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Biomedical subjects

J H Rodman

Publications and source records attributed to J H Rodman.

62 records · Page 4Linked to original sources
PubMedDate not supplied

High dose chemotherapy with autologous peripheral blood progenitor cell transplantation in an anephric child with multiply recurrent Wilms tumor.

PURPOSE: An autologous peripheral blood progenitor cell (APBPC) transplant in an anephric child with multiply recurrent Wilms tumor using a conditioning regimen of high dose chemotherapy in conjunction with hemodialysis (HD) and peritoneal dialysis is described. PATIENT AND METHODS: The child had a left nephrectomy at 9 months of age for a stage II Wilms tumor. At 6 years of age, she required a right nephrectomy because of progressive, recurrent disease unresponsive to treatment with doxorubicin, actinomycin, and vincristine. She was maintained on peritoneal dialysis. Salvage chemotherapy consisted of 5 cycles of carboplatin and cyclophosphamide after APBPCs were collected after granulocyte colony-stimulating factor mobilization. After a preparative regimen of carboplatin, cyclophosphamide, and etoposide with closely timed HD, peripheral blood progenitor cells were infused and peritoneal dialysis was resumed. RESULTS: No nonhematopoietic toxicity occurred. Pharmacokinetic studies demonstrated that HD effectively eliminated carboplatin and provided safe, effective plasma concentrations in this anephric patient. Trilineage engraftment occurred by day +10 and the child was discharged from the hospital on day +14. She had a local recurrence on day +194 and died of progressive disease on day +660. CONCLUSIONS: With dialysis support and dose modification, high-dose chemotherapy followed by APBPC transplantation can be successfully performed in the anephric child. Given the lack of organ toxicity in this patient, increased doses of the drugs used in this preparative regimen may be possible for anephric children.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Cyclophosphamide for the treatment of progressive low-grade astrocytoma: a Pediatric Oncology Group phase II Study.

PURPOSE: Results of a phase II trial of cyclophosphamide (CPM) for children with progressive low-grade astrocytoma are reported. PATIENTS AND METHODS: Fifteen patients with a median age of 39 months (range, 2 to 71) were included in this study. The tumors of 11 children were located in the optic pathway, hypothalamus, or thalamus. Four courses of intravenous CPM 1.2 g/m2 were administered every 3 weeks during the upfront window portion of this protocol. Subsequently, chemotherapy was to continue with CPM, vincristine, and carboplatin for 2 years. RESULTS: By study design, the first 14 patients were centrally reviewed after completion of the initial 4 CPM courses. Toxicity was primarily hematologic. One patients had a complete response, 8 had stable disease, and 5 had progressive disease (PD). The excessive number of children with PD prompted study closure. CONCLUSION: CPM as used in this protocol showed insufficient activity against astrocytoma to justify further patient accrual.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Renal function and methotrexate clearance in children with newly diagnosed leukemia.

STUDY OBJECTIVES: To determine whether glomerular filtration rate (GFR) changes during induction chemotherapy in children with leukemia, and to examine GFR as a determinant of pharmacokinetic variability of methotrexate clearance. DESIGN: Prospective, unblinded observational study in consecutive patients. SETTING: A research hospital. PATIENTS: Thirty-eight children newly diagnosed with acute lymphoblastic leukemia. INTERVENTIONS: The patients received either high-dose methotrexate 1 g/m2 intravenously over 24 hours or low-dose methotrexate 30 mg/m2 orally every 6 hours for six doses; both regimens were followed by an intensive six-drug chemotherapy regimen given over 6 weeks. Glomerular filtration rate was determined in each subject before and at the conclusion of induction therapy. MEASUREMENTS AND MAIN RESULTS: The GFR was determined from 99mTc-DTPA serum clearance in all patients, and methotrexate clearance was estimated from serial serum concentrations in 18 of these children who received high-dose methotrexate. Median values for GFR at diagnosis (131 ml/min/1.73 m2) and after induction therapy (120 ml/min/1.73 m2) were not significantly different (p = 0.26) but were highly variable (range 49-274 ml/min/1.73 m2). Body size, age, and serum creatinine were correlated significantly with GFR at diagnosis. Amphotericin B therapy (6 patients) significantly decreased GFR (p = 0.046) without a corresponding increase in serum creatinine. Methotrexate clearance (58-155 ml/min/m2) was significantly (p = 0.007) correlated with GFR, but GFR accounted for only 37% of the variability of methotrexate clearance. CONCLUSIONS: The GFR was normal but highly variable in these children with leukemia and was significantly altered by amphotericin. Our results explain little of the intersubject variability in methotrexate clearance.

Administration, Oral↗
PubMedDate not supplied

Measurement of Tc-99m DTPA serum clearance for estimating glomerular filtration rate in children with cancer.

Clearance of the radiopharmaceutical Tc-99m DTPA estimated from blood samples with no urine collection can provide a reliable estimate of glomerular filtration rate (GFR) in adults, but has not been well studied in children. The disposition of Tc-99m DTPA was determined in 17 children with cancer, and the influence of binding and study design on the estimates for serum clearance were evaluated. Nine blood samples were obtained over 6 hours in each patient, and serum was assayed for total and free Tc-99m. Free Tc-99m DTPA was determined by ultrafiltration. Estimates of clearance derived from a two-compartment model for ultrafiltrable Tc-99m DTPA were determined from all nine measured concentrations, and these results served as a reference value for GFR in each subject. Total Tc-99m DTPA concentrations also were best described by a two-compartment model, but the median total clearance (35 ml/min) was significantly (p < 0.01) lower than the ultrafiltrate clearance (58 ml/min). The effect of a simplified sampling schedule was assessed from clearance estimates based on a 3-point subset of the ultrafiltrable data. The median clearance of 69 ml/minute was significantly higher (p < 0.01) than the reference GFR. However with a correction factor included to account for the positive bias arising from the limited sampling schedule, the reference estimates for GFR were well predicted (r2 = 0.99) with no significant bias. Ultrafiltrable Tc-99m DTPA serum clearance using a limited sampling schedule can provide a consistent and clinically feasible estimate of glomerular filtration rate in children, but binding in serum and study design are potentially important confounding factors.

Adolescent↗
PubMedDate not supplied

Formation of platinum-DNA adducts in pediatric patients receiving carboplatin.

STUDY OBJECTIVE: To determine the extent of platinum-DNA (Pt-DNA) adduct formation in peripheral white blood cells of children with cancer. DESIGN: Prospective study. SETTING: Pediatric research hospital. PATIENTS: Twenty-seven children receiving carboplatin as part of therapy as defined by clinical research protocols. INTERVENTIONS: Patients received various dosages of carboplatin over 1, 3, or 24 hours as a primary component of combination chemotherapy for pediatric solid tumors, brain tumors, or large cell lymphoma. MEASUREMENTS AND MAIN RESULTS: The Pt-DNA adducts were detectable in 10 (37%) of 27 patients. The median value was 3.4 fmol Pt/micrograms DNA (range 1.7-31.2 fmol) in patients with measurable values. CONCLUSION: The Pt-DNA adducts were detected less frequently in pediatric patients than reported in adults. Variables that influenced their detection were higher carboplatin dosages or systemic exposure and short (1-3 hrs) versus prolonged (24 hrs) infusions.

Adult↗
PubMedDate not supplied

Fentanyl pharmacokinetics in patients undergoing renal transplantation.

STUDY OBJECTIVE: To describe the pharmacokinetics of fentanyl in patients undergoing renal transplantation. DESIGN: Prospective. SETTING: A large university teaching hospital. PATIENTS: Eight patients (mean +/- SD age 35.5 +/- 11.5 yrs, weight 73.4 +/- 24.8 kg) with end-stage renal failure receiving kidneys from a living relative; three patients were never dialyzed, three were receiving peritoneal dialysis, and two were receiving hemodialysis. INTERVENTIONS: Plasma was sampled before and at intervals up to 8 hours after intravenous injection of fentanyl 25 microg/kg before skin incision. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD (range) preoperative values were blood urea nitrogen (BUN) 66 +/- 30 (35-111) mg/dl; albumin 3.6 +/- 0.7 (2.6-4.5) g/dl; and triglycerides 414 +/- 352 (156-1270) mg/dl. Elimination half-life was 382 +/- 205 minutes; volume of distribution for the central compartment 0.74 +/- 0.48 L/kg; volume of distribution at steady state (Vd(ss)) 3.1 +/- 2.0 L/kg; total body clearance 7.5 +/- 5.1 ml x kg(-1) x min(-1). A significant inverse relationship between degree of azotemia and fentanyl clearance was found. The two patients with the highest preoperative BUNs had the lowest multiple of clearance and Vd(ss), and were also the only ones to require postoperative mechanical ventilation. CONCLUSION: Although all patients received a kidney that functioned well after revascularization, the large intersubject variability in fentanyl kinetics may, in part, reflect their heterogeneity in dialysis status and renal failure-induced abnormalities. Marked decreases in fentanyl clearance do occur in these patients, appear to be related to very high BUN concentrations, and can lead to prolonged postoperative ventilatory depression.

Adjuvants, Anesthesia↗
PubMedDate not supplied

Pharmacokinetics of azithromycin after single- and multiple-doses in children.

STUDY OBJECTIVE: To characterize the disposition and tolerance of azithromycin after single and multiple oral doses of 12 mg/kg in children with and without cancer. DESIGN: Open-label, nonrandomized pharmacokinetic study. SETTING: Two pediatric hospitals. PATIENTS: Twelve children with cancer admitted to the inpatient unit for empiric antibiotic treatment of febrile neutropenia, and 16 hospitalized patients receiving antibiotic therapy INTERVENTIONS: Patients received azithromycin suspension either as a single dose or daily dose every morning for 5 consecutive days. Serial blood samples were collected up to 120 hours after a single dose or during and after multiple doses to characterize the pharmacokinetic parameters estimated for a two-compartment absorption model. MEASUREMENTS AND MAIN RESULTS: All 28 patients were evaluable for safety. Azithromycin was well tolerated except in one patient with cancer who experienced abdominal cramps and withdrew from the study. Pharmacokinetic results were not determined in five patients because of insufficient concentration-time data. The mean +/- SD estimates of oral clearance, terminal half-life, maximum concentration in serum (Cmax), and time to achieve Cmax in the 23 evaluable patients were 4.83 +/- 3.59 L/hour/kg, 54.5 +/- 36.4 hours, 318.2 +/- 174.5 microg/L, and 2.4 +/- 1.1 hours, respectively. These estimates did not differ between single-dose (14 patients) and multiple-dose (9 patients) groups. Pharmacokinetic parameters were not different between the 11 children with cancer and the 12 without cancer. CONCLUSION: Azithromycin 12 mg/kg results in proportionately higher serum concentrations than previously published results for lower doses (5 mg/kg). Variability in concentration profiles among patients is substantial, and age or other yet unidentified clinical factors may explain some of the differences observed.

Adolescent↗