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Biomedical subjects

M R Lewin

Publications and source records attributed to M R Lewin.

At least 19 recordsLinked to original sources
PubMed1991

Is there a fibre-depleted aetiology for colorectal cancer? Experimental evidence.

In 1971, Denis Burkitt put forward his now famous hypothesis of a fibre-depleted aetiology for colorectal cancer. This was based on his careful clinical observations of the difference in patterns of diseases between Western and traditional African societies. He noted the rarity of colorectal cancer in African countries compared to the West and found that African diets were generally higher in dietary fibre and lower in refined carbohydrates. Since these pioneering observations there have been numerous epidemiological studies but many have failed to support Burkitt's attractive hypothesis. The purpose of this review is to examine the role of dietary fibre in the animal model of colon cancer and to assess critically the findings in the light of current knowledge of the theory of carcinogenesis. The findings from the studies of the experimental model of colon cancer did not support the theory of a fibre-depleted diet as a causative factor in the aetiology of colorectal cancer in man. However, the experimental evidence did suggest that an increase in dietary fibre does have a role in protection from this disease. It was concluded that in colorectal cancer, the effect of a fibre-depleted diet was through a mechanism of promotion (co-carcinogenesis) and that the protective effect of a high fibre diet was by an anticarcinogenic mechanism.

Animals↗
PubMed1990

Direct measurement of collagenase in colonic anastomosis.

Collagenase has been implicated in colonic anastomotic dehiscence but the enzyme has not previously been specifically measured in colonic healing. A 72 h tissue culture method for colonic tissue and a radiochemical assay for collagenase were adapted to measure the enzyme in healing rabbit colon, with specificity of the assay confirmed by sodium dodecylsulphate polyacrylamide gel electrophoresis. Normal and postoperative colon secreted collagenase, predominantly in a latent form, in the first 24 h of culture. Total activity reached a plateau after 48 and 72 h in culture, when 50-70 per cent of the enzyme was in an active form. At these times in culture, activity was significantly higher than after 24 h (P less than 0.001). One day after anastomosis the total amount of collagenase secreted in culture was higher than normal but the increase did not achieve significance. Three days after anastomosis the colon secreted more collagenase than explants from 1 day postoperative tissue (P less than 0.002). The proportion of active enzyme in the first 24 h in culture was also increased. Since active collagenase can be measured in culture medium from both normal and postoperative colon, the tissue may be secreting plasminogen activator which allows plasmin to activate the enzyme. The increase in collagenase after operation coincided with a decrease in collagen concentration in the colon wall, measured by hydroxyproline. This supports previous suggestions that collagenase contributes to anastomotic dehiscence. However, the findings must be interpreted with caution as the variance of the results was shown to be predominantly due to time in culture, suggesting this could be a bigger influence than the operation itself. In addition, our previously reported immunohistochemical study of this system indicated that collagenase only occurred in a localized region, restricted to the everted portion of the anastomosis, with the activity being tightly controlled by its inhibitor, tissue inhibitor of metalloproteinases.

Anastomosis, Surgical↗
PubMed1990

A gastrectomy population: 25-30 years on.

Prior to 1960 a Polya gastrectomy was the most frequent operation for duodenal ulcer. The majority of these patients now have reached the age of sixty or older. A prospective longitudinal study of a cohort of patients who underwent gastrectomy between 1955 and 1960 was undertaken. Twenty five to thirty years later the study has revealed the extent of the nutritional problems that may arise with the passage of time and shows that these numerically far outweigh the mechanical post-gastrectomy syndromes and weight loss which tended to dominate the earlier post-gastrectomy scene. By the end of the first decade, iron deficiency was the commonest nutritional problem. Vitamin B12 deficiency assumed more importance in the second decade. During the third decade both reached equal prevalence, being found in some 90% of the female and 70% of the male residual population. Vitamin D deficiency and early osteomalacia was a lesser problem, reaching its climax in the second decade. Evidence suggested a high incidence of osteoporosis and this requires further investigation. Overall, women fared worse than men with a higher and earlier incidence of iron deficiency, particularly in the pre-menopausal group. This study emphasizes the increasing need for regular screening of post-gastrectomy patients to detect early iron, vitamin B12 and vitamin D deficiencies as patients grow older.

Celiac Disease↗
PubMed1990

The relationship of plasminogen activators and oncogenes to tumour invasion.

Accruing evidence suggests an association between increased activity of plasminogen activators and transformed cells, and urokinase activity with tumour aggressiveness. The PIP2 pathway seems to provide a link between oncogene-associated transformation, cellular proliferation, plasminogen-activator expression and tumour invasion and metastasis.

Cell Division↗
PubMed1989

Differences in mucosal appearances and in relapse rates in duodenal ulceration treated with sucralfate or cimetidine.

A total of 46 patients with duodenal ulcer were randomly assigned, without the knowledge of the investigators, to treatment with cimetidine 200 mg three times daily and 400 mg at night or sucralfate 1 g four times daily followed by one year of maintenance treatment with cimetidine 400 mg at night or sucralfate 1 g twice daily, respectively, in those patients with healed ulcers. The endoscopic healing rates and relapse rates during the maintenance period were similar, four relapses occurring in each group. All four relapses in the sucralfate group occurred at 12 months and only two were symptomatic. All the cimetidine relapses were symptomatic, two occurring at six months, one at nine months, and one at 12 months. Following the one year maintenance period, 13 cimetidine patients and 11 sucralfate patients were followed up for 36 months. During the first two years, nine of 13 (69 percent) cimetidine-treated and two of 11 (18 percent) sucralfate-treated patients had relapses. During the third year, three more sucralfate-treated patients and one more cimetidine-treated patient had relapses, making a total of 10 of 13 (77 percent) and five of 11 (45 percent) in the cimetidine and sucralfate groups, respectively. Duodenal biopsy specimens obtained before and after healing and after one year of maintenance were examined by light and electron microscopy. The sucralfate group showed greater improvement after one year of maintenance therapy than did the cimetidine group, although the appearances in either group were not predictive of subsequent relapse. The results show that relapses are less frequent and occur later after sucralfate therapy and also that the morphologic appearances are more normal after treatment with sucralfate than after treatment with cimetidine.

Adolescent↗
PubMed1989

Leucine kinetics in surgical patients. I: A study of the effect of surgical 'stress'.

At present there is no consensus about the effect of surgical and accidental trauma on protein metabolism. Leucine kinetics, an index of protein turnover, have been studied in ten patients before intra-abdominal surgery and on either the third (n = 5) or seventh (n = 5) postoperative day. Only small changes in leucine kinetics were noted in the early postoperative study but, by the seventh day, there was evidence of increased synthesis as part of an overall elevation of turnover rates. It is suggested that the previously expressed opinion that protein synthesis is reduced after surgery must be re-examined.

Aged↗
PubMed1989

Leucine kinetics in surgical patients. II: A study of the effect of malignant disease and tumour burden.

Isotope studies of protein turnover have given conflicting evidence about the effects of a malignant tumour on the protein metabolism of the host. Leucine kinetics have been studied, as an index of protein turnover, using a well established methodology. Twenty patients were studied, five with benign disease of the colon, ten with localized malignant tumours of the large bowel, and five in whom there was evidence of metastatic disease from a colonic primary. No effect was observed on the leucine turnover of the patients that might be attributable to the presence or size of the tumour burden. It is suggested that some of the previously conflicting results may be attributable to variability in the experimental design, the heterogeneous patient groups studied and the methods used to express the results obtained.

Aged↗
PubMed1989

Duodenal and antral mucosal prostaglandin E2 synthesis in a study of normal subjects and all stages of duodenal ulcer disease treated by H2 receptor antagonists.

We tested the hypothesis that the production of prostaglandin E2 (PGE2) is impaired in duodenal ulcer disease and affected by treatment and healing. This was investigated by a study of maximal PGE2 synthesis rates in duodenal and antral mucosal biopsies obtained at endoscopy. The patients were divided into three groups. Group (a): endoscopically normal controls (n = 56); group (b): treatment controls (non-DU disease: gastric ulcer or oesophagitis treated by histamine H2 receptor antagonists) (n = 41); and group (c): patients with DU disease (n = 183) further subdivided into group (c1) active ulcer not on treatment (n = 47), (c2) treated active ulcer (n = 35), (c3) healed ulcer on treatment (n = 86), and (c4) healed ulcer not on treatment (n = 15). Group (a) synthesised (mean (SD] 106.6 (39.0) pg PGE2/mg wt of tissue from the duodenal bulb and 129.9 (56.9) from the second part of the duodenum. No difference was found between group (a) and (b) at either site. Group (c1) ulcer rim made 49.8 (22.7) and at all stages ulcer rim and scar made less than the control duodenal bulb (p less than 0.02). Uninvolved duodenal bulb form groups (c1) (63.4 (31.0], (c2) (83.6 (38.5], and (c3) (81.5 (31.1], however, also made significantly less than controls (p less than 0.02) and a similar though non-significant trend was seen in group (c4). Biopsies from the second part of the duodenum did not synthesise significantly less than the control group but a similar trend was noticed at each stage of ulcer treatment. Biopsies of control antrum synthesised 124.5 (32.2) but only 93.7 (44.2) in group (cl) (p < 0.005). All stages of duodenal ulcer healing were associated with a decreased capacity to synthesise the major prostaglandin PGE2 at the ulcer site and the uninvolved duodenal bulb and, in acute untreated duodenal ulcer, the uninvolved antrum. This decreased capacity may be the consequence of the disease process itself and not secondary to the treatment, indicating a basic pathophysiological abnormality which may explain the characteristic tendency of the disease to relapse.

Adult↗
PubMed1989

Comparison of relapse rates and of mucosal abnormalities after healing of duodenal ulceration and after one year's maintenance with cimetidine or sucralfate: a light and electron microscopy study.

Forty six patients with endoscopically diagnosed duodenal ulceration were randomly allocated to treatment with either sucralfate 1 g qds (n = 24) or cimetidine 200 mg tds and 400 mg nocte (n = 22). When the ulcers healed, a maintenance dose of sucralfate 1 g bd or cimetidine 400 mg nocte was given for one year (or until relapse if earlier). Biopsies of duodenal mucosa adjacent to ulcer sites for light and electron microscopy were obtained before and after healing and again after one year's maintenance if the ulcer remained healed. Duodenal biopsies were also taken from 20 age and sex matched controls. Rates of healing and relapse during maintenance did not differ between the two treatments, although relapses occurred earlier with cimetidine. In the three year post-maintenance follow up period 10/13 cimetidine patients relapsed compared with four of 11 sucralfate patients (p less than 0.05), the relapses occurring significantly earlier in the cimetidine treated patients (p less than 0.05). Mucosal biopsies from both treatment groups still showed considerable abnormalities after healing. During maintenance, however, the sucralfate scores fell significantly (p less than 0.02) to near control levels unlike the cimetidine scores which remained raised at pretreatment values. The histological and ultrastructural changes were not predictive of later relapse. These findings favour the use of sucralfate in preference to cimetidine for maintenance treatment in the prevention of relapse of healed duodenal ulcers.

Adolescent↗
PubMed1986

Collagenase inhibition in colonic mucosa by proteinase inhibitors.

The effect of proteinase inhibitors on collagenase activity in rabbit colonic mucosa, both in vitro and in vivo, has been measured by a tissue culture method. Aprotinin, when applied to colonic explants at doses of 20 and 40 KIU, significantly reduced the lytic activity by 97.3% and 99.1% respectively (P less than 0.001). At doses of 100, 200 and 400 KIUs, lysis was completely abolished. Rectal biopsies taken from rabbits at 4, 24, 48 and 72 h following either intramuscular, oral or rectal administration of soy or lima bean trypsin inhibitor showed significant reductions in collagenolytic activity (P less than 0.001). The effects were greater and more rapid by the enteral routes of administration and the lima bean trypsin inhibitor was more effective than that of soy bean. The results suggest an inhibitory effect on collagenase by local lumenal action on colonic mucosa. Proteinase inhibitors may thus have a role to play in colorectal surgery by reducing collagen breakdown and increasing the strength of the healing anastomosis.

Animals↗
PubMed1979

Therapeutic effect of cimetidine in patients undergoing haemodialysis.

Blood concentrations of cimetidine were measured and the therapeutic effect of the drug assessed patients undergoing maintenance haemodialysis. Thirteen patients were given a single oral 200-mg dose of cimetidine a mean of 2.7 hours before the start of dialysis. Dialysing for 6--12-6 m2 hours led to a mean fall of 71% in blood cimetidine concentration during haemodialysis. Nine patients with various upper gastrointestinal lesions diagnosed endoscopically were treated for up to six weeks with a reduced cimetidine dose of 200 mg 12-hourly; two patients received two courses of treatment. Repeat endoscopy after treatment disclosed satisfactory healing, and the drug did not accumulate. This lower dose regimen is recommended for patients receiving dialysis who develop upper gastrointestinal lesions for which a histamine H2-receptor antagonist is indicated.

Adult↗
PubMed1979

Gastric function and histology in chronic renal failure.

Gastric function and histology were investigated in 24 patients with untreated chronic renal failure. At endoscopy nine patients had oesophagitis, 12 patients were considered to have gastritis, and the duodenum appeared inflamed in 20 patients. Endoscopic biopsies were taken at standard sites in the stomach and duodenum; gastritis was found in all patients, and 17 patients had duodenitis. Stimulated acid secretion was impaired in seven out of 20 patients and acid hypersecretion was found in a further two patients. Pepsin output correlated well with acid output in these patients. Fasting serum gastrin levels were elevated in 12 of the 19 patients tested. Patients with atrophic gastritis had low acid outputs and hypergastrinaemia, and when extensive gastritis was present, the patients tended to have more severe renal failure and hyposecretion of acid. Three patients were studied again after regular haemodialysis or renal transplantation and were found to show marked endoscopic and histological improvement.

Adult↗
PubMed1979

Effects of bile acids on mucus secretion in the dog colon.

The effects of unconjugated bile acids on colonic mucus production have been studied in the dog. Isolated segments of both ascending and descending colon were simultaneously perfused with either chenodeoxycholic, deoxycholic or cholic acid and the mucus production estimated from the total hexose output. Each bile acid produced a significant increase in mucus output in both the right and left colonic segments. There were no differences between the right and left colon in terms of mucus output for any of the bile acids studied. Deoxycholic had a greater effect than chenodeoxycholic which had a greater effect than cholic acid in colonic mucus production. Further, these effects on mucus secretion were completely reversible. In diarrhoea associated with disease or resection of the ileum, the effect of bile acids on mucus secretion may be as important as their effects on the inhibition of water and electrolyte absorption.

Animals↗
PubMed1978

Failure of bran to protect against experimental colon cancer in rats.

The ability of dietary fibre to prevent colon cancer was tested in rats injected with 1,2-dimethylhydrazine (D.M.H.), a substance which induces cancer of the colon. 60 rats were fed the same formula solid diet but allocated three different amounts of dietary fibre--20 were given 4.8% w/w crude fibre, 20 were given 20% w/w bran, and 20 received no fibre. Half of the animals in each fibre group received a course of subcutaneous D.M.H. and half were given subcutaneous saline. After a year's observation, there was no significant difference in the incidence of, or mortality from, colonic carcinoma between the D.M.H.-treated groups.

Adenocarcinoma↗