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Biomedical subjects

C Pratt

Publications and source records attributed to C Pratt.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1992

Evaluation of CHIP (iproplatin) in recurrent pediatric malignant solid tumors. A phase II study (Pediatric Oncology Group).

CHIP (325 mg/M2), a second generation cisplatin derivative, was administered intravenously every 3 weeks to 85 pediatric patients with recurrent sarcomas (19), osteosarcomas (20), neuroblastoma (23), germ cell tumors (10), and other malignant tumors (7). Thirty-eight of them had been previously exposed to cisplatin. Partial remissions were only observed in 3 of 23 (13% SE = 7%) patients having neuroblastoma. Severe thrombocytopenia (65%) and neutropenia (35%) were the dose limiting factors.

Adolescent↗
PubMed1992

Radiological features during and following treatment of spinal tuberculosis.

A retrospective study was performed in order to document the sequence and time scale of radiological changes occurring during the healing of spinal tuberculosis. 28 episodes occurred in 26 patients, of whom only two were Caucasian. All demonstrated good response to conventional chemotherapy. Soft-tissue masses increased in size for up to 1.5 months and took about 12 months to resolve. Bone destruction was seen in all cases and progressed in 70% of patients, whilst on treatment. There was loss of vertebral body height in 79%, which progressed for up to 14 months; any recovery of height was a very late feature. Sclerosis was seen at presentation in 52% and developed in most of the remaining patients within 5 months of instigating treatment. It progressed for up to 14 months and took, on average, 31 months to return to normal. Reduction in disc height was commonly seen and the vertebrae fused in three-quarters of those affected, the time of onset of fusion being very variable. To manage patients with spinal tuberculosis, an appreciation of the variability of radiological changes that can occur during treatment is necessary.

Adolescent↗
PubMed1992

Agreement between patients and their self-selected surrogates on difficult medical decisions.

BACKGROUND: Several studies have demonstrated that surrogate decision makers often are unable to use substituted judgment when asked to make decisions for incompetent patients. This study further explored this question, using a relatively young, healthy sample of 50 patient/surrogate pairs. METHODS: Patients were randomly recruited from a community family practice clinic and asked to select a surrogate. Five case vignettes were presented to patients and surrogates during separate interviews. Vignettes asked for decisions related to ventilation, resuscitation, and tube feeding for a patient in permanent coma, amputation as life-extending treatment for a mentally confused patient, and chemotherapy for a decisionally incapacitated patient with advanced cancer. Factors considered important to decision making were also investigated. RESULTS: As groups, patients and surrogates were similar as they chose to withdraw or continue treatment in the same proportions. However, within individual pairs, agreement on treatment occurred only 70% of the time even though surrogates were asked to base their treatment decisions on substituted judgment. The kappa coefficients indicated that the rate of agreement in individual vignettes was low. Patients considered "burden on the family" and "time left to live" as the most important factors in choosing among difficult treatment options, while surrogates identified the patients' pain as the most important factor. CONCLUSIONS: The high rate of discrepant decisions underscores the importance of effective patient-surrogate communication before medical decision-making incompetence occurs. The potential of increasing patient-surrogate agreement on difficult medical decisions by educational interventions should be explored.

Adult↗
PubMed1991

Leisure activities of adolescent school students: predictors of participation and interest.

Frequency of participation and levels of interest in more than 60 leisure pursuits were measured via a questionnaire administered to 1248 adolescent high school students. The relationship between participation and levels of interest was measured by correlation as well as by asking the students to nominate up to three activities they would like to participate in but cannot and to indicate the reason for their non-participation. Factor analyses reduced the Participation and Interest items to six factors each. Multiple regressions were then conducted on the derived factor-score variables. Sex was the major predictor of participation in sports and vocational activities and of interest in sporting and gregarious activities. Age, school location, ethnicity and SES were lesser predictors for groups of activities such as the social and outdoor pursuits. The results are discussed in terms of the theoretical and practical implications of the relationship between participation and interest as well as the prediction of participation and interest levels by developmental and social factors.

Adolescent↗
PubMed1990

Local-regional non-rhabdomyosarcomatous soft tissue sarcomas of the head and neck.

Between 1962 and 1987, 112 consecutive patients were treated at St. Jude Children's Research Hospital for soft tissue sarcomas of the head and neck region; 18 of these children (16%) had histologic subtypes other than rhabdomyosarcoma. We evaluated the impact of surgery, postoperative chemotherapy, and irradiation on local control and survival in these cases. Three patients who had complete resection of tumors and received no further treatment are alive without disease at 36, 42, and 162 months. Local control was achieved in 1 of 2 patients with microscopic residual tumor and 4 of 9 patients with gross residual tumor who were treated with irradiation (2500-5040 cGy). Chemotherapy was the only postoperative treatment in three patients; only one achieved lasting local control. One patient was treated with irradiation only; his primary site showed no tumor cells at autopsy following an automobile accident. Overall, local control was achieved in 50% of patients; the disease-free survival rate at 3 years was 44%. The prognosis for patients with nonresectable tumors remains unsatisfactory because of the difficulty in securing local control. A revised therapeutic approach to these patients is presented.

Adolescent↗
PubMed1990

Young children understanding that looking leads to knowing (so long as they are looking into a single barrel).

3 experiments were conducted to investigate the claim made by Wimmer, Hogrefe, and Perner that 3-4-year-old children do not understand that people gain knowledge about something by looking at it. The first experiment involved a simple forced-choice procedure in which children had to judge which of 2 assistants knew what was inside a box when one of the assistants had looked inside and the other had lifted it up. In this experiment, the children did realize that the assistant who had looked in the box knew its contents. The second experiment followed the Wimmer et al. procedure, but with a simpler question form. The children were just asked to state whether someone knew what was in the box. Again, the children were able to work out that a person who had looked in a box knew what was inside it. In the third experiment, a direct comparison was made between the simpler question and the more complex, double-barreled question asked by Wimmer et al. The children found the more complex question considerably harder. The results of these experiments suggest that, in contrast to the claims made by Wimmer et al., 3- and 4-year-old children do understand that looking leads to knowing, and that their difficulty in the Wimmer et al. study was mainly with the form of the question that they were asked.

Attention↗
PubMed1989

A model legal-financial education workshop for families caring for neurologically impaired elders.

A program is described through which families become acquainted with the issues, legal terminology, and resources for planning to provide and finance care to neurologically impaired elders. A survey of 68 participating families indicated over 90% had taken one or more planning actions following the workshop, including developing a specific plan for providing and financing services and developing a power-of-attorney for decision-making. Implications for other programs are discussed.

Aged↗
PubMed1989

Comparison of parent and teacher ratings of adaptive behavior of children with mental retardation.

The Adaptive Behavior Scale-School Edition was administered to 22 parents and 22 teachers, using the third party assessment method to obtain ratings of the adaptive behavior of children with mental retardation. No significant differences in parents' and teachers' ratings for Personal Self-Sufficiency, Community Self-Sufficiency, and Personal-Social Responsibility were found. Teachers and parents also did not differ significantly in ratings of the importance of the behaviors subsumed by these factors. Difficulty in rating some items reflected differences in the accessibility of these behaviors for teachers and parents. Results suggest that group differences may not exist between parents' and teachers' ratings once the method of administration and familiarity with the instrument are controlled. Occasionally, however, a parent's rating may differ from a teacher's sufficiently to lead to a different classification.

Activities of Daily Living↗
PubMed1988

Thrombolysis in Myocardial Infarction (TIMI) Trial--phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase.

Two hundred ninety patients with acute myocardial infarction were treated according to random assignment with an intravenous infusion of either 80 mg of recombinant tissue plasminogen activator (rt-PA) over 3 h or 1.5 million units of streptokinase over 1 h. Patients received an intravenous bolus of heparin (5,000 U [USP]) before pretreatment coronary angiography and a continuous infusion (1,000 U/h) starting 3 h later. The frequency of major and minor hemorrhagic events (33% rt-PA, 31% streptokinase) and associated transfusions (22% rt-PA, 20% streptokinase) were comparable in both groups. More than 70% of bleeding episodes in each group occurred at catheterization or vascular puncture sites. Precipitable fibrinogen levels, measured in plasma samples collected in the presence of a protease inhibitor (aprotinin), declined in rt-PA and streptokinase groups by averages of 26 and 57% at 3 h and by 33 and 58% at 5 h, respectively (rt-PA versus streptokinase, p less than 0.001). At 5 h the plasma plasminogen declined by 57% (rt-PA) and 82% (streptokinase) (p less than 0.001); plasma fibrin(ogen) degradation products were higher in streptokinase-treated patients (244 +/- 12 micrograms/ml, mean +/- SE) than in rt-PA-treated patients (97 +/- 9 micrograms/ml, p less than 0.001). At 27 h, plasma fibrinogen and plasminogen levels were lower and fibrin(ogen) degradation products higher than pretreatment levels in both groups. The frequency of hemorrhagic events was higher in patients with greater changes in plasma factors at 5 h; within treatment groups the levels of fibrin(ogen) degradation products correlated with bleeding complications (p less than 0.005). Thus, in the doses administered, rt-PA induces systemic fibrinogenolysis that is substantially less intense than that induced by streptokinase. The high frequency of bleeding encountered is related to the protocol used, including vigorous anticoagulation, arterial punctures and thrombolytic therapy. These findings emphasize the need for avoidance of invasive procedures and for meticulous care in the selection and management of patients subjected to thrombolytic therapy.

Clinical Trials as Topic↗
PubMed1987

Participation and interest in leisure activities by adolescent schoolchildren.

Knowledge of the leisure activities and pursuits of adolescents is important as it can provide a greater understanding of the social world of the adolescent. Further, it is necessary not only to know what adolescents actually do in their leisure time, but what they are interested in doing. In this study, the relationship between levels of participation and levels of interest in leisure activities was investigated via analysis of a comprehensive 77 item questionnaire administered to 247 adolescents. Factor analytic techniques were used to summarize the data, enabling comparisons to be made between boys and girls. Adolescents were found to engage in and be interested in activities characterised by their sex stereotyped nature, although in general none of the popular pursuits was either physically or mentally demanding. There was a high correlation between participation and interest, with adolescents participating in activities that interested them. The implications of these findings are discussed.

Adolescent↗
PubMed1987

Nocturnal cough in asthma.

The timing of nocturnal cough and its association with change in ambient temperature was documented in 11 asthmatic children, median age 5.1 years, while they were receiving continuous prophylaxis. Studies were performed in their homes on three nights. A voice activated system with electronic time signal recorded coughing. Ambient temperature was recorded every five minutes throughout the night on a Grant Squirrel data logger. Ten children coughed on 27 nights with a median of six bouts of coughing a night (range 0-272). The cough rate in the two hours after going to bed was significantly higher than the cough rate in the middle of the night (2-4 am or 4-6 am). Peak coughing times were 7-9 pm and 6-8 am. The room temperature was lowest between 5 and 7 am. There were no significant differences between cough rates during periods of rapid temperature change (more than 1 degree C an hour). The timing of nocturnal cough observed in this study differed from the known basophase of circadian cycles described for adults and children.

Asthma↗