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Biomedical subjects

M Fischbach

Publications and source records attributed to M Fischbach.

At least 73 records · Page 4Linked to original sources

Management of fluid overload in infants by tidal peritoneal dialysis: is there a benefit compared with continuous cycling peritoneal dialysis?

Dialysed infants are sometimes characterized by a hyperpermeable peritoneal state. In this situation decreasing dwell time and/or increasing dialysate tonicity are usually proposed to achieve adequate ultrafiltration (UF). We have investigated UF capacity under different peritoneal dialysis modalities in three infants. UF was not obtained with isotonic continuous ambulatory peritoneal dialysis (CAPD), and was only achieved with short dwell times and hypertonic CAPD. For the prescription of automated peritoneal dialysis, a shorter dwell time of hourly sequences is needed, which consequently decreases the phosphate diffusion time. Continuous cycling peritoneal dialysis with sequences of 1 h allowed efficient UF [UF/glucose absorption (UF/G) 4.2 +/- 0.9] but the dialysate/plasma (D/P) phosphate ratio was low (0.47 +/- 0.12). In contrast, tidal peritoneal dialysis gave a better UF/G ratio (6.8 +/- 0.7) without a decrease in the D/P phosphate ratio (0.64 +/- 0.18).

Body Fluids↗

Short-term niflumic-acid-induced acute renal failure in children.

Several reports emphasize the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on renal function. We have observed over the last 10 years seven cases of acute renal failure (ARF) due to immune interstitial nephritis in children. A recommended oral or rectal dose of niflumic acid was prescribed for ear-nose-throat disorders. Length of exposure was 1-5 days. Clinical symptoms (oedema, oliguria or anuria) appeared between 3 and 6 days. Three patients had previously received the drug. Hypersensitivity signs (fever, skin rash, eosinophilia, and/or increased IgE) were present in all cases, leukocyturia in five cases, and haematuria in six cases. Renal biopsy showed interstitial lesions with lymphocyte, eosinophil, and plasma cell infiltrates without tubular cell necrosis. Glomeruli were normal on light-microscopy, except in one patient. Electron-microscopy showed extensive podocyte fusion in two patients, who had clinical and laboratory evidence of nephrotic syndrome (NS). ARF rapidly disappeared after NSAID withdrawal, except in two patients whose renal failure was irreversible despite methylprednisolone bolus. ARF is very rare in children treated with niflumic acid. When ARF occurs, different pathophysiological mechanisms are involved but the most common is immunological.

Acute Kidney Injury↗

[Gitelman syndrome in children: true hypokalemia but false Bartter syndrome].

BACKGROUND: Gitelman's syndrome or familial hypokalemia-hypomagnesemia and Bartter syndrome share some common features but their prognosis is quite different. CASE REPORT: Four unrelated children, aged 5 to 12 years, were studied because they suffered from muscle cramps and/or abdominal pain. Supportive findings included: hypokalemia (2.1 to 2.9 mmol/l), metabolic alkalosis (31 to 34 mmol/l), hyperkaliuresis (5.8 to 7.1 mmol/kg/day), hypomagnesemia (0.58 to 0.64 mmol/l), hypermagnesuria (0.19 to 0.23 mmol/kg/day), hypocalciuria (0.012 to 0.021 mmol/kg/day). Blood pressure contrasting with high renin activity (19.04 to 20.03 ng/ml/hr) was normal. Chloride fractional excretion after oral water supplementation was only slighty decreased and hypercalciuric response to furosemide administration was not observed. Supplementation with magnesium chloride failed to correct hypomagnesemia while potassium chloride improved hypokalemia. CONCLUSIONS: Age of onset, tetany manifestations, absence of growth retardation, hypermagnesuria despite, hypomagnesemia, hypocalciuria not improved by furosemide favor the diagnosis of Gitelman's syndrome rather than that of Bartter syndrome initially considered.

Bartter Syndrome↗

Hydrostatic intraperitoneal pressure in children on peritoneal dialysis: practical implications. An 18-month clinical experience.

Intraperitoneal pressure (IPP) is easy to measure routinely in children on peritoneal dialysis (PD) (especially with the twin bag Y-set) as described in adults: value expressed in centimeters of water, average of IPP (mean IPP) at inspiration and at expiration, with point zero located on the mid-axillary line while the patient rests in a perfectly supine position. IPP remained high during the first two to three days postsurgical peritoneal catheter implantation (15 +/- 4 cm) despite low dialysate volume per exchange (10 mL/kg). Afterwards, IPP decreased (10 +/- 2 cm) despite increasing dialysate volume from 10-50 mL/kg. Mean IPP seemed lower in infants (5 +/- 3 cm) in contrast to children (10 +/- 2 cm) on chronic PD with dialysate volume of 1000 mL/m2. There was a strong negative linear correlation between ultrafiltration (UF) volume and mean IPP with isotonic dialysate (1.36% dextrose concentration). By contrast, there was only a weak positive linear correlation between UF volume and mean IPP with hypertonic dialysate (3.86% dextrose concentration).

Adolescent↗

Optimization of CCPD prescription in children using peritoneal equilibration test.

Continuous cycling peritoneal dialysis (CCPD) is automatically performed by a cycler as a repetition several times per session of the same programmed exchange. We have investigated the efficiency, in terms of ultrafiltration (UF) capacity and solute clearance (phosphate), of an adapted (optimized) CCPD versus a conventional CCPD. Adapted CCPD was performed manually in order to allow a combination of short dwell times (optimal ultrafiltration) and long dwell times (optimal purification). The ratio of ultrafiltration over glucose absorbed (UF/G) was higher with adapted CCPD (5.7 +/- 0.8) compared with conventional CCPD (4.8 +/- 1.3). Phosphate purification was also enhanced with adapted CCPD (0.21 +/- 0.05 versus 0.16 +/- 0.05 mL/min/kg). These results confirm the usefulness of the concept of adapted CCPD with variable dwell times for optimization of peritoneal dialysis performances in children.

Absorption↗

Cloning of a human IgM autoantibody bearing a cross-reactive idiotype in a lambda expression vector: a new approach to studying autoantibodies.

The monoclonal antibody 4B4 is a human IgM,kappa which expresses a cross-reactive lupus-associated idiotype and has anti-Sm binding activity. We find that the VL nucleotide sequence of 4B4, like the 4B4 VH region, is encoded by unmutated germline genes. The 4B4 VH and VL were cloned into the ImmunoZap lambda expression vector to produce three recombinant immunoglobulin polypeptides. These recombinant polypeptides expressed, respectively, either the 4B4 VH or VL alone or a VH/VL heterodimer. ELISA showed that the VH/VL heterodimer retained anti-Sm antibody activity. The 4B4 idiotype was found predominantly on the VH. This report describes: (i) a method for producing recombinant immunoglobulin molecules from an IgM-secreting B cell line and (ii) the ability of recombinant antibody fragments expressed in Escherichia coli to retain the structural and antigenic properties of the native molecule.

Amino Acid Sequence↗

The intensity of vanadium(V)-induced cytotoxicity and morphological transformation in BALB/3T3 cells is dependent on glutathione-mediated bioreduction to vanadium(IV).

Cytotoxicity and morphological transformation has been studied in BALB/3T3 Cl A31-1-1 mouse embryo cells for ammonium vanadate [vanadium(V)] and vanadyl sulphate [vanadium(IV)] alone or in combination with diethylmaleate (DEM), a cellular glutathione (GSH)-depleting agent. Cells exposed for 24 h to 10(-5) M vanadium(V) alone or in combination with 3 x 10(-6) M DEM showed the characteristic hyperfine EPR signal of vanadium(IV), which was more obvious in the case of exposure to vanadium(V) alone. This suggests that the amount of vanadium(V) reduced to vanadium(IV) decreased in GSH-depleted cells. While vanadium(IV) at concentrations of 3 x 10(-6) M and 10(-5) M was not transforming in the cells, vanadium(V) showed neoplastic transforming activity (P < 0.025 and P < 0.001 for the two doses, respectively) in comparison to controls (vanadium unexposed cells). Cytotoxicity and morphological transformation in cells exposed to vanadium(V) in combination with 3 x 10(-6) M DEM were significantly more intensive (P < 0.005 and P < 0.01 for the two doses of vanadate tested) compared to the corresponding values observed in cells exposed to vanadium(V) alone. This suggests that the final transforming activity response is dependent on the intracellular GSH-mediated mechanism of reduction of vanadium(V) to vanadium(IV): (i) the extent to which vanadium(V) should be bioreduced to less toxic vanadium(IV) via intracellular GSH is a key point in determining the intensity of the observed neoplastic action; (ii) the carcinogenic potential of vanadium(V) should be strictly dependent on its intracellular persistence which could lead to changes in normal metabolic patterns of vanadium(V) in the oxidized form due to lack of GSH-mediated reduction.

3T3 Cells↗

Use of cell cultures, nuclear and radioanalytical techniques for metallotoxicological studies at the JRC-Ispra.

This paper reviews the JRC-Ispra research activity on toxicological studies related to the environmental and occupational exposure of trace metals, as carried out by a combination of cell culture methodologies with nuclear and radioanalytical techniques. Applications concern the setting of uptake-effect relationships and the study of the mechanisms of toxicity of specific metals (Al, As, Cd, Co, Cr, Mo, Se, V), as well as the establishment of ranking of metal toxicity by carrying out systematic studies (screening tests).

Animals↗

[Effectiveness of and tolerance to human recombinant erythropoietin in the treatment of kidney failure anemia in children undergoing continuous peritoneal dialysis. Multicenter study].

Eight young children with renal failure, undergoing continuous peritoneal dialysis (CDP) and presenting an anemia (hemoglobin level [Hb] 57 to 89 g/l) were treated by subcutaneous recombinant human erythropoietin (rHu EPO) twice weekly. The initial dose of 75 U/kg was adjusted to induce progressive increase of Hb with a target level of 100-120 g/l. Treatment duration was 24 weeks in five of these children and 10 to 13 weeks in the three others. In seven cases out of eight, anemia was corrected. The target Hb level was reached in 3 to 21 weeks with rHu EPO doses of 150 to 300 U/kg/w (mean: 200 U/kg/w) for four children without recent transfusion; then the median maintenance dose was 135 U/kg/w (range: 50-300 U/kg/w). In only one patient, Hb never reached a level higher than 77 g/l despite weekly dose of 350 U/kg, a reticulocytosis of 5.6%, rHu EPO treatment lasting up to 24 weeks and the absence of iron deficiency. In any case, no transfusion was necessary after the first day of rHu EPO treatment. In three patients, the increase of a preexisting hypertension required the adaptation of antihypertensive treatments. One patient presented a marked thrombocytosis. In conclusion, twice-a-week subcutaneous injections of 75 to 150 U/kg of rHu EPO appear to be well tolerated and effective in the treatment of anemia of CPD children.

Anemia↗

Mental retardation, ataxia, seizures, dysmorphia, and hydrocephaly in two sibs. Angelman syndrome or new syndrome.

We report two sibs with Angelman syndrome or an apparently new syndrome. In addition to severe mental retardation and seizures, clinical examination showed an ataxic and stiff legged gait, truncal hypotonia with hypertonia of the limbs, dysmorphic facial features (brachycephaly, large mouth, pointed chin and a prominent jaws) and scoliosis. Brain CT scan and MRI revealed ventricular enlargement and squared frontal horns. Pregnancy and delivery were uneventful. Karyotypes were normal. No deletion of chromosome 15q11-13 region was shown by molecular genetic techniques. The parents who are normal are second cousins. The condition is therefore probably inherited as an autosomal recessive one.

Angelman Syndrome↗

Phosphate dialytic removal: enhancement of phosphate cellular clearance by biofiltration (with acetate-free buffer dialysate).

Phosphate dialytic removal (PDR) depends in part on the type (acetate or bicarbonate) and the concentration of the buffer dialysate. Plasma phosphate reduction or PDR during a dialysis treatment is the algebraic sum, of phosphate cellular flux (removal or captation) and of phosphate tissular precipitation. High bicarbonate levels induce an intracellular shift of phosphate, thus not available for dialytic removal. On the contrary, acidosis prevents P shifting into the intracellular space, thus more P is available for dialytic removal. In order to evaluate cellular phosphate sequestration (CPS) we tested PDR in a crossover study. Three children were dialyzed (18 sessions) successively using either biofiltration with free buffer dialysate and a constant bicarbonate fluid infusion rate (BF) or using sequential biofiltration (SBF) with an initial controlled acidosis period realized by bicarbonate reinjection fluid rate modelling. PDR was higher in SBF (32 +/- 4 mmol/session) than in BF (24 +/- 6 mmol/session). SBF seemed to be efficient against CPS; it clearly demonstrates that bicarbonate modelling is a promising dialytic approach to enhance PDR. The real clinical relevance of these biological results needs clinical long-term evaluation.

Adolescent↗

[Acute kidney failure and nutrition].

Acute renal failure (ARF) is characterized by a persistently high mortality rate, mainly in prerenal, postaggressive forms. Nutritional perturbations are related to the metabolic response to stress, ie mainly an elevation of the basal caloric expenditure and a marked proteic hypercatabolism, and to specific consequences of the loss of renal function. Identification of characteristic metabolic patterns and of their mediators, leading to a nutritional support adjusted to the elevated demand rather than to the impairment of renal excretion faculties, may improve the prognosis. Benefits of such a nutritional support may be restricted to hypercatabolic forms of ARF in the intensive care unit, provided extrarenal failures are reversible.

Acute Kidney Injury↗

[Clinical examination of children with urination disorder].

The management of a child with disorders of urination must begin with a high-quality clinical examination. Detailed questioning in an atmosphere of confidence yields information on the type of disorder (dysuria, frequencies, urgencies, burning sensation at voiding, enuresis, incontinence) either alone or in association. Physical examination aims to find signs pointing to the cause of the disorder. Particular attention must be paid to an inspection fo the external genitalia and to a search for possible abnormalities affecting the pinna of the ear and the extremities, since they are frequently found in association with deep malformations of the urinary tract. Collecting the urine provides an opportunity to observe the process of urination and possible abnormalities in the initial, middle and terminal voiding streams. The reagent dipstick is a minute but true laboratory test accessible to children, which makes it possible to detect glomerular, tubular and interstitial lesions. This clinical examination will lead to a precise diagnosis, inform on the need, if any, for additional explorations and enable the clinician to select the correct treatment.

Humans↗