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Biomedical subjects

J Cassidy

Publications and source records attributed to J Cassidy.

At least 181 records · Page 10Linked to original sources
PubMed1989

Phase I clinical and pharmacokinetic study of LY 195448.

LY 195448 is a phenethanolamine that has shown anti-tumour activity in a range of murine tumour models, although its mechanism of action is unknown. Pre-clinical studies have indicated the absence of "standard" side effects such as myelosuppression and gastrointestinal toxicity. The present phase I trial was carried out in nine patients at doses ranging up to 133 mg/m2. The major toxicities up to that dose were mild, reversible hypotension, tachycardia and tremor. No haematological or biochemical toxicity was observed. Murine pharmacokinetics were assessed at a dose level that was effective in experimental tumours and compared with human pharmacokinetic parameters derived from this study. The results indicated the clinical possibility of reaching peak drug levels associated with experimental activity. However, no responses were seen at the doses used. This study was terminated prior to its completion due to an unexplained loss of activity against murine tumours since September 1987. No significant loss of the in vitro anti-mitotic activity originally reported by Boder et al. [3] was observed. Possible reasons for the apparent loss of in vivo activity have been intensively investigated, but no cause has been determined. Therefore, clinical trials with LY 195448 have been discontinued.

Adult↗
PubMed1989

Could interspecies differences in the protein binding of flavone acetic acid contribute to the failure to predict lack of efficacy in patients?

We investigated the differences in plasma protein binding of flavone acetic acid (FAA) in mice and men in an attempt to explain the inter-species differences in response. In vitro data indicate both qualitative and quantitative differences in FAA protein binding: approximately 80% is bound in humans, with two different types of binding site identified; in mice, 70% is bound and only one binding site could be described. Protein binding is dose-dependent in both species. Plasma samples from 20 patients receiving FAA showed that most achieved levels that would be active in mice. We conclude that these differences in protein binding are insufficient to explain totally the observed differences in response.

Animals↗
PubMed1989

Herpes simplex virus, Candida albicans and mouth ulcers in neutropenic patients with non-haematological malignancy.

Mouth ulcers are a frequent cause of morbidity in patients rendered neutropenic as a result of chemotherapy. We report here a series of 28 such patients from whom swabs were taken for viral isolation and mycological culture. In 13 patients, herpes simplex virus (type I) was isolated and in 17 patients Candida albicans was cultured. Both organisms were isolated in 9 patients. Our results suggest that both a viral and fungal element may be important in the aetiology of oral ulceration and that antiviral and antifungal agents may each have a role in the prophylaxis and treatment of such patients.

Agranulocytosis↗
PubMed1989

Hypersensitivity reaction to epirubicin.

A patient with metastatic breast cancer treated with epirubicin (Pharmorubicin) developed a severe urticarial reaction which progressed to ulceration following possible sensitisation to the drug by preceding extravasation.

Bone Neoplasms↗
PubMed1988

Flavone acetic acid: a nonlinear pharmacokinetic model.

Flavone acetic acid pharmacokinetics were studied in 31 patients in a phase I clinical trial. The drug was given by i.v. infusions over 1, 1.5, 3, and 6 h at doses ranging from 0.5 to 6.4 g/m2. The pharmacokinetic parameters were determined according to a nonlinear model including Michaelis-Menten-type kinetics. The mean elimination half-life is 4.8 h and the mean volume of distribution of the central compartment, 7.61. Our model predicted a maximal tolerated dose (MTD) of 11.1 g/m2 on the basis of the "therapeutic window" concept, very close to the clinically observed MTD of 10 g/m2. This model is also operational when different protocols of inoculation are considered, such as a divided-dose schedule vs a unique infusion, and indicates that, at the MTD, injections should be made every 72 h to avoid drug accumulation.

Algorithms↗
PubMed1988

Cardiotoxicity of mitozantrone assessed by stress and resting nuclear ventriculography.

Fourteen patients with advanced breast cancer were treated with a combination of vincristine, mitozantrone and prednisolone. Before, during and after cessation of treatment radionuclide assessment of ventricular performance was obtained at rest, in response to cold pressor-induced stress and on recovery from stress. Six of 14 patients (46%) developed abnormalities of left ventricular ejection fraction (LVEF). One patient developed clinical signs of cardiac failure. Mitozantrone is an active agent in the treatment of advanced breast cancer but it can produce cardiotoxicity. In this particular middle-aged population, changes in LVEF occurred over a wide range of cumulative doses. Further investigation is required to determine the nature and prognosis of this iatrogenic toxicity.

Adult↗
PubMed1988

Pharmacokinetics and anti-emetic efficacy of BRL43694, a new selective 5HT-3 antagonist.

Twenty patients receiving a variety of emetogenic cytotoxics (including cisplatin in 5) were given a single i.v. infusion of 40 micrograms kg-1 of BRL43694 (as the hydrochloride salt) in successive groups of 3-4 patients between 0-6 hours after chemotherapy. Eleven patients were completely protected from vomiting; 9 had mild to moderate nausea and vomiting, but none severe enough to require alternative anti-emetic 'rescue'. In 4 of the patients in whom BRL43694 was delayed until 4-6 h after chemotherapy, vomiting had already begun; in each case immediate termination of vomiting occurred when BRL43694 was infused. No adverse effects attributable to the anti-emetic were observed. Mean pharmacokinetic parameters in 14 patients in whom plasma assay data are available were: Maximum observed concentration = 30.7 ng ml-1; terminal phase half-life = 8.96 h; total body clearance = 0.376 (1 h-1) kg-1; apparent volume of distribution = 2.85 l kg-1. This study shows BRL43694 to be an effective and well tolerated anti-emetic. Further studies aimed at defining an optimal dose and schedule for use against the most emetogenic cytotoxics are in progress.

Adolescent↗
PubMed1988

Family members as third parties in dyadic family conflict: strategies, alliances, and outcomes.

Systems theorists have argued that triads rather than dyads need to be considered as a basic interaction unit, particularly in regard to episodes of conflict. While theoretically appealing, the description of the strategies used and alliances formed when third parties intervene in dyadic conflict presents a number of conceptual and empirical challenges. In the present report, a reliable system for coding such third-party participation in verbal conflicts is described and is used to analyze routine family conflicts that were observed during dinner. A number of specific findings of interest are reported, including that girls were more likely than boys to intervene in all family disputes except marital conflicts, that mothers and fathers rarely sided against each other when intervening as third parties, and that the third-party strategies most commonly used corresponded with family roles: fathers used authority strategies, mothers used mediational tactics, and children used distraction. Of greater importance, however, are the general findings that document the influence of third parties on dyadic conflict. Additional family members frequently joined dyadic family conflicts, they were about equally likely to attempt to end or to continue the conflict, they formed alliances about half of the time, and their intervention strategies were related to the outcome of the conflict as well as its patterning.

Adolescent↗
PubMed1988

Child-mother attachment and the self in six-year-olds.

Bowlby has proposed that child-parent attachment is important in the child's representation of self. In this study, the child's representation of self was examined in connection with child-mother attachment in a sample of 52 white, middle-class 6-year-olds. Children were seen in 2 play sessions, 1 month apart. Quality of attachment was assessed in each session based on the child's behavior on reunion following a laboratory separation of approximately 1 hour, using a system devised by Main and Cassidy. Aggregated attachment ratings and classifications were assigned based on the child's behavior in both reunions. Assessments of the self consisted of (a) assessment of the self within the relationship with the attachment figure (an incomplete doll stories procedure), (b) assessment of the child's perceptions of how an unspecified "other" views him or her (a puppet interview), (c) direct assessment of global self-esteem independent of the attachment relationship (the subscale of global self-esteem from Harter's Perceived Competence Scale for Children), (d) a second direct assessment of global self-esteem (an interview with the child), and (e) assessment of feelings of competence and acceptance in specific domains that may be precursors of self-esteem (Harter's Scale of Perceived Competence and Social Acceptance for Young Children). Significant, albeit modest, connections between attachment and the self were established; furthermore, specific patterns of self-perceptions were related to particular patterns of attachment.

Adult↗