Electric genes. Current flow in DNA could lead to faster genetic testing.
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Biomedical subjects
Publications and source records attributed to D Paterson.
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Colour Doppler scans were carried out on 80 patients with breast carcinoma. Both the tumour and the lower axilla were scanned in all 80 patients. Seventy-five patients subsequently underwent axillary lymph node dissection and histological examination. The sensitivity of colour Doppler scanning for axillary node involvement was 70%, with a specificity of 98% and a positive predictive value of 96%.
Eighty patients with impalpable breast lesions detected by mammographic screening underwent hookwire-guided wide local excision. Excision specimens were orientated with Ligaclips and submitted to radiography; if, on the specimen radiograph, the mammographic lesion crossed any visible margin, further tissue was excised. Clear histological margins were obtained on the initial excision in 52 (68 per cent) of 77 carcinomas. After inspection of the orientated specimen radiograph, further tissue was excised from 22 patients; this significantly increased the rate of complete excision to 86 per cent (P < 0.01). Significantly more patients with invasive cancer had a complete excision than those with ductal carcinoma in situ (52 of 57 versus 14 of 20, P < 0.02).
In this study we have examined the expression and modulation of the human granulocyte colony-stimulating factor (G-CSF) receptor (R) in immature and differentiated myeloid cells using a 125I labelled human G-CSF analogue (TG50). Equilibrium binding data revealed a single affinity class of receptor on all cell types expressing G-CSFR (KD 235-606 pM) with neutrophils expressing 2883 +/- 672 Rs/cell. Rapid internalization of surface receptor-bound ligand at 37 degrees C was detected in both immature cells (U937) and neutrophils with > 70% of specifically bound ligand internalized within 5 min. Concentration-response data showed that the level of occupancy of neutrophil G-CSFRs by ligand at 37 degrees C was approximately 5-fold greater than predicted by equilibrium binding data and correlated closely with concentration-response data for biological activity. Re-expression of G-CSFRs following down-regulation by internalization was not detected. Down-regulation of the neutrophil G-CSFR by several agents including granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF), lipopolysaccharide (LPS), f-met-leu-phe (fMLP), phorbol ester (TPA) and C5a was observed at 37 degrees C but not at 4 degrees C. In contrast, G-CSFRs on immature myeloid cells were significantly down-regulated by TPA only. Differentiation of myeloid leukaemic cell line HL-60 with DMSO, a frequently used model of granulocytic differentiation, was associated with a significant reduction in G-CSFR expression (11 +/- 5% of control) whereas treatment with retinoic acid led to increased G-CSFR expression (161 +/- 3%).
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Colour Doppler scanning was carried out on 53 patients with solid, discrete breast masses. Twenty-five of 32 breast cancers and none of 21 benign lesions gave a positive scan, giving a sensitivity of 78 per cent for association with malignancy, a specificity of 100 per cent and a positive predictive value of 100 per cent. Tumours less than 1 cm in diameter and invasive lobular cancers were least likely to give a positive scan. Axillary node scans were performed in 31 of 32 patients with breast cancer with 29 undergoing an axillary staging procedure. Nine patients had a positive axillary scan and all nine had involved axillary nodes. Three patients had involved axillary nodes, but a negative axillary scan. The sensitivity of colour Doppler scanning for axillary node involvement was 75 per cent, with a specificity of 100 per cent and a positive predictive value of 100 per cent.
Several widely used non-steroidal anti-inflammatory drugs have been reported as causing severe hepatitis. Three cases of severe acute hepatitis have been reported in association with piroxicam. A fatal submassive necrosis that occurred in a 68 year old lady who had received piroxicam for 15 months is described. A 48 year old man who developed submassive hepatic necrosis six weeks after beginning piroxicam but was successfully treated with orthotopic liver transplantation is also reported. Piroxicam may induce submassive necrosis of the liver, probably as an idiosyncratic reaction.
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Xenograft tumours from an oestrogen-dependent human breast cancer cell line MCF-7 have been established and characterised in thymectomised, irradiated female CBA strain mice. There was evidence for selection in xenografts of a subpopulation of MCF-7 cells with an altered pattern of gene expression as measured by mRNA levels compared with the original cells in vitro. Tumorigenicity increased significantly on repeated animal passage but oestrogen dependence was retained. Following injection of the mice with oestrogen, mitosis was induced in the tumour cells with associated increases in thymidine uptake and percentage of cells in S-phase. In accord with these changes, c-myc and p53 expression were increased and TGF-beta was suppressed. Thereafter the expression of the c-myc and p53 genes fell whilst that of the TGF-beta gene was induced as the oestrogenic-stimulus declined. The oestrogen-regulated mRNA pS2 showed a biphasic response to oestrogen and levels declined as the serum oestrogen fell to undetectable levels. This xenograft system demonstrates that changes in transcription of oncogenes, growth factor and oestrogen-regulated genes can be detected in vivo in response to oestrogen. It thus provides an in vivo model for studies of the biochemical and molecular basis for therapeutic manipulation of hormone-sensitive human breast cancer.
While there are new techniques for lengthening long bones, there are, nevertheless, contraindications and preoperative considerations for lengthening the femur or tibia, such as the presence of acetabular dysplasia, fixed deformity around joints, peripheral vascular and metabolic bone disease, and the age of the patient. Lengthening a long bone may be associated with many complications, especially in a congenitally short bone. It is important to anticipate and prevent complications, especially nonunion, subluxation of joints, muscle contractures, and neurologic complications. Lengthening of the femur and tibia are not for the occasional operator. However, as Bosworth noted in 1938, attention to great detail when lengthening the bone and skilled and detailed postoperative care will allow excellent results to be obtained. Time alone will tell what, biologically, is the best method for lengthening a long bone.
Congenital pseudarthrosis of the tibia was perhaps described almost 300 years ago, yet it remains one of the most difficult conditions to treat in orthopedic surgery. Recent advances in surgical techniques have given much more encouraging results. Coleman has played a significant role in this progress with his concept of complete correction of the tibial and fibular deformities and fixation with strong and long intramedullary rods. To this technique have been added autologous cancellous bone grafting and electrical stimulation. These advances have increased the rate of successful union of the pseudarthrosis of the tibia. More recently, transfer of a vascularized fibular graft with correction at the same time of the leg-length discrepancy has offered even greater hope for achieving successful bony union of the tibia. This treatment involves surgery on the normal leg. Long-term results of this method of management are eagerly awaited.
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A survey of 3660 Year 10 students, with an average age of 15 years, was carried out in a random sample of Adelaide secondary schools to determine the prevalence of structural scoliosis and the need for implementing a programme of scoliosis screening. By means of the Forward Bending Test and a specially devised scoring system 144 (3.9%) children were found to have signs that were suggestive of scoliosis; all but 12 were assessed subsequently by standardized clinical and radiological examinations. One hundred and three children were found to have structural scoliosis of 5 degrees or more; this represented a prevalence of 3.1%. The prevalence in girls (4.3%) was significantly higher than in boys (1.9%), and girls tended to have more severe curves and require treatment more frequently. Only one third (34) of the cases of structural scoliosis had been detected before this survey; most (28) of these had been detected through an earlier, subsequently discontinued, school screening programme. This study concludes that screening for scoliosis by means of a scored Forward Bending Test should be carried out in South Australian schools for all students in Year 8 and for girls in Year 10. The policy of screening boys in Year 8 should be the subject of further research. An educational programme for health professionals, parents, students and physical education teachers should support the programme.