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Biomedical subjects

A J Smit

Publications and source records attributed to A J Smit.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effects of amlodipine and lisinopril on left ventricular mass and diastolic function in previously untreated patients with mild to moderate diastolic hypertension.

The aim of the study was to compare the effects of two long-acting antihypertensive agents, the calcium-antagonist amlodipine and the ACE inhibitor lisinopril, on left ventricular mass and diastolic filling in patients with mild to moderate diastolic hypertension from primary care centres. It is a 1-year prospective, double-blind, randomized, parallel group, comparative study. Patients between 25 and 75 years of age with untreated hypertension with elevated diastolic blood pressure (> or = 95 mmHg) on three occasions (twice on the first visit and once only on the second and third visits) were recruited from a population survey. After 4 weeks placebo run-in 71 patients were randomized to dosages of amlodipine 5-10 mg or lisinopril 10-20 mg, which were titrated on the basis of the effects on blood pressure. Fifty-nine patients completed the study period. Primary endpoints were left ventricular mass index and early to atrial peak filling velocity. Office and ambulatory blood pressure and other echocardiographic measurements were considered secondary. Decrease in blood pressure was equal for both treatment regimens. A statistically significant decrease in left ventricular mass index in both treatment groups was observed: -11.0 g/m2 (95% CI: -6.0, -16.1) in the amlodipine group and -12.6 g/m2 (95% CI: -8.2, -17.0) in the lisinopril group. The higher the baseline value of left ventricular mass before treatment, the more the decrease after treatment. Early to atrial peak filling velocity did not change significantly within the treatment groups: +0.07 (95% CI: -0.01, +0.15) in the amlodipine group and +0.01 (95% CI: -0.06, +0.08) in the lisinopril group. However, analysis of time measurements of the early peak showed significant changes for both treatment groups. No significant differences in primary and secondary endpoints between treatment groups were found. Twelve patients did not complete the study, seven in amlodipine and five in lisinopril, basically due to adverse events. The effects of amlodipine and lisinopril on left ventricular mass and early to atrial filling peak velocity after 1 year of treatment in patients with previously untreated mild to moderate hypertension are similar. Further studies are recommended, particularly with a larger sample size and a follow-up of longer duration.

Adult↗
PubMed1997

Evidence for differential sympathetic and parasympathetic reinnervation after heart transplantation in humans.

During heart transplantation (HTX) all neural connections are severed. In humans, signs of autonomic reinnervation have been found. In this study non-invasive tests were used to compare signs of sympathetic and parasympathetic reinnervation. Non-invasive autonomic function tests and heart rate variability parameters (HRV; 24 h electrocardiographic registration) were used to investigate signs of reinnervation. 16 HTX patients (14 males) were compared with age-and sex-matched controls. Parasympathetic heart rate changes in HTX compared to controls were attenuated during the diving test, deep breathing, the Valsalva maneuver and standing up but not during carotid sinus massage. Sympathetic heart rate increases were lower during the cold pressor test and mental stress. The blood pressure responses were comparable to the control group, but not during active standing and tilting. This finding suggests an obligatory 'blood pressure' role for the innervated heart in these two tests. All HRV parameters were lower in HTX. One or more normal parasympathetic responses were found in 13 out of 16 patients versus 4 out of 16 with normal sympathetic responses (p < 0.05). Heart rate variations were less in case of a higher donor age, and higher in case of a longer time after HTX. Parasympathetic signs of reinnervation are more common than sympathetic signs of reinnervation. A higher donor age reduces signs of reinnervation. If the sympatho-vagal balance is a prognostic factor in HTX patients as it is in other cardiac diseases these findings are clinically relevant.

Adult↗
PubMed1997

Arteriolar constriction in mild-to-moderate essential hypertension: an old concept requiring reconsideration?

OBJECTIVE: To investigate differences between in-vivo properties of a vascular bed in hypertensive patients and normotensive controls. DESIGN: Despite the controversy about the origin of essential hypertension and its accompanying vascular changes, it is generally assumed that the characteristic increase in peripheral resistance when hypertension progresses is caused by arteriolar constriction. Yet, there is little experimental evidence that this assumption generally holds in vivo. METHODS: A non-invasive technique was used for studying properties of the complete vascular bed of an upper arm segment under an occluding cuff in 23 previously untreated hypertensive patients and their matched normotensive controls. The method used the segment's electrical impedance to assess the volumes of extravascular fluid and of arterial and venous blood under varying arterial transmural pressures. RESULTS: Compared with that of matched normotensive controls, the compliance of the large arteries of the vascular bed was on average 50.9% lower (P < 0.001) in the hypertensive patients. The compliance of the complete arterial bed at the operating blood pressure level was also lower (40.0%, P < 0.01), but appeared to be significantly higher (45.9%, P < 0.05) at the normotensive blood pressure level. On the venous side, the patients had a higher blood volume (60.0%, P < 0.01) and an increased myogenic response (68.5%, P < 0.05). CONCLUSIONS: The increase in vascular resistance in the hypertensive patients is due primarily to changes in the large and small vessels of the arterial bed. We found no evidence for a generally increased arteriolar constriction.

Adult↗
PubMed1997

Bedside autonomic function testing in patients with vasovagal syncope.

The factors that determine the individual susceptibility to vasovagal syncope (VVS) are largely unknown, including the role of the autonomic nervous system. We therefore studied common vagal and sympathetic reflexes in 12 patients with VVS (mean age 37 (18-75) years, 6 men). The Valsalva maneuver and deep breathing were performed to assess vagal responsiveness and mental arithmetic stress; the cold-pressor test and isometric handgrip were performed to assess sympathetic responsiveness. Standing up was performed to assess the combined responsiveness. With the exception of a subnormal response to deep breathing in one patient, all vagal tests were normal. In contrast, the response to mental stress, the cold-pressor test, and isometric handgrip was subnormal in 4 patients, 6 patients, and 4 patients, respectively. The response to standing up was normal in all patients. It is concluded that many patients with VVS are characterized by normal vagal responsiveness, but sympathetic hyporesponsiveness. Sympathetic hyporesponsiveness might explain the inadequate vasoconstruction, which plays an important, early role in VVS.

Adolescent↗
PubMed1997

Renal function in cancer patients treated with hyperthermic isolated limb perfusion with recombinant tumor necrosis factor-alpha and melphalan.

Hyperthermic isolated limb perfusion (HILP) with recombinant tumor necrosis factor-alpha (r-TNF alpha) and melphalan has been shown to result in a sepsis-like syndrome due to leakage of r-TNF alpha from the perfusion system to the systemic circulation. We have studied renal function parameters in 11 cancer patients, who underwent 12 perfusions. Three patients, perfused with melphalan only, served as controls. All patients treated with r-TNF alpha developed a sepsis syndrome and needed volume replacement and inotropes to remain normotensive; controls had an uneventful postoperative course. Creatinine clearance decreased transiently on the day of perfusion in both groups (mean preperfusion clearance 118 ml/min, mean post-perfusion clearance 68 ml/min, p < 0.02, n = 15). Follow-up measurements of renal plasma flow and glomerular filtration rate in 9 r-TNF alpha-treated patients did not suggest permanent damage. One patient became hypotensive and developed transient multiple organ dysfunction with renal failure needing hemofiltration. In r-TNF alpha-treated patients, but not in controls, a transient increase in clearance of beta2-microglobulin (0.05 vs. 8 ml/min, p < 0.001) and urinary excretion of phosphate (12 vs. 48 mmol/l, p < 0.05) was seen, compatible with proximal tubular dysfunction. These data suggest that HILP with melphalan decreases glomerular function, whether or not r-TNF alpha is added to the perfusion circuit. Extension of the treatment regimen with r-TNF alpha may result in additional proximal tubular dysfunction. If hypotension can be avoided, this deterioration in renal function seems to be transient, with full recovery within weeks.

Antineoplastic Agents, Alkylating↗
PubMed1997

Reproducibility of vitreous fluorophotometry in patients with type 1 diabetes mellitus.

We assessed the day-to-day reproducible of vitreous fluorophotometry in 7 type 1 diabetic patients and in 1 healthy control subject. The coefficient of variation for duplicate measurements was 33.7, 40.3 and 23.6%, for the right eyes, the left eyes and mean values of both eyes, respectively. Assessment of reproducibility in 1 healthy subject, measured 4 times, resulted in coefficients of variation of about 60%. These values are somewhat worse than those obtained by others in healthy subjects. Since technical problems do not seem to play a significant role in this regard, our reproducibility results reflect the true biological variability of the permeability of the blood-retina barrier assessed by vitreous fluorophotometry in diabetic patients. This variability is substantial. Therefore, we conclude that this method is not precise enough to be used in intervention studies with a limited number of subjects.

Adult↗
PubMed1997

High prevalence of concentric remodeling in elderly individuals with isolated systolic hypertension from a population survey.

Echocardiographic determination of left ventricular mass index (LVMI) is shown to be valuable in the assessment of cardiovascular risk. Determination of left ventricular geometry, including concentric remodeling, provides additional prognostic information. In isolated systolic hypertension (ISH), the few echocardiographic studies available show an increased LVMI, but criteria and patient populations differ. No comparison with diastolic hypertension (DH) has been made, nor has left ventricular geometry (with concentric remodeling) been evaluated. We compared both LVMI and left ventricular geometry of newly diagnosed ISH subjects with normotensive and DH subjects, all previously untreated and from the same population. The echocardiographic LVMI of 97 previously untreated ISH subjects (4 x systolic pressure > or = 160 mm Hg, diastolic pressure < 95 mm Hg) was clearly elevated compared with values in age- and sex-matched normotensive subjects (98 and 71 g/m2, respectively; P < .001). The geometric pattern was abnormal in most ISH subjects, with a high prevalence (43%) of concentric remodeling. Both LVMI and left ventricular geometry of ISH subjects did not differ significantly from values in DH subjects (LVMI, 92 g/m2; concentric remodeling, 56%). Sex differences in LV geometry in ISH were present only with the Framingham criteria, not with the Koren criteria. This study shows a high prevalence of concentric remodeling in elderly individuals with previously untreated ISH. The increase of LVMI and abnormality in left ventricular geometry are comparable with those in DH subjects, further defining the place of ISH as a cardiovascular risk factor in the elderly. Whether there are sex differences in cardiac adaptation in ISH and whether the geometric classification can be used to adjust treatment remain to be investigated.

Age Factors↗
PubMed1997

A young female patient with reflex sympathetic dystrophy of the upper limb in whom amputation became inevitable.

Reflex sympathetic dystrophy (RSD) is characterized mostly by: (burning) pain, restricted range of motion, oedema and autonomic disturbances. Amputations in case of RSD patients should only be performed in cases of a dysfunctional limb, life threatening conditions such as untreatable infections or in cases in unbearable pain. The authors describe a patient in whom amputation became inevitable because of threatening infections.

Adult↗
PubMed1996

[Thromboangiitis obliterans (Buerger's disease) in 2 women].

In two female patients with an ischaemic peripheral disease, 49 and 32 years old, thromboangiitis obliterans (Buerger's disease) was diagnosed. One suffered from ulceration of her left second toe, the other from pain of both hands followed by ulceration of two fingers. Both were smokers. Surgical treatment (amputation) was required, and they also had a prostacyclin infusion. They recovered and stopped smoking. Thromboangiitis obliterans is a non-arteriosclerotic, segmental occlusive disease of medium-sized and small arteries and veins, occurring predominantly in young male habitual smokers. In the nineteen-seventy less than 2% were women, but recent publications mention 23%, an increase which may be attributed to increased smoking in women. Recognition of Buerger's disease in women with peripheral occlusive arterial disease is important; the prognosis is good if they stop smoking.

Adult↗
PubMed1996

Predictive value of ambulatory blood pressure shortly after withdrawal of antihypertensive drugs in primary care patients.

OBJECTIVE: To determine whether ambulatory blood pressure eight weeks after withdrawal of antihypertensive medication is a more sensitive measure than seated blood pressure to predict blood pressure in the long term. DESIGN: Patients with previously untreated diastolic hypertension were treated with antihypertensive drugs for one year; these were withdrawn in patients with well controlled blood pressure, who were then followed for one year. SETTING: Primary care. SUBJECTS: 29 patients fulfilling the criteria for withdrawal of antihypertensive drugs. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive value of seated and ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs. RESULTS: Eight weeks after withdrawal of medication, mean diastolic blood pressure returned to the pretreatment level on ambulatory measurements but not on seated measurements. One year after withdrawal of medication, mean diastolic blood pressure had returned to the pretreatment level both for seated and ambulatory blood pressure. For ambulatory blood pressure, the sensitivity and the positive predictive value eight weeks after withdrawal of medication were superior to those for seated blood pressure; specificity and negative predictive value were comparable for both types of measurement. Receiver operating characteristic curves showed that the results were not dependent on the cut off values that were used. CONCLUSION: Ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs predicts long term blood pressure better than measurements made when the patient is seated.

Adult↗
PubMed1996

Prediction of the left ventricular mass from the electrocardiogram in systemic hypertension.

Although echocardiography provides a reliable method to determine left ventricular (LV) mass, it may not be available in all settings. Numerous electrocardiographic (ECG) criteria for the detection of LV hypertrophy have been developed, but few attempts have been made to predict the LV mass itself from the ECG. In a community-based survey program in the general population, 277 subjects were identified with untreated diastolic hypertension (diastolic blood pressure 95 to 115 mm Hg, 3 occasions) or isolated systolic hypertension (diastolic blood pressure <95 mm Hg and systolic blood pressure 160 to 220 mm Hg, 3 occasions). All subjects underwent ECG and echocardiography on the same day. A multiple linear regression analysis was performed using a random training sample of the data set (n = 185). The independent variables included both ECG and non-ECG variables. The resulting model was used to predict the LV mass in the remainder of the data set, the validation sample (n = 92). Using sex, age, body surface area, the S-voltage in V1 and V4, and the duration of the terminal P in V1 as independent variables, the model explained 45% of the variance (r = 0.67) in the training sample and 42% (r = 0.65) in the validation sample. This result exceeded that of 2 existing ECG models for LV mass (r = 0.40 and 0.41). The correlations between LV mass and combinations of ECG variables used for the detection of LV hypertrophy, such as the Sokolow-Lyon Voltage (r = 0.03) and the Cornell Voltage (r = 0.31), were comparatively low. In settings where echocardiography is not available or is too expensive and time-consuming, prediction of the LV mass from the ECG may offer a valuable alternative.

Adult↗
PubMed1996

ROC analysis of noninvasive tests for peripheral arterial disease.

The purpose of this study is to evaluate the diagnostic accuracy of selected noninvasive tests for assessing peripheral arterial disease. The ankle/brachial index (ABI) and the femoral and popliteal pulsatility indices (PI), and combinations of these tests, were evaluated using receiver operating characteristic (ROC) analysis to determine their diagnostic accuracy depending on the localization of the disease. Verification bias, introduced by the preferential selection of patients for angiography based on the noninvasive test results, was examined. This study suggests that, in assessing whether a patient has significant peripheral arterial disease (lesions > or = 50%), determining an ABI is justified (ROC area 0.95 +/- 0.02). For disease localized to the aortoiliac segment, performing a single test, the femoral PI, is sufficient (ROC area 0.80 +/- 0.04). For disease including the femoropopliteal and infrapopliteal segments, a combination of tests is necessary. Utilized threshold values need to be adjusted for verification bias.

Adult↗
PubMed1996

Normal insulin release during sustained hyperglycaemia in hypokalaemic periodic paralysis: role of the potassium channel opener pinacidil in impaired muscle strength.

1. Hypokalaemic periodic paralysis is characterized by attacks of muscle weakness. Glucose, insulin and an abnormal regulation of ATP-sensitive potassium channels may be involved in these attacks. We studied the effect of hyperglycaemia and of the potassium channel opener pinacidil on insulin release and muscle strength in patients with hypokalaemic periodic paralysis. 2. Insulin release was assessed on two occasions in four patients with hypokalaemic periodic paralysis and in eight matched control subjects, with and without treatment with 25 mg pinacidil orally, during a hyperglycaemic glucose clamp at a blood glucose level of 10 mmol/l, in a placebo-controlled, double-blind study. Muscle strength was measured in the hypokalaemic periodic paralysis patients before and during hyperglycaemia using a handheld dynamometer. 3. During the clamp, the mean glucose concentration (10-180 min) in control subjects was 9.9 +/- 0.07 and 10.0 +/- 0.03 mmol/l with and without pinacidil respectively, and in patients with hypokalaemic periodic paralysis was 10.0 +/- 0.04 and 10.1 +/- 0.06 mmol/l respectively (not significantly different). In both groups, the areas under the insulin curve from 0 to 10 min (first-phase insulin release) and from 30 to 180 min (second phase) were not different on the pinacidil study day compared with on the placebo day. The areas under the insulin curve of the first and second phases also did not differ between control subjects and patients with hypokalaemic periodic paralysis (with or without pinacidil). The M/I ratio, a measure of insulin sensitivity, was not different in the two groups. On the placebo day, baseline muscle strength in patients with hypokalaemic periodic paralysis was 165 +/- 16 N for the hip abductors and 168 +/- 19 N for the knee flexors. During the period of hyperglycaemia on the placebo day, muscle strength did not decrease in either muscle group. On the pinacidil study day, an increase in muscle strength was found only in the two hypokalaemic periodic paralysis patients with the lowest mean muscle strength (< 150 N) on the placebo day. The two hypokalaemic periodic paralysis patients with a mean muscle strength on the placebo day > 150 N showed no increase in muscle strength with pinacidil. 4. Insulin secretion and sensitivity were normal in patients with hypokalaemic periodic paralysis. Hyperglycaemia during hyperglycaemic clamping did not provoke paralytic attacks and did not result in a decrease in muscle strength. The potassium channel opener pinacidil had no effect on insulin secretion in hypokalaemic periodic paralysis patients or in normal subjects. Pinacidil may enhance muscle strength in those hypokalaemic periodic paralysis patients who suffer partial paralytic attacks.

Adult↗
PubMed1996

Phentolamine precludes inhibitory effect of the K+ channel opener pinacidil on insulin release.

The K+ channel opener pinacidil, in clinical use as an antihypertensive agent, acts by opening ATP-sensitive K+ channels in striated and smooth muscle cells. In vitro and in vivo studies have suggested that it also diminishes insulin secretion. Insulin secretion can be influenced directly--by acting on the ATP-sensitive K+ channels of the pancreas--or indirectly--by activation of the sympathetic nervous system, caused by vasodilation. Therefore we studied the effect of pinacidil on insulin release after intravenous glucose challenge during alpha-adrenergic blockade with phentolamine. We found, that phentolamine precludes the effect of pinacidil on glucose induced insulin release in healthy man. This finding suggests that the inhibitory effect of pinacidil on insulin release is indirect and due to activation of the sympathetic nervous system. The latter effect is caused by the antihypertensive action of pinacidil. However, the suggestion of others, that pinacidil inhibits insulin secretion secretion via a direct action on ATP-sensitive K+ channels can not be excluded.

Adrenergic alpha-Antagonists↗
PubMed1996

Lack of specific renal haemodynamic effects of different doses of dopamine after infrarenal aortic surgery.

Dopamine is administered frequently in the operating theatre and intensive care unit patients undergoing mechanical ventilation with the aim of specifically enhancing renal blood flow. In an uncontrolled, open study, we administered sequentially different doses of dopamine (0, 2, 4, 8 and 0 microgram kg-1 min-1) during a 1-h period each. Systemic haemodynamic and renal haemodynamic variables were measured simultaneously using a pulmonary artery catheter and radiopharmaceuticals, respectively. We studied seven haemodynamically stable patients (mean age 66 yr), with a serum creatinine concentration < 160 mumol litre-1, after elective infrarenal abdominal aortic reconstruction. All patients received extradural analgesia with bupivacaine and sufentanil, and none had a previous history of heart failure. Dopamine induced a dose-dependent increase in cardiac index which returned to baseline after cessation of the dopamine infusion. Glomerular filtration rate (GFR) increased with all doses of dopamine, whereas renal blood flow (RBF) increased significantly only with the 2- and 4-microgram kg-1 min-1 doses. However, the ratio RBF/cardiac output remained unchanged with the 2- and 4-microgram kg-1 min-1 doses, but decreased with 8 micrograms kg-1 min-1 from 14 (1.5)% to 10 (1.3)%. We conclude that dopamine increased RBF and GFR as a result of an increase in cardiac output.

Aged↗
PubMed1996

Alteration of peripheral vasodilatory reserve capacity after cardioversion of atrial fibrillation.

In atrial fibrillation, exercise capacity is often reduced. This is usually ascribed to a decreased cardiac output as compared with sinus rhythm. Very few studies, however, have focused on changes in the peripheral blood flow during atrial fibrillation as a potential mechanism for exercise limitation. The aim of the present study was to determine the effect of conversion of atrial fibrillation to sinus rhythm on peripheral blood flow. Calf blood flow, using an electrocardiogram-triggered venous occlusion plethysmograph, and peak oxygen consumption (peak VO2), using treadmill exercise testing, were studied in 28 patients with chronic atrial fibrillation eligible for electrical cardioversion. Measurements were performed before cardioversion, and repeated 1 day and 1 month thereafter. Calf blood flow at rest, maximal calf blood flow, and minimal calf vascular resistance during the hyperaemic response immediately following 700 J of calf exercise were determined plethysmographically. One day and 1 month after cardioversion, 23 and 14 patients were still in sinus rhythm, respectively. In patients who still had sinus rhythm after 1 month, maximal calf blood flow increased from 33.7 +/- 12 to 40.0 +/- 13 ml. 100 ml-1.min-1 (P < 0.01) and minimal calf vascular resistance fell from 3.2 +/- 0.9 to 2.7 +/- 0.7 mmHg. ml-1. 100 ml-1. min-1 (P < 0.01); peak VO2 increased from 21.3 +/- 4 to 24.2 +/- 5 ml. min-1. kg-1 (P < 0.001). Calf blood flow at rest did not improve. In contrast, no significant changes in maximal calf blood flow, minimal calf vascular resistance and peak VO2 occurred in patients who had atrial fibrillation 1 month after cardioversion. A significant correlation was found between changes in maximal calf blood flow and peak VO2 1 month after cardioversion (r = 0.53, P < 0.01). One day after cardioversion, no changes in calf blood flow or peak VO2 were found, either in patients with sinus rhythm or atrial fibrillation. In conclusion, transition from chronic atrial fibrillation to sinus rhythm is associated with a (delayed) improvement in maximal calf blood flow, minimal calf vascular resistance, and peak VO2. Our findings suggest that increase in vasodilatory reserve capacity may contribute to the improvement of exercise capacity after cardioversion of atrial fibrillation.

Aged↗