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Biomedical subjects

S Cooley

Publications and source records attributed to S Cooley.

14 recordsLinked to original sources

Study of ovarian cancer management.

Ovarian cancer is the most lethal gynecological malignancy. Many patients present at an advanced stage as the symptoms of early stage disease can be vague. AIM We evaluated the demographics, treatment regimens and survival rates of ovarian cancer patients attending Beaumont Hospital Dublin over a nine year period. A retrospective chart review of ovarian cancer patients attending Beaumont Hospital between 11/10/94 and 30/6/3 was performed. Patients were selected from pathology records. Patients with borderline histology and those who died of unrelated causes were excluded. 31% of individuals presented with distension as their only clinical sign. 20% presented with a mass as their only clinical sign. The most common cell type was papillary serous adenocarcinoma in two thirds of cases. 54% presented with advanced disease [stage IIl-IV]. Treatment involved surgical clearance or debulking +/- chemotherapy. 5 year survival for Stage I was 95% versus 19% for Stage IlI. This highlights the importance of early diagnosis.

Adult↗

Signal amplification by rolling circle amplification on DNA microarrays.

While microarrays hold considerable promise in large-scale biology on account of their massively parallel analytical nature, there is a need for compatible signal amplification procedures to increase sensitivity without loss of multiplexing. Rolling circle amplification (RCA) is a molecular amplification method with the unique property of product localization. This report describes the application of RCA signal amplification for multiplexed, direct detection and quantitation of nucleic acid targets on planar glass and gel-coated microarrays. As few as 150 molecules bound to the surface of microarrays can be detected using RCA. Because of the linear kinetics of RCA, nucleic acid target molecules may be measured with a dynamic range of four orders of magnitude. Consequently, RCA is a promising technology for the direct measurement of nucleic acids on microarrays without the need for a potentially biasing preamplification step.

Alleles↗

Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu.

Treatment of advanced breast cancer with autologous stem cell transplantation is limited by a high probability of disease relapse. In clinical trials, interleukin 2 (IL-2) alone can expand natural killer (NK) cells in vivo and increase their cytotoxic activity against breast cancer cell lines, but this increase is modest. Understanding the mechanisms that mediate NK cell lysis of breast cancer targets may lead to improvements of current immunotherapy strategies. NK cells from normal donors or patients receiving subcutaneous IL-2 were tested in cytotoxicity assays against five breast cancer cell lines. The role of adhesion molecules and antibodies that interact through Fc receptors on NK cells was explored. NK cell lysis of breast cancer targets is variable and is partially dependent on recognition through ICAM-1 and CD18. While blocking CD2 slightly decreased cytotoxicity, contrary to expectations, an antibody against CD58 (the ligand for CD2), failed to block killing and instead mediated an increased cytotoxicity that correlated with target density of CD58. The CD58 antibody-enhanced killing was dependent not only on FcRgammaIII but also on CD2 and ICAM-1/CD18. To further elucidate the mechanism of this CD58 antibody-dependent cellular cytotoxicity (ADCC), another antibody was tested. Trastuzumab (Herceptin), a humanized antibody against HER2/neu, mediated potent ADCC against all the HER2/neu positive breast cancer targets. Unlike CD58 antibody-mediated ADCC, Herceptin ADCC was minimally affected by blocking antibodies to CD2 or ICAM-1/CD18, which suggests a different mechanism of action. This study shows that multiple mechanisms are involved in NK cell lysis of breast cancer targets, that none of the targets are inherently resistant to killing, and that two distinct mechanisms of ADCC can target immunotherapy to breast cancer cells.

Antibodies↗

Three-year trials of personal therapy among schizophrenic patients living with or independent of family, I: Description of study and effects on relapse rates.

OBJECTIVE: The study of individual psychotherapeutic approaches to the treatment of schizophrenia has yielded equivocal findings, partly because of methodologic problems. Further, the ability of psychosocial treatments to prevent psychotic relapse appears to lessen over time. The authors' goal was to develop and test a demonstrably effective individual therapy for schizophrenia. METHOD: Using a study design that addressed previous methodologic issues, the authors evaluated personal therapy specifically designed to forestall late relapse in patients with schizophrenia. They evaluated the effectiveness of personal therapy over a period of 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder diagnosed according to Research Diagnostic Criteria. The patients were randomly assigned to receive either personal therapy or contrasting therapies in one of two concurrent trials. One trial studied patients who were living with family (N = 97); the other studied patients who were living independent of family (N = 54). RESULTS: All of the patients had extensive psychiatric histories, but only 44 (29%) experienced recurrent psychotic episodes over the 3-year study period, and only 27 (18%) prematurely terminated the study; most of those who left the study were in the no-personal-therapy conditions. Among patients living with family, personal therapy was more effective than family and supportive therapies in preventing psychotic and affective relapse as well as noncompliance. However, among patients living independent of family, those who received personal therapy had significantly more psychotic decompensations than did those who received supportive therapy. CONCLUSIONS: Personal therapy had a positive effect on adverse outcomes among patients who lived with family. However, personal therapy increased the rate of psychotic relapse for patients living independent of family. The application of personal therapy might best be delayed until patients have achieved symptom and residential stability.

Adolescent↗

Three-year trials of personal therapy among schizophrenic patients living with or independent of family, II: Effects on adjustment of patients.

OBJECTIVE: Previous analyses of the personal and social adjustment of outpatients with schizophrenia have either relied on the assessment of unrepresentative patients who survived without relapse or used analyses that included relapse assessments, a potential confound when different rates of relapse existed among treatment conditions. The authors' goal was to conduct a study of the effects of personal therapy on outcome that was designed to take into consideration the effects of relapse. METHOD: They evaluated the effectiveness of personal therapy over 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder. The patients were randomly assigned to receive personal therapy or contrasting therapies in one of two concurrent trials. One trial included patients who were living with family (N = 97); the other included patients who were living independent of family (N = 54). Patients were assessed at 6-month intervals over 3 years of treatment on measures of personal and social adjustment; patients who relapsed and restabilized and those who did not relapse were included. RESULTS: Personal therapy had positive effects on broad components of social adjustment (role performance) but had few differential effects on symptoms, and patients receiving personal therapy remained more anxious than patients who received family or supportive therapy. For patients who were living with family, personal therapy led to better outcomes in overall performance than did the other treatments. Although family therapy had only one positive effect on patients' social adjustment, the personal adjustment (residual symptoms) of patients who received family therapy appeared to improve more than that of patients receiving personal or supportive therapy. For patients not living with family, personal therapy was more successful than supportive therapy in improving work performance and relationships out of the home. Longitudinal effects of personal therapy on symptoms were similar to those of family and supportive therapies, particularly in the first 2 years, but personal therapy effect sizes increased over time on measures of social adjustment. CONCLUSIONS: Personal therapy has pervasive effects on the social adjustment of patients with schizophrenia that are independent of relapse prevention. Supportive therapy, with or without family intervention, produces adjustment effects that peak at 12 months after discharge and plateau thereafter. However, personal therapy, a definitive psychosocial intervention, continues to improve the social adjustment of patients in the second and third years after discharge. Brief treatment would appear to be less effective than a long-term, disorder-relevant intervention for schizophrenia.

Adaptation, Psychological↗

A model of time-effective group psychotherapy for patients with personality disorders: the clinical model.

This article describes a model of time-limited psychotherapy for patients with personality disorders that emphasizes the group as a social microcosm. The patient population described is relatively high functioning, although the majority of the group members meet DSM-III-R (American Psychiatric Association, 1987) criteria for an Axis II diagnosis. The clinical model's key theoretical concepts, for example, interpersonal focus; active therapist stance; emphasis on group interaction and processes; use of time limits; primary care/intermittent treatment philosophy; and emphasis on patients' strengths, goals, and resources are described. The relationships between the phases of group therapy and the key theoretical concepts are delineated.

Adult↗

Pharmacotherapy of impaired affect in recovering schizophrenic patients.

BACKGROUND: Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken. METHODS: In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks. RESULTS: For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression. CONCLUSION: Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature.

Adolescent↗

Personal therapy: a disorder-relevant psychotherapy for schizophrenia.

While the long-term care of ambulatory schizophrenia patients requires highly effective interpersonal treatment skills among clinicians, there is little evidence to support an empirically validated individual psychotherapy of schizophrenia. Personal therapy (PT) attempts to address the apparent limitations of traditional psychotherapy by modifying the "model of the person" to accommodate an underlying pathophysiology, minimizing potential iatrogenic effects of maintenance antipsychotic medication, controlling sources of environmental provocation, and extending therapy to a time when crisis management has lessened and stabilization is better ensured. By means of graduated, internal coping strategies, PT attempts to provide a growing awareness of personal vulnerability, including the "internal cues" of affect dysregulation. The goals are to increase foresight through the accurate appraisal of emotional states, their appropriate expression, and assessment of the reciprocal response of others. The strategies are supplemented by phase-specific psychoeducation and behavior therapy techniques. Practical issues in the application of this new intervention are discussed. Preliminary observations from two samples of patients, one living with and the other living independent of family, suggest differential improvement over time among PT recipients.

Activities of Daily Living↗

The metabolizable energy value of Polydextrose in a mixed diet fed to rats.

The digestible energy (DE) and metabolizable energy (ME) values of a commercial Polydextrose product and the polymer that it contained were determined by metabolic energy balance in male Wistar rats and compared with values obtained by radiochemical balance using a radiochemical analogue. The energy values of the whole preparations and of the polymer fractions were estimated. In the energy-balance study of 6 d duration, 100 g maize starch/kg control diet were replaced by Polydextrose to provide a test diet. Polydextrose had no significant effects on food intake, body-weight gain, digestibility of nitrogen and N retention but significantly increased the water consumption to 143% of the control value (P less than 0.05) and the water content of fresh faecal pellets from 548 (SE 10) to 646 (SE 15) g/kg wet weight (P less than 0.01). By energy balance the DE in the Polydextrose product and in the polymer that it contained were 13.5 and 12.8 (SE 1.9) kJ/g respectively. The corresponding ME values were 12.7 and 12.1 (SE 1.8) kJ/g respectively. These values were higher (P less than 0.05) than the corresponding values obtained by the radiochemical balance procedure: DE 8.8 and 8.6 (SE 0.4) kJ/g polymer respectively and ME 8.0 and 7.8 (SE 0.5) kJ/g polymer respectively. These findings indicate relatively high energy values for Polydextrose by comparison with previously published values and illustrate a potential difficulty when using energy values obtained by certain radiochemical methods to estimate the energy values of a mixed diet given to rats. Several alternative explanations of the discrepancies are advanced.

Animals↗

Free associations of older adults to single words and conceptually related word triads.

Verbal free association responses were elicited to 56 single-word stimuli and 30 triads of conceptually related words from 95 older adults (52 to 90 years) and 31 younger adults (23 to 49). For single words, the distribution of paradigmatic and syntagmatic associations was similar for the older and younger samples; multiple regression analysis indicated that, although vocabulary scores were a good predictor of type of response, age was not. Specific responses to single words were similar for older and younger adults; there was some evidence of a slight reduction in commonality of associations with aging. For triad stimuli, the levels of responses reflecting shared membership in a natural category or a shared characteristic (sensory) feature were similar for younger and older adults; again vocabulary scores consistently predicted such responses, but age did not.

Adult↗