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Biomedical subjects

A Distler

Publications and source records attributed to A Distler.

At least 127 records · Page 7Linked to original sources

[Effect of erythropoietin therapy on alpha receptor density in chronic dialysis patients].

The effect of a six months therapy with human recombinant erythropoietin (rHu-EPO) on blood pressure and on several parameters of sympathetic nervous activity was studied in chronic haemodialysis patients in a controlled and randomized trial in order to gain further insight into the mechanism of rHu-EPO-induced blood pressure elevation. Treatment was started at a dose of 3 X 80 IE/kg/week in eleven patients aiming to increase the initial hemoglobin concentration (7.0 +/- 0.3 [SEM] g%) to 10.0 g% by dose adjustments, while another untreated eleven patients served as a control group. Diastolic arterial pressure measured before and after haemodialysis increased on rHu-EPO treatment by 7 and 8 mm Hg respectively (p less than 0.05). Plasma noradrenaline concentration was increased (p less than 0.05) after the six months treatment period in the presence of unchanged dry weights. Conversely platelet alpha 2-adrenoceptor density (3H-yohimbine binding) and the fraction of high affinity binding sites for alpha 2-agonists (3H-UK 14.304) decreased (p less than 0.01) along with a decrease in reactivity to exogenous noradrenaline (p less than 0.05). None of these parameters changed in the control group compared to pretreatment values. The results obtained demonstrate that increased plasma noradrenaline concentrations may participate in rHu-EPO induced blood pressure increases. The decrease in platelet alpha 2-adrenoceptor densities and the decrease in noradrenaline reactivity in the presence of increased plasma noradrenaline concentrations suggest an intact regulation of alpha 2-adrenoceptors in chronic haemodialysis patients on chronic rHu-EPO therapy.

Blood Platelets↗

Outcome prediction of acute renal failure in medical intensive care.

Data acquired prospectively from 134 patients with acute renal failure requiring dialysis in a medical intensive care unit (ICU) were analysed in order to derive indicators predicting ICU-survival. Mortality in the ICU was 56.7%. Linear discriminant analysis correctly predicted outcome in 79.9% at the start of dialysis, and 84.7% at 48 h after the first dialysis. The most important predictive variables were mechanical ventilation and low blood pressure. On the other hand, the total correct classification rates achieved by a standardised system for scoring ICU-patients (APACHE II) did not exceed 58.2%. It is concluded that outcome prediction by APACHE II and even by the discriminant functions is too inaccurate to become the basis for clinical decisions either concerning the initiation or the continuation of dialysis treatment in ARF.

Acute Kidney Injury↗

Regulation of the superoxide-forming NADPH oxidase of human neutrophils is not altered in essential hypertension.

Neutrophils possess a plasma-membrane-bound reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase which catalyzes superoxide (O2-) formation and is activated by a variety of stimuli. Recently, neutrophils of patients with essential hypertension (EHT) have been reported to generate O2- at rates up to fourfold higher than those of normotensive (NT) subjects upon exposure to the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe). We studied regulation of O2- formation in neutrophils of 25 EHT subjects and 25 age- and sex-matched NT subjects. The intercellular signal molecules fMet-Leu-Phe, platelet-activating factor and leukotriene B4 activated O2- formation in neutrophils, but the latter two receptor agonists were less effective than the former. fMet-Leu-Phe activated O2- formation with a 50% effective concentration (EC50) of about 30 nmol/l, the effect of the chemotactic peptide being maximal at 0.1-1 mumol/l. fMet-Leu-Phe-induced O2- formation was potentiated by platelet-activating factor, adenosine 5'-[gamma-thio]triphosphate and cytochalasin B and was inhibited by the activators of adenylyl cyclase, isoproterenol, prostaglandin E1 and histamine. 4 beta-Phorbol 12-myristate 13-acetate, 1,2-dioctanoyl-sn-glycerol, gamma-hexachlorocyclohexane and arachidonic acid, which circumvent receptor stimulation, also activated O2- formation. Significant differences between NT and EHT subjects were not evident in respect of any of the parameters studied. Our data suggest that regulation of the neutrophil NADPH oxidase is not disturbed in EHT and that altered O2- formation does not represent a genetic marker for abnormalities in plasma-membrane signal transduction in EHT.

Adult↗

Salt sensitivity in young normotensive subjects is associated with a hyperinsulinemic response to oral glucose.

Insulin resistance associated with a hyperinsulinemic response to oral glucose intake has been found in patients with essential hypertension and is believed to play a role in inducing hypertension by causing renal sodium and water retention. We therefore examined whether salt-sensitive, young normotensives, assumed to be predisposed to essential hypertension, exhibit impaired glucose tolerance in a similar way. The plasma insulin and glucose response to oral glucose intake (75 g) was assessed in 23 healthy, lean, male volunteers ingesting either 20 mmol or 260 mmol NaCl/day for 6 days each in a single-blind randomized crossover study. Salt sensitivity was defined as a significant drop in mean arterial blood pressure greater than 3 mmHg (means of 30 readings in the supine subject; P less than 0.05) under the low-salt diet. Following the glucose load, plasma levels of both glucose and insulin were significantly higher (P less than 0.01) in the salt-sensitive (n = 10) compared with the salt-resistant subjects (n = 13) during the high-salt diet but not during the low-salt diet. Whereas in the salt-sensitive group glucose tolerance improved with dietary salt restriction (P less than 0.01), it deteriorated in the salt-resistant group (P less than 0.05). Following the glucose load under the high-salt diet, there was a significant drop in blood pressure in the salt-sensitive (P less than 0.005) but not the salt-resistant subjects. The hyperglycemic and hyperinsulinemic response in salt-sensitive subjects suggests that insulin resistance is present in these subjects prior to the development of hypertension and that it can be ameliorated by salt restriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Endothelin increases [Ca2+]i, protein phosphorylation, and O2-. production in human alveolar macrophages.

The goal of the present study was to investigate whether endothelin (ET) increases O2-.production in alveolar macrophages and to establish which second messengers are activated by ET. We measured the effects of ET on cytosolic free calcium concentration [Ca2+]i, protein phosphorylation, and O2-.production in human alveolarmacrophages (HAM). Human macrophages were obtained by bronchoalveolar lavage. [Ca2+]i was measured by the fura-2 method both in cell suspensions and in isolated single macrophages. Protein phosphorylation was assessed by gel electrophoresis and autoradiography after labeling the cells with 32P. ET increased [Ca2+]i in a dose-dependent manner (50% effective concentration = 1 x 10(-7)M). At a concentration of 10(-6)M ET, [Ca2+]i rose from basal values of 121 +/- 23 to 456 +/- 41 nM. This increase was comparable with the increase of [Ca2+]i induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine and platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). The initial rise in [Ca2+]i and the sustained phase were significantly reduced in calcium-free medium (1 mM ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid) and after preincubation of HAM with the calcium channel blocker nitrendipine (10(-7)M). Exposure of 32P-labeled HAM to ET for 1 min induced the phosphorylation of a group of 48-kDa proteins and of a 35-kDa protein. The ET-induced 32P incorporation into the 48-kDa proteins was less pronounced than the 12-O-tetra-decanoylphorbol-13-acetate or PAF-induced response (168 +/- 24 vs. 356 +/- 68 and 278 +/- 61% of control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hydrochlorothiazide and verapamil in the treatment of hypertension. The Verapamil Versus Diuretic (VERDI) Trial Research Group.

The efficacy and tolerability of hydrochlorothiazide, sustained-release verapamil, and their combination was compared in patients with mild to moderate hypertension. The design was a multicenter, randomized, double-blind clinical trial with a single-blind placebo baseline period of 2 weeks. Three hundred sixty-nine patients with a diastolic blood pressure of 95-120 mm Hg were included. Treatment consisted of 12.5 mg of hydrochlorothiazide once daily, then 25 mg once daily, and finally 25 mg twice daily; the other group received verapamil at a dose of 120 mg once daily, then 240 mg once daily, and finally 240 mg twice daily. Patients not achieving target blood pressure (less than 90 mm Hg diastolic) were given the combination of hydrochlorothiazide and verapamil, that is, 25 and 240 mg once daily and twice daily. During all time points during the study patients receiving verapamil achieved target blood pressure more often than patients receiving hydrochlorothiazide (after 8 weeks, 57.7 and 42.7%; after 24 weeks, 46.8 and 26.4%; and after 48 weeks, 44.8 and 24.7%, respectively). Adding verapamil to hydrochlorothiazide was more effective in lowering blood pressure than adding hydrochlorothiazide to verapamil. The number of treatment withdrawals was essentially the same with the two drugs. Therefore, in the doses currently used in antihypertensive treatment, verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension.

Adult↗

[Detection of cardiac risk in hypertensive patients with left heart hypertrophy].

Arterial hypertension is a consistent and modifiable cause of cardiovascular disease. The risk is further increased by left ventricular hypertrophy as an independent contributor to these cardiovascular events. However, the incidence of coronary mortality and sudden death could not be reduced by antihypertensive drug therapy. It seems possible that there is a subgroup of patients with arterial hypertension with excess risk associated with increased left ventricular mass, ventricular arrhythmias, and silent myocardial ischemia. These patients could be detected by a more developed diagnostic approach using echocardiography, 24-h ECG, and noninvasive 24-h blood-pressure measurement.

Arrhythmias, Cardiac↗

Abnormal acid-base regulation in salt-sensitive normotensive man.

Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. Studies in normotensive salt-sensitive men have likewise demonstrated slightly but significantly lower arterial pH and bicarbonate levels, relating salt-sensitivity to the presence of a relative acidosis in man. The administration of alkalinizing sodium salts such as sodium bicarbonate or citrate have been shown to have no effect on or to even lower blood pressure in patients with essential hypertension. Possible factors contributing to the perturbation in acid-base status include an enhanced Na+/H(+)-antiport activity, lower intracellular pH levels and altered renal electrolyte handling as found in rat models of hypertension and in patients with essential hypertension.

Acid-Base Imbalance↗

[Diagnosis of deep leg vein thrombosis with color-coded duplex sonography and sonographic determination of the duration of the thrombosis].

In a prospective study, 188 patients with suspected deep venous thrombosis were examined by color-coded duplex sonography. In 114 patients the diagnosis of deep venous thrombosis was based on the criteria of 1) compressibility, 2) blood flow changes during compression, and 3) pelvic level during Valsalva maneuver. In all patients the results were compared with data from contrast venography. Venography was performed by an investigator, who was blinded to the prior findings. Sensitivity and specificity of the color-coded duplex sonography in diagnosing deep vein thrombosis were 96% and 97%, respectively. In the other 74 patients, in which the diagnosis of deep vein thrombosis was made by phlebography and/or ultrasound, a follow-up by color-coded duplex sonography was performed to determine the age of thrombosis. Criteria considered to determine the thrombus age included 1) margin of the vessel, 2) echogenicity; and 3) venous diameter. In 20 patients the results were compared to the age of thrombus that had been determined by histologic criteria (group I). In 54 patients the results were compared with the age that had been determined by patient history and symptoms (group II). A significant correlation was found between the age of thrombosis and the venous diameter (p less than 0.001). When thrombosis was less than 10 days old, the venous diameter was at least twice that of the diameter of the accompanying artery. The two other criteria, echogenicity and margin of the venous wall, however, did not prove to be accurate criteria to determine the age of deep venous thrombosis.

Adolescent↗

Diagnostic procedure in renovascular hypertension.

Detection of a renal artery stenosis (RAS) as a cause of arterial hypertension is of great practical importance because dilatation of the stenosis frequently results in an improvement or cure of the hypertension. In recent years, a number of screening procedures aimed at diagnosing renovascular hypertension have been developed, e.g., duplex sonography of the renal arteries, determination of plasma renin activity, or renal scintigraphy following administration of captopril. The possibilities and limitations of these screening procedures are described here. The best method for detecting renal artery stenosis is angiography, which can now be performed on an outpatient basis, using thin catheters.

Angiography, Digital Subtraction↗

[Technical possibilities and limits of ambulatory 24-hour blood pressure measurement].

Noninvasive automatic 24-h indirect ambulatory monitoring of blood pressure (ABPM) and heart rate has been performed in more than 2000 subjects from 1983-1990 using 12 different devices. According to the requirements of national validation authorities (e.g. AAMI, PTB and BHS) only four devices have passed at least two protocols. These monitors were equipped with auscultatory and/or oscillometric devices; they provided accurate readings and were repeatedly used up to eight times in some patients. Up to 100 data points per 24-h provided diurnal blood pressure profiles for over 91% of the patients in clinical and non-clinical situations. Early identification of borderline hypertensives at risk and detailed information on the efficacy of different anti-hypertensive regimes may in part justify the high costs of the monitors. Although sleep disturbance continued in more than 20% of investigated patients, the new lighter, quieter monitors (e.g., SL 90207, 380 g) were well received by patients and nurses. In the future, simultaneous registration with 24-h ECG may help in identifying the effects of different antihypertensive therapies on blood pressure variabilities and rhythmicity of the heart rate. The cost-benefit-ratio and the prognostic importance have yet to be defined.

Adult↗

Dietary sodium restriction: adverse effect on plasma lipids.

In order to examine the effect of dietary sodium intake on plasma lipids, 15 healthy male volunteers were given a low-salt diet (20 mmol/day) for 3 weeks, adding either placebo, sodium chloride (200 mmol/day), or a non-chloride sodium salt (sodium citrate, 200 mmol Na/day) for one week each, in a single-blind randomized crossover study. Plasma levels of total cholesterol and LDL cholesterol were significantly higher at the end of the placebo period than with either sodium chloride (by 8.7 and 11.9%, respectively) (P less than 0.005) or sodium citrate (by 11.3% and 16.8%, respectively) (P less than 0.005). Thus this effect was dependent on sodium but not on chloride intake. Triglyceride and HDL-cholesterol levels were not affected by the dietary regimens. We conclude that short-term dietary sodium restriction may lead to a rise in plasma total and LDL cholesterol, thereby possibly increasing the risk of atherosclerotic vascular disease. Our findings render it possible that diuretic-induced lipid disturbances may also be caused by sodium depletion.

Adult↗

Impairment of renal function in medical intensive care: predictability of acute renal failure.

Acute causes and chronic risk factors for the development of acute renal failure were analyzed in prospective acquired data of 261 patients in a medical ICU. The population was divided into a group requiring dialysis treatment for established renal failure (n = 95) and a collective maintaining mild renal insufficiency (n = 166). Bivariate and linear discriminant analyses revealed that, above all, variables related to bacterial infections (sepsis and administration of antibiotic agents) and pancreatitis contributed to the discrimination, followed by bleeding, volume depletion, and chronic liver disease in the discriminant function. Bivariate analysis also yielded significant results for mechanical ventilation, CNS depression, and surgery. The importance of the nephrotoxic properties of aminoglycosides may be outweighed by their role as an indicator of severe infectious disease. The overall correct classification rate of the discriminant function was 78.5%, which reflects the importance of the predictor variables, but does not allow individual predictions.

Acute Kidney Injury↗

Outcome prediction models on admission in a medical intensive care unit: do they predict individual outcome?

Prospectively acquired data from 941 patients staying greater than 24 h in a medical ICU were analyzed to determine the relevance of scoring on ICU admission by the following methods of outcome prediction: Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS), and Mortality Prediction Model (MPM). Analysis was performed separately for all patients (group A) and for a subsample (group B), obtained by excluding coronary care patients. Calculation of risk and classification of patients were carried out as recommended in the literature for MPM, APACHE II, and SAPS. In group A, sensitivities (correct prediction of hospital mortality) were 44.7%, 51.1%, and 21.2% and specificities (correct prediction of survival) were 84.5%, 85.4%, and 96.8%, respectively; overall correct classification rates were 73.3%, 75.8%, and 75.6%. In group B, sensitivities were slightly higher, but total correct classification rates did not reach group A levels. Goodness-of-fit testing showed low levels of fit for all methods in both groups. Application of APACHE II to diagnostic subgroups, using disease-adapted risk calculations, revealed marked inconsistencies between the estimated risk and the observed mortality. We conclude that the estimation of risk on admission by the three methods investigated might be helpful for global comparisons of ICU populations, although the lack of disease specificity reduces their applicability for severity grading of a given illness. The inaccuracy of these methods makes them ineffective for predicting individual outcome; thus, they provide little advantage in clinical decision-making.

Female↗

Effect of erythropoietin on parameters of sympathetic nervous activity in patients undergoing chronic haemodialysis.

The effect of erythropoietin (rHu-EPO) on blood pressure and on parameters of sympathetic nervous activity of patients undergoing chronic haemodialysis treatment was evaluated in a controlled and randomized 6-months study. Both groups did not differ significantly at the onset of the study in terms of dialysis protocol, haematological parameters, blood chemistry, weight, blood pressure and parameters of sympathetic nervous activity. Haemoglobin increased from 7.0 +/- 0.3 g dl-1 to 10.0 +/- 0.3 g dl-1 by 6 months on rHu-EPO (n = 11) and remained constant in the control group (n = 11). After 6 months diastolic blood pressure was higher in the treatment group compared with the control group as well as compared with pretreatment values, whereas reactivity to exogenous noradrenaline and platelet alpha 2-adrenoceptor densities ([3H]-yohimbine- and [3H]-UK 14,304-binding sites) were lower. Plasma noradrenaline concentration increased during rHu-EPO compared with pretreatment values, while dry weights were unchanged during the study. The results demonstrate alterations of some parameters of sympathetic nervous activity during rHu-EPO-therapy which were absent in the control group.

Blood Platelets↗

Control of renovascular hypertension by renal embolization.

Two cases with medically well-controlled renovascular hypertension due to unilateral contracted kidney were treated by percutaneous renal embolization. One of the patients had two aneurysms of the renal artery in addition to the stenosis. Both patients remained normotensive without medication after follow-ups of 6 and 24 months, respectively.

Adult↗