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Biomedical subjects

R Ungerleider

Publications and source records attributed to R Ungerleider.

7 recordsLinked to original sources
PubMed2000

Impact of modifying priming components and fluid administration using miniaturized circuitry in neonatal cardiopulmonary bypass.

Following a succession of changes in circuitry and priming additives between 1993 and 1998, a comprehensive re-evaluation of neonatal cardiopulmonary bypass (CPB) practice was undertaken. Samples from 10 infants (Group 1) undergoing CPB were evaluated for osmolality, oncotic pressure, total protein, hematocrit, glucose, and electrolytes (Na+, K+, iCa2+). These samples were tested at six measurement points: (1) after priming, (2) patient pre-CPB, (3) CPB-start, (4) CPB-mid, (5) CPB-end, and (6) post-modified ultrafiltration (MUF). Prime volumes were also carefully measured as well as the type and amount of volume given during CPB. After evaluating the initial data, changes in protocol regarding mannitol, calcium correction, and oncotic strength on CPB were made. Following implementation of these protocol changes, a second set (Group 2) of 10 infants was identically evaluated. Group 1 prime osmolality was 379 +/- 44 mOsm/kg, while Group 2 prime osmolality was 324 +/- 14 mOsm/kg (p = 0.003). There were no differences in osmolality between groups during bypass and osmolality was unaffected by modified ultrafiltration. Ionized calcium levels were significantly different at the end of bypass between Group 1, 0.6 +/- 0.1 mmol/l; and Group 2, 1.17 +/- 0.24 mmol/l (p < 0.001). In Group 1, there was a 40% drop (p = 0.001) in colloid osmotic pressure (COP) levels from pre-CPB (13.3 +/- 3.4 mmHg) to CPB-end (8.8 +/- 1.2 mmHg). In Group 2, there were no differences in COP during CPB. COP levels of Group 1 and Group 2 at CPB-end were 8.8 +/- 1.2 mmHg and 14 +/- 1.9, respectively (p < 0.0001). Total volume addition during bypass for Group 1 was 363.5 +/- 148.7 ml and for Group 2 was 245.1 +/- 92.2 ml (p < 0.05). In conclusion, progressive changes in neonatal circuits and techniques can have potentially wide-ranging effects on electrolyte and osmotic/oncotic homeostasis. An audit of perfusion management through expanded laboratory tests is recommended, especially in periods of change.

Blood Substitutes↗
PubMed1998

Conduct of phase I trials in children with cancer.

PURPOSE AND METHODS: Future progress in the care of children with cancer requires appropriate evaluations of promising new agents for pediatric indications, beginning with well-conducted phase I trials. This report summarizes current guidelines for the conduct of pediatric phase I trials and represents a consensus between American and European investigators. The primary objective of pediatric phase I trials is to define safe and appropriate doses and schedules of new agents that can subsequently be used in phase II trials to test for activity against specific childhood malignancies. Prioritization of agents for evaluation in children is critical, since many more investigational agents are evaluated in adult patients than can be systematically evaluated in children. Considerations used in prioritizing agents include activity in xenograft models, novel mechanism of action, favorable drug-resistance profile, and activity observed in adult trials of the agent. RESULTS AND CONCLUSION: Distinctive characteristics of pediatric phase I trials, in comparison to adult phase I trials, include the necessity for multiinstitutional participation and their higher starting dose (typically 80% of the adult maximum-tolerated dose [MTD]), both of which reflect the relative unavailability of appropriate patients. The application of uniform eligibility criteria and standard definitions for MTD and dose-limiting toxicity (DLT) help to assure that pediatric phase I trials are safely conducted and reliably identify appropriate doses and schedules of agents for phase II evaluation. Where possible, pediatric phase I trials also define the pharmacokinetic behavior of new agents in children.

Antineoplastic Agents↗
PubMed1996

Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia.

PURPOSE: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. RESULTS: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.

Adolescent↗
PubMed1981

Phase I study of 2'-deoxycoformycin in acute lymphoblastic leukemia.

2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzyme elevations, and conjunctivitis. Lymphopenia occurred in all patients. The most serious adverse effects were acute tubular necrosis and central nervous system toxicity, which appeared to be dose related. In addition, two patients given the 0.75-mg/kg dose developed severe hepatic toxicity, although this could not be ascribed definitively to 2'-dCF. Antitumor activity was observed in eight patients, two of whom experienced a complete remission. Inhibition of lymphoblast adenosine deaminase activity was noted in the majority of cases and was observed at all doses. Antileukemic activity occurred at doses of 2'-dCF which were not associated with limiting toxicities. These results suggest that 2'-dCF is active against acute lymphoblastic leukemia and that a starting dose of 0.5 mg/kg/day be utilized in Phase II studies.

Adenosine Deaminase Inhibitors↗