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Biomedical subjects

M Donnelly

Publications and source records attributed to M Donnelly.

At least 91 records · Page 5Linked to original sources
PubMed1991

Translocation (9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia.

The prognostic implications of t(9;22)(q34;q11) were assessed at a median follow-up of 3.5 years in 434 children receiving intensive treatment for acute lymphoblastic leukemia (ALL). Four-year event-free and overall survivals were 81% and 88%, respectively, in 419 children lacking t(9;22), but were 0% and 20%, respectively, in 15 children with t(9;22) (P less than .001). Poor outcome for children with t(9;22)-positive ALL was particularly notable because we have reported improved survival in other historically poor prognosis ALL cytogenetic categories when treated with similarly intensive therapy. We recommend that very intensive treatment approaches, including bone marrow transplantation in first remission, be considered for all children with t(9;22)-positive ALL.

Adolescent↗
PubMed1990

More is better! Update of Dana-Farber Cancer Institute/Children's Hospital childhood acute lymphoblastic leukemia trials.

Between 1973 and 1985, 553 children with childhood acute lymphoblastic leukemia were treated on Dana-Farber Cancer Institute/Children's Hospital, Boston, protocols. The programs featured intensive remission induction therapy, CNS treatment with cranial irradiation and intrathecal drugs, doxorubicin intensification with or without asparaginase, and 2-21/2 years of conventional continuation therapy. There has been progressive improvement in event-free survival for each successive program. Leukemia control concerns pertain to: 1. late relapses (at greater than 5 years) in "standard-risk" patients; 2. an increased incidence of CNS relapses, especially in "standard-risk" patients, as preventative treatment is reduced in intensity; and 3. bone marrow relapses in "high-risk"patients. Comparisons of patients receiving the more intensive arm of each protocol with those receiving the less intensive arm support the hypothesis that more intensive chemotherapy results in improved event-free survival.

Adolescent↗
PubMed1989

Prognostic implications of cytogenetic studies in an intensively treated group of children with acute lymphoblastic leukemia.

We assessed the prognostic significance of leukemia cell cytogenetics by analyzing bone marrow aspirates obtained at time of diagnosis in 165 children on a single protocol for acute lymphoblastic leukemia (ALL). These children were assigned to six mutually exclusive cytogenetic categories as follows: (1) hyperdiploid, with 50 or more chromosomes (n = 35); (2) hyperdiploid, with 47 to 49 chromosomes (n = 11); (3) diploid (n = 42); (4) pseudodiploid (n = 34); (5) hypodiploid (n = 9); and (6) insufficient data (n = 34). At a median follow-up of 5 years, there were no statistically significant differences between any of these cytogenetic categories in either event-free or overall survival. Those children with chromosomal translocations (n = 26) appeared to fare the same as those lacking translocations (n = 105). The absence of karyotypic prognostic significance was observed not only within the overall group, but also when the results were stratified by standard-risk and high-risk status. Of the specific structural chromosome changes that we studied, only the Philadelphia chromosome (Ph) appeared to confer a poor prognosis, although there were too few such cases to achieve statistical significance. Although we did not detect the event-free survival differences that have been described previously in hyperdiploid, hypodiploid, and pseudodiploid childhood ALL, our findings must be viewed as preliminary given the small number of children in some of the cytogenetic categories. We think that the prognostic implications of these cytogenetic features might have been nullified by improvements in therapy.

Adolescent↗
PubMed1989

Fenfluramine and dextroamphetamine treatment of childhood hyperactivity. Clinical and biochemical findings.

Twenty boys (mean age, 9 +/- 2 years) with attention deficit disorder with hyperactivity received three weeks each of dextroamphetamine sulfate (0.5 mg/kg/d), fenfluramine hydrochloride (0.6 mg/kg/d increased to 2.0 mg/kg/d), and placebo in a double-blind, random-order, crossover design. Half the boys also met criteria for conduct disorder. Dextroamphetamine produced immediate and marked improvement in disruptive, overactive behaviors. Fenfluramine had no effect on any behavioral measure at either the low or high dosage. Both drugs decreased levels of urinary norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid. Fenfluramine, however, also produced a significant decrease in plasma MHPG levels and a larger decrease in urinary norepinephrine levels. It reduced urinary epinephrine levels as well, an effect opposite to that of dextroamphetamine. These findings suggest that different mechanisms of action are involved in the ability of the two drugs to reduce levels of MHPG and vanillylmandelic acid. Fenfluramine increased plasma prolactin levels and decreased platelet serotonin levels. Despite the structural similarity of the two drugs, some common overall effects on catecholamine metabolism, and similar effects on weight, fenfluramine had none of the motor activity or therapeutic effects of dextroamphetamine.

Attention Deficit Disorder with Hyperactivity↗
PubMed1989

Urinary free cortisol output and disruptive behavior in children.

Hostile, impulsive, and aggressive behaviors have been associated with decreased urinary free cortisol (UFC) output. This is the first study to assess 24-hour UFC output in disruptive behavior disorders. The UFC of 19 boys with attention deficit and/or conduct disorder was compared with that of 19 age, race, and IQ matched normal controls studied as inpatients. Continuous Performance Test scores showed greater impulsivity in the disruptive group. UFC output did not differ between groups. However, UFC and difficulty were positively correlated on the continuous performance test in the form of longer interstimulus intervals and longer reaction times.

Adolescent↗
PubMed1988

The diagnosis of childhood hyperactivity. A U.S.-U.K. cross-national study of DSM-III and ICD-9.

The unequal prevalence of hyperactivity in Britain and the U.S. was investigated with a cross-national diagnostic study. Case histories of 6-11-yr-old boys were evaluated by British and American research teams as well as British and American clinician panels using both ICD-9 and DSM-III. Interrater agreement was acceptably high only for the specially trained research teams. ICD-9 generated fewer diagnoses of Hyperkinetic Syndrome than did DSM-III of Attention Deficit Disorder with Hyperactivity. The difference was greatest for U.K. clinicians. Diagnostic scheme and clinician training both contribute to the difference in reported rates.

Attention Deficit Disorder with Hyperactivity↗
PubMed1986

Treatment of childhood hyperactivity with desipramine: plasma drug concentration, cardiovascular effects, plasma and urinary catecholamine levels, and clinical response.

Twenty-nine boys with attention deficit disorder/hyperactivity were randomly assigned to receive desipramine (DMI; n = 17) or placebo (n = 12) for 14 days in a noncrossover, double-blind study. There was immediate behavioral improvement with DMI at day 3 that was sustained for 2 weeks; behavioral improvement did not correlate with plasma concentrations of DMI, hydroxy-DMI, or their sum at either days 3 or 14. There were no untoward side effects; there was a drug-induced increase in pulse and diastolic blood pressure. During drug therapy, the urinary excretion of norepinephrine, vanillymandelic acid, and 3-methoxy-4-hydroxyphenylglycol (MHPG) was decreased at both days 3 and 14. The plasma MHPG level was decreased at days 3 and 14 and (standing) plasma NE levels increased at day 14. The decreases in both urinary and plasma MHPG levels showed significant correlations with behavioral improvement during the second week. These data corroborate previous findings on sympathomimetic effects of tricyclic antidepressants in children and support a noradrenergic mechanism in the mediation of drug effects on attention deficit disorder/hyperactivity.

Administration, Oral↗
PubMed1986

A model for predicting performance on the NBME Part I examination.

Multiple regression analyses were employed to determine the relationships between achievement variables as predictors of the performance on Part I of the National Board of Medical Examiners examinations (NBME-I) of 366 medical students. The students' examination score averages in first- and second-year basic science courses were sequentially added to a composite Medical College Admission Test (MCAT) score to investigate the increases in prediction accuracy. Four prediction equations were cross validated on two subsequent medical school classes. While the multiple correlation between the predicted NBME-I score and the actual score significantly increased as first- and second-year course examination scores were added to the equations, the overall accuracy in predicting passing or failing did not substantially increase. The most useful equation employed a combination of the MCAT score and the first semester anatomy course examination score. The NBME-I predictions were given by letter to the 1984 and 1985 students approximately a year before they were to take the NBME-I examination so that students at risk of failure could undertake remedial study.

College Admission Test↗
PubMed1986

'Situational hyperactivity' in a U.S. clinical setting.

Eight of 69 males referred to a Hyperactivity Clinic for participation in psychopharmacological trials were not rated hyperactive by their primary caretaker on a parent symptom questionnaire. In comparison to eight boys for whom both parent and teacher ratings of hyperactivity were high, the group differed only in caretaker status. 'Situational' children were less likely to be living with both biological parents (P less than 0.05). In contrast, direct observation and actometer measurement of activity did not differ significantly between the groups. The findings suggest that at least in clinical settings, a distinction between 'situational' and 'pervasive' hyperactivity reflects caretaker status or attitude and not characteristics of the child.

Attention Deficit Disorder with Hyperactivity↗
PubMed1985

Cardiovascular and metabolic effects of cervical epinephrine infiltration.

Ventricular arrhythmia may follow the infiltration of dilute, epinephrine-containing solutions to achieve hemostasis during surgery. The objective of this study was to determine the cardiovascular and metabolic changes associated with the infiltration of 1.5 micrograms/kg epinephrine 1:200,000 in 0.5% lidocaine into the cervix of patients having a cervical cone biopsy under epidural anesthesia. These observations were compared with a control group who were infiltrated with 0.5% plain lidocaine under similar epidural anesthesia during cone biopsy. In the epinephrine-treated group, marked heart rate, rhythm, and systolic/diastolic blood pressure changes from baseline values were observed as well as significant glycogenolysis, lactic acidosis, and hypokalemia. Based on these observations, the total dose of injected epinephrine should be less than 1 microgram/kg; the solution should be diluted to 1:400,000 concentration, and the injection, after careful aspiration, should be performed over at least five minutes into the less vascular anterior and posterior cervix sites.

Anesthesia, Epidural↗