Severe interferon associated retinopathy.
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Biomedical subjects
Publications and source records attributed to K Schofield.
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The last 10 years has been an interesting time for Australian medical education despite reduced funding. WORKFORCE: There are five main workforce trends: a rural/urban maldistribution, a need for more specialists, public hospital staffing difficulties, increasing female practitioners and under-representation of indigenous practitioners. ISSUES FACING THE DEANS: Lack of resources is a problem facing Deans, with pressure for clinical service in teaching hospitals. Entrepreneurial activities have been undertaken including the enrollment of overseas students. Medical schools have also responded to important government initiatives. DEVELOPMENTS IN MEDICAL EDUCATION: Australia's 11 medical schools have undergone significant reform in the last decade. There is a mix of four (graduate), five and six year courses. AUSTRALIA'S NEW MEDICAL SCHOOL: James Cook University opened the first medical school in northern Australia in 2000. The School admits students from rural, northern Australian and indigenous backgrounds. It has a strong regional mission. RURAL AND COMMUNITY-BASED EDUCATION: Government funding to address the maldistribution of the workforce has led to the establishment of rural clubs, Departments of Rural Health and community-based programs. THE FIRST TWO POSTGRADUATE YEARS: There have been recent moves to improve education in the two years following graduation. This includes the initiation of national projects in curriculum and assessment. POSTGRADUATE AND CONTINUING MEDICAL EDUCATION: Postgraduate programs in Australia are being reformed to build on the changes in undergraduate education. CME is also under review. CONCLUSION: Australian medical educators should build on the recent reforms and take on some of the new directions in medical education.
Invasive Staphylococcus aureus infection frequently involves bacterial seeding from the bloodstream to other body tissues, a process necessarily involving interactions between circulating bacteria and vascular endothelial cells. Staphylococcus aureus fibronectin-binding protein is central to the invasion of endothelium, fibronectin forming a bridge between bacterial fibronectin-binding proteins and host cell receptors. To dissect further the mechanisms of invasion of endothelial cells by S. aureus, a series of truncated FnBPA proteins that lacked one or more of the A, B, C or D regions were expressed on the surface of S. aureus and tested in fibronectin adhesion, endothelial cell adhesion and invasion assays. We found that this protein has multiple, substituting, fibronectin-binding regions, each capable of conferring both adherence to fibronectin and endothelial cells, and endothelial cell invasion. By expressing S. aureus FnBPA on the surface of the non-invasive Gram-positive organism Lactococcus lactis, we have found that no other bacterial factor is required for invasion. Furthermore, we have demonstrated that, as with other cell types, invasion of endothelial cells is mediated by integrin alpha5beta1. These findings may be of relevance to the development of preventive measures against systemic infection, and bacterial spread in the bacteraemic patient.
The distinction between reactive mesothelial cells and carcinoma in pleural, peritoneal, and pericardial fluids is often difficult. We and others previously showed that E-cadherin, an epithelial-specific adhesion protein, can be useful for this distinction. In this study we tested the sensitivity and specificity of E-cadherin compared to, and in combination with, conventional cytology for assessment of carcinoma in fluids. Cytyc ThinPreptrade mark slides (Marlborough, MA) from 102 sequential fluids were evaluated for E-cadherin expression by routine immunologic techniques. No evidence of E-cadherin staining was seen in 71 cases, while 31 showed unequivocally positive staining. Sensitivity and specificity were independently determined for E-cadherin alone (72% and 97%, respectively), cytomorphology alone (62% and 100%, respectively), and both together (92% and 100%, respectively). We conclude that assessment of E-cadherin expression has sensitivity and specificity comparable to, or better than, conventional cytomorphology. If both cytomorphology and E-cadherin are used together, a definitive and correct diagnosis could have been made on nearly every case in this study.
Basic fibroblast growth factor (bFGF) is dependent on heparan sulphate for its ability to activate the cell surface signal transducing receptor. We have investigated the FGF dual receptor mechanism in a novel model of the transformation from human colon adenoma to carcinoma in vitro. Reverse transcription-polymerase chain reaction showed that mRNA for FGF receptors 1 and 2 were expressed in both the adenoma and carcinoma cells whereas immunocytochemistry showed that the expression of the FGF R1 was reduced significantly in the carcinoma cells. We have reported previously that the composition and sequence of human colon adenoma and carcinoma heparan sulphate (HS) differ in a defined and specific manner. The functional significance of these changes was assessed by affinity co-electrophoresis, which showed that the affinity of adenoma HS for bFGF was 10-fold greater than that of the carcinoma HS (Kd 220 nM vs. 2493 nM, respectively). In addition, Northern studies of the expression of syndecan 1 and 4 mRNA showed that proteoglycan core protein expression was reduced significantly in the carcinoma cells. These findings were associated with a reduced biological response to bFGF in the carcinoma cells that could be partially reversed by the addition of exogenous heparin, suggesting that both the proteoglycan and signal transducing receptor control the cells' response to bFGF.
Chronic rhinitis is the manifestation of a heterogeneous group of disease entities and often proves difficult to manage successfully. We present the investigations of the mucociliary system in 40 patients with mucoid rhinorrhoea as their principal symptom of whom 20 had pan respiratory disease. The saccharin clearance time (SCT) was measured and classified as normal if it was below 20 min. Objective measurement of clearance was made using 99mTechnetium-labelled human serum albumin (99mTc-HSA). We have standardized our method using a micrometer syringe driver to produce a droplet of consistent size (droplet size, 0.01 ml, SD 0.0002 ml) that reduces the dose of radiation. The movement of the droplet was measured over 20 min (RLT). The mean, maximum rate and percentage moved were calculated. Patients were divided into those who had chest disease (20) and those without and a chi 2-test was performed for the mean RLT time between the two groups. There was a strong correlation between mean and maximum rates (r = 0.91). One patient has a normal SCT and normal RLT. Patients with chest disease had a significantly lower mean RLT (P > 0.01). Assuming that RLT is the standard investigation, six patients were normal but had an abnormal SCT, this is a false positive error of 15%. The false negative error was 4/40 (10%). The association between sinus and chest disease with abnormal mucociliary clearance is stressed.
A detailed transcription map of the prolate-headed lactococcal phage c2 has been constructed. Transcription of about one-third of the genome, encoding 22 open reading frames, began within the first 2 min of infection and produced at least 12 overlapping transcripts that persisted until lysis occurred at 30 min after initiation of infection. The remaining two-thirds of the genome, encoding 17 open reading frames, was divergently transcribed, beginning between 4 and 6 min after initiation of infection, and resulted in at least 18 overlapping transcripts that persisted until lysis. Five very strong, simultaneously active, and probably unregulated early promoters and a single positively regulated late promoter were identified. The late promoter had an extended -10 sequence, had a significant basal level of activity in the uninduced state, and was induced to high activity by a phage gene product. The complex overlapping pattern of transcripts resulted from the action of the multiple early promoters, inefficient termination of transcription, and (possibly) processing of a late precursor transcript(s). Phage proteins were not required for these processes, and the host RNA polymerase was probably used for both early and late transcription.
BACKGROUND: The distinction between benign reactive mesothelial cells and well differentiated carcinoma can be difficult in pleural, peritoneal, and especially pericardial fluids. E-cadherin is an adhesion protein that is specifically expressed in cells of epithelial lineage. In this study, anti-E-cadherin antibodies were used to identify and distinguish carcinoma cells from reactive mesothelial cells. METHODS: Pleural, peritoneal, and pericardial fluids were prepared using the Cytyc Thin Prep processor. The specimens were comprised of a mix of 45 cases that were diagnosed as carcinoma, suspicious, or reactive by Papanicolaou staining of routine material seen by the authors' service. Routine immunologic techniques were used with a commercially available E-cadherin antibody. RESULTS: In most cases of carcinoma, tumor cells showed a strong positive membranous reaction product (32 of 37). This included four cases that were not cytomorphologically diagnosed as malignant, but subsequently proved to be malignant. E-cadherin staining was not observed in five tumors, two of which were not expected to express this protein. One benign case showed cells staining for E-cadherin, although the cells were not malignant by morphologic criteria. Because this case was a surgical pelvic washing, these cells more likely were epithelial contaminants than true false-positives. CONCLUSIONS: The epithelial specific cell-cell adhesion marker E-cadherin reliably distinguishes reactive mesothelial cells from carcinoma and is a useful adjunctive test to distinguish benign reactive mesothelial cells from well differentiated carcinoma cells in fluid specimens.
On-site adequacy assessments (OSAA) are reported to decrease the unsatisfactory and nondiagnostic rates of fine needle aspirations (FNAs). These have been routine in many institutions but were only recently introduced to our large teaching hospital. The results of FNAs performed in diagnostic radiology between January to December 1992 were compared to aspirations done by the same clinical staff during the first year (1993) after the addition of an on-site adequacy assessment service. In the year prior to OSAA, 154 FNAs were performed in diagnostic radiology and the material obtained was processed by a cytotechnologist. Of these, 89 (58%) cases were positive for malignant cells. Approximately half of these cases had confirmatory tissue biopsies processed in the surgical pathology department of our institution. The remaining 65 (42%) of cytology specimens were determined to be negative or nondiagnostic for malignancy. These canes either had no tissue follow-up or the tissue obtained was nondiagnostic. Before beginning OSAA, nine cases (6%) were interpreted as negative for malignancy, but subsequent tissue biopsies were malignant. There were no false positives during this time. Diagnostic sensitivity was 86% before OSAA. One hundred seventy-seven image directed FNAs were performed in the first year following the establishment of OSAA. Of these, 102 (58%) cases were interpreted as positive for malignant cells. About half of these patients went on to have confirmative tissue biopsies. Fifty-six (32%) cases were interpreted as negative for malignancy or nondiagnostic on FNA and follow-up tissue biopsies were also either negative or nondiagnostic. The false negative rate was 1% after OSAA and there were no false positives during this period. Diagnostic sensitivity was 98% after OSAA. In addition, the average overall number of passes per patient have decreased from 2.4 before OSAA to 1.6 after OSAA.
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OBJECTIVES: To determine the significance of a "suspicious" cytology report, to evaluate diagnostic accuracy for these specimens in the laboratory and to review the correlation of tumor subclassification in cytology versus histology. STUDY DESIGN: Retrospective review and comparison of 269 bronchoscopic cytology and histology specimens from a six-year period, 1984-1990. The relative and combined sensitivities of the sampling methods were studied. RESULTS: There were 17 suspicious cytologic diagnoses during this period. One of 17 was a false suspicious diagnosis, representing 0.03% of all reports on submitted samples. There were no false positive cytologic diagnoses. The majority (94%) of patients with a suspicious cytologic report had a final diagnosis of malignancy. Carcinoma was diagnosed in 244 of the 269 patients. CONCLUSION: Combined bronchoscopic cytology and biopsy was more sensitive (92%) than biopsy alone (82%) in making the initial diagnosis.