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Biomedical subjects

M L Nicholson

Publications and source records attributed to M L Nicholson.

At least 181 records · Page 10Linked to original sources

Dietary and erythrocyte fatty acids in experimental colorectal carcinogenesis.

The influence of dietary fat on the erythrocyte stearic:oleic acid ratio was investigated in an experimental model of colorectal cancer. One hundred male Wistar rats were divided into four separate dietary groups: A (5% saturated fat), B (20% saturated fat), C (5% n-6 unsaturated fat) or D (20% n-6 unsaturated fat). Colorectal tumours were induced by intraperitoneal injection of azoxymethane (n = 60) and control animals received saline (n = 40). Animals were killed after 26 weeks and erythrocyte fatty acid profiles were determined by gas liquid chromatography. Although there were no differences in the incidence of adenoma formation in the four dietary groups, there was a significantly lower incidence of carcinomas in rats fed a 5% or 20% unsaturated fat diet when compared with either a 5% (P less than 0.05) or a 20% saturated fat diet (P less than 0.01). Multivariate analysis of fatty acid profiles demonstrated that both the type and quantity of dietary fat had a highly significant influence on the fatty acid profile of erythrocytes. The stearic:oleic acid ratio varied considerably between the four dietary groups but was only significantly lower in tumour bearing animals compared with controls in group B (20% saturated fat diet).

Animals↗

Anti-rejection therapy in renal transplantation: Use of the monoclonal antibody OKT3.

The success of anti-rejection therapy was evaluated in 65 cadaveric renal allografts immunosuppressed with cyclosporin. All first rejection episodes were treated with 0.5 g methylprednisolone given daily for 3 days. Second rejection episodes were treated with either a further identical 3-day course of methylprednisolone or a 10-14-day course of the monoclonal antibody OKT3. The peak creatinine during second rejection episodes was higher in patients treated with OKT3 (481 +/- 54 mumol/l; mean +/-SEM) than in those treated with methylprednisolone (320 +/- 59 mumol/l) (P = 0.036), suggesting more severe rejection in the OKT3 group. Despite this the rejection reversal rate was higher in the OKT3-treated group (100%) when compared to the high-dose methylprednisolone group (64%) (P less than 0.05) and the creatinine at 6 months was less in the OKT3 group (162 +/- 17 mumol/l) than in the methylprednisolone group (230 +/- 22 mumol/l). These data suggest that OKT3 is a very effective treatment for second rejection episodes following renal transplantation and yields improved renal functions in comparison with high-dose steroids.

Adolescent↗

Increased cell membrane arachidonic acid in experimental colorectal tumours.

Tumour cell membrane fatty acid composition was investigated using an animal model of colorectal carcinogenesis. Eighty six male Wistar rats were fed experimental diets containing either 5% saturated fat or 20% saturated fat. Colorectal tumours were induced by intraperitoneal injection of azoxymethane, and control rats received saline. Animals were killed at intervals up to 26 weeks after the last injection of carcinogen for histology and lipid analysis. Cell membrane fatty acids in colonic mucosa and colorectal tumours were determined by gas liquid chromatography. Animals fed the 20% fat diet developed more carcinomas (28 cancers in 14 rats) than those fed the 5% fat diet (14 cancers in 15 rats; chi 2 = 8.03, p = 0.0046) but they did not develop significantly more adenomas (28 and 24 respectively). Cell membrane fatty acid analysis showed a considerable increase in the content of arachidonic acid (20:4, n-6) in the tumours (mean (SEM) 11.7 (1.5)%) compared with colonic mucosa (4.2 (0.4)%; p less than 0.05). Dietary fatty acid composition was also found to influence the profile of fatty acids in the colonic mucosa. This study suggests that a high saturated fat diet promotes the malignant transformation of colorectal adenomas. The colorectal tumours were characterised by an increased cell membrane arachidonic acid, the precursor of putative cancer promoting prostaglandins.

Animals↗

The role of omentectomy in continuous ambulatory peritoneal dialysis.

Long-term survival of the peritoneal catheter is essential for successful CAPD. In our unit, all CAPD catheters are now placed by an open surgical technique, which in some cases has included performing a partial omentectomy. The aim of this study was to assess the influence of omentectomy on CAPD catheter survival. Three hundred consecutive CAPD catheters inserted over a 5-year period were analyzed. Omentectomy was performed in 113 cases (38%). Data relating to a number of potentially significant risk/benefit factors were analyzed using multiple regression analysis (proportional hazards method of Cox). Performing a partial omentectomy at the time of catheter insertion was found to significantly improve CAPD catheter survival (p = 0.0002).

Adolescent↗

Urological complications of renal transplantation: the impact of double J ureteric stents.

In a 10 year series of 350 consecutive renal transplant operations, the overall urological complication rate was 7.7%. During this period double J stents were introduced and were used either in the treatment of actual urological complications or as a prophylactic measure to protect ureters which had been damaged at retrieval. A total of 34 double J stents were used in 33 patients. The indications were: ureteric obstruction (n = 13), urinary leak (n = 5), short transplant ureter anastomosed using an extravesical ureteroneocystostomy (n = 10) and ureteric injury at the time of organ retrieval (n = 6). Thirty-two double J stents were inserted at open operation and two were inserted by an antegrade method after percutaneous nephrostomy. Improvement in renal function occurred in 16 out of the 18 cases of urological complications. No kidneys were lost and there were no deaths as a direct result of these complications. In a number of cases the insertion of a double J stent was the only treatment, thus eliminating the need for more complex surgery. All 16 patients who had a ureteric stent inserted as a prophylactic measure at the time of transplantation made uncomplicated postoperative recoveries. Urinary tract infection was relatively common (27%) after double J stent insertion, but other complications were rare. In conclusion, double J stents have proved to be a useful adjunct in the management of renal transplant related urological complications.

Adolescent↗

Prospective study of the value of ultrasound measurements in the diagnosis of acute rejection following renal transplantation.

In this prospective study we have used ultrasonographic measurements of the cross-sectional area of transplanted kidneys, as an objective assessment of graft size, for diagnosis of acute rejection episodes. Sixty episodes of acute graft dysfunction (serum creatinine rise of greater than or equal to 30 mumol/l) were studied in 40 patients. Tru-Cut biopsy under ultrasound control was performed in all cases and 36 episodes of acute cellular rejection were identified. An increase in graft cross-sectional area of greater than or equal to 10 per cent was defined as a positive scan, indicative of an acute rejection episode. Using these criteria, ultrasound correctly diagnosed rejection in 29 out of 36 cases (sensitivity 81 per cent) and there were four false positive results (specificity 83 per cent). The investigation had a predictive value of 88 per cent when positive and 74 per cent when negative.

Graft Rejection↗

Intraoperative air testing of colorectal anastomoses: a prospective, randomized trial.

A total of 145 consecutive patients receiving a colorectal anastomosis were randomized to 'test' or 'no test' once the anastomosis had been completed. Anastomotic testing was performed with the pelvis filled with saline and the rectum distended by sigmoidoscopic insufflation of air. Any leaks demonstrated were oversewn. A water-soluble contrast enema was performed on the tenth postoperative day. Seventy-four patients were randomized to 'test' and 71 to 'no test' but one patient was withdrawn from each group leaving a total of 143 for analysis. The two groups were well matched for age, sex, diagnosis and operative details. Eighteen (25 per cent) air leaks were detected and repaired in the 'test' group. After operation there were three (4 per cent) clinical leaks in the 'test' group and ten (14 per cent) in the 'no test' group (Fisher's exact test, P = 0.043). There were eight (11 per cent) radiological leaks in the 'test' group and 20 (29 per cent) in the 'no test' group (P = 0.006). Intraoperative air testing and repair of colorectal anastomoses significantly reduces the risk of postoperative clinical and radiological leaks.

Adult↗

Inhibition of experimental colorectal carcinogenesis by dietary N-6 polyunsaturated fats.

The influence of dietary fats on azoxymethane-induced colorectal carcinogenesis and erythrocyte, adipose, colon mucosa and tumour tissue fatty acids was investigated in 228 Wistar rats. The two main diets compared were beef suet rich in saturated fatty acids and corn oil rich in a linoleic acid, an N-6 polyunsaturated fatty acid. The animals were placed in one of four dietary groups: A = 5% saturated fat, B = 20% saturated fat, C = 5% N-6 fat and D = 20% N-6 fat. There was no difference in the number of adenomas between any of the dietary groups. The mean (+/- SEM) carcinoma yield per rat was A = 0.93 +/- 0.28, B = 1.93 +/- 0.50, C = 0.70 +/- 0.07, D = 0.13 +/- 0.04; the tumour yields in rats fed the saturated fat diets were significantly different from each other and from those fed the N-6 fat diets. The fatty acid profiles in all tissues were dependent upon the type and level of dietary fat and the tissue type. Arachidonate was higher in tumours compared to normal mucosa. Significant correlations were found between adipose linoleate (reflecting dietary intake) and tumour oleate and tumour arachidonate but not with the colorectal mucosa of control animals. This is the first in vivo study to show reduced colorectal carcinogenesis by N-6 polyunsaturated fatty acids.

Adenoma↗

Age-matching improves the results of renal transplantation with older donors.

Whilst HLA matching is routine for renal transplantation, the possible benefits of matching donor and recipient age have not been previously examined. In this study we examined the simultaneous effect of donor to recipient age difference on the graft survival of 141 consecutive first cadaver transplant recipients treated by cyclosporin immunosuppression. Multivariate regression analysis, taking into account other variables of moderately matched recipients (i.e. dialysis time and type, donor/recipient sex, local/imported kidneys, recent sensitivity, total ischaemic time, preoperative transfusions), indicated that age-difference was the single most important variable (P less than 0.05). Individually there was no significant effect of recipient age, whilst older donors (aged greater than 50 years) were associated with significantly worse graft survival than those younger (P less than 0.01). When dealing with donors aged greater than or equal to 50 years the corresponding recipient 1-year graft was improved when the donor was no more than 5 years older than the transplant recipient. Donor age to recipient age difference is a potentially important selection criterion in renal transplantation.

Adolescent↗

Treatment of lymphocele associated with renal transplant.

A new method of operative drainage of lymphoceles following renal transplantation is described. The technique involves intraperitoneal marsupialisation of the lymphocele cavity followed by insertion of a Tenckhoff peritoneal dialysis catheter to splint open the peritoneal window and act as an internal drain.

Drainage↗

Diverticulosis of the appendix.

Diverticulosis of the appendix is rarely reported. Two cases with this condition, including a unique example of appendiceal diverticulosis presenting at herniorrhaphy, are described. The aetiology of the condition and factors involved in incidental appendicectomy are considered.

Adult↗

Factors influencing peritoneal catheter survival in continuous ambulatory peritoneal dialysis.

The success of continuous ambulatory peritoneal dialysis (CAPD) is to a great extent determined by the survival of the peritoneal catheter. The aim of this study was to identify technical factors which influence CAPD catheter survival. A total of 453 CAPD catheters inserted into 310 patients over an 8-year period were analysed. Access to the peritoneum was gained either by an open surgical technique (n = 290) or by a closed technique using a trocar and introducer (n = 163). Data relating to a number of potentially significant risk/benefit factors were analysed using multiple regression analysis (proportional hazards method of Cox). Three factors were found to be independently associated with improved catheter survival. They were: using an open surgical insertion technique, performing a partial omentectomy at the time of catheter insertion and the procedure being performed by a consultant.

Adolescent↗