Biomedical subjects

C Pratt

Publications and source records attributed to C Pratt.

At least 19 recordsLinked to original sources

PubMed1999

Cardiovascular safety of fexofenadine HCl.

BACKGROUND: Certain first- and second-generation H1-receptor antagonists are associated with prolongation of the corrected QT interval (QTc) and, in rare instances, with ventricular dysrhythmias, including torsades de pointes ventricular tachycardia. OBJECTIVE: To assess the effect of fexofenadine HCl, a new non-sedating antihistamine, on QTc. METHODS: Dose-tolerance, safety, and drug-interaction studies with healthy volunteers; and clinical efficacy studies with seasonal allergic rhinitis patients were conducted. Twelve-lead ECG data were collected pre- and postdosing or serially throughout these studies. Outliers were defined as QTc >440 msec with a >/=10 msec increase from baseline. RESULTS: Fexofenadine HCl at single doses up to 800 mg q.d. (once daily) and multiple doses up to 690 mg b.d. for 28 days in healthy volunteers resulted in no increases in QTc (recommended dose range is 120-180 mg daily); QTc changes were similar to placebo. Compared with placebo, there were no statistically significant QTc increases in patients receiving fexofenadine HCl 80 mg b.d. for 3 months, 60 mg b. d. for 6 months, or 240 mg q.d. for 12 months. No statistically significant increases in QTc were detected when fexofenadine HCl 120 mg b.d. was administered in combination with erythromycin (500 mg t. d.) or ketoconazole (400 mg q.d.) after dosing to steady-state (6.5 days). In seasonal allergic rhinitis patients (n = 1160) treated with 40, 60, 120, or 240 mg b.d. fexofenadine HCl for 2 weeks, there were no dose-related increases in QTc and no significant increases in mean QTc compared with placebo. Frequency and magnitude of QTc outliers with fexofenadine HCl and placebo were similar in all studies. No case of fexofenadine-associated torsades de pointes has been observed in controlled trial experience with more than 6000 patients. CONCLUSION: Fexofenadine HCl has been investigated more extensively for possible electrophysiological effects than any other antihistamine. Fexofenadine HCl has no significant effect on QTc, even at doses much higher than those used in clinical practice.

Dose-Response Relationship, Drug↗

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↗

PubMed1998

Phase I trial of 9-aminocamptothecin in children with refractory solid tumors: a Pediatric Oncology Group study.

PURPOSE: A phase I trial of 9-aminocamptothecin (9-AC) was performed in children with solid tumors to establish the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and the pharmacokinetic profile in children and to document any evidence of activity. PATIENTS AND METHODS: A 72-hour infusion of 9-AC dimethylacetamide formulation was administered every 21 days to 23 patients younger than 21 years of age with malignant tumors refractory to conventional therapy. Doses ranged from 36 to 62 microg/m2 per hour. Pharmacokinetics were to be performed in at least three patients per dose level. The first course was used to determine the DLT and MTD. RESULTS: Nineteen patients on four dose levels were assessable for toxicities. At 62 microg/m2 per hour, three patients experienced dose-limiting neutropenia and one patient experienced dose-limiting thrombocytopenia. Pharmacokinetics were performed on 15 patients (nine patients had complete sets of plasma sampling performed). The pharmacokinetics of both lactone and total 9-AC were highly variable. The percentage of 9-AC lactone at steady-state was 10.8% +/- 3.6%. Total 9-AC and its lactone form had a terminal half-life of 8.1 +/- 3.8 and 7.1 +/- 3.9 hours, respectively, and a volume of distribution at steady-state (Vdss) of 21.2 +/- 13.3 L/m2 and 135.3 +/- 52.5 L/m2, respectively. Hepatic metabolism and biliary transport had an important role in 9-AC disposition. CONCLUSION: The recommended phase II dose of 9-AC administered as a 72-hour infusion every 21 days to children with solid tumors is 52 microg/m2 per hour. Neutropenia and thrombocytopenia were dose limiting.

Adolescent↗

PubMed1998

Utilizing parent report to investigate young children's fears: a modification of the Fear Survey Schedule for Children--II: A research note.

The Fear Survey Schedule for Children-II (FSSC-II) (Gullone & King, 1992) was modified for parent report and a younger age group. The modified instrument (FSSC-IIP) was completed by 753 parents of children within the age range 3.0 to 8.9 years. Results revealed a stable eight-factor solution that was sensitive to age and gender differences. Parents reported a higher overall level of fear for school children compared to preschool children, and a higher overall level of fearfulness for girls compared to boys. The most common fears reported were getting lost in a crowd and in a strange place.

Child↗

PubMed1998

Belief term development in children with autism, Asperger syndrome, specific language impairment, and normal development: links to theory of mind development.

This study examined the relationship between the development of theory of mind and the development of the belief terms think, know, and guess. Children with autism and Asperger syndrome, matched to children with specific language impairment and normal development, completed false belief, belief term comprehension, and belief term expression tasks. The autistic group's performance on the false belief, belief term comprehension, and belief term expression tasks was significantly poorer than that of the Asperger, language impaired, and normal groups. Across groups an association was found between false belief and belief term performance. Results support a growing body of literature demonstrating links between the development of theory of mind and communicative competence.

Autistic Disorder↗

PubMed1997

Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization.

BACKGROUND: Patients with ischemia during stress testing and ambulatory ECG monitoring have an increased risk of cardiac events, but it is not known whether their prognosis is improved by more aggressive treatment with anti-ischemic drugs or revascularization. METHODS AND RESULTS: The Asymptomatic Cardiac Ischemia Pilot study randomized 558 such patients who had coronary anatomy suitable for revascularization to three treatment strategies: angina-guided drug therapy (n=183), angina plus ischemia-guided drug therapy (n=183), or revascularization by angioplasty or bypass surgery (n=192). Two years after randomization, the total mortality was 6.6% in the angina-guided strategy, 4.4% in the ischemia-guided strategy, and 1.1% in the revascularization strategy (P<.02). The rate of death or myocardial infarction was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (P<.04). The rate of death, myocardial infarction, or recurrent cardiac hospitalization was 41.8% in the angina-guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (P<.001). Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison. CONCLUSIONS: A strategy of initial revascularization appears to improve the prognosis of this population compared with angina-guided medical therapy. A larger long-term study is needed to confirm this benefit and to adequately test the potential of more aggressive drug therapy.

Adrenergic beta-Antagonists↗

PubMed1997

Outcome of treatment for pediatric sarcoma of the foot: a retrospective review over a 20-year period.

Soft tissue sarcomas (STS) arising in the foot are rare in children. From 1975 to 1994, 18 children (median age, 13.5 years) were treated at St Jude Children's Research Hospital for STS of the foot. Five children had rhabdomyosarcoma (RMS), with alveolar histology in four cases. All of these patients presented with metastatic disease, which proved fatal within 9 to 24 months despite combined modality treatment with chemotherapy, radiation, and surgery. Thirteen patients had nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). The most common histological variant was synovial sarcoma (7 patients). Of the 10 who presented with localized disease, seven survived 1 to 12 years (median, 7 years). Surgical treatment for these consisted of local excision (n = 2), wide local excision (n = 3), below knee amputation (n = 1 ), ray amputation (n = 1). Three received supplemental radiation, and one was also treated with chemotherapy. Local or distant recurrence proved fatal in the three other children who had localized disease. Three children who presented with metastatic NRSTS died 8 to 14 months after diagnosis. All surviving patients are without significant functional disability. In our experience, pediatric RMS of the foot has a poor outcome, attributable to both alveolar histology and presence of metastatic disease at diagnosis. In contrast, NRSTS of the foot is more often localized, and limited surgery with adjuvant radiation in the absence of clear margins should be the treatment of choice.

Adolescent↗

PubMed1996

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study. Relationship between exercise-induced and ambulatory ischemia in patients with stable coronary disease.

BACKGROUND: We investigated whether the presence and frequency of asymptomatic ischemic episodes recorded during ambulatory ECG (AECG) monitoring could be predicted on the basis of clinical characteristics or exercise treadmill test (ETT) performance in patients with stable coronary disease and whether the estimate of ischemia severity was similar between the AECG and ETT. METHODS AND RESULTS: Patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) study were selected for the current analysis if data were available from 48-hour AECG monitoring as well as from an ETT during which the patient developed > or = 1-mm ST-segment depression. Exercise ECG data were available for 143 of the 910 patients without ischemic episodes and for 659 of the 910 patients with ischemic episodes during AECG monitoring. Angina was more frequent among patients with ambulatory ischemic episodes than among patients without such ischemia (P < .001). Patients with AECG ischemia had a consistently more marked ischemic response on the ETT than patients without AECG ischemia; patients likely to have AECG ischemia could be predicted on the basis of ETT performance characteristics. However, the correlation coefficients between the severity of ischemia estimated by ETT and by AECG were small. CONCLUSIONS: There are significant relations between ischemia detected by AECG monitoring and by ETT, but the relations are limited, indicating that the two tests are not redundant to characterize coronary patients. A larger study investigating the prognostic significance of the ischemia identified by each modality, with follow-up for clinical events, will be necessary to determine the most appropriate methods to evaluate patients with stable coronary disease.

Coronary Disease↗

PubMed1996

Relation of patient characteristics to cardiac ischemia during daily life activity (an Asymptomatic Cardiac Ischemia Pilot Data Bank Study).

Cardiac ischemia during daily life activities, detected by ambulatory electrocardiographic (AECG) monitoring has been associated with increased risk for adverse outcomes. Because daily life ischemia is usually asymptomatic, prevalence and descriptive data of patients with asymptomatic cardiac ischemia (ACI) are not well defined. Accordingly, patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial by 48-hour AECG monitoring were investigated to identify factors associated with ACI. A total of 1,820 patients with ischemia on a screening stress test and/or known or suspected coronary artery disease underwent AECG monitoring. Their mean age was 61 years, range 33 to 89; 83% were men and 81% were white. On AECG monitoring, ACI occurred in 897 patients (49%). There was a modest trend (p = 0.04) between increasing age and ACI prevalence. Increased risk for ACI was observed in patients reporting angina 6 weeks before screening (odds ratio 1.38, 99% confidence interval 1.08 to 1.77, p = 0.0008). There was a positive association between increases in heart rate during daily life and ACI prevalence (p < 0.0001). No daily, monthly, or seasonal variation in ACI prevalence was found, although ACI was more prevalent in northern than southern sites. In this group of clinically stable patients, selected on the basis of high risk for coronary artery disease, the prevalence of ACI was higher than expected from previous reports. Several readily available clinical characteristics (i.e., advanced age, recent angina, increased heart rate change with daily activity) were associated with significantly increased probability of ACI.

Activities of Daily Living↗

PubMed1996

Effects of a red background on magnocellular functioning in average and specifically disabled readers.

Two experiments were conducted using metacontrast masking to examine responses in the magno system of adults, average reading adolescents and adolescents with specific reading disability. In Experiment 1 the effects of a red background field on the metacontrast functions of adult subjects were investigated. Results showed that a red, compared to a photometrically matched white background field, significantly attenuated metacontrast magnitude, supporting the interpretation of metacontrast as due to magno system suppression of parvo system responses. The finding of a red background effect was replicated in Experiment 2 with the two adolescent groups. The metacontrast functions of the adolescent groups also differed significantly, with those with specific reading disability exhibiting weaker metacontrast than the average readers. This result is consistent with a deficit in the magno system of individuals with specific reading disability and indicates the continuation of the deficit beyond childhood.

Adolescent↗

PubMed1996

Blurring the image does not help disabled readers.

Previous research has found that poor readers performed a visual search task more slowly than good readers, but that this difference was virtually eliminated by blurring of the search array. Whereas blurring had little effect on the performance of the good readers, it led to a dramatic improvement in the search rate of the poor readers. The present study set out to replicate this research with groups of 10-12 yr old disabled and average readers but with methodological improvements in the procedure and the analysis. It was found that the disabled readers performed the search task as well as the average readers, and that blurring of the display conferred no advantage on either group. The results are discussed in relation to the transient deficit theory of reading disability.

Child↗

PubMed1996

Epithelioid sarcoma in children.

Literature regarding the natural history and prognosis of epithelioid sarcoma in the pediatric population is sparse. During the past 11 years, eight patients with epithelioid sarcoma were treated at St Jude Children's Research Hospital. Of the eight children, six of whom were male, seven presented with localized disease and one with metastatic disease. The primary tumor was located in the upper extremity in four patients; the other sites were the scalp, external ear, back, and mediastinum. The mean duration of symptoms before diagnosis was 8.3 months (range, 1 to 12 months). Surgical treatment comprising amputation or wide local excision was performed in six patients, three of whom had additional lymph node dissection. Three patients received multiagent chemotherapy, and four patients were treated with supplementary radiation. Two patients died of progressive local and distant disease within 9 months of diagnosis. The other six patients are alive and have no evidence of disease 12 months to 10 years 6 months after the completion of treatment.

Adolescent↗

PubMed1996

Psychosocial influences on the use of health care by children.

A prospective cohort study examined the influence of psychosocial factors on the use of general practitioners over a six-month period by 271 children (aged four to nine years) and their mothers. The study was conducted in 10 general practices in the metropolitan area of Perth. The influences of psychosocial factors on use, nonuse and frequency of use by the children were examined, taking into account sociodemographic and morbidity factors. Physical health status, maternal use and financial factors were directly associated with the children's use or nonuse of general practitioners, while maternal stress, a mother's attitude towards her child and the child's psychosocial morbidity were indirectly related. Physical health status, doctor-initiated consultations, maternal stress, children's ages and birth order were directly associated with the children's frequency of use of general practitioners. Depression and anxiety in the mothers, measured with standardised instruments, were not associated with use by the children nor was a mother's level of social support. The results point to the importance of family relationships and illness behaviour in the family when considering use of general practitioners and the importance of using standardised measuring instruments and multivariate designs when studying such complex behaviours as the use of health care.

Attitude to Health↗

PubMed1996

Treatment costs and use of community mental health services for schizophrenia by age cohorts.

OBJECTIVE: Research on schizophrenia has tended to ignore patterns and costs of mental health service use in late life. The present study examined the types of mental health services used and their costs for several age-defined cohorts in a large community mental health system. METHOD: The data covered all users of the mental health system included in the San Diego county billing information system in fiscal years 1986 and 1990. Community mental health service use and codes were modeled as a function of patient demographic characteristics, diagnosis, and age. The patients were grouped into the following age categories: 18-29, 30-44, 45-54, 55-64, 65-74, and > or = 75 years of age. RESULTS: The total costs for schizophrenia were higher than those for other psychiatric disorders, and they were also age dependent. In both fiscal years, the costs of schizophrenia were higher for the youngest and oldest cohorts than for the patients in the 30-65-year range. CONCLUSIONS: The economic burden of late-life schizophrenia to the public mental health system is at least as high as that of schizophrenia in younger adults.

Adolescent↗

PubMed1995

A comparison of temporal integration in children with a specific reading disability and normal readers.

Previous research has suggested that whereas some techniques show that subjects with a specific reading disability (SRD) have greater visible persistence than controls, a temporal integration of form technique does not. It has been suggested that the failure of the temporal integration task to show a difference results from the spatial separation between stimuli used in the technique. In this study SRD and control subjects were compared on a new version of a temporal integration task, under two conditions varying the spatial separation of elements in the display. It was predicted that there would be no difference between groups when spatial separation was large, but that the SRD subjects would show greater visible persistence at small separations. Neither prediction was confirmed, denying previous explanations of why the temporal integration task does not discriminate between groups. Analysis of errors showed that the result was not due to inattention nor to a general deficit on the part of the SRD subjects.

Afterimage↗

PubMed1995

Asymptomatic Cardiac Ischemia Pilot (ACIP) study: impact of anti-ischemia therapy on 12-week rest electrocardiogram and exercise test outcomes. The ACIP Investigators.

OBJECTIVES: This report from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study examines differences in the magnitude of reduction of myocardial ischemia as determined by exercise treadmill testing in patients randomized to three different treatment strategies: angina-guided medical therapy, ischemia-guided medical therapy and coronary revascularization. BACKGROUND: No prospective randomized clinical trials in patients with exercise electrocardiographic (ECG) abnormalities and asymptomatic cardiac ischemia on ambulatory ECG monitoring have compared the impact of different treatment strategies, including coronary revascularization, in terms of reducing myocardial ischemia. METHODS: The ACIP exercise protocol was used. Exercise variables measured included final exercise stage; presence of exercise-induced angina or ischemia; time to angina; time to 1-mm ST segment depression; number of exercise ECG leads with abnormalities; maximal depth of ST segment depression in any lead; sum of ST segment depression; ST/HR index; and rate-pressure product at time to angina, at time to 1-mm ST segment depression and at peak exertion. RESULTS: Peak exercise time was increased by 0.5, 0.7 and 1.6 min in patients assigned to the angina-guided, ischemia-guided and coronary revascularization strategies, respectively, from the qualifying visit to the 12-week visit (p < 0.001). At the qualifying visit, the sum of exercise-induced ST segment depression was 9.4 +/- 5.0 (mean +/- SD), 9.6 +/- 4.7 and 9.9 +/- 5.5 mm (p = NS) in the three treatment strategies, respectively. At the 12-week visit, the sum of exercise-induced ST segment depression was 7.4 +/- 5.7, 6.8 +/- 5.3 and 5.6 +/- 5.6 mm (p = 0.02) in the three treatment strategies, respectively. Each treatment strategy resulted in a significant reduction in all exercise-induced variables of myocardial ischemia measured at 12 weeks. CONCLUSIONS: Coronary revascularization significantly reduced the extent and frequency of exercise-induced myocardial ischemia compared with either medical strategy. The prognostic impact of these observations should be evaluated in a large-scale multicenter clinical trial.

Analysis of Variance↗

PubMed1995

The use of props in a syntactic awareness task.

The study investigated the effects of using props to illustrate the meaning of sentences in a syntactic awareness task in which subjects were required to correct ungrammatical sentences. Forty preschool children (aged 4; 11 to 5; 11) were asked to correct 20 sentences, 10 of which were illustrated using props, and 10 of which were not. Children scored significantly higher in the props condition though the proportion of meaning-changing errors to total errors was not significantly lower in this condition. It is argued that the use of props, by providing contextual support, reduces the processing capacity required to complete the task.

Awareness↗

PubMed1995

Second malignant neoplasms in children with retinoblastoma: the St. Jude Children's Research Hospital experience.

A retrospective review of 172 children with primary diagnosis of retinoblastoma (RB) was completed at St. Jude Children's Research Hospital to evaluate the incidence of second malignant neoplasm (SMN) development. Sixty-five patients presented with bilateral RB and 107 with unilateral RB. During follow-up, which ranged from 6 to 340 months (median = 170 months), 6 children (3.5%) developed SMN. All patients who developed SMN presented with bilateral disease (n = 5) or asynchronous bilateral disease (n = 1); two patients had a family history of RB. All had received irradiation. Four patients developed osteogenic sarcoma within this irradiated volume, one developed a basal cell carcinoma in the temporal region (within the irradiation field), and one was diagnosed with a lower extremity Ewing's sarcoma. Time to development of SMN ranged from 125 to 194 months post-irradiation. Initial irradiation total dose ranged between 32 and 45.76 Gy. Three patients were treated with anterior field irradiation and three received lens-sparing techniques (anterior/lateral n = 2, lateral n = 1). At last follow-up, 4/6 patients had died of SMN. The crude incidence is 3.5% with an estimation of risk using the density method of 24% at 20 years for SMN development. The specifics of the treatment associated with these second malignancies and the possible reasons for the reported incidence of SMN will be discussed.

Child↗