[Hemoperfusion with activated charcoal in the treatment of drug overdose. Clinical experiences with 20 patients].
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Biomedical subjects
Publications and source records attributed to H Schiffl.
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Calcium ATPase, an enzyme involved in intestinal calcium transport, was measured in homogenates of duodenal mucosal scrapings of normal and uremic rats. The effects of calcium deprivation and treatment with 1 alpha,25-dihydroxycholecalciferol [1,25-(OH)2D3] were investigated as well. Uremia decreased the enzyme activity and impaired the rise after calcium deprivation as observed in intact rats. The 1,25-(OH)2D3 treatment increased the enzyme activity in uremic animals and resulted in an identical response to calcium deprivation as observed in intact rats; parathyroidectomy abolished this effect. A striking correlation between everted duodenal gut sac calcium transport and calcium ATPase activity could be demonstrated for all groups of rats studied. It is concluded that the calcium ATPase activity is linked to the production of 1,25-(OH)2D3 as well as to an additional factor, probably parathyroid hormone. The close relationship between enzyme activity and in vitro calcium transport, even during constant physiological supplementation with 1,25-(OH)2D3, suggests an autonomous role of the calcium ATPase activity for mediation of calcium transport in the duodenum in addition to the well-known mechanisms related to vitamin D and its metabolites.
The hypercalcaemic response to 1,25 dihydroxycholecalciferol (1,25(OH)2D3) treatment was studied in mild uraemic rats (5/6-nephrectomy) under conditions of varying magnesium intake of 0.05% (control) and 0.75% (experimental). After 3 weeks' exposure to the high magnesium diet a loss of the hypercalcaemic effect of 1,25(OH)2D3 when given as 40pmoles i.p. during 5 days was observed. By use of standard clearance experiments a similarity of the renal magnesium and calcium handling could be demonstrated. At high serum magnesium levels, the fraction of filtered magnesium excreted in the urine rose, concomitant with an increased fractional excretion of calcium (r=0.81). The bone magnesium content was correlated with serum levels and therefore increased after high dietary magnesium. Treatment with 1,25(OH)2D3 resulted in an increase of the bone calcium content (p less than 0.05) after low magnesium diet, but not after high magnesium feeding. It is concluded that high urinary calcium excretion after magnesium loading contributes to the impaired calcaemic response of 1,25(OH)2D3 in azotaemic rats, while calcium uptake of bone is impaired.
The excretion of the diuretic substance DADMP (I,4-diamino-6.7-dimethylpteridine) and of DMP (6.7-dimethylpterin) was studied on single nephrons of the rat kidney using microperfusion and microinjection techniques. In the proximal tubule only DADMP was reabsorbed to a significant degree. Fractional reabsorption rate was independent of the load applied and the permeability constant was found to be 2.2 . 10(-4) cm . s-1. Similar results were obtained in nephrons in which the substances, with inulin, were injected from middle proximal tubular puncture sites and recovered in the urine. DMP appeared in the urine quantitatively and simultaneously with the injected inulin. DADMP recovery, however, was only 20--30% of the injected load during the injection period and after 2 h some 70% was recovered from the urine of both kidneys. The reabsorbed fractions were independent of the loads applied, which varied between 2 . 10(-13) mol . min-1 and 10(-9) mol . min-1. A comparison of the microperfusion and the microinfusion data suggests that the reabsorption of DADMP occurs predominantly in the proximal convolution, and it appears that the differences between the renal handling of DMP and DADMP are explicable by their different lipid solubilities.
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Dietary polyethylene glycol (PEG) induces an increase in the specific activity of Na+-K+-activated adenosine triphosphatase (Na-K-ATPase) in the cecum mucosa of rats. Using cecum mucosa homogenates and cellular subfractions obtained by differential centrifugation, the induction process was studied with respect to time course, subcellular distribution and properties of the enzyme. In comparison with controls, Na-K-ATPase specific activity was stimulated in PEG treated rats in the total homogenate and the microsomal (105000 X g) but not in the mitochondrial (9000 X g) or nuclear (1000 X g) sediment. The specific activity of Mg-ATPase did not change in any of the fractions. Na-K-ATPase induction was statistically significant after 2 days and complete after 1-2 weeks, in parallel with the previously described stimulation in net sodium absorption. Kinetic analysis showed Vmax for ATP to be doubled while Km for ATP, Na and K as well as the optimal Mg/ATP ratio and Ki for ouabain remained unchanged. It is proposed that Na-K-ATPase and active sodium transport are closely associated in rat cecum and that dietary Na-K-ATPase stimulation is due to the induction of more enzyme molecules per unit basolateral cell membrane.
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The mortality of critically ill patients with acute renal failure (ARF) requiring hemodialysis remains high (> 50%), even though major improvements in the management of this disorder have been made. Sepsis has been identified as a major cause of death in ARF. Experimental data have suggested that bioincompatible membranes aggravate uremia induced neutrophil dysfunction. In the following two combined prospective, randomized, clinical studies, the effects of the biocompatibility of dialysis membranes on the susceptibility to infection were compared in 72 surgical and medical patients with ARF. The group of patients treated with biocompatible polyacrylonitrile membranes had a significantly lower incidence of bacterial infections and a lower relative and absolute mortality rate due to sepsis, compared to patients treated with bioincompatible cuprophane membranes. These investigations identified bioincompatibility as a factor that adversely affects the prognosis of critically ill patients with ARF.
The mortality rate of critically ill patients with acute renal failure (ARF) has remained high. The impact of vigorous intermittent hemodialysis (IHD) on the outcome of ARF has not been validated. In this retrospective multicenter analysis, 154 patients with ARF were treated daily (intensive) or on alternate days (conventional) using complement and cell activating cuprophane (bioincompatible) or high-flux polysulfone dialyzer membranes with insignificant effects on circulating complement or cells (biocompatible). At initiation of IHD, all four groups were similar in patient characteristics and ARF factors. The use of synthetic membranes resulted in a reduced mortality rate (18% vs 45%; p < 0.001) and shorter duration of ARF (8 vs 15 sessions; p < 0.001). Daily IHD with cellulose based membranes tended to increase mortality rates compared with conventional cuprophane dialysis (37% vs 53%). Intensive IHD with polysulfone membranes resulted in a further decrease in overall mortality rates (15% vs 22%). This retrospective analysis shows that bioincompatibility of dialyzer membranes may be more important for the outcome of patients with ARF than the dose of dialysis. Its impact on outcome occurs independently of the dose of dialysis delivered.
OBJECTIVE: While most hypertensive patients with end-stage renal disease normalize high blood pressure with fluid removal by continuous ambulatory peritoneal dialysis (CAPD), there is a significant proportion of CAPD patients whose blood pressure can be controlled only by antihypertensive drugs. METHOD AND PATIENTS: To study the hypothesis that such patients are still volume overloaded, we used plasma cyclic guanosine monophosphate (cGMP) as a marker for hydration status. Thirty-two CAPD patients were divided into 3 groups: group 1, normotensive patients (n = 12); group 2, hypertensive patients who normalized their blood pressure with fluid removal (n = 12); group 3, hypertensive patients whose blood pressure was refractory to intensified fluid removal (n = 8). RESULTS: Mean cGMP levels were significantly higher in dialysis-sensitive hypertension (27 +/- 5 pmol/mL) than in dialysis-refractory hypertension (15 +/- 2 pmol/mL), or in normotensive patients (13 +/- 4 pmol/mL). Reduction of excess fluid in volume overloaded hypertensive CAPD patients resulted in a normalization of cGMP levels (14 +/- 8 pmol/mL), but did not affect this volume marker in patients with dialysis-resistant hypertension (10 +/- 4 pmol/mL). CONCLUSION: Plasma cGMP levels are elevated in volume overload-induced hypertension complicating CAPD. Hypertensive CAPD patients whose plasma cGMP levels are within normal limits have raised blood pressure refractory to volume removal. Our findings are consistent with the hypothesis that inadequate removal of excess volume plays a major role in a subset of patients with CAPD hypertension.
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OBJECTIVES: Residual renal function (RRF) is of paramount importance to dialysis adequacy, morbidity, and mortality, particularly for long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Residual renal function seems to be better preserved in patients on CAPD than in hemodialysis (HD) patients. We analyzed RRF in 45 patients with end-stage renal disease (ESRD), commencing either CAPD or HD, to prospectively define the time course of the decline in RRF, and to evaluate dialysis-technique-related factors such as cardiovascular stability and bioincompatibility. STUDY DESIGN: Single-center prospective investigation in parallel design with matched pairs. MATERIALS: Fifteen patients starting CAPD and 15 matched pairs of patients commencing HD were matched according to cause of renal failure and RRF. Hemodialysis patients were assigned to two dialyzer membranes differing markedly in their potential to activate complement and cells (bioincompatibility). Fifteen patients were treated exclusively with the cuprophane membrane (bioincompatible) and the other 15 patients received HD with the high-flux polysulfone membrane (biocompatible). MEASUREMENTS: Residual renal function was determined at initiation of dialytic therapy and after 6, 12, and 24 months. Dry weight (by chest x ray and diameter of the vena cava) was closely recorded throughout the study, and the number of hypotensive episodes counted. RESULTS: Residual renal function declined in both CAPD and HD patients, although this decline was faster in HD patients (2.8 mL/minute after 6 months and 3.7 mL/min after 12 months) than in CAPD patients (0.6 mL/min and 1.4 mL/min after 6 and 12 months respectively). It declined faster in patients with bioincompatible than with biocompatible HD membranes (3.6 mL/min vs 1.9 mL/min after 6 months). Eleven percent of the HD sessions were complicated by clinically relevant blood pressure reductions, but there were no differences between the two dialyzer membrane groups. None of the CAPD patients had documented hypotensive episodes. None of the study patients suffered severe illness or received nephrotoxic antibiotics or radiocontrast media. CONCLUSIONS: The better preservation of RRF in stable CAPD patients corresponded with greater cardiovascular stability compared to HD patients, independently of the membrane used. Furthermore, there was a significantly higher preservation of RRF in HD patients on polysulfone versus cuprophane membranes, indicating an additional effect of biocompatibility, such as less generation of nephrotoxic substances by the membrane. Thus, starting ESRD patients on HD prior to elective CAPD should be avoided for better preservation of RRF.
A 19-year-old patient on chronic ambulatory peritoneal dialysis experienced severe neurologic disturbances caused by uremia. Increased signal intensity was seen bilaterally in the cortical and subcortical areas of the occipital and parietal lobe on cranial magnetic resonance imaging (MRI). Insufficient peritoneal dialysis efficacy was documented and the patient was switched from peritoneal to hemodialysis. Cranial MRI indicated a marked regression of the lesions to nearly normal, confirming the diagnosis of uremic encephalopathy.
OBJECTIVE: The present study is aimed at gaining insight into coagulation and fibrinolysis in the peritoneal cavity of patients on continuous ambulatory peritoneal dialysis (CAPD). For this purpose we measured coagulation- and fibrinolysis-related antigens in plasma and dialysate, comparing patients with and without peritonitis. DESIGN: Markers of activated coagulation and fibrinolysis in plasma and dialysate of CAPD patients were determined at different time points (0 hr, 2 hr, 4 hr) after infusion of the dialysis solution in the peritoneal cavity. Prothrombin fragment (F1 + 2), thrombin-antithrombin III complex (TAT), and fibrin monomer (FM) were chosen as parameters of activated coagulation. Fibrin degradation products (FbDP), D-dimer (DD), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) were measured as parameters for ongoing fibrinolysis. Beta 2-microglobulin, albumin, and IgG were used as marker proteins for the diffusion of proteins of intravascular origin into the peritoneal cavity. PATIENTS: Eleven clinically stable CAPD patients, who had not suffered from peritonitis during the last six months, and 5 CAPD patients with an acute episode of bacterial peritonitis were studied. RESULTS: In the dialysate of stable CAPD patients (n = 11) the concentration of activation markers of coagulation and fibrinolysis increased continuously with dwell time. After four hours we found remarkably high levels of the coagulation markers F1 + 2 (0.4 +/- 0.1 nmol/L), TAT (6.5 +/- 1.0 ng/mL), and FM (24.5 +/- 7.1 micrograms/mL), and the fibrinolysis markers DD (851 +/- 26 ng/mL), FbDP (1.0 +/- 0.3 microgram/mL), t-PA (3.3 +/- 0.8 ng/mL), and PAI-1 (2.6 +/- 1.2 ng/mL). The dialysate-to-plasma (D/P) ratios of all of these antigens were significantly higher compared to the D/P ratios of proteins with similar molecular weight, which are not produced intraperitoneally (beta 2-microglobulin, albumin, and IgG). These findings point to a local, thrombin-induced intraperitoneal fibrin generation during regular CAPD. Compared with clinically stable CAPD patients, the patients with bacterial peritonitis (n = 5) had significantly higher levels of F1 + 2 (5.3 +/- 1.6 nmol/L), TAT (57.8 +/- 10.7 ng/mL), FM (972 +/- 3.2 micrograms/L), FbDP (16.4 +/- 2.9 micrograms/L), and PAI-1 (7.3 +/- 2.4 ng/mL) in the dialysate (4-hr dwell time), and a 2.4-times higher ratio between FM and FbDP. These results can be interpreted as an intraperitoneal imbalance between coagulation and fibrinolysis during peritonitis. CONCLUSION: Our study demonstrates a high intraperitoneal fibrin formation, not only during peritonitis but also in clinically stable CAPD patients. The remarkably high levels of coagulation (F1 + 2, TAT, FM) and fibrinolysis (FbDP, DD, t-PA, PAI-1) related antigens in the dialysate of patients without peritonitis cannot be explained by transport from plasma into the peritoneal cavity and may reflect a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin is obviously disturbed in CAPD patients with peritonitis, who had significantly higher levels of coagulation markers in the dialysate and a higher ratio between FM and FbDP.
OBJECTIVE: To report on 3 patients with inflammatory demyelinating peripheral neuropathy in strong temporal coincidence with the initiation of peritoneal dialysis (PD) therapy. SETTING: Nephrology and Neurology Department of the University Hospital, Munich, Germany. PATIENTS: Three patients with end-stage renal failure presented with the clinical picture of inflammatory demyelinating peripheral neuropathy within 4 to 10 weeks after start of continuous ambulatory peritoneal dialysis (CAPD). They had acute or subacute onset of lower extremity or generalized weakness, diminished reflexes, elevated spinal fluid protein levels, and signs of demyelinating neuropathy on electrophysiological testing. MEASURES: Clinical follow-up, nerve conduction studies, cerebral spinal fluid (CSF). RESULTS: All patients did not improve under intensified PD therapy but took profit from immunomodulatory therapy. One bed-bound patient improved after change to hemodialysis and showed complete remission after renal transplantation. CONCLUSION: Because of strong temporal coincidence, a causal relationship between CAPD and inflammatory demyelinating peripheral neuropathies can be suspected in these 3 patients.