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Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 271 records · Page 15Linked to original sources

An aetiological model of non-melancholic depression: study design and validity of the measures.

OBJECTIVE: The aim of this paper is to describe an approach to sub-typing non-melancholic depression and to determine which raters from a variety of backgrounds provided the most valid information on study variables. METHOD: A sample of non-melancholic depressed patients is described. Multiple raters (i.e. patients, psychiatrists, referrers and corroborative witnesses) completed measures of the patient's trait anxiety levels, severity of recent life event stressors and personality functioning. RESULTS: The study and representative data are reported. Congruence between several measures employed indicated that psychiatrist rating of disordered personality was superior to corroborative witness report. Assessment of anxiety traits indicated reasonable agreement between referrers and corroborative witnesses but poor agreement between those ratings and interview-elicited ratings. There were also discrepancies in quantifying 'severity' of life event stress, with patients and their corroborative witnesses rating such events as more severe than either the interviewing psychiatrist or psychiatrists involved in consensus rating sessions. Importantly, the psychiatrists' capacity to quantify the relative contribution of disordered personality, anxiety and life-event stress to the particular depressive episode was supported. CONCLUSIONS: Results indicate some of the difficulties in operationalising determinants that may contribute to and sub-type the non-melancholic depressions, and demonstrate the advantages of using a range of rating strategies and raters. In this study, psychiatrist-generated judgements are clearly favoured, although the advantages of also assessing trait anxiety and life-event stress impact by self-report strategies are conceded. Some techniques for estimating the contribution of disordered personality function, anxiety and life-event stress are offered for both their research and their clinical utility.

Adjustment Disorders↗

Bilingual professionals in community mental health services.

OBJECTIVE: This paper presents results from research that explored the roles of bilingual professionals in community mental health services in the Sydney metropolitan area of New South Wales. There were two main objectives to the research: (i) to identify and describe the roles of bilingual professionals that are important in improving the quality of community mental health services for clients from non-English-speaking backgrounds (NESB); and (ii) to identify and describe the factors that facilitate and inhibit the conduct of these roles. METHOD: Data collection involved indepth interviews with bilingual professionals and team leaders in community mental health services and various other community health services; and various staff responsible for policy and service development with regard to cultural diversity. RESULTS: Bilingual mental health workers were found to have at least four critical roles. These were (i) direct clinical service provision to NESB clients; (ii) mental health promotion and community development; (iii) cultural consultancy; and (iv) service development. Respondents reported that the latter three roles were seriously underdeveloped compared to the clinical service provision role. CONCLUSIONS: It is critical that service managers implement strategies to make better use of the linguistic and cultural skills of bilingual professionals. In addition to their role in clinical service provision ways must be found to facilitate the community-focused, cultural consultancy and service development roles of bilingual professionals employed in mental health services.

Case Management↗

Neural network subtyping of depression.

OBJECTIVE: To examine the applicability of a neural network classification strategy to examine the independent contribution of psychomotor disturbance (PMD) and endogeneity symptoms to the DSM-III-R definition of melancholia. METHOD: We studied 407 depressed patients with the clinical dataset comprising 17 endogeneity symptoms and the 18-item CORE measure of behaviourally rated PMD. A multilayer perception neural network was used to fit non-linear models of varying complexity. A linear discriminant function analysis was also used to generate a model for comparison with the non-linear models. RESULTS: Models (linear and non-linear) using PMD items only and endogeneity symptoms only had similar rates of successful classification, while non-linear models combining both PMD and symptoms scores achieved the best classifications. CONCLUSIONS: Our current non-linear model was superior to a linear analysis, a finding which may have wider application to psychiatric classification. Our non-linear analysis of depressive subtypes supports the binary view that melancholic and non-melancholic depression are separate clinical disorders rather than different forms of the same entity. This study illustrates how non-linear modelling with neural networks is a potentially fruitful approach to the study of the diagnostic taxonomy of psychiatric disorders and to clinical decision-making.

Behavioral Symptoms↗

Hematological indices in an older population sample: derivation of healthy reference values.

Factors affecting hematological values were explored, and healthy reference values were estimated from a cross-sectional survey of a population (n = 4433), ages 49 years or more, residing permanently in a defined geographic region. Nursing home residents were excluded. Details of medication use and medical history were obtained by interview, and participants were asked to return after an overnight fast for blood sampling. The participation rate was 82.4%, of whom 88.4% provided a fasting blood sample. Hemoglobin, hematocrit, and erythrocyte counts were higher in men, whereas platelet counts were higher in women. Statistical associations between each hematological index and smoking, alcohol intake, use of certain drugs, chronic disease, and high creatinine values were tested by unpaired t-tests. Separate reference groups were defined for each hematological index by excluding subjects with any of the factors found to be of importance. The resulting reference values are particularly appropriate for evaluating hematological test results in older individuals.

Aged↗

Refractive error and age-related maculopathy: the Blue Mountains Eye Study.

PURPOSE: To assess associations between refractive error (hyperopia, myopia, and spherical equivalent [SEq]) and age-related maculopathy (ARM) in an older population. METHODS: A population-based survey examined 3654 people aged 49 years or older, 82% of whom were permanent residents in an area west of Sydney, Australia. Participants had a detailed eye examination, including standardized refraction and stereo macular photographs. ARM was diagnosed from blinded photographic grading. Autorefractor measurements and subjective refraction were used to assess SEq refractive error for each eye in diopters. Mean SEq of the two eyes was used to define emmetropia, myopia, and hyperopia in each person. RESULTS: After known ARM risk factors (age, sex, ARM family history, current smoking) had been adjusted for, no association was found between mean SEq (two eyes) and late ARM (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.9-1.1). However, a statistically significant increased risk of early ARM was found for each diopter of increase in mean SEq (OR, 1.1; CI, 1.0-1.2). In logistic regression models, moderate to high hyperopia was significantly associated with increased early ARM risk (OR, 2.0; CI, 1.2-3.4). When a generalized estimating equation model (GEE), which assessed the relationship at eye level while accounting for the correlation between the two eyes, was used, this association was marginally insignificant (OR, 1.3; CI, 0.9-1.9). No significant associations were found between myopia and any ARM stage with either model. CONCLUSIONS: These population-based data suggest a weak association between hyperopia and early ARM.

Age Distribution↗

The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases.

We identified a complex in S. cerevisiae, the "exosome," consisting of the five essential proteins Rrp4p, Rrp41p, Rrp42p, Rrp43p, and Rrp44p (Dis3p). Remarkably, four of these proteins are homologous to characterized bacterial 3'-->5' exoribonucleases; Rrp44p is homologous to RNase II, while Rrp41p, Rrp42p, and Rrp43p are related to RNase PH. Recombinant Rrp4p, Rrp44p, and Rrp41p are 3'-->5' exoribonucleases in vitro that have distributive, processive, and phosphorolytic activities, respectively. All components of the exosome are required for 3' processing of the 5.8S rRNA. Human Rrp4p is found in a comparably sized complex, and expression of the hRRP4 gene in yeast complements the rrp4-1 mutation. We conclude that the exosome constitutes a highly conserved eukaryotic RNA processing complex.

Amino Acid Sequence↗

Dysfunctional parenting: over-representation in non-melancholic depression and capacity of such specificity to refine sub-typing depression measures.

We examine the proposition that dysfunctional parenting is more likely to be experienced by those with non-melancholic (compared to melancholic) depression and that, as a consequence, such specificity allows the validity of varying definitions of melancholia to be examined and their utility sharpened. We study a sample of 245 non-psychotic patients meeting DSM-III-R criteria for a major depressive episode and assign them to melancholic and non-melancholic sub-sets according to five separate sub-typing measures (DSM-III-R; DSM-IV; Newcastle; 'Clinical' and CORE criteria). We assess dysfunctional parenting by use of the Parental Bonding Instrument (PBI), and by structured psychiatrist assessment and self-report ratings of a range of dysfunctional parental experiences, with independent assessment and self-report ratings of a range of dysfunctional parental experiences, with independent assessment of the last by reports from corroborative witnesses and from the patients' referring therapists. The five sub-typing measures assigned varying percentages of the sample (24-42%) to a 'melancholic' sub-type. When Newcastle Index assignments were examined, there was no evidence that dysfunctional parenting had any specificity to non-melancholic depression. Neither the DSM-III-R nor DSM-IV systems demonstrated specificity in relation to PBI scores, but several interview-assessed dysfunctional parenting characteristics were over-represented in their non-melancholic sub-sets. 'Clinical' definition showed the greatest over-representation of dysfunctional parenting to those assigned as having non-melancholic depression. The CORE measure, a behaviourally weighted measure of psychomotor disturbance, was the next most differentiating. Importantly, those assigned as having non-melancholic depression by all five measures were more likely to be rated by corroborative witnesses as being exposed to anomalous parenting, validating the subjects' self-reports, arguing against results being an artefact of clinician-based assessment, and supporting the specificity of dysfunctional parenting to a depressive sub-type.

Adolescent↗

Maintenance of elevated lead levels in drinking water from occasional use and potential impact on blood leads in children.

The variation in lead concentration was measured by thermal ionisation mass spectrometry isotope dilution in household tap water throughout the day when the plumbing system was not fully flushed. After collection of an initial 125-ml water sample containing 119 micrograms/l and a 2-l sample, 125-ml samples were collected at hourly intervals for 8 h. The concentrations in the hourly samples remained in the range 35-52 micrograms/l compared with 1.7 micrograms/l for fully flushed water. High precision lead isotopic measurements showed that approximately 50% of the lead in these water samples derives from the tap 'housing' compared with the overall household system. A health risk assessment was performed employing the US Environmental Protection Agency Integrated Exposure Uptake Biokinetic Model. Predicted blood lead levels in infants only exceeded the 'levels of concern' of 10 micrograms/dl when 100% of the water consumed contained 100 micrograms Pb/1. It would appear that unless the infant consumed 100% of first flush water at lead concentrations of approximately 100 micrograms/l, the blood lead would not exceed the recommended 'level of concern'. However, if more than 0.51 was consumed in drinks and formulae using first flush water, then the blood lead could easily exceed the recommended level. Likewise, a pregnant mother could be at risk of consuming considerably more than the 0.51/day first flush water of the concentrations measured, or throughout the day, if the system were not fully flushed.

Adult↗

Use of inhaled corticosteroids and the risk of cataracts.

BACKGROUND: The use of systemic corticosteroids is a risk factor for the development of posterior subcapsular cataracts, but the association between inhaled corticosteroids and cataracts is uncertain. METHODS: We conducted a population-based, cross-sectional study of vision and common eye diseases in an urban area of the Blue Mountains, near Sydney, Australia. We recruited 3654 people 49 to 97 years of age; the participation rate was 82 percent. We collected information by questionnaire on potential risk factors for cataracts, including the current or prior use of inhaled corticosteroids (beclomethasone or budesonide). Photographs of the subjects' lenses were graded, without information on the subjects, to determine the presence and severity of cortical, nuclear, and posterior subcapsular cataracts. RESULTS: Three hundred seventy subjects reported using inhaled corticosteroids, 164 currently and 206 previously. Among these subjects, after adjustment for age and sex, there was a higher prevalence of nuclear cataracts (relative prevalence, 1.5; 95 percent confidence interval, 1.2 to 1.9) and posterior subcapsular cataracts (relative prevalence, 1.9; 95 percent confidence interval, 1.3 to 2.8) than among the subjects with no inhaled-corticosteroid use, but the prevalence of cortical cataracts was not significantly higher (relative prevalence, 1.1; 95 percent confidence interval, 0.9 to 1.3). Higher cumulative lifetime doses of beclomethasone were associated with higher risks of posterior subcapsular cataracts (P for trend <0.001); the highest prevalence (27 percent) was found in subjects whose lifetime dose was over 2000 mg (relative prevalence, 5.5). Adjusting for the use of systemic corticosteroids and other potential confounders had little effect on the magnitude of the associations. The associations with posterior subcapsular cataracts, but not those with nuclear cataracts, were less marked when the analyses were restricted to subjects who had never used systemic corticosteroids. CONCLUSIONS: The use of inhaled corticosteroids is associated with the development of posterior subcapsular and nuclear cataracts.

Administration, Inhalation↗

Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage.

We demonstrate the direct involvement of increased collagenase activity in the cleavage of type II collagen in osteoarthritic human femoral condylar cartilage by developing and using antibodies reactive to carboxy-terminal (COL2-3/4C(short)) and amino-terminal (COL2-1/4N1) neoepitopes generated by cleavage of native human type II collagen by collagenase matrix metalloproteinase (MMP)-1 (collagenase-1), MMP-8 (collagenase-2), and MMP-13 (collagenase-3). A secondary cleavage followed the initial cleavage produced by these recombinant collagenases. This generated neoepitope COL2-1/4N2. There was significantly more COL2-3/4C(short) neoepitope in osteoarthritis (OA) compared to adult nonarthritic cartilages as determined by immunoassay of cartilage extracts. A synthetic preferential inhibitor of MMP-13 significantly reduced the unstimulated release in culture of neoepitope COL2-3/4C(short) from human osteoarthritic cartilage explants. These data suggest that collagenase(s) produced by chondrocytes is (are) involved in the cleavage and denaturation of type II collagen in articular cartilage, that this is increased in OA, and that MMP-13 may play a significant role in this process.

Adult↗