Search PubMed⌕ Search

Biomedical subjects

R Vanholder

Publications and source records attributed to R Vanholder.

At least 145 records · Page 8Linked to original sources
PubMed1995

Mechanisms of uremic inhibition of phagocyte reactive species production: characterization of the role of p-cresol.

It is generally recognized that the uremic syndrome results in a depression of immune function, but the uremic solutes responsible remain largely unidentified. In this study, the effect of 18 known uremic retention solutes, including urea and creatinine, on hexose monophosphate shunt (HMS)-dependent glucose-1-C14 utilization (G1C-U), chemiluminescence production (CL-P) and flow cytometric parameters (FCP) of respiratory burst and phagocytosis were evaluated in granulocytes and/or monocytes. Among the compounds studied, only p-cresol depressed whole blood respiratory burst reactivity (G1C-U, CL-P) dose dependently at concentrations currently encountered in end-stage renal disease (ESRD) (P < 0.05 from 5 micrograms/ml on). The effect of p-cresol was enhanced by increasing incubation times from 10 to 120 minutes. HMS activity of isolated packed erythrocytes remained unaffected. FCP of respiratory burst activity (Bursttest, expressed as log fluorescence units, LFU) revealed a marked depression in the presence of p-cresol (from 700 +/- 167 to 291 +/- 128 LFU for granulocytes, from 278 +/- 102 to 146 +/- 52 LFU for monocytes, P < 0.01), whereas particle ingestion (Phagotest) remained unaffected. Cell-free myeloperoxidase activity was also markedly depressed in the presence of p-cresol. Polarity based HPLC-elution of a standard solution containing all the solutes studied, using a gradient from 100% formic acid to 100% methanol during 60 minutes, revealed elution of p-cresol after 46.6 minutes, pointing to its relative hydrophobicity. Conjugation of p-cresol to p-cresylsulfate anihilated the depressive effect of p-cresol on granulocyte function, and at the same time caused a shift in HPLC-elution pattern to a less lipophilic range.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1995

Middle molecules: toxicity and removal by hemodialysis and related strategies.

Renal failure results in the retention of metabolites which may arbitrarily be grouped according to their molecular weight: low (< 300 daltons molecular weight), middle (300-15,000 daltons), and high (> 15,000 daltons). Opinion in respect to the relative importance of these groups varies. Initially it was thought that small molecules were important. In the mid-1970s, investigators identified the possible pathophysiological role of middle molecules. However, since positive identification of such molecules was difficult, opinion has shifted back in favor of small molecules, and little attention, with the exception of beta 2 microglobulin, has been paid to middle molecules and their removal by hemodialysis and related therapies. In this review current knowledge regarding middle molecules identified as uremic toxins and their removal by hemodialysis and associated therapies are discussed.

Ascorbic Acid↗
PubMed1995

Inhibition of calcitriol receptor binding to vitamin D response elements by uremic toxins.

The genomic action of calcitriol (1,25-dihydroxy-vitamin D3) is mediated through the interaction of the calcitriol receptor (VDR) with vitamin D response elements (VDREs). Although renal failure is associated with resistance to the action of calcitriol, the mechanism of this resistance is not well understood. Therefore, we used the electrophoretic mobility shift assay to compare the ability of VDRs from normal and renal failure rats to bind to the osteocalcin gene VDRE. The results indicate that VDRs from renal failure rats have only half the DNA binding capacity as VDRs from control rats, despite identical calcitriol binding. Furthermore, incubation of normal VDRs with a uremic plasma ultrafiltrate resulted in a loss of > 50% of the binding sites for the osteocalcin VDRE. When VDRs bound to DNA as heterodimers with retinoid X receptors, the inhibitory effect of the uremic ultrafiltrate was due to a specific interaction with the VDR, not retinoid X receptors. In addition, uremic ultrafiltrate blocked calcitriol-induced reporter gene activity in transfected JEG-3 cells. Taken together, the results indicate that an inhibitory effect of a uremic toxin(s) on VDR-VDRE binding could underlie the calcitriol resistance of renal failure.

Animals↗
PubMed1994

Influence of erythropoietin on dialyzer reuse, heparin need, and urea kinetics in maintenance hemodialysis patients.

The administration of erythropoietin (EPO) in maintenance hemodialysis may affect urea kinetic parameters by altering dialyzer function during first use and reuse, and dietary protein intake as a consequence of increased appetite. In the present study, the effect of EPO treatment on urea kinetic parameters in case of reuse (n = 14) and first use (n = 10) of dialyzers was assessed in 24 clinically stable hemodialysis patients who were evaluated before and during EPO treatment. In addition, the heparin need and the number of uses before discarding the dialyzer were registered. No significant differences between urea kinetic parameters before compared with during EPO treatment were noted in the overall population or in the subgroups treated with reused or first-use dialyzers. However, in 13 patients with a low baseline protein catabolic rate (pcr(wt)) (pcr(wt) < 1.0 g/kg/24 hr before EPO treatment), pcr(wt) increased from 0.81 +/- 0.04 to 0.93 +/- 0.06 (+ 15%, P < 0.01). The heparin dosage increased from 6,693 +/- 419 IU/session to 7,659 +/- 566 IU/session and from 5,538 +/- 594 IU/session to 6,918 +/- 649 IU/session (P < 0.05) in the subgroups treated with reused or first-use dialyzers, respectively. Nevertheless, when dialyzer reprocessing was performed, the number of achieved uses before discarding the dialyzers was reduced after the introduction of EPO (5.4 +/- 0.4 v 3.4 +/- 0.4, P < 0.01). In conclusion, during EPO treatment urea kinetic parameters were not affected in case of dialyzer first use or in case of reuse. In patients with low pretreatment values, pcr(wt) increased, possibly indicating improved protein intake in malnourished patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Inhibition of nuclear uptake of calcitriol receptor by uremic ultrafiltrate.

The biological action of calcitriol is mediated through a hormone-receptor complex interacting with nuclear chromatin. Interaction of the calcitriol receptor (VDR) with VDR response elements produces bioactive proteins which carry out the physiological actions of calcitriol. Since biological response to calcitriol appears to be diminished in renal failure, we studied the effect of uremic toxins on the interaction of VDR with nuclear chromatin using in vitro nuclear uptake of the 3H-calcitriol labeled VDR by intestinal nuclei. We found that nuclear uptake of the labeled intestinal VDR from renal failure rats was significantly lower than that from the control animals. HPLC fractionated uremic ultrafiltrate directly inhibited nuclear uptake of the labeled VDR when the labeled VDR was incubated with 50% of the ultrafiltrate for various time intervals ranging from 15 minutes to 6 hours. Infusion of uremic ultrafiltrate to normal rats for 20 hours also produced intestinal VDR with a lower binding affinity for intestinal nuclei when compared to the controls infused with normal ultrafiltrate. The latter study suggests that uremic toxins are responsible for the decreased nuclear uptake of VDR of rats with renal failure. Although it is difficult to extrapolate these results directly to the intact cells, our findings suggest that part of the calcitriol resistance in renal failure could be explained by decreased entry of receptor into the nucleus.

Animals↗
PubMed1994

Factors and complications affecting catheter and technique survival with permanent single-lumen dialysis catheters.

This long-term study on the outcome of permanent silicone single-lumen dialysis catheters consisted of 43 surgically inserted catheters in 33 patients. All catheters were attached to a pressure-pressure single-cannula dialysis system. Technique and catheter survival were 80 and 59% at 1 year, and 63 and 50% at the 3rd year respectively. These parameters were not different in older patients (> or = 70 years, n = 12). Factors corresponding to a less successful outcome were placement in the left jugular vein (3-month actuarial survival of 44%) and absence of distal side holes (1-year actuarial survival of 44%). Insertion in both subclavian veins was not different to the classical right jugular vein. Infectious complications (incidence of 0.72 per 1000 catheter days) often caused simultaneous catheter and technique failure (14 versus 15%), whereas inadequate flow (incidence of 2 per 1000 catheter days) caused catheter rather than technique failure (30 versus 12%). The incidence of both complications declined significantly with time after insertion during the follow-up period. The first 3 months after insertion were more predisposed to the occurrence of inadequate flow than catheter-related infections. The general performance of these permanent single-lumen catheter devices justifies their long-term application in haemodialysis, even as a first choice of vascular access, especially in the elderly. Insertion in the left jugular vein and use of catheters without side holes should be avoided, providing a better catheter survival.

Adult↗
PubMed1994

Vascular access for hemodialysis.

Indwelling central venous catheters were consecutively used as access for acute and chronic hemodialysis, emergency treatment of pulmonary fluid overload, intoxication and electrolyte disturbances, plasmapheresis, and semiacute continuous dialysis strategies, such as continuous arteriovenous hemofiltration (CAVH). Modification in catheter structure also made it possible to use this access for long-term treatment (e.g., surgically insertable catheters [Hickman], soft large-bore catheters for blind insertion). We discuss the remaining open questions in this field: Which is the insertion site of preference (i.e., subclavian, femoral, or deep jugular)? Should we prefer stiff or soft catheters? Should soft catheters be positioned surgically or is blind insertion by nonsurgeons as adequate? Is it necessary to couple catheter insertion to adjuvant techniques, such as echographic guidance, to reduce complications? Is the currently used polymer structure of the catheters acceptable? Should catheter dialysis be used with single or double vascular access?

Catheterization, Central Venous↗
PubMed1994

Subclavian vein hemodialysis catheters: advantages and disadvantages.

The pros and cons of subclavian vein hemodialysis catheters are reviewed. The subclavian vein catheter offers rapid and adequate vascular access. Other advantages are preservation of patient mobility and the ease with which the dressing can be secured. In contrast, subclavian vein stenosis has recently been identified as an important long-term complication of subclavian vein catheters that seriously compromises the creation and long-term viability of later ipsilateral arteriovenous fistulas. For this reason, we recommend restricting use of the subclavian hemodialysis catheter for acute situations and preferential use of internal jugular catheters for more chronic approaches because they better preserve venous integrity.

Catheterization, Central Venous↗
PubMed1994

Uraemic toxic retention solutes depress polymorphonuclear response to phagocytosis.

Previous studies from our laboratory have demonstrated that the activity of the hexose monophosphate shunt (HMS) pathway in phagocytosis-related respiratory burst is disturbed in end-stage renal disease. To determine whether uraemic solute retention is responsible for this defect the HMS-path was evaluated by measurements of glucose-1-C14 utilization and determination of 14CO2 production in polymorphonuclear cells (PMNLs), suspended in normal plasma or uraemic biological fluids. Normal PMNLs, while suspended in normal or uraemic plasma, were stimulated with either latex, zymosan or Staph. aureus; CO2 generation (measured as DPM/10(3) PMNL, normal versus uraemic plasma) was depressed in uraemic plasma in response to latex (from 43 +/- 5 to 20 +/- 3), zymosan (from 72 +/- 8 to 47 +/- 4) (P < 0.01), and Staph aureus (from 73 +/- 17 to 47 +/- 8 DPM/10(3) PMNL) (P < 0.05). The degree of inhibition was similar for each stimulus. To characterize the substances responsible for this defect we fractionated uraemic plasma ultrafiltrate by polarity-based semipreparative C18 reversed phase HPLC and found a decreased response to Staph. aureus in the presence of fraction 2 (from 102 +/- 13 to 23 +/- 10 DPM/10(3) PMNL, P < 0.05), and in fractions 8 and 11 (lowest value in fraction 8, 54 +/- 14 DPM/10(3) PMNL, P < 0.05 versus control). The pattern of HPLC elution on a gradient from 100% formiate (pH 4.0) to 100% methanol indicates that there are at least two chemically distinguishable groups of compounds, one hydrophilic (in fraction 2), and one lipophilic (in fractions 8 and 11). We conclude that uraemic biological fluids contain factors that inhibit HMS activity related to phagocytosis, and that at least two groups of components with different characteristics are involved.

Adult↗
PubMed1993

Factors influencing drug protein binding in patients with end stage renal failure.

Investigations were undertaken to evaluate which uraemic solutes decrease drug protein binding. This was done by performing HPLC-fractionation of uraemic biological fluids and studying the effect of addition of a lyophilisate of each fraction to normal plasma containing standard quantities of radiolabelled drugs. From a first study, based only on fractionation of uraemic ultrafiltrate with an HPLC-gradient mainly aimed at elution of hydrophilic compounds, hippuric acid appeared to be a major protein binding inhibitor for theophylline and phenytoin. The problem with this approach was that it did not include the compounds with the most substantial protein binding. Therefore, studies were planned to fractionate deproteinized uraemic sera, but first it was necessary to define which deproteinisation methods gave the highest yields of protein bound ligand. Heat denaturation was found to be one of the most effective deproteinisation methods. When a lyophilisate of uraemic serum, deproteinised by this method, was added to normal plasma, a higher capacity to displace theophylline from protein binding sites was found compared to the effect of an identical volume of an ultrafiltrate of the same samples. Fractionation of the deproteinised sample by HPLC revealed a larger number of fractions able to inhibit drug protein binding.

Humans↗
PubMed1993

Cyanoacrylate tissue adhesive for closing skin wounds: a double blind randomized comparison with sutures.

A comparative double blind randomized study was undertaken in the rat, to compare the external cosmetic and the morphologic aspect of skin wounds, treated by the local application of adhesive glue (ethyl-2-cyanoacrylate-Mediglue) or classical suture technique. Skin incisions were applied and treated by a plastic surgeon, then photographed or biopsied, and evaluated and scored by independent observers, not aware of the initial treatment. Small (1.5 cm) or long (8 cm) incisions were made, on both sides of the back, and treated randomly on one side by glue and on the other side by sutures. Evaluations were performed at 1, 2, 4 and 8 wk. Both small and large wounds scored identically, irrespective of the treatment (overall score 1.5 cm wounds: 8.8 +/- 1.4 for glue versus 8.8 +/- 1.0 for sutures; 8 cm wounds: 8.3 +/- 1.9 versus 8.3 +/- 1.5; P = not significant). A morphological study demonstrated no adverse effects for the adhesive treatment, with a minor inflammatory infiltrate. Sutured wounds had a higher tendency to develop abscesses and/or major inflammation. Adhesive-treated wounds scored better than non-treated wounds (8.9 +/- 1.3 versus 7.4 +/- 3.3, P < 0.01). In conclusion, this controlled comparative study shows no difference in cosmetic aspect between adhesive and suture-treated skin incisions. Morphologically, the glue treatment is not related to any adverse effect or damage to the skin structures.

Adhesives↗