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Biomedical subjects

A Distler

Publications and source records attributed to A Distler.

At least 145 records · Page 8Linked to original sources
PubMed1990

Soluble interleukin 2 receptor and tissue polypeptide antigen serum concentrations in end-stage renal failure.

Serum concentrations of soluble interleukin 2 receptor (IL-2R) were measured in 65 hemodialysis patients and compared with serum levels of beta 2-microglobulin and tissue polypeptide antigen (TPA). Elevated IL-2R levels, found in 85% of examined patients, correlated with elevated TPA serum concentrations (p less than 0.05). Patients with high IL-2R levels were significantly younger (p less than 0.05) than patients with low levels. Primary renal disease and residual renal function had no significant influence on TPA or IL-2R serum concentrations. In 16 patients with carpal tunnel syndrome, increased serum concentrations of IL-2R (p less than 0.005) and TPA (p less than 0.001) were found. We conclude that a non-specific dialysis-induced activation of epithelial and lymphoid cells rather than a specific immune response could explain the concomitant elevation of IL-2R and TPA serum concentrations in hemodialyzed patients. Patients with pronounced cell turnover, reflected by elevated IL-2R and TPA levels, may show an increased susceptibility to dialysis-associated amyloidosis.

Aged↗
PubMed1990

Salt sensitivity in humans is associated with abnormal acid-base regulation.

Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis, we performed arterial blood gas analyses in young (20-31 years old) normotensive subjects (n = 40) who were placed on a low salt diet (20 mmol NaCl/day) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a randomized, single-blind crossover order. Furthermore, a subset of the subjects (seven salt-sensitive and eight salt-resistant) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week. During each regimen, blood pressure as well as arterial pH and bicarbonate levels were measured. Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg (mean of 30 readings taken during each diet, p less than 0.05) while the subject was on the low salt diet. According to this definition, 16 subjects were salt-sensitive and 24 salt-resistant. During the high sodium chloride regimen, arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group (p less than 0.0001). The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH (r = -0.57, p = 0.0002) and bicarbonate levels (r = -0.52, p = 0.0007) during the high salt diet. Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects; sodium citrate did not. Sodium citrate led to an increase in pH and bicarbonate levels in both groups. Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects.

Acid-Base Equilibrium↗
PubMed1990

Clinical aspects of antihypertensive therapy with urapidil. Comparison with hydrochlorothiazide.

To define the efficacy and tolerability of urapidil as a monotherapy in ambulatory patients with hypertension, we compared urapidil with a standard first-line antihypertensive agent, hydrochlorothiazide (HCT), in a multicentre general practice trial. The study was an 8-week double-blind randomised parallel-group comparison, with a 3-week pretreatment phase (1 week of gradual reduction of antihypertensive agents, 2 weeks of placebo). Blood pressure and heart rate were monitored using an automatic device (boso-digital S II), in the morning after the last intake of medication in the evening before. The dosages of urapidil used were 30mg, 60mg or 90mg twice daily; the dosages of HCT were 12.5 mg/day or 12.5 or 25mg twice daily. If necessary, dosage adjustments were performed every 2 weeks. Data from 165 patients could be evaluated (urapidil, n = 78; HCT, n = 87). Sitting blood pressure was reduced significantly, by 9.4/7.1 mm Hg with urapidil and by 20.7/11.2 mm Hg by HCT. The effect of HCT on systolic (p less than 0.001) and diastolic (p less than 0.05) blood pressure was significantly more pronounced than that of urapidil. The response rates (diastolic blood pressure decreased to less than or equal to 90mm Hg or by greater than or equal to 10mm Hg) were 36% of patients with urapidil and 56% with HCT. Heart rate was not significantly affected by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1990

Clinical aspects during therapy with the serotonin antagonist ketanserin.

Ketanserin, a selective S2-serotoninergic antagonist with an additional alpha 1-receptor-blocking effect and a central component of action, represents a new type of antihypertensive drug. It decreases blood pressure by reducing total peripheral resistance. Cardiac output and heart rate remain practically unaltered. The antihypertensive effect of 2 x 20 to 2 x 40 mg/day corresponds to that of therapeutic doses of metoprolol, nifedipine, hydrochlorothiazide or captopril. The main subjective side effects are somnolence, dizziness and dryness of the mouth. No serious metabolic side effects have been observed. Ketanserin can lead to a prolongation of the QTc interval and therefore should not be given to patients with preexisting QTc prolongation, atrioventricular or sinoauricular block of higher degree or with severe bradycardia (less than 50/min). If a diuretic is to be prescribed simultaneously, it must contain a potassium-sparing component. Since its antihypertensive effect is more pronounced in older age, ketanserin should preferentially be given to patients over 60 years of age.

Adrenergic beta-Antagonists↗
PubMed1989

[Treatment of hypertension in the aged].

Previous studies carried out on the treatment of hypertension in the elderly patient indicate that, in this group of patients, antihypertensive treatment can reduce cardiovascular mortality mainly by reducing mortality from cerebrovascular diseases. To date, the success of hypertensive treatment in over-80-year-olds with uncomplicated hypertension, and patients with isolated systolic hypertension, has not been documented. In the treatment of the elderly patient, age-specific pathophysiological changes need to be taken into account. Such changes are deteriorating renal performance, increased vasoconstriction, decreasing baroreceptor function, declining cardiac performance, and changes in the autoregulation of cerebral blood flow. For this reason, in geriatric hypertensives, the blood pressure should be reduced gradually over a period of weeks. Antihypertensive drugs with a natriuretic or vasodilative effect are pathophysiologically meaningful, while substances that result in a loss of potassium, depression of the sympathetic nervous system and negative inotropism are not so favorable.

Aged↗
PubMed1989

Verapamil versus hydrochlorothiazide in the treatment of hypertension: results of long term double blind comparative trial. Verapamil versus Diuretic (VERDI) Trial Research Group.

OBJECTIVE: To compare the efficacy and tolerability of hydrochlorothiazide, sustained release verapamil, and their combination in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial of 48 weeks' duration with a double blind comparison of hydrochlorothiazide and verapamil followed by an open trial of combined treatment for patients not achieving the target diastolic blood pressure (less than 90 mm Hg) during treatment with a single drug. SETTING: Outpatient departments in 10 clinics and 10 private practices of general practitioners or internists. PATIENTS: 369 Hypertensive patients with a diastolic blood pressure of 95-120 mm Hg during a placebo run in period of two weeks. INTERVENTIONS: Initial treatment consisted of 12.5 mg hydrochlorothiazide (n = 187) or 120 mg sustained release verapamil (n = 182) once daily (regimen I). If the target diastolic blood pressure of less than 90 mm Hg was not achieved within four weeks doses were increased to 25 mg hydrochlorothiazide or 240 mg verapamil once (regimen II) and twice daily (regimen III). Patients not achieving target blood pressure were given the combination of hydrochlorothiazide and verapamil--that is, 25 and 240 mg once (regimen IV) and twice daily (regimen V). MAIN OUTCOME MEASURE: Blood pressure determined with a device permitting automatic repeated measurements with printouts. RESULTS: After eight weeks of treatment with a single drug 76 out of 178 (43%) and 101 out of 175 (58%) patients achieved the target blood pressure with hydrochlorothiazide and verapamil, respectively. During follow up until 48 weeks patients treated with verapamil reached the target blood pressure more often and at lower doses and were less likely to switch to combination treatment than patients randomised to hydrochlorothiazide treatment. Adding verapamil to hydrochlorothiazide was more effective than the addition of hydrochlorothiazide to verapamil. At the end of the study 42 out of 169 (25%) and 73 out of 163 (45%) patients initially randomised to hydrochlorothiazide and verapamil, respectively, were at target blood pressure without combination treatment. After adding verapamil to hydrochlorothiazide or hydrochlorothiazide to verapamil an additional 58 (34%) and 29 (18%) patients reached the target blood pressure, respectively. Altogether 92 out of 332 (28%) patients failed to achieve target blood pressure with regimen V. There were four, 10, seven, and seven withdrawals due to possible adverse effects to treatment with hydrochlorothiazide, verapamil, combining verapamil with hydrochlorothiazide, and combining hydrochlorothiazide with verapamil, respectively. CONCLUSIONS: In doses currently used in antihypertensive treatment verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension, whereas withdrawal rates caused by side effects possibly related to treatment were similar.

Adult↗
PubMed1989

Reliability of salt-sensitivity testing in normotensive subjects.

We examined the reliability of dietary salt-sensitivity testing by repeatedly studying the effects of a high (220 mmol/day) and low (20 mmol/day) salt diet in 15 normotensive subjects. Reliability of classification of salt-sensitivity as described by the kappa statistic was 0.87 implying an almost perfect strength of agreement between the two parts of the study. Whereas only 20% of the subjects with negative familial histories of hypertension were salt-sensitive, this was the case with 68% of the subjects with positive familial histories. Our results show that salt-sensitivity can be reliably tested in normotensive subjects and that it is related to a familial history of hypertension.

Adult↗
PubMed1989

Increased intracellular free calcium and sensitivity to angiotensin II in platelets of preeclamptic women.

Preeclampsia is characterized by a generalized vasoconstriction and increased vascular sensitivity to angiotensin II. Intracellular free calcium, implicated in vascular smooth muscle contraction, has been found to be elevated in platelets of other hypertensive disorders. We therefore measured intracellular free calcium concentrations by using the fluorescent probe quin-2 in platelets of six patients with preeclampsia and compared them to measurements in ten normotensive pregnant women and ten age-matched nonpregnant women. Intracellular free calcium was also determined in the preeclamptic women after delivery. We found that intracellular free calcium was slightly elevated in normal pregnancy (102 +/- 13 nmol/L v 87 +/- 17 nmol/L) but was markedly increased in preeclampsia (138 +/- 13 nmol/L, P less than .05). This increase disappeared six weeks after delivery (84 + 10 nmol/L, P less than .01). To investigate whether the increased intracellular free calcium was related to angiotensin II, the platelets were exposed to thrombin and angiotensin II in vitro. Exposure to thrombin and angiotensin II caused a dose-dependent increase in intracellular free calcium. The intracellular response to thrombin was not significantly different in the three groups. However, stimulation with angiotensin II revealed an increased response in intracellular free calcium in preeclampsia (P less than .05) that disappeared after delivery. Our findings show a sustained increase in platelet intracellular free calcium in preeclampsia and suggest a functional alteration of the angiotensin II receptor in this disease.

Adult↗
PubMed1989

Increased forskolin stimulation of lymphocyte-adenylate cyclase in normotensive subjects predisposed to essential hypertension.

Since a significant heritability has been shown for forskolin stimulation of lymphocyte adenylate cyclase activity in twins, we evaluated lymphocyte forskolin-stimulated adenylate cyclase activity with respect to a familial predisposition towards essential hypertension. Lymphocyte adenylate cyclase activity was measured in broken cell preparations of 32 male normotensive volunteers with (n = 15) and without (n = 17) a positive family history of hypertension. The maximal forskolin stimulation of adenylate cyclase activity was significantly higher in the positive compared with the negative group (maximal stimulation of activity 53.5 +/- 3.4 versus 41.2 +/- 1.9 pmol cyclic AMP (cAMP)/mg protein per min; P less than 0.01). Dose-response curves showed a significantly greater stimulation of adenylate cyclase activity in the positive group at forskolin concentrations of 10(-7) to 2 x 10(-4) mol/l. The median effective dose (ED50) and adenylate cyclase activity in the absence of forskolin were similar in both groups. We conclude that lymphocyte forskolin-stimulated adenylate cyclase activity may depend in part on hereditary factors associated with a familial predisposition to essential hypertension.

Adenylyl Cyclases↗
PubMed1989

Alpha 2- and beta 2-adrenoceptor downregulation in marathon runners.

The regulation of platelet alpha 2- and lymphocyte beta 2-adrenoceptor densities by alterations in endogenous catecholamines was examined. In order to activate the sympathetic nervous system eight trained male normotensive subjects carried out a marathon run. Adrenoceptor densities and plasma catecholamine concentrations were measured before and immediately after the run. Platelet alpha 2-adrenoceptor density and lymphocyte beta-adrenoceptor density decreased after the run (P less than 0.05), whereas both plasma noradrenaline and adrenaline concentrations increased (P less than 0.01). Mean arterial pressure decreased (P less than 0.05), and the heart rate increased (P less than 0.001). The data suggest that increases in endogenous catecholamine concentrations cause downregulation of both alpha- and beta-adrenoceptor densities on human blood cells.

Adult↗
PubMed1988

Different effects of furosemide on alpha-adrenoceptors and on platelet aggregation in man.

The effect of a long-term administration of furosemide (2 x 30 mg/day for 3 weeks) on platelet alpha 2-adrenoceptor density and the fraction of high-affinity binding sites, as well as on platelet aggregation induced by adrenaline and ADP, was studied ex vivo in 8 normotensive volunteers. For comparison the in vitro effect of furosemide on platelet aggregation was also evaluated. Furosemide decreased alpha 2-adrenoceptor-density (P less than 0.01) and the fraction of high-affinity binding sites (P less than 0.05). Adrenaline-induced platelet aggregation was not altered ex vivo and in vitro. Furosemide inhibited ADP-induced platelet aggregation ex vivo (P less than 0.05) and in parallel in vitro (P less than 0.01) in a dose-dependent manner. The reduction of the density of alpha 2-adrenoceptors in the high affinity state may be of functional importance for the hemodynamic effects of furosemide. The inhibitory effect of furosemide on ADP-induced platelet aggregation ex vivo and in vitro, which is not related to the effects on adrenoceptors, seems to involve direct effects of furosemide on platelet function. It remains to be seen whether the latter effect is of clinical importance.

Adult↗
PubMed1988

Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin.

Aggregating platelets release serotonin, which induces contraction of most vascular smooth muscle by activation of S2-serotoninergic receptors. Serotonin released in the circulation may contribute to the increase in peripheral resistance of hypertension as the responsiveness of blood vessels from hypertensive animals and humans to the vasoconstrictor action of the monoamine is augmented. The data obtained with the new antihypertensive agent ketanserin may favor that interpretation. Ketanserin is a selective S2-serotoninergic antagonist with additional alpha 1-adrenergic blocking properties. In humans, it has a terminal half-life of 12 to 25 hours and is eliminated predominantly by the liver. The hemodynamic profile of ketanserin is that of a vasodilator drug with actions on both resistance and capacitance vessels. On short-term intravenous administration, it lowers blood pressure in hypertensive patients with minimal reflex changes in cardiovascular function. When given orally long term to hypertensive patients, ketanserin causes a sustained reduction in arterial blood pressure, comparable to that obtained with either beta-adrenergic blockers or diuretics. Several studies have shown a greater efficacy in older (greater than 60 years of age) than in younger patients independent of starting pressure. Side effects mainly consist of dizziness, somnolence, and dry mouth, but they are usually not severe. The mechanism underlying the antihypertensive effect of ketanserin is unclear. It cannot be attributed to either S2-serotoninergic or alpha 1-adrenergic blockade alone, but an interaction between the two effects appears to be required.

Humans↗