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Biomedical subjects

B Faller

Publications and source records attributed to B Faller.

At least 37 records · Page 2Linked to original sources
PubMed1995

Clinical evaluation of an optimized 1.1% amino-acid solution for peritoneal dialysis.

A significant percentage of dialysed patients have inadequate protein intake. One strategy for treating the protein malnutrition in peritoneal dialysis patients is to replace glucose in the dialysis solution by amino acids. A new peritoneal dialysis solution containing 1.1% amino acids in a formulation optimized for renal patients and with a lactate concentration of 40 mmol/l has been evaluated. Fifteen CAPD patients completed a non-randomized prospective 3-month study. Each patient received 2 litres of the optimised 1.1% amino acid solution for the second exchange of the day with a dwell time of 5-6 h. Indicators of efficacy were serum albumin and transferrin. After 3 months of intraperitoneal amino acids, serum albumin levels significantly increased from 32.7 +/- 2.3 to 35.1 +/- 2.2 g/l (mean +/- SD; P < 0.01). This occurred in parallel with a significant increase in transferrin levels from 2.21 +/- 0.26 to 2.39 +/- 0.27 g/l (P < 0.05). As expected, urea rose from 23.7 +/- 6.8 to 29.9 +/- 9.4 mmol/l. Interestingly bicarbonate did not change (25.5 +/- 4.2 versus 25.2 +/- 3.3 mmol/l). These results suggest that the optimized formulation is effective in improving nutritional parameters in CAPD patients while avoiding unwanted side-effects such as acidosis.

Adult↗
PubMed1995

Prognostic factors in CAPD patients: a retrospective study of a 10-year period.

A prognostic study was retrospectively performed on a cohort of 201 ESRD patients having started CAPD in one single centre between 1983 and 1993 (mean follow-up 24 months). At the end of the study 74 patients had died, 63 were transplanted, and 19 had been transferred to another dialysis modality. The purpose of the study was to estimate patient and technique survivals according to clinical and biological variables recorded at the beginning of the treatment. The authors decided to focus on the possible prognostic role of urea kinetic parameters which are still controversial in the literature. Concerning patient survival, the Cox proportional hazards model selected seven prognostic factors, including urea Kt/V (relative risk = 1.69). The division of the study group according to three levels of Kt/V (< or = 1.7, between 1.7 and 2.2, and > 2.2) allowed us to estimate 1.7 as an index of an adequate CAPD prescription. NPCR at the limit of significance for patient survival was clearly a prognostic factor for technique survival (relative risk = 2.50). Creatinine clearance was closely linked to both technique and patient survival (relative risk > 3). These three factors, in addition to the clinical and biological variables generally described in the literature, must be taken into account in the evaluation of a prognosis for CAPD.

Adolescent↗
PubMed1994

Evolution of clinical parameters and peritoneal function in a cohort of CAPD patients followed over 7 years.

The clinical results and the long-term evolution of some peritoneal transport characteristics were retrospectively analysed in a cohort of 23 patients who had been maintained continuously on CAPD for at least 7 years. Several clinical and biological results like blood pressure, peripheral nerve conductivity, total protein, and serum phosphorus showed relatively stable values. On the other hand increases were noted in body weight, consumption of antihypertensive drugs; creatinine, serum calcium and parathormone concentration. Haematocrit, cholesterol, and triglycerides significantly increased during the first 2-4 years but returned to the predialysis values after 5-7 years. In contrast with patients never exposed to acetate dialysate, there was a continuous loss of peritoneal ultrafiltration from 1000 ml/day to 780 ml/day (P < 0.05) in patients who had been treated with acetate. However, peritoneal creatinine clearances and the D/P creatinine ratios remained constant. The Kt/V urea index declined from 0.88 +/- 0.8 during the first year to 0.62 +/- 0.06 after 7 years (P < 0.001). This was due to a decline in contribution of the residual renal Kt/V urea index from 21.6% at the start to less than 3% after 7 years. A negative correlation between the Kt/V urea index per year and the hospitalization rate and a positive correlation with the peripheral nerve conductivity were found. In conclusion, the long-term peritoneal diffusive capacity can remain stable over 7 years in CAPD; in some patients a continuous fall in peritoneal ultrafiltration appears which can be counterbalanced by stimulation of their daily diuresis with high doses of frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Demonstration of a two-step reaction mechanism for the inhibition of heparin-bound neutrophil elastase by alpha 1-proteinase inhibitor.

Heparin decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor as a result of its strong binding to the enzyme. Here, we used the slow-binding kinetic approach to decide whether the enzyme-inhibitor interaction proceeds via a two-step mechanism and to identify the step that is affected by heparin. The inhibition kinetics was assessed under pseudo-first-order conditions using conventional or stopped-flow spectrophotometry. In the absence of heparin, the pseudo-first-order rate constant of inhibition increased linearly with the inhibitor concentration indicating that within the experimental concentration range (< or = 6 microM) the enzyme-inhibitor association conforms either to a simple bimolecular reaction (E+I kass-->EI with kass = 10(7) M-1 s-1) or to a two-step reaction (E+I Ki*<==>EI* k2-->EI with Ki* > 0.4 microM and k2 > 4 s-1). In the presence of heparin, the rate constant of inhibition varied hyperbolically with the inhibitor concentration, indicating that the inhibition is a two-step process with Ki* = 80 nM and K2 = 0.15 s-1. Thus, heparin has two opposite effects on the elastase + alpha 1-proteinase inhibitor interaction: it favors the association by decreasing Ki* but impairs it by decreasing k2. This rationalizes the previously demonstrated rate-depressing effect of the sulfated polymer. Heparin does not significantly alter the stability of the irreversible elastase-alpha 1-proteinase inhibitor complex.

Amino Acid Sequence↗
PubMed1993

Finasteride: a slow-binding 5 alpha-reductase inhibitor.

A microsomal preparation of human prostatic tissue was used to study the kinetics of interaction of steroid 5 alpha-reductase with finasteride, a known 5 alpha-reductase inhibitor. This molecule has been reported to reversibly bind 5 alpha-reductase in a competitive manner to testosterone with a Ki value in the 10 nM range. The results presented in this paper show that enzyme-inhibitor complex formation does not take place instantaneously as assumed in previous studies. At neutral pH and 37 degrees C, the association of enzyme with inhibitor is governed by a rate constant, kon, of 2.7 x 10(5) M-1 s-1. This low kon value, in combination with the high energy of activation of the association reaction (150 kJ mol-1), indicates that the association process is not diffusion controlled and may proceed through intermediate steps. However, such an intermediate was not detected kinetically under the inhibitor concentrations investigated. We therefore conclude that the equilibrium dissociation constant, Ki*, for the initial binding of the enzyme to the inhibitor is higher than 1.5 x 10(7) M. Even at inhibitor concentrations as low as 1 nM, the reaction was completely displaced to the EI complex and no residual activity detected once the equilibrium was reached. Hence, the interaction between finasteride and 5 alpha-reductase can also be characterized by a very low overall equilibrium dissociation constant (Ki << 10(-9) M), at least 1 order of magnitude lower than previously reported values.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1993

Daily subcutaneous administration of recombinant human erythropoietin (rhEPO) in peritoneal dialysis patients: a European dose-response study.

In a prospective randomized open multicenter study, 107 anemic (Hct < = 28%) peritoneal dialysis (PD) patients were treated with s.c. rhEPO daily. The mean observation period was 299 days (range 14-479 days). Patients were randomly assigned to 3 groups with different initial doses: 5 U/kg (G5), 10 U/kg (G10), 20 U/kg (G20). Initial doses were maintained for at least 8 weeks unless the target Hct (30-35%) was achieved earlier. The weekly increase of Hct was significantly (p < 0.05) dose-dependent: 0.19% in G5, 0.5% in G10 and 0.94% in G20. In case of insufficient response (< 0.5% per week), the dose was doubled every 4 weeks. Final doses on achieving the target Hct ranged from 5 to 40 U/kg (median 20 U/kg). The dose was then reduced to 50% and adjusted individually. The median maintenance dose was 9.9 U/kg/day. No tendency towards higher blood pressure or intensification of antihypertensive treatment was observed. When rhEPO is administered daily, 10 U/kg/day (70 U/kg weekly) is the recommended starting dose. The need for higher doses used in unsatisfactory response, should lead to further examination to rule out iron deficiency and other reasons for non-response. The median maintenance dose reported here is the lowest published in the literature for PD patients and seems to be linked to the daily injections.

Anemia↗
PubMed1992

Heparin-induced conformational change and activation of mucus proteinase inhibitor.

Low molecular mass heparin (5.1 kDa) forms a tight complex with mucus proteinase inhibitor, the physiologic neutrophil elastase inhibitor of the upper respiratory tract. This binding strongly enhances the intrinsic fluorescence of the inhibitor and the rate of neutrophil elastase inhibitor association. One mole of this heparin fragment binds 1 mol of inhibitor with a Kd of 50 nM. From the variation of Kd with ionic strength, it is inferred that (i) 85% of the heparin--inhibitor binding energy i due to electrostatic interactions, (ii) about seven ionic interactions are involved in heparin--inhibitor binding. strength, it is inferred that (i) 85% of the heparin--inhibitor binding energy is due to electrostatic interactions, (ii) about seven ionic interactions are involved in heparin--inhibitor binding. and (iii), about one-third of low quantum yield of Trp30, the single tryptophan residue of the inhibitor, blue-shifts its maximum emission wavelength by 6 nm, decreases the acrylamide quenching rate constant by a factor of 4, and increases the mean intensity weighted lifetime by a factor of 2.5. These important spectroscopic changes evidence a heparin--induced conformational change of the inhibitor which buries Trp30 in a very hydrophobic environment. Heparin accelerates the inhibition of elastase in a concentration-dependent manner. When both enzyme and inhibitor are saturated by the polymer, the second-order association rate constant is 7.7 x 10(7) M-1 s-1, a value that is 27-fold higher than that measured with the free partners. This finding may have important physiologic and therapeutic bearing.

Amino Acid Sequence↗
PubMed1992

Heparin interferes with the inhibition of neutrophil elastase by its physiological inhibitors.

Heparin depresses the second-order rate constant kass for the inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. For high and low molecular weight heparin the decrease in kass is 290-fold and 40-fold, respectively. This is due to a tight binding of the polymer to elastase: Kd = 3.3 nM or 89 nM for high or low molecular weight heparin respectively. In contrast heparin increases the rate of inhibition of elastase by mucus proteinase inhibitor. For low molecular weight heparin, there is a 27-fold increase in kass. This is due to a strong binding of the polymer to the inhibitor (Kd = 50 nM) which undergoes a conformational change.

Chromatography, Affinity↗
PubMed1991

Kinetics of the interaction of chymotrypsin with eglin c.

The kinetics of binding of recombinant eglin c to bovine pancreatic chymotrypsin was studied by conventional and stopped-flow techniques. With nanomolar enzyme and inhibitor concentrations, the inhibition was fast and pseudo-irreversible (k(assoc.) = 4 x 10(6) m-1.s-1 at 7.4 and 25 degrees C). Reaction of the enzyme-inhibitor complex with alpha 1-proteinase inhibitor, an irreversible chymotrypsin ligand, resulted in a slow release of free eglin c, which was monitored by electrophoresis (k(dissoc.) approximately 1.6 x 10(-6) s-1, t1/2 approximately 5 days). The proflavin displacement method and a stopped-flow apparatus were used to monitor the association of chymotrypsin with eglin c under a wide range of inhibitor concentration and under pseudo-first-order conditions. At pH 7.4 and 25 degrees C or 5 degrees C, or at pH 5.0 and 25 degrees C, the pseudo-first-order rate constant of proflavin displacement increased linearly with eglin c up to the highest concentration tested, suggesting a one-step bimolecular association reaction: E + I in equilibrium with EI. However, kassoc. is much lower than the rate constant for a bimolecular reaction and its activation energy (66 kJ.mol-1 at pH 7.4 and 78 kJ.mol-1 at pH 5.0) is far too high for a diffusion-controlled step. The enzyme-inhibitor association may therefore occur via a loose pre-equilibrium complex EI* (Ki* much greater than 5 x 10(-4) M) that rapidly isomerizes (k2 much greater than 2 x 10(3) s-1) into an extremely stable final complex (Ki approximately 4 x 10(-13) M). Unlike other proteinase-inhibitor systems, the chymotrypsin-eglin association is virtually pH-independent.

Amino Acid Sequence↗
PubMed1991

Heparin strongly decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor.

Heparin depresses the second-order rate constant ka for the inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. High molecular mass heparin decreases ka from 1.3 x 10(7) M-1 s-1 to a limit of 4.6 x 10(4) M-1 s-1. Low molecular mass heparin is about 7-fold less effective. Dermatan sulfate and chondroitin sulfate are less efficient. Heparin preparations used in clinical care also strongly depress ka when tested at concentrations corresponding to their clinical efficacy. Heparin also decreases the ka for the elastase/eglin c and the cathepsin G/alpha 1-proteinase inhibitor systems but not that for the alpha 1-proteinase inhibitor/pancreatic elastase or trypsin pairs. These results, together with Sepharose-heparin binding studies, indicate that the ka-depressing effect of the polymer is related to its ability to form a tight complex with elastase but not with alpha 1-proteinase inhibitor. One mol of high molecular mass heparin binds 3 mol of neutrophil elastase with a Kd of 3.3 nM. Low molecular mass heparin binds elastase with a 1:1 stoichiometry and a Kd of 89 nM. For both heparins ka is lowest when elastase is fully saturated with heparin. From this we conclude that heparin decreases ka, because the heparin-elastase complex is able to slowly react with alpha 1-proteinase inhibitor and not because the inhibitor slowly dissociates the heparin-elastase complex. These findings may have important pathophysiological bearing.

Cathepsin G↗
PubMed1991

[Continuous ambulatory peritoneal dialysis].

In contrast with hemodialysis (HD) Continuous Ambulatory Peritoneal Dialysis (CAPD) is a permanent dialysis procedure proposed to the chronic renal patients. Through a permanent peritenoal catheter the patients exchange 2 litres of dialysate 4 times a day, 7 days a week, as soon as the dialysat/plasma concentration for urea reaches 1. Inflow and outflow of the fluid is obtained by gravity, without machine. The short term survival rate is comparable between HD and CAPD. After 5 years, some patients, loosing the residual renal function, need to increase the possibilities of CAPD. The recent disconnect systems reduce the rate of peritonitis down to 1 episode every 36 months. With the actual technology the severe complications such as sclerosing peritonitis decrease or even disappear. Maintenance of an adequate nutritional status in the patients remains an often difficult problem. CAPD may be proposed to nearly all the patients who prefer to be treated at home: children, working adults, diabetics and elderly. Long term studies are still needed to follow the peritoneal performances over time.

Acute Kidney Injury↗
PubMed1991

[Treatment of chronic renal insufficiency: hemodialysis at a center or continuous ambulatory peritoneal dialysis? Comparative retrospective study of the success of both methods].

In a retrospective study, the authors analyse the dialysis-technique success rate in 276 chronic renal patients. 137 patients have been treated with in-center Hemodialysis (CHD) since 1972, 139 patients with Continuous Ambulatory Peritoneal Dialysis (CAPD) since 1978. The 6-year technic success rate reaches 28% in CAPD and 31% in CHD (not statistically significant). The risk factors influence the technic-success rate of both methods in the same way. The results suggest that in the analysed patients CAPD is at least as effective as CHD at maintenance in the technic.

Adolescent↗