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Biomedical subjects

S Byrne

Publications and source records attributed to S Byrne.

At least 19 recordsLinked to original sources

Healthy and pre-eclamptic placental basal plate lining cells: quantitative comparisons based on confocal laser scanning microscopy.

Immunocytochemical confocal laser scanning microscope images of the monolayer of cells lining the intervillus space at the basal plate of term placentae were analysed using stereology. Immunoreactively-distinct regions of this mosaic layer were measured. In basal plate from healthy pregnancies, trophoblast epithelium occupied 18.91% of the surface area and endothelium 60.81%. In pre-eclampsia the equivalent areas were 15.57% and 67.63%. Acellular fibrinoid covers the remaining area and this component decreases in area in pre-eclampsia. The statistically significant increase in the cellular endothelial compartment may be relevant to the hypertensive pathology of pre-eclampsia as endothelial signalling plays a major role in regulation of blood pressure.

Endothelial Cells↗

Confocal laser scanning microscope study of cytokeratin immunofluorescence differences between villous and extravillous trophoblast: cytokeratin downregulation in pre-eclampsia.

Pre-eclampsia is a disease characterized by failures in interstitial implantation. One product of the implantation process is the basal plate; a structure whose complexity makes it hard to fully appreciate the pathological changes in significant diseases of pregnancy. This article describes our use of CLSM immunofluorescence to examine the cytokeratin composition of the cells of trophoblastic origin in the term placental basal plate. Large differences in the content of the structural polymeric protein were compared using analysis of digital images. We show that greater pancytokeratin immunofluorescence is observed in extravillous cytotrophoblast cells as compared with villous trophoblast. There is a >30-fold difference in the mean area percent of the most intensely immunofluorescent pixels in the tissue containing these cells. This is a very high, statistically significant difference as defined by the Wilcoxon Signed Ranks Test Asym. Sig. (two-tailed): P < 0.001. The most invasive population of cells of the trophoblast lineage (the extravillous trophoblast) exhibits a significant reduction in cytokeratin immunofluorescence when comparisons of healthy and pre-eclamptic pregnancies are made. This ratio was 2.4:1. It was tested using the Mann-Whitney U-test. From healthy to pre-eclamptic the reduction was from mean rank 83.42((healthy)) to 51.13((pre-eclamptic)). The difference was very highly statistically significant (n = 53 + 75 = 128; U = 984.500; Z = -4.852; P < 0.001). There was also less cytokeratin-related immunofluorescence in villous trophoblast when healthy villi were compared with pre-eclamptic villi. The observed alterations in trophoblastic cytoskeletal components are expected to damage the anchorage and motility of cells. The extravillous trophoblast is known to be necessary for implantation. This leads to a cellular hypothesis of the failure of implantation resulting in reduced depth of uterine invasion and failure to adapt the spiral arterioles for low-pressure perfusion of the intervillus space, two well-known features of pre-eclampsia. The reduction in cytokeratin-related immunofluorescence in the villus trophoblast seen on comparing healthy term placentae with those from pre-eclamptics implies that the trophoblast is a weaker epithelial layer in the hypertensive pregnancy. This could account for the rise in deported trophoblast associated with pre-eclampsia. Deported trophoblast has been invoked as the systemic messenger that leads to generalized maternal hypertension seen in this condition.

Cell Differentiation↗

Virus characterization, clinical presentation, and pathology associated with H7N3 avian influenza in British Columbia broiler breeder chickens in 2004.

Low-pathogenicity avian influenza (LPAI) subtype H7N3 was diagnosed on a two-age broiler breeder farm in Abbotsford, British Columbia (BC), in early February 2004. The presenting complaint in the older index flock was feed refusal, with 0.5% mortality over 72 hr that resolved over the following week Ten days after the initial complaint in the index flock, a younger flock in an adjacent barn experienced an abrupt spike in mortality (25% in 48 hr). The gross lesions of tracheal hyperemia and hilar pulmonary consolidation were subtle and nonspecific, and the diagnosis of avian influenza required laboratory confirmation. Two different viruses were isolated from the index farm: a LPAI (H7N3) was isolated from the older flock and a high-pathogenicity avian influenza (HPAI) (H7N3), which had an additional 21 base insertion at the hemagglutinin-cleavage site, was isolated from the younger flock. The presence of this insertion sequence and the similarity of adjacent sequences indicate that the LPAI had mutated into HPAI at some point between the first and second barn. Despite enhanced on-farm biosecurity measures, the virus was not contained on the index farm and eventually spread to over 40 commercial poultry facilities before massive depopulation efforts enabled its eradication.

Animals↗

Weight maintenance and relapse in obesity: a qualitative study.

OBJECTIVE: To investigate, among women with obesity who have lost weight, the psychological factors associated with successfully maintaining the new lower weight, as opposed to weight regain. DESIGN: Qualitative research methods (in-depth individual interviews and group interviews) were used to assess the characteristics of successful weight maintainers, as compared with weight regainers and healthy-weight women. SUBJECTS: In all, 76 females were recruited from the community, comprising 28 formerly obese women who had lost weight and maintained their new lower weight for at least 1 y; 28 obese women who had lost weight but regained the weight that they had lost; and 20 women with a stable weight in the healthy range. RESULTS: Certain psychological factors were identified which characterised the regainers but not the maintainers. These factors were: failure to achieve weight goals and dissatisfaction with the weight achieved; the tendency to evaluate self-worth in terms of weight and shape; a lack of vigilance with regard to weight control; a dichotomous (black-and-white) thinking style; and the tendency to use eating to regulate mood. CONCLUSION: The results suggest that psychological factors may provide some explanation as to why many people with obesity regain weight following successful weight loss. The factors identified in this study need to be examined further using prospective designs.

Adult↗

The problem of bias in training data in regression problems in medical decision support.

This paper describes a bias problem encountered in a machine learning approach to outcome prediction in anticoagulant drug therapy. The outcome to be predicted is a measure of the clotting time for the patient; this measure is continuous and so the prediction task is a regression problem. Artificial neural networks (ANNs) are a powerful mechanism for learning to predict such outcomes from training data. However, experiments have shown that an ANN is biased towards values more commonly occurring in the training data and is thus, less likely to be correct in predicting extreme values. This issue of bias in training data in regression problems is similar to the associated problem with minority classes in classification. However, this bias issue in classification is well documented and is an on-going area of research. In this paper, we consider stratified sampling and boosting as solutions to this bias problem and evaluate them on this outcome prediction problem and on two other datasets. Both approaches produce some improvements with boosting showing the most promise.

Bias↗

Elite athletes: effects of the pressure to be thin.

This study represented the first attempt to examine the prevalence of eating disorders in a large sample of both male and female elite athletes compared to a matched control group of non-athletes. The subjects were 263 Australian elite athletes representing a variety of sports, and 263 non-athletes. All subjects were interviewed using the Composite International Diagnostic Interview and completed a number of self-report questionnaires. Both male and female athletes competing in sports that emphasise a lean body shape or a low body weight evidenced a significantly higher prevalence of eating disorders and eating disorder symptoms than other athletes and non-athletes. The results suggest that athletes do, in fact, have a higher prevalence of eating disorders than non-athletes. However, it is not so much being an athlete that places an individual at increased risk for developing an eating disorder; rather it is athletes competing in sports which emphasise the importance of a thin body shape or a low body weight who appear to be particularly vulnerable.

Adolescent↗

The distribution of caveolin-3 immunofluorescence in skeletal muscle fibre membrane defined by dual channel confocal laser scanning microscopy, fast Fourier transform and image modelling.

Membrane domains rich in caveolin-3 overlie sarcomeric actin in skeletal muscle. The membrane exhibits a regular array of caveolin-3 immunofluorescence using confocal laser scanning microscopy (CLSM). Fourier analysis of tissue imaged by CLSM accurately defines a repeating intensity with a long-axis spacing of 1.48 microm confirmed by measurement of direct images. Reverse fast Fourier transform (FFT) and image-modelling allow reconstruction of the pattern. Mathematical modelling has allowed replication of several features of the FFT, including the second order maxima that confirm the relatively high information content of the original images. Measurements of membrane-pattern primary long-axis spacings are consistent with our measurements of the I-band sarcomere repeat in similarly prepared specimens labelled with fluorescent phalloidin or imaged using differential interference contrast microscopy. Dual-channel CLSM analysis of the sarcomeric banding pattern of actin and the repeating pattern of muscle fibre membrane caveolin showed that caveolae overlie the I-band. The anti-caveolin immunofluorescence is deficient over the Z-disc and maximal toward each of the I-band extremities. A mechanism of membrane shape change in which membrane-lipid molecules are interposed between more stable anchored rafts associated with caveolae can be envisaged. Thus, increasing girth and reducing length of the sarcolemma in rapid contraction may be explained.

Animals↗

Eating disorders in athletes: a review of the literature.

Over the last two decades an increasing amount of research has begun to examine the issue of eating disorders in athletes. While a number of studies in this area have been published, the results have not been able to clarify the nature of the relationship between athletic involvement and eating problems. This review critically evaluates existing studies of eating disorders in athletes, highlighting various methodological limitations. Studies are grouped under three main headings: uncontrolled studies; controlled studies; and studies comparing athletes with different body type requirements. A fourth section of the paper evaluates studies which have addressed the issue of gender differences in eating disorders among athletes. Suggestions are made for guidelines that will improve future research in this area.

Adolescent↗

Immunocytochemical localization of a caveolin-1 isoform in human term extra-embryonic membranes using confocal laser scanning microscopy: implications for the complexity of the materno-fetal junction.

This immunochemical, immunocytochemical, histological and ultrastructural study demonstrates the presence of caveolin 1 in a number of locations in term human extra-embryonic membranes. Strong expression was observed in fetal blood vessel endothelial cells of chorionic villi (cv) and in cv, amniotic and chorionic plate mesenchymal cells, but weak expression was characteristic of trophoblast. Expression in the amniotic epithelium indicated a stronger association with apical as opposed to baso-lateral membranes. Strong immunoreactivity in the thin lining layer of the maternal blood space of the basal plate was a surprising finding. Previously defined as trophoblast, we argue that this is at least partly endothelium based on this new histological, ultrastructural and immunocytochemical data.

Amnion↗

Regions responsible for organizing the microtubular cytoskeletons of extra-embryonic membranes.

We have identified putative microtubule-organising centres in whole mounts and frozen sections of full term human placenta, amniochorion and first trimester chorionic villus tissue by indirect immunofluorescence confocal laser scanning microscopy. These sites may perform a crucial executive role in the morphogenesis of human extra-embryonic membranes, and also may establish polarity in the amniotic epithelium and mediate the branching pattern of growth essential to the production of the chorionic villus tree.

Amnion↗

Expression of tissue type and urokinase type plasminogen activators as well as plasminogen activator inhibitor type-1 and type-2 in human and rhesus monkey placenta.

The distribution of mRNAs and antigens of tissue type (t) and urokinase type (u) plasminogen activators (PA) plus their corresponding inhibitors, type-1 (PAI-1) and type-2 (PAI-2) were studied in human and rhesus monkey placentae by in situ hybridisation and immunocytochemistry. Specific monkey cRNA and antibodies against human tPA, uPA, PAI-1 and PAI-2 were used as probes. The following results were obtained. (1) All the molecules tPA, uPA, PAI-1 and PAI-2 and their mRNAs were identified in the majority of the extravillous cytotrophoblast cells of the decidual layer between Rohr's and Nitabuch's striae and in cytotrophoblast cells of the chorionic plate, basal plate, intercotyledonary septae and cytotrophoblast cells of the chorionic villous tree. (2) Expression of uPA and PAI-2 was noted in villous trophoblast whereas tPA and PAI-1 were mainly concentrated where detachment from maternal tissue occurs. (3) No expression of tPA, uPA, PAI-1 and PAI-2 was observed in the basal plate endometrial stromal cells, chorionic plate connective tissue cells, septal endometrial stromal cells or villous core mesenchyme. (4) The distribution of probes observed following in situ hybridisation is generally consistent with the immunofluorescence pattern of the corresponding antigens and no significant interspecies differences were noted. It is possible that both decidual and extravillous trophoblast cells of placentae of human and rhesus monkey are capable of producing tPA, uPA, PAI-1 and PAI-2 to differing extents. Coordinated expression of these genes in the tissue may play an essential role in the maintenance of normal placentation and parturition. The differences in distribution we observed are consistent with the suggestion that coordinated expression of tPA and its inhibitor PAI-1 may play a key role in fibrinolytic activity in the early stages of placentation and separation of placenta from maternal tissue at term. On the other hand, uPA with its inhibitor PAI-2 appears mainly to play a role in degradation of trophoblast cell-associated extracellular matrix, and thus may be of greatest importance during early stages of placentation.

Animals↗

Rapid geographic spread of a methicillin-resistant Staphylococcus aureus strain.

In May 1993, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) was identified at our tertiary care teaching center. The epidemic MRSA strain was transmitted efficiently in the hospital environment. Subsequent investigations indicated that the strain had been introduced into western Canada by a patient who had recently been hospitalized for 3 months in the Punjab, India, and had been admitted to a hospital in rural British Columbia shortly after his arrival in Canada. Transfer of the patient to a hospital in Vancouver and subsequent transfer of a colonized patient contact to a hospital in Winnipeg, Manitoba, resulted in major outbreaks of MRSA at these two large tertiary care centers within 6 weeks of the arrival of the index case in Canada. Epidemiological typing of the S. aureus coagulase gene with use of a polymerase chain reaction method and pulsed-field gel electrophoresis documented clonality of this strain. These outbreaks again illustrate both the propensity of certain strains of S. aureus to produce epidemic disease, including rapid spread within the institutional setting, and the global nature of problems with antimicrobial resistance.

Bacterial Typing Techniques↗

Psychiatrists' responses to failure of maintenance therapy with antidepressants.

Some patients being treated for recurrent major depression experience a return of depressive symptoms despite a constant maintenance dose of an antidepressant, a phenomenon known as breakthrough depression. A total of 145 psychiatrists who were members of the Massachusetts Psychiatric Society responded to a survey about intervention in hypothetical cases of breakthrough depression if the patient was taking either 20 mg of fluoxetine, 100 mg of sertraline, 100 mg of nortriptyline, or 40 mg of fluoxetine. For all drugs and dosages, the most popular choice was increasing the dosage, followed by augmenting with lithium or another antidepressant or changing to a different drug.

1-Naphthylamine↗

Leucocyte and endothelial cell adhesion molecule expression in porcine histiocytic leiomyofibrosarcoma.

A histiocytic sarcoma was present at birth in a pig. On the basis of ultra-structure and structural-protein composition (presence of alpha-smooth-muscle actin but not keratin), the sarcoma component was identified as a leiomyofibrosarcoma. Lipid-laden macrophages (histiocytes), which permeated the tumour in an apparently random fashion, were somewhat atypical in that they were negative for some macrophage markers; they gave a reaction, however, for CDw14. Despite its aggressive metastatic capacity, this tumour occurred almost exclusively in the subcutis, dermis and skeletal muscle. The tumour was extensively vascularized with many small capillaries which did not express E-selectin (CD69E), MHC class II or the L-selectin (CD69L) ligand, markers characteristic of inflamed (activated) endothelial cells in pig skin. Significant numbers of the histiocytes were positive for the integrins CD18 and VLA-4 (CD49d), indicating involvement of integrin pathways in the spread or growth, or both, of the leiomyofibrosarcoma. Most of the fibrous sarcoma cells also had extensive reactivity with an antibody to the standard variant form of CD44 (CD44s).

Animals↗

Thrombelastography changes in pre-eclampsia and eclampsia.

We have measured platelet count, bleeding time and thrombelastography (TEG) variables and the correlation between these variables in 49 pregnant patients presenting with pre-eclampsia or eclampsia. Eighteen patients (37%) had a platelet count < or = 150 x 10(9) litre-1 and seven (14%) had a platelet count < or = 100 x 10(9) litre-1. Bleeding time was prolonged > 9.5 min in 13 (27%) patients and the TEG was abnormal in four (8%). The TEG variables, k time and maximum amplitude (MA) had a strong correlation with platelet count (k time-platelet count < or = 150 x 10(9) litre-1, r = -0.68, P = 0.003, platelet count < or = 100 x 10(9) litre-1, r = -0.84, P = 0.02; MA--platelet count < or = 150 x 10(9) litre-1, r = 0.72, P = 0.001, platelet count < or = 100 x 10(9) litre-1, r = 0.78, P = 0.04). There was no correlation between bleeding time and thrombocytopenia (platelet count < or = 150 x 10(9) litre-1, r = -0.18, ns; platelet count < or = 100 x 10(9) litre-1, r = 0.09, ns). There was no correlation between bleeding time and any measured TEG variable. Of the 10 (20%) patients with an adequate platelet count (> 100 x 10(9) litre-1) but prolonged bleeding time, the TEG was normal, suggesting adequate haemostasis. An MA of 53 mm, which is the lower limit for normal pregnancy, correlated with a platelet count of 54 x 10(9) litre-1 (95% confidence limits 40-75 x 10(9) litre-1). Although the number of patients with severe thrombocytopenia was small, a platelet count of 75 x 10(9) litre-1 should be associated with adequate haemostasis.

Anesthesia, Conduction↗

An exploration of the quality of peer review group activities within Australasia.

OBJECTIVE: To describe a two-phase study of the structure of Australasian psychiatrist peer review groups. METHOD (Phase one): Initially, information was sought from chairs/coordinators of psychiatrist peer review groups regarding the nature and organisation of their group. RESULTS (Phase one): One hundred and three questionnaires were returned describing a number of models of peer review. Three principal models were identified: a teaching hospital model, a private practice model, and a private institution model. METHOD (Phase two): The second-phase questionnaire sought information on the quality of the review, using six proposed standards developed by the Quality Assurance Committee of the Royal Australian and New Zealand College of Psychiatrists. RESULTS (Phase two): Many groups indicated that four of the proposed standards (those relating to documentation, having clear goals, reviewing actual clinical cases, and rigorous protection of confidentiality) were either already being followed or would be relatively easy to implement. The remaining two proposed standards (including structure, process and outcome dimensions of health care in the case discussion, and the use of explicit criteria) presented more difficulty. CONCLUSION: The application of such standards to peer review group meetings should assist groups to provide a forum for presentation and evaluation of clinical work where participants know they will be challenged in an environment which is both supportive and educational.

Attitude of Health Personnel↗

Clinical evaluation of meropenem versus ceftazidime for the treatment of Pseudomonas spp. infections in cystic fibrosis patients.

Cystic fibrosis patients (children and young adults) with Pseudomonas spp. chest infections were treated with meropenem or ceftazidime. This study was the first to investigate the use of meropenem in cystic fibrosis. Meropenem was well tolerated with only transient elevations of serum transaminases. No patient experienced nausea and vomiting, even when meropenem was administered as a bolus injection. This allowed home therapy to be used. Meropenem appeared to be at least as active as ceftazidime even at the low doses used. Patients showed a greater improvement in respiratory function on meropenem than ceftazidime. Only one patient (out of 60 courses) failed to respond to meropenem (98% success rate) compared with two failures out of 21 episodes with ceftazidime (90% success rate). There was little emergence of resistance to meropenem even though some patients were treated up to eight times over a 2 year period.

Adolescent↗