PubMed Health⌕ Search

Biomedical subjects

A J Smit

Publications and source records attributed to A J Smit.

At least 109 records · Page 6Linked to original sources

The influence of chronic treatment with betablockade and angiotensin converting enzyme inhibition on the peripheral blood flow in hypertensive patients with and without concomitant intermittent claudication. A comparative cross-over trial.

In a comparative cross-over trial we examined the influence of the betablocker bisoprolol and the ACE-inhibitor lisinopril on the peripheral blood flow of 2 groups of hypertensive patients with and without concomitant intermittent claudication. In 11 patients with hypertension without peripheral arterial obstructive disease and 11 patients with hypertension and claudication we assessed the blood pressure, leg blood flow, vascular resistance, walking distance, transcutaneous oxygen consumption and Laser-Doppler flow after treatment of one month with 10 mg bisoprolol once daily or 20 mg lisinopril once daily. The walking distance of patients with claudication improved in all patients while participating in an exercise program. For both treatment groups this improvement was significant (p < 0.05) compared to baseline, from 264 m at baseline to 313 m with bisoprolol and to 400 m with lisinopril. The difference was not significant between the both drugs. In patients without peripheral vascular obstructive disease we found a significant (p < 0.05) reduction in blood flow for both drugs. The peripheral blood flow parameters of 38 legs showed no statistical significant effect of bisoprolol nor lisinopril on the local vascular resistance at rest, after occlusion or after exercise.

Adult↗

Potassium channels in hypokalaemic periodic paralysis: a key to the pathogenesis?

1. A possible role for the ATP-sensitive potassium channels in the pathogenesis of hypokalaemic periodic paralysis was investigated. 2. We assessed insulin release and muscle strength after intravenous glucose loading with and without the potassium channel opener pinacidil and the potassium channel blocker glibenclamide in three patients with hypokalaemic periodic paralysis and in a pair of matched control subjects for each patient. 3. A significantly higher initial insulin response (1.5-30 min) was found in the patients with hypokalaemic periodic paralysis in comparison with the control subjects. During potassium channel blocking with glibenclamide the insulin release was more enhanced in patients than in control subjects. On the other hand, the potassium channel opener pinacidil impaired the insulin release in healthy control subjects but not in patients. The serum glucose levels showed no differences between patients and control subjects. In one of the patients with hypokalaemic periodic paralysis glucose loading resulted in a fall in muscle strength, which did not occur during the administration of pinacidil. 4. These findings suggest a disturbance in the ATP-sensitive potassium channel in patients with hypokalaemic periodic paralysis, which is not limited to pancreatic beta cells, but may be also involved in the abnormal behaviour of skeletal muscle.

Adult↗

Effects of ibopamine on renal haemodynamics in patients with severe congestive heart failure.

The effects of a single dose of ibopamine on renal haemodynamics, sodium excretion, blood pressure (BP) and heart rate (HR) were investigated in 10 patients (aged 52-82 years) with severe congestive heart failure (CHF) who were in NYHA class IV. All patients used ACE inhibitors, digoxin and diuretics. After determining baseline values, ibopamine 100 mg was administered. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously using radio pharmaceuticals. An increase in GFR and ERPF was observed during 3 and 2 h, with a maximum of 15 and 11%, respectively. The ratio GFR/ERPF representing the filtration fraction (FF) was markedly elevated at baseline, 34%, and remained unchanged. No clinically significant increase of sodium excretion was found. No changes in blood pressure, heart rate, plasma renin activity (PRA) and aldosterone or norepinephrine were observed. We conclude that ibopamine increases both ERPF and GFR in patients with severe CHF, possibly as a consequence of both inotropic cardiac and specific renal effects with equal preglomerular and postglomerular vasodilation. The lack of the presumed fall in FF may be the consequence of the expected DA1-induced renal vasodilation, partially reversed by the alpha adrenergic properties of ibopamine for this dose. Ibopamine caused no clinically significant natriuresis in these salt-depleted patients. No changes in PRA, aldosterone and catecholamines were found.

Aged↗

Characterization of hypertensive subjects who become normotensive during three months of office BP follow-up: comparison with subjects with sustained hypertension and normotensives, and follow-up after two years.

After an observation period of three months, 83% of new hypertensives (n = 84), identified in a population survey, became normotensive. Those with sustained hypertension (n = 14) were compared with 14 initially hypertensives who became normotensive and 14 normotensives, matched for age and sex, using ambulatory and exercise BP and echocardiography (both M-mode and Doppler). The initially hypertensive group (n = 11) was re-examined after two years follow-up. The 24h mean ambulatory and submaximal systolic exercise BP did not differ between sustained (139/92 and 210 mmHg) and initially hypertensives (143/95 and 217 mmHg), being significantly lower in the normotensive group (129/85 and 198 mmHg). Left ventricular mass did not differ between the initially hypertensive and the normotensive groups, being significantly higher in the sustained hypertensives. In both hypertensive groups, as compared with normotensives, the ratio between flow velocity in early and late diastole (E/A ratio) tended to be lower and the early diastolic deceleration time (DT) was significantly shorter. After two years, in the untreated initially hypertensives, office DBP had increased to hypertensive values, without change in ambulatory BP, left ventricular mass or early diastolic deceleration time. The E/A ratio had decreased to a level < 1. We conclude that the subjects who became normotensive after three months office BP follow-up have a BP load and signs of compromised left ventricular diastolic function similar to that of the sustained hypertensives, but without increased left ventricular mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Medical treatment of peripheral vascular disease: are there new perspectives?

In Raynaud's phenomenon few new medical treatment options have become available in recent years, but the merits and demerits of drugs already longer available have been established more firmly. Calcium antagonists remain the treatment of first choice even despite their frequent side effects. Prostacyclin analogues are effective but oral formulations are still eagerly awaited. In PAOD attention is shifting from the often disappointing medical treatment of symptoms to possible secondary prevention. Except for the effects of some prostanoids little clinical benefit is obtained from vasodilators and rheologically active drugs. Attempts to influence skeletal muscle metabolism with carnitine-analogues like 1-carnitine are interesting but clinical benefit has not yet been proven. In the next few years results of trials with lipid-lowering drugs to stop progression of atherosclerotic lesions will become available.

Arterial Occlusive Diseases↗

Rheological properties of blood in Raynaud's phenomenon.

Rheological tests were performed in four rigorously defined groups of patients with Raynaud's phenomenon: primary family-related (n = 21), primary family-unrelated (n = 30), 'possible scleroderma' (n = 26), and scleroderma (n = 19). Whole blood and plasma viscosity, and hematocrit were significantly higher in the 'possible scleroderma' group. We conclude that the contribution of central rheological abnormalities in the pathogenesis of Raynaud's phenomenon is limited.

Blood Viscosity↗

Assessment of pinacidil in patients with primary Raynaud's phenomenon.

In fourteen patients with primary Raynaud's phenomenon we performed a double-blind, controlled study, comparing single doses of 12.5 and 25 mg of the potassium channel opener pinacidil with placebo and the active control nifedipine in randomised order. The main response criterium was the area under the curve (AUC) of the photoelectric plethysmography (PEP) during cooling and rewarming, performed 2-3 hours after administration of the study medication. Single doses of 12.5 and 25 mg pinacidil were shown not to be superior to placebo in respect of the AUC of PEP. Nifedipine, on the contrary, was significantly better than placebo. We conclude that no efficacy can be expected from the potassium channel opener pinacidil in the treatment of primary Raynaud's phenomenon. The efficacy of nifedipine cannot be explained from central rheological effects, as total blood viscosity was the same after pinacidil, nifedipine and placebo.

Adult↗

Successful long-term control of idiopathic hypereosinophilic syndrome with etoposide.

A 38-year-old man with idiopathic hypereosinophilic syndrome had an inadequate response to steroids and severe side effects from hydroxyurea treatment, which necessitated withdrawal of the treatment. Successful control of clinical symptoms and eosinophil counts was obtained with etoposide (VP16-213) for 18 months. VP16-213 may be valuable in idiopathic hypereosinophilic syndrome treatment.

Adult↗

The effects of alpha-adrenoceptor blockade on dopamine-induced renal vasodilation and natriuresis.

To establish the effects of alpha-adrenoceptor blockade on dopamine-induced changes in renal hemodynamics and sodium excretion, dopamine dose-response curves were performed without and with pretreatment with the selective postsynaptic alpha 1-adrenoceptor antagonist prazosin in normal volunteers and in patients with renal disease and moderately impaired renal function. Prazosin (1 mg p.o. every 4 h) in 7 volunteers did not significantly affect baseline values but impaired the response of effective renal plasma flow (ERPF) and filtration fraction (FF) to infusions of dopamine in doses ranging from 0.5 to 8 micrograms/kg per minute and completely abolished the dopamine-induced increase in sodium excretion. In 7 patients with renal disease and a glomerular filtration rate (GFR) ranging from 38-85 ml/min pretreatment with prazosin did not affect baseline ERPF, GFR or FF or their response to dopamine infusion, but sodium excretion and its response to dopamine infusion were reduced (fractional excretion of sodium at baseline 1.78 without and 0.89 with prazosin pretreatment). We conclude that alpha 1-adrenoceptor blockade with prazosin abolishes the effects of exogenous dopamine on sodium excretion in normal man. Prazosin also impairs the renal vasodilatory action of dopamine. However, the effect on sodium excretion is not directly related to inhibition of dopamine-induced renal vasodilation since in patients with renal disease prazosin also markedly reduces sodium excretion but does not influence the renal hemodynamic effects of dopamine.

Adult↗

Renal and neurohumoral effects of ibopamine and metoclopramide in normal man.

The effects of 100 mg ibopamine, an orally active nonselective dopamine agonist on renal haemodynamics, sodium excretion, blood pressure (BP), heart rate (HR) and neurohumoral parameters were investigated in 10 healthy volunteers, with and without metoclopramide pretreatment. A small and temporary rise of glomerular filtration rate (GFR) was found after ibopamine without but not with metoclopramide pretreatment. No differences in effective renal plasma flow (ERPF) but a small rise in sodium excretion were observed comparing ibopamine with control. Metoclopramide induced a fall in sodium excretion which was not reversed by ibopamine. Ibopamine failed to affect BP and HR and no changes of PRA or plasma aldosterone concentration (PAC) were found. Metoclopramide induced a pronounced increase of PAC which was blunted by ibopamine. Plasma and urinary catecholamines were unchanged for all study days. We conclude that ibopamine induces natriuresis probably not by the observed small and temporary renal haemodynamic effects but by direct stimulation of DA1 dopamine receptors in the proximal tubule.

Adolescent↗

Effects of cisapride on the esophageal motor function of patients with progressive systemic sclerosis or mixed connective tissue disease.

In a double-blind crossover study lower esophageal sphincter pressure and distal esophageal motility were studied in 10 patients with progressive systemic sclerosis or mixed connective tissue disease, following a single intravenous dose of cisapride or placebo. The measurements were carried out under basal conditions and 30 min after intravenous administration of 10 mg cisapride or placebo. No effects on lower esophageal sphincter pressure or distal esophageal motility were observed.

Adult↗

Transcutaneous electrical nerve stimulation (TENS) in Raynaud's phenomenon.

Transcutaneous nerve stimulation (TENS) has been described as resulting in vasodilatation. The effect of 2 Hz TENS of the right hand during forty-five minutes on skin temperature and plethysmography of the third digit of both hands and feet and on transcutaneous oxygen tension (TcpO2) of the right hand was compared with that of a control study using indifferent stimulation of the iliopsoas region in 8 patients with primary Raynaud's phenomenon. After TENS a slight increase in skin temperature of both hands was found, while plethysmographic amplitude was increased in the contralateral hand only. No changes in TcpO2 occurred. The authors conclude that the observed small effects of TENS are of no clinical value in primary Raynaud's phenomenon.

Adult↗

The oral dopamine agonist, ibopamine, in normal man: effects on rhythm, heart rate, blood pressure and catecholamines.

To evaluate the effects of the oral aselective dopamine congener ibopamine, heart rate, blood pressure, cardiac rhythm, electrocardiographic (ECG) parameters and plasma catecholamines were studied in ten healthy subjects on three occasions: without medication, after 100 mg oral ibopamine and after combined treatment of ibopamine and the dopamine antagonist metoclopramide. Ibopamine was well tolerated by all subjects. No significant changes in heart rate or blood pressure were seen during either ibopamine alone or during concomitant metoclopramide administration. In addition, there were no differences in PR-, QRS- and QTc- intervals on the ECG and plasma norepinephrine, epinephrine and dopamine levels were unchanged. None of the ten volunteers showed proarrhythmia from ibopamine. However, in one subject, episodes of accelerated idioventricular rhythm were observed after ibopamine, which were asymptomatic and did not exceed a rate of 51 beats/minute. During concomitant metoclopramide infusion, ibopamine did not induce accelerated idioventricular rhythm. In conclusion, in healthy subjects ibopamine appears to be a safe drug and causes neither proarrhythmia, nor changes in heart rate, blood pressure, ECG-parameters, or plasma catecholamines.

Administration, Oral↗