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Biomedical subjects

H Schiffl

Publications and source records attributed to H Schiffl.

At least 73 records · Page 4Linked to original sources
PubMed1995

Preserved antioxidative defense of lipoproteins in renal failure and during hemodialysis.

Contact to artificial surfaces during hemodialysis activates leukocytes, which then form oxidized arachidonic acid products and free radicals. This might promote the oxidative modification of low-density lipoproteins (LDL) that play a key role in the initiation of atherosclerosis. Thus, leukocyte activation could specifically contribute to the high mortality from atherosclerotic complications on long-term hemodialysis. Therefore monitored LDL and high-density lipoprotein (HDL) resistance to copper-stimulated oxidation in patients with end-stage renal disease on maintenance hemodialysis with cellulose acetate or polysulfone membranes (n = 12), in patients with chronic renal failure (n = 13) and in healthy controls (n = 12). Six of the dialysis patients were restudied during a single cuprophane dialysis. Circulating leukocytes were reversibly reduced early in hemodialysis with cellulose acetate (minimum, 83.6% +/- 7.4% of baseline values at 30 minutes after dialysis start), polysulfone (minimum, 80.4% +/- 10.5% at 15 minutes; P < 0.05) and cuprophane (minimum, 24.5% +/- 8.5% at 60 minutes; P < 0.0001). Despite the leukocyte activation, LDL oxidation lag time was not shortened in comparison with healthy controls and was even prolonged at the end of cellulose acetate (P < 0.05) and cuprophane (P < 0.05) dialysis. HDL oxidation lag time increased (12.6% +/- 0.9%; P < 0.0001) 15 to 60 minutes after start of hemodialysis and returned to predialysis values thereafter. In patients with chronic renal failure, the lag time of HDL oxidation was significantly prolonged (13.34 minutes +/- 0.9) compared with healthy controls (10.91 +/- 2.0 minutes; P < 0.01) as well as compared with the dialysis patients at baseline (9.9 minutes +/- 1.4; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1995

Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells.

We compared peritoneal dialysis effluents from 18 CAPD patients who had not suffered from peritonitis during the last 6 months (group 1) with the effluents from five patients with acute peritonitis (group 2), measuring activation markers of coagulation and fibrinolysis. These markers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP). In the dialysate of group 1 we found remarkably high levels of F1 + 2, TAT and FM concomitant with a high concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin was disturbed in untreated patients of group 2, who had significantly higher levels of coagulation markers and a higher ratio between FM and FbDP. Seven days after treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fibrin turnover we investigated the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Biocompatible intermittent hemodialysis.

Since intermittent hemodialysis was first used systemically during the Korean war, the mortality of acute renal failure (ARF) in critically ill patients has remained high ( > or 50%). The lack of improvement may be a result of better resuscitation techniques and intensive care management that allow more severely ill patients to survive long enough to develop ARF. The concept that those patients with ARF die with, but not of, renal failure was challenged recently by the results of three prospective randomized trials. Each tested the hypothesis that the course of ARF and the fate of critically ill patients may be affected adversely by bioincompatibility reactions due to the dialysis membrane used (activation of complement and neutrophils). Schiffl and colleagues were the first to publish a full report on the results of their investigation comparing bioincompatible cuprophane (CUP) and biocompatible acrylonitrile AN 69 (Hospal, Lyon, France) membranes in 52 patients with ARF following cardiovascular surgery. The AN 69 group had a lower death rate (38% vs. 65%, p = 0.052), a lower proportion of patients dying from Gram-negative sepsis (40% vs. 71%, p = 0.0162), and an improved recovery of renal function. A similar trial comparing the use of CUP with biocompatible polymethyl-methacrylate (PMMA) was performed in 72 patients with medical categories of ARF. Again, the use of a biocompatible membrane resulted in an improved survival rate (57% vs. 37%, p = 0.11) and better recovery of renal function (62% vs. 37%, p = 0.04). Of the 20 patients in each group who initially had nonoliguric ARF, the survival rates were 80% with PMMA and 40% with CUP (p = 0.01). The preliminary results of another multicenter study including 121 patients dialyzed with either bioincompatible cellulosic membranes or PMMA or polysulfone membranes seem to confirm these findings. The management of critically ill patients is sophisticated and expensive. The use of biocompatible membranes adds little to the overall costs and appears to be justified.

Acute Kidney Injury↗
PubMed1994

Biocompatible membranes in acute renal failure: prospective case-controlled study.

The mortality of critically ill patients with acute renal failure has been halved through intervention by haemodialysis. However, several reports suggest that the course of the disorder may be prolonged by this procedure. Our prospective randomised study was done to see whether the generation of inflammatory mediators by bio-compatible membranes has an adverse effect on the outcome of acute renal failure. 52 patients, similar in age, severity of acute renal failure, general disease status (APACHE II), and management of acute renal failure or its related conditions, were divided into two groups. Haemodialysis was done with cuprophane or polyacrylonitrile membranes. Cuprophane membranes induced intense activation of the complement system (as judged by measurement of C3a) and lipooxygenase pathway (leukotriene B4) resulting in alterations of neutrophil kinetics and function. The cuprophane group had a lower survival rate (38 vs 65%), a higher proportion of patients dying from sepsis (71 vs 40%), required more haemodialysis sessions (12 vs 9), and demonstrated delayed resolution and recovery from acute renal failure than the polyacrylonitrile group. The difference in mortality regarding lethal sepsis as cause of death was statistically significant. Our observations indicate that the outcome of critically ill patients with acute renal failure may be influenced by bio-incompatibility reactions to the dialysis membrane. These results have direct implications for such patients on haemodialysis.

Acrylic Resins↗
PubMed1993

Hypertension secondary to early-stage kidney disease: the pathogenetic role of altered cytosolic calcium (Ca2+) homeostasis of vascular smooth muscle cells.

We have examined cardiovascular pressor responsiveness to infused norepinephrine (NE) as related to endogenous plasma NE and plasma renin and to platelet free cytosolic (Ca2+) in 36 patients with early-stage kidney disease and 27 matched normal subjects. The 27 hypertensive patients and the normal subjects did not differ in blood volume, plasma renin, and NE; however, the hypertensive patients had a higher exchangeable body sodium content. Basal plasma NE levels, the relationship between plasma NE measured during NE infusion and the corresponding NE infusion rate, as well as the total plasma clearance for NE did also not differ significantly between the two study groups. In contrast, the threshold or pressor doses of infused NE significantly decreased in the patients with kidney disease. Antihypertensive pharmacotherapy with (Ca2+) channel blockers and/or loop diuretics normalized blood pressure and cardiovascular NE hyperresponsiveness and reduced blood volume, exchangeable body sodium, and platelet free cytosolic (Ca2+). In contrast, experimental digitalisation as a model for in vivo sodium/potassium adenosine triphosphatase inhibition augmented NE responsiveness and raised platelet free cytosolic (Ca2+). Incubation of platelets from normal subjects with plasma ultrafiltrate from hypertensive patients gave evidence for an endogenous factor capable to raise free cytosolic (Ca2+) and to act synergistically with digoxin. Hypertension secondary to early-stage kidney disease is related to an impairment of sodium excretion leading to an expansion of blood volume and exchangeable body sodium. This may result in increased secretion of endogenous factors, leading to alterations of cytosolic (Ca2+) homeostasis of vascular smooth muscle cells followed by elevated peripheral resistance and thus blood pressure.

Adult↗
PubMed1993

Assessment of acute parathyroid responsiveness to high calcium dialysate in uremic patients.

The response of the parathyroid glands to dialysis-induced changes in calcium has been studied in 83 normocalcemic patients receiving maintenance hemodialysis. Predialysis concentrations of intact parathyroid hormone (iPTH) were normal in 13 patients; 70 patients had increased iPTH levels of different degrees. All patients had analytically significant changes in total serum calcium (2.3 +/- 0.2 vs 2.8 +/- 0.2 mmol/l) without additional parenteral calcium loading during a standard dialysis session with a dialysis solution of 1.75 mmol calcium chloride. During hemodialysis the concentration of iPTH fell in 77 patients and was normalized in 48 of these patients. The remaining 6 patients showed no or an inadequate response (less than 30% suppression of predialysis iPTH) to the increase in Ca. Parathyroidectomy was performed in patients with refractory iPTH secretion. Histological evidence of marked parathyroid hyperplasia was obtained in all these patients. All patients with normal or partial responsiveness of the parathyroids tolerated at least small doses of 1.25 (OH)2-vitamin D3. Quantification of predialysis and postdialysis iPTH concentrations is a useful and simple method for identifying those uremic patients with true autonomy of the parathyroid glands at an early stage.

Adolescent↗
PubMed1993

Plasma cGMP level as a marker of the hydration state in renal replacement therapy.

We investigated, whether plasma cyclic guanosine 3':5'-monophosphate (cGMP) may be suited as a marker of hyperhydration in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). In 81 HD patients the levels of atrial natriuretic peptide (ANP) and cGMP were markedly elevated before HD (ANP: 165 +/- 11.1 pg/ml; cGMP 43.5 +/- 2.2 pmol/ml). Significantly lower values (P < 0.01) were found after HD (ANP: 97 +/- 8.4 pmol/ml; cGMP 19.5 +/- 1.5 pmol/ml). Twenty-three patients had cGMP levels above 20 pmol/ml after HD. Therefore "dry body weight" was reduced in these patients. This resulted in a "normalization" of cGMP values to a postdialytic range below 20 pmol/ml in the majority of patients. All seven patients with persistently high cGMP levels despite weight reduction had left sided heart failure. In 33 CAPD patients ANP was slightly lower than after HD (68 +/- 10.4 pg/ml), and the cGMP level (22.4 +/- 2.3 pmol/ml) was between pre- and postdialytic values in HD. In eight CAPD patients with clinical signs of hypervolemia plasma cGMP, but not ANP, was significantly elevated. We conclude that the plasma cGMP level appears to be a reliable marker for fluid overload in patients on renal replacement therapy with normal heart function.

Adult↗
PubMed1992

Anticardiolipin antibodies and lupus anticoagulant in patients treated with different methods of renal replacement therapy in comparison to patients with systemic lupus erythematosus.

Antiphospholipid antibodies were found to be associated with certain clinical manifestations such as recurrent venous thrombosis or arterial occlusions in a wide spectrum of immune disorders [6]. We analyzed the plasma concentration of two isotypes (IgG, IgM) of anticardiolipin antibodies (ACA) and lupus anticoagulant (LAC) activity in 84 patients with end-stage renal disease. They were receiving different types of renal replacement therapy and had a high frequency of thrombotic vascular complications. The prevalence of positive tests and the mean ACA concentration obtained in the plasma of renal patients were compared with those in patients with systemic lupus erythematosus (SLE) and in healthy controls. When analyzed as a whole group, renal patients maintained on dialysis (n = 45: hemodialysis, n = 20; peritoneal dialysis) or with a functioning kidney transplant (n = 19) did not differ in mean ACA concentration and LAC activity (n = 84, ACA: IgG 10 +/- 7 U/ml, IgM 2 +/- 1 U/ml, LAC ratio: 1.0 +/- 0.2) from healthy subjects (n = 50, ACA: IgG 10 +/- 3, IgM 2 +/- 1 U/ml, LAC ratio: 1.0 +/- 0.1) but they had a higher incidence of raised IgG-ACA titers (renal replacement 14% vs. normal controls 4%, p less than 0.05). No significant correlation was found between thrombotic events and raised ACA or LAC activity in dialysis patients. In contrast, the proportion of SLE patients (n = 51) with a raised concentration of ACA was significantly higher (IgG: 69%, IgM: 29%) than that among patients with renal replacement therapy (IgG: 14%, IgM: 4%) or normal controls (IgG: 4%, IgM: 2%, p less than 0.002). Moreover, recurrent manifestations of thrombosis in SLE were associated with very high IgG-ACA (n = 11, IgG 117 +/- 91 U/ml) and LAC activity (LAC ratio: 2.4 +/- 0.7) in comparison to SLE patients without thrombotic events (n = 40, ACA: IgG 23 +/- 13). The results of our investigations demonstrate that the pathogenetic role of these phospholipid antibodies in end-stage renal disease is far from established.

Adult↗
PubMed1992

The postdialytic plasma cyclic guanosine 3':5'-monophosphate level as a measure of fluid overload in chronic hemodialysis.

The postdialytic plasma level of cGMP, a marker for the release of atrial natriuretic peptide (ANP) in humans, is closely related to hypervolemia in chronic hemodialysis patients. In order to test the practicability of routine postdialysis cGMP determination for the detection of fluid overload, ANP and cGMP levels in the total hemodialysis population of 81 patients were measured with blood samples drawn immediately after hemodialysis. Twenty-three patients had a cGMP level of more than 20 pmol/mL. In 13 of these, pulmonary congestion was present on the chest roentgenogram. Two of these patients refused a gradual reduction of their dry body weight. In the remaining 21 patients, the weight reduction was associated with a decrease in cGMP levels in all cases and with a decrease in ANP levels in all but two cases. Fourteen of the 21 patients reached a cGMP level below 20 pmol/mL after weight reduction, and at that time, none of these showed signs of pulmonary congestion on chest x-ray. All seven patients, whose cGMP levels remained above 20 pmol/mL despite the reduction, had documented heart disease with impairment of left ventricular function. These results suggest that the plasma cGMP level after hemodialysis is more apt for the determination of dry body weight than is ANP or a chest roentgenogram.

Adult↗
PubMed1992

Removal of beta 2-microglobulin by hemodialysis and hemofiltration: a four year follow up.

Efficient removal of total body burden beta 2-Microglobulin (beta 2-M) in uremia is a continuing challenge, as dialysis-related amyloidosis represents a major complication of chronic renal replacement therapy. To investigate long-term beta 2-M removal we studied 3 groups of stable end-staged renal failure patients over a period of 4 years; we compared low flux (cuprophane) hemodialysis (n = 12), high flux (polysulfone) hemodialysis (n = 12) and hemofiltration using high flux polysulfone (n = 8). In contrast to the cuprophane membrane, the polysulfone membrane eliminated considerable amounts of beta 2-M. This was associated with a sustained reduction of predialysis serum beta 2-M-levels (by 20%). Compared with high flux hemodialysis, hemofiltration provided a 50% higher elimination of beta 2-M. Thus, our long-term evaluation of beta 2-M removal suggests that hemofiltration rather than hemodialysis may be the treatment of choice for delaying the incidence of dialysis-related amyloidosis.

Adult↗
PubMed1992

Correlation of blood pressure in end-stage renal disease with platelet cytosolic free calcium concentration during treatment of renal anemia with recombinant human erythropoietin.

The hemodynamic hallmark of hypertension complicating the treatment of renal anemia with recombinant human erythropoietin (rHu-EPO) is increased total peripheral vascular resistance, but the mechanisms underlying the arteriolar vasoconstriction are still an enigma. We studied body fluid volumes, plasma renin activity, plasma norepinephrine, and calcium metabolism in platelets in 40 previously normotensive hemodialysis patients before and after 12 weeks of rHu-EPO treatment. Partial correction of anemia caused a rise in arterial pressure (94 +/- 6 mmHg vs 124 +/- 7 mmHg, p less than 0.05) and in platelet cytosolic calcium concentration (113 +/- 5 nM vs 171 +/- 18 nM, p less than 0.05) in eight patients. Hypertensive patients had significantly higher plasma noradrenaline concentrations, but they did not differ significantly in body fluid volumes and plasma renin activities. There was a close correlation between free calcium concentration in platelets and mean arterial pressure in patients developing rHu-EPO-induced-hypertension (r = 0.95). Short-term antihypertensive treatment resulted in a reduction of free calcium concentrations in platelets and a concomitant fall in blood pressure. The main results of the present studies suggest that rHu-EPO-induced hypertension might be associated with altered cellular calcium homeostasis and hyperactivity of the sympathetic nervous system. If rHu-EPO therapy induces alterations of pressor factors or the hormone itself raises the cytosolic calcium not only in platelets but also in vascular smooth muscle cells, altered cellular calcium influx may contribute to the arteriolar vasoconstriction.

Anemia↗