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Biomedical subjects

M E French

Publications and source records attributed to M E French.

At least 19 recordsLinked to original sources
PubMed2001

Prostate cancer risk: associations with ultraviolet radiation, tyrosinase and melanocortin-1 receptor genotypes.

Exposure to ultraviolet radiation may reduce prostate cancer risk, suggesting that polymorphism in genes that mediate host pigmentation will be associated with susceptibility to this cancer. We studied 210 prostate cancer cases and 155 controls to determine whether vitamin D receptor (VDR, Taql and Fokl variants), tyrosinase (TYR, codon 192 variant) and melanocortin-1 receptor (MC1R, Arg151Cys, Arg160Trp, Val92Met, Asp294His and Asp84Glu variants) genotypes are associated with risk. UV exposure was determined using a questionnaire. MC1R Arg(160)/Arg(160) homozygotes were at increased risk (P = 0.027, odds ratio = 1.94) while TYR A2/A2 homozygotes were at reduced risk of prostate cancer (P = 0.033, odds ratio = 0.48). These associations remained significant after correction for UV-exposure. Stratification of cases and controls by quartiles of exposure, showed that the protective effect of TYR A1A2 (P = 0.006, odds ratio 0.075) and A2A2 (P = 0.003, odds ratio 0.055) was particularly strong in subjects who had received the greatest exposure. Our data show for the first time, that allelism in genes linked with skin pigment synthesis is associated with prostate cancer risk possibly because it mediates the protective effects of UV. Importantly, susceptibility is associated with an interaction between host predisposition and exposure.

Adult↗
PubMed2001

Exposure to ultraviolet radiation: association with susceptibility and age at presentation with prostate cancer.

A positive association between latitude and prostate cancer mortality has been interpreted to indicate that ultraviolet radiation (UVR) protects against development of this cancer. We aimed to examine this hypothesis. We compared exposure between 210 cases and 155 controls. Childhood sunburn (odds ratio 0.18, 95% CI 0.08-0.38), regular foreign holidays(0.41, 0.25-0.68), sunbathing score (0.83, 0.76-0.89), and low exposure to UVR (3.03, 1.59-5.78) were associated with development of prostate cancer. Furthermore, cases with low UVR exposure developed cancer at a younger median age (67.7 years, IQR 61.5-74.6) than cases with higher exposure (72.1 years, 67.5-76.4); p=0.006. These findings are compatible with UVR having a protective role against prostate cancer.

Case-Control Studies↗
PubMed2001

Outcome in prostate cancer associations with skin type and polymorphism in pigmentation-related genes.

Epidemiological studies have suggested that UV exerts a protective effect on prostate cancer. Accordingly, we determined, in 210 prostate cancer cases, whether parameters of exposure, skin type and polymorphism in MC1R, VDR and TYR were associated with the outcome parameters, histological grade, clinical stage and presence of bone metastases. We used logistic regression analysis, with correction for age and metastases, stage and grade in the models, to determine if the frequencies of individual factors were different in the patient groups. The development of metastases was not associated with UV exposure parameters. Paradoxically, patients with skin type 1 were at significantly reduced risk [P = 0.027, odds ratio (OR) 0.17, 95% CI 0.03-0.82] of developing metastases compared with cases with skin type 4. MC1R Val92/Val92 and VDR ff were associated with increased risk of metastases (ORs 4.30 and 4.98, respectively). Further, cumulative exposure (P = 0.005, OR 0.85/year) and increasing proportion of outdoor occupation (P = 0.001, OR 0.84/unit) were associated with reduced risk of advanced stage tumours. Skin types, MC1R or VDR genotypes were not significantly associated with advanced stage. None of the exposure parameters, skin types or genotypes were associated with tumour grade. While MC1R Val92/Val92 and VDR ff were only associated with bone metastases, TYR genotypes were associated with each of the outcome parameters. Thus, in logistic regression models that included age, but not advanced stage and high grade histology, TYR A1A2 was significantly associated with reduced risk of metastases (P = 0.033, OR 0.41). Similarly, in models that included age but not the other outcome parameters, associations between TYR A2A2 and high-grade and advanced stage were significant (P = 0.040, OR 0.41) or approached significance (P = 0.052, OR 0.44), respectively. These data indicate for the first time that pigmentation response to UV is associated with outcome in prostate cancer.

Adenocarcinoma↗
PubMed1991

Management of acute retention of urine: a reappraisal.

Our standard policy for the management of retention of urine due to prostatic hypertrophy is that the patient is catheterised and sent home, later to be seen and assessed in the Out-patient Department where he is given an admission date for operation. A detailed audit of 166 patients cared for in this way is presented and the results compared with those in 25 patients who remained in hospital in the interval between catheterisation and operation and in 402 patients not previously catheterised. Although the mortality rate was significantly higher in the retention group (3.3 vs 0.25%), we feel that this is a reflection of the fitness of the patients with retention rather than a consequence of the management policy. The advantages of the "catheterise and send home" policy are discussed.

Acute Disease↗
PubMed1983

A controlled trial of cyclosporine in renal transplantation with conversion to azathioprine and prednisolone after three months.

Thirty-five patients given an HLA-DR-incompatible cadaver kidney that was diuresing immediately after transplantation were randomly allocated to treatment with cyclosporine alone for 3 months followed by conversion to azathioprine and prednisolone (AP), or to conventional treatment with AP. Although many patients had to be converted to AP before 90 days because of rejection requiring more than two treatment courses of high-dose i.v. methylprednisolone, 16 of 21 grafts were functioning at 3 months, and 12 of 14 grafts in the control group were functioning. However 3 further grafts were lost from chronic rejection in the control group, and none were lost from chronic rejection in the cyclosporine group. All but one patient on cyclosporine had depressed renal function, and in all these patients function improved on conversion to AP. This depression of renal function is attributed both to cyclosporine nephrotoxicity and to a low-grade rejection reaction, the latter suggesting that the addition of steroids to cyclosporine might be beneficial in some patients. The strategy of a three-month course of cyclosporine followed by conversion to AP provides satisfactory immunosuppression, and it may be of value if long-term side effects of cyclosporine emerge with further experience.

Adult↗
PubMed1982

Low dose oral prednisolone in renal transplantation.

Azathioprine and steroids (prednisone or prednisolone) form the basis of conventional immunosuppression after renal transplantation. Most of the morbidity in the early months after transplantation. Most of the attributed to steroids, which are normally give in high doses. The only justification for giving high doses is a historical one. For this reason a randomised controlled trial was carried out to compare the efficacy of high dose (39 patients) and low dose (33 patients) oral prednisolone, both in combination with azathioprine, in patients given cadaveric renal allografts. Patients were followed up for at least two years after the transplantation. Patient and graft survival were identical in the two groups and the morbidity associated with steroids was impressively lower in patients receiving a low steroid dose. Although the optimal dose of steroids is still unknown, there seems little justification for continued use of high doses of oral steroids with azathioprine after cadaveric renal transplantation.

Administration, Oral↗
PubMed1981

Canine intestinal intussusception following renal and pancreatic transplantation.

In 138 mongrel dogs given renal transplants, 10 developed postoperative intussusceptions. The sites were jejunojejunal (seven), ileo-ileal (two) and ileocolic (one). In 30 puppies given intrasplenic autografts of dispersed pancreatic fragments after total pancreatectomy, five developed jejunojejunal intussusceptions. Presenting signs included vomiting, failure to eat, periodic attacks of pain, straining with the passage of bloodstained mucous, dehydration, weight loss, abdominal wall rigidity and an abdominal mass. The majority of dogs presented within the first seven days following transplantation, occasionally as late as the third week. Early operative intervention was essential to save the dogs and at laparotomy eight of nine intussusceptions were successfully reduced manually; one small bowel resection was performed for irreducibility. Recurrence was not observed in this series but reoperation in the puppies was invariably fatal. Factors contributing to the development of intussusception in the puppies included round worm infestation, recent dietary change following weaning, malabsorption and diarrhoea due to pancreatic insufficiency following pancreatectomy and respiratory infections suggesting an infective origin for the intussusceptions.

Animals↗
PubMed1980

Peroperative blood-transfusion improve cadaveric renal-allograft survival in non-transfused recipients. A prospective controlled clinical trial.

The effect of peroperative transfusion was studied in 27 patients who had never had a blood-transfusion or been pregnant and who were receiving their first cadaver renal allograft. 13 patients in the treatment group were given 2 units of whole stored blood at transplantation, whereas 14 patients in the control group were given no blood. Actuarial analysis after 2 years showed a graft survival of 85% at 1 year in the treated group compared with 34% at 1 year in the control group (p = 0.03). Transfusion of non-transfused patients during transplantation may be as effective as pregraft transfusion.

Adult↗
PubMed1980

Studies on the effects of cyclosporin A upon renal allograft rejection in the dog.

Dose and time response studies of the new immunosuppressive agent, cyclosporin A, have been performed in a dog renal allograft model. Rejection of a renal allograft only occurred in one of six dogs receiving 20 mg/kg/day continuously, but in 10 of 11 dogs receiving 10 mg/kg/day. Doses of 10 or 20 mg/kg/day given for 2 or 3 weeks delayed rejection, but rejection occurred in all animals when the drug was stopped. This suggests that the drug does not produce clonal deletion of the lymphocytes engaged in the immune reaction against the graft, but merely their suppression. The histological picture of rejection was markedly improved by therapeutic doses of cyclosporin A. No consistent histological or biochemical evidence for heptatoxicity or nephrotoxicity was found even in the higher doses tested. One fatal and four non-fatal infectious complications were seen in 29 dogs receiving doses of 5 mg/kg/day or higher.

Animals↗