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Biomedical subjects

R M Schaefer

Publications and source records attributed to R M Schaefer.

At least 109 records · Page 6Linked to original sources
PubMed1990

Evaluation of a new polyamide membrane (Polyflux 130) in high-flux dialysis.

Removal of beta 2-microglobulin has become a major objective of dialysis therapy. The present study was performed to evaluate both compatibility and elimination capacity for beta 2-microglobulin of a newly developed high-flux polyamide membrane (Polyflux 130) during hemodialysis. The degree of leukopenia was moderate (-22%) and comparable with Polysulfone 600 (-25%). C3a desarg generation had a tendency to be lower with the Polyflux 130 membrane, and C5a desarg formation was identical with both types of membranes. As for degranulation of polymorphonuclear leukocytes, plasma elastase levels increased by 209% with Polyflux 130 and by 160% with Polysulfone 600 membranes. Likewise, plasma lactoferrin values rose during hemodialysis by 233% (Polyflux 130) and 160% (Polysulfone 600). The differences between membranes, however, were statistically not significant. There was a sharp drop in the serum levels of beta 2-microglobulin during dialysis with both membranes (Polyflux 130: -46%; Polysulfone 600: -48%). Accordingly, sieving coefficients were calculated to be 0.77 +/- 0.06 for Polyflux 130 and 0.80 +/- 0.06 for the Polysulfone 600 membrane. Both membranes were capable to remove large quantities of beta 2-microglobulin, amounting to 235 +/- 11 and 250 +/- 10 mg/4 h of dialysis for Polyflux 130 and Polysulfone 600, respectively.

Adult↗
PubMed1990

Dialysis membranes inhibit in vitro release of beta-2-microglobulin from human lymphocytes.

In the present study the effect of different dialysis membrane materials on in vitro beta 2-microglobulin (beta 2M) release by human lymphocytes was investigated. Lymphocytes were isolated from 11 long-term haemodialysis patients and 9 healthy controls. Cells were cultured either on flat sheet membranes made from Cuprophan, Hemophan and polyacrylonitrile or on polystyrol. beta 2M concentrations in the supernatant were measured at 3 and 7 days of culture, respectively. The beta 2M release from lymphocytes obtained from uraemic patients was almost identical with the release from healthy subjects. In the presence of all three membranes the release of beta 2M was less of what was produced on polystyrol. This held true for lymphocytes isolated from both healthy and uraemic subjects. As for the three membrane materials, the release of beta 2M into the supernatants was statistically not different when the adsorptive capacity of polyacrylonitrile was taken into account. However, there was a tendency for Cuprophan to exert the strongest inhibition, while Hemophan and polyacrylonitrile reduced beta 2M release to a lesser degree. Based on these data it seems that the increase in serum beta 2M which has been observed during dialysis with Cuprophan membranes is not caused by direct interaction of lymphocytes with Cuprophan membranes.

Acrylic Resins↗
PubMed1990

Assembly of terminal SC5b-9 complement complexes: a new index of blood-membrane interaction.

Activation of the complement system during the course of hemodialysis was recognized more than 20 years ago and since then the generation of C3a and C5a desarg has been used as parameters of blood-membrane interaction. More recently, determination of terminal C5b-9 complement complexes has become feasible. In the present study we determined plasma concentrations of C5b-9 complexes during hemodialysis using Cuprophan or Hemophan membranes. As early as 10 min into dialysis, Cuprophan membranes led to higher arterial plasma concentrations of C5b-9 complexes in comparison to Hemophan-containing devices. With Cuprophan, systemic arterial peak values of 237 +/- 27 U/ml were reached 45 min after the onset of dialysis, while corresponding peak values using Hemophan were only 58 +/- 16 U/ml. Venous concentrations of C5b-9 complexes, measured at the outlet of the dialyzer, were 489 +/- 102 U/ml with Cuprophan and 77 +/- 19 U/ml with Hemophan dialyzers. As an index of red cell lysis, plasma levels of free hemoglobin were evaluated. There was hemolysis with both membranes. Free hemoglobin levels increased threefold with Cuprophan and only twofold with Hemophan membranes. Taken together, plasma concentrations of C5b-9 complexes clearly discern between dialysis membranes of high or low compatibility. The fact that there is simultaneous lysis of red cells might indicate that deposition of C5b-9 complexes on innocent cells occurs which would lead subsequently to an array of diverse pathophysiological reactions.

Adult↗
PubMed1989

Independence of enhanced protein catabolism from glucocorticoids in chronically uremic rats.

Patients with chronic renal failure are prone to develop negative nitrogen balance resulting clinically in wasting and malnutrition. To study the role of glucocorticoids in the pathogenesis of uremic catabolism, we determined urinary excretion rates of urea and Nt-methylhistidine in chronically uremic rats with and without RU 38486, a potent antiglucocorticoid. In comparison to pair-fed non-uremic animals, chronically uremic rats displayed significantly enhanced ureagenesis, as demonstrated by increased urinary urea excretion, and myofibrillar protein breakdown, as indicated by increased excretion rates of urinary Nt-methylhistidine. The administration of RU 38486 to chronically uremic rats, however, did not result in a normalization of urinary excretion of Nt-methylhistidine. Similarly, the antiglucocorticoid did not influence the extent of ureagenesis in our uremic animals, as it was demonstrated by comparable levels of urinary urea excretion. This suggests that glucocorticoids are not involved in the pathogenesis of enhanced catabolism in chronic renal insufficiency.

Animals↗
PubMed1989

Effect of parathyroid hormone on elastase release from human polymorphonuclear leucocytes.

Acute and chronic renal failure are clinical states associated with secondary hyperparathyroidism and increased catabolism. It has been suggested that elevated proteolytic activity is present in the blood in these clinical states. It is, theoretically, possible that the excess blood levels of parathyroid hormone (PTH) in patients with these disorders stimulate release of proteases, since this latter process is calcium dependent and PTH enhances entry of calcium into cells. The present study examined the effect of PTH and its amino- and carboxyterminal fragments on elastase release from polymorphonuclear leucocytes (PMNL), and evaluated the mechanisms underlying such an action. 1-84 PTH stimulated elastase release from PMNL in a dose-dependent and time-dependent manner. This effect of the hormone was abolished by its inactivation as well as by the presence of EDTA. Verapamil, trifluoperazine and W-7 reduced but did not abolish the 1-84 PTH-induced stimulation of elastase release from PMNL. Phorbol ester (PMA) also stimulated elastase release but both PTH or PMA-induced elastase release was blunted by staurosporin, an inhibitor of protein kinase C. The 19-84 carboxyterminal PTH also produced significant stimulation of elastase release from PMNL but the amino-terminal 1-34 PTH or other peptide hormones (insulin, calcitonin, and ACTH) had no stimulatory effect on elastase release.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Carnitine and carnitine esters in acute renal failure.

Plasma concentrations of carnitine and carnitine esters were determined in patients with multiple forms of acute renal failure with and without sepsis, and also before and after haemodialysis therapy. Total carnitine, free carnitine, short-chain and long-chain acylcarnitine values of both groups of acute renal failure patients were markedly elevated compared with healthy subjects and chronically uraemic patients undergoing regular haemodialysis treatment. Carnitine and carnitine esters did not differ between septic and non-septic patients before and after haemodialysis with dialysers made of cuprophane or polysulphone. Animal experiments with acutely uraemic rats were performed in order to determine whether the liver or the kidney may be responsible for elevated carnitine and carnitine esters in acute renal failure. Plasma and liver total carnitine, free carnitine, short-chain acylcarnitine and long-chain acylcarnitine were significantly elevated in sham-operated animals, and further in ureter ligated and bilateral nephrectomised rats. Skeletal muscle and heart muscle carnitine and carnitine esters remained the same as in sham-operated controls. Our data demonstrate markedly increased liver carnitine synthesis and carnitine acylation in an acute uraemic rat model even after binephrectomy and 48-h food depletion and in the presence of elevated serum carnitine concentrations. Furthermore, from our clinical study we conclude that there is no need for carnitine supplementation in patients who developed acute renal failure in the postoperative and post-traumatic state under adequate nutrition even when requiring daily haemodialysis.

Acute Kidney Injury↗
PubMed1989

Decreased proteinase activity in isolated glomeruli of streptozotocin diabetic rats.

The important initiating process of diabetic nephropathy is the glomerular accumulation of proteins which has been proposed to be due to a synergistic interaction of the disturbed intrarenal hemodynamic and the altered chemical composition of glomerular components. This study was performed to investigate whether there might be a reduced activity of glomerular proteinases in streptozotocin diabetic rats. Three weeks after the induction of diabetes by means of streptozotocin, we found a decreased proteinase activity in ultrasonically destroyed isolated glomeruli obtained by a differential sieving technique in comparison to nondiabetic controls. This held true at acidic (16.59 +/- 1.56 vs. 22.19 +/- 1.94 U/min/mg protein) as well as at neutral pH (7.82 +/- 0.55 vs. 10.67 +/- 0.81 U/min/mg protein) and could be confirmed when proteinase activity was related to the single glomerulus or DNA instead of protein. Treatment with insulin was effective in improving the degradative capacity at both pH levels. We suggest that decreased proteinase activity in diabetic glomeruli may, at least partly, explain the glomerular protein accumulation in diabetic nephropathy.

Animals↗
PubMed1989

Enhanced plasma and intracellular levels of main granulocyte components in diabetics on dialysis.

Intracellular and plasma levels of main granulocyte components (elastase, lactoferrin) were investigated in 25 diabetic and 27 nondiabetic patients undergoing regular hemodialysis treatment (RDT) as well as in 14 diabetic and 11 nondiabetic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Diabetic patients on dialysis released more intragranular enzymes from neutrophils than their nondiabetic counterparts. Intracellular concentrations of granulocyte elastase and lactoferrin were only slightly higher in uremic diabetics than in uremic nondiabetics. However, both diabetic and nondiabetic hemodialysis patients displayed significantly lower cellular elastase and lactoferrin levels than healthy subjects. In addition, the diabetic dialysis patients had more protein catabolic fragments in the plasma as determined by trichloroacetic acid solubility. These observations were cited to support the hypothesis that not only is the hemodialysis procedure itself (with exposure to membranes) catabolic, but the diabetics are in double jeopardy. Thus, neutrophil abnormalities in diabetics on dialysis might affect the plasmatic proteinase inhibitor system and contribute to enhanced plasma protein degradation as well as to enhanced susceptibility to infections.

Adult↗
PubMed1989

Catabolic effects of ethanol in chronically uremic rats.

Both ethanol consumption and uremia are considered to be associated with wasting, malnutrition and debilitation. The present study was designed to investigate as to whether ethanol exerts a stimulatory effect on the catabolic state of renal failure. Rats underwent 5/6-nephrectomy and were fed either with or without ethanol. The degree of uremia was comparable in both groups. Ethanol-fed uremic rats, however, displayed higher serum levels of urea (+ 103%) and glucose (+29%), as compared to uremic animals without alcohol. Subsequently, the urea N appearance was enhanced (+60%) in uremic rats with alcohol as compared to uremic animals without alcohol. In sham rats urea N appearance was also increased (+39%) following ethanol administration in comparison to sham-operated rats without alcohol, albeit to a lesser degree. Urinary Nt-methylhistidine excretion, an indicator of myofibrillar protein breakdown, was enhanced throughout the experiment in uremic rats receiving ethanol. Finally, ethanol caused higher urinary excretion rates of corticosterone in uremic animals as compared to uremic rats without ethanol. There was a significant correlation between urinary corticosterone excretion and both urea N appearance and urinary Nt-methylhistidine excretion. We conclude that ethanol consumption further aggravates the catabolic state of uremia and that this is mediated by an increment in glucocorticoid production.

Alcohol Drinking↗
PubMed1989

In vivo viability of 111In-labelled granulocytes demonstrated in a sham-dialysis model.

In seven febrile patients undergoing regular dialysis treatment, sham-dialysis with a dialyzer equipped with a cuprophane membrane was performed during a routine 111In-oxine white blood cell scan with "pure" granulocytes isolated on a discontinuous gradient (Percoll/plasma: n = 5; Metrizamide/plasma: n = 2). The patients were in contact with the cuprophane membrane over 45 or 90 min. Twenty-five (+/- 5) minutes after the start of the dialysis, the peripheral leucocyte count (59 +/- 22%) and the 111In activity in the peripheral blood decreased to a minimum of their initial range (64 +/- 21%) because of leucocyte activation. The activity over both lungs increased symmetrically (29 +/- 15%), the spleen activity decreased (14.8 +/- 8%) and the liver activity remained constant. At the end of the dialysis (45-90 min post-injection), the number of circulating neutrophils, peripheral 111In activity and activity distribution in the organs regained their initial level. In conclusion, these data confirm previously described data concerning the sequestration of neutrophils into the lung during dialysis treatment. The data demonstrate the origin of the activated neutrophils in the circulation and the spleen. The identical behaviour of 111In-oxine-labelled and unlabelled granulocytes is demonstrated. Additionally, the accumulation of activity in the spleen is due not to opsonized cells but to sequestrated neutrophils, which are able to migrate from the spleen after adequate activation. The migration of activated cells into the lung explains the diagnostic difficulties posed by diffuse lung uptake in leucocyte scans in patients with leucocyte-activating diseases.

Adult↗