Acadian variant of Fanconi syndrome is caused by mitochondrial respiratory chain complex I deficiency due to a non-coding mutation in complex I assembly factor NDUFAF6.

The Acadian variant of Fanconi Syndrome refers to a specific condition characterized by generalized proximal tubular dysfunction from birth, slowly progressive chronic kidney disease and pulmonary interstitial fibrosis. This condition occurs only in Acadians, a founder population in Nova Scotia, Canada. The genetic and molecular basis of this disease is unknown.

Suppression of early and chronic BK polyoma virus replication by mycophenolic acid in Vero cells.

Consensus is lacking about which immunosuppressant agents potentiate BK virus infection. The effects of mycophenolic acid (MPA) were investigated in BK virus (BKV)-infected Vero E6 cells. MPA (1-16 mg/l) exhibited a dose-dependent anti-viral effect (10(1)-10(4) fold reduction in BKV DNA copies/ml) in supernatant, similar to cidofovir (2.

Two formulations of the agricultural pesticide adjuvant, Toximul, reduce the glycogen content of HepG2 cells.

Young mice exposed dermally to the Toximul (Tox) class of agricultural pesticide adjuvants have reduced levels of hepatic glycogen, a marker of subclinical toxicity. The present study determined whether these effects on glycogen also occurred in cultured HepG2 cells. Exposure (3 hr) to Tox resulted in significant, concentration-dependent glycogen reductions (up to 70%) relative to control values (76 +/- 3 microg glycogen/mg protein).

The pesticide adjuvant, Toximul, alters hepatic metabolism through effects on downstream targets of PPARalpha.

Previous studies demonstrated that chronic dermal exposure to the pesticide adjuvant (surfactant), Toximul (Tox), has significant detrimental effects on hepatic lipid metabolism. This study demonstrated that young mice dermally exposed to Tox for 12 days have significant increases in expression of peroxisomal acyl-CoA oxidase (mRNA and protein), bifunctional enzyme (mRNA) and thiolase (mRNA), as well as the P450 oxidizing enzymes Cyp4A10 and Cyp4A14 (mRNA and protein). Tox produced a similar pattern of increases in wild type adult female mice but did not induce these responses in PPARalpha-null mice.

Pamidronate distribution in pediatric renal and rheumatologic patients.

Objective: To evaluate the distribution and elimination of pamidronate in a population of pediatric patients with renal and rheumatologic disease.

Methods: Pamidronate whole blood levels were collected for the first 4 h after first exposure in 7 patients. The relationship between the rate of urinary excretion of pamidronate and bone formation or resorption was examined in 18 patients while receiving pamidronate at a total dose of 1 mg/kg/dose infused intravenously over a 4-h period.

Pamidronate treatment of pediatric fracture patients on chronic steroid therapy.

Pediatric nephrology and rheumatology patients with steroid-induced osteopenia are at risk of skeletal fracture. Bisphosphonate therapy has not been routinely advocated as a primary or secondary intervention for steroid-associated fractures in this population. This case control study evaluates the role of pamidronate therapy as a secondary fracture intervention.

Paradoxical cyclosporine A requirements in pediatric renal transplants receiving high-dose steroids.

The potent immunosuppressant cyclosporine A (CyA) is a mainstay of treatment in the renal transplant population. During episodes of acute allograft rejection, therapy also includes the pulse administration of high-dose steroids such as prednisone or methylprednisolone. Both steroids and CyA are metabolized by the CYP3A4 isoenzyme of the cytochrome P450 catalytic system.

A comparison of the pharmacokinetics of tacrolimus and microemulsified cyclosporin in paediatric renal transplant recipients.

Objective: Our objective was to identify common factors that determine the dose of tacrolimus and microemulsified cyclosporin in paediatric renal transplant recipients.

Methods: The concentration profiles of tacrolimus and cyclosporin in blood were determined in 68 children who had received a renal transplant. To avoid disruption of therapy, measurements were made at 2-h intervals over an 8-h period during normal dosing regimens.

Effects of insulin-like growth factor-type 1 on weight gain and hepatic glycogen during early development in a surfactant/virus mouse model of acute liver failure: correlation with mortality.

Acute liver failure (ALF) was reproduced in young mice exposed daily for 12 days to the industrial surfactant, Toximul 3409F (Tox), and infected on postnatal day (P) 14 with sublethal doses of mouse-adapted human influenza B (Lee) virus (FluB). Combined Tox + FluB treatment potentiated mortality due to non-necrotic ALF. This study tested the hypothesis that mortality would decline if the known losses in energy production due to compromised fatty-acid beta-oxidation were compensated by pharmacological manipulation of hepatic glycogen stores.

Determination of pamidronate in human whole blood and urine by reversed-phase HPLC with fluorescence detection.

Pamidronate is a bisphosphonate that is effective in treating bone disease including osteopenia and osteoporosis in adults. A sensitive and reliable method for the analysis of pamidronate in whole blood and urine is key to the development of this drug for use in children. A previously described method for pamidronate analysis serum and urine did not consistently detect the drug at satisfactory levels in whole blood.

Phenotypic heterogeneity in pediatric autosomal dominant polycystic kidney disease at first presentation: a single-center, 20-year review.

Background: The presentation of autosomal dominant polycystic kidney disease (ADPKD) in childhood provides an insight into comorbidities and potential areas for interventions and investigation.

Methods: Phenotypic heterogeneity at the time of first presentation was studied with respect to age of diagnosis, mode of presentation, parental inheritance pattern, renal function, associated hypertension, and hyperlipidemia. Fifty-five children (median age of presentation, 8.

Neuropsychological outcome in children with acquired or congenital renal disease.

The neuropsychological abilities of children with congenital ( n=13) or acquired ( n=11) end-stage renal disease (ESRD) were compared. Patients were being treated with or being prepared for dialysis and were awaiting transplantation. None of the children had an identifiable syndrome with associated central nervous system (CNS) dysfunction or had exposure to drugs with known CNS toxicity.

A multicenter, open-label, pharmacokinetic/pharmacodynamic safety, and tolerability study of basiliximab (Simulect) in pediatric de novo renal transplant recipients.

Background: Basiliximab (Simulect) has been shown to be safe and effective in adult renal transplant recipients, when used in combination with cyclosporine (Neoral) and corticosteroids. We report on the safety and preliminary efficacy of basiliximab in pediatric de novo renal transplant recipients.

Methods: This was an open-label, 12-month study of basiliximab in 41 patients (2 cohorts: <9 and 9 to <16 years).

T-cell/periodic acid-Schiff stain: a useful tool in the evaluation of tubulointerstitial infiltrates as a component of renal allograft rejection.

Distinguishing between tubulitis and tubulointerstitial mononuclear cell infiltrates and determining the severity of tubulitis are critical components of diagnosing and grading renal allograft rejection using the 1993 Banff schema, the revised 1997 Banff schema, or the Cooperative Clinical Trials in Transplantation grading system. We describe a novel staining method, the T-PAS stain (CD3 and periodic acid-Schiff), which removes some of the subjectivity in the evaluation of tubulointerstitial infiltrates in renal allograft biopsies. The method simply combines two routine stains, immunoperoxidase staining for T cells (CD3) and periodic acid-Schiff (PAS) staining for tubular basement membrane, on the same section.