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Biomedical subjects

M Charbit

Publications and source records attributed to M Charbit.

At least 19 recordsLinked to original sources
PubMed2001

Long term results of liver-kidney transplantation in children with primary hyperoxaluria.

From 1990 to 2000, we performed eight liver-kidney transplants in eight children, aged 1-16 years, with end-stage renal failure (ESRF) due to primary hyperoxaluria (PH1). The duration of dialysis before transplantation ranged from 2 to 42 months (mean 14 months) and was <1 year in four patients. Only the first patient underwent postoperative hemodialysis; in the other five, we chose to induce maximal diuresis from the first hours with intravenous and intragastric hyperhydration (> or =3 l/m2 per day). High water intake with nocturnal tube hydration was maintained for 6 months to 5 years, as long as oxaluria exceeded 0.5 mmol/day. A quadruple sequential immunosuppressive regimen was used. Two patients died during liver graft surgery. The other six patients are alive and well, with a mean follow-up of 7.4 years (range 5-11 years). Patient and graft survival is 75% at 5 years. At latest follow-up, liver tests were normal in all six patients; creatinine clearance ranged from 55 to 95 ml/min per 1.73 m2 (mean=74). Oxaluria was lower than 0.4 mmol/day in all patients (mean=0.22). The six patients underwent 15 renal biopsies, 1-11 years after transplantation. Chronic transplant nephropathy was present in four patients and mild cyclosporin nephrotoxicity in another. No oxalate crystals were seen and repeat ultrasonography has been consistently normal in all patients. The three patients with bone oxalosis showed progressive complete healing of bone lesions. All six children or adolescents now live a normal life. From this series, we conclude that early combined liver-kidney transplantation is the treatment of choice for children with ESRF due to primary hyperoxaluria.

Adolescent↗
PubMed2001

High serum levels of a non-(1-84) parathyroid hormone (PTH) fragment in pediatric haemodialysis patients.

The measurement of serum intact parathyroid hormone (PTH) is routinely made in haemodialysed (HD) patients to diagnose and monitor secondary hyperparathyroidism. We measured pre- and post-dialysis serum ionized calcium (Ca2+) and PTH in 12 HD children (7 boys) aged 13.8+/-3.6 years. A group of 27 normal short-statured children served as controls. Serum PTH was assessed by a new assay (CAP) recognizing only the (1-84) molecule and an older one (Allegro) recognizing both the 1-84 and a non-(1-84) PTH equally. The concentrations obtained with the CAP assay were lower than those obtained with the Allegro assay both in controls and in HD patients. They were still lower in HD patients when expressed as multiples of the median of the control group. The Allegro/CAP ratio, was highly variable from one subject to another and was lower (P<0.0001) in controls (1.46+/-0.26) than in HD patients, both before (3.06+/-1.60) and after dialysis (2.94+/-0.65). During dialysis, Ca2+ increased significantly (P<0.0001) and PTH decreased significantly (P<0.0001) with both the CAP and the Allegro assays, but was more often normal or low with the CAP than with the Allegro assay. Although the two assays correlate well, they may provide different clinical information in some HD children which could lead to different therapeutic decisions.

Adolescent↗
PubMed2001

Urological complications after renal transplantation using ureteroureteral anastomosis in children.

PURPOSE: Ureterovesical reimplantation is most often performed for renal transplantation in children. We reviewed our experience to evaluate the safety and efficacy of ureteroureteral reimplantation in pediatric renal transplantation. MATERIALS AND METHODS: We retrospectively evaluated the charts of 92 boys and 72 girls who underwent a total of 166 ureteroureteral anastomoses for renal transplantation from January 1990 to December 1999. Spatulated end-to-end anastomosis was performed between recipient and graft ureters without stenting and with a bladder catheter for at least 10 days. RESULTS: Mean patient age at transplantation was 11.2 years (range 1 to 21.5). There were 22 living related donor and 144 cadaveric grafts. Urological anomalies and nephropathy were the cause of end stage renal disease in 146 and 20 patients, respectively. Urological complications were noted in 14 of the 166 transplantations (8.4%) in 10 boys and 4 girls, including 12 initial and 2 repeat grafts from 2 living related and 12 cadaveric donors. Five of these patients had undergone previous urological surgery. The 2 children (1.2%) with acute ureteral obstruction underwent repeat intervention after stent failure. Anastomotic leakage in 7 cases (4.2%) was treated conservatively in 1 and with a Double-J stent (Medical Engineering Corp., New York, New York) only required in 3. Reoperation was required in 3 cases. One patient (0.6%) with late ureteral stenosis underwent repeat anastomosis, 1 (0.6%) required reimplantation for recurrent pyelonephritis due to vesicoureteral reflux in the graft, 1 (0.6%) with a valve bladder required bladder augmentation and ureteral reimplantation, and 1 (0.6%) with lymphocele and 1 (0.6%) with lithiasis were successfully treated conservatively. Complications were associated with acute rejection in 6 cases. Mean followup without graft loss in patients who presented with versus without complications was 58.3 months (range 1 to 112) versus 75 (range 1 to 118). In the former patients with a mean age of 16 years 9 months versus those without urological complications mean serum creatinine was 116 and 108 mol./l., respectively. Two grafts were lost in patients with urological complications, including 1 who died of pulmonary embolism and 1 with refractory chronic rejection. Seven patients were lost to followup after 54 months (range 12 to 113) of adequate graft function. CONCLUSIONS: Ureteroureteral anastomosis is a safe and effective technique for pediatric renal transplantation with a low complication rate, which may be due to better vascularization of the shorter ureteral end of the graft. Our results should encourage the use of this technique in pediatric renal transplantation. Efforts to preserve the recipient ureters should be made at nephrectomy.

Adolescent↗
PubMed2000

Pretransplant blood transfusions with cyclosporine in pediatric renal transplantation.

Pretransplant transfusions were repeatedly shown to be associated with improved graft survival in the "pre-cyclosporine era," and have recently been shown to be beneficial in patients on modern immuno-suppressive regimes. In an attempt to improve this transfusion effect and minimize the potential development of cytotoxic antibodies, we have given these transfusions, with concomitant cyclosporine cover, prior to transplantation. Ninety-two renal transplantations were performed in 91 children in the study group (group 1) and all received pretransplant transfusions with cyclosporine cover. Results were compared with a preceding group of 102 children (104 transplantations) who had received pretransplant transfusions without cyclosporine cover (group 2). There were 70 cadaver and 22 living-related donor (LRD) transplants in group 1, and 88 cadaver and 16 LRD transplants in group 2. Graft survival rates (1- and 5-year) for cadaver transplantation were 96% and 90% in group 1 compared with 78% and 64% in group 2 (P = 0.001). For LRD transplantation, these figures were 95% and 87% in group 1 and 81% and 69% in group 2. There was no difference between the two groups in terms of age at transplantation, sex, donor age, HLA-A, -B, -DR mismatches, or cold and warm ischemia times. All cadaver graft recipients received quadruple, sequential immunosuppression post transplant. However, 9 patients in group 1 were changed to tacrolimus for recurrent rejection episodes. No patient developed persistent lymphocytotoxic antibodies post transfusion or side effects of cyclosporine. Cyclosporine can be safely given with whole blood prior to transplantation with no adverse effect and no sensitization. Graft survival was significantly improved in this group of patients and graft loss due to rejection was exceptional. This effect should be further evaluated in prospective studies.

Anticoagulants↗
PubMed1999

[Passage from sandimmun to neoral in kidney transplantation in children].

BACKGROUND: The cyclosporine microemulsion formulation Neoral, which allows a better absorption and a more regular pharmacokinetic profile, is proposed for replacing the original formulation, Sandimmun. The present study reports the results of conversion from Sandimmun to Neoral in children with a kidney graft, a population for which information remains limited. METHODS AND PATIENTS: Twenty children, 2.5 to 10.5 years of age, who had a kidney graft with a stable renal function for between six months to five years (m = 2.6) were the subjects of this study. The patients were switched from Sandimmun to Neoral at the same dose, adjusted afterwards on a cyclosporine trough level. RESULTS: After six months, the mean dose decreased from 9.1 mg/kg/d to 8.4 mg/kg/d, i.e., 12.5%. After one year, the mean dose was 7 mg mg/kg/d, i.e., 28%. Of the 65% of patients who had a decreased dose, most of them had the highest dose of Sandimmun at the start. Mean serum creatininemia levels slightly increased from 85.6 to 89.5 mumol/L after six months (P = 0.03). None of the patients had a rejection crisis during the first six months under Neoral. Blood pressure did not change significantly, hirsutism improved in two cases but increased or appeared in two cases as well. Gingival hypertrophy increased or appeared in four cases. DISCUSSION: A decrease in the dose was decided on either to maintain the trough CsA blood level in the desired range or because of the appearance of a symptom suggesting a side effect of cyclosporine, especially the increase of creatinemia. The trough level did not appear to be the best index for adapting the dose. CONCLUSION: In stable pediatric kidney transplant recipients, the switch from Sandimmun to Neoral provided a reduction in drug dosage in 65% of cases without an increase in adverse events.

Age Factors↗
PubMed1997

Nitric oxide and the renin angiotensin system: contributions to blood pressure in the young rat.

The present study was designed to investigate the effects of chronic administration of the arginine analogue L-Name (50 mg/kg body weight), the angiotensin converting enzyme inhibitor, perindopril (2 mg/kg body weight), and perindopril (2 mg/kg) plus L-Name (50 mg/kg) on blood pressure, plasma renin activity, plasma angiotensinogen, and hepatic angiotensinogen mRNA levels in young and adult rats. The drugs were given daily from birth to day 21 to puppies and for 15 days to adults. Analytical procedures were performed on day 21 for the puppies and at 10 weeks for the adults. In puppies, blood pressure did not change with L-Name, it decreased to 45% of control values (P < 0.001) with perindopril, and decreased to 77% of control values (P < 0.05) with perindopril plus L-Name. In adults, blood pressure increased to 129% of control values (P < 0.02) with L-Name, decreased to 80% of control values (P < 0.05) with perindopril, and did not change with perindopril plus L-Name. Compared with controls, plasma renin activity was unchanged in puppies and adults with L-Name, undetectable in puppies and slightly increased in adults with perindopril, undetectable in puppies and slightly decreased in adults with perindopril plus L-Name. With L-Name, angiotensinogen mRNA levels were unchanged in puppies and slightly increased in adults, while plasma angiotensinogen levels were decreased (P < 0.05) in puppies and increased (P < 0.01) in adults; with perindopril, angiotensinogen mRNA levels were unchanged in puppies and slightly decreased in adults, while plasma angiotensinogen levels were undetectable in puppies and decreased (P < 0.05) in adults; with perindopril plus L-Name, angiotensinogen mRNA levels were unchanged in puppies while plasma angiotensinogen levels were undetectable in puppies and decreased (P < 0.01) in adults. This study suggests that during the early postnatal period (1) nitric oxide does not exert a basal vasodilator tone but contributes to the hypotensive state induced by perindopril, (2) angiotensin II is essential to maintain blood pressure, (3) and angiotensinogen mRNA levels are not influenced by nitric oxide or angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Decrease in endothelin-1 renal receptors during the 1st month of life in the rat.

Endothelin-1 (Et1), like angiotensin II, is implicated in postnatal maturation and development. The present study was designed to identify Et1 receptors and subtype Et1 receptors present in rat kidney between 1 and 30 days of postnatal life. On day 1, high-affinity and high-density Et1 binding sites were identified in rat kidney. The dissociation constant and maximum binding for ET1 to membranes from whole kidney were 0.073 +/- 0.05 nM and 1,345.9 +/- 73 fmol/mg protein, respectively. On day 30, affinity and receptor density were markedly decreased. The dissociation constant and maximum binding were 0.147 +/- 0.021 nM (P < 0.01) and 633.2 +/- 56.4 fmol/mg protein (P < 0.001), respectively. Using BQ 123 (EtA-selective antagonist) and sarafotoxin S6c (EtB-selective agonist), the two Et1 receptor subtypes EtA and EtB were identified in 1- and 30-day-old rat kidney. BQ 123 selectively recognized EtA receptors with high affinity (2.9 +/- 0.44 on day 1 and 4.0 +/- 0.5 nM on day 30) and sarafotoxin S6c bound with higher affinity EtB receptors (0.871 +/- 0.14 on day 1 and 0.717 +/- 0.12 nM on day 30). Between birth and day 30, the EtA binding capacity was decreased (304 +/- 27 vs. 752 +/- 202 fmol/mg protein, P < 0.05), whereas EtB binding was not affected (514 +/- 87 vs. 656 +/- 171 fmol/mg protein, NS). The decrease in the total number of Et1 receptors during the 1st month of life may be due to the concomitant decrease in the number of EtA receptors. Increased Et1 receptor density in early postnatal life suggests an influence of Et1 on immature kidney circulation and/or kidney growth.

Animals↗
PubMed1995

Deleterious effects of inhibition of the renin-angiotensin system in neonatal rats.

The angiotensin I converting enzyme inhibitor (ACEI) perindopril (2 mg/kg body weight), the peripheral vasodilator dihydralazine (DHL) (25 mg/kg body weight) or distilled water was given daily from birth to day 14 to neonatal rats. Blood pressure, plasma creatinine, plasma renin activity (PRA), substrate (PRS) and concentration (PRC) and renin content of kidney tissue sections were evaluated on days 14 and 28. By day 14, a high mortality in the ACEI group was observed. ACEI, but not DHL, led to a significant fall (P < 0.01) in blood pressure, 57 +/- 11 versus 89 +/- 25 in the DHL group and 103 +/- 24 mmHg in controls, and to a dramatic increase in plasma creatinine. PRA and PRS were undetectable in ACEI-treated rats; in contrast, PRC and renal staining with anti-renin antibody were significantly increased in ACEI rats. On day 28, the blood pressure was normal in all groups and plasma creatinine returned to the normal range in ACEI rats. PRA, PRS and PRC were not significantly different in the ACEI group and controls. These results suggest that the renin-angiotensin system (RAS) plays a major postnatal role in the neonatal rat. Inhibition of the RAS during the first 2 weeks of life leads to high mortality, severe hypotension, reversible renal failure and a defect in circulating angiotensinogen.

Aging↗
PubMed1994

Endothelin-1 in children with chronic renal failure.

Endothelin-1 (ET-1) was measured after extraction from plasma of normal adults (5.9 +/- 1.9 pg/ml, n = 22), normal children (7.1 +/- 1.86 pg/ml, n = 29), non-haemodialysed children with chronic renal failure (CRF) (11.1 +/- 1.8 pg/ml), n = 10), renal graft recipients (9.5 +/- 3.4 pg/ml, n = 37), haemodialysed children 24 h after a haemodialysis session (20.02 +/- 10.9 pg/ml, n = 26) and haemodialysed children before and after a haemodialysis session (15.31 +/- 10.6 and 13.8 +/- 8.5 respectively, n = 14). A sensitive and specific radioimmunoassay was used. ET-1 was significantly higher in non-haemodialysed CRF children and in renal graft recipients than in normal children (P < 0.001 and P < 0.01, respectively) and significantly higher in haemodialysed children when compared with normal children, non-haemodialysed CRF children and renal graft recipients (P < 0.001). ET-1 concentrations were similar in normal children and normal adults. ET-1 was inversely correlated with glomerular filtration rate in non-haemodialysed CRF children (r = -0.39, P < 0.01) and positively correlated with extracellular volume in haemodialysed children (r = 0.435, P < 0.03). After haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied before and after a haemodialysis session.

Adolescent↗
PubMed1993

[Renal transplantation in children under five years of age. Experience at the Hopital des Enfants-Malades].

From 1976 through 1991, 50 renal transplants (with 7 kidneys from living related donors and 43 cadaver kidneys) were performed in 47 children under five years of age (range 11 to 59 months) at the Enfants-Malades Hospital, Paris, France. Donor age ranged from 3 months to 53 years. Six of the seven kidneys from living related donors are currently functioning after a follow-up of 6 months to 8 years, whereas actuarial survival of cadaver kidneys was 70% at one year and 66% at five years. The main cause of graft loss was vascular thrombosis (40% of lost kidneys). In the most recent years of the study period, graft survival was substantially improved by routine prophylactic anticoagulant therapy with low-molecular weight heparin: one-year graft survival rate was 83% in the 23 children grafted between 1989 and 1991. Posttransplantation growth was closely related to quality of graft function: among the 29 children with sufficiently long follow-up the 19 patients with normal renal function exhibited normal or catch-up growth, whereas the ten patients with chronic renal failure or recent rejection had poor growth. Complications were uncommon with the exception of hypertension. Mortality rate was 12%, i.e., only slightly higher than in older pediatric kidney recipients. Achievement at school was normal in most cases (with a lag in only five patients). Provided effective therapy is given to prevent the main adverse outcome (i.e., vascular thrombosis), renal transplantation does not involve excessive risks even in infants as young as one year of age.

Actuarial Analysis↗
PubMed1991

[Clinical evaluation of 70 pediatric renal transplants after 10 to 17 years].

Among 149 kidneys transplanted in 141 children and teenagers aged 4 1/2 to 20 years, from November 1972 through December 1979, 70 (47%) were still functioning after ten years (67/145 cadaver donor grafts and 3/4 living related donor grafts). Medical and social status at the last follow-up visit (10 to 16 1/2 years after transplantation; m = 12 years) was analyzed. Patients were divided into five groups on the basis of glomerular filtration rate (GFR; ml/min/1.73 m2) and blood pressure (BP): 1) GFR greater than 80 ml and normal BP: 23 patients (33%); 2) GFR in the 60-80 ml range and/or high BP: 24 patients (34%/3) GFR in the 40-60 range: 6 patients; 4) GFR in the 15-40 range: 7 patients; and 5) hemodialysis restarted 10 1/2 to 13 years after transplantation. Mean adult stature was 155.7 +/- 10.4 cm in males and 149.8 +/- 10 cm in females. Osteoporosis was found in 88% of patients who underwent bone density quantitation. Twenty-four per cent of patients had aseptic osteonecrosis with variable degrees of impairment as a result. Chronic HBsAg carrier status was found in 37% of patients and was accompanied with persistent cytolysis in half the cases. Only one malignancy was seen (carcinoma of the urinary bladder in a child under cyclophosphamide). Six deaths were recorded between 10 and 13 years after transplantation; causes included septicemia (2 cases), cancer (1 case), hepatitis B (1 case), cerebral cystinosis (1 case), and unexplained sudden death (1 case).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[Long term results in 70 pediatric renal transplants after more than 10 years. Histological study].

A clinicopathologic study of 41 biopsy specimens from renal grafts transplanted at least ten years earlier showed normal findings or only mild tubulointerstitial lesions in 63% of cases. Results confirmed the good prognostic value of renal graft biopsy performed ten years after transplantation. A very close correlation was demonstrated between histologic evidence of chronic rejection (interstitial fibrosis, tubular atrophy, and fibrous endarteritis) and long-term graft outcome. Severity of interstitial fibrosis was apparently a more reliable indicator of prognosis than severity of fibrous endarteritis. Among 16 patients with a history of acute rejection, none had residual parenchymatous lesions. In contrast, among patients with major tubulointerstitial and/or vascular lesions, most had previously experienced one or several episodes of acute rejection. Evidence of allograft glomerulopathy was seen in approximately one case in four (11 patients). Among these patients, only eight had proteinuria and only four lost their graft. Among the four patients who developed recurrent membranoproliferative glomerulonephritis (type I in three cases and type II in one case), three lost the deposits previously detected by immunofluorescence, probably as a result of immunosuppressive therapy.

Adolescent↗
PubMed1989

[Gastroduodenal complications of hepatic intra-arterial chemotherapy of hepatic metastases of colorectal origin].

Fifty-eight patients with colorectal liver metastases were treated by intra-arterial hepatic chemotherapy (IAHC) containing 5 FU (n = 42) or FUDR (n = 16). Twenty-three patients (39.6 p. 100) complained of abdominal pain. In three of these patients, the course was complicated by digestive hemorrhage. Endoscopic explorations and angioscintigraphy were normal in 4, showed oesophagitis in 3, superficial gastritis or duodenitis in 8 (34.7 p. 100) and gastric (2) or duodenal ulceration (6) in 8 (34.7 p. 100). The duodenal ulceration was extensive and considered to be cause of hemorrhage in two cases. Duodenal perforation due to the catheter was discovered in two other cases, one of which was secondary to tumoral extension revealed by forceps biopsy. This patient died 3 months later. Surgical treatment was mandatory in the other case due to digestive hemorrhage but did not prevent death. Angioscintigraphy performed in 15 patients with gastroduodenal inflammation or ulceration was normal in 7 patients, revealed arterial thrombosis in 5 and an extra-hepatic perfusion in the gastroduodenal area in 3 : this was related to a small pyloric artery which was occluded secondarily. IAHC was continued there after. This experience underlines the importance of exploring patients with digestive symptoms during IAHC so that it may be temporarily discontinued while an inadequately positioned infusion catheter may be corrected should gastroduodenal ulceration occur.

Antineoplastic Agents↗
PubMed1988

Aluminium overload of parathyroid glands in haemodialysed patients with hyperparathyroidism: effect on bone remodelling.

In the course of chronic renal failure, aluminium may deposit and accumulate in different tissues. The aluminium content of parathyroid glands was measured in 31 haemodialysis patients at the time of a parathyroidectomy. The values were compared with those obtained from ten control patients with primary hyperparathyroidism without renal failure, and were related to bone remodelling. Of the 31 patients, 27 had a bone biopsy after double tetracycline labelling, at the time of parathyroidectomy. Twenty-one patients had severe hyperparathyroidism, three patients had hyperparathyroidism associated with osteomalacia, three patients had mild hyperparathyroidism with reduced bone formation. Seven patients had bone aluminium deposits, associated with osteomalacia in one case. The parathyroid aluminium was 62 +/- 35.7 (mumol/g glandular dry weight) in haemodialysis patients and 14.3 +/- 6.3 in control patients (P less than 0.001). A significant positive correlation existed between parathyroid aluminium and serum aluminium (P less than 0.01). The parathyroid aluminium was not different in the patients with and without bone aluminium deposits. A weak correlation was found between parathyroid aluminium and plasma parathyroid hormone. A significant negative correlation existed between parathyroid aluminium and osteoblastic surfaces (P less than 0.05), but no correlation was found with bone formation rate at tissue and bone multicellular units levels. We conclude that aluminium accumulates in parathyroid glands of dialysed patients. Severe hyperparathyroidism may coexist with aluminium overload of parathyroid glands. A marked aluminium overload, however, may cut short the course of hyperparathyroidism and may decrease parathyroid function and cellular activity in bone.

Adult↗