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Biomedical subjects

H Schiffl

Publications and source records attributed to H Schiffl.

At least 91 records · Page 5Linked to original sources

Modulation of platelet Ca2+ homeostasis by hypertensive plasma factor(s) derived from patients with early-stage renal disease.

To determine whether blood-borne factors in hypertension accompanying early-stage kidney disease might be responsible for altered cellular calcium homeostasis, we measured changes in cytosolic calcium before and after incubating platelets in plasma ultrafiltrates from normotensive and hypertensive renal patients. With the use of the chelating agent quin 2, we found the free-calcium concentrations in platelets to be higher in the hypertensive than in the normotensive group. When both groups of participants were combined, a direct correlation was found between arterial pressure and cytosolic calcium. The cytosolic calcium concentration in platelets of normotensive renal patients increased after incubation with plasma from patients with untreated renal hypertension, but it was unchanged after incubation with plasma from normotensive subjects. These data indicate that the total cell burden of calcium is increased in platelets of hypertensive patients with early-stage renal disease, and that plasma from these patients contains a substance that is capable of increasing the cytosolic calcium concentration in platelets. If the plasma factor (or factors) acts not only on platelets, but also on vascular smooth muscle cells, it may contribute to the increased peripheral vascular resistance associated with hypertension of renal origin.

Adult↗

Generation of leukotriene B4 by hemodialyzer membranes: a novel index of biocompatibility.

Leukotriene B4 (LTB4) plays an important role in acute and chronic inflammatory and hypersensitive reactions. We studied the time course of LTB4 biosynthesis in whole blood in 18 patients with end-stage renal failure maintained on regular hemodialysis with two different membranes, cuprophane and polyacrylonitrile (AN 69). The basal levels of LTB4 from dialysis patients did not differ significantly from a normal control group. Compared to predialytic values, the cuprophane membrane caused a maximal release of LTB4 by a factor of about 4.5 (p less than 0.01) within the first 10 to 20 minutes. Thereafter the level fell and returned to baseline range at the end of the hemodialysis session. With the use of the AN 69 membrane no significant increase of LTB4 could be demonstrated. The changes in LTB4 concentration showed a close temporal correlation to the alterations in white blood cell count. We conclude that (1) LTB4 is a biologically important mediator of neutrophil activation during hemodialysis, and (2) LTB4 may be a sensitive marker of biocompatibility in vivo.

Acrylic Resins↗

Hemodialysis-related leukotriene B4 generation and neutropenia during calcium channel blockade.

Cuprophane membranes elict intense blood-surface interactions during clinical hemodialysis. The goal of the present studies was to determine whether calcium channel blockade may alter hemodialysis-related leukotriene B4 (LTB4) generation and neutropenia in 12 patients with end-stage renal failure. The patients were randomized to receive either placebo or nitrendipine for six weeks. Compared with untreated patients, the calcium channel blocker treatment group had significantly lower predialysis plasma LTB4 levels, Nitrendipine reduced both the magnitude of LTB4 generation and of neutropenia during the early phase of hemodialysis, but did not alter the close temporal relation of LTB4 accumulation and neutrophil activation. Therefore, the generation and release of LTB4 by neutrophils may be a calcium-dependent event. Furthermore, these results suggest that activation of neutrophil 5-lipoxygenase may contribute to the alterations in neutrophils of hemodialysis patients.

Aged↗

Leukotriene B4 is involved in hemodialysis-associated neutropenia.

Biosynthesis of leukotriene B4 (LTB4) was studied in ten patients with end-stage renal failure undergoing chronic hemodialysis with a cuprophane membrane. As compared to healthy subjects the low basal plasma levels of LTB4 quantified by radioimmunoassay after extraction and purification by HPLC showed no significant difference. The time-course of LTB4 release after contact of the blood with the dialysis membrane without further in vitro stimulation was characterized by a rapid increase by about 500% within the first 10 min, appearing approximately at the same time as the known fall of white blood cell count which reaches its nadir after 20 min. Analysis of further release showed a decline of LTB4 biosynthesis to basal levels at the end of hemodialysis. These results indicate that activation of the 5-lipoxygenase pathway is involved in hemodialysis-associated leukopenia and may contribute to the alterations in neutrophils of patients with chronic dialysis therapy.

Arachidonate 5-Lipoxygenase↗

Hemodialysis, membrane-related neutrophil dysfunctions, and pentoxifylline--a pilot study.

Hemodialysis treatment is associated with activation of neutrophil granulocytes. Pentoxifylline has been shown to inhibit neutrophil activation in vitro and in vivo. We investigated the effect of pentoxifylline on leukocyte and platelet counts and on plasma levels of extracellularly released neutrophil elastase and lactoferrin during a four-hour hemodialysis treatment. Eight patients received 400 mg of pentoxifylline or placebo orally twice a day over 14 days and an additional dose of 400 mg of pentoxifylline intravenously during hemodialysis. Each subject served as his own control in a randomized, double-blind, cross-over study. Combined oral and intravenous treatment with pentoxifylline prevented neither leukopenia nor neutrophil degranulation during the time interval studied. Elastase plasma levels paralleled the drop in leucocyte counts and thereafter increased similarly in both groups. Lactoferrin plasma levels exhibited less increase in the treated group; however, this effect was not statistically significant. This may be due to the small number of cases studied and to difficulties in reaching effective plasma levels without side effects.

Double-Blind Method↗

Effects of a small bolus dose of ANF in healthy volunteers and in patients with volume retaining disorders.

Thirty-seven patients with volume-retaining disorders (liver cirrhosis with ascites, n = 8; heart failure NYHA III-IV, n = 12; endstage renal failure, n = 17) and twelve healthy age-matched controls were given a small dose (33 micrograms) of hANF (human atrial natriuretic factor). We tested the resulting hemodynamic and renal effects as well as the effect on plasma cyclic GMP levels and compared them with the properties of platelet ANF receptors. The ANF injection evoked an increase in cyclic GMP plasma levels of 19.3 +/- 2.2 nM in healthy controls. This increase tended to be smaller in the cirrhosis group (15.5 +/- 3.3 nM) and in the heart failure group (16.8 +/- 2.3 nM) than in the dialysis group (20.5 +/- 2.5 nM). The invasion rates of cyclic GMP were comparable in all groups, but the evasion rates increased more in the heart failure and endstage renal failure groups (27.9 +/- 7.7 min and 26.1 +/- 3.4 min, respectively) than in the cirrhosis and control groups (14.9 +/- 1.9 min and 14.2 +/- 1.9 min, respectively). Patients with endstage renal failure and congestive heart failure showed a smaller decrease in diastolic blood pressure than controls and patients with liver cirrhosis. Renal actions of ANF were diminished in cirrhosis and heart failure patients. Binding capacities of platelet ANF receptors were higher in the control group (12.2 +/- 1.5 receptors/cell) than in the patient groups (cirrhosis, 7.8 +/- 1.2; endstage renal failure, 8.0 +/- 0.9; heart insufficiency, 8.0 +/- 1.0 receptors/cell), with no differences among the patient groups. Binding affinities were not significantly different. Correlation analysis showed that the relationship between the actions of ANF and the increases in plasma cyclic GMP levels is loose and cannot predict the hemodynamic or renal effects of exogenous ANF in a given patient. Although the behavior of plasma cyclic GMP levels fails to predict the responsiveness of the body to ANF in a given patient, it does reflect the differences between the patient groups and the control group. In contrast, we found no correlation between the properties of platelet ANF receptors and ANF action.

Adult↗

Correlation of blood pressure in end-stage renal disease with platelet cytosolic free-calcium concentration.

The fluorescent probe Quin-2 showed the cytosolic free-calcium concentration in platelets to be elevated in 12 hypertensive hemodialysis patients, who were compared with 12 normotensive hemodialysis patients. There was a close correlation between the free-calcium level of platelets and mean arterial pressure (r = 0.88). Short-term antihypertensive treatment resulted in a reduction of free-calcium concentration and a concomitant fall in blood pressure. These results suggest an integrative contributory role for calcium in the pathophysiology of hypertension accompanying end-stage renal disease.

Adult↗

[The quality of life of older patients under the conditions of long-term dialysis].

A questionnaire enquiry was undertaken to assess aspects of quality of life of 100 older patients (60 women, 40 men; mean age 73.2 [65-88] years) who underwent haemodialysis for an average of 35.6 +/- 28.3 months. The majority of patients (85%) showed a positive attitude towards the haemodialysis treatment, but 14 signified that they would not again submit to this form of treatment. The replies of these patients in other ways, too, corresponded to a depressive state (P less than 0.001) with problems of coping with therapeutic measures (P less than 0.005). Reasons for this were, first, severe physical impairment by additional disease and, secondly, psychosocial factors. Nine of the 14 patients were women living alone who showed signs of loneliness. It would seem that a "negative" attitude towards haemodialysis is largely determined by a patient's social environment.

Aged↗

Assessment of dry body-weight in haemodialysis patients by the biochemical marker cGMP.

We investigated whether cGMP might be a suitable marker of ideal weight in chronic haemodialysis patients. In 20 patients on chronic haemodialysis (10 males, 10 females, mean age 55.5 +/- 7.4 years; mean interdialytic weight gain 2.4 +/- 1.1 kg) we determined plasma ANP and cGMP values before and after several haemodialysis treatments. ANP and cGMP before haemodialysis were markedly elevated (ANP 255 +/- 190 pg/ml; cGMP 28.6 +/- 16.2 pmol/ml). A significant decrease was found after haemodialysis (ANP 169 +/- 88 pg/ml; cGMP 13.5 +/- 7.4 pmol/ml). These values were still well above normal. There was a significant positive correlation between excessive body-weight delta P (difference between actual weight and estimated ideal weight), indicating fluid overload and ANP before (r = 0.57; P less than 0.001) and after haemodialysis (r = 0.47; P less than 0.001) as well as cGMP before (r = 0.42; P less than 0.01) and after haemodialysis (r = 0.85; P less than 0.0001). With cGMP and delta P after haemodialysis, the correlation appeared to be close enough for clinical application. All patients with a cGMP value of 18 pmol/ml or more after haemodialysis had an excessive body-weight of at least 0.5 kg. We conclude from these data that the plasma cGMP value determined immediately after haemodialysis is a sensitive marker for hyperhydration in patients with end-stage renal disease.

Atrial Natriuretic Factor↗

Induction of leukotriene B4 formation by dialyzer membranes.

Interactions between blood and dialysis membranes lead to activation of the 5-lipoxygenase pathway of the arachiodonic acid metabolism during hemodialysis. Newly generated leukotriene B4 (LTB4) may contribute to the multifaceted granulocyte abnormalities of uremic patients.

Aged↗

Platelet cytosolic free calcium concentration in hypertension associated with early stage kidney disease.

Chronic hypertension accompanying early stage kidney disease is characterized by increased vascular resistance, but the underlying processes responsible for the enhanced vascular tone are unclear. We studied free calcium levels in blood platelets with the fluorescent dye quin-2. Platelets have many features in common with vascular smooth muscle cells. The cytosolic calcium concentration in platelets was elevated in 27 renal hypertensive patients, who were compared with 12 normotensive subjects (P less than 0.001). There was a close correlation between the free calcium level and mean blood pressure (r = 0.88, P less than 0.001). Short-term antihypertensive treatment with a calcium entry blocker or a diuretic resulted in a significant reduction in cytosolic calcium (P less than 0.05), and this correlated with the fall in blood pressure (r = 0.95, P less than 0.001). These data suggest an integrative contributory role of calcium in the pathophysiology of hypertension accompanying early stage kidney disease.

Adult↗

[Effective long-term treatment of primary hyperlipoproteinemias with bezafibrate].

Bezafibrate, a new hypolipidemic agent, was evaluated in a single blind, placebo-controlled study lasting 14 months to 3 years in 40 patients with primary hyperlipoproteinemia of various types (23 patients with type II, 15 with type IV and 2 with type V). Bezafibrate in a dose of 200 mg 3 times daily reduced total serum cholesterol by an average of 17% (p less than 0.001) in hyperlipoproteinemia type II and by 24% (p less than 0.001) in type IV or V, lowered serum triglycerides by 31% (p less than 0.001) in hyperlipoproteinemia type II and by 58% (p less than 0.001) in type IV or V, while high-density-lipoprotein-cholesterol was increased by 17% (p less than 0.001) in type II and by 36% (p less than 0.001) in type IV or V. The few side effects encountered were only mild and transient. These findings show that bezafibrate affords safe and effective long-term treatment of patients with hyperlipoproteinemia.

Adult↗

Metabolic consequences of long-term thiazide-based antihypertensive treatment of renal hypertension.

In 72 outpatients with early stage disease and mild to moderate hypertension, metabolic parameters were evaluated before and during 6 years of treatment with two different thiazide diuretic-based antihypertensive therapy regimens. Compared to the untreated state, chronic diuretic treatment caused a persisting increase in serum lipids in men or postmenopausal women. The high incidence of electrocardiographic abnormalities indicative of ischemic changes suggests a possible negative influence of diuretic-induced metabolic alterations on coronary heart disease in these patients.

Adolescent↗

Clinical efficacy and safety of long-term diuretic treatment in renal parenchymal hypertension.

In 48 patients with early stage renal disease and mild to moderate hypertension, control of high blood pressure and metabolic alterations during long-term diuretic treatment (mean duration, 71 months) were assessed. Compared to the untreated state, administration of thiazide-potassium sparing diuretics, a single table per day, supplemented by dietary sodium restriction, led to normalization of high blood pressure. Renal function was preserved. Gross abnormalities in electrolyte metabolism did not occur. Deterioration of glucose tolerance was noted in 3 patients. Preexisting hyperlipidemia was aggravated by the diuretics in men and postmenopausal women, but premenopausal women were protected. Long-term diuretic treatment was well tolerated, and caused remarkably few significant untoward reactions. The unfavorable metabolic response to diuretic treatment may, however, cancel part of the potential benefit of blood pressure control in certain patients. During long-term diuretic treatment of renal patients, attention should be given to monitoring of metabolic parameters and the introduction of specific dietary treatment may become the cornerstone of patient management.

Adult↗

Clinical features and management of nifedipine overdosage in a patient with renal insufficiency.

Overdosage with 280 mg nifedipine, verified by plasma nifedipine levels, led in a 23-year-old female patient with advanced renal insufficiency to features of marked vasodilation. Despite profound hypotension and preexisting anemia, tissue perfusion was adequately maintained. Neither cardiac conductance disturbances nor myocardial depression occurred. There was no evidence for major organ or organ system toxicity. The patient was successfully treated with intravenous calcium. Hemoperfusion did not significantly influence the clinical course. The recovery was uneventful. No late sequelae were observed.

Adult↗

Diazoxide and labetalol in acute hypertension during haemodialysis.

The antihypertensive effect of the peripheral vasodilator diazoxide in 13 patients and the alpha-beta adrenoceptor blocking agent labetalol in 12 patients were compared in 46 severe acute hypertensive episodes during haemodialysis. A single dose of diazoxide 150 mg or labetalol 50 mg was effective in 74% and 70% of the hypertensive episodes, respectively. In the diazoxide-treated patients blood pressure fell from 192 +/- 3/115 +/- 4 mmHg to 141 +/- 8/85 +/- 4 mmHg 2 h after injection. In 7 hypertensive episodes a second dose of diazoxide 150 mg was given 60 +/- 11 min after the first injection. The reduction in mean arterial blood pressure at the end of haemodialysis was 21.5 +/- 2.6% in patients treated with a single dose and 24.8 +/- 3.5% in patients treated with the repeated dose of diazoxide. In the labetalol-treated patients blood pressure in 17 instances fell from 198 +/- 5/104 +/- 4 mmHg to 143 +/- 7/89 +/- 5 mmHg 180 min following injection of labetalol 50 mg. In 6 episodes a second dose labetalol 50 mg was given 41 +/- 9 min after the first injection. At the end of haemodialysis the decrease in mean arterial blood pressure was 17.2% in patients treated with a single dose and 18 +/- 5% in patients given the repeated dose of labetalol. The reduction in blood pressure caused by diazoxide was slightly greater than that due to labetalol. At the end of haemodialysis the percentage reduction in mean arterial blood pressure was 23 +/- 2% in the diazoxide-treated group and 17 +/- 2% after labetalol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗