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Biomedical subjects

J O'Donnell

Publications and source records attributed to J O'Donnell.

At least 19 recordsLinked to original sources

Identification of the GalNAc kinase amino acid sequence.

A new kinase that forms GalNAc-1-P was purified from pig kidney cytosol and identified on gels by labeling with N3-[32P]ATP (Pastuszak, I., Drake, R., and Elbein, A. D. (1996) J. Biol. Chem. 271, in press). A 50-kDa labeled protein was eluted, digested with trypsin, and the sequences of four peptides representing 49 amino acids showed 90% identity to sequence of human galactokinase reported to be on chromosome 15. To resolve this dilemma, activities and substrate specificities of galactokinase and GalNAc kinase from human and pig kidney, as well as of galactokinase from the yeast clone transfected with the cDNA from presumptive human galactokinase, were compared. The purified galactokinases phosphorylated galactose, but not GalNAc, whereas GalNAc kinase also phosphorylated galactose when this sugar was present at millimolar concentrations. Extracts of gal 1(-) yeast clone, transfected with presumptive human galactokinase cDNA, had very low galactokinase activity even when yeast were grown on galactose, but good activity with GalNAc. On the other hand, the wild type yeast phosphorylated galactose, but not GalNAc. These data indicate that the sequence reported for galactokinase on chromosome 15 is that of GalNAc kinase, which can phosphorylate galactose when this sugar is present at millimolar concentrations. This transfection thus allows the yeast mutant to grow slowly on galactose-containing media.

Acetylgalactosamine

The effect of testing time on students' performance for the subject examination for internal medicine.

The authors tested the hypothesis that increasing the allotted testing time from two to four hours for the National Board of Medical Examiners medicine subject examination would increase the score on this examination when given as part of the clerkship evaluation. One-hundred six students who completed their medicine clerkships between September 1991 and August 1992 (group 1) were compared with 96 students who completed their clerkships between September 1992 and August 1993 (group 2). The mean medicine subject examination score for group 1 was 462 +/- 86, vs 518 +/- 108 for group 2 (p = 0.0003). Regression analysis using the medicine subject examination score as the dependent variable and all baseline characteristics, group assignment, and time of year the test was taken as independent variables demonstrated significant interactions only for United States Medical Licensing Examination (USMLE) Step 1 score (R2 = 0.48, beta weight = 0.68, p = 0.0000) and group assignment (R2 = 0.05, beta weight = 0.18, p = 0.002). The authors conclude that increased testing time for the medicine subject examination from two to four hours is associated with a significant increase in scores; however, scores on the preclinical USMLE Step 1 showed a stronger association.

Adult

Predicting serious delinquency and substance use among aggressive boys.

Early aggressive behavior puts boys at increased risk for involvement in a variety of later problem behaviors, including delinquency and drug abuse. However, not all boys who evidence aggressive behavior in childhood continue to engage in problem behaviors in adolescence. This 3.5-year prospective study examined the role of factors hypothesized by the social development model to inhibit or increase the likelihood of subsequent involvement in serious delinquency and substance use within a sample of boys identified as aggressive by teacher report at ages 10 and 11. At ages 12 and 13, a combination of the constructs of skills for prosocial involvement, school bonding and achievement, family bonding and management practices, norms against substance use, and interaction with peers and adults involved in antisocial behavior significantly discriminated between boys who were and were not involved in serious delinquent behavior and substance use at ages 13 and 14, although family bonding and management practices appeared to contribute little to the discriminant function. Implications of the results for preventive interventions with aggressive boys are discussed.

Adolescent

Preventing school failure, drug use, and delinquency among low-income children: long-term intervention in elementary schools.

A six-year, school-based prevention program, which modified classroom teacher practices, offered parent training, and provided child social skills training, was evaluated for its effects on school failure, drug abuse, and delinquency among low-income urban children. Compared to a low-income control group, children in the intervention group showed enhanced school commitment and class participation. The girls in the group also evidenced lower rates of substance use initiation, while the boys exhibited increased social and school work skills.

Adolescent

Expert panel method for nurse staffing and resource management.

The Expert Panel Nurse Staffing and Resource Management Method is a bold new approach for the identification of nurse staffing requirements and the management of resources. Expert panels comprised of those most knowledgeable of the patient population and the uniqueness of specific patient care areas identify staff needed to meet clinical, administrative, education, continuous quality improvement, and research needs. In addition, the expert panels explore opportunities for systems improvements, work redesign, and administrative restructuring within the context of budgetary realities.

Decision Making, Organizational

Dacarbazine, cisplatin and carmustine, with or without tamoxifen, for metastatic melanoma: 5-year follow-up.

Metastatic melanoma has a grim prognosis. Response rates and survival of patients treated with combination chemotherapy are not superior to single-agent chemotherapy. This study seeks to evaluate the objective response rate and survival of patients with metastatic melanoma treated with multiagent chemotherapy, with or without tamoxifen. Forty-two patients with metastatic melanoma were treated from March 1982 to February 1988 with dacarbazine, cisplatin and carmustine, with or without tamoxifen. An overall objective response rate of 43% was seen (complete response rate 17%; partial response rate, 26%). The response rate was 54% for patients treated with tamoxifen and 25% for patients treated without tamoxifen, but the results did not achieve statistical significance. Median overall survival was 412 days, and was significantly longer in the tamoxifen-treated group. Combination chemotherapy as described in this study is well-tolerated. The observation that tamoxifen appears to impact on survival should be interpreted with great caution due to the deficiencies in the design of the trial and small patient numbers. A randomized trial of this regimen vs single-agent chemotherapy is indicated and is currently being conducted.

Adult

Infant sleep position: pediatricians' advice to parents.

OBJECTIVE: The American Academy of Pediatrics' (AAP) recommendation for side or supine sleep position in healthy babies has generated much controversy. We surveyed primary care physicians to determine the effect of the AAP statement on physician attitude toward infant sleep position and advice to parents. METHODS: We sent a 23-question survey to 194 physicians in Western New York. The survey addressed their attitude toward the AAP recommendations and its impact on their advice to parents. RESULTS: Of the 149 physicians treating newborns, 121 (82%) completed the questionnaire; 98% were aware of the AAP statement. The most common sources of information were the AAP (86%) and professional literature (77%). Of the respondents, 79% agreed with the AAP statement. Reasons for reservation were lack of data (64%), potential adverse consequences of supine position (52%), and their own experience (47%). Gender, years in practice, and type of reimbursement did not influence attitude toward the AAP recommendation. The AAP statement increased the frequency with which physicians routinely discussed sleep position from 34 to 70% (P < .02). Physicians recommending the prone position decreased from 57 to 7% (P < .001), while those recommending supine sleep position increased from 10 to 42% (P < .001). CONCLUSIONS: Most physicians agreed with the AAP statement and more frequently discussed sleep position following the AAP recommendations. However, they did not routinely recommend supine sleep position. The majority (69%) recommended the side position even though it is unstable. Although the AAP statement has increased discussion of infant sleep position by primary care physicians in WNY, only a minority recommend that infants sleep supine.

Data Collection

Infective endocarditis due to Pasteurella dagmatis: case report and review.

We report a case of endocarditis due to Pasteurella dagmatis complicated by vertebral osteomyelitis in a 55-year-old former alcoholic woman. To our knowledge, this is the second report of endocarditis attributed to that organism in the English-language medical literature. Rare cases of endocarditis due to other Pasteurella species and their varied clinical features are summarized.

Animals

Effects of changes in acid base and calcium concentration on fasting serum insulin, proinsulin, and glucose concentrations.

AIMS: To test the hypothesis that alterations in acid base or calcium concentration may affect proinsulin processing or the insulin secretion mechanism. METHODS: Changes in proinsulin secretion or cleavage were assessed by measuring serum intact proinsulin and immunoreactive insulin concentrations in three models of acid base and calcium disturbance: (1) subacute changes in acid base status in six volunteers who received oral placebo, ammonium chloride, or sodium bicarbonate for three five day periods; (2) acute changes in calcium concentration in eight subjects who received 25 mmol oral calcium; (3) chronic changes in calcium concentration in seven patients with primary hyperparathyroidism and five with pseudohypoparathyroidism. RESULTS: Acid base changes were confirmed by rises in serum bicarbonate concentrations (p < 0.01). No changes in serum insulin, intact proinsulin, or the proinsulin:insulin molar ratio were found. Serum calcium concentrations increased (2.49 v 2.38 mmol/l; p < 0.05) and parathyroid hormone concentrations decreased (1.1 v 1.9 pmol/l; p < 0.01) two hours after acute calcium loading. There were no significant differences in serum glucose, insulin, or intact proinsulin concentrations. Fasting proinsulin concentrations were significantly lower in the hyperparathyroid group (1.1 v 2.1 pmol/l; p < 0.05) and increased significantly after parathyroidectomy (2.1 v 1.1 pmol/l; p < 0.05). CONCLUSIONS: The results indicate that subacute acid base changes do not affect proinsulin cleavage. Although acute calcium loading has no demonstrable effect, chronic hypercalcaemia may influence the mechanism of insulin secretion.

Acid-Base Equilibrium

Adverse drug reactions.

Clearly, adverse drug reactions continue to induce injury and harm to patients, despite careful considerations, prescribing, dispensing, and administration. New drugs represent unknown risks and require intense scrutiny and monitoring in their early market stages. Deterioration of good monitoring, selection of more toxic drugs, and poor history taking from patients will continue to present challenges and increased risks from this partially reversible morbidity and mortality to patients.

Adverse Drug Reaction Reporting Systems

Theophylline misadventures: Part I.

Theophylline intoxication has become an important clinical problem in the NICU, in large part because of its increased and extensive use for treatment of neonatal respiratory diseases. This article reviews the mechanisms of action involved in current methylxanthine uses, outlines the range of dosage recommendations and target plasma levels in the neonate, describes reported toxicities as extensions of the pharmacologic effects, summarizes some recent litigation reports addressing theophylline toxicity, and shares recommendations from practitioners who have written about the clinical use of this class over the past 50 years. By using suitable initial dosing guidelines and aggressive early serum concentration monitoring, practitioners can use theophylline safely and effectively in neonates.

Humans

Theophylline misadventures: Part II.

Except for overdose ingestions, excessive theophylline serum concentrations can be attributed predominantly to therapeutic misadventure. Utilizing medico-legal case reports as a core, this article considers how theophylline toxicity is manifested in several major organ systems and discusses drug/disease interactions with theophylline that may alter serum theophylline concentrations, necessitating dose adjustments. Theophylline overdose is associated with significant morbidity and mortality risks. Overdose treatment, based on use of serum concentrations, is addressed. An understanding of all these factors can help caregivers avoid theophylline morbidity and mortality in neonatal patients.

Central Nervous System Diseases

Phase I/II trial of etoposide and carboplatin in extensive small-cell lung cancer. A report from the Cancer and Leukemia Group B.

Previously untreated extensive small-cell lung cancer (SCLC) patients with performance status 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and carboplatin doses of 50, 100, or 125 mg/m2/day on days 1-3 in a Phase I format. Among the ten eligible patients treated with 125 mg/m2/day of carboplatin, grade 3 or 4 infection occurred in six patients, grade 4 thrombocytopenia in four patients, and there was one death with myelosuppression. Thus, this dose was considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted utilizing this treatment program. In the Phase II trials, 81% of the 48 eligible patients had grade 3 or 4 leukopenia, 76% had grade 3 or 4 thrombocytopenia, and 55% had grade 3 or 4 anemia. There were three (6%) toxic deaths from myelosuppression. The objective response rate was 63% (17% complete responders) with a median response duration of 6.2 months for complete responders and 6.4 months for partial responders. Median survival was 12 months. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 25% increase in carboplatin compared to prior studies. Cancer and Leukemia Group B (CALGB) plans to study further dose intensification of this regimen with colony-stimulating factors.

Adult