Non quisquam melior medicus, quam fidus amicus: there is no better physician than a true friend--Cato.
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Artificial Organs↗
Biomedical subjects
H Klinkmann
Publications and source records attributed to H Klinkmann.
Survival of patients on chronic hemodialysis: single center experience.
Patient survival from our hemodialysis (HD) center over the past 11 years was analyzed. Four hundred four patients, 212 female and 192 male, were treated by chronic intermittent HD. Patients were offered standard acetate-cellulosic membranes of 1.0-1.3 m2. During this period 181 patients died. One hundred three patients were transferred to other HD centers, and some were transplanted. One hundred twenty patients are still on HD treatment. The 5 year survival rate of patients treated in our center was 58%. Women lived longer than men, and age correlated significantly with survival rate. Patients with chronic glomerulonephritis and adult polycystic kidney disease had the best survival rates while diabetic patients and those with post hypertensive nephropathy had the poorest survival rates. Forty-four percent of patients had a cardiac related cause of death, cerebrovascular accident was the cause in 15%, and 11% died due to septic condition (infection) while 8% died due to liver disease.
Adult↗
Beta2-microglobulin and low-flux synthetic dialyzers.
The aim of this study was to compare the effect on beta2-microglobulin (beta2-M) plasma levels of dialyzers with 3 low-flux synthetic membranes and regenerated cellulose (Cuprophan) in 12 chronic dialysis patients. The synthetic membrane materials chosen were low-flux polymethylmethacrylate (PMMA), low-flux polysulfone (PS 400), and polycarbonate-polyether (Gambrane). Adequate and comparable removal of small solutes was provided by dialyzers with all 4 membrane materials used under similar conditions. A significant reduction of beta2-M plasma levels was seen only with Gambrane while the other 2 synthetic membrane materials gave rise to increases similar to those known to occur with Cuprophan. After correction for the hemoconcentration caused by ultrafiltration, dialysis with Gambrane showed a 24% lower plasma beta2-M level while the beta2-M concentrations with the other 3 membrane materials were practically unchanged. In addition, the efficiency of Gambrane dialyzers in beta2-M removal was able to significantly lower the predialysis plasma beta2-M levels after only 5 dialysis sessions. The hemocompatibility of the 3 synthetic low-flux membranes as judged by the white blood cell (WBC) count and complement activation was similar and therefore cannot be used to explain the different beta2-M plasma levels. In anticipation of gaining further insight into the mechanisms of accumulation and deposition of beta2-M in dialysis patients, a worthwhile approach may be to use a low-flux membrane such as Gambrane which combines removal with protection against potential activating factors in the dialysis fluid.
Aged↗
Low protein diet in the management of patients with chronic renal failure: a controversial discussion.
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Diet, Protein-Restricted↗
A tribute to W.J. Kolff, the father of artificial organs.
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Artificial Organs↗
Structure and binding properties of serum albumin in uremic patients at different periods of hemodialysis.
Few diagnostic methods are available that describe uremia related changes of the albumin molecule structure in hemodialysis patients. The impaired human serum albumin (HSA) function is an essential part of the uremic syndrome and probably influences the long-term outcome of patients on maintenance dialysis. The albumin binding capacity (characterized for different binding centers on the molecule) is one of the relevant clinical parameters. During the current study, marker substances were utilized to evaluate center-specific binding capacity. Patients were divided into 3 groups depending on the time on hemodialysis (HD) treatment (in years) with healthy blood donors as control. Compared to healthy persons, results demonstrate a considerable impairment of binding characteristics in HD patients. Only in patients on maintenance HD for more than 5 years did ligand binding properties improve significantly. A correlation between the time of chronic HD and the recovery in binding capacity was found for the majority of binding centers of the HSA molecule. Similar results were seen applying such analytical methods as thermography (melting points) and thermofluorescence. Binding capacity impairment found for specified binding centers on the HSA molecule as the main serum carrier protein may have a direct impact on different clinical situations and the HD long-term outcome.
Adult↗
A comparison of dialysers with low-flux membranes: significant differences in spite of many similarities.
The solute removal characteristics and haemocompatibility of low-flux dialysers containing Cuprophan, cellulose acetate, polymethylmethacrylate (PMMA), and polycarbonate-polyether (Gambrane) membranes were compared in a multicentre cross-over clinical trial. While all four dialysers provided comparable removal of urea and creatinine, the dialyser containing PMMA membrane showed a reduced ability to remove phosphate compared to that containing Cuprophan membrane. Significant beta 2-microglobulin removal was obtained with the dialyser containing Gambrane membrane, whereas the other three dialysers had no impact on plasma beta 2-microglobulin concentrations. The ability to activate complement, measured as changes in the plasma concentrations of C3a des Arg and the terminal complement complex, and to produce leukopenia was greater for the dialyser containing Cuprophan membrane than for the other three. The ability to activate complement and cause leukopenia was not consistent among the remaining three dialysers and the degree of leukopenia could not be predicted from the level of complement activation. Neutrophil degranulation, as indicated by the release of elastase-alpha 1-proteinase inhibitor, occurred to a greater extent with the dialysers containing Cuprophan and Gambrane membranes. None of the dialysers was overtly thrombogenic as judged by changes in platelet count and plasma concentrations of the thrombin-antithrombin III complex. Our results demonstrate that although there are many similarities between dialysers containing low-flux membranes, there are also significant differences. These differences may enable improvements in therapy, while allowing continued use of low-flux dialysers.
Adult↗
Comparative evaluation of different membranes for the construction of an artificial liver support system.
During the past decades, many technological improvements have been made in the construction of extracorporeal liver support systems. Among these achievements, membranes of artificial capillary system, used as substrates of hepatocyte growth, aroused our interest in their application for the construction of bioreactors. The present paper studied the comparison of hepatocyte growth and function on six different membranes. Four of them are cellulose based membranes, Cuprophan, Hemophan, Cellulose acetate, and Bioflux; two are synthetic polymer SPAN and Polysulphone. Human hepatoma cell line SMMC-7721, with moderately differentiated hepatocyte-specific functions, was inoculated into the hollow fiber cartridges. These cells were allowed to attach and to grow over these membranes. It was found that there existed differences in hepatocyte immobilization and growth among these membranes. They influenced the growth and functions of hepatoma cells in vitro to some extent. These results show that membrane is an important factor in the construction of capillary membrane bioreactors for artificial liver support.
Acrylic Resins↗
Biophysical studies on the correction of uremic human serum albumin binding defects by in vitro charcoal adsorption treatment.
Spectrofluorimetry, flow microcalorimetry, and differential scanning microcalorimetry (DSMC) were used to study the conformation, binding function, and ligand loading of uremic albumin obtained from the blood plasma of 2 end-stage renal disease (ESRD) patients before and after charcoal plasma treatment at different pH values (3.0-9.0). The spectrofluorimetric patterns of conformational N-F transition at low pH (4.2-3.5) are practically identical for both samples of uremic human serum albumin (HSA) and control HSA from healthy donors. After the charcoal treatment at pH 3.0 and 4.0, the enthalpies of complexing on uremic HSA with bromsulfalein and sodium dodecylsulfate approach that of donor HSA. The binding affinity of uremic HSA for sodium octanoate, phenol red, and salicylic acid following low pH charcoal treatment even exceed those of donor HSA. At the same time the charcoal treatment of uremic plasma at neutral and alkaline pH does not notably improve the binding characteristics of isolated HSA. Adsorption at low pH values completely restores the tryptophan fluorescence spectrum position of uremic albumin and improves the thermodynamic characteristics of its melting process. Using DSMC data, it can nevertheless be concluded that some conformational changes or a certain amount of high-affinity bound endogenous ligands still remain after low pH uremic HSA purification. The latter conclusion requires additional improvements of adsorption treatment of uremic plasma.
Adsorption↗
Dilemma of membrane biocompatibility and reuse.
Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation, leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.
Anaphylaxis↗
Geographic factors and plasma selenium in uremia and dialysis.
The importance of selenium (Se) as an essential trace element for man has been increasingly recognized. Blood Se levels in chronic uremic patients are frequently reported to be lower than in controls. Definitive determination of the Se status in uremic patients, however, is hampered by the wide range of blood Se content in humans from different parts of the world. The present study was designed to assess and compare the Se status in two European populations from Rostock (Germany) and Chieti (Italy). Plasma Se levels were evaluated in healthy controls, chronic renal failure nondialyzed patients (CRF) and hemodialysis patients (HD). All Se determinations were performed in a single laboratory. The Se concentration was significantly higher (p < 0.005) in Italian healthy controls than in German healthy controls. In contrast, Se levels were similar in both CRF and HD patients from both cities. In both countries, the Se concentration in CRF and HD patients was significantly lower (p < 0.001) than in their corresponding controls, but no difference between CRF and HD was found. CRF and HD patients from the two countries showed quite similar laboratory and anthropometric data. In CRF patients in Chieti, a significant (p < 0.05) negative correlation between plasma Se and serum creatinine was found. In both HD groups, the length of time on HD and type of membrane dialyzer used did not influence the Se status. A significant positive correlation (p < 0.01) between Se levels and the protein catabolic rate was found in both HD groups. Uremia seems to be a strong factor which overrules the difference in Se levels that is present in healthy adults from different European countries. Uremia in itself may influence and level the Se concentration in patients with geographic diversity.
Adult↗
In vitro blood compatibility evaluation of hollow fibre membrane using a controlled flow system: a comparative study.
A procedure has been established for the in vitro assessment of hollow fibre haemodialysis membranes. A 30 ml syringe containing 20 ml of fresh non-anticoagulated blood was mounted onto a non-pulsatile syringe pump and blood was perfused through minimodules constructed from 80 fibres retrieved from Cuprophan (Baxter ST15), cellulose acetate (M57-12, JMS Co Ltd, Hiroshima, Japan), and AN69HF (Filtral 20, Hospal, France) dialysers. Samples were collected before perfusion, 3, 6, 9 and 12 minutes. The modules were clamped vertically to minimise the effect of red cell pooling and the dialysate compartment was filled with 0.9% saline to minimise ultrafiltration. After sample processing, complement C3a, thrombin-antithrombin III complexes, prothrombin F1 + 2, and factor XII-like activity were evaluated. The results indicated that the system could discriminate between the membranes evaluated and therefore was a relevant procedure for the assessment of hollow fibre haemodialysis membranes.
Antithrombin III↗
Membranes for dialysis.
Today, more than 30 different polymers or polymer blends are used as materials for dialysis membranes. They can be categorized following the scheme of a family tree of haemodialysis membranes. The trunk represents membranes from regenerated cellulose, major branches show either synthetically modified cellulose membranes or membranes manufactured from synthetic polymers. As the latter are standardly hydrophobic, small branches elucidate the technique on how these materials have been rendered partially or completely hydrophilic. Complications may arise, when comparing membranes only following their polymer names, such as polysulfone, polyacrylonitrile or polyamide. Due to varying polymer compositions, membranes with the same polymer names may differ in their haemocompatibility, flux properties and adsorption characteristics. Adsorption of proteins like beta 2-microglobulin, fibrinogen and coagulation factors, complement proteins, or hormones like parathormon and erythropoietin are differently adsorbed by dialysis membranes and thus adsorption contributes to the removal characteristics. Of central interest for membrane development and application is the question of how these membranes can be sterilized, as a series of patient adverse reactions has been attributed to the dialyser sterilization procedures. Apart from the cellulosic membranes Cuprophan and Hemophan, the majority of membranes cannot be sterilized by steam, as these materials degrade when exposed to above their class-point temperature. Finally, future aspects of modern membrane development should not neglect the needs of patient populations with specific blood properties, such as diabetics.
Animals↗
Hemodialysis with regenerated cellulosic membranes does not reduce plasma selenium levels in chronic uremic patients.
Selenium (Se) is considered an essential and very important trace element for humans. Se blood levels are frequently low in end-stage renal disease (ESRD) patients, but very little has been established concerning the mechanisms that could modify Se status in uremia, including a supposed dialysis-mediated Se depletion. In order to verify whether hemodialysis (HD) can induce a loss of Se, thereby leading or contributing to a low plasma Se concentration, we investigated the effect of HD procedure with the most commonly used regenerated cellulosic membrane (Cuprophan) on plasma Se levels in 20 uremic patients on HD for 62.5 +/- 49.4 months. Plasma Se levels were also determined in 15 chronic renal failure (CRF) nondialyzed patients and in 28 age-matched healthy controls. Se concentration was determined by atomic absorption spectrophotometry. Plasma Se levels of both HD patients (61.3 +/- 8.5 micrograms/L) and CRF nondialyzed patients (56.4 +/- 10.1 micrograms/L) were significantly lower than in normal subjects (78.3 +/- 9.7 micrograms/L, p < 0.001). In CRF nondialyzed patients, a significant (p < 0.05) negative correlation was found between the plasma Se concentration versus serum creatinine values. Within the HD group, plasma Se levels significantly increased after the HD procedure (72.8 +/- 17.2 micrograms/L, p < 0.02) together with hematocrit and total plasma protein values (p < 0.05 and p < 0.001, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Cellulose↗
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↗
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↗
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↗
The biocompatibility puzzle--partly solved, partly enigmatic.
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Biocompatible Materials↗