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Biomedical subjects

S Ringoir

Publications and source records attributed to S Ringoir.

At least 19 recordsLinked to original sources

Influence of feeding, blood sampling method and type of anaesthesia on renal function parameters in the normal laboratory rat.

With sophisticated experiments it is necessary to handle laboratory animals many times. To determine the effect of minor handling a series of experiments was performed to measure the impact of fasting, anaesthesia, blood collection method and serum creatinine analysis on renal function. Simple clinical methods to measure renal function parameters such as diuresis, urinary osmolality, urinary creatinine excretion and serum creatinine were used. During fasting a significant increase (P < 0.01) in diuresis and a significant decrease (P < 0.01) in urinary osmolality were noted. Fasting and anaesthesia have the additional effect of significantly decreasing (P < 0.05) urinary creatinine excretion. Blood sampling method also has a significant impact on serum creatinine: venous sampling causes false-positive differences compared with simultaneous arterial sampling.

Anesthesia

Contrast media injection in the rat after multiple renal insults. No evidence of additional nephrotoxicity.

Experiments were performed to determine whether water-soluble contrast media (CM) show nephrotoxic properties when injected into rats after multiple renal insults. The latter consisted of combinations of prostaglandin synthesis inhibition (with indomethacin) and/or salt depletion and/or uninephrectomy. Renal function was evaluated by standard clinical methods to measure parameters such as urinary output, urinary osmolality, urinary creatinine excretion and serum creatinine. CM injected after prostaglandin synthesis inhibition alone did not influence urinary creatinine excretion or serum creatinine. After a combination of renal insults a significant increase in median serum creatinine values from 61.88 mumol/l [interquartile range (IR) 17.68] [0.70 mg% (IR 0.20)] to 97.24 mumol/l (IR 79.56) [1.10 mg% (IR 0.90)] was observed but CM or sham injections did not prevent a normalization of serum creatinine. The pattern of recovery of serum creatinine was not influenced by previous kidney mass reduction. It is concluded that the nephrotoxic properties of CM cannot be detected with standard clinical methods in rats after multiple renal insults.

Analysis of Variance

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

Evaluation of renal function before and after intravenous injection of non-cholangiographic water soluble contrast media in rats.

In the present study, normal laboratory rats (n = 22), were injected intravenously with water soluble contrast media (CM) or saline. Renal function was monitored before and followed after challenge. Seven animals were injected with saline, the others with 3 different types of contrast media. The absolute urinary creatinine output decreased significantly in the saline group, from 0.0247 mumol/min 100 g BW (IR: 0.0052) to 0.0167 mumol/min 100 g BW (IR: 0.0019) (p < 0.01), while in the CM groups only a significant decrease was seen after ioxaglate injection, from 0.0250 mumol/min 100 g BW (IR: 0.0014) to 0.0174 mumol/min 100 g BW (IR: 0.0027) (p < 0.01). ANOVA between the groups showed no difference. The median values for serum creatinine after injection of the test products did not differ from the control values. It seems therefore that the challenge of a normal laboratory rat with CM is not a suitable model for the detection of subtile nephrotoxic properties of CM.

Animals

Recombinant hirudin: a specific thrombin inhibiting anticoagulant for hemodialysis.

The first experience with hirudin as an alternative anticoagulant for heparin in hemodialysis is reported. Recombinant hirudin (HBW 023) was administered in 20 patients as a bolus before dialysis with low flux polysulfone dialyzers (PS400), the dosage being adapted stepwise from patient to patient by 0.02 mg/kg to the occurrence of clotting or bleeding. Four different administration schedules were studied. The first three schedules (0.02 mg/kg, N = 1; 0.04 mg/kg, N = 1; 0.06 mg/kg, N = 4) were discontinued because of clotting. The 0.08 mg/kg schedule was maintained without clotting event in 14 patients. Bleeding was not observed. Plasma hirudin averaged 503.9 +/- 214.0 and 527.7 +/- 217.1 ng/ml after two and four hours of dialysis, and decreased during an interdialytic interval of 44 hours to 223.2 +/- 86.2 ng/ml. Modified antithrombin III (P < 0.05) and activated partial thromboplastin times were lower (P < 0.01) under hirudin compared to heparin; these coagulation parameters were closer to normal during hirudin treatment. The patients developing clotting could be distinguished from those without clotting by the registration of the activated clotting times (9.2 +/- 3.0 vs. 18.7 +/- 3.2 min after 2 hr, P < 0.01; 8.1 +/- 3.0 vs. 16.2 +/- 3.8 min after 4 hr of dialysis, P < 0.05); cut-off value below which clotting is to be expected was 12 min). It is concluded that administration of hirudin as a bolus before the start of dialysis, at a dosage of 0.08 mg/kg, is not complicated by clotting or by bleeding. Coagulation tendency can optimally be monitored by the registration of the activated clotting time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

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

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

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

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

Cefodizime: enhancement of depressed phagocytosis-associated respiratory burst activity in chronic uremic patients.

Patients with renal failure are highly susceptible to infection, in part because uremia decreases the killing capacity of phagocytic leucocytes. Phagocytosis-associated respiratory burst activity was investigated at different stages of renal impairment by measuring the 14CO2 production during metabolism of labeled glucose by phagocytic cells. Non-dialyzed end-stage renal failure and haemodialysis patients showed a decrease in phagocytosis to about 50% of normal (p less than 0.05). In a second phase of the study, six haemodialysis patients received 2 g cefodizime (CDZ) i.v. after dialysis for ten days (five doses). Phagocytosis was determined at baseline and was followed until day 29. A clear, long-lasting stimulatory effect of CDZ on phagocytosis after both latex and zymosan challenge was found. It is concluded that a usual CDZ dosage regimen stimulates depressed phagocytosis in haemodialysis patients, and that this stimulatory effect persists for at least two weeks after the end of treatment. Uremic patients with infection may benefit from this additional property of CDZ.

Cefotaxime

Correction of deficient phagocytosis during erythropoietin treatment in maintenance hemodialysis patients.

Studies on the influence of erythropoietin (EPO) on granulocyte or monocyte function are scant. In this study, the effect of EPO on polymorphonuclear cell (PMN) respiratory burst activity was evaluated in a double-blind, placebo-controlled study in 22 patients on maintenance hemodialysis. As an index of phagocyte respiratory burst activity, the increase in 14CO2 production from labeled glucose-1-C, after challenge with latex and zymosan, was measured on predialysis whole blood samples, before and after EPO-treatment. As controls, 56 nonuremics and 49 non-EPO-treated hemodialysis patients were evaluated. Before EPO treatment 14CO2 production was depressed to 75.7% (latex) and 54.6% (zymosan) of healthy controls (P less than 0.01). A marked improvement was observed after a mean treatment period of 4 months (latex, 115 +/- 12 to 172 +/- 14; zymosan, 178 +/- 19 to 412 +/- 36 dpm/10(3) PMN, P less than 0.01). Placebo treatment induced no changes. The improvement became more pronounced with prolongation of treatment. A significant correlation between hematocrit and 14CO2 production was observed in the EPO treatment group (latex: n = 44, r = 0.47, P less than 0.05; zymosan: n = 44, r = 0.57, P less than 0.001). No correlation was found with serum ferritin. We conclude that the depressed phagocyte glycolytic activity of hemodialyzed uremics is normalized during correction of anemia by EPO. This may be attributed to factors other than a reduction in the body iron stores.

Adult

A longitudinal, five year survey of urea kinetic parameters in CAPD patients.

This study reports on the five years' evolution of the KT/V urea index and protein catabolic rate (PCR) in 16 CAPD patients who were treated with a constant daily dialysis dose. Total KT/V urea index decreased with time from a value of 0.96 +/- 0.06 at the start to 0.55 +/- 0.05 at five years of treatment. This decline was due to the opposite changes of two important parameters affecting the index. First, the contribution of the residual urinary KT/V gradually decreased from 28.6% at the start to 8 to 9% after four years. Second, the distribution volume of urea calculated as a constant fraction of body weight gradually increased. The body weight increased from 58.2 +/- 2.79 kg at start to 70.6 +/- 3.33 kg at five years. Peritoneal urea clearances and ultrafiltration rates remained stable. In 12 patients with stable body weight between 24 and 48 months, PCR decreased from 0.98 +/- 0.05 to 0.87 +/- 0.05 g/kg/day. A positive correlation between KT/V urea and PCR and a negative correlation between KT/V urea and number of hospitalization days, peritonitis rates and peripheral nerve conductivity was found. The same negative correlation was found when only the KT/V urea index obtained during the first year of treatment was considered. In conclusion, the KT/V urea index decreases in CAPD patients primarily because residual renal function decreases and body weight increases, while the peritoneal clearing for urea is maintained. The index correlates with some clinical parameters, and may have some prognostic value.

Adult