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Biomedical subjects

C Pearce

Publications and source records attributed to C Pearce.

At least 19 recordsLinked to original sources

Anticoagulant therapy. Will computer use improve outcomes?

BACKGROUND: Anticoagulant therapy has been steadily increasing in clinical practice. With its narrow therapeutic range for efficacy and adverse events, this trend can lead to greater morbidity and mortality, making it an increasingly significant clinical, economic, medicolegal and public health issue. OBJECTIVE: To examine issues and challenges arising from the increasing use of anticoagulants in general practice. DISCUSSION: Adherence and regular monitoring by an effective multidisciplinary health care team is critical to optimise anticoagulant therapy. Clinicians, carers and patients need good information, training and support. Adherence to anticoagulation therapy is influenced by clinician interest, skills and involvement in shared decision making and risk counselling. Computerised decision support, based on relevant and comprehensive guidelines for anticoagulant therapy, can improve the way patients and clinicians manage anticoagulant therapy.

Anticoagulants↗

Mechanics of an educational exchange.

Rural general practitioners occasionally exchange practices internationally. The process of exchanging is a complicated one, which involves multiple bureaucarcies. Exchanging is not for the anxious or impatient. We exchanged with a family physician in Canada and had to arrange registration, provider numbers and immigration for our Canadian colleague, as well as for ourselves in Canada. In addition, there are many personal details (cars, house, etc.) that must also be sorted out.

Alberta↗

8-methyl-pyridoxatin: A novel N-hydroxy pyridone from fungus OS-F61800 that induces erythropoietin in human cells.

In the course of screening for small-molecule modulators of erythropoietin gene expression, a novel N-hydroxy pyridone was isolated from a culture of OS-F61800. Its structure was elucidated by extensive 1H and 13C NMR spectroscopic and chemical studies. This compound induced erythropoietin gene expression fivefold at a concentration of 0.3 microM, which is about threefold greater potency than our previously identified erythropoietin inducers.

Cell Line↗

Epolones: novel sesquiterpene-tropolones from fungus OS-F69284 that induce erythropoietin in human cells.

In the course of our screening for small molecule modulators of erythropoietin gene expression, two novel sesquiterpene tropolones and pycnidone were isolated from a culture of OS-F69284 (ATCC 74390). Their structures were elucidated by extensive 1H and 13C NMR spectroscopic studies and chemical reactions. These compounds induced erythropoietin gene expression 5-fold at a concentration of 1-1.6 microM.

Carbohydrate Sequence↗

Destruxin-A4 chlorohydrin, a novel destruxin from fungus OS-F68576: isolation, structure determination, and biological activity as an inducer of erythropoietin.

In the course of screening for small-molecule modulators of erythropoietin gene expression, five destruxins were isolated from the fungal culture of OS-F68576. The structures were elucidated by extensive 1H and 13C NMR spectroscopy and by hydrolytic modification. One compound (destruxin-A4 chlorohydrin, 1) is a novel destruxin. All these compounds induced erythropoietin gene expression 5-fold at concentration of 0.2-2 microM.

Cell Line↗

Isolation and characterization of the fungal metabolite 3-O-methylviridicatin as an inhibitor of tumour necrosis factor alpha-induced human immunodeficiency virus replication.

The cytokine tumour necrosis factor alpha (TNF-alpha) has been shown to play a role in human immunodeficiency virus (HIV) replication by activating transcription of the provirus in both T cells and macrophages. Therefore, agents that block TNF-alpha-induced HIV expression could have therapeutic value in the treatment of AIDS. We have sought to identify antiviral agents that block TNF-alpha induction of HIV LTR-directed transcription, using a cell-based, virus-free assay system in automated high-throughput screening. HeLa cells were transfected with an HIV LTR-luciferase reporter plasmid and a stable line was isolated in which TNF-alpha increased luciferase production by two- to threefold. This cell line was used to screen approximately 15,000 fungal extracts. An inhibitory activity specific for TNF-alpha-induced HIV LTR transcription was observed in culture OS-F67406. The active component was isolated and identified as a known metabolite, 3-O-methylviridicatin, by NMR and mass spectrometry. No biological activity has been associated with this compound previously. This compound blocks TNF-alpha activation of the HIV LTR in the HeLa-based system, with an IC50 of 5 microM, and inhibited virus production in the OM-10.1 cell line, a model of chronic infection responsive to induction by TNF-alpha, with an IC50 of 2.5 microM.

Anti-HIV Agents↗

Cell wall active antifungal compounds produced by the marine fungus hypoxylon oceanicum LL-15G256. I. Taxonomy and fermentation.

The cell wall targeted antifungal activity of Hypoxylon oceanicum LL-15G256 extracts resulted from the production of novel lipodepsipeptides and previously reported macrocyclic polylactones. In an optimized medium, titers of the lipodepsipeptide and the polylactones reached approximately 200-400 mg/liter and 25-50 mg/liter, respectively. The optimum fermentation temperature for production of 15G256 gamma was 28 degrees C. Seawater appeared to have an inhibitory effect on metabolite accumulation at lower fermentation temperatures.

Antifungal Agents↗

Effects of diethylamine/nitric oxide on blood perfusion and oxygenation in the R3230Ac mammary carcinoma.

The effects of intravenous diethylamine/nitric oxide (DEA/NO), a short-acting nitric oxide (NO) donor, on systemic haemodynamics, muscle and tumour blood flow (MBF and TBF) and tumour oxygenation were examined in rats bearing subcutaneous R3230Ac carcinoma in the leg. The effects of DEA/NO on the diameters of tumour-feeding and normal arterioles were evaluated in window chambers with and without implanted tumours. DEA/NO reduced mean arterial pressure (MAP) when given at doses > or = 100 nmol kg(-1), with maximal suppression at 0.5-1 min followed by return to baseline within 20 min. DEA/NO did not affect MBF except at the highest doses (500 and 1000 nmol kg(-1)). In contrast, DEA/NO reduced TBF and constricted tumour arterioles at doses > or = 100 nmol kg(-1). Tumour arteriolar vasomotion occurred in more than half the animals during hypotension and with a significantly higher frequency than in normal granulating tissue at a dose of 500 nmol kg(-1). Normal arterioles rapidly and significantly vasodilated for about 3 min and then returned to baseline. The reductions in TBF and MAP were accompanied by synchronous reduction in tumour pO2. Our findings suggest that DEA/NO decreases TBF in two ways. In the window chamber model, vascular steal occurs as normal arterioles adjacent to tumour dilate more than tumour arterioles during the initial period of hypotension. In leg tumours, the predominant mechanism is attributable to reduced perfusion pressure induced by lowered MAP, which decreases flow to the tumour, probably because of relatively higher flow resistance. The vasoconstriction and vasomotion in tumour arterioles during DEA/NO-induced hypotension may reflect differences in regulatory metabolism of NO between neoplastic and normal arterioles. Thus, intravenous injection of a short-acting NO donor, DEA/NO, decreases MAP and heart rate, leading to subsequent decreases in tumour blood flow and oxygenation.

Animals↗

Clonal diversity of Streptococcus mitis biovar 1 isolates from the oral cavity of human neonates.

The clonal diversity of 101 isolates of the pioneer bacterium Streptococcus mitis biovar 1 obtained from the oral cavities of 40 human neonates 1 to 3 days, 2 weeks, and 1 month postpartum was examined by using rRNA gene restriction patterns. There was a high degree of genetic diversity, with the 101 isolates comprising 93 unique PvuII ribotypes. There were eight identical pairs of ribotype patterns, and seven of the eight pairs were obtained from individual neonates. Only one identical pair comprised isolates obtained from different neonates. In all but two cases, isolates with matching ribotypes were obtained at one visit. Two pairs of isolates with matching ribotype patterns were obtained from neonates on successive visits. The ribotype patterns of the isolates were examined by cluster analysis. The isolates forming each cluster were very similar, yet each cluster was well separated from its neighbors. When several isolates were obtained from individual neonates at a particular visit, in some instances they were contained in a single cluster, whereas in other cases each isolate was contained in a separate cluster. Isolates obtained from individual neonates on successive visits tended to be contained in different clusters. This high degree of diversity, which has been observed in other mucosal commensal bacteria, may serve as a mechanism for avoiding immune elimination of these bacteria.

Cloning, Molecular↗

Identification of pioneer viridans streptococci in the oral cavity of human neonates.

Three hundred and sixty-seven strains of pioneer streptococci isolated from the mouths of 40 healthy, full-term infants during the first month of life were examined by two taxonomic schemes that incorporated biochemical and physiological characteristics, IgA1 protease production and glycosidase activities. Streptococcus mitis biovar 1 and S. oralis comprised 55.0% of the pioneer streptococci isolated from neonates. S. salivarius constituted 25.3% of the isolates, while S. anginosus, S. mitis biovar 2, S. sanguis and S. gordonii accounted collectively for 11.4%. Difficulties in identifying streptococci were encountered and 8.4% of the 367 isolates could not be assigned to a recognised species.

Bacterial Proteins↗

Adolescent suicide, depression and family dysfunction.

This study investigated associations between adolescents' perceptions of their family dynamics (McMaster Family Assessment Device, FAD) and depression, suicide thoughts and attempts. High school students (mean age 15.2 years) completed self-report questionnaires including the Beck Depression Inventory (BDI), the FAD, questions about suicidal thoughts, plans and attempts, deliberate self harm, and selected life experiences. Univariate analysis showed that family dysfunction measured on the FAD is associated with thinking and planning suicide, deliberate self harm, suicide attempts, as well as severe depression (BDI > or = 22). Despite this, stepwise regression indicated that family dysfunction influences suicide behaviors indirectly through other variables such as depression. The FAD is recommended as a useful addition to questionnaires seeking to identify vulnerability to both depression and adolescent attempted suicide in early detection studies.

Adolescent↗

Continuing medical education in marital and family therapy: a survey of South Australian psychiatrists.

OBJECTIVE: South Australian psychiatrists were surveyed to determine their impressions of the usefulness of marital and family therapy (MFT) in the management of serious psychiatric conditions and to ascertain their previous experience with Continuing Medical Education (CME) about family therapy. It was expected that psychiatrists' preferences regarding CME would be related to their clinical experience of the usefulness of MFT. METHOD: One hundred and twenty psychiatrists returned a questionnaire about their training, clinical and research interests, with ratings of the usefulness of MFT and CME preferences. This represented 65% of those eligible for the CME programme. RESULTS: Thirteen percent of the respondents found MFT to be extremely useful and a further 47% found it moderately useful in their current practice. There was evidence of a possible training effect: respondents who had previous CME rated MFT as more useful, especially for mood disorders. Furthermore, the treatment of mood disorders seemed to have a particular relevance in family psychiatry, making a statistically unique contribution to ratings of MFT usefulness in the respondents' total practice. Sixty-nine percent of the respondents requested further CME in family therapy. This represented 45% of all South Australian psychiatrists. Respondents who rated MFT as more useful in practice were significantly more likely to be interested in CME. CONCLUSIONS: There seems to be sufficient interest and clinical experience among psychiatrists for MFT to be included in CME courses. It is recommended that further training focus on major mental disorders, especially mood disorders and schizophrenia.

Adult↗

Pioneer oral streptococci produce immunoglobulin A1 protease.

As part of a longitudinal study of the relationship between bacterial colonization and the secretory immune response, 367 isolates of pioneer viridans streptococci collected from 40 breast- and bottle-fed neonates within the first month postpartum were tested for the production of immunoglobulin A1 (IgA1) protease and glycosidases. Fifty percent of the streptococci isolated produced IgA1 protease, including all isolates of Streptococcus oralis and S. sanguis, 60.7% of S. mitis biovar 1 isolates, and some isolates that could not be identified. Three cleavage patterns of alpha 1 heavy chains were observed. Six isolates of S. mitis biovar 1 that did not produce IgA1 protease attacked the alpha 1 chain. Incubation of IgA1 protease-negative S. mitis biovar 1 isolates with IgA1, either prior to or together with S. sanguis, rendered the IgA1 paraprotein resistant to cleavage by the IgA1 protease of S. sanguis. The ability of some pioneer streptococci in the human oral cavity to produce IgA1 protease and of others to modify the susceptibility of IgA1 to cleavage by IgA1 protease perhaps enhances their ability to survive in this habitat.

Female↗

Adolescent suicide: music preference as an indicator of vulnerability.

OBJECTIVE: This preliminary study investigated possible relationships between adolescents' music preference and aspects of their psychological health and lifestyle. METHOD: Students (mean age 14.76 years) from two randomly chosen high schools completed self-report questionnaires on preferred music types and messages in the music. In addition the Youth Self-Report provided information about suicide ideation, deliberate self-harm, "depression," and "delinquency." Brief risk taking and drug taking scales were administered in addition to questions about family environment. RESULTS: A marked gender bias was shown to exist with 74% of girls preferring pop music compared with 70.7% of boys preferring rock/metal. Significant associations appear to exist between a preference for rock/metal and suicidal thoughts, acts of deliberate self-harm, "depression," "delinquency," drug taking, and family dysfunction. This was all particularly true for girls. In addition, feeling sadder after listening to the preferred music appeared to distinguish the most disturbed group. CONCLUSIONS: The authors recommend that further academic study of these associations is warranted. Both preference for rock/metal music, particularly in girls, and feeling worse after listening to the music may be indicators in adolescents of vulnerability to suicidal thoughts and actions.

Adolescent↗