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Biomedical subjects

R Vanholder

Publications and source records attributed to R Vanholder.

At least 181 records · Page 10Linked to original sources
PubMed1992

Polymorphonuclear cell function and infection in dialysis.

End-stage renal disease is characterized by enhanced susceptibility for infectious diseases, carrying an important risk of morbidity and mortality. In the host's defense against bacterial infection, a central role is played by phagocytic ingestion of bacteria, followed by their destruction after metabolic production of oxygen free radical species. Our studies have concentrated on the energy delivery by the hexose monophosphate shunt (HMS) to NAD(P)H-oxidase, the enzyme responsible for free radical production. This evaluation was realized by measuring, in whole blood, the CO2 produced from standard quantities of radiolabeled glucose, with data normalized for the number of polymorphs in each sample. Our studies indicate that: (1) glycolysis is disturbed in uremic outpatients from a SCrea of 6 mg/dl and a CCr of 15 ml/min; (2) similar functional disturbances are found in pre-dialysis blood samples of hemodialyzed patients; (3) this functional disturbance is further intensified during dialysis with cuprophan, which is not the case for non-complement activating dialyzers; (4) the response is especially suppressed towards Staphylococcus Aureus, the bacterial species responsible for the majority of infections in uremia; (5) that functional disturbances are mainly related to uremic toxicity, dialyzer membrane bio(in)compatibility, and uremic anemia. Biochemical disturbances in PMNL, induced by a multifactorial patho-physiologic process, may therefore be related to the enhanced incidence of infection in uremic patients.

Glycolysis↗
PubMed1992

The effect of adding Br or Zn supplements to the dialysate on the concentrations of Br and Zn in the blood of hemodialysed patients.

The effect of adding Br or Zn supplementation to the dialysate on the concentrations of Br and Zn in the blood of hemodialysed patients, is investigated. Patients with end-stage renal failure on hemodialysis show an abnormal trace element pattern. Our patients showed lowered serum Br and Zn concentrations. Four patients were subjected to dialysates with varying Br content. The impact on their serum and packed cells concentrations was evaluated. The supplementation resulted in an increase in the concentrations in serum and in packed cells. The Br concentration in serum and packed cells closely followed the dialysate content. In order to restore the Zn concentration to the normal level a ZnCl2 solution was added to the dialysate of 4 other patients. Zn accumulated in the patient as a consequence of its diffusion against the concentration gradient.

Bromine↗
PubMed1992

Behaviour of 12 trace elements in serum of uremic patients on hemodiafiltration.

The concentrations of the trace elements As, Au, Cd, Cs, Cu, Fe, Hg, Mo, Rb, Se and Zn were studied in the serum of 5 patients with end-stage renal failure who were undergoing treatment with hemodiafiltration. The concentrations of the following elements differ significantly from the reference values: As, Cd, Cu, Hg and Mo are higher, while Rb, Se, Zn and some of the Cs values are lower. The observed concentration deviations may be due to the uremic state and/or the dialysis process. To asses the contribution of the latter, the elements were determined in the substitution fluid and in the dialysate before and after blood contact and passage through the artificial kidney. Our findings suggest that the concentration abnormalities could be related to the substitution fluid for Cs, Rb, Se and Zn and to the dialysate for Mo and Rb.

Aged↗
PubMed1992

Pseudomonas septicemia due to deficient disinfectant mixing during reuse.

We describe a cluster of four septicemias with pseudomonas, that occurred in a unit performing formaldehyde reuse of capillary dialyzers. Samples of blood, heparin solutions, dialysate and effluent of reused dialyzers, were evaluated bacteriologically and upon the adequacy of the reuse procedure. Pseudomonas aeruginosa, vesicularis and/or xanthomonas maltophilia were found on the blood cultures obtained during the septicemic reactions, and in the effluent of two reprocessed dialyzers not yet used (greater than 10(4) CFU/ml). These two dialyzers had also extremely low formaldehyde concentrations (0.0014 and 0.005% versus the expected 4%). Membrane and antibiogram characteristics of a Pseudomonas aeruginosa strain, recovered from the blood cultures in one patient, and of a strain found in the effluent of one of the two contaminated reprocessed dialyzers, were the same. The problem was attributed to the inadequate mixing of the disinfectant with the tap water used in the automated reprocessing device, in the absence of an alarm disclosing this failure.

Aged↗
PubMed1992

Phagocyte metabolic activity during hemodialysis with different dialyzers not affecting the number of circulating phagocytes.

Overall leukocyte counts decrease during certain forms of hemodialysis, but little information is available on the intradialytic evolution of phagocytic metabolic function, especially during dialysis with dialyzers not affecting the number of circulating phagocytes. This study evaluated the phagocytic capacity of granulocytes and monocytes to generate CO2 out of glucose under basic unchallenged conditions and after stimulation with latex or zymosan, before and after 15, 60 and 240 minutes of dialysis with reused cuprophan, AN69S, polysulphone, polymethylmethacrylate and hemophan hemodialyzers. Phagocytic metabolic function was assessed in whole blood on the basis of 14CO2-production from labelled glucose during the phagocytic process. There were no changes in basic unchallenged CO2-production with any of the dialyzers. Reactivity to latex and zymosan, expressed per number of phagocytes, showed no decrease, irrespective of the membrane type. For polymethylmethacrylate and reused cuprophan, a slight but significant increase in metabolic reactivity was observed in response to latex and zymosan. The test employed may give a screening picture of the phagocytic reaction to contact with dialyzers and membranes and thus of their degree of biocompatibility towards the phagocyte system.

Biocompatible Materials↗
PubMed1991

Subfractions in uremic plasma ultrafiltrate inhibit calcitriol metabolism.

Previous study from our laboratory has demonstrated that uremic plasma ultrafiltrate suppresses both the production rate (PR) and metabolic clearance rate (MCR) of calcitriol in normal rats. To characterize the the substances responsible for the suppression of the synthesis and degradation of calcitriol, we fractionated 20 ml uremic plasma ultrafiltrates into 13 fractions using high-performance liquid chromatography (HPLC) and studied the effect of each fraction on calcitriol metabolism. We measured the MCR and PR of calcitriol in normal rats after they were infused for 20 hours with each fraction dissolved in 20 ml normal saline. Using a UV absorption and fluorescence emission technique, several known uremic compounds were identified as individual peaks corresponding to the fractions. We found that fractions 4, and 6 to 13 markedly reduced the MCR of calcitriol. The patterns of the MCR suppression by the HPLC fractions suggest that there were at least two groups of chemically distinguishable compounds. Infusion of a solution containing all 13 fractions of the uremic ultrafiltrate also inhibited the calcitriol synthesis. One of the 13 fractions (fraction 4, containing uric acid, xanthine, and hypoxanthine) was further fractionated into eight subfractions. Infusion of subfractions 4 to 7 markedly reduced both the PR and MCR of calcitriol. We conclude that uremic plasma ultrafiltrate contains factors that inhibit calcitriol synthesis and degradation. These substances have molecular weight less than 2,000 Daltons.

Animals↗
PubMed1991

Phagocytosis in uremic and hemodialysis patients: a prospective and cross sectional study.

Leukocyte response to phagocytic challenge was assessed in uremic and hemodialysis patients in a prospective and cross sectional study. Using latex, zymosan and staphylococcus as phagocytic challenge, the utilization of glucose-I-C14 and the generation of reactive oxygen species was measured in these patients. In uremic, non-dialysis dependent patients, the response to phagocytosis was significantly reduced when creatinine exceeded 6 mg/dl and prior to initiation of dialysis (mean serum creatinine 9.3 +/- 0.3 mg/dl) was less than half that of patients with normal renal function (P less than 0.01). In a prospective study of 15 patients initiated on dialysis, the metabolic response of their leukocytes was assessed sequentially. In eight patients, initiation of dialysis with cuprophane (Cu) membrane lead to a further decline (60%) in their metabolic response to phagocytosis at the end of four weeks of dialysis compared to pre-initiation of dialysis (P less than 0.01), whereas in seven other patients, dialysis with non-complement activating membranes did not result in a significant decline. Prospective cross-over studies of chronic hemodialysis patients corroborated these findings; eight patients dialyzed with new CU membranes had a significant decline of their metabolic response to phagocytic challenge acutely at the end of each dialysis and in pre-dialysis samples after two weeks of Cu dialysis, whereas their response returned back to baseline after two weeks of dialysis with non-complement activating membrane. In prospective and cross sectional studies, a decreased response to phagocytic stimulus was a predictor of hospitalization, primarily for infectious reasons.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellulose↗
PubMed1991

Effects of purine derivatives on calcitriol metabolism in rats.

The effects of theophylline and sodium urate on metabolic production (PR) and clearance rate (MCR) of calcitriol were determined by the constant isotope infusion method in normal rats. Calcitriol PR was significantly reduced after infusion for 20 h of either theophylline (1 mg/h, PR = 22.3 +/- 1.6 ng.kg-1.day-1, P less than 0.001, n = 5) or sodium urate (0.5 mg/h, PR = 18.6 +/- 1.2 ng.kg-1.day-1, P less than 0.001, n = 5) compared with control rats infused with saline (PR = 32.0 +/- 1.5 ng.kg-1.day-1, n = 5). Renal 1 alpha-hydroxylase activity of kidney homogenate was significantly inhibited in rats infused with theophylline or urate. Suppression of 1 alpha-hydroxylase activity was also observed when the kidney homogenate was preincubated for 3 h with various concentrations of xanthine (0.11-3.0 mg/dl). In addition, the MCR of calcitriol was decreased in rats infused with either theophylline (MCR = 21.0 +/- 0.88 microliter.min-1.100 g-1, P less than 0.005) or urate (MCR = 22.9 +/- 0.91 microliter.min-1.100 g-1, P less than 0.05) compared with saline-infused control rats (MCR = 25.2 +/- 0.41 microliter.min-1.100 g-1). Because calcitriol degradation is a receptor-mediated process that requires binding of the receptor-hormone complex to chromatin, we studied the binding affinity of labeled calcitriol receptor for DNA-cellulose in the presence of theophylline or urate. Both theophylline and urate inhibited receptor binding affinity for DNA-cellulose. We conclude that these purine derivatives suppress calcitriol synthesis and inhibit receptor binding affinity for DNA. The altered receptor binding affinity could explain the decreased MCR of calcitriol.

Animals↗
PubMed1991

[Phagocyte function in uremic patients].

Phagocytosis is the process where specific cells, phagocytes, ingest foreign material, include it in a cytoplasmatic vacuole, called phagosome, and destroy it. The function of phagocytosis in the immune response has been underevaluated for a very long time. Phagocytosis however, appears to be more and more important in our defense against infection and cancer. The uremic patient presents a well known and increased tendency for infectious disease as well as an increased incidence of cancer. Modern methodology for investigation of phagocytic function consists of: 1. measuring the respiratory burst during phagocytosis; by examining the radio-active CO2 production during the glucose metabolization of phagocytosis. 2. During the chemical reaction of the respiratory burst light is produced. This chemiluminescence can be measured in a Lumetron. In uremia the registration of that chemiluminescence can however be disturbed by the presence of uremic toxins, acting as scavengers of free radicals. 3. Measurement of interleukin-1, interleukin-6 or tumor necrosis factor production during phagocytosis. In the present study, we investigated glucose metabolization and radioactive CO2 production without stimulation and after a challenge with Latex, Zymosan or Staphylococcus Aureus. All tests have been performed on 50 microliter whole blood samples. The following uremic situations have been investigated: 1. Several degrees of increasing renal failure. 2. First weeks of hemodialysis maintenance treatment. 3. Hemodialysis session. 4. Course of hemodialysis maintenance treatment. 5. Continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. 6. Changes after chemical stimulation by a cephalosporin (cefodizime (R)). The Authors report their detailed results of these investigations and conclude as follows: --uremia is a prototype of acquired immune deficiency. --Contact with bio-incompatible membranes during hemodialysis is disastrous for phagocytosis. --Other toxins than the classical urea or creatinine are apparently responsible for the phagocytic disturbances. --Stimulations of phagocytosis with medication such as the cephalosporin, Cefodizime(R) (Hoechst) is possible.

Biocompatible Materials↗
PubMed1991

In vivo solute elimination of paired filtration dialysis.

Paired filtration dialysis (PFD) is a new dialysis strategy whereby a hemofilter and a hemodialyzer are coupled in series. It has been assumed that this approach allows a better solute elimination than conventional hemodialysis (HD), allowing a shortening of dialysis time. To evaluate this hypothesis, solute elimination with PFD either with 0.4 m2 polysulphone (PS) and 1.36 m2 cuprophan (CU) 3x3 h/wk, or with 0.4 m2 PS and 1.06 m2 CU 3x4 h/wk, was compared to HD with 1.36 m2 CU, 3x4 hours weekly in the same patients. During PFD, 10L were ultrafiltered and substituted by saline. Overall extraction of UV absorbing solutes (MW less than 10,000 Dalton), and extraction of individual solutes identified by high performance liquid chromatography (HPLC) were compared as well as urea kinetics. For PFD 3x3 h overall extraction of UV-absorbing compounds and of hippuric acid was significantly higher than for HD 3x4 h (p less than 0.05). Overall extraction of UV-absorbing compounds and of all but one individual compound under study was markedly higher for PFD 3x4 h vs conventional HD 3x4 h (p less than 0.01), in spite of a higher diffusive area with the latter technique. No differences in urea kinetics were observed for the 3 strategies. It is concluded that solute extraction during PFD is higher than during HD, if the treatment time is the same. Even if treatment is shortened to 3x3 h weekly, solute extraction with PFD is at least as efficient as with HD.

Biocompatible Materials↗
PubMed1990

Comparison of two methods for the estimation of urea kinetics and introduction of a third simplified method.

It has been claimed that computed urea kinetic (UK) modelling in hemodialysed patients, for the estimation of protein intake, leads to an overestimation of protein catabolic rate (PCR). In the present study, three different methods of kinetic modelling for the determination of PCR and Kt/V are compared in 24 patients. The first method was the direct quantification method (DDQ) based on the collection of all urea eliminated from the body. The first computed method (ICMI) was the urea kinetic modelling method as described by Sargent. Dialyzer clearances were measured directly and not estimated by theoretical extrapolation. The second computed method (ICMII) is based on the indirect calculation of urea distribution volume (Vu), according to Watson, and of dialyzer clearances from this Vu and from pre- and post-dialysis urea concentrations. All three methods resulted in PCR's that were not significantly different (DDQ: 1.03 +/- 0.19; ICMI: 1.04 +/- 0.22; ICMII: 1.08 +/- 0.25 mg/Kg BW.24 hrs; p greater than 0.05). When the results were correlated, the following results were obtained: ICMI vs ICMII: r = 0.89, p less than 0.001; ICMI vs DDQ: r = 0.68, p less than 0.01; DDQ vs ICMII: r = 0.78, p less than 0.001. Intermutual comparison of Kt/V values resulted in virtually identical results, especially when comparing ICMI and ICMII, where the regression line equalled the identity line. In conclusion, all methods seem equally reliable in determining mean PCR and Kt/V. Our data, obtained with directly measured dialyzer urea clearances, do not confirm the earlier held opinion that computed modelling results in an overestimation of PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗