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Biomedical subjects

P Cochat

Publications and source records attributed to P Cochat.

At least 109 records · Page 6Linked to original sources
PubMed1995

Deletions of both alpha 5(IV) and alpha 6(IV) collagen genes in Alport syndrome and in Alport syndrome associated with smooth muscle tumours.

Diffuse oesophageal leiomyomatosis (DL), an inherited smooth muscle proliferation process, has been reported to be associated with Alport syndrome (AS), a familial nephropathy, mainly dominant X-linked inherited, and characterized by ultrastructural changes of the glomerular basement membrane. The COL4A5 gene, encoding the alpha 5 chain of type IV collagen, has been identified as the site of mutations in families with X-linked AS. Recently, a novel alpha 6(IV) collagen chain encoding gene has been mapped closely upstream of COL4A5, and disruption of the 5' end of both genes has been reported in four patients with DL and AS (DL-AS). Here, we report a long-range restriction map around the COL4A6 locus, and show that the COL4A5/COL4A6 deletion observed in seven patients with DL-AS encompasses only the two first exons of COL4A6, with a breakpoint located in the second intron of COL4A6, whose size exceeds 65 kb. Furthermore, we demonstrate that three patients with AS without DL, known to have a deletion of the 5' part of the COL4A5 gene, display a larger deletion in COL4A6. Moreover, a COL4A6 mRNA product was detected by reverse-transcription-polymerase chain reaction in an oesophageal tumour sample of a patient with DL-AS. These results suggest that DL-AS could be caused by an abnormal truncated alpha 6(IV) chain.

Adolescent↗
PubMed1995

Epidemiology of primary hyperoxaluria type 1. Société de Néphrologie and the Société de Néphrologie Pédiatrique.

Primary hyperoxaluria type 1 (PH1) always leads to oxalate accumulation throughout the body (oxalosis). Currently available epidemiological data only concern patients with end-stage kidney disease requiring renal replacement therapy (RRT). French nephrologists have been questioned about PH1 patients who were under their care between 1988 and 1992. Exhaustive answers were obtained and 90 cases of PH1 were collected. The average prevalence rate of PH1 was 1.05/10(6) and its average incidence rate was 0.12/10(6)/year. The median age at onset was 5 years (0-63) and initial symptoms involved the urinary tract in 82% of the cases. Half the patients were younger than 10 years at the time of diagnosis on the basis of urine oxalate (89%) +/- urine glycolate (43%) +/- plasma oxalate (71%) +/- hepatic alanine:glyoxylate amino-transferase activity (48%). At the time of the survey, 36% of patients were on a conservative treatment, 37% were transplanted and 27% were on maintenance haemodialysis; the crude mortality rate was 19% (median age 36 years). Patients on dialysis started RRT at a median age of 25 years. Transplanted patients received their first transplant at a median age of 29.5 years; among those patients with more than 1 year follow-up, 15 received an isolated kidney transplant (one success), one had a isolated liver transplant (one success) and 10 combined liver-kidney transplant (eight successes). These data confirm the rarity of PH1 together with its poor prognosis; as shown in the European experience, early combined liver-kidney transplantation seems to be the best therapeutic proposal.

Adolescent↗
PubMed1995

Transplantation for primary hyperoxaluria in the USA.

US data were sought for transplantation in primary hyperoxaluria (PH). The USRDS recorded 194 patients since 1974. By lifetable analysis, survival was better for transplanted than for non-transplanted patients (P < 0.001), even after trimming data for age < 55 and end-stage renal disease since 1985 (63 patients, 39 transplanted, 24 not transplanted). Transplant survival was longer for living related donor (21) vs cadaveric (17) transplants. Twenty-nine kidney transplants in 22 children were registered in NAPRTCS. Interview data with physicians showed that eight of 17 living related donor kidneys functioned well, three were borderline and six were lost. All six cadaver kidneys were lost. Four of six kidney-liver transplants functioned, and two died. United Network for Organ Sharing recorded 13 kidney-liver transplants in 11 patients. Six initially functioned well; two were retransplanted. Ultimately seven lived and four died. Overall, transplant is better than no transplant; cadaver donation results are poor; living related kidney donation can succeed; and kidney-liver transplant is still problematic in the US, and rarely follows appropriate investigation. Until more cooperative effort can be achieved, isolated kidney living related donor transplant is preferable, and does not preclude kidney-liver transplant later.

Adolescent↗
PubMed1995

When should isolated liver transplantation be performed in primary hyperoxaluria type 1? Follow-up report of two children.

The value of isolated liver transplantation in primary hyperoxaluria type 1 (PH1) and its timing are controversial. Two children with PH1 were followed up for 6 years after liver transplantation. A boy aged 5 years with a glomerular filtration rate (GFR) of 65 ml/min/1.73 m2 at the time of transplantation subsequently showed regression of calcium deposits in the kidneys, but GFR slightly declined, probably related to cyclosporin A toxicity. A girl with a severe neonatal form of PH1 received a liver at the age of 2 years when GFR had already declined to about 15 ml/min/1.73 m2 and extrarenal manifestations (bones, eyes) were present. In spite of these and further complications post-transplantation GFR stabilized. Growth failure was efficiently treated by growth hormone. Plasma and urinary oxalate concentrations, however, remained increased. It is suggested that in PH1 liver transplantation should be considered only if GFR is not rapidly declining and stays above 30 ml/min/1.73 m2. For an individual decision the different risks of liver transplantation and of combined kidney-liver transplantation as well as the possible benefits from previous conservative treatment must be considered.

Child, Preschool↗
PubMed1995

Selection of transplantation procedures and perioperative management in primary hyperoxaluria type 1.

This paper outlines the different options of transplant procedures in patients with primary hyperoxaluria type 1. Isolated kidney, isolated liver and combined liver-kidney grafting are discussed. Combined liver-kidney grafting appears to be the preferred treatment for patients already in end-stage renal failure. The potential value of the two other procedures is outlined. Guidelines for perioperative care are given. These involve fluid regime, pyridoxine supplementation, immunosuppression and administration of crystallization inhibitors such as phosphate and citrate. Special emphasis is put on selection of appropriate dialysis procedures and reasons why haemodialysis and continuous haemodiafiltration are the methods of choice.

Fluid Therapy↗
PubMed1994

[Extrarenal hemofiltration in pediatric resuscitation].

Peritoneal dialysis, continuous hemofiltration (HF) and continuous hemodiafiltration (HDF) are the most convenient methods for blood purification in pediatric intensive care units. HF is based on the ultrafiltration process and removes not only water but also Na, K, bicarbonate, urea and creatinine with sieving coefficient close to 1. HDF is based on both ultrafiltration and diffusion processes and increases the removal of low molecular weight solutes (urea). These procedures are indicated in: 1) neonates presenting with oligo-anuric acute renal failure (ARF) or fluid overload withstanding diuretics or some metabolic diseases; 2) children presenting with ARF, fluid overload or some metabolic disorders, poisonings or shocks.

Age Factors↗
PubMed1994

Survey of the attitudes to management of acute pyelonephritis in children. GEP.

Although urinary tract infections are of particular concern in young children, as they may lead to permanent health problems, there is no consensus for their acute management. We carried out a mailed survey of 455 general practitioners, 143 paediatricians (randomly selected from a list of physicians in the Rhône-Alpes region of France) and 45 paediatric nephrologists (all the members of the "Société de Néphrologie Pédiatrique") to examine their attitudes to the management of a fictitious case of a young girl with symptoms indicative of acute pyelonephritis. The responses given by the general practitioners and paediatricians were similar, whereas those given by the paediatric were similar, whereas those given by the paediatric nephrologists were often different, for example 20% of the general practitioners and 17% of the paediatricians said they would hospitalize the child, compared with 69% of the paediatric nephrologists. The majority of the general practitioners and paediatricians favoured single oral antibiotic therapy, whereas the paediatric nephrologists were split between single and combined antibiotic therapy, but preferred intravenous administration. The most frequently prescribed drug was a penicillin. The heterogeneity of the results from this survey stresses the need for the assessment of various strategies in terms of their efficacy for preventing kidney scarring and their risk-to-benefit ratios in well-designed randomised controlled trials.

Acute Disease↗
PubMed1994

Bone mineral density after renal transplantation in children.

Longitudinal bone mineral changes after renal transplantation were studied in 14 children aged 8 +/- 4 years. Combination immunosuppressive therapy was given to all patients (prednisone, azathioprine, cyclosporine). Bone mineral density (BMD) measurements of the first through fourth lumbar vertebrae by dual-energy X-ray absorptiometry were performed within 1 year preceding renal transplantation and 6, 12, and 24 months afterward (M0, M6, M12, and M24, respectively). The results of BMD obtained in grams of hydroxyapatite per square centimeter of spine projected area were subsequently transformed to standard deviation scores for a normal pediatric population. In addition, we used a mathematical spine volume correction to give the results in grams per cubic centimeter. All patients had a well-functioning renal graft at M6, M12, and M24 and a normal serum creatinine level. Significant decreases in BMD, standard deviation score, and spine volume-corrected BMD were observed 6 months after renal transplantation (p < 0.05, p < 0.01, and p < 0.01 respectively); the median loss of BMD and spine volume-corrected BMD was 9.2% and 15.6% at M6, respectively, and the median serum parathyroid hormone level dropped from 125 to 34 pg/ml. Between M6 and M12, BMD increased significantly up to 95% (median) of pretransplantation values and reached 97.2% (median) at M24. Similar but less marked improvement was observed in spine volume-corrected BMD results, reaching 87.7% and 87.4% at M12 and M24, respectively. A negative correlation was found between the cumulative prednisone dose and BMD in grams per square centimeter at M6 (r2 = 0.603; p = 0.006), M12 (r2 = 0.532; p = 0.015), and M24 (r2 = 0.40; p = 0.014). There was no correlation between cumulative prednisone dose and spine volume-corrected BMD or standard deviation score. Mean 6-month cyclosporine levels did not correlate with any measure of BMD. We conclude that after renal transplantation children have a significant decrease of BMD during the first 6 months after the operation, despite normal graft function and growth improvement.

Absorptiometry, Photon↗
PubMed1994

Outcome of cadaver kidney transplantation in small children.

Small children have often been reported to have poor outcome after kidney transplantation (KT). Recent reports from North America have shown that the use of living-related donors improves patient and graft survival. We report the experience in one centre of primary cadaveric KT using sequential immunosuppression in nine children aged 8-30 months and weighing 5.4-9.8 kg; donors were 0.7-12.3 years old. Four patients had pre-emptive KT and the other five were on peritoneal dialysis; the mean +/- SD waiting time was 2.0 +/- 2.4 months. Perioperative care has been published previously. The surgical approach was intraperitoneal if the aorta and vena cava were used (n = 7) and extraperitoneal for common iliac vessels anastomosis (n = 2); the duration of surgery was 3.5 +/- 0.9 h and the time for vascular anastomosis was 32 +/- 6 min. The recipients received ATG, azathioprine, prednisone and delayed administration of cyclosporin A. The patients were followed for 12-98 (median 41) months and showed good graft function (inulin clearance 63-100 ml/min/1.73 m2); only one child with recurrent haemolytic uraemic syndrome lost his graft three months post-transplantation and died after he had received a second graft. None of the recipients required post-transplant dialysis; arterial hypertension involved four children and was related to graft artery stenosis in two. Growth improved by 0.24 +/- 0.48 SD score of height per year.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadaver↗
PubMed1994

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↗
PubMed1994

[Molecular pathology of type 1 primary hyperoxaluria].

Type 1 is the most common form of primary hyperoxaluria, also called oxalosis when systemic involvement has occurred. This recessive autosomal inherited inborn error of metabolism is characterized by a defect of alanine: glyoxylate aminotransferase (AGT), which is a specific liver enzyme. This protein is responsible for glyoxylate detoxification only when it is located in the peroxisome. The clinical and biochemical phenotypes are neither correlated with the residual catalytic activity of AGT nor with its immunoreactivity. Most patients display less than 2% catalytic activity (enz-) or no immunoreactive protein (crm-); peroxisome-to-mitochondrion mistargeting is the main feature of patients crm+/enz+ or crm+/enz-. The cDNA and genomic DNA have been cloned and sequenced and the gene has been located on the long arm of chromosome 2 in the q36-37 region. Three polymorphisms have been identified which are preferentially associated, leading to two alleles; six point mutations have been currently reported.

Alanine Transaminase↗