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Biomedical subjects

H Klinkmann

Publications and source records attributed to H Klinkmann.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effects of selenium supplementation on immune parameters in chronic uraemic patients on haemodialysis.

BACKGROUND: The involvement of selenium (Se) in immune response has been increasingly recognized, cell-mediated immunity being principally affected by Se deficiency. Blood Se levels in chronic uraemic patients are frequently lower than in controls, and in these patients cellular immunity in generally impaired. METHODS: The present study was designed to assess the effects of Se supplementation over 6 consecutive months on immune parameters in haemodialysis (HD) patients from Rostock (Germany) and Chieti (Italy). In both cities, five patients were supplemented with Se (500 micrograms thrice weekly for 3 months, then 200 micrograms thrice weekly for the next 3 months), whereas another five patients received placebo. All Se determinations were performed in a single laboratory. RESULTS: In both cities, basic plasma Se levels were significantly lower in patients than in their corresponding normal controls. After beginning Se supplementation, plasma Se concentration promptly normalized and levelled off in the normal range throughout the study. Se administration was well tolerated by all patients, and no side-effects attributable to Se toxicity were observed. Although no major change in immunocompetent cells (white blood count, total lymphocyte count, lymphocyte subpopulations) was observed during Se therapy, an improvement in T-cell response to phytohaemoagglutinin (as evaluated in Rostock patients) and a significant progressive increase in delayed-type hypersensitivity (as evaluated in Chieti patients) was observed in supplemented patients. After 6 months of Se therapy, the increase in delayed-type hypersensitivity of supplemented patients proved to be significantly higher when compared to both presupplementation values and to the results found in non-supplemented patients. Three months after suspension of Se supplementation, plasma Se levels and delayed hypersensitivity significantly decreased in Chieti patients, with both parameters returning similar to presupplementation values. CONCLUSIONS: In accordance with previous studies done in non-uraemic subjects, our investigation demonstrates for the first time the immunostimulatory properties of Se in HD patients. Though several problems on Se metabolism in uraemia remain unresolved, in our opinion moderate and safe Se supplementation can be beneficial in chronic uraemic patients.

Adjuvants, Immunologic↗
PubMed1994

Membranes for dialysis.

In the submitted review the authors give an account of contemporary problems of membranes for dialysis available at present. Although the authors mention also cellulose based membranes (membranes made from unmodified regenerated cellulose, synthetic modified cellulose membranes produced by chemical transformation of cellobiose), the main attention is paid to polymer membranes--typical synthetic polymers, i.e. polysulphone (PSu), polyacrinon nitrate (PAN), polyamide (PA), ethyl vinyl alcohol polymers (EVAL), polyester mixtures formed by polyacrylonitrile and polyether sulphone (PEPA). The authors describe their adsorption capacity, possibility of sterilization and specific problems of interaction with different drugs. In the conclusion the authors outline demands on the development of modern membranes and their problems in future.

Humans↗
PubMed1994

Effect of recombinant human erythropoietin treatment in uremic patients on oxygen affinity of hemoglobin.

Anemia of chronic renal failure is associated with a reduced affinity of hemoglobin for oxygen (Hb-O2 affinity). It has been reported that the correction of renal anemia by recombinant human erythropoietin (rhuEPO) treatment could be associated paradoxically with a further decrease in Hb-O2 affinity. We investigated changes in the compensatory mechanisms of chronic renal anemia during 25 weeks of rhuEPO treatment, in 19 chronic hemodialyzed (HD) patients. There was no significant variation of mean standard P50 (P50std). Average 2,3-diphosphoglycerate (DPG) increased after 13 weeks and remained stable. The large interindividual variations prompted us to study delta P50std and delta Hb. We demonstrated a negative correlation between delta P50std and delta Hb. Thus, P50std increased in patients who did not immediately correct their anemia and decreased in patients whose Hb values rose. These data showed that the major factor influencing variations of Hb-O2 affinity in chronic HD patients treated by rhuEPO is the variation of Hb concentrations. In our study, it was demonstrated that the most important rise in P50std and 2,3-DPG occurred in patients who were late responders to rhuEPO.

Adult↗
PubMed1993

Behaviour of platelets and beta-thromboglobulin.

Platelet count, platelet aggregation responses, and plasma beta-thromboglobulin were assessed before and at intervals during each study dialysis. As expected, modest thrombocytopenia was observed following treatment with all dialysers, but Filtral showed the least effect. Concordantly, modest increases in plasma beta-thromboglobulin were observed with all devices except Filtral (caveat: the device also seems to adsorb beta-thromboglobulin). Interpatient variability was more striking for platelet aggregation responses, and made it difficult to discern patterns; however, aggregation in response to ADP was augmented during haemodialysis with the Filtral device, and blunted when the G120 M was employed. Differences between hollow-fibre and parallel plate devices with the same membrane material suggest that membrane geometry, manufacturing residues, membrane support, or potting materials may also contribute to platelet activation.

Adenosine Diphosphate↗
PubMed1993

Introduction, demography, and general methods.

The International Cooperative Biocompatibility Study was planned to analyse the symptomatic and laboratory response to seven different dialysers studied in five centres in four countries. The dialysers used were the G10-3N, G120 M, CD 4000, T 150, Duo-Flux, F 60, and Filtral (see below for full description). A total of 37 patients in the Veterans Administration Lakeside Medical Center, Chicago; Henry Ford Hospital, Detroit; Osaka City University Hospital, Osaka; Wilhelm Pieck University Hospital, Rostock; and Huddinge University Hospital, Stockholm were studied. All patients had been dialysed for a minimum of 6 months, were non-diabetic, stable, and compliant; and most were middle-aged and male. Patients were treated three times per week for 2 weeks with each new dialyser with random assignment to one of four orders of dialyser use. The same manufacturing lot of each dialyser, blood line sets and needles were used by all centres. Delivery systems were volumetric controlled except for some patients in Osaka treated with negative-pressure equipment. Individual patient prescriptions (Kt/Vs for urea), in use prior to the study, were continued. Kt/Vs for all treatments were derived from reported blood flows and blood water corrected mass transfer coefficients multiplied by dialyser surface area. Clinical data were measure pre-, intra- and postdialysis. Hourly signs, symptoms, drugs, and nursing interventions were recorded using the identical treatment record at all centres. In addition, patients completed a questionnaire form (translated into the appropriate language) at least weekly, relating symptoms experienced with each dialyser. Laboratory investigations were performed during the sixth consecutive treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

beta 2-Microglobulin and granulocyte elastase.

Plasma beta 2-M was measured by radioimmunoassay in samples obtained before and after dialysis with seven different dialysers, tested according to the protocol of the International Cooperative Biocompatibility Study (ICBS). Plasma beta 2-M was corrected for contraction of its distribution volume, which was assumed to be equal to the extracellular fluid volume. The uncorrected plasma beta 2-M concentration increased with all conventional dialysers, including the G10-3N, (cuprammonium cellulose plate), G120 M (cuprammonium cellulose hollow fibre), CD 4000 (cellulose acetate) and T 150 (polymethylmethacrylate). However, no significant differences were found between the predialysis and the corrected postdialysis plasma beta 2-M concentrations with these conventional dialysers, and thus no evidence of net generation or release of beta 2-M was found in this study. With high-permeability membranes, the corrected postdialysis beta 2-M values were decreased by 27.1% with the Duo-Flux Artificial Kidney, 53.5% with F 60, and 34.6% with Filtral, indicating that dialysers with these membranes eliminate plasma beta 2-M to a certain extent. The complex of granulocyte elastase with alpha 1-antiproteinase in plasma was also measured in samples from the arterial blood line collected before, and after 30 and 120 min of dialysis with each of the seven dialysers in this study. All dialysers elicited an increase in the mean plasma elastase concentrations which was more than twice as high with cuprammonium cellulose plate than with all of the others. The change of elastase at 120 min of dialysis varied considerably with each dialyser and was statistically significant with all except CD 4000, F 60, and Filtral.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellulose↗
PubMed1993

Dialysis-induced hypoxaemia.

A crossover study to compare the effects of seven different dialysers on blood gas conditions during dialysis using acetate-containing dialysate was carried out at five centres in four countries. A significant decrease in pO2 was noted at both 15 and 60 min after the start of dialysis for all dialysers, with the greatest decrease at 60 min. Filtral caused the greatest reduction and F 60 the least change at both 15 and 60 min. These differences were statistically significant according to the ANOVA multiple-range test for variance. pCO2 also declined by 1.0-2.7 mmHg at 15 min and by 0.7-3.8 mmHg at 60 min. The delta pCO2 was comparable across dialysers and no significant differences were found. Although pH showed no change at 15 min, it was slightly but significantly increased at 60 min across all dialysers compared to predialysis values. There were no statistical differences between dialysers. Calculated blood bicarbonate content significantly decreased at 15 min and recovered at 60 min. Along with the greater decrease in pO2, a larger loss of total CO2 was noted for Filtral. On the other hand F 60 caused the least change in total CO2. This difference may be due to membrane characteristics affecting the diffusion coefficient for O2, CO2, and bicarbonate. Multifactorial mechanisms are likely to be involved, but reflex hypoventilation and an increase in O2 consumption also contributed to hypoxaemia in this study.

Acetates↗
PubMed1993

Behaviour of white blood cells and the complement system.

Seven different types of dialysers were investigated in five dialysis centres in four countries with respect to behaviour of white blood cells and the complement system. The results of this controlled crossover study demonstrated significant differences in the dialysers. Those containing cuprammonium cellulose (G10-3N and G120 M) showed the greatest changes in white blood cell count, including monocytes and neutrophils, as well as the greatest complement activation. With regard to lymphocytes the subpopulation of low-mobility cells, which were predominantly the B-cells, showed the greatest mobility with dialysers containing cuprammonium cellulose. The PAN copolymer- and PMMA-containing dialysers Filtral and T 150 clearly caused the least changes in white blood cells and complement factors. Dialysers containing cellulose acetate and polysulphone membranes (Duo-Flux Artificial Kidney, CD 4000, and F 60) produced only a moderate decrease of WBC, monocyte, neutrophil, and lymphocyte counts, and this result corresponded to a relatively small change in complement factors.

Acrylic Resins↗
PubMed1993

Biocompatibility of a new high-permeability modified cellulose membrane for haemodialysis.

The biocompatibility and solute permeability characteristics of a high-permeability modified cellulose membrane (Hemophan-HP) (He-HP) were compared with those of two synthetic membranes (poly(ethylene-co-vinyl alcohol) (EVAL) and poly(acrylonitrile-co-sodium methallyl sulphonate) (AN69)) and Cuprophan in a multicentre, four-way cross-over clinical trial. Cuprophan membranes caused significant complement activation, leukopenia, and granulocyte elastase release. He-HP membranes demonstrated a lesser effect, which was similar to that observed for the EVAL membrane, although less than that seen with the AN69 membrane. A similar order for the four membranes was seen for their effect on platelets. Cuprophan membranes provided superior small-molecule removal to the other three membranes. In contrast, Cuprophan was essentially impermeable to beta 2-microglobulin, whereas He-HP, EVAL, and AN69 allowed the removal of 60-90 mg of beta 2-microglobulin per treatment. However, a decrease in the plasma concentration of beta 2-microglobulin was observed only with the AN69 membrane, most probably as a result of the ability of that membrane to adsorb proteins. Our results demonstrate that high-permeability membranes of comparable biocompatibility to some synthetic membranes can be fabricated from cellulose derivatives.

Adult↗
PubMed1993

Adverse events of subcutaneous recombinant human erythropoietin therapy: results of a controlled multicenter European study.

In a controlled European multicenter study, clinical tolerance of subcutaneously administered recombinant human erythropoietin (rh-EPO) therapy and its influence on the course of illness in 362 hemodialyzed patients (162 males, 200 females) from 16 European dialysis centers was studied. Of these, 181 patients served as a control group in the first year and received rh-EPO therapy in the second year. Of the 837 adverse events that occurred, 277 were classified as serious and 560 as nonserious. Thirty-two deaths have been reported for the study population: 18 in the control group and 14 in the therapy group. The individual analysis of the serious adverse events including death demonstrates a protective effect of rh-EPO on the high-risk cardiovascular situation of dialysis patients. Hypertension was no problem, and under rh-EPO therapy an increase in resistance to infection was observed. Subcutaneous rh-EPO treatment might have an even better safety profile than intravenous application.

Adult↗
PubMed1993

Extracorporeal endotoxin removal by immobilized polyethylenimine.

The neutralization of bacterial endotoxins (ET) is still an unsolved problem in therapeutic medicine. The efficacy of anti-endotoxin antibodies or receptor antagonists and other substances interfering with the endotoxin-induced pathomechanisms is dependent on an intact cellular degradation system of the host. However, the phagocytosis function of that system seems to be impaired regularly in patients with intense or long-lasting endotoxemia or septic shock and in patients undergoing hemodialysis. Extracorporeal adsorption of ET might well be an effective support in the anti-ET therapy by lowering the amount of circulating ET and thus relieving the defense system of the body. In this work a new ET-adsorbent based on macroporous cellulosic beads with immobilized polyethylenimine (PEI) was tested for its ET-removal capacity in vitro. A test solution with 100 ng/ml ET from Escherichia coli 055:B5 was recirculated in a system containing the adsorbent beads. Polymyxin B immobilized to the same carrier was used for comparison. PEI as well as polymyxin B showed complete removal of ET from plasma and water as was measured by the Limulus Amebocyte Lysate (LAL) test (Chromogenix). The biocompatibility of the PEI absorber was superior to that of polymyxin B. The results indicate that the PEI absorber is of high efficacy and possibly of interest for the treatment of endotoxemia.

Adsorption↗
PubMed1993

Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins.

The removal of protein-bound substances of pathogenetic relevance from blood is of therapeutic interest for drug intoxications, renal and liver failure, and metabolic disorders. Current methods using adsorbents are effective but often not specific enough. This work presents an alternative method that enables the dialyzability of albumin-bound toxins from plasma by the use of a high-flux dialyzer (F 60 Fresenius) and an albumin solution circulating on the dialysate side to increase selectively the affinity for albumin-bound toxins. This method resulted in effective removal of unconjugated bilirubin, drugs with a high protein-binding ratio (sulfobromophthalein, theophylline), and a protein-bound toxin (phenol). The additional removal of PBS could extend the applicability of dialysis, for example, to drug intoxications and liver failure or could improve the elimination of protein-bound uremic toxins in chronic renal failure.

Adsorption↗
PubMed1993

Endothelium: the next frontier in biocompatibility.

Vascular endothelium plays a central role in two specific functional systems. It controls vascular tone, hemostasis, and substance transport. The endothelium is the "docking station" for trapping, deactivation, and regeneration of activated blood compounds and provides the principal clearance mechanism for biologically active mediators released by different cell types. The second function is a regenerational one. During the period between insults (or between dialysis sessions), the endothelium has to restore the "first line of defense," that is, to regenerate the injured athrombogenic surface of the vessel wall and its antioxidative potential, defoliate damaged endothelial cells, and interpolated new ones. These two important endothelial activities are required over and above its basic functions. Future research in artificial organs must take into account that continuous or intermittent blood-membrane contact creates an altered endothelial response. These altered responses may result in adaptional reactions that may differ substantially in the acutely ill patient on continuous venovenous hemofiltration (CVVH) or in a stable patient on maintenance hemodialysis. By a reduction in such factors as immediate or delayed cell-cell interactions (direct or indirect), it may be possible to influence the long-term outcome of chronic hemodialysis patients. Other research should strive to enhance those factors of endothelial function that are essential in the defensive and restorative properties of endothelial tissue. This is especially important in such continuous therapies as CVVH, long-term membrane oxygenation, and artificial heart and blood vessels. Currently, there are more unanswered questions than possible answers concerning endothelial functions in long-term hemodialysis patients, but it is clear that excluding endothelial cell behavior from investigation of extracorporeal therapy in the future would be a substantial omission.

Animals↗
PubMed1993

Prolonged biochemical and morphological stability of encapsulated liver cells--a new method.

In this work a new type of polyelectrolyte complex capsules is introduced as an artificial housing for liver cells. Male Wistar rat hepatocytes were encapsulated using cellulose sulphate and polydimethyldialyllammonium chloride as polyelectrolytes. Amino acid metabolism rate and urea synthesis of the cells increased over the investigation period in contrast to the decrease observed in control monolayer cultures. The encapsulated cells were morphologically characterized. The described procedure represents a sufficient method for the cultivation of living cells in mechanically stable semipermeable microcapsules.

Amino Acids↗