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Biomedical subjects

D Blowey

Publications and source records attributed to D Blowey.

10 recordsLinked to original sources

Evaluation of the PRISMA M10 circuit in critically ill infants with acute kidney injury: A report from the Prospective Pediatric CRRT Registry Group.

Currently available extracorporeal circuits in the US often require blood priming to prevent hypotension/anemia in smaller pediatric patients. The PRISMA M10 circuit, available in other countries has not received extensive study and has not been cleared for use in the US. We performed an FDA mandated study of the M10 circuit in the US for use in critically ill pediatric patients with acute kidney injury <15 kg in size. FDA guidelines allowed for maximal blood pump flow of 20 ml/min. Fifteen pts (9 M, 6 F, mean size 5.8+/-2.8 kg, range 2.6-12.5 kg, age 4 d - 13 mo, mean creatinine =1.2+/-0.7 mg/dL) were studied at 4 ppCRRT centers. Sixty-one filters (range 1-4 circuits per pt) were used (mean circuit life 28.6+/-22.5 h, range 1 to 74.5 h, 55%>24 h). No blood leaks occurred. All circuits achieved Qb 20 ml/min. Forty-two out of 61 filters clotted and mean circuit life was lower for these filters than those changed for other reasons (23+/-17 vs. 41+/-28 h, <0.005). Circuits using larger access demonstrated significantly longer survival. We conclude that the M10 filter can serve well for CRRT in small pediatric patients. Further study is needed to determine in higher blood flow rates would decrease clotting rates and increase filter life span and ultrafiltration rates.

Acrylic Resins↗

The Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry: design, development and data assessed.

Many issues plague the pediatric ARF outcome literature, which include data only from single center sources, a relative lack of prospective study, mixture within studies of renal replacement therapy modality without stratification and inconsistent use of methods to control for patient illness severity in outcome analysis. Since January 2001, the Prospective Pediatric CRRT (ppCRRT) Registry Group has been collecting data from multiple United States pediatric centers to obtain demographic data regarding pediatric patients who receive CRRT, assess the effect of different CRRT prescriptions on circuit function and evaluate the impact of clinical variables on patient outcome. The aim of the current paper is to describe the ppCRRT Registry design, review the decision process and rationale for the options chosen for the ppCRRT format and discuss the analysis plan and future projects envisioned for the ppCRRT Registry.

Acute Kidney Injury↗

The use of mycophenolate mofetil suspension in pediatric renal allograft recipients.

Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adults after renal, cardiac, and liver transplantation. This study investigated the safety, tolerability, and pharmacokinetics of MMF suspension in pediatric renal allograft recipients. One hundred renal allograft recipients were enrolled into three age groups (33 patients, 3 months to <6 years; 34 patients, 6 to <12 years; 33 patients, 12 to 18 years). Patients received MMF 600 mg/m2 b.i.d. concomitantly with cyclosporine and corticosteroids with or without antilymphocyte antibody induction. One year after transplantation, patient and graft survival (including death) were 98% and 93%, respectively. Twenty-five patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) or presumptive acute rejection within the first 6 months post-transplantation. Analysis of pharmacokinetic parameters for mycophenolic acid (MPA) and mycophenolic acid glucuronide showed no clinically significant differences among the age groups. The dosing regimen of MMF 600 mg/m2 b.i.d. achieved the targeted early post-transplantation MPA 12-h area under concentration-time curve (AUC0-12) of 27.2 microg h per ml. Adverse events had similar frequencies among the age groups (with the exception of diarrhea, leukopenia, sepsis, and anemia, which were more frequent in the <6 years age group) and led to withdrawal of MMF in about 10% of patients. Administration of MMF 600 mg/m2 b.i.d. is effective in prevention of acute rejection, provides predictable pharmacokinetics, and is associated with an acceptable safety profile in pediatric renal transplant recipients.

Adolescent↗

The pharmacokinetics of enalapril in children and infants with hypertension.

Forty children with hypertension between the age of 2 months and 15 years received 0.07 to 0.14 mg/kg of enalapril as a single daily dose. Enalapril was administered orally as a novel extemporaneous suspension in children younger than 6 years of age and as tablets in older children. First-dose and steady-state pharmacokinetics were estimated in children ages 1 to 24 months, 25 months to < 6 years, 6 to < 12 years, and 12 to < 16 years. Maximum serum concentrations for enalapril occurred approximately 1 hour after administration. Serum concentrations of enalaprilat, the active metabolite of enalapril, peaked between 4 and 6 hours after the first dose and 3 and 4 hours after multiple doses. The area under the concentration versus time curve (AUC), adjusted for body surface area, did not differ between age groups. Based on comparison of first-dose and steady-state AUCs, the accumulation of enalaprilat in children ranged from 1.13- to 1.45-fold. For children ages 2 to 15 years, mean urinary recovery of total enalaprilat ranged from 58.3% in children ages 6 to < 12 years to 71.4% in children ages 12 to < 16 years. Urinary recovery for children ages 2 to < 6 years was 66.8%. The mean percentage conversion of enalapril to enalaprilat ranged from 64.7% for children ages 1 to 24 months to 74.6% for children ages 6 to < 12 years. The median effective half-life for accumulation ranged from 14.6 hours in children ages 12 to < 16 years to 16.3 hours in children ages 6 to < 12 years. There were two serious adverse events, neither of which was attributed to enalapril or resulted in discontinuation of the study drug. The extemporaneous suspension used in this study was tolerated well. The pharmacokinetics of enalapril and enalaprilat in hypertensive children ages 2 months to 15 years with normal renal function appears to be similar to that previously observed in healthy adults.

Adolescent↗

A randomized prospective crossover trial of amlodipine in pediatric hypertension.

Amlodipine has potential advantages in children since it can be dissolved into a liquid preparation and has a long elimination half-life, allowing for once-daily administration. The objective of this study was to compare the efficacy and compliance of amlodipine with that of standard long-acting calcium channel blockers (felodipine or nifedipine) in hypertensive children. A randomized, prospective, crossover study of 11 hypertensive children (9-17 years of age, 10 renal transplant patients) was performed with electronic monitoring of compliance. Each treatment arm was 30 days. No significant differences were observed in mean systolic (SBP) and diastolic blood pressures (DBP) between amlodipine and the other calcium channel blockers. Using 24-h blood pressure monitoring there were no significant differences over each drug treatment period in both mean day-time and night-time SBP and DBP. Patient compliance was similar in both the amlodipine and the nifedipine/felodipine treatment periods. These data suggest that amlodipine is as effective in pediatric nephrology patients as nifedipine and felodipine. Amlodipine may be optimally suited for treatment of young children because at present it is the only calcium channel blocker which can be administered once daily as a liquid preparation.

Adolescent↗

Hypothetical framework for enhanced renal tubular secretion of drugs in cystic fibrosis.

Several clinical studies demonstrate reduced serum concentrations of renally excreted drugs in patients with cystic fibrosis (CF). To explain this phenomenon, we propose a model supporting increased proximal tubular secretion of certain drugs in individuals with CF. We hypothesize that the chloride channel located on the apical surface of renal proximal tubular cells and controlled by the cystic fibrosis transmembrane conductance regulator (CFTR) operates suboptimally in CF patients, and that the abnormal CFTR decreases Cl- reabsorption, resulting in an increased concentration of Cl- in the tubular lumen. We postulate that, in an effort to maintain homeostasis, luminal Cl- moves intracellularly in exchange for organic anions. The result of stimulating this anion exchanger is an increased rate of organic anion secretion by the renal tubule. Hence, due to enhanced tubular secretion, individuals with CF demonstrate increased tubular clearance of organic anion drugs, resulting in lower steady state serum concentrations.

Chlorides↗