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Biomedical subjects

J Cassidy

Publications and source records attributed to J Cassidy.

At least 145 records · Page 8Linked to original sources
PubMed1993

Pharmacokinetics of high molecular weight agents.

The various high molecular weight agents discussed in this chapter are at different stages of gestation, but as yet none have had a clear clinical impact despite many years of scientific effort. The problems that have been encountered along the way for many agents are similar: how to avoid reticuloendothelial trapping and how to achieve adequate penetration of a macromolecule into a solid tumour. The solutions offered to these problems are as diverse as the agents themselves, and, as a spin-off, our understanding of tumour cell behaviour (eg endocytosis) has improved. For many of the systems discussed, it remains unclear whether this approach is just a complex way of administering a continuous low dose infusion of the cytotoxic component. Advances in this field appear to have accelerated over the last 2-3 years, and it should not be much longer before these scientifically pleasing and elegant systems are shown to have clinical advantages over conventional cytotoxic drug delivery.

Antineoplastic Agents↗
PubMed1993

Pharmacokinetics and early clinical studies of selected new drugs.

The five examples given here illustrate new cytotoxic agents at different stages of evaluation. In all cases, considerable effort has gone into detailed pharmacokinetic studies conducted before and during the clinical phase I studies. Has this effort contributed significantly to the development of these agents? At present, it has to be said that the contribution made in the case of these particular agents has been modest. For the anthrapyrazoles, the availability of the pharmacokinetic data did not permit a pharmacokinetically guided dose escalation to be performed because of non-linear kinetics, and a similar comment can be made for rhizoxin, since the human plasma AUC values at the MTD were much lower than in the mouse. For the camptothecin analogues, a detailed knowledge of the kinetics of the closed and open forms of the various agents did not influence the way in which the studies were conducted, nor did pharmacokinetic information appreciably do so for EO9, although some comfort was gained by clinical investigators when the short half-life seen in preclinical species was also observed in humans. For suramin, therapeutic drug monitoring is clearly essential, although toxicity remains a problem. Of course, a proper understanding of the pharmacokinetics and metabolism of these agents greatly improves the interpretation of the clinical observations made and is often critical in planning the next stages of development. This is more clearly seen with agents that have unusual forms of toxicity, such as flavone acetic acid, for which the achievement of notional target concentrations is a key element in clinical trials (Kerr et al, 1987; Maughan et al, 1992). Moreover, as reviewed elsewhere (Graham and Workman, 1992; see also Graham and Kaye, this volume), there are several other instances where pharmacokinetically guided dose escalation has greatly improved the conduct of a phase I study. Good examples of this are iododoxorubicin (Gianni et al, 1990), mitotic inhibitor CI-980 (Brodfuehrer et al, 1992) and DNA intercalator CI-958 (Whitfield et al, 1992). Not surprisingly then, pharmacokinetics can help guide early clinical studies of some compounds but not others and whether they will be of value can only be determined by carrying out the pharmacokinetic measurements. The real value of the pharmacokinetic studies for the five compounds reviewed may not yet have been seen. Interpatient variations in drug handling can play a major part in determining levels of anti-tumour activity as well as toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

The role of the data manager in clinical cancer research. An opportunity for nurses.

A clinical trial is a research study conducted in humans and designed to answer specific questions using scientifically controlled methods. These trials require considerable effort to assure that the data obtained are reliable, reproducible, and readily available. Data managers play a key role in this research effort. A nurse with a clinical background, computer knowledge, and some experience in the research environment is well suited for the role of data manager. The data manager performs a variety of tasks in this position that will enhance the quality of the data gathered in a research study. These responsibilities include designing forms, monitoring protocol accrual, abstracting data, entering data onto protocol-specific forms and/or specifically designed computerized data-entry screens, assuring the quality and the integrity of the data, and providing investigators with interim and summary reports. In addition, the data manager can be responsible for the management of a computerized clinical data base system, including the training of users and the designing of basic reports for the investigators. A nurse, functioning as a data manager, who understands research methodology, is detail oriented, and is well organized, could be a valuable asset to the clinical trials team in the successful management of any clinical study.

Clinical Trials as Topic↗
PubMed1992

Phase I and pharmacokinetic study of rhizoxin.

Rhizoxin is a tubulin-binding cytotoxic compound, isolated from the fungus Rhizopus chinensis, with significant antineoplastic activity in several murine and human tumor models. In this Phase I study, the drug was administered by i.v. bolus injection at 3-wk intervals. Twenty-four patients with refractory solid tumors were treated; 60 courses of rhizoxin were given, at doses ranging from 0.8 to 2.6 mg/m2. Grade 3 mucositis, Grade 4 leukopenia, and Grade 3 diarrhea were dose limiting but reversible at 2.6 mg/m2, the maximum tolerated dose for both previously untreated and heavily pretreated patients. Alopecia and moderate discomfort at the injection site occurred at all doses. Other sequelae, including peripheral neuropathy, phlebitis, and nausea and vomiting, were sporadic and mild. Two heavily pretreated patients with recurrent breast cancer had minor responses to rhizoxin, one at 1.6 mg/m2 and the other at 2.6 mg/m2. Plasma concentrations of rhizoxin were measured by high-performance liquid chromatography. The drug was not detectable (less than 5 ng/ml) at doses of 0.8 mg/m2 and 1.6 mg/m2 and was not measurable 10 min after injection at 2.0 mg/m2. At 2.6 mg/m2, there was considerable intersubject variation in the plasma concentration-time profiles; the area under the curve ranged from 0.29 to 0.96 microgram/ml.min. Rhizoxin has shown some clinical activity in this Phase I study, and a dose of 2.0 mg/m2 is recommended for Phase II studies using this schedule.

Adult↗
PubMed1992

Case report: superior vena cava obstruction complicated by central venous thrombosis--treatment with thrombolysis and Gianturco-Z stents.

Expandable wire stents can provide effective palliation of superior vena cava obstruction (SVCO). We describe a case of SVCO unresponsive to radiotherapy and chemotherapy, which was complicated by extensive central venous thrombosis. Successful thrombolysis occurred with low-dose streptokinase allowing subsequent stent placement.

Brachiocephalic Veins↗
PubMed1992

The changing role of surgery in metastatic non-seminomatous germ cell tumour.

In the last 2 years (1989-1990) we have treated a total of 53 patients with metastatic nonseminomatous germ cell tumours (teratoma). In ten cases surgery to remove residual abdominal masses was required on completion of chemotherapy and normalisation of tumour markers (HCG and AFP). In a further three patients with large intra-abdominal masses and little or no other sites of disease surgery was performed as a therapeutic intervention, in the context of plateauing or rising tumour markers despite intensive chemotherapy. In all three, this approach resulted in a rapid fall in tumour markers, and following further chemotherapy all three remain disease free at 7, 12 and 25 months. For this small sub-group of patient failing to respond to chemotherapy who have resectable lesions, interventional surgery should be considered as part of a combined approach to treatment.

Adult↗
PubMed1992

Loneliness and peer relations in young children.

Recent studies indicate that feelings of loneliness and social dissatisfaction can be reliably assessed with third- through sixth-grade children, and that children who are sociometrically rejected by their peers are significantly more lonely than other children. The present research was designed (a) to examine whether loneliness could be reliably assessed in a population younger than previously studied, (b) to learn whether young children who are poorly accepted by peers report elevated levels of loneliness and social dissatisfaction, (c) to assess whether young children understand the concept of loneliness, and (d) to examine the behavioral characteristics of lonely young children. Kindergarten and first-grade children (N = 440) responded to a questionnaire about feelings of loneliness and social dissatisfaction in school. A subset of children (N = 46) were individually interviewed to assess their understanding of loneliness. To assess sociometric status and behavior, peers were asked to respond to various sociometric measures and behavioral assessment items. Teachers also provided behavioral information about children using a newly developed instrument. Results indicated that nearly all children understood loneliness, that loneliness was reliably assessed in young children, and that poorly accepted children were more lonely than other children. In addition, children who reported the most loneliness were found to differ from others on several behavioral dimensions.

Age Factors↗
PubMed1992

Family-peer connections: the roles of emotional expressiveness within the family and children's understanding of emotions.

The purpose of this study was to explore patterns of parent and child emotional expressiveness within the family context, to examine links between these patterns and children's peer relations, and to examine whether these links might be mediated by children's understanding of emotions. Subjects were 61 kindergarten and first-grade white, middle-class children and their parents. Parent and child expressiveness were assessed in a laboratory ring-toss game designed to elicit a range of emotional responses. Parent expressiveness in the home was also assessed with Halberstadt's Family Expressiveness Questionnaire. The questionnaire, completed by both mother and father, assesses a range of emotions in a variety of settings typical of many families, and consists of items tapping both positive and negative expressiveness. Children were interviewed about their understanding of emotions across a broad range of areas. Results indicated that maternal expressiveness (home) and paternal expressiveness (home and laboratory) but not children's expressiveness with parents were associated with children's peer relations. Although children's understanding of emotions was generally not associated with family expressiveness, understanding predicted children's peer relations. In addition, children's understanding influenced the links between maternal expressiveness in the home and peer relations and between paternal expressiveness in the laboratory and peer relations. This pattern of results underscores the importance of the emotional climate of the family for the development of children's social relations with peers.

Child↗
PubMed1992

Ondansetron compared with metoclopramide in the control of emesis and quality of life during repeated chemotherapy for breast cancer.

This was a multicentre, randomised, double-blind, parallel-group study which included female breast cancer patients, receiving their first of 6 scheduled courses of chemotherapy (cyclophosphamide greater than or equal to 500 mg/m2). Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide. On day 1 of their first course of treatment 91 and 60% of patients in the ondansetron and metoclopramide groups respectively were free of emesis (p less than 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p less than 0.001). The results for nausea also revealed highly statistically significant treatment differences (p less than 0.001) in favour of ondansetron for both day 1 and day 1-5 analyses of the first treatment course. Over the series of courses, 67% of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day, compared with 28% of patients receiving metoclopramide (p less than 0.001). A similar analysis for nausea revealed that 49% of patients receiving ondansetron completed all 6 courses with 'none' or 'mild' nausea compared with 27% of patients receiving metoclopramide (p less than 0.001). These differences were reflected in quality of life data (Rotterdam Symptom Checklist). After the first course of treatment, a statistically significant improvement (p = 0.002) in the psychological subscale scores was observed after ondansetron compared with metoclopramide. No differences were observed in the physical or functional activity subscales after the first course. However, the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores (p less than 0.001) as well as trends in favour of ondansetron in the physical (p = 0.096) and functional activity (p = 0.056) subscales. Extrapyramidal symptoms were reported in 19% of patients in the metoclopramide group and resulted in 15% of patients withdrawing from their randomised anti-emetic schedule, either during or between treatment courses. Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment. In conclusion, this study shows that ondansetron is significantly superior to metoclopramide (each with a single pre-treatment dose of dexamethasone) in the control of emesis over 6 courses of chemotherapy for breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Perceptions of new AICPA (American Institute of Certified Public Accountants) audit guide.

A survey was conducted by authors Bitter and Cassidy to assess hospital providers' and auditors' perceptions of the reporting requirements of the new Audits of Providers of Health Care Services guide published by the American Institute of Certified Public Accountants. Responses indicated that there is still much dissent in the healthcare community as to what is useful information and what the effects of the new guide will be on hospital providers, auditors, and users.

Accounting↗