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Biomedical subjects

A J Woittiez

Publications and source records attributed to A J Woittiez.

At least 19 recordsLinked to original sources
PubMed2001

Resistance to antihypertensive medication as predictor of renal artery stenosis: comparison of two drug regimens.

BACKGROUND: Renal artery stenosis is among the most common curable causes of hypertension. The definitive diagnosis is made by renal angiography, an invasive and costly procedure. The prevalence of renal artery stenosis is less than 1% in non-selected hypertensive patients but is higher when hypertension is resistant to drugs. OBJECTIVE: To study the usefulness of standardised two-drug regimens for identifying drug-resistant hypertension as a predictor of renal artery stenosis. DESIGN AND SETTING: Prospective cohort study carried out in 26 hospitals in The Netherlands. PATIENTS: Patients had been referred for analysis of possible secondary hypertension or because hypertension was difficult to treat. Patients < or =40 years of age were assigned to either amlodipine 10 mg or enalapril 20 mg, and patients >40 years to either amlodipine 10 mg combined with atenolol 50 mg or to enalapril 20 mg combined with hydrochlorothiazide 25 mg. Renal angiography was performed: (1) if hypertension was drug-resistant, ie if diastolic pressure remained > or =95 mm Hg at three visits 1-3 weeks apart or an extra drug was required, and/or (2) if serum creatinine rose by > or =20 micromol/L (> or =0.23 mg/dL) during ACE inhibitor treatment. RESULTS: Of the 1106 patients with complete follow-up, 1022 had been assigned to either the amlodipine- or enalapril-based regimens, 772 by randomisation. Drug-resistant hypertension, as defined above, was identified in 41% of the patients, and 20% of these had renal artery stenosis. Renal function impairment was observed in 8% of the patients on ACE inhibitor, and this was associated with a 46% prevalence of renal artery stenosis. In the randomised patients, the prevalence of renal artery stenosis did not differ between the amlodipine- and enalapril-based regimens. CONCLUSIONS: In the diagnostic work-up for renovascular hypertension the use of standardised medication regimens of maximally two drugs, to identify patients with drug-resistant hypertension, is a rational first step to increase the a priori chance of renal artery stenosis. Amlodipine- or enalapril-based regimens are equally effective for this purpose.

Adolescent↗
PubMed2000

The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group.

BACKGROUND: Patients with hypertension and renal-artery stenosis are often treated with percutaneous transluminal renal angioplasty. However, the long-term effects of this procedure on blood pressure are not well understood. METHODS: We randomly assigned 106 patients with hypertension who had atherosclerotic renal-artery stenosis (defined as a decrease in luminal diameter of 50 percent or more) and a serum creatinine concentration of 2.3 mg per deciliter (200 micromol per liter) or less to undergo percutaneous transluminal renal angioplasty or to receive drug therapy. To be included, patients also had to have a diastolic blood pressure of 95 mm Hg or higher despite treatment with two antihypertensive drugs or an increase of at least 0.2 mg per deciliter (20 micromol per liter) in the serum creatinine concentration during treatment with an angiotensin-converting-enzyme inhibitor. Blood pressure, doses of antihypertensive drugs, and renal function were assessed at 3 and 12 months, and patency of the renal artery was assessed at 12 months. RESULTS: At base line, the mean (+/-SD) systolic and diastolic blood pressures were 179+/-25 and 104+/-10 mm Hg, respectively, in the angioplasty group and 180+/-23 and 103+/-8 mm Hg, respectively, in the drug-therapy group. At three months, the blood pressures were similar in the two groups (169+/-28 and 99+/-12 mm Hg, respectively, in the 56 patients in the angioplasty group and 176+/-31 and 101+/-14 mm Hg, respectively, in the 50 patients in the drug-therapy group; P=0.25 for the comparison of systolic pressure and P=0.36 for the comparison of diastolic pressure between the two groups); at the time, patients in the angioplasty group were taking 2.1+/-1.3 defined daily doses of medication and those in the drug-therapy group were taking 3.2+/-1.5 daily doses (P<0.001). In the drug-therapy group, 22 patients underwent balloon angioplasty after three months because of persistent hypertension despite treatment with three or more drugs or because of a deterioration in renal function. According to intention-to-treat analysis, at 12 months, there were no significant differences between the angioplasty and drug-therapy groups in systolic and diastolic blood pressures, daily drug doses, or renal function. CONCLUSIONS: In the treatment of patients with hypertension and renal-artery stenosis, angioplasty has little advantage over antihypertensive-drug therapy.

Aged↗
PubMed2000

Incidence and onset of critical illness polyneuropathy in patients with septic shock.

BACKGROUND: To estimate the incidence and onset of critical illness polyneuropathy (CIP) in patients in septic shock. METHODS: Prospective, observational study, no interventions, in a general 9-bed ICU of a large teaching hospital. Twenty-five patients consecutively admitted to the ICU for treatment of septic shock were studied. Within 72 h of admission to the ICU a complete neurological examination and electromyografic studies were done. Studies were repeated weekly until discharge of ICU or death or CIP confirmed. RESULTS: Nineteen patients developed CIP (76%), with a majority (80%) within 72 h after onset of septic shock. All twenty-two patients with multi organ dysfunction syndrome (MODS) had CIP. The three patients without MODS did not have CIP (P<0.01). CONCLUSIONS: In a group of patients suffering from septic shock the incidence of CIP is high (76%). The onset is early, within 72 h after onset of septic shock. CIP is an early feature of MODS, developing after septic shock.

Adult↗
PubMed1999

Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) for ostial atherosclerotic renal-artery stenosis has poor results. Angioplasty with stent placement (PTAS) may be more effective. We undertook a randomised prospective study to compare PTA with PTAS in patients with ostial atherosclerotic renal-artery stenosis. METHODS: Patients with ostial atherosclerotic renal-artery stenosis were assigned to receive PTA or PTAS. Secondary PTAS was allowed if PTA failed immediately or during 6 months' follow-up. Analysis was by intention to treat. FINDINGS: 42 patients were assigned PTA and 43 were assigned PTAS, but one patient in the PTAS group was excluded from the study. Primary success rate (<50% residual stenosis) of PTA was 57% (24 patients) compared with 88% (37 patients) for PTAS (difference between groups 31% [95% CI 12-50]). Complications were similar. At 6 months, the primary patency rate was 29% (12 patients) for PTA, and 75% (30 patients) for PTAS (46% [24-68]). Restenosis after a successful primary procedure occurred in 48% of patients for PTA and 14% for PTAS (34% [11-58]). 12 patients underwent secondary stenting for primary or late failure of PTA within the follow-up period: success was similar to that of primary PTAS. Evaluation based on intention to treat showed no difference in clinical results at six months for PTA or PTAS. INTERPRETATION: PTAS is a better technique than PTA to achieve vessel patency in ostial atherosclerotic renal-artery stenosis. Primary PTAS and primary PTA plus PTAS as rescue therapy have similar outcomes. However, the burden of reintervention after PTA outweighs the potential saving in stents, so primary PTAS is a better approach to use.

Aged↗
PubMed1999

Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function.

OBJECTIVE: We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype 1 (AT1) receptor antagonist that is administered orally as candesartan cilexetil which is converted in the active compound. METHODS: Twenty-three patients were included, divided into groups according to creatinine clearance (cr cl. group A >60 nl x min(-1) x 1.73 m(-2), group B 30-60 ml x min(-1) x 1.73 m(-2) and group C 15-30 ml x min(-1) x 1.73 m(-2)). RESULTS: Trough serum concentrations of candesartan were higher in group C compared with group A. The values did not increase after multiple dosing, indicating absence of accumulation. There was a significant negative correlation between the area under the concentration-time curve extrapolated to time infinity (AUCinf) and the glomerular filtration rate (GFR) indicating a lower renal clearance of candesartan in patients with impaired renal function. The onset of haemodynamic and hormonal effects was gradual. During the single-dose study blood pressure as well as plasma renin activity (PRA) and angiotensin II were unchanged at peak. At day 5 of the multiple-dose study blood pressure was lower and both PRA and angiotensin II were higher compared with baseline. CONCLUSION: Although serum trough levels increased during repeated administration and half-life was higher in patients with impaired renal function, candesartan cilexetil at a dose of 8 mg per day does not lead to drug accumulation in these patients. This dose is effective in lowering blood pressure and appears to be suitable for patients with renal function impairment.

Adult↗
PubMed1999

Neutrophil function capacity to express CD10 is decreased in patients with septic shock.

OBJECTIVE: To evaluate the performance of a newly developed assay to assess neutrophil function capacity. After optimization, the assay was performed on samples derived from patients with septic shock and compared with healthy controls and patients with a systemic viral infection. DESIGN: Prospective evaluation of the performance of a new assay. SETTINGS: Medical intensive care unit, hospital laboratory. PATIENTS: Ten patients with septic shock, ten patients with infectious mononucleosis, and ten healthy controls. MEASUREMENTS AND MAIN RESULTS: We report an assay to assess neutrophil function capacity, in which CD10 membrane expression is measured by FACS before and after in vitro stimulation with Staphylococcus aureus bacteria. This assay evaluates the early activation state of circulating neutrophils and is shown to be of value in diagnosing a sepsis syndrome. First the assay was optimized. As an anticoagulant, sodium-citrate gave the best results. Blood samples must be kept on ice to reduce activation inside the siliconized tube and can be stored in this way for at least 8 hrs without affecting the test results. Kinetic studies showed a maximal expression of CD10 on neutrophils of healthy volunteers after 15 mins of stimulation with S. aureus bacteria. Second, the test was performed on samples derived from ten septic patients and ten patients with infectious mononucleosis. Septic patients had a significantly decreased CD10 expression capacity compared with healthy controls. Patients with infectious mononucleosis have a significantly higher CD10 expression capacity compared with septic patients, but in approximately one-half of them, the expression capacity was below the range found in controls. CONCLUSIONS: These results indicate that in circulating neutrophils, the secretory vesicles have been mobilized completely in patients with septic shock. The assay proves to be of acceptable analytical quality and can be quickly and easily performed. Regarding clinical performance, this assay may be helpful in diagnosing septic shock.

Adolescent↗
PubMed1998

A comparison of the safety and efficacy of mibefradil and nifedipine SR in patients with renal disease and hypertension.

The antihypertensive efficacy and safety of mibefradil and nifedipine SR were compared in 143 patients with chronic renal failure and mild-to-moderate hypertension in a multicenter, double-blind, randomized, parallel-design study. At treatment week 12, a significantly greater decrease in sitting diastolic blood pressure (SDBP) was seen with mibefradil than with nifedipine SR (12.8 mmHg vs 8.1 mmHg, respectively; p = 0.014). A significantly greater number of mibefradil-treated patients achieved normalization of SDBP by week 12 (62% vs 37%; p < 0.01). The changes in renal function parameters and the incidence of adverse events were similar in both groups. In this population, 12 weeks of treatment with mibefradil were more effective than nifedipine SR for lowering blood pressure and had similar effects on renal function parameters.

Adult↗
PubMed1993

Efficacy and tolerability of the renin inhibitor Ro 42-5892 in patients with hypertension.

The efficacy of multiple oral administration of the renin inhibitor Ro 42-5892 [(S)-alpha-](t-butylsulfonyl)-methyl]hydrocinnamamido]-N-[1S , 2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]-imi dazole-4- propionamide] was studied. Forty-nine patients with moderate essential hypertension were randomly assigned to three groups that entered an 8-day double-blind oral treatment period: daily administration of placebo (group A), 300 mg Ro 42-5892 (group B), or 600 mg Ro 42-5892 (group C). Four hours after the last oral drug intake, placebo was administered intravenously to subjects in group A and 100 mg Ro 42-5892 was administered intravenously to subjects in groups B and C. Sitting systolic and diastolic blood pressures were measured on days 1 and 8 with a blood pressure device. On day 1, systolic blood pressure maximally decreased by 13.3 +/- 9.3, 20.2 +/- 11.2, and 24.1 +/- 11.3 mm Hg in groups A, B, and C, respectively (mean +/- SD; p < 0.01 for group A versus group C). Diastolic blood pressure maximally decreased 9.4 +/- 5.7, 13.9 +/- 8.7, and 11.8 +/- 5.7 mm Hg (difference not significant). On day 8, systolic blood pressure maximally decreased 19.5 +/- 16.5, 26.5 +/- 17.4, and 30.5 +/- 18.4 mm Hg and diastolic blood pressure maximally decreased 14.8 +/- 5.0, 16.2 +/- 9.0, and 17.9 +/- 12.7 mm Hg (difference not significant) compared with pretreatment values. Intravenous drug administration did not further reduce blood pressure, suggesting that the mode of action and not the low bioavailability was the limiting factor for the low efficacy.

Administration, Oral↗
PubMed1992

Hemodynamic and humoral effects of the novel calcium antagonist Ro 40-5967 in patients with hypertension.

The tolerability and hemodynamic and humoral effects of the structurally novel calcium antagonist Ro 40-5967 were investigated in 64 patients with hypertension. In a double-blind, placebo-controlled study, ascending oral doses of 50, 100, 150, or 200 mg were administered once daily for 8 days in a solution. Ro 40-5967 was well tolerated up to 150 mg, but treatment was stopped in one patient in the 200 mg group because of bradycardia. Blood pressure was dose-dependently reduced over the full 24-hour dosing period with more pronounced effects on day 8 than on day 1. The maximum blood pressure reduction was obtained after 150 mg (supine blood pressure, -34/-25 mm Hg, p less than 0.001). Despite a slight decrease in supine heart rate, cardiac output increased. PQ time was dose-dependently increased and concentration-effect analysis showed that relevant atrioventricular conduction disturbances occur only at concentrations much higher than those required to reduce blood pressure. Changes in catecholamines, plasma renin activity, and aldosterone were small and inconsistent. In conclusion, Ro 40-5967 has a long-lasting antihypertensive effect after once-daily administration.

Aldosterone↗
PubMed1992

Betaxolol in obese hypertensive patients. Long-term effects on blood pressure and serum lipids.

The antihypertensive and metabolic effects of betaxolol (20 mg/day) were monitored in 40 patients (17 male), aged 54 +/- 2 yr (mean +/- SEM), with moderate essential hypertension. In a subgroup, consisting of 35 obese patients with a Quetelet index greater than 25.0, blood pressure, heart rate, side effects and biochemical variables were registered bi-monthly for a period of 6 months and after a placebo run-in and run-out period of 2 weeks. Betaxolol decreased blood pressure from 165 +/- 3/107 +/- 1 to 151 +/- 3/95 +/- 2 mmHg after 2 weeks and further to 151 +/- 3/93 +/- 2 mmHg after 6 months (p less than 0.001). Ninety percent of the patients responded to therapy with betaxolol. Heart rate fell from 77 +/- 2 to 64 +/- 1 bpm (p less than 0.001). No significant changes were observed in levels of total cholesterol, LDL-cholesterol or HDL-cholesterol. Triglycerides tended to increase from 2.2 +/- 0.3 to 2.8 +/- 0.4 mmol/l after 4 months of treatment (NS). Renal function was not influenced by betaxolol. Side effects, recorded on a standard questionnaire, did not differ between betaxolol and placebo. In conclusion, betaxolol in a fixed dose of 20 mg/day is an effective antihypertensive drug in the long-term treatment of obese, hypertensive patients, without adverse effects on lipoproteins.

Betaxolol↗
PubMed1991

A comparative study of the effects of nitrendipine and enalapril in essential hypertension.

In this study, we compared the effects of nitrendipine (20-40 mg daily) and enalapril (20-40 mg daily) in 44 patients with mild to moderate essential hypertension. After a 4-week placebo period, the patients entered a double-blind, crossover study of 16 weeks, divided by a second 4-week placebo period. Sitting and standing blood pressures (standard mercurymeter) were measured every 2 weeks. Ten patients dropped out, so 34 patients were evaluable. Two patients dropped out because of surgery, one patient was withdrawn because of accelerating hypertension, and seven patients discontinued because of side effects (two on placebo, four on enalapril, and one on nitrendipine). Sitting blood pressures decreased from 172 +/- 3/107 +/- 1 to 159 +/- 3/94 +/- 1 mm Hg on nitrendipine (p less than 0.001) and to 157 +/- 4/96 +/- 2 mm Hg on enalapril (p less than 0.001). The heart rate did not change. Both compounds had no significant effect on serum lipids and on renal function. With regard to side effects, flushing occurred in 10 patients on nitrendipine and in 3 on enalapril (p less than 0.05); cough was noted in 3 patients on enalapril. When using a diastolic pressure less than 95 mm Hg as a response, 72% responded on nitrendipine and 64% on enalapril (n.s.). In conclusion, nitrendipine and enalapril, given as monotherapy, were equally effective antihypertensive agents in this group of patients with uncomplicated, moderate, essential hypertension. The use of either of the tested agents seems to be more limited by its specific side effects than the lack of antihypertensive efficacy.

Blood Pressure↗