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Biomedical subjects

R G Wilson

Publications and source records attributed to R G Wilson.

At least 91 records · Page 5Linked to original sources

Aspirate cellularity as a rapid indicator of renal allograft rejection.

No rapid and unequivocal test exists to diagnose renal allograft rejection. Despite advances in immunosuppression over the last 20 years, rejection is still the major problem in clinical organ transplantation. Most transplant centres report a renal graft survival rate of about 60 per cent at 5 years and the majority of graft losses are due to rejection. An influx into the graft of various cell types has been implicated in the diagnosis of rejection but it takes up to 24 h to obtain such information histologically. We have carried out fine needle aspiration biopsy of the allografts and estimated the number of white cells in the aspirate using a fluorescence activated cell sorter. Studies were performed in 34 cases of normal allograft function, 8 of rejection, 8 of acute tubular necrosis and 8 of cyclosporin nephrotoxicity. There was a statistically significantly higher cell number in the group undergoing rejection (P less than 0.01; Wilcoxon unpaired test) when compared to each of the other three groups. We believe that this technique, which takes only a few minutes to perform, could yield much valuable information. It deserves further study.

Biopsy, Needle↗

A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer.

We randomized 122 premenopausal women to receive tamoxifen or to undergo a surgical oophorectomy. Of 54 evaluable women treated with tamoxifen, 24% had an objective response, as compared with 21% of 53 women having an oophorectomy. The median duration of response for tamoxifen (20 months) was longer than that for surgical oophorectomy (7 months), but this did not achieve statistical significance (P = .056). Overall median survival was 15 months for 58 patients receiving tamoxifen and 25 months for 53 patients undergoing oophorectomy (P = .18). Toxicity was greater in those undergoing oophorectomy, though both treatments were well tolerated. In those premenopausal women for whom hormonal therapy is indicated, tamoxifen is a suitable alternative to surgical oophorectomy.

Adult↗

The detection of renal allograft rejection by fine-needle intrarenal manometry.

The causes of early renal allograft malfunction include rejection, acute tubular necrosis, cyclosporin nephrotoxicity and vascular complications. Fine-needle intrarenal manometry is a potential method of distinguishing rejection from the other causes of malfunction and has been used by Salaman and Griffin in patients' treated with cyclosporin. The technique involves inserting a fine-needle, which is connected to a specially designed manometer, into the substance of the transplant kidney. One hundred and six measurements of intrarenal pressure have been made in 28 patients immunosuppressed with either azathioprine and prednisolone or cyclosporin. Thirteen rejection episodes were identified and confirmed by biopsy. These were treated by pulse steroid (methylprednisolone) therapy. Seven episodes of cyclosporin toxicity were identified and there were fifteen episodes of acute tubular necrosis. The mean intrarenal pressure in the rejecting group was 52.8 mmHg compared with 22.3, 24.1 and 24.3 mmHg for the normal function, acute tubular necrosis and cyclosporin nephrotoxicity groups, respectively (P less than 0.01; Wilcoxon unpaired test). There were no differences within these groups related to the type of immunosuppression used. There were no clinical complications associated with the procedure. Thus in newly transplanted patients, fine-needle intrarenal manometry accurately identified rejection and distinguished it from normal function, acute tubular necrosis and cyclosporin nephrotoxicity in all the patients regardless of the immunosuppressants used.

Cyclosporins↗

A comparison of phospholipase activity, cellular adherence and pathogenicity of yeasts.

Phospholipase A and lysophospholipase activities were measured in the culture fluid and in the blastospores of Candida albicans. When phospholipase activity was measured in six yeasts (four strains of C. albicans and a single strain each of Candida parapsilosis and Saccharomyces cerevisiae) a correlation was found between this activity and two potential parameters of pathogenicity. The C. albicans isolates which adhered most strongly to buccal epithelial cells and were most pathogenic in mice had the highest phospholipase activities. Non-pathogenic yeasts, including C. albicans isolates which did not adhere and did not kill mice, had lower phospholipase activities.

Candida↗

Vindesine as a stathmokinetic agent in human rectal tumours in organ culture.

Organ culture, using human colorectal mucosa and tumours, is a good system in which to test a new stathmokinetic agent such as vindesine. Using this system we have found that vindesine has similar metaphase-arresting properties to vincristine, including at least a 6-fold dose response difference in its ability to arrest mitosis in mucosa and tumour, mucosa being the more sensitive. Vindesine is a satisfactory stathmokinetic agent, but in view of its greater cost offers no particular advantages over vincristine.

Carcinoma↗

Pharyngeal lymphoid hyperplasia in Thoroughbred racehorses in training.

The prevalence of pharyngeal lymphoid hyperplasia in Thoroughbred racehorses in training was investigated using a fibre optic endoscope. Of the 70 horses examined, all but 8 showed evidence of pharyngeal lymphoid hyperplasia and the severity of the pharyngeal changes decreased with age. Two-year old horses had greater pharyngeal lymphoid hyperplasia (p less than 0.05) when compared to all other age groups. More horses (p less than 0.05) with Grade 3 or Grade 4 pharyngeal lymphoid hyperplasia experienced recent mild respiratory disease than did horses with Grade 2 or less pharyngeal lymphoid hyperplasia. None of the horses examined had a history of diminished racing performance although 30% had either Grade 3 or Grade 4 pharyngeal lymphoid hyperplasia.

Age Factors↗

Duodenal perforation associated with tolazoline.

A neonate, managed with tolazoline for pulmonary hypertension after repair of a congenital diaphragmatic hernia, developed a duodenal perforation. The role of tolazoline in this condition is discussed, and possible measures to reduce its gastrointestinal side effects are proposed.

Duodenal Diseases↗

Cell proliferation in human colorectal mucosa in organ culture: the early adaptive changes.

In organ culture tissues undergo adaptive changes which complicate the assessment of proliferative indices. In the present study, a technique devised to preserve collagen metabolism and mesenchymal stroma in tissues of mixed origin was employed to investigate the kinetic behaviour of human colorectal mucosa over the first 24 hours in culture. During this period the structural preservation of tissue is good. The mitotic index in mucosa is profoundly depressed throughout the explants during the first 2-6 hours in culture. During this same period, however, heavy uptake of tritiated thymidine, indicating DNA synthesis, is observed within 150 micron of the cut edge of the samples but not centrally. This phenomenon has been described previously and assumed to be the result of inadequate diffusion of oxygen into the tissue. The 'edge labelling' phenomenon is followed by a wave of mitosis in the tissue edge at 8-18 hours in culture. This delay between tritiated thymidine uptake and the appearance of mitoses in the tissue edge may simply represent the duration of the S + G2 phase of the cell cycle, but is more likely to be due to cells in G1 moving into the S phase followed by cells hitherto blocked in G2 being stimulated into the M phase. After 18 hours the mitotic and labelling indices become more uniform throughout the samples suggesting that 'edge labelling' is partly due to local stimulation of cell proliferation by trauma rather than central inhibition due to diffusion problems. These results suggest that in this organ culture system, assessment of proliferative indices should be carried out after these adaptive changes have settled.

Adaptation, Physiological↗

Vitamin B6 intake and plasma pyridoxal phosphate concentrations in the first 2 weeks of life.

Plasma pyridoxal phosphate concentrations were measured in 178 hospitalised neonates. A reference interval for neonates less than 7 day old, of 25 to 78 nmol/l has been established. Vitamin B6 intakes did not correlate well with plasma pyridoxal concentrations despite 26 neonates receiving less than the Recommended Allowance (0.3 mg/d) and 19 receiving amounts below which convulsions have been associated (0.1 mg/d). Ten percent of those infants fed breast milk had plasma pyridoxal phosphate levels below the reference interval compared with only 4% of those fed milk formulae. Breast milk from mothers with babies less than 14 days old had a total vitamin B6 contents reference interval of 5 to 40 micrograms/l. Twenty percent of breast milk samples had virtually no vitamin B6 detected.

Bilirubin↗

Azole resistance in Candida albicans.

Two isolates of Candida albicans from chronic mucocutaneous candidosis patients who initially responded to ketoconazole treatment but who later relapsed, have shown an abnormal response to ketoconazole in four out of five systems in vitro and in three animal models of vaginal or systemic infection. They have also shown abnormal resistance to inhibition of ergosterol biosynthesis in whole cells, but not in cell-free systems, and to inhibition of amino acid uptake. We conclude that the behaviour of the isolates is consistent with the development of drug resistance to ketoconazole. In all systems the two isolates have shown cross-resistance to the triazole antifungal ICI 153,066. In addition they fail to take up radiolabelled ICI 153,066--in contrast to normal isolates--indicating that resistance is due to changes in the properties of the cell membrane rather than internal enzymology.

Amino Acids↗