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Biomedical subjects

R Vanholder

Publications and source records attributed to R Vanholder.

At least 109 records · Page 6Linked to original sources
PubMed1998

Application of Kohonen neural networks for the non-morphological distinction between glomerular and tubular renal disease.

BACKGROUND: A Kohonen topological map is an artificial intelligence system of the connectionist school (neural networks). The map learns the typical features of the subclasses in the learning set by means of a shortest Euclidean distance algorithm, after which self-adaptation of the neurons occurs. By its ability of self-organization and generalization, a Kohonen map is useful for pattern recognition, and its application in the medical field as an aid for decision making seems promising. This study describes the use of a Kohonen topological mapping system in the classification of renal diseases as being glomerular or tubular on basis of clinical characteristics and laboratory results. METHODS: Forty-one parameters from 75 patients were retrospectively retrieved and used to train four different Kohonen maps of 10 x 10 neurons. For reference diagnostic classification, we referred to the results of the light-microscopic examination. The classification of the patients by the four different Kohonen networks was compared to the classification by a rule-based system and by three nephrologists. We also developed a 'hybrid' decision system that makes a classification on basis of the opinion of the four networks and that of the rule-based system. RESULTS: The results show that a Kohonen map is capable of classifying the patients as having glomerular or tubular disease with a higher sensitivity and predictive value than the nephrologists and the rule-based system, and that the best classification was performed by the hybrid system: sensitivity and predictive value for the diagnosis 'glomerular' respectively 100 and 88% for the network with the most adequate results, 90 and 83% for the nephrologists, 90 and 95% for the rule-based system, and 95 and 96% for the hybrid system; sensitivity and predictive value for the diagnosis 'tubular' respectively 50 and 100% for the neural networks, 31 and 45% for the nephrologists, 81 and 68% for the rule-based system, and 87 and 82% for the hybrid system). CONCLUSION: We conclude that a Kohonen map is capable of classifying the patients as having glomerular or tubular disease with a high sensitivity and predictive value. The rule-based system performs worse than the neural networks. The most adequate results were obtained with the hybrid system.

Adult↗
PubMed1998

Citrate anticoagulation does not correct cuprophane bioincompatibility as evaluated by the expression of leukocyte surface molecules.

BACKGROUND: Citrate, used for the anticoagulation of the extracorporeal dialysis circuit, reduces ionized calcium by chelation and has been claimed to attenuate dialyser membrane bioincompatibility. Dialysis with complement-activating cuprophane membranes is associated with leukopenia which has been related to an increase in adhesion molecule expression on the surface of circulating leukocytes. METHODS: The effect of citrate anticoagulation on the expression of CD11b, CD11c and CD45 on the surface of granulocytes and CD14 on monocytes during haemodialysis with cuprophane membranes, was evaluated by flow cytometric analysis. A comparison of standard heparin vs citrate was performed in 14 chronic haemodialysis patients. During citrate anticoagulation a calcium-free dialysate was used and citrate was infused to obtain a concentration of 4.3 mmol/l blood. The unchallenged 'baseline state' expression of the surface molecules and the increase after ex vivo stimulation with phorbol 12-myristate 13-acetate (delta-PMA) or formyl-methionyl-leucyl-phenylalanine (delta-fMLP) was studied. RESULTS: With heparin, as well as with citrate, a sharp fall in granulocyte and monocyte count was observed after 15 min of dialysis, followed by a recovery at the end of the session. The expression of CD11b, CD11c and CD45 on granulocytes increased markedly during cuprophane dialysis with a peak at 15 min; there were no differences in response between heparin and citrate anticoagulation. Delta-PMA and delta-fMLP for CD45, CD11c and CD14 showed a decrease during cuprophane dialysis vs t0; again there were no differences between heparin and citrate. CONCLUSION: We conclude that the use of citrate was not associated with reduced leukocyte activation as measured by the expression of surface molecules during cuprophane dialysis and that no effect on dialysis leukocytopenia could be registered.

Aged↗
PubMed1998

The haematopoietic effect of recombinant human erythropoietin in haemodialysis is independent of the mode of administration (i.v. or s.c.).

BACKGROUND: Previous studies comparing intravenous (i.v.) and subcutaneous (s.c.) administration of recombinant human erythropoietin (rHuEpo) often did not achieve optimal iron reserve, were restricted to a limited follow-up period (not allowing equilibration) and/or did not exclude the role of other confounding factors. In addition all papers focused on the conversion from i.v. to s.c. METHODS: In this study, 30 equilibrated patients on s.c. rHuEpo were randomized into two groups, one converting to i.v. after 6 months of follow-up and one remaining on s.c. rHuEpo. In both groups rHuEpo was administered three times weekly. Only patients completing a further 6 months follow-up were considered for statistical evaluation. Serum ferritin was targeted at 200 ng/ml and haematocrits between 28 and 36% were pursued. RESULTS: The average haematocrit levels before conversion were 31.9 +/- 1.1% in the conversion group and 31.4 +/- 1.6% at the same time point in the nonconversion group (P = NS). After 6 months haematocrits were 31.5 +/- 0.5% in the conversion group and 31.1 +/- 0.9% in the non-conversion group (P = NS). Ferritin concentration in the conversion group was 219 +/- 49 ng/ml before and 230 +/- 83 ng/ml after the conversion. For the non-conversion group ferritin was 224 +/- 25 ng/ml and 236 +/- 52 ng/ml respectively (P = NS). The weight-standardized average rHuEpo dose per injection remained the same in the conversion group before and after conversion (44.0 +/- 1.8 U/kg/injection vs 45.4 +/- 4.7 U/kg/injection) (P = NS). In the non-conversion group the corresponding rHuEpo doses were 32.9 +/- 4.2 U/kg/injection and 39.6 +/- 7.0 U/kg/injection respectively (P = NS). There were no differences in serum PTH, aluminium, vitamin B12, folic-acid levels, and intake of co-trimoxazole, ACE inhibitors or theophylline. CONCLUSION: No changes in rHuEpo dose were observed after conversion from s.c. to i.v. There were no significant differences between the conversion and non-conversion group. These results are in contrast to some earlier studies suggesting lower rHuEpo requirements in case of s.c. administration.

Adult↗
PubMed1998

Inhibition of calcitriol-induced monocyte CD14 expression by uremic toxins: role of purines.

End-stage renal disease is associated with a defect in immunologic functions. Previous studies have demonstrated that uremic ultrafiltrate (UUF) contains factors that suppress calcitriol synthesis and its biological actions. In the present study, the effect of UUF on basal and calcitriol-induced membrane bound CD14 expression of monocytes activated by phorbol 12-myristate 13-acetate was evaluated. CD14 acts as a receptor for the complexes of lipopolysaccharide and lipopolysaccharide-binding protein. Monocytes isolated from normal donors were used for the assay of monocyte CD14 expression. A calcitriol induced rise in monocyte CD14 expression (1966+/-423 to 2421+/-436 fluorescence intensity) was found. However, UUF not only suppressed basal CD14 expression of monocytes (from 1966+/-423 to 1240+/-203, P < 0.05) but also significantly blunted calcitriol-induced CD14 expression (from 2421+/-436 to 1744+/-229, P < 0.05). HPLC fractionated UUF collected from 8 to 16 min (fraction 1, F1) and from 25 to 40 min (fraction 3, F3) also significantly suppressed the expression of CD14. Because purine derivatives coeluted within F1, their effect on monocyte CD14 expression was also tested. Uric acid, xanthine, and hypoxanthine was found to suppress basal as well as calcitriol-induced CD14 expression of monocytes in a dose-dependent manner. In conclusion, UUF contains factors that impair calcitriol activated function of monocytes.

Calcitriol↗
PubMed1998

Analysis of the reasons for transfers between hemodialysis and peritoneal dialysis and their effect on survivals.

Data on the outcomes of patients who are transferred between hemodialysis (HD) and peritoneal dialysis (PD) are scant. This study analyzes data on patients transferred from their initial modality at the University Hospital Gent between 1978 and 1996 for the reasons for, and outcomes from, the transfer. The reasons for the transfer from HD to PD (n = 35) were access problems (25%), cardiovascular (40%) and blood pressure problems (25%), and personal choice (10%). For the transfer from PD to HD (n = 32) peritonitis (50%), social problems (14%), adequacy or ultrafiltration problems (25%), and leakage (11%) were the reasons. There were no differences in survivals between patients who started on HD and who were transferred to PD, and those who remained on HD (P = 0.4). There were improved survivals for the patients who started on PD and who were transferred to HD compared to those remaining on PD (P = 0.01). It is concluded that transferring problematic HD patients to PD does not improve their survivals, whereas the survival of patients with PD-related complications is improved by transferring them to HD. This is due to the differences in the reasons for transfer, which are PD-related complications in the case of PD patients, and cardiovascular problems in the case of HD patients.

Comorbidity↗
PubMed1998

Peripheral motor and sensory nerve conduction studies in haemodialysis patients. A study of 54 patients.

Peripheral motor and sensory nerve conduction velocities were studied prospectively in 54 chronic haemodialysis patients. The most sensitive parameters for the detection of polyneuropathy were the deep peroneal nerve motor conduction velocity, the sural nerve sensory conduction velocity and the H-reflex latency and H-index of the S1 roots. All patients examined were found to present at least one abnormal nerve conduction parameter. In the present study the side of the arteriovenous shunt had no statistically significant effect on the sensory and motor nerve conduction velocities in the upper extremities. There was a significant correlation between H-reflex latency and H-reflex index, and between H-reflex latency and sural nerve sensory conduction velocity.

Adolescent↗
PubMed1997

Binding of indole-3-acetic acid to human serum albumin and competition with L-tryptophan.

Indole-3-acetic acid (IAA) is a product of tryptophan (Trp) metabolism and is found to be markedly increased in uremic sera. IAA binding to defatted human serum albumin at 37 degrees C and pH 5, 7.4, and 8.5 was studied by equilibrium dialysis, and data were analyzed assuming two independent high affinity binding sites plus a class of low affinity sites. The estimated values of the association constant of dominant site were: 7.96 x 10(3) M-1 at pH 5, 11.57 x 10(3) M-1 at pH 7.4, and 6.30 x 10(3) M-1 at pH 8.5. The competition between IAA and Trp for albumin binding at pH 7.4 was investigated. The results suggest that one specific albumin site is common for IAA and Trp, but the data were not adequately predicted by a purely competitive scheme. A better prediction was achieved assuming that the binding of IAA to a site different from the common site inhibits Trp binding.

Binding Sites↗
PubMed1997

Serum uremic toxins from patients with chronic renal failure displace the binding of L-tryptophan to human serum albumin.

The level of free tryptophan (Trp) and its metabolites in serum appears to be related to some pathologic states, such as chronic renal failure and neuropsychiatric disorders, so that a precise characterization of tryptophan binding to serum albumin is of interest. In the present paper, the binding of L-tryptophan to defatted human serum albumin at 37 degrees C and at pH 7.4 was studied by means of equilibrium dialysis. The competition between L-tryptophan and serum solutes extracted from uremic patients undergoing hemodialysis, before dialysis treatment, was also investigated. Solutes were extracted from uremic pools of sera using two different deproteinization methods: serum ultrafiltration and heat denaturation of serum proteins followed by ultrafiltration. We found 1.10 +/- 0.03 binding sites for Trp to defatted albumin with an association constant 11.37 +/- 1.03 x 10(3) M-1. The competition experiments suggested that the number of Trp binding sites were not significantly modified by the addition of solutes obtained with the method of ultrafiltration with respect to the binding of L-tryptophan to albumin in the absence of competitors, while their affinity constant was markedly reduced (2.66 +/- 0.18 x 10(3) M-1). Moreover, a significant reduction of the affinity constant was observed when competitors for Trp were obtained using heat deproteinization associated with ultrafiltration (1.91 +/- 0.15 x 10(3) M-1 vs. 2.66 +/- 0.18 x 10(3) M-1; P < 0.005). These results might be ascribed to the fact that the last procedure has a higher yield with a more complete liberation of uremic toxins from serum proteins, so that they became probably totally free thus competing at higher extent with L-tryptophan for albumin binding sites.

Binding Sites↗
PubMed1997

Estimation of parameters in a two-pool urea kinetic model for hemodialysis.

A two-pool, variable volume urea kinetic model for estimation of solute removal in hemodialysis is solved analytically, and closed form expressions are presented for urea concentration in both compartments, both during dialysis and between dialyses. This approach also includes an estimation of the extent of the post dialysis rebound phenomenon of urea concentration. A method is presented to estimate values for the urea generation rate G, the distribution volume V and its partition in two compartments with volumes alpha 1V and alpha 2V (alpha 1-alpha 2-1), the total clearance K, and intercompartmental transfer coefficient X. To apply this analysis, several measurements are needed as input; the urea concentration at the end of a dialysis, the evolution of this concentration during the next dialysis, with at least four measurements including the initial and the final concentration, the volume of the dialysate, and its urea concentration. The main results are: the magnitude of the rebound is approximately proportional to alpha 2(2) K/X; the accuracy of the parameter estimation does not improve much further by taking more than six measurements during dialysis.

Humans↗
PubMed1997

HPLC fractions of human uremic plasma inhibit the RBC membrane calcium pump.

We have reported that uremic plasma filtrates (UF) inhibit the red blood cell (RBC) membrane calcium pump. The inhibitor was dialyzable, smaller than 3,000 molecular weight, heat-stable, and protease-resistant. In the present study, we used reverse-phase preparative HPLC, analytical HPLC, and Sephadex G-25 elution to identify inhibitory fractions. Inhibition was confirmed in three different bioassays: (1) Sr2+ efflux in intact RBC, the primary bio-assay; (2) 45Ca efflux in intact RBC; and (3) calcium ATPase activity in isolated RBC membranes. Active fractions were analyzed by mass spectrometry, capillary electrophoresis, enzymatic analysis, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy. These demonstrated a number of compounds, including: sugars, polyols, osmolytes like betaine and myoinositol, amino acids, and other metabolites, such as 3-D-hydroxybutyrate, dimethylglycine, trimethylamine-N-oxide, guanidinoacetic acid and glycine. Many individual compounds were then tested for an effect on the calcium pump. Thus, HPLC was able to separate a substantial number of compounds in inhibitory fractions. Efforts are under way for precise identification of the inhibitor, to advance our understanding of uremic toxicity and/or hypertension in CRF.

Adult↗
PubMed1997

Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective post-mortem study.

The histological prevalence of beta-2 microglobulin amyloidosis (A beta 2m) was evaluated in a prospective study of joint samples obtained at autopsy in 54 patients on hemodialysis (HD) for 2 to 163 (median 47) months, aged 20 to 80 (median 63) years at HD onset. Carpal tunnel syndrome surgery or radiological signs of A beta 2m were present in 2 and 4% of them, respectively. A control group of 34 patients without end-stage renal disease, autopsied during the same period was used as a reference. The 153 sampled joints (1 to 8, median 2 per patient) were sternoclavicular joints (N = 77), shoulders (N = 35), knees (N = 28), others (N = 13). A beta 2m was diagnosed (positive Congo red with typical birefringence and positive immunostaining of deposits for beta 2m) in 26 of 54 (48%) patients. Prevalence reached respectively 21%, 33%, 50%, 90% and 100% within two years, after 2 to 4 years, 4 to 7 years, 7 to 13 years and more than 13 years HD. The calculated sensitivity of the various joints for A beta 2m detection is significantly higher (P < 0.03) for sternoclavicular joints (97%) and knees (91%) than for shoulders (57%). Multivariate stepwise logistic regression with discriminant analysis identified both HD duration (P = 0.0008) and age at HD onset (P = 0.0093) but not diabetic nephropathy (P = 0.23) or gender (P = 0.25) as independent risk factors for A beta 2m. The probability of joint A beta 2m was quantitated as a function of age and HD duration. In conclusion, A beta 2m may be observed in the large joints early after HD onset. Overall prevalence reaches 48% of the patients on HD for a median of 47 months. It is much higher than that reported on the basis of clinical or radiological evidence. The sternoclavicular and knee joints are more frequently (P < 0.03) involved than the shoulder. The easily accessible sternoclavicular joint therefore appears to be the best site for the early detection of A beta 2m. Both HD duration and age at HD onset, but not diabetic nephropathy, are independent risk factors for A beta 2m.

Aged↗
PubMed1997

P-Cresol, a uremic compound, enhances the uptake of aluminum in hepatocytes.

In the end-stage renal disease patient, certain uremic compounds could influence the cellular accumulation of aluminum (Al). In this study, we examined the effect of 15 uremic ultrafiltrate fractions obtained by HPLC on the uptake and toxicity of Al in mouse hepatocytes (MH) in culture, a model system in which Al is taken up bound to transferrin (Tf). Uremic fractions 4 to 8, 12, 14, and 15 increased cellular Al uptake and aspartate aminotransferase release and decreased cell growth when Tf-Al, not Al citrate, was added to culture media. Compounds that have been extracted previously from these ultrafiltrate fractions (p-cresol, xanthine, tryptophan, hippuric acid, and o-hydroxyhippuric acid) were then tested for their effect on Al uptake and toxicity in MH at concentrations found in uremic serum. Significant Al uptake by MH was observed only when p-cresol was added together with Tf-Al. Time-response curves showed increased Al uptake and toxicity at p-cresol concentrations of 3 mg/dl in culture media. Dose-response curves confirmed that Al uptake and cell toxicity were proportional to p-cresol from 1.5 mg/dl to 3 mg/dl in culture media. p-Cresol was not toxic to MH in the absence of Tf-Al in media. p-Cresol increased Tf-associated Al uptake only because there was no effect on Al uptake when Al citrate was substituted, and studies with Tf-I125-Al in the presence of this compound showed increased Tf-I125 taken up by MH. p-Cresol did not increase Tf saturation with Al. p-Cresol also increased Tf-Al uptake in Friend erythroleukemia and neuroblastoma cells in culture. Our studies suggest that p-cresol and uremic fractions 4 to 8, 12, 14, and 15 increase the uptake and toxicity of Al in cultured MH. These compounds may play a role in the accumulation and toxicity of Al in the liver of end-stage renal disease patients and possibly in all cells that express Tf receptors.

Aluminum↗