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Biomedical subjects

M B Harris

Publications and source records attributed to M B Harris.

159 records · Page 9Linked to original sources
PubMedDate not supplied

Topotecan in pediatric patients with recurrent and progressive solid tumors: a Pediatric Oncology Group phase II study.

PURPOSE: A phase II study was designed to determine the efficacy of topotecan, an inhibitor of topoisomerase I, in the treatment of patients with progressive or recurrent pediatric extracranial solid tumors (STs). PATIENTS AND METHODS: Patients younger than 21 years at the time of initial diagnosis with refractory STs were treated with 2 mg/m2 topotecan given by 30-minute infusions for 5 days repeated every 3 weeks. Granulocyte colony stimulating factor (G-CSF) was added to the regimen only after occurrence of severe neutropenia or therapy delay due to sustained neutropenia. RESULTS: One hundred forty-one patients were treated with 539 courses of topotecan. Responses were seen in 34 patients (3 had complete responses [CRs], 2 had partial responses [PRs], and 24 had minor responses [MRs] or stable disease [SD]). The number of administered courses in patients with SD varied between 5 and 24, with a median of 10. The median time on the study for patients with SD was approximately 8.5 months. In patients without bone marrow involvement, the most frequent toxicity was myelosuppression: hemoglobin < 8 g/dl in 83 of 341 courses, absolute granulocyte count < 1,000/microl in 221 of 341 courses, and platelet count < 50,000/microl in 162 of 341 courses. Nausea and vomiting were infrequent; many patients were pretreated with ondansetron or granisetron. A recurrent rash developed in 16 patients and was usually well controlled with diphenhydramine and hydrocortisone. G-CSF was administered in 203 of 539 courses because of neutropenia. Therapy was delayed over 1 week in 33 instances. CONCLUSION: In previously treated patients, topotecan produced CRs and PRs in patients with neuroblastoma, Ewing's tumor, and retinoblastoma. In hepatoblastoma, rhabdomyosarcoma, and a few rare tumors, long-lasting MRs and SDs with excellent symptom control were seen. The toxicity of topotecan, predominantly myelosuppression, was tolerable.

Adolescent↗
PubMedDate not supplied

Phase II trial of pyrazoloacridine in children with solid tumors: a Pediatric Oncology Group phase II study.

PURPOSE: Pyrazoloacridine (PZA), a rationally synthesized deoxyribonucleic acid (DNA) binding agent that preferentially inhibits ribonucleic acid rather than DNA synthesis, is active against hypoxic and noncycling tumor cells and has greater in vitro activity against a broad range of human solid tumor lines than against the L1210 murine leukemia line. The Pediatric Oncology Group conducted a phase II study to determine the activity of PZA administered as a 3-hour infusion. PATIENTS AND METHODS: The activity of PZA was evaluated in patients with a variety of childhood solid tumors including rhabdomyosarcoma, Ewing sarcoma/peripheral neuroectodermal tumor, neuroblastoma, osteogenic sarcoma, Wilms tumor, or other solid tumors (excluding brain tumors). In addition to a standard three-stage design to test the drug's activity in each tumor type, a global stopping rule was used such that if no complete or partial responses (CR or PR) occurred in the first 35 patients (pooled across all strata except "other"), the study would be closed. RESULTS: A total of 47 patients were entered into the study. Myelosuppression was the primary toxicity. Severe nonhematologic toxicity was uncommon. Only one patient exhibited grade 3 neurologic toxicity (anxiety). No CRs or PRs were observed. CONCLUSION: Use of the global stopping criterion permitted early identification of lack of activity of PZA against childhood solid tumors.

Acridines↗
PubMedDate not supplied

Paclitaxel for the treatment of progressive or recurrent childhood brain tumors: a pediatric oncology phase II study.

PURPOSE: To assess the efficacy and define the toxicity of paclitaxel given at a dosage of 350 mg/m2 every 3 weeks as a 24-hour continuous infusion to children with recurrent or progressive primary brain tumors. PATIENTS AND METHODS: Seventy-three eligible patients, ages 4 months to 19 years, with progressive or recurrent primary brain tumors were treated according to a Pediatric Oncology Group (POG) phase II protocol with paclitaxel (POG 9330). Tumor histologic strata included: astrocytoma (n = 4), malignant glioma (n = 13), medulloblastoma (n = 16), brain stem glioma (n = 15), ependymoma (n = 13), and miscellaneous histologies (n = 12). All patients had previous histologic confirmation of a primary intracranial or spinal cord tumor with magnetic resonance imaging or computed tomography documentation of unequivocally measurable progressive or recurrent disease. All patients had received previous therapy including surgery, radiation therapy, and/or chemotherapy, but no patient had been previously treated on more than one phase II trial. Paclitaxel was administered as a 24-hour intravenous infusion at a dosage of 350 mg/m2 every 3 weeks. Neurologic and neuroradiologic reevaluations were performed after every second course. Patients were allowed to continue therapy for a total of 18 cycles in the absence of progressive disease or unacceptable toxicity. RESULTS: Seventy-five patients were enrolled onto the POG 9330 protocol; two ineligible patients were removed from the study before receiving any therapy. Of the 73 eligible patients, 72 were evaluable for toxicity and 70 were either fully or partially evaluable for disease response. There was one complete response and three partial responses (5.7%). Twenty patients had stable disease for more than 2 months. Toxicities included mild nausea, central nervous system toxicity, myelosuppression, and febrile neutropenia, including one septic death. One grade 2 and two grade 3 allergic reactions occurred. No cardiac toxicities or arthralgias were reported. CONCLUSION: Paclitaxel is well tolerated in children with recurrent or progressive brain tumors at this dosage and schedule and may result in short-term disease stabilization in this patient population. The lack of a significant number of patients with measurable disease regression, however, precludes it from being identified as an active agent when administered as a single agent by 24-hour continuous infusion.

Adolescent↗
PubMedDate not supplied

Presurgical window of carboplatin and surgery and multidrug chemotherapy for the treatment of newly diagnosed metastatic or unresectable osteosarcoma: Pediatric Oncology Group Trial.

PURPOSE: Relapse remains a significant problem in patients with metastatic osteosarcoma. The response to carboplatin of patients with newly diagnosed metastatic or unresectable osteosarcoma was assessed in an upfront phase II window, which was followed-up by surgery and intensive multiagent chemotherapy. PATIENTS AND METHODS: Thirty-seven patients, ages 3 to 23 years with histologically confirmed diagnoses of osteosarcoma, were treated between January 1992 and November 1994 with carboplatin 1,000 mg/m2 per dose administered as a 48-hour continuous infusion. Two courses were administered in 3-week intervals, depending on marrow recovery. After radiographic reevaluation, patients underwent surgical removal of tumor (if feasible) and then 40 weeks of chemotherapy with high-dose methotrexate, ifosfamide, doxorubicin, and cisplatin. RESULTS: One of the 37 evaluable patients demonstrated a partial response to carboplatin; there were no complete responses. Patients were additionally analyzed by the response of pulmonary metastases to therapy and the extent of tumor necrosis of the primary lesion. By these criteria, 8 of 37 (22%) of patients showed a response at one or more sites, whereas 20 of 37 (54%) had unequivocal disease progression. Severe myelosuppression was the major toxicity. The projected 3-year event-free and overall survival rates were 23.9% and 31.9%, respectively. Only 1 of 17 patients with unresectable disease or distant bone metastases remains alive, in contrast to 6 of 17 patients with the lung as their only metastatic site and two of three patients with resected regional bone metastases. CONCLUSIONS: Continuous-infusion carboplatin demonstrated limited activity as an upfront agent in patients with metastatic osteosarcoma at diagnosis, even at doses that result in severe and prolonged myelosuppression. Patients with isolated pulmonary metastases or resectable bone metastases have a longer median survival time and greater chance of long-term survival than do patients with unresectable bone disease, for whom the prognosis remains dismal.

Adolescent↗
PubMedDate not supplied

Cost of skin care in the myelomeningocele population.

This study was undertaken to illustrate the magnitude of the skin breakdown problem in children with myelomeningocele. Seventy-five of the 650 spina bifida patients treated at the Newington Children's Hospital during a 13-year period comprised our final study group. The criterion for inclusion was hospitalization solely for treatment of skin breakdown. Multiple parameters were reviewed. Skin breakdown remains prevalent in this patient population, despite significant improvements in patient care. These improvements are readily demonstrated by (a) an increase in age at time of admission, (b) a significant reduction in average length of hospital stay, and (c) more aggressive admission policies with earlier operative intervention. More than two million dollars and the equivalent of 17 years in hospital days were needed to treat these patients during the 13-year study period.

Adolescent↗
PubMedDate not supplied

Gay and lesbian parents.

An anonymous survey of 23 gay and lesbian parents and 16 heterosexual single parents was conducted in order to see whether the parents' homosexuality created special problems or benefits or both, for their children. Both sets of parents reported relatively few serious problems and generally positive relationships with their children, with only a minority encouraging sex-typed toys, activities, and playmates. Heterosexual parents made a greater effort to provide an opposite-sex role model for their children, but no other differences in their parenting behaviors were found. Gay and lesbian parents saw a number of benefits and relatively few problems for their children as a result of their homosexuality, with lesbians perceiving greater benefits than gay men. Conversely, the gay males reported greater satisfaction with their first child, fewer disagreements with their partners over discipline, and a greater tendency to encourage play with sex-typed toys than did the lesbians. The findings suggest that being homosexual is clearly compatible with effective parenting and is not a major issue in parents' relationships with their children.

Adult↗
PubMedDate not supplied

Measuring knowledge of school-based occupational therapy.

OBJECTIVE: The primary purpose of this study was to develop a measure of Knowledge of Occupational Therapy in School settings (KNOTS) for occupational therapy students. A secondary purpose was to develop a scale of Self-Efficacy in School Settings (SESS) for occupational therapy students. METHOD: One hundred forty-five university students enrolled in either occupational therapy classes or education classes completed a questionnaire consisting (in part) of the 60-item KNOTS scale and the SESS scale. Analyses of internal reliability, group comparisons, and correlations were computed on the scores. RESULTS: The reliabilities of the KNOTS (.85) and SESS (.94) were reasonably high. Occupational therapy students performed significantly better than did education students, and senior occupational therapy students scored significantly higher than did juniors on the KNOTS. SESS scores were positively but not significantly correlated with KNOTS scores. CONCLUSION: If further investigation provides additional evidence for the reliability and validity of the KNOTS and SESS, both measures have a number of potential practical applications.

Adult↗
PubMedDate not supplied

Comparison of stress and coping in male and female dentists.

This study was designed to examine how female dentists withstand the pressures of dental practice in comparison to male dentists. Two-hundred thirty-eight dentists responded to a national survey that collected demographic data, information about the kinds and degree of stress experienced, coping strategies used and coping effectiveness. The greatest amount of stress experienced was attributed to interactions with patients. The business aspects of dentistry were also associated with significant amounts of stress. In general, male and female dentists' responses to stress were similar, although female dentists experienced more personal/domestic stress. The coping styles of males and females were similar in most respects, except that females were more inclined to discuss their problems. Coping strategies were seen as moderately effective by both sexes. It was suggested that dental students receive training in interpersonal skills, stress management and practice management along with technical training to better prepare them to cope with the realities of dental practice. An alternative suggestion was to address these nontechnical topics through continuing education programs designed for dentists beginning their practice.

Adaptation, Psychological↗
PubMedDate not supplied

Stress and health problems in dentists.

Dental literature has suggested that dentists are particularly vulnerable to health problems due to stress associated with dental practice. However, much of the literature on this subject has been based on anecdotes or opinions rather than systematic research. This study provides current data based on a national sample of 238 dentists. The study compared the degree of stress experienced by male and female dentists and their ability to cope with stress, and then related stress and coping to various somatic and psychologic health problems, workdays missed, and alcohol and drug use. Results indicated that, in general, dentists were reasonably healthy and missed few days of work because of illness. Male and female dentists seemed about equally vulnerable to health problems, although women reported more headaches. Most dentists used alcohol and/or drugs in moderation, but men were more likely to consume alcohol. Both sexes used alcohol more frequently than other drugs.

Adult↗
PubMedDate not supplied

Controlling receptor-ligand contact to examine kinetics of T cell activation.

A method for controlling the contact of cell-surface receptors with immobilized ligands has been developed. Cells are trapped in an asymmetric liquid film that can be quantitatively thinned by reducing the film's capillary pressure. Ligands adsorbed to the liquid-solid interface are forced into increasingly tighter contact with the cells as the air-liquid interface is drawn down. Controlling the degree of thinning allows study of repulsive forces, and controlling its time course produces a definite time 0 for analyzing signal transduction. This system was tested by examining the time course of calcium mobilization in T cells upon activation with anti-CD3 antibody at different dilutions and ionic strengths. The averaged calcium transient of the responding cells was essentially the same for each condition. However, the fraction of responding cells decreased with anti-CD3 dilution, and indicated that the critical ligand density for T cell activation lies between approximately 35 and 70 molecules of anti-CD3 per microm2. Decreasing the medium's ionic strength from the normal value of 157 mM to 57 mM did not affect either the average calcium response profile or the fraction of responding cells, but strongly affected receptor-ligand contact, decreasing the percent of spontaneous activation from 38% to 5%. Such an imposed decrease sets the stage for film thinning to impose much greater control of receptor-ligand contact.

Animals↗