Biomedical subjects

C Pratt

Publications and source records attributed to C Pratt.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1995

Asynchronous bilateral retinoblastoma: the St. Jude Children's Research Hospital experience.

Between May 1962 and July 1993, 172 children presented at the St. Jude Children's Research Hospital for evaluation and/or treatment of retinoblastoma (RB). Of these, 65 presented with bilateral disease, while 107 had unilateral tumors. Of these 107 patients, nine subsequently developed RB in the unaffected eye. Initial age at diagnosis of these nine patients ranged from 3 weeks to 24 months (median = 2 months); five of the nine had a family history of RB at the time of initial diagnosis and one patient, without a family history of RB, presented with unilateral multiple tumors indicating inheritance of a germinal mutation and increased risk of RB development in the companion eye. Time to development of companion eye RB was 1-61 months postinitial diagnosis. Treatment of the initial eye included enucleation (n = 4), chemotherapy (n = 3), irradiation (n = 7), or a combination of these three modalities. Reese-Ellsworth grouping of the companion eye disease included I A (n = 7), III A (n = 1), and IV A (n = 1). Treatment of the second affected eye included irradiation in seven patients, cryotherapy in four, and chemotherapy in three. No companion eye has required enucleation to date. At last followup, 14/18 eyes remain intact. There have been no cases of metastatic dissemination; however, one patient has developed a second malignant neoplasm outside the field of irradiation. Eight of the nine patients remain alive. This experience reinforces the need for close follow-up of patients diagnosed with unilateral RB, especially those with a family history of RB and those with unilateral multiple tumors.

Child, Preschool↗

PubMed1995

Asymptomatic cardiac ischemia pilot (ACIP).

This pilot study demonstrated that (1) patients with CAD and asymptomatic cardiac ischemia can be randomized to medical or revascularization strategies using a complex and demanding protocol, (2) asymptomatic cardiac ischemia can be suppressed in 40-50% of patients with clinically advanced coronary disease with relatively low to moderate doses of medication titrated over a period of 12 weeks (3). Revascularization was the most effective of the treatment strategies studied in reducing ischemia. Any type of therapy, whether it be drugs or revascularization requiring repetitive monitoring with ambulatory ECG or other methods to detect ischemia over a long period of time, will escalate the cost of quality medical care for our patients. Thus, the health care costs implications and treatment of asymptomatic ischemia are enormous. But the apparent cost advantage of treating only symptoms, that is ignoring all ischemia, could disappear if treatment of ischemia reduces the risk of adverse events. The clinical question to be addressed in the future is what is necessary to reduce the cardiac-event rates of death and myocardial infarction in this group of patients? Will more aggressive drug therapy eliminate more ischemia and will therapy directed at the elimination of all detectable ischemia improved clinical outcome better than therapy directed to control angina only? These questions can only be answered by a large clinical trial. The results of such a trial will provide the basis and rationale for safe and effective therapy for patients with coronary disease and evidence of cardiac ischemia. Whatever the answer to this important medical and scientific question is, it will have tremendous economic implications.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Photoaffinity labeling for evaluation of uridinyl analogs as specific inhibitors of rat liver microsomal UDP-glucuronosyltransferases.

The UDP-glucuronosyltransferases (UGT) involved in glucuronidation of endogenous and exogenous toxic compounds transfer the glucuronic acid residue from UDP-glucuronic acid (UDP-GlcUA), to various acceptor groups. A series of compounds that contain N-acyl phenylaminoalcohol derivatives linked to uridine or isopropylideneuridine were tested as UGT inhibitors. The potency of these inhibitors was determined by studying their effect on the photoaffinity labeling of rat liver microsomal UGTs by two photoaffinity probes, [beta-32P]5-azido-UDP-glucuronic acid (5N3UDP-GlcUA) and [beta-32P]5-azido-UDP-glucose (5N3UDP-Glc) and on the enzymatic formation of the two glucuronide conjugates (3-O- and carboxyl-specific) of lithocholic acid. All but one of the compounds tested proved to have an inhibitory effect on UGTs, both in the photoaffinity labeling system and in the enzymatic glucuronidation assay. In the photoaffinity labeling system, the inhibitors containing the isopropylidene moiety were less effective than their unprotected derivatives; however, the protected forms were, with one exception, more potent inhibitors of enzymatic activity. The photoaffinity labeling of UGTs with [beta-32P]5N3UDP-Glc was more susceptible to inhibition by all derivatives than that with [beta-32P]5N3UDP-GlcUA. The effect of one inhibitor, PP50B, on the two enzymatic activities involved in LA glucuronidation was extensively tested. A double-reciprocal plot suggested a competitive inhibition for UDP-GlcUA with an apparent Ki of 35 microM for LA 3-O-glucuronide formation and 94 microM for the carboxyl-linked glucuronide of the same substrate.

Affinity Labels↗

PubMed1994

Neurofibromatosis type I and malignancy: review of 32 pediatric cases treated at a single institution.

Thirty-two cases of neurofibromatosis Type I (NF1) were identified among 6,678 pediatric cancer patients treated at St. Jude Children's Research Hospital over a 29-year period. A total of 35 malignant neoplasms have been diagnosed in these patients. Two of three patients with second malignant neoplasms had colon cancer at the primary or second tumor. Of particular interest are two cases in which both NF1 and malignant peripheral nerve sheath tumors were present in multiple successive generations: a patient with colon cancer and non-Hodgkin lymphoma who has a constitutional abnormality of the p53 gene, and a patient with acute lymphoblastic leukemia with the Philadelphia chromosome and other cytogenetic abnormalities, including the t(8;14). Outcome of patients in the largest subgroup, that of malignant peripheral nerve sheath tumors, was favorable only for those patients having resectable extremity lesions. In contrast, all patients with central nervous system tumors are surviving. These cases reflect the molecular and cytogenetic abnormalities that can be present in NF1 and the variety of tumors that may result in these patients.

Adolescent↗

PubMed1994

Effects of treatment strategies to suppress ischemia in patients with coronary artery disease: 12-week results of the Asymptomatic Cardiac Ischemia Pilot (ACIP) study.

OBJECTIVES: The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was initiated to determine the feasibility of a large trial in evaluating the effects of treatment of ischemia on outcome (mortality and myocardial infarction). The study was designed to examine the effects of medical treatment to control angina compared with treatment strategies guided by ambulatory electrocardiographic (ECG) ischemia or coronary anatomy. BACKGROUND: Treatments to suppress ischemia (asymptomatic and symptomatic) have not been evaluated in a large prospective, randomized trial. Before undertaking such a trial, issues about recruitment and treatment strategies must be addressed. METHODS: The 618 enrolled patients had coronary artery disease suitable for revascularization, ischemia on stress test and asymptomatic ischemia on ambulatory ECG. Patients were assigned randomly to one of three treatment strategies: 1) angina-guided medical strategy with titration of anti-ischemic medication to relieve angina (angina-guided strategy); 2) angina-guided plus ambulatory ECG ischemia-guided medical strategy with titration of anti-ischemic medication to eliminate both angina and ambulatory ECG ischemia (ischemia-guided strategy); and 3) revascularization by angioplasty or bypass surgery (revascularization strategy). RESULTS: Ambulatory ECG ischemia was no longer present at the week 12 visit in 39% of patients assigned to the angina-guided strategy, 41% of patients assigned to the ischemia-guided strategy and 55% of patients assigned to the revascularization strategy. All strategies reduced the median number of episodes and total duration of ST segment depression during follow-up ambulatory ECG monitoring. Revascularization was the most effective strategy. Treadmill test results were concordant with those of ambulatory ECG monitoring. For most patients in the two medical strategies, angina was controlled with low to moderate doses of anti-ischemic medication, and the majority of patients (65%) in the revascularization strategy did not require medication for angina. CONCLUSIONS: This pilot study demonstrated that cardiac ischemia can be suppressed in 40% to 55% of patients with either low or moderate doses of medication or revascularization and that a large trial is feasible.

Aged↗

PubMed1994

Phase I study of oral etoposide in children with refractory solid tumors.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and plasma concentrations of orally administered etoposide (VP-16) in pediatric oncology patients. PATIENTS AND METHODS: In a phase I study, 20 children with refractory solid tumors received oral VP-16 (the intravenous preparation diluted with sodium chloride) three times daily for 21 days. Daily dose levels studied were 50 mg/m2 (n = 5), 60 mg/m2 (n = 7), and 75 mg/m2 (n = 8). VP-16 concentrations were measured in blood samples collected on days 1, 7, 14, and 21. RESULTS: Grade 3 to 4 thrombocytopenia and/or neutropenia causing interruption of the 21-day course or persisting for more than 7 days after the last day of chemotherapy was seen at all dose levels, but was not dose-limiting. One patient treated at the 50-mg/m2 daily dose died of sepsis. At the 75-mg/m2 dose level, diarrhea was dose-limiting. Estimated plasma VP-16 concentrations were greater than 1 micrograms/mL for median periods of 9.4, 15.4, and 13.5 hours per day at daily doses of 50, 60, and 75 mg/m2, respectively. Responses were observed in seven of 14 patients who received at least one additional course of etoposide after a rest period of 7 days. There was one complete and two objective responses. Four patients were considered to have stable disease. CONCLUSION: The intravenous preparation of VP-16 administered orally appears to be well tolerated by heavily pretreated pediatric patients. On the three-times daily, 21-day schedule, a daily dose of 75 mg/m2 exceeds the MTD, with diarrhea as the dose-limiting toxicity. The recommended dose for oral etoposide is 60 mg/m2/d administered every 8 hours.

Administration, Oral↗

PubMed1994

Phase I trial of continuous infusion carboplatin and etoposide in children with refractory acute leukemia: a Pediatric Oncology Group study.

PURPOSE: The purpose of this phase I study was to determine the toxicities and response to continuous infusion carboplatin in combination with a fixed dose of etoposide (VP-16) in children with refractory acute leukemia. PATIENTS AND METHODS: From January 1989 to February 1992, 20 patients received 28 courses of treatment. Each course of treatment consisted of a 1-hour intravenous (IV) infusion of VP-16 100 mg/m2/d for 5 days, followed by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day dose of carboplatin (1,000 mg/m2) was escalated by 250- to 375-mg increments to a final, total dose of 1,875 mg/m2 over 5 days. RESULTS: Significant marrow suppression was observed in all patients, with prolonged marrow aplasia at the 1,875-mg/m2 dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocytopenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%). CONCLUSION: In view of the apparent antileukemic efficacy and minimal extramedullary toxicity, carboplatin deserves further study in a phase II trial.

Acute Disease↗

PubMed1993

A 60 kDa polypeptide of skeletal-muscle sarcoplasmic reticulum is a calmodulin-dependent protein kinase that associates with and phosphorylates several membrane proteins.

Activation of a calmodulin (CaM)-dependent protein kinase associated with rabbit skeletal-muscle sarcoplasmic reticulum (SR) results in the phosphorylation of polypeptides of 450, 360, 165, 105, 89, 60, 34 and 20 kDa. Radioligand-binding studies indicated that a membrane-bound 60 kDa polypeptide contained both CaM- and ATP-binding domains. Under renaturing conditions on nitrocellulose blots, the 60 kDa polypeptide of the membrane exhibited CaM-dependent autophosphorylation activity, suggesting that it was the CaM-dependent protein kinase of SR. Ca2+/CaM-independent autophosphorylation of polypeptides of 62 and 45 kDa was found to occur in the light SR, whereas the Ca2+/CaM-dependent autophosphorylation activity was enriched in the heavy SR. Both these kinase activities were absent from transverse tubules, although these membranes were enriched in CaM-binding polypeptides of 160, 100 and 80 kDa. In the absence of Ca2+, CaM bound to a 33 kDa polypeptide of the membrane. The purified ryanodine receptor was not phosphorylated by the purified CaM kinase, although it was a substrate for protein kinase C. Affinity-purified antibodies to brain CaM kinase II cross-reacted with the 60 kDa polypeptide in Western blots and immunoprecipitated the 60 kDa polypeptide, along with the 360, 105, 89, 34 and 20 kDa phosphoproteins, from Nonidet-P-40-solubilized SR membranes. Antibodies raised against the 60 kDa kinase polypeptide did not cross-react with the other phosphoproteins, suggesting that these polypeptides were distinct and unrelated. Subcellular distribution of the 60 kDa kinase indicated the specific association of the polypeptide with the junctional-face membrane of SR. The CaM-dependent incorporation of 32P into various membrane proteins was inhibited by the CaM kinase II fragment (290-309), with an IC50 value of 2 nM for the inhibition of incorporation into the 60 kDa kinase polypeptide. Recent studies [Wang and Best (1992) Nature (London) 359, 739-741] have shown that a CaM kinase activity intrinsic to the membrane can inactivate the Ca(2+)-release channel of skeletal muscle SR. Since our results demonstrate that the 60 kDa polypeptide of SR is a CaM-dependent protein kinase, we suggest that this kinase, through its associations, may be responsible for gating the Ca(2+)-release channel.

Adenosine Triphosphate↗