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Biomedical subjects

C Loirat

Publications and source records attributed to C Loirat.

At least 73 records · Page 4Linked to original sources

Cyclosporine pharmacokinetics in nephrotic and kidney-transplanted children.

The pharmacokinetic parameters of cyclosporine (CsA) were determined in 23 kidney transplant recipients and 19 children with nephrotic syndrome, after intravenous and oral administration. The mean bioavailability was 39%, blood clearance was 0.55 l.h-1.kg-1 and volume of distribution at steady-state was 2.77 l.kg-1. The absorption profile was monophasic (67%), biphasic (29%) or poor (4%). The maximum blood concentration of CsA was significantly higher in children with a monophasic profile than in children with a biphasic profile (550 vs 380 ng.ml-1). Blood clearance was significantly higher in the transplant recipients than in the patients with nephrotic syndrome (0.65 vs 0.43 l.h-1.kg-1. Although age, haematocrit, creatinine clearance, serum albumin and cholesterol differed between the two groups, only haematocrit and creatinine clearance were significantly (negatively) correlated with CsA clearance.

Absorption↗

Complete inherited deficiency of the fourth complement component in a child with systemic lupus erythematosus and his disease-free brother in a north African family.

Although null alleles of complement C4 genes (C4A*Q0 and C4B*Q0) are frequent in the normal population, the occurrence of two null alleles on the same chromosome is very rare and therefore complete C4 deficiency is exceptional. We describe a 16-year-old North African boy who presented with systemic lupus erythematosus with renal involvement and persistent undetectable classical pathway activity and C4 protein and hemolytic activity in plasma, with normal C3 levels. Similar complement abnormalities were observed in his healthy 12-year-old brother. Complete C4 deficiency was documented in the two brothers by investigation of the family and the lack of C4A and C4B bands upon phenotyping of C4. Southern blot analysis of the C4/CYP21 gene organization in the family indicated that the deficiency resulted from a deletion of the C4B/CYP21A genes associated with nonexpression of a C4A gene. The double-null haplotype was found to be associated with homozygous A2 B17 C2C BFF C4 AQ0 BQ0 DR7 HLA haplotype. Thus, similar C4 deficiencies with HLA identity may lead to different clinical presentations.

Adolescent↗

[Treatment of anemia in hemodialyzed children using recombinant human erythropoietin (Eprex). Results of a French multicenter clinical trial].

Intravenous recombinant human erythropoietin (Eprex Cilag) was used in 28 hemodialyzed children, treated in 3 French paediatric centers, from November 1989 to November 1990. Transfusion dependency disappeared in all cases: the number of transfusions decreased from 7.3 unit/patient/year to 0.6 unit/pt/year. The mean haemoglobin concentration for the whole group increased from 6.6 +/- 0.8 g/dl, to 9.2 +/- 1.2 at 6 months and 9.7 +/- 0.7 g/dl at 1 year. Twenty-two out of 28 children reached the target haemoglobin value of 9.6 g/dl (6 mmol/dL) within a mean time of 16.5 weeks. Poor responses were due to either a premature withdrawal of treatment because of renal transplantation, or too low a dosage for the age. The study showed indeed that the dose requirement was significantly dependent on physical development: the mean dosage required to maintain haemoglobin concentration at the target value was 300 U/kg/week in children weighing less than 20 kg, 222 U/kg/week in 20-30 kg children, and 135 U/kg/week in those weighing more than 30 kg (p = 0.02). The only complication was an increase in blood pressure, observed in 43% of cases. The increase of anti-hypertensive medication was always successful in controlling blood pressure, and hospitalization was required in only one case. The improvement in general condition was obvious, and in several cases, the cognitive abilities seemed to improve. The growth deficit remained unchanged.

Adolescent↗

Identification of a clone of Escherichia coli O103:H2 as a potential agent of hemolytic-uremic syndrome in France.

In a French multicenter study, six verocytotoxin-producing Escherichia coli strains were isolated from the stools of 6 of 69 children suffering from hemolytic-uremic syndrome. All strains belonged to serotype O103:H2, a serotype commonly associated with diarrhea in weaned rabbits in France. To determine whether the strains from humans and rabbits were genetically related, they were compared by analyzing their esterase electropherotypes and the restriction fragment length polymorphisms of the ribosomal DNA regions. A common clonal origin of these pathogenic strains was suggested by their identical esterase electropherotypes and their identical ribotypes, in addition to their identical serotypes. However, strains from humans, which are cytotoxic for HeLa cells through the production of verocytotoxin type 1, do not show adhesion in vitro to HeLa 229 cells and cannot infect rabbits. On the other hand, strains from rabbits do not carry the verocytotoxin type 1 gene, are not cytotoxic for Hela cells, and adhere to ileal villi and HeLa 229 cells because of the expression of their 32-kDa adhesin. Our results therefore identify a clone of verocytotoxin-producing E. coli O103:H2 as a potential agent of hemolytic uremic syndrome in France. They further suggest that clones from humans and rabbits probably have a common origin but that adaptation to the two species occurred by different mechanisms. Thus, they eliminate the hypothesis that the species is horizontally transmitted between rabbits and humans.

Bacterial Toxins↗

[Treatment of renal vein thromboses in the newborn].

Surgical thrombectomy is not a rational approach to neonatal renal vein thrombosis since the occlusion mainly involves intrarenal branches rather than the main renal vein, which is even patent in some instances. Conservative management combines supportive therapy for renal failure and systemic hypertension, if needed, and either heparin or thrombolytic agents. Streptokinase has proven difficult to handle in neonates and should not be used. Urokinase has been used in 18 patients but results are difficult to interpret because these cases occurred over an 18-year period. Plasminogen tissue activator, the latest thrombolytic agent developed, has been used in few pediatric patients. An international task force is currently studying whether or not a randomized study is warranted to provide data for standardizing thrombolytic therapy in pediatric renal vein thrombosis.

Clinical Trials as Topic↗

[Thrombosis of the renal veins in the newborn: treatment and long term prognosis].

Thirty-nine neonates with renal vein thrombosis diagnosed in our hospital department between 1973 and 1991 were studied retrospectively. Twenty-five patients were and 14 were not treated with urokinase (UK). Among the five deaths (13%), four occurred at the acute stage from non-renal complications and one occurred at the age of three months from end-stage renal failure. Eight patients (21%) have moderate renal failure after a mean follow-up of 7.4 years; a single patient (2%) developed end-stage renal failure after 7.9 years and 25 patients (64%) have a normal glomerular filtration rate after a mean follow-up of 4.5 years. Rates of death and chronic renal failure were 8% and 32%, respectively, in the group given UK and 21% and 7%, respectively, in the group not given UK. Among 54 involved kidneys, only 10 (19%) recovered normal function and morphological features. Functional impairment was seen in 11 of 37 (30%) kidneys treated by UK and 10 of 17 (59%) kidneys not treated by UK. Although these data suggest that UK may be effective in promoting recanalization of renal veins obstructed by thrombosis, confirmatory evidence could be obtained only by performing a prospective therapeutic trial.

Female↗

[Antenatal form of Bartter's syndrome].

Six cases of tubular disorder of antenatal onset responsible for biological manifestations characteristic of Bartter syndrome and severe hypercalciuria are reported. In all six cases, severe hydramnios occurred during pregnancy between the 26th and 28th week after the last menstrual period. All six patients were born prematurely; gestational age ranged from 20 to 35 weeks. Major polyuria with dehydration occurred immediately after birth. The amounts of water and sodium needed to compensate urinary losses ranged from 280 to 370 ml/kg/day and 25 to 43 mmol/kg/d, respectively, during the first two postnatal months. Decreased serum potassium levels and increased plasma levels of renin and aldosterone were seen in all six patients. Increased urinary excretion of calcium was evidenced during the first postnatal week in three cases. Urinary calcium excretion in the six patients ranged from 15 to 30 mg/kg/d. Nephrocalcinosis developed in all six patients and two patients developed urinary lithiasis. One patient died at one month of age from necrotizing enteropathy. The five remaining patients gradually developed severe growth failure with measurements between 4 and 5.5 SDs below the mean. These five patients had evidence of hyperparathyroidism including increased serum levels of parathyroid hormone (5/5), increased serum alkaline phosphatase activity (4/5), and roentgenographic bone changes (1/5). Ionized calcium assays performed in three of the five patients disclosed low values (range 1.25-1.47 mmol/l; mean = 1.35; normal values = 1.42-1.62), although total serum calcium levels were normal or high (range 2.16-2.98 mmol/l; mean 2.61; normal values = 2.45-2.65) probably as a result of chronic dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Pharmacokinetics of ganciclovir in renal transplant children.

Three cytomegalovirus (CMV)-seronegative children received renal transplants from CMV-seropositive donors and developed clinical symptoms of CMV infection between days 20 and 34 post transplantation. Ganciclovir (DHPG) was administered in a 1-h infusion, and the doses and dose intervals were adapted to the degree of renal insufficiency, according to the manufacturer's recommendations for adults. Individual pharmacokinetic parameters of DHPG were determined and were markedly altered. Plasma clearances were 0.4, 1.1 and 2.2 ml/min per kg and were related to individual creatinine clearances (20, 45 and 60 ml/min per 1.73 m2); the corresponding elimination half-lives were 23.7, 9.9 and 3.9 h. In two patients, the doses had to be further reduced in order to maintain plasma levels within the recommended values for peak and trough plasma concentrations. Therefore, monitoring of DHPG appears essential in adjusting dosage for optimal efficacy and minimal toxicity.

Adolescent↗

[Ambulatory blood pressure measurement in children and adolescents with kidney transplants].

Arterial hypertension (HT) is a common complication after renal transplantation. We evaluated ambulatory blood pressure profiles during 24 h in 30 pediatric patients (pts) aged 6-22 years who had been transplanted 2 months to 7 years previously. Creatinine clearance was 14-121 (median 57) ml/min/1.73 m2. Twenty-three pts were being treated with ciclosporin. Sixteen pts received antihypertensive drugs. Using the monitor Nippon Collins 630 (Baxter), blood-pressure (BP) values were taken every 20 min during the day and overnight (10 p.m.-7 a.m.). Five out of 10 pts with elevated office BP readings were normotensive by ambulatory blood pressure monitoring (ABPM). Ambulatory hypertension was discovered in one child with normal office BP. Echocardiography was performed in 23 pts. Five of six pts with significant left-ventricular hypertrophy (LVH), but none of the 17 pts without LVH had ambulatory HT (p less than 0.01). The physiological decline of BP during the night was significantly reduced when compared to 21 subjects of similar age with essential HT (-9.2% vs. -15.4%; p less than 0.02); no correlation was found with renal function or prednisone dose. Ciclosporin tended to reduce the day-night gradient (-14.5% vs. -9.2%; p = 0.11). One child showed a severe nocturnal BP rise of 25 mmHg. We conclude that abnormalities of nyctohemeral BP rhythm, as described in transplanted adults, can be observed to a lesser extent in children. ABPM allows a better evaluation of BP compared to office BP and, thus, may contribute to a better management of these patients.

Adolescent↗

Button sequestrum of the tibia and pheochromocytoma.

A 16-year-old boy suffers from headaches. A bilateral adrenal pheochromocytoma is diagnosed and removed. After surgery, the image of bone sequestrum has disappeared. Osseous microthrombi secondary to hemoconcentration are responsible for the image of button sequestrum.

Adolescent↗