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C Woffindin

Publications and source records attributed to C Woffindin.

At least 19 recordsLinked to original sources
PubMed1997

Synthetically modified cellulose: an alternative to synthetic membranes for use in haemodialysis?

Renal replacement therapy relies predominantly on the use of cellulose-based membranes. Such membranes have a biocompatibility profile which is inferior to membranes manufactured from synthetic polymers. Synthetically modified cellulose (SMC) is a new, low-flux haemodialysis membrane in which hydroxyl groups have been replaced with benzyl groups. The biocompatibility profile characterized by changes in white cell and platelet counts and the activation of complement components (C3a, C5a and C5b-9) have been studied in vivo and compared with those of cellulose acetate, unmodified cellulose (Cuprophan ) and low-flux polysulphone (Fresenius Polysulfone) in the same group of patients. For SMC, the white cell count at 15 min declined to 65.6% of pretreatment level, compared with 63.8% for the cellulose acetate, 79.6% for low-flux polysulphone and 28.1% for Cuprophan, thereafter returning to pretreatment levels. Both modified cellulose membranes were superior to unmodified cellulose (P = 0.001); the differences between the modified cellulose membranes were not significant statistically. The changes induced by all three cellulose-based membranes exceeded those for low-flux polysulphone (P = 0.001). Associated with the neutropenia was a reduction in platelet count, but this was independent of membrane type. The mean time-averaged concentrations of C3a(des Arg) over 150 min were 1168 ng ml(-1) (SMC), 1030 ng ml(-1) (cellulose acetate), 1297 ng ml(-1) (Cuprophan) and 790 ng ml(-1) (low-flux polysulphone). Equivalent values for C5a(des Arg) were 6.12 (SMC), 2.98 (cellulose acetate), 11.03 (Cuprophan) and 1.33 ng ml(-1) (low-flux polysulphone). C5b-9 values were 385 (SMC), 386 (cellulose acetate), 177 (Cuprophan) and 185 ng ml(-1) (low-flux polysulphone). For each of the complement components the differences between the membranes were significant [P = 0.0009 (C3a(des Arg)), P = 0.0001 (c5a(des Arg) and C5b-9)]. The levels of C5b-9 generated during dialysis also showed a significant positive correlation compared to C5a for all membranes considered as a single group (Pearson's correlation coefficient = 0.870, P = 0.0001). It is concluded that the modification of the cellobiosic unit is a promising approach to improve the biocompatibility profile of cellulose-based membranes. The two different methods of modification lead to similar improvements in biocompatibility compared with unmodified cellulose, but as yet do not match that of low-flux polysulphone.

Biocompatible Materials↗
PubMed1997

Clinical characterization of Dicea a new cellulose membrane for haemodialysis.

A prospective randomised clinical study comparing the functional performance and biocompatibility of a new cellulose diacetate variant (Dicea) in which the degree of hydroxyl group substitution differs, with cellulose diacetate and low flux polysulfone incorporated into commercially produced hollow fiber hemodialysers with a surface area 1.5-1.6 m2 has been undertaken. All dialysers studied demonstrated clinically acceptable performance in terms of their small molecular removal characteristics, with minor statistical but not clinical differences. Use of both cellulose diacetate membranes but not low flux polysulfone resulted in a reduction in plasma beta(2) microglobulin levels. The membranes were impermeable to albumin, but showed some permeability to low molecular weight proteins. The average protein recovery from the dialysis fluid was 3105 mg for Dicea, 2913 mg for cellulose diacetate and 2842 mg for low flux polysulfone. For Dicea the white cell count by 15 minutes had declined to 68% of pre treatment value, compared with 59% and 86% for cellulose diacetate and low flux polysulfone. The differences between Dicea and cellulose diacetate were not significant, but both cellulose based membranes differed from low flux polysulfone (p = 0.0015). There was a strong evidence of differences between the membranes in respect of C5a and C5b-9 generation (p = 0.0001) but not for C3a (p = 0.16) furthermore the levels of C5b-9 generated during dialysis also showed a significant positive correlation compared to C5a for all membranes. (Pearson's correlation coefficient = 0.856, p = 0.0001). It is concluded that the two cellulose diacetate membranes are not identical, with the differences observed being a consequence of the degree of acetyl substitution, resulting in alteration of membrane structure and the method of sterilization. The clinical significance of these differences are difficult to characterize but the modification of the cellulose structure appears to be a promising method to improve the biocompatibility of cellulose membranes. The improved biocompatibility offered by this method still falls short of that achieved with low flux synthetic membranes such as Fresenius Polysulfone.

Adult↗
PubMed1996

A comparison of three brands of polysulfone membranes.

A prospective clinical crossover study comparing the functional performance and biocompatibility of three brands of polysulfone membranes (Fresenius Polysultone (Fresenius Ag, Bad Homburg, Germany), Polyphen (Minntech Corp., Minneapolis, MN), and Biosulfane (WR Grace Inc., Danvers, MA)) incorporated in ethylene oxide-sterilized dialyzers of comparable surface area (1.3 to 1.35 m2) was undertaken. The clearance of small molecules by each membrane was comparable. Plasma levels of beta 2 microglobulin fell to 49.9% of pretreatment values by 210 min when using the Fresenius Polysulfone membrane, 60.2% with the Polyphen membrane, and 63.1% with the Biosulfane membrane. The reduction achieved by the Fresenius Polysulfone membrane was superior (P = 0.003). The plasma reductions were associated with the recovery of 195 mg beta 2 microglobulin from the dialysate for the Fresenius Polysulfone membrane and 158 mg for the Polyphen membrane, but no beta 2 microglobulin was recovered from the dialysate with the Biosulfane membrane. The dialysate collected with the Fresenius Polysulfone membrane also contained a mean of 6853 mg of total protein, compared with 5490 mg with the Polyphen membrane and 8422 mg with the Biosulfane (P = 0.04) membrane. The neutropenia was slight and independent of membrane brand, as were the changes in C3a des arg and SC5b-9 complement components. The reduction in platelet counts was higher for the Biosulfane membrane than for the other brands (P = 0.003). This study indicates that whereas the polymer base of the membrane is the same, its production and subsequent handling during dialyzer production induce changes that attain statistical significance, most notably in the way that the membrane removes beta 2 microglobulin and interacts with proteins. The differences observed are a consequence of the different alloying polymers used during manufacture and, consequently, the membranes cannot be considered equivalent.

Adult↗
PubMed1995

Biocompatibility of membranes used in the treatment of renal failure.

Haemodialysis membranes with a wide range of solute and hydraulic permeabilities are used clinically. Such membranes are manufactured from either cellulose or synthetic co-polymers and their biocompatibility is commonly characterized by the complement activation and white cell changes observed during their use. The cellobiosic unit may be modified by the partial or total replacement of the hydroxyl groups by diethylaminoethyl (Hemophan), acetate (cellulose acetate), triacetate (cellulose triacetate) or 2,5-acetate (Diaphan). We have undertaken a prospective study in which such renal membranes have been studied in terms of the complement activation and neutropenia produced with the aim of investigating the relationship between modification of the cellobiosic unit and the magnitude of neutropenia and complement activation, and the extent to which membrane base material influences these parameters, by comparing the changes observed in modified cellulose membranes with that for a synthetic membrane (polysulphone). Our findings show that, while the degree of substitution varies between < 1% and total substitution, there is no correlation between the numbers of hydroxyl groups replaced and alteration of complement activation and neutropenia. However, by modification of the cellobiosic unit it is possible to produce a membrane whose biocompatibility is similar to that of a membrane manufactured from a synthetic co-polymer such as polysulphone.

Biocompatible Materials↗
PubMed1995

Hemodialyzer performance: a review of the trends over the past two decades.

Using data generated in the course of an evaluation program for hemodialyzers and associated devices, which was supported by the Medical Devices Agency of the Department of Health, we have compared the performance characteristics of 23 hemodialyzers evaluated 20 years ago with those of 18 hemodialyzers evaluated during 1993-1994. Surface areas of the two groups ranged from 0.6-2.5 m2 (mean 1.13 m2) and 0.6-1.8 m2 (mean 1.18 m2), respectively. The device performance has been compared both in vivo (small molecular clearance) and in vitro (middle molecular clearance and ultrafiltration coefficient) at blood and dialysate flows of 200 and 500 ml/min, respectively. Our comparison shows that over the past 2 decades there has been a marked improvement in functional performance. For clearance of small molecules, current dialyzers using cellulose-based membranes offer a 47% improvement for urea clearance, within the surface area range < 1.2 m2, while for dialyzers whose surface area is > 1.2 m2 the improvement is less marked (12%). The improvements noted in the clearance of creatinine were similar. Associated with the improved clearance of small molecules was an improved middle molecular clearance (74% for surface areas < 1.2 m2 and 63% for surface areas > 1.2 m2) and an increased ultrafiltration coefficient, higher by 154 and 133%, respectively, for the two surface area groups. Due to the smaller number of devices in the modified cellulose and synthetic membrane categories, it has not been possible to make such a detailed comparison. However, the experimental data demonstrate that devices currently produced incorporating modified cellulose and synthetic membranes overlap in performance and that in those devices that were in clinical use 20 years ago using synthetic membranes, current equivalents have also improved. These improvements are reflected in the concomitant reduction of treatment times from 30 h/week in 1970 to 12 h or less currently.

Cellulose↗
PubMed1995

Application of a standard method to characterize clearance blood flow relationships in hemodialysis.

The effectiveness of solute removal of a hemodialyzer may be judged by the ability of the device to remove solutes over the clinical range of blood flow rates. The expression of solute removal characteristics of hemodialyzers at standard or specific blood flow rates is important for clinical use and comparison. The solute removal at a specific blood flow rate is derived mathematically, usually by the fitting of a curve to the blood flow solute removal characteristics established experimentally over a range of blood flow rates. The commonly used methods of obtaining such a relationship are discussed and a new method of curve fitting is described. This method is derived from the mathematical theory defining the overall dialyzer mass transport relationship which governs the clearance blood flow relationship in any dialyzer. The derived relationship between the blood flow rate and the clearance has been validated using data generated for a commercially produced hemodialyzer.

Blood Flow Velocity↗
PubMed1994

Clinical comparison of high-flux cellulose acetate and synthetic membranes.

Solute transport and alterations in complement and clotting induced by a new high-flux cellulose acetate membrane (CA-HF800-E, Diaphan) were compared with those for cellulose triacetate (CTA) and polysulphone in a cross-over clinical study. The membranes are similar in their small-molecule removal. Serum beta 2-microglobulin decreased with all membranes but the decrease was independent of membrane type. Associated with beta 2-microglobulin removal was a protein loss which averaged 2636 mg for Diaphan, 4937 mg for CTA, and 2500 mg for polysulphone. Albumin presence in the dialysate was less than the limit of detection (5 mg/l) but for each of the membranes, occasional readings above the limit of detection were noted. C3a generation for Diaphan is comparable with that for CTA and polysulphone, but differed for C5a and neutropenia. A highly significant correlation of the area under the concentration time curve of the two complement components was noted for the cellulose based membranes (r = 0.875, P = 0.0002 for Diaphan, r = 0.823, P = 0.006 for CTA) this relationship was less marked for polysulphone (r = 0.396, P = 0.29). Induction of clotting characterized by the thrombin-antithrombin III (TAT) complex were similar for the three membranes, as were changes in platelet counts. Our findings indicate that while it is possible to modify cellulose to produce a membrane whose solute transport and biocompatibility is similar to synthetic membranes such as polysulphone, the structural modifications induce considerable differences in the amount of protein lost.

Adult↗
PubMed1993

Urea kinetic modeling: comparing the options.

In this study 6 commercially produced kinetic modeling packages utilizing a variable volume, single pool urea model, as well as formulae to determine the delivery of therapy, have been compared by applying to each the same set of rigorously collected data for a group of 12 patients. Comparison of the kinetically derived parameters (urea generation rate [G], urea distribution volume [V], delivery of therapy [Kt/V], and normalized protein catabolic rate [nPCR]) showed that the values obtained for both G and V differed between packages owing to the numerical methods and the clearance used in the solution of the differential equations. Although a broad agreement between the values established for Kt/V and nPCR was noted, the 95% limits of agreement indicated that it would be prudent to exercise caution when comparing results established by different modeling packages.

Adult↗
PubMed1993

A technique for the laboratory determination of recirculation in single needle dialysis.

Recirculation is an important factor in single needle dialysis and, if high, can compromise treatment efficiency. To provide information regarding recirculation characteristics of access devices used in single needle dialysis, we have developed a new technique to characterise recirculation and have used this to measure the recirculation of a Terumo 15G fistula needle and a VasCath SC2300 single lumen catheter. The experimentally obtained results agreed well with those established clinically (8.5 +/- 2.4% and 18.4 +/- 3.4%). The experimental results have also demonstrated a dependence on access type, pump speeds and fistula flow rate. A comparison of experimental data with theoretical predictions showed that the latter exceeded those measured with the largest contribution being due to the experimental fistula.

Arteriovenous Shunt, Surgical↗
PubMed1992

Cellulose-based haemodialysis membranes: biocompatibility and functional performance compared.

Regenerated cellulose membranes are widely used in the treatment of renal failure. The presence of hydroxyl (OH) groups on the membrane surface plays an important role in initiating complement activation and also influences thrombogenicity. The OH groups may be masked or reduced by alteration of the manufacturing process of the membrane. We have undertaken a clinical study of four cellulose-based membranes (Cuprophan, Hemophan, cellulose acetate, and cellulose triacetate) in which the hydroxyl groups of the membrane have been replaced and the magnitude of replacement has varied from less than 1% to greater than 80%, to assess the role that these modifications play in functional performance, biocompatibility (neutropenia, leukocyte activation, anaphylatoxin generation, and hypoxaemia). Our findings indicate that there does not appear to be a straightforward correlation between the numbers of hydroxyl groups replaced and modification of biocompatibility, suggesting that not all hydroxyl groups behave in a similar way.

Cellulose↗
PubMed1992

Characterisation and evaluation of a new double lumen central venous catheter.

The performance of a new double lumen central venous haemodialysis catheter was tested in two laboratory models. In a bench model the patient's venous system was simulated by a reservoir from which water or glycerol was drawn through a fixed tube. A double lumen silastic catheter was then inserted into the tube, as it would in a major vein, with the tip directed away from the direction of flow. The catheter was linked to a dialysis circuit incorporating pressure sensors and dye was infused at constant rate so that recirculation at the tip could be measured and found to be less than 5%. The same catheters were inserted operatively into the superior vena cava via the external jugular vein of three pigs (weight 27-31 kg). The catheters remained patent for four weeks and when connected to an extracorporeal circuit had recirculation and pressure flow characteristics comparable to the bench model in the range 50-400 ml/min. The new double lumen catheter is worthy of clinical evaluation.

Animals↗
PubMed1988

Blood-membrane interactions during haemodialysis with cellulose and synthetic membranes.

Haemodialysis is associated with transient leucopenia, hypoxia and activation of the patient's complement system, mediated by blood-membrane contact. Changes in white blood cell counts, blood gases (PaO2 and PaCO2), carbon monoxide diffusing capacity (DLCO) and complement activation (C3d and C3a) were measured pre-treatment and during dialysis. The degree of complement activation, leucopenia and changes in DLCO were influenced by membrane type; these changes were most marked for cellulosic membranes and were much reduced for synthetic membranes. A significant relationship between the degree of leucopenia and the magnitude of change in DLCO during dialysis was demonstrated.

Acrylic Resins↗
PubMed1986

Biocompatibility of haemodialysis membranes.

Haemodialysis is widely used as a method of treatment for renal failure; it relies on diffusion across a semipermeable membrane. The exposure of blood to the membrane is associated with a rapid transient fall in white cells, activation of the complement system and a fall in arterial oxygenation. The interrelationship between these phenomena, their dependence on the type of membrane used and their clinical implications are reviewed and discussed.

Cellulose↗
PubMed1986

Haemodialysis-induced activation of complement. Effects of different membranes.

The ability of cellulose-based (Cuprophan, saponified cellulose ester) and synthetic (polyacrylonitrile, polycarbonate, polymethylmethacrylate) haemodialysis membranes to activate complement during treatment was compared, using functional, immunochemical, radioimmunoassays, and fast centrifugal analysis assay techniques. Cellulosic and synthetic membranes show a striking similarity in their complement activation when measured by immunochemical assays. Functional haemolytic assays for alternate pathway and CH50 demonstrate no significant differences from predialysis values. C3d levels were also unable to demonstrate differences between the membranes. C3a levels, on the other hand, demonstrated significant differences between cuprophan, polyacrylonitrile, and polymethylmethacrylate but not between Cuprophan and polycarbonate membranes. Since comparable alternate-pathway activity of both cellulosic and synthetic membranes was demonstrated, but their C3a release differed, it is possible that certain surfaces that activate complement also possess the ability to absorb components of the alternate pathway.

Acrylic Resins↗