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Biomedical subjects

T Thien

Publications and source records attributed to T Thien.

At least 19 recordsLinked to original sources

The influence of different beta-blocking drugs on the peripheral circulation in Raynaud's phenomenon and in hypertension.

In a double-blind, randomized, placebo-controlled study, the authors investigated the effects of different beta-adrenoceptor blocking drugs on the peripheral circulation. A single intravenous injection of the nonselective beta-blocker propranolol (0.20 mg/kg), the beta 1-selective adrenoceptor blocker metoprolol (0.25 mg/kg), and the nonselective beta-blocker with partial agonistic activity (PAA) pindolol (0.04 mg/kg) and of placebo (saline) was given to eight patients with a primary Raynaud's phenomenon and to nine untreated patients with primary hypertension. The authors measured finger skin temperature (FST), and laser Doppler estimated finger skin blood flux (LDF) before, during, and after a standardized finger cooling test, performed 25 minutes after the administration of the drugs. In both patients groups propranolol, metoprolol, and pindolol had no significant effect on FST and LDF in the first 25 minutes after administration both in comparison to baseline value and to placebo. Also, no significant differences were found in the recoveries of FST and LDF after cold challenge between all drugs and placebo in both groups. The authors conclude that no adverse effect of any type of beta-adrenoceptor blocker in comparison to placebo could be detected after a single administration on both the baseline finger skin perfusion and the recovery after cold-induced vasoconstriction. In addition, the authors could not demonstrate a favorable effect of beta 1-selectivity or PAA in comparison to a nonselective beta-adrenoceptor blocker without PAA, in any group.

Adrenergic beta-Antagonists

Does treatment with beta-adrenergic blocking agents cause a decrease in beta 2-adrenoceptor affinity?

The effect of beta-adrenoceptor antagonists (BAAs) differing in lipophilicity and partial agonist activity (PAA), and a full agonist, on the dissociation constant for [125I]-(-)- iodocyanopindolol binding to beta 2-adrenoceptors (KD) has been investigated. Twelve healthy, normotensive male volunteers (mean age 22.3 y) were treated with different BAAs according to a cross-over design. The drugs used were propranolol (highly lipophilic BAA, no PAA), pindolol (moderately lipophilic BAA, strong PAA), dilevalol (highly lipophilic BAA, weak PAA) and salbutamol (full agonist). Before and after a single dose and an 8 day course of one of the drugs, blood pressure and the beta 2-adrenoceptor characteristics of mononuclear leukocytes (MNL) were determined. Between the treatment periods, there was a washout interval of 14 days. All BAAs decreased the blood pressure, but only propranolol lowered heart rate. Treatment with salbutamol decreased the diastolic and increased the systolic blood pressure and heart rate. Three hours after the single dose of any of the BAAs, a more than 2-fold increase in KD was observed, and the increase became larger after 8 days of administration (up to 3.7-fold increase). In contrast, no effect on KD was observed after treatment with salbutamol. BAAs with PAA and salbutamol induced a 30% decrease in beta 2-adrenoceptor density. It is concluded that treatment with BAAs, irrespective their lipophilicity or PAA, induces a decrease in the affinity of MNL beta 2-adrenoceptors for antagonists. This phenomenon may help to explain the contradictory relationship between the kinetics and dynamics of BAAs.

Adrenergic beta-Antagonists

Kinetics of atrial natriuretic peptide in young and elderly subjects.

To study the influence of age on the kinetics of atrial natriuretic peptide (ANP) in man, human (99-126) ANP 2.0 micrograms.min-1 was infused IV for 60 min in 8 healthy young (18 to 25 y) and 9 healthy elderly (71 to 84 y) subjects. Both baseline ANP values and the levels at the end of infusion were higher in the elderly subjects. The mean residence time of ANP in the two age groups was not significantly different, whereas total body clearance (CL) was markedly diminished in the elderly as compared to the young subjects (mean +/- SD 3.1 +/- 1.0 l.min-1 and 6.2 +/- 4.1 l.min-1, respectively). The apparent volume of distribution at steady state was lower in the elderly than in the young, but the difference was not significant (mean +/- SD 44 +/- 19 and 103 +/- 111, respectively. The decrease in CL largely explained the higher ANP levels found in the elderly subjects. The MRT and the plasma half-life of the terminal phase did not differ between the two groups. In the elderly but not in the young subjects the calculated endogenous creatinine clearance was closely correlated with the CL (r = 0.90, P less than 0.001), thereby emphasizing the importance of the kidney in the metabolic clearance of ANP in the elderly.

Adolescent

Value of the plasma norepinephrine/3,4-dihydroxyphenylglycol ratio for the diagnosis of pheochromocytoma.

PURPOSE: The purpose of this study was to assess whether the plasma norepinephrine/3,4-dihydroxyphenylglycol ratio (NE/DHPG) is of diagnostic relevance for patients with a pheochromocytoma. SUBJECTS AND METHODS: In 18 patients with a histologically proven pheochromocytoma and in nine patients with congestive heart failure, plasma levels of NE, epinephrine (EPI), and DHPG (radioenzymatic method) were determined after 20 minutes of supine rest. In 10 healthy subjects, the plasma catecholamine responses to active standing (5 minutes) and mental arithmetic (5 minutes) were measured. From the plasma NE and DHPG levels, the plasma NE/DHPG ratio was calculated. In order to analyze whether NE or EPI was the major secreted catecholamine, the patients with a pheochromocytoma were divided into two groups based on the increase of plasma NE above normal relative to that of EPI: Group 1 included patients with increased plasma NE or increased plasma NE and EPI. Group 2 included patients with increased plasma EPI in combination with a nearly normal NE. RESULTS: Both active standing and mental arithmetic increased the plasma NE/DHPG ratio by 105% and 13.6%, respectively, but in all subjects the ratio did not exceed 1.0. Patients with heart failure demonstrated a threefold higher plasma NE/DHPG ratio than did healthy subjects, and the ratio also did not exceed 1.0. The plasma NE/DHPG ratio was about seven to eight times higher in Group 1 (mean: 1.62, range: 0.81 to 2.84) than in Group 2 (mean: 0.24, range: 0.12 to 0.68). Nearly all patients in Group 1 had a NE/DHPG ratio that was higher than 1.0. In contrast, five of six samples of Group 2 demonstrated a NE/DHPG ratio within the normal range. The calculated positive and negative predictive values of a basal plasma catecholamine level were higher than that for the plasma NE/DHPG ratio. CONCLUSIONS: In contrast to earlier reports, a normal plasma NE/DHPG ratio does not exclude the presence of a pheochromocytoma. In patients with a pheochromocytoma that produces EPI predominantly, this ratio may be normal. On the other hand, in patients with congestive heart failure, the plasma NE/DHPG ratio is increased, although there is no clear overlap with values of patients with a pheochromocytoma. Although the prevalence of pure EPI-producing pheochromocytomas is low, the plasma NE/DHPG ratio should be used with caution in the diagnostic evaluation of patients with a suspected pheochromocytoma.

Adrenal Gland Neoplasms

An automated computerized method using Finapres for measuring cardiovascular reflexes.

1. The major drawback of the cardiovascular reflex tests used to study autonomic failure is the time involved in calculating the results. To overcome this disadvantage, we have developed an automated computerized program using a FINger Arterial PRESsure instrument for the measurement of beat-to-beat heart rate and blood pressure on a finger. 2. This program calculates heart rate variability during three standardized tests, forced breathing, standing up and the Valsalva manoeuvre, and records blood pressure values in response to standing up and sustained handgrip. The time taken to perform the test and to calculate the results is usually 25 min. 3. The reproducibility of the tests in 21 normal subjects was comparable with the reproducibility obtained with conventional test methods using an ECG and a sphygmomanometer. 4. In addition, we determined the age-dependent normal values of the seven test parameters in 124 subjects aged 20-90 years. 5. Using this program in 10 patients with longstanding (14-50 years) complicated diabetes, in each of them four or more abnormal test results were found.

Adult

Reproducibility of electrocardiographic criteria for left ventricular hypertrophy in hypertensive patients in general practice.

Before changes in ECG voltage criteria can be accepted as evidence for changes in LVH, the variability of ECG measurements must be known. Here we report on the results of a study, on the variability of electrocardiographic single lead voltage parameters and (voltage) criteria for left ventricular hypertrophy in hypertensive patients in general practice. Two electrocardiograms were recorded, from 64 patients at an interval of 2 min, to measure the minute-to-minute variability. From 77 patients, two electrocardiograms were recorded at an interval of one week to measure the day-to-day variability. The coefficient of variation of voltage parameters for single leads ranged in the day-to-day group from 9.2% in R/I to 42% in T/V1, and the coefficient of variation for voltage combinations in this group ranged from 10.0% for the Sokolow-Lyon criteria to 13.7% for Gubner-Ungerleider criteria. The reclassification percentages in the day-to-day group ranged from 0% for Gubner-Ungerleider to 17% for Minnesota code criteria. A factor analysis showed that studies which use the Romhilt-Estes score, the Sokolow-Lyon or the Minnesota criteria to detect ECG-LVH are not comparable with studies which use the Cornell or Gubner-Ungerleider criteria.

Aged

Doppler ultrasound scanning in the detection of renal artery stenosis in hypertensive patients.

The diagnostic accuracy of Doppler ultrasound in the detection of renal arterial disease has been assessed in a prospective study of 61 hypertensive patients. The findings of Doppler ultrasound were compared with the results of renal angiography. In 15 patients (24.5%) no accurate Doppler signs could be obtained and the Doppler ultrasound examination was considered a technical failure. Of the remaining 46 patients, 24 had renal artery stenosis. Nine of the stenoses were not detected by Doppler ultrasound and in three patients a false positive diagnosis of renal artery stenosis was made. The sensitivity of Doppler ultrasound was 62.5%, the specificity 86.4% and the overall diagnostic accuracy was 73.9%. By comparing the 15 patients in whom Doppler ultrasound failed with the 46 in whom it was successful, age appeared to be higher and creatinine clearance lower in the failure group. By comparing the 34 patients with true positive and true negative results with the 12 patients with false results, no significant differences were found. In a multivariate analysis, higher age showed a significant relation to failure of Doppler ultrasound. Doppler ultrasound has limited value in the screening of hypertensive patients for renal artery stenosis.

Female

First dose hypotension after captopril; can it be predicted? A study of 240 patients.

We have studied prospectively the acute blood pressure lowering effect on an oral dose of captopril, 25 mg in 240 hypertensive patients. The mean relative reduction of systolic and diastolic BP was 16 and 15% respectively and the mean time to the mean arterial pressure nadir was 59 minutes. Systolic BP fell by more than 30% in 4.6% of patients and diastolic BP and mean arterial pressure dropped by more than 30% in 4.2 and 3.3% of patients respectively. Patients over 60 years of age showed a significantly larger fall in systolic and diastolic BP. Patients with renal artery stenosis reached the BP nadir in a significantly shorter time compared with patients with essential hypertension (50.5 vs. 59.7 minutes, P less than 0.05) and showed a significantly larger fall in systolic BP (20.7 vs. 15.4%, P less than 0.05). A forward stepwise regression analysis showed that only baseline plasma renin activity had a significant relation to the fall in BP (P less than 0.01, R = 0.57). We conclude that according to our definition of a greater than 30% decrease of the mean arterial pressure, a first dose hypotension after captopril was seen in 3.3% of 240 patients. Captopril treatment should be introduced carefully since not all those patients at risk of hypotension can be identified in advance.

Aldosterone

Dose-dependent inhibition of the hemodynamic response to dipyridamole by caffeine.

We investigated the effects of the adenosine antagonist caffeine on the hemodynamic response to dipyridamole infusion (0.4 mg/kg for 4 minutes). According to a randomized, placebo-controlled double-blind protocol, eight normotensive volunteers each participated in five tests: placebo after placebo, dipyridamole after placebo, and dipyridamole after 1, 2, and 4 mg/kg caffeine. Infusion of caffeine alone (4 mg/kg) induced an increase in mean arterial pressure of 6.1 +/- 0.5 mm Hg versus 1.5 +/- 0.9 mm Hg after placebo (p less than 0.05). Infusion of dipyridamole alone exerted a characteristic hemodynamic response with an increase in systolic blood pressure (+8.4 +/- 2.4 mm Hg), pulse pressure (+7.0 +/- 2.4 mm Hg), heart rate (+25.7 +/- 3.8 beats/min) and calculated rate-pressure product (+3419 mm Hg x beats per minute), all being significantly different from the changes induced by placebo. Caffeine induced a dose-dependent attenuation of the response to dipyridamole, with a significant negative correlation between the dose of caffeine on the one hand (0, 1, 2, and 4 mg/kg) and the dipyridamole-induced increments in systolic blood pressure (r = -0.53), pulse pressure (r = -0.50), heart rate (r = -0.95), and rate-pressure product (r = -0.93) on the other hand. We conclude that caffeine attenuates the hemodynamic response to dipyridamole infusion in humans in a dose-dependent fashion. Because of the wide-spread use of caffeine, this pharmacologic interaction may be of clinical importance, for example, in the diagnostic use of dipyridamole in thallium-201 myocardial imaging.

Adult

Adrenoceptors on blood cells from patients with primary Raynaud's phenomenon.

1. alpha 2-Adrenoceptors on platelet membranes and beta 2-adrenoceptors on lymphocytes were studied in 24 patients with primary Raynaud's phenomenon and in 24 age- and sex-matched control subjects. In two subgroups, a standardized mental arithmetic test and a finger-cooling test were performed. 2. Baseline blood pressure, heart rate and forearm blood flow did not differ between the two groups. 3. Baseline skin microcirculation (laser Doppler flux) was decreased in primary Raynaud's phenomenon (19 +/- 15 arbitrary units) compared with control subjects (33 +/- 14 arbitrary units) (P less than 0.01). 4. Baseline plasma noradrenaline concentration (2.00 +/- 1.44 versus 1.16 +/- 0.36 nmol/l) and alpha 2-adrenoceptor density (301 +/- 119 versus 210 +/- 82 fmol/mg) were increased in patients with primary Raynaud's phenomenon in comparison with the control subjects. The alpha 2-adrenoceptor density/beta 2-adrenoceptor density ratio in patients with primary Raynaud's phenomenon was, with a value of 0.37 +/- 0.04, higher than in the control subjects, where a value of 0.25 +/- 0.02 was measured (P less than 0.001). Plasma adrenaline concentration, beta 2-adrenoceptor density and the antagonist affinity to both receptor subtypes did not differ between both groups under baseline conditions. 5. Whereas during the finger-cooling test no differences were seen in the responses of the parameters measured, the mental arithmetic test induced an increase in laser Doppler flux in patients with primary Raynaud's phenomenon and a decrease in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Role of the wrist cuff in forearm plethysmography.

1. To determine whether a wrist cuff is necessary to measure the forearm blood flow correctly, we studied the effects of wrist cuff inflation to supra-venous and supra-systolic pressure values over a large range of forearm blood flow values: in the basal state, during post-occlusive hyperaemia of the hand, and during heating of the hand with warm air. Eleven healthy men participated, and the study was carried out at two different ambient temperatures of 20 and 25 degrees C. 2. In the basal state, the measured forearm blood flow was lowest with the wrist cuff at supra-systolic pressure. With the wrist cuff at supra-venous pressure the forearm blood flow was also lower than with an uninflated cuff, but only significantly so when the basal forearm blood flow was higher (at a room temperature of 25 degrees C). 3. During post-occlusive hyperaemia, inflating the wrist cuff to supra-systolic pressure produced the lowest forearm blood flow value at both room temperatures. In addition, with the wrist cuff at supra-venous pressure, forearm blood flow values were lower than with the uninflated cuff, but the supra-venous cuff pressure was clearly less efficient in excluding the hand blood flow than the supra-systolic cuff pressure. 4. During heating of the hand, both supra-systolic and supra-venous cuff pressures were effective in excluding the hand blood flow at both room temperatures. The forearm blood flow measured with the wrist cuff at supra-systolic pressure was lower than that measured with the wrist cuff at supra-venous pressure, but the difference was only significant at a room temperature of 20 degrees C. 5. In conclusion, we have demonstrated that a wrist cuff at supra-systolic pressure is most appropriate for the exclusion of the hand circulation in order to measure the forearm blood flow correctly.

Forearm

The effect of caffeine on renal vein renin concentration in patients with renal arterial disease.

The aim of this study was to investigate whether caffeine stimulates selectively renal vein renin levels at the side of unilateral stenosis in patients with renovascular hypertension. In this study seven of the involved patients had renal arterial stenosis and four had no stenosis. Four of the seven patients with a stenosis had retrospectively-proven renovascular hypertension. Renal vein renin sampling was performed before and after intravenous administration of caffeine. Caffeine did not induce any consistent effect on plasma renin activity in the renal veins, either on the stenotic side or on the contralateral side in patients with renovascular hypertension. There were no consistent caffeine mediated changes in systemic plasma renin activity.

Caffeine

Adenosine attenuates the vasoconstrictor response to the cold pressor test in humans.

The forearm vasoconstrictor response to a standardized cold pressor test (CPT) was studied twice in eight healthy subjects, once during local intraarterial infusion of adenosine and once during infusion of equipotent dosages of the control vasodilator sodium nitroprusside (SNP). During local SNP infusion, the forearm vascular resistance (FVR) decreased from 70 +/- 14 to 30 +/- 7 arbitrary units (AU). Adenosine induced a comparable vasodilator response, with a decrease in FVR from 56 +/- 14 to 28 +/- 6 AU. Subsequent cold exposure induced a mean percentage increase in FVR of 62 +/- 17% during SNP, whereas the increase was only 27 +/- 12% during adenosine infusion (p = 0.014). There were no differences in the calculated cold-induced changes in forearm production of norepinephrine (NE) between the SNP and the adenosine tests. We conclude that adenosine attenuates forearm vasoconstrictor response to the CPT, probably by a postjunctional mechanism of action.

Adenosine

Age-dependent vasodilation of the skin microcirculation by atrial natriuretic factor.

The microcirculatory responses to systemically administered alpha-human atrial natriuretic factor [99-126)hANF) (ANF) were investigated in the skin of eight young (18-25 years) and eight elderly (71-84 years) healthy volunteers in a double-blind, randomized, placebo-controlled study. Laser-Doppler flux (LDF), transcutaneous oxygen pressure (TcPO2), and skin temperatures on the finger (Td) and on the cheek (Tc) were measured during 60 min of i.v. ANF administration at a low rate (0.25 micrograms/min), resulting in plasma ANF concentrations in the upper normal range, and at a high rate (2.0 micrograms/min), inducing a 17- to 23-fold increase in plasma ANF. ANF infusion did not induce consistent changes in TcPO2 or Td at either rate. Placebo-corrected LDF increased significantly following low-rate ANF infusion in the elderly but remained unchanged in the young (mean +/- SD) +22 +/- 21% (p less than 0.05) and +7 +/- 32% (p greater than 0.1), respectively; following high-rate ANF infusion in LDF the changes were greater, with +28 +/- 56% and +19 +/- 42%, respectively. Because of the large SD the increases were no longer significant. During high-rate ANF infusion Tc remained unchanged in the young, but in the elderly Tc decreased--1.1 +/- 1.3% (p less than 0.05), which is probably due to the fall in blood pressure, which was more pronounced in the elderly than in the young: mean arterial blood pressure (MAP) decreased -9 +/- 3% (p less than 0.05) in the elderly and just -6 +/- 3% (p less than 0.05) in the young, both corrected for placebo changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Double-blind placebo-controlled crossover study of oral nicardipine in the treatment of Raynaud's phenomenon.

The purpose of this study was to measure the efficacy and side effects of oral nicardipine in the treatment of Raynaud's phenomenon (RP). The study consisted of a 3-week baseline period followed by a double-blind, randomized, two-period placebo-controlled, balanced crossover design. Both treatment periods of 3 weeks with either oral nicardipine (3 x 30 mg) or matching placebo were interrupted by a 2-week washout period. Twenty-five patients with either primary (n = 16) or secondary (n = 9) RP participated. Twelve of them had taken part in a previous study on the acute effects of i.v. nicardipine to find out whether long-term efficacy could be predicted by the acute circulatory effects. No statistically significant differences were found between nicardipine and placebo for number, duration, or severity of vasospastic attacks or for any of the microcirculatory parameters (finger skin temperature and laser Doppler flux) measured during a finger cooling test. In patients with primary RP, heart rate significantly increased during nicardipine treatment (mean +/- SD: 9 +/- 6 beats/min; p less than 0.05). The long-term effects could not be predicted by the outcome of the i.v. study. Plasma nicardipine concentrations varied considerably, but in general were on the low side (17.4 +/- 3.7 ng/ml; range, 0-55.4 ng/ml). The adverse effects reported with nicardipine were similar to those with placebo, and required withdrawal of two patients on nicardipine and one on placebo. In conclusion, the results show that oral nicardipine does not significantly alter the course of RP.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Poikilothermia in man: pathophysiology and clinical implications.

Poikilothermia, the inability to maintain a constant core temperature independent of ambient temperature, markedly influences both the mental and physical function of affected patients; furthermore, prolonged hypothermia can induce numerous complications. To establish the pathophysiology of thermoregulation underlying poikilothermia in man, we compared 4 women with acquired poikilothermia, with 9 female control subjects. The activity of the main thermoregulatory effector mechanisms was assessed in a thermoneutral environment, and during subsequent cold stress and heat exposure. At thermoneutrality the patients had a significantly lower rectal temperature and resting metabolic rate compared with the controls; no patient showed peripheral vasoconstriction or shivering. Cooling revealed markedly reduced peripheral vasoconstriction in 3 patients and failure of the metabolic response in 2 patients; unlike controls, no patient exhibited shivering. Heat challenge revealed severely reduced capacity for heat dissipation in all patients. We conclude that in patients with poikilothermia, the mechanisms for both heat conservation and heat dissipation are seriously attenuated. Careful monitoring of the core temperature and adequate measures to maintain normothermia are of great importance in patients with poikilothermia in order to provide adequate treatment, improve the quality of life, and prevent serious complications.

Adipose Tissue