of ipratropium bromide and fenoterol on the bronchial hyperresponsiveness to histamine in children with asthma.

We studied the effects of the anticholinergic ipratropium bromide (40 micrograms three times daily) and the beta-agonist, fenoterol (0.2 mg three times daily), both administered by powder inhaler, on bronchial hyperresponsiveness (BHR) to histamine in children, aged 7 to 15 years with mild stable asthma and limited bronchoconstriction who had a highly increased BHR. The double-blind, randomized, parallel study was conducted and performed in spring and early summer. BHR and FEV1 were measured on two occasions, before the start of treatment and monthly thereafter for 4 months. Symptoms, peak expiratory flow, and concomitant medication were registered daily. Nine of the 12 patients receiving ipratropium bromide and all eight patients receiving fenoterol completed the study. Patients completing treatment had few symptoms and were in a stable condition throughout the treatment period. Neither the administration of ipratropium bromide nor fenoterol resulted in a significant change of BHR. We concluded that long-term treatment with ipratropium bromide or fenoterol had no effect on BHR in children with mild stable asthma.

Adolescent↗

PubMed1989

[Potassium agonists: regional vasodilator profile in rats].

The systemic and regional (kidney, mesentery, hindlimb) hemodynamic effects of (a) two potassium agonists: cromakalim (1 to 8 micrograms.kg-1.min-1/15 min) and SR 44866 (0.125 to 2 micrograms.kg-1.min-1/15 min) and (b) a calcium antagonist, nicardipine (0.5 to 2 micrograms.kg-1.min-1/15 min) have been investigated by the pulsed doppler technique, and compared in the anesthetized normotensive rat. The two potassium agonists and nicardipine lowered blood pressure (BP) and total peripheral resistance (TPR) dose-dependently and slightly increased heart rate. Cardiac output (QC) remained unchanged. SR 44866 was as potent as nicardipine in reducing BP and about three to four times more potent than cromakalim (the DE20s, doses producing a 20 p. 100 decrease in BP, being: SR 44866: 0.7 micrograms.kg-1.min-1, cromakalim: 2.8 micrograms.kg-1, nicardipine: 0.8 micrograms.kg-1.min-1). At these equihypotensive doses, the three drugs (a) similarly decreased TPR (SR 44866: -16 p. 100, cromakalim: -17 p. 100, nicardipine: -19 p. 100, (b) reduced mesenteric vascular resistance (MVR) (SR 44866: -18 p. 100, cromakalin: -20 p. 100, nicardipine: -21 p. 100) and renal vascular resistance (RVR) (SR 44866: -16 p. 100, cromakalim: -21 p. 100, nicardipine: -13 p. 100 to the same extent as TPR, but (c) SR 44866 and nicardipine reduced hindlimb vascular resistance (HVR) to a larger extent than TPR (SR 44866: -25 p. 100, nicardipine: -25 p. 100.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Contrasting response to cyclosporin in refractory nephrotic syndrome.

We studied the effects of cyclosporin A (CsA), given for three months, in 14 patients with nephrotic syndrome refractory to treatment with prednisone and/or other immunosuppressants. CsA was given in a starting dose of 6 mg/kg and plasma through levels (RIA) were kept between 50 and 150 ng/ml. Diagnosis included: idiopathic membranous glomerulonephritis (n = 6), focal segmental glomerulosclerosis (n = 3), minimal change disease (n = 3) and membranoproliferative glomerulonephritis (n = 2). Three patients with non-immunologically mediated nephrotic syndrome due to Alport's syndrome were studied as well. Considering all patients and diagnostic groups together, proteinuria decreased from 9.0 +/- 4.3 to 4.7 +/- 3.8 g/24 h during CsA treatment (mean +/- SD; p less than 0.01). However, serum creatinine increased from 121.8 +/- 60.5 to 150.4 +/- 64.6 mol/l (p less than 0.01) and glomerular filtration rate as estimated by 24-hour creatinine clearance fell from 85.5 +/- 33.7 to 72.1 +/- 37.2 ml/min (p less than 0.05). When compared to other diagnostic groups, fractional excretion of protein, i.e. protein excretion corrected for changes in glomerular filtration rate, fell only in IMGN (ANOVA, p less than 0.05). We conclude that CsA reduced proteinuria in patients with refractory nephrotic syndrome. In the majority of these patients this reduction could be due to a renal hemodynamic, rather than an immunomodulatory effect of the drug. Only in IMGN the latter action of the drug may be of importance.

Adult↗

PubMed1988

Support for adrenaline-hypertension hypothesis: 18 hour pressor effect after 6 hours adrenaline infusion.

In a double blind, crossover study 6 h infusions of adrenaline (15 ng/kg/min; 1 ng = 5.458 pmol), noradrenaline (30 ng/kg/min; 1 ng = 5.911 pmol), and a 5% dextrose solution (5.4 ml/h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra-arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0.001). Thus, "stress" levels of adrenaline (230 pg/ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline-hypertension hypothesis in man.

Adult↗

PubMed1988

Excess fatigue as a precursor of myocardial infarction.

To test the hypothesis that feelings of exhaustion are predictive of future coronary heart disease, a prospective study was done among 3877 males, aged 39-65. Feelings of exhaustion were assessed by the Maastricht Questionnaire. Among those who were free of coronary heart disease at screening, 59 subjects experienced a fatal or non-fatal myocardial infarction during the 4.2 year follow-up period. A multiple logistic regression analysis revealed that feelings of exhaustion were predictive of future myocardial infarction when controlling simultaneously for blood pressure, smoking, cholesterol, age and the use of antihypertensive drugs.

Adult↗

PubMed1988

Twenty-four hour pressor effect of infused adrenaline in normotensive subjects: a randomized controlled double-blind cross-over study.

Stimulation of prejunctional beta 2-adrenoceptors on sympathetic nerve terminals increases vasoconstrictor nerve activity by facilitating release of noradrenaline. Therefore, man's endogenous beta 2-adrenoceptor agonist adrenaline has been implicated in the pathogenesis of hypertension. To test this hypothesis, adrenaline (15 mg/kg per min), noradrenaline (30 ng/kg per min) and saline (0.9% NaCl, 5.4 ml/h) were infused in 10 supine, resting healthy volunteers for 6 h (1000-1600 h) in random order 2 weeks apart in a double-blind crossover fashion. During infusion of noradrenaline and adrenaline, venous plasma concentrations rose to 705 +/- 58 (mean +/- s.e.m) and 230 +/- 28 pg/ml, respectively. Mean arterial pressure rose by 4% (P less than 0.001) during noradrenaline and fell by 5% (P less than 0.001) during the adrenaline infusion compared with the saline infusion. In the postinfusion period (1600-0900 h) mean arterial pressure was 7% higher (P less than 0.01) after adrenaline compared with the saline infusion, whereas after the noradrenaline infusion, values of mean arterial pressure were not different from those during the saline infusion. The pressor effect of adrenaline could not be explained by a central mechanism or by activation of the renin-angiotensin system. Thus, 'stress levels' of adrenaline mediate a delayed and protracted pressor effect. This is most likely due to stimulation of prejunctional beta 2-adrenoceptors, since 'stress levels' of noradrenaline are devoid of such activity. Our data support the 'adrenaline-hypertension' hypothesis in man.

Adult↗

PubMed1988

Determinants of polychlorinated biphenyls (PCBs) in human milk.

In a longitudinal pilot study on the course of the PCB concentration in human milk during six months of lactation, some important PCB determinants could be studied in 23 women and their infants. PCB values were within the range of those found in the literature. Pearson correlation coefficients were calculated to investigate the association of the mean PCB concentration over the first half year of lactation with maternal parameters, such as age, height, weight, previous lactation period, education, occupation, residence, smoking, drinking and dietary habits as well as the infant parameters gestational age, birthweight and weight gain in the first six months of life. Since the PCB concentration on fat basis and the fat content of the milk were strongly inversely related, statistical analyses were carried out both on fat and on milk basis. In univariate analyses the PCB concentration on fat basis was most strongly associated with pre- versus post-pregnancy weight gain, age and occupation. After multiple regression analysis PCB concentration on fat basis remained significantly associated with weight gain changes and remained borderline (p less than 0.10) significantly related with occupation. The pre-pregnancy Quetelet Index of the mother (height/weight) and the estimated PCB content of the diet (primarily fish) were strongly correlated with the PCB concentration on milk basis. Only the Quetelet Index remained significantly related after multiple regression analysis.

Adult↗

PubMed1987

A prospective study of the Jenkins Activity Survey as a risk indicator for coronary heart disease in the Netherlands.

Type A behavior was assessed in Rotterdam in 3171 males, aged 45-59 years, by the Jenkins Activity Survey (JAS) as part of the Kaunas-Rotterdam Intervention Study (KRIS). During a follow-up period of 9 1/2 years, 112 fatal and 157 non-fatal cases of myocardial infarction occurred. The JAS did not predict future cases of fatal or non-fatal myocardial infarction. Persons scoring highest on the hard-driving scale or the Dutch adaptation of the JAS tended to have higher incidences of angina pectoris. However, overall the validity of this test as a predictor of CHD was not substantiated in this population.

Angina Pectoris↗

PubMed1987

A questionnaire to assess premonitory symptoms of myocardial infarction.

To test the hypothesis that feelings of vital exhaustion precede the onset of myocardial infarction, and to develop a short questionnaire to assess these feelings, a prospective study was done among 3877 males, aged 39-65 years. During a 4.2-year follow-up period, 59 fatal or non-fatal infarctions occurred. The mean score of future coronary causes as determined by a questionnaire assessing feelings of vital exhaustion was significantly higher than the mean score of a control group matched for age, blood pressure, cholesterol and smoking. Given the validity of the model, it was possible to reduce markedly the size of the questionnaire.

Adult↗

PubMed1987

The clinical pharmacology of bopindolol, a new long-acting beta-adrenoceptor antagonist, in hypertension.

Bopindolol is a new long-acting, nonselective beta-adrenoceptor antagonist with partial agonist activity. Its acute (24 hours, 2 mg, administered orally) and long-term (3 weeks, 2 to 4 mg) hemodynamic and hormonal effects were studied in a single-blind placebo-controlled trial in 10 hypertensive subjects. The initial response (mean +/- SE) to bopindolol was a fall in cardiac output (-12% +/- 2%) and heart rate (-11% +/- 2%). Mean arterial pressure began to fall 3 to 4 hours after administration in parallel with a decrease in systemic vascular resistance, which had increased initially. Twenty-four hours after administration, mean arterial pressure and systemic vascular resistance were reduced by 12% +/- 2% and 12% +/- 5%, respectively. By that time heart rate and cardiac output did not differ from baseline values despite beta-blockade. After 3 weeks of treatment mean arterial pressure had fallen by 9% +/- 2% and renal blood flow and glomerular filtration rate were not changed. One week after withdrawal from treatment mean arterial pressure and heart rate were no longer reduced, but beta-blockade could still be demonstrated, establishing the long duration of action of the drug.

Adrenergic beta-Antagonists↗

PubMed1987

Are sleep complaints predictive of future myocardial infarction?

In a prospective study of 3877 males, aged 39-65 years, the hypothesis was tested that sleep complaints are predictive of myocardial infarction. It was found that complaints about troubles in falling asleep and about feeling exhausted when one wakes up were predictive of myocardial infarction occurring in a 4.2 years follow-up period. However, this predictive power was confounded by age, and especially by vital exhaustion. It is concluded that sleep complaints are long term determinants of myocardial infarction because they are part of the syndrome of vital exhaustion.

Adult↗

PubMed1985

Type A behavior and myocardial infarction. A 9.5-year follow-up of a small cohort.

To test the hypothesis that type A behavior is associated with the incidence of myocardial infarction in groups outside the U.S.A., 243 healthy males, aged 45-59 years, who participated in the Kaunas-Rotterdam Intervention Study (KRIS) were interviewed and followed for 91/2 years. No association between type A behavior and the incidence of all coronary events (myocardial infarction and cardiac death) was found. Fatal coronary events, however, were found to have occurred in types A only (P = 0.04). This weak, but positive association indicates that in Europe too the incidence of fatal coronary heart disease is associated with type A behavior.

Angina Pectoris↗

PubMed1984

Imminent myocardial infarction: a psychological study.

Unstable angina pectoris and feelings of fatigue and general malaise are often mentioned as premonitory symptoms of myocardial infarction. From a psychological point of view these feelings of fatigue and malaise reflect a syndrome of vital exhaustion and depression (VED). A questionnaire which measures this syndrome was given to 3,571 males who participated in a voluntary health check up. It was found that the prevalence of "imminent myocardial infarction," defined as unstable angina pectoris plus electrocardiographic signs of ischaemia, was more than four times higher among exhausted and depressive persons, than among persons not so affected.

Adult↗

PubMedDate not supplied

Chronic decrease in flow contributes to heart failure-induced endothelial dysfunction in rats.

Chronic heart failure (CHF) impairs endothelium-dependent, nitric oxide (NO)-mediated dilation. This decreased dilation may be partly secondary to the chronic decrease in blood flow, but this hypothesis has not yet been tested. Thus, we assessed whether a localized, chronic increase in blood flow in vivo reverses endothelial dysfunction of small arteries in rats with CHF. Two months after coronary artery ligation or sham surgery, second-order side branches of the superior mesenteric artery were ligated in order to obtain persistently elevated blood flow (HF) in the adjacent first-order side branch compared with normal vessels (NF). One month later, responses to acetylcholine and flow-mediated vasodilatation (FMD) were assessed in vitro in an arteriograph. Chronic heart failure induced a decrease in mesenteric blood flow (374 +/- 25 and 305 +/- 27 micro L/min for sham and CHF, respectively; P < 0.05). Neither CHF nor the chronic increase in flow affected the responses to acetylcholine. Chronic heart failure decreased FMD (maximal response in sham and control 34 +/- 6 and 13 +/- 4%, respectively; P < 0.05). Chronic increases in blood flow did not modify FMD in sham, but restored FMD in CHF rats (28 +/- 4%; P < 0.05 vs CHF NF). The restored response was abolished by an inhibitor of NO synthesis (N(G)-nitro-l-arginine). Chronic heart failure did not affect the abundance of mesenteric endothelial NO synthase (eNOS) mRNA. A chronic increase in flow significantly increased the abundance of eNOS mRNA in sham rats, but only moderately and non-significantly in CHF rats. Thus, endothelial dysfunction of small arteries in CHF appears to be largely the consequence of the chronic decrease in flow.

Acetylcholine↗

PubMedDate not supplied

[Oxidative stress and endothelial dysfunction in heart failure].

Chronic heart failure is characterized by increased vascular systemic resistances secondary to activation of various vasoconstrictor systems and to decreased endothelium-dependent vasodilatation. Endothelial dysfunction, described both in animals and in humans, may be caused by an increased inactivation of nitric oxide (NO) by reactive oxygen species, leading to decreased NO bioavailability and impaired vasodilatation. Increased levels of free radicals in heart failure may result either from increased production or a decrease in the cellular antioxidant reserves. Free radicals are produced by three enzymatic systems: NADH/NADPH oxidase (after stimulation by angiotensin II or TNF-alpha), xanthine oxidase or endothelial NO-synthase (NOS) itself. However, oxidative stress alone cannot explain endothelial dysfunction. Other mechanisms involved in the regulation of the production of NO (e.g. decreased expression and/or activity of the NOS) and/or changes in production of vasoconstrictors may participate in this impaired endothelium-dependent vasodilatation in heart failure.

Animals↗