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Biomedical subjects

P Finlay

Publications and source records attributed to P Finlay.

10 recordsLinked to original sources

Precision branching ratio measurement for the superallowed beta+ emitter 62Ga and isospin-symmetry-breaking corrections in A>or=62 nuclei.

A high-precision branching ratio measurement for the superallowed beta+ decay of 62Ga was performed at the Isotope Separator and Accelerator radioactive ion beam facility. Nineteen gamma rays emitted following beta+ decay of 62Ga were identified, establishing the dominant superallowed branching ratio to be (99.861+/-0.011)%. Combined with recent half-life and Q-value measurements, this branching ratio yields a superallowed ft value of 3075.6+/-1.4 s for 62Ga decay. These results demonstrate the feasibility of high-precision superallowed branching ratio measurements in the A>or=62 mass region and provide the first stringent tests of the large isospin-symmetry-breaking effects predicted for these decays.

Journal Article↗

Comparison of Australian and international guidelines for grading severity of chronic obstructive pulmonary disease.

AIM: To compare grading of chronic obstructive pulmonary disease (COPD) using Australian guidelines Confirm diagnosis, Optimize function, Prevent deterioration, Develop a self-management plan and manage eXacerbations (COPD-X) versus Global initiative for Obstructive Lung Disease (GOLD) guidelines and to assess whether this is associated with differences in other health domains affected by COPD. Adult outpatients (n = 61) with COPD were studied using lung function measurements, six-minute walk test and body composition assessments. Subjects also completed self-rated dyspnoea scores and health-related quality-of-life scales. For each patient, COPD severity was graded using both COPD-X and GOLD guidelines, and results were collectively analysed. If significant discrepancies were observed, comparisons of other health domains were carried out. After grading severity using COPD-X and GOLD guidelines, significant discrepancies were noted. Of nine subjects with no disease (normal) based on COPD-X, seven were judged to be 'mild' according to GOLD. Similarly, 11 of 12 patients with mild disease (COPD-X) had 'moderate' disease judged by GOLD, and 9 of 23 with moderate severity (COPD-X) had 'severe' COPD using GOLD. Finally, 6 of 17 patients with COPD-X-rated severe disease had 'very severe' disease using the GOLD criteria. Among patients with COPD-X severe disease, those with GOLD discordant (very severe) severity had a poorer quality of life compared with those with GOLD concordant (severe) severity (P = 0.006). Similarly, there was also a trend towards lower six-minute walk test distance and greater subjective dyspnoea in GOLD very severe patients compared with GOLD severe patients. Significant discrepancies in grading of severity exist between Australian and international COPD guidelines. Current Australian guidelines for severity grading may not fully reflect the effect COPD has on other key domains of health.

Aged↗

Psychological consequences of maxillofacial trauma: a preliminary study.

AIMS: To identify the prevalence of post-traumatic psychological symptoms after maxillofacial trauma and prognostic factors related to poor outcome. METHODS: Thirty-nine patients were assessed within 10 days of injury and 24 again 4-6 weeks later using five standardised self-report measures on each occasion and a short structured interview at the time of initial contact. RESULTS: Specific post-traumatic psychological symptoms were present at initial assessment in 21 patients (54%), with 9 (41%) meeting diagnostic criteria for post-traumatic stress disorder at review 4-6 weeks later. Other psychiatric problems, such as anxiety and depression, were identified by the General Health Questionnaire and the Hospital Anxiety and Depression Scale. Characteristics associated with poorer outcome included: a previous history of psychological distress; fear of the unknown, and female sex. CONCLUSION: These findings highlight the adverse psychological effect of maxillofacial trauma both immediately after the event and 4-6 weeks after injury. Proper assessment of injured patients must include psychological aspects and further research is needed to identify the most appropriate response.

Adolescent↗

Immunocytochemical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy.

The protein product of the bcl-2 gene is though to be involved in inhibition of apoptosis; it may therefore be important in the modulation of hormonal/anti-hormonal responsiveness exhibited by tumours. This study immunocytochemically investigates (i) relationships between bcl-2 protein expression in primary breast cancers and other markers of prognostic and therapeutic value and (ii) associations of the bcl-2 protein with breast cancer responsiveness to endocrine therapy. The bcl-2 protein was found within the tumour epithelial cell cytoplasm of 32/46 breast cancer specimens; inter-patient staining was heterogeneous. Immunostaining for steroid hormone receptors was strongly associated with that for the bcl-2 protein, and it is thus possible that this protein, like progesterone receptor, is under oestrogen regulation via oestrogen receptor. The protein was inversely related to 2 markers of endocrine insensitivity, epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein, while no associations were observed with either transforming growth factor (TGF)-alpha or Ki-67 proliferative status. A highly significant relationship was observed between response to endocrine therapy and the presence of bcl-2 protein. Indeed, bcl-2 immunostaining proved to be a more accurate predictor of response than oestrogen receptor status. Patients with elevated bcl-2 immunostaining (particularly those who coexpressed high oestrogen receptor levels) appeared to derive the greatest benefit from endocrine therapy. Our results are paradoxical since it was expected that the bcl-2 protein would counteract the tumour inhibitory effects of endocrine therapies as it is thought to prevent programmed cell death.

Apoptosis↗

Relationship between EGF-R, c-erbB-2 protein expression and Ki67 immunostaining in breast cancer and hormone sensitivity.

The expression of the epidermal growth factor receptor (EGF-R), c-erbB-2 protein product and Ki67 have been evaluated in 105 breast cancers of known responsiveness to endocrine therapy using immunohistochemistry. EGF-R staining was observed in 62 of the tumours and was significantly associated with elevated rates of cell proliferation (%Ki67 positive cells) and loss of hormone sensitivity. In contrast, c-erbB-2 expression was not correlated with cell proliferation rates and was less strongly related to hormone insensitivity. Subdivision of the EGF-R data according to c-erbB-2 measurements revealed an association between c-erbB-2 immunostaining and worsened patient outlook and hormone insensitivity in moderately EGF-R-positive tumours. c-erbB-2 immunostaining in highly EGF-R-positive tumours did not further contribute to the already poor prognosis of these patients. These data confirm the prognostic importance of EGF-R measurements in breast cancer and may infer a functional interaction between this protein and the c-erbB-2 protein product in the aberrant growth of a subset of breast tumours.

Breast Neoplasms↗

A multicentre study into the reliability of steroid receptor immunocytochemical assay quantification. British Quality Control Group.

Qualitative and semiquantitative assessments of oestrogen receptor and progesterone receptor positivity determined on previously immunocytochemically stained slides were performed by eight independent assessors. Concordance between assessments of steroid receptor status was good (24/25, 96%). Interassessor variations in estimates of positive immunostaining levels were high, varying by between 10 and 75% for individual slides. In 2 cases estimates for the same section ranged between 15% nuclei positive and 90% nuclei positive. Wide variations were also recorded for slides stained for progesterone receptors. Results using an assessment procedure combining staining intensity and percentage positivity estimates were also subject to marked discordance. A computerised image analysis system, also used to assess slides gave results similar to the mean manually determined percentage positivity values. It is suggested that quality control of steroid receptor immunocytochemical quantification be considered and that automated image analysis may represent an accurate and valid means of achieving this.

Breast Neoplasms↗

Automated quantitation of immunocytochemically localized estrogen receptors in human breast cancer.

Frozen sections of breast tumor tissue have been stained using an immunoperoxidase [estrogen receptor (ER)-immunocytochemistry] kit incorporating a monoclonal antiserum [H222] to visualize nuclear human ERs. Quantitation of specific staining has been performed by manual procedures using optical microscopy and by a computer-assisted image analysis system (CAS 100). Initial investigations with a test panel of ER-immunocytochemistry-positive tumors revealed a good qualitative agreement between CAS and manual assessments. Reduced variance was, however, observed between quantified ER-immunocytochemistry results from four experienced investigators using the CAS analysis. An extended study confirmed the relationships between CAS and manual methods of assessment. These findings were evident when studies were scored either by assessment of the percentage of positively stained cells (n = 92; r = 0.919; P less than 0.01) or by H-score calculations (n = 92; r = 0.913; P less than 0.01). A good correlation was also found between CAS quantification and the results of an ER enzyme immunoassay of 48 primary breast cancer specimens (r = 0.715; P less than 0.05). In 49 cases it was possible to relate CAS-defined ER status and levels to the subsequent response of patients to endocrine therapy. ER was assessed on specimens obtained prior to commencement of treatments for recurrent breast cancer. Presuming the presence of ER to be a prerequisite for successful therapy, very good correlations between response and both status and levels of positivity were recorded. None of 16 patients with CAS-ER-negative tumors responded to treatment, while 16 of 33 (48.4%) CAS-ER-positive patients achieved an objective response according to International Union Against Cancer criteria. A relationship between response and the degree of CAS-ER positivity was obtained when the CAS score divisions of 0, 1-100, and greater than 100 (response rates, 0, 41, and 64%, respectively) were used. These data demonstrate that automated image analysis offers a reliable, reproducible procedure for quantifying ER in immunocytochemically stained sections. It has potential advantages over manual procedures, providing less opportunity for subjective influences in scoring sections. Future advances in software design should further reduce elements of subjectivity and increase both the speed and reliability of results. We anticipate image analysis becoming a valuable tool in investigations concerning, for example, the influence of heterogeneity of steroid receptor distribution on the rate of recurrence of breast cancer after mastectomy and in the clinical course of the disease.

Breast↗

Evaluation of an enzyme immunoassay for estrogen receptors in human breast cancers.

An estrogen receptor enzyme immunoassay kit (ER-EIA) has been evaluated in 70 human breast carcinomas against a routine cytoplasmic [3H]estradiol binding assay (ERU). A linear correlation between the ER-EIA and the ERU was observed for binding values up to 400 fmol/mg of cytosol protein. Above this value, the ERU underestimates the concentration of receptor. The ERU gave a lower number of estrogen receptor-positive tumors (50 of 70) than did the ER-EIA assay (59 of 70). In the ERU-negative ER-EIA-positive tumors, receptor values as determined by the ER-EIA assay all fell below 50 fmol/mg of protein (mean, 19.9 +/- 4.2 fmol/mg of protein). Application of an exchange procedure which estimates the total steroid binding capacity of the cytosol gave positive results in 7 of 9 ERU-negative ER-EIA-positive tumors (mean, 16.9 +/- 2.95 fmol/mg of protein). Subdivision of the binding data according to the menopausal status of the patient indicates low receptor values in premenopausal women by each assay. A correlation between the ER-EIA assay and the histological grade of tumors was observed; Grade I well-differentiated tumors were all positive, while Grade II and III tumors were 86% and 75% positive, respectively. No correlation between the ER-EIA assay and tumor lymph node stage or tumor size was observed.

Adult↗