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Biomedical subjects

H Schiffl

Publications and source records attributed to H Schiffl.

At least 55 records · Page 3Linked to original sources
PubMed1997

Hypertension induced by recombinant human erythropoietin (rHU-EPO) can be prevented by indomethacin. Pathogenetic role of cytosolic calcium.

Hypertension complicating the therapy of renal anemia with rHU-EPO is characterized by an increase in total peripheral vascular resistance, but the mechanisms underlying arteriolar vasoconstriction remain unclear. To assess the role of altered cellular calcium metabolism, resting platelet cytosolic calcium was measured in 12 previously normotensive patients with end-stage renal disease before and after 12 weeks of EPO-therapy, after 12 weeks of combined antihypertensive pharmacotherapy of EPO-induced hypertension, and after 12 weeks of concurrent administration of EPO and indomethacin. Patients with EPO-induced hypertension showed a significant raise in platelet calcium by comparison with calcium levels prior to EPO (179 +/- 15 vs 120 +/- 8 nmol/l), and there was a positive correlation between their blood pressure and platelet calcium levels (r = 0.9, p < 0.001). Antihypertensive therapy of EPO-induced hypertension resulted in a reduction of blood pressure and a reduction of platelet calcium to near normal levels (128 +/- 6 nmol/l). The non-steroidal antiinflammatory drug indomethacin prevented EPO-induced hypertension and EPO-associated alterations in platelet calcium. The results of the present study suggest that EPO-induced hypertension might be related to altered cellular calcium homeostasis. If EPO therapy induces alterations in calcium metabolism not only in platelets but also in vascular smooth muscle cells, these changes in calcium influx may contribute to arteriolar vasoconstriction during EPO therapy.

Anemia↗
PubMed1997

[Patient survival, a change in methods, and hospitalization in CAPD abd hemodialysis].

UNLABELLED: BACKGROUND AND OBJECTIVE OF STUDY: Continuous ambulatory peritoneal dialysis (CAPD) still plays a minor role in Germany compared with haemodialysis (HD) in the management of terminal renal failure. An investigation was undertaken to compare mortality rate, change of dialysing method as well as number and duration of hospital stays of patient undergoing CAPD or HD at a nephrological centre. PATIENTS AND METHODS: All 166 patients in terminal renal failure (except those with a malignancy) admitted between January 1987 and December 1992 were included (63 women and 103 men, aged 19-84 years). The choice between the two dialysis methods was made by the patients after detailed information had been given. Taking into account basic disease and any secondary illness as well as age and sex, survival time, any change of dialysing method and hospitalisation details were prospectively analysed for the two dialysing methods. RESULTS: After 4 years there were no significant differences in mortality rate between the two methods (HD 37%, CAPD 29%). The Cox model revealed no influence of various parameters on the mortality rate of the two methods. However, cumulative patients survival was significantly decreased by arterio-sclerotic disease (P < 0.05; probability of survival after 4 years was 53% and 73%, respectively, for HD and 57% and 77% for CAPD). Similarly, age > or = 60 years at onset of dialysis significantly lowered probability of survival (after 4 years of dialysis, 53% vs 70% for HD, 45% vs 80% for CAPD: P < 0.05). But there were no significant differences between the two methods with respect to these two factors. After 4 years, "method survival" was more common with HD (94%) than CAPD (64%), P < 0.05). In particular diabetics had a significantly lower "method survival" after 4 years than non-diabetics (29% vs 74%). There was no significant difference between the two methods regarding number and duration of hospital stays. CONCLUSIONS: These data show that, in a nephrological centre with long experience in both methods of dialysis, CAPD is an equal alternative to HD.

Adult↗
PubMed1997

Biocompatible membranes preserve residual renal function in patients undergoing regular hemodialysis.

Initiation of hemodialysis causes a further decrease of residual renal function (RRF). To assess the impact of the biocompatibility of the dialysis membrane, we performed a prospective randomized investigation in 20 normotensive patients with tubulointerstitial nephritis. The patients were randomly allocated to treatment with either a high-flux polysulfone or cellulose membrane over a period of 12 months. RRF, defined by creatinine clearance and daily urine volume, was found to decrease in both groups of patients after the initiation of hemodialysis. Of the two membranes used, however, the cellulose membrane caused an accelerated decrease of RRF (P < 0.05). The better maintenance of RRF in patients treated with polysulfone membranes was associated with higher Kt/V values and increased hematocrit values (P < 0.05). The pathophysiologic mechanism underlying the more rapid decline of RRF could not be explained by intradialytic hypotension, but may be related to the nephrotoxic effects of inflammatory mediators due to bioincompatibility. Therefore, the use of polysulfone membranes might be preferable in patients with relevant RRF.

Biocompatible Materials↗
PubMed1997

Noradrenergic blood pressure dysregulation and cytosolic calcium in primary hyperparathyroidism.

The purpose of this study was to characterize the changes in noradrenergic blood pressure regulation and the causes of this dysregulation in patients with histologically proven primary hyperparathyroidism before and after parathyroidectomy. In untreated hypertensive patients with primary hyperparathyroidism slightly higher plasma levels of norepinephrine, enhanced cardiovascular reactivity to norepinephrine (p<0.05) and increased cytosolic free calcium concentration in platelets (p<0.05) were found. Parathyroidectomy resulted in the correction of noradrenergic blood pressure dysregulation and in the reduction of cytosolic free calcium and led to normotension. In vitro incubation of platelets from normal subjects with heterologous plasma ultrafiltrates from either hypertensive patients with primary hyperparathyroidism or normotensive uremic patients with secondary hyperparathyroidism led to raised platelet calcium in primary hyperparathyroidism but not in secondary hyperparathyroidism, although in both conditions intact parathormone levels were elevated equally. Furthermore, when platelets of normotensive subjects were preincubated with commercially available parathormone, no effect on resting platelet cytosolic calcium was observed. Our results suggest that hypertension in primary hyperparathyroidism may be caused in part by noradrenergic blood pressure dysregulation and seems to be causally linked to the secretion of a parathyroid hypertensive factor, which increases cytosolic calcium and alters vascular tone and reactivity.

Adult↗
PubMed1997

Hemodialysis-induced upregulation of granulocyte adhesion molecules CD11b/CD18 is independent from 5-lipoxygenase activity.

Hemodialysis with new cuprophane membranes upregulates expression of granulocyte adhesion molecules and activates 5-lipoxygenase as reflected by the enhanced generation of leukotriene B4 (LTB4). We assessed the role of 5-lipoxygenase activity in hemodialysis-induced upregulation of the granulocyte adhesion molecules, CD11b and CD18, and granulocyte adhesion to human umbilical vein endothelial cells in an ex vivo dialysis model. 5-Lipoxygenase was effectively inhibited by preincubation of human whole blood with the specific inhibitor, BAY X1005. Dialysis with new cuprophane but not with new acrylonitrile membranes significantly upregulated expression of CD11b and CD18 by 6-fold and 4-fold, respectively. Inhibition of 5-lipoxygenase did not affect the expression of CD11b and CD18 during dialysis with either of the two membranes. In contrast to the enhanced expression of CD11b and CD18, adhesion of granulocytes to human umbilical vein endothelial cells did not increase during dialysis, nor was it affected by BAY X1005. These data indicate that ex vivo dialysis with cuprophane membranes upregulates expression of CD11b and CD18 on granulocytes independent of the activation of 5-lipoxygenase.

Adult↗
PubMed1996

Continuous ambulatory peritoneal dialysis impairs T lymphocyte selection in the peritoneum.

Peritoneal lymphocytes (PCL) of 45 healthy individuals, four uremic patients with end-stage renal disease (ESRD) and 25 long-term continuous ambulatory peritoneal dialysis (CAPD) patients were characterized by flow cytometry to investigate whether CAPD alters the phenotype of PCL. B lineage cells constitute a minority of PCL (2.5% of cells). Although the majority of peritoneal T cells expressed alpha beta T cell receptor (TcR), 7% expressed gamma delta TcR, a proportion which was significantly higher than that in peripheral blood (PBMC) (approximately 4%). The majority of PCL T cells exhibited markers of the thymus-dependent lineage (CD2, CD3, TcR alpha beta, CD8 alpha beta or CD4) and surface antigens associated with memory and activation (CD45RO, CD11a, CD18, CD49d, HLA-DR). An average of 75% of both CD4+ and CD8+ PCL T cells of healthy subjects and CAPD patients were CDw60+, thus characterizing the T cell subset containing the helper activity for the mitogen-driven B cell differentiation. CD44s was abundantly expressed on PCL T cells. In contrast to PCL T cells of healthy subjects peritoneal T lymphocytes of CAPD patients exhibited CD44 splice variants containing products of exon-v9 and the proportion of CD44v9+ cells correlated with the frequency of peritonitis episodes the patients had gone through. The majority of PCL T cells of both healthy subjects and CAPD patients were CD8+. A large proportion of CD8+ PCL T cells from healthy subjects expressed the homodimeric CD8 alpha alpha isoform; however, such cells were not found in CAPD patients. In healthy subjects mRNA for the recombination activating gene 1 (RAG-1) was detectable in a PCL population containing CD7-CD34+ and CD7+CD34+ cells. In contrast, neither mRNA transcripts of the RAG-1 gene nor CD34+ cells were detectable in PCL of CAPD patients.

Adult↗
PubMed1996

Modulation of procoagulant and fibrinolytic system components of mesothelial cells by inflammatory mediators.

Human peritoneal mesothelial cells (HMC) play a critical role in maintaining the intraperitoneal balance between fibrinolysis and coagulation by expressing the fibrinolytic enzyme tissue-type plasminogen activator (t-PA) as well as a specific plasminogen activator inhibitor, PAI-1, and the procoagulant protein tissue factor (TF). Of three compounds known to stimulate t-PA synthesis in cultured human endothelial cells, i.e., retinoic acid, the protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate (PMA), and sodium butyrate, only butyrate (1 mM) caused about a threefold increase in t-PA synthesis and mRNA expression in HMC after 24 h of incubation, without markedly affecting PAI-1 synthesis. PMA (10 nM) induced a threefold increase in urokinase-type plasminogen activator (u-PA) mRNA, but u-PA antigen levels in the HMC conditioned media remained below the detection level (0.5 ng/ml), possibly as a result of rapid uptake and degradation by the u-PA receptor. The u-PA receptor mRNA levels were about fivefold enhanced above control levels after PMA treatment of the cells. An increase in intracellular adenosine 3',5'-cyclic monophosphate levels by forskolin (10 microM) diminished t-PA and PAI-1 levels 43 and 17%, respectively. Among the inflammatory mediators tested [tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha, and bacterial lipopolysaccharide], TNF-alpha (10-1,000 U/ml) showed the strongest procoagulant effects. We found that the isoflavone compound genistein (25 micrograms/ml) prevented the TNF-alpha-induced expression of PAI-1 and TF while also slightly counteracting the decrease in t-PA synthesis. The protein kinase C inhibitor R0-318220 (3 microM) only moderately opposed the TNF-alpha-induced changes in t-PA and PAI-1 synthesis but completely prevented the induction of TF mRNA. In summary, our results demonstrate that t-PA synthesis in HMC is relatively insensitive to pharmacological stimulation. To restore the balance between fibrinolysis and coagulation under inflammatory conditions, attempts to interfere with the TNF-alpha-signaling pathway were more successful.

Blood Coagulation↗
PubMed1996

High-flux hemodialysis postpones clinical manifestation of dialysis-related amyloidosis.

Amyloidosis due to the retention of beta 2-microglobulin (beta 2-MG) is a frequent complication of hemodialysis (HD). Significant amounts of beta 2-MG can be removed from the body by highly permeable HD membranes, whereas conventional low-flux membranes are impermeable for the molecule. In a prospective and controlled study we investigated whether high-flux HD could delay the onset of dialysis-related amyloidosis (DRA). Twenty patients treated with cuprophane low-flux HD membranes were matched for age and previous time on HD either to continue their HD regimen or to receive HD treatment with high-flux polysulfone membranes. For 6 years each patient was examined for manifestations of DRA once a year or upon individual needs, additionally, serum beta 2-MG levels were monitored. After 6 years of follow-up no clinical signs of DRA were found in any of the patients dialyzed with high-flux polysulfone membranes, whereas 8/10 of the conventionally dialyzed patients had CTS and/or osteoarticular lesions. Serum levels of beta 2-MG were significantly reduced in patients treated with high-flux polysulfone membranes.

Adult↗
PubMed1996

Dietary salt, intracellular ion homeostasis and hypertension secondary to early-stage kidney disease.

Abnormal salt metabolism plays a central role in the pathogenesis of hypertension caused by early-stage renal disease. The mechanisms by which alterations in salt balance and the vasoconstrictor state are related are unclear. We studied the effects of three different salt diets (3, 6-9 and 12 g sodium chloride) on cellular ion homeostasis in platelets in 20 patients with renal hypertension. Compared to normal subjects, patients with renal hypertension had raised cytosolic sodium and calcium concentrations. The platelet sodium pump activity was significantly depressed and calcium ATPase activity increased. These abnormalities of cellular ion metabolism were aggravated by salt overload. On the other hand, dietary salt restriction tended to normalise these parameters. The data presented indicate that a circulating inhibitor of the sodium pump plays a central role in the pathogenesis of salt-induced renal hypertension and that the final common pathway of hypertension secondary to early-stage parenchymal renal disease is an elevation of resting cytosolic calcium followed by an elevation of peripheral vascular resistance.

Adolescent↗
PubMed1995

Limitations of pulse oral calcitriol therapy in continuous ambulatory peritoneal dialysis patients.

Calcitriol is increasingly used for therapy of secondary hyperparathyroidism in patients with end-stage renal disease. Its therapeutic efficacy, however, often has been limited by the associated increase in intestinal calcium and phosphorus absorption. Previous studies reported that these side effects could be avoided by intermittent administration of calcitriol in high doses, subsequently referred to as pulse therapy. The present study was designed to investigate pulse oral calcitriol therapy in a patient subgroup especially susceptible to the development of hypercalcemia and hyperphosphatemia under standard continuous calcitriol treatment. We examined 15 peritoneal dialysis patients with moderate degrees of hyperparathyroidism (intact parathyroid hormone [iPTH] levels, 150 to 903 pg/mL) ingesting between 1.5 and 6 g of calcium salts as the sole phosphate binders. Treatment consisted of 0.5 microgram calcitriol twice weekly. Eight of these patients had been previously converted to low calcium dialysate to tolerate the necessary doses of phosphate-binding calcium salts. During the study period, comprising 8 pretreatment weeks and 8 weeks of therapy, dialysates and doses of calcium salts were not changed, so that only calcitriol influenced the determined parameters. As expected, iPTH levels decreased rapidly in all patients (P < 0.0001). However, within 4 weeks of treatment a marked increase in calcium phosphorus products was observed (P < 0.0001). Overt hypercalcemia developed in five patients. We concluded that pulse oral calcitriol has to be carefully monitored in peritoneal dialysis patients receiving high doses of calcium salts because of the increased risk for hypercalcemia and hyperphosphatemia.

Administration, Oral↗