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Biomedical subjects

M R Lewin

Publications and source records attributed to M R Lewin.

At least 55 records · Page 3Linked to original sources
PubMed1986

Gastric secretory responses to modified sham feeding (MSF) and insulin after vagotomy.

Modified sham feeding (MSF) and insulin tests were carried out in 28 patients after vagotomy. Basal and pentagastrin collections were also performed. Using the secretory data from 9 of the patients with endoscopically proven recurrent ulcer as a reference, 20 gastric secretory indices were studied and critical levels were chosen to provide the maximum sensitivity and specificity. The eleven most discriminating indices were then used to evaluate the remaining 19 patients. There was agreement between the responses to MSF and insulin as to the adequacy of vagotomy in 16 of the patients (84 per cent) and contradictory responses in 3 patients (16 per cent). Overall, MSF responses were as discriminating as the responses to insulin. A simplified ward test, based on crude volume measurements in response to MSF is proposed.

Adult↗
PubMed1986

Surgery for peptic ulceration associated with hypergastrinaemia.

Between 1971 and 1983, 31 males and 13 females were found to have peptic ulceration associated with hypergastrinaemia. An antral G-cell lesion was present in 11 (25 per cent) and a gastrinoma in 14 (32 per cent). There were 11 patients with multiple endocrine adenomatosis (MEA) (25 per cent) and 4 (9 per cent) with primary hyperparathyroidism. Four patients (9 per cent) were unclassified. Length of history and level of gastrin did not differentiate between the groups and an average of 2.5 operations was performed per patient, while the overall mortality was 27.3 per cent. The patients with G-cell lesions were significantly younger than all the other groups (P less than 0.01). Partial gastrectomy adequately treated G-cell hyperplasia. Total gastrectomy was required to treat pancreatic gastrinomata but additional pancreatic resection did not improve the outcome. In MEA, parathyroidectomy did not influence the treatment of a gastrinoma. This is the first recorded experience of surgery for hypergastrinaemia in the United Kingdom and the outcome of such a retrospective study may be a guide to the future management of these conditions.

Adenoma, Islet Cell↗
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↗
PubMed1985

Induction of nephroblastoma-like renal tumours in rats by a single dose of 1,2-dimethylhydrazine.

A single injection of 1,2-dimethylhydrazine (200 mg/kg s.c.) resulted in the development of renal tumours in 70 per cent of treated rats within 1 year. The tumours were frequently bilateral (36 per cent) and grew to a large size (up to 100 g) before causing death. Lung metastases were found in one case. Histologically, the majority of the tumours (73 per cent) exhibited the classical triphasic morphological features of nephroblastoma (Wilms' tumour) with varying proportions of epithelial (glomeruloid and tubular structures), stromal (fibrous tissue, smooth muscle, cartilage) and blastematous elements. This pathological resemblance to human nephroblastoma suggests the possibility of using dimethylhydrazine-induced renal tumours as a model of Wilms' tumour.

1,2-Dimethylhydrazine↗
PubMed1985

Measurement of blood cortisol and acid output in patients with duodenal ulceration and normal subjects during insulin hypoglycaemia.

The blood cortisol and gastric acid responses to insulin hypoglycaemia were investigated in 18 healthy control subjects and 14 patients with endoscopically proven duodenal ulceration. In both controls and patients, insulin hypoglycaemia caused blood cortisol and acid output to rise and peak simultaneously, the rises being significantly greater in patients with duodenal ulcer than in control subjects. The peak acid output and the base to peak cortisol increments were also found to be significantly greater in patients with duodenal ulcer than in control subjects (P less than 0.001 and P less than 0.005 respectively). We conclude that insulin hypoglycaemia causes stimulation of the sympathetic and parasympathetic nervous systems and of the hypothalamo-pituitary-adrenal axis, resulting in the simultaneous elevation of gastric juice acidity and blood cortisol levels. We have shown that synchronous rises in gastric acid and blood cortisol occur during insulin hypoglycaemia and that these rises are greater in patients with duodenal ulcer.

Adult↗
PubMed1984

Which electrode? A comparison of four endoscopic methods of electrocoagulation in experimental bleeding ulcers.

Several inexpensive endoscopic methods of electrocoagulation have been advocated for treatment of gastrointestinal haemorrhage. We compared four types of electrode: dry monopolar - Cameron Miller (M), liquid monopolar - Storz (L), bipolar - Bicap ACMI (B), and heater probe - Seattle (H). The electrical and thermal properties of these probes were studied using computerised monitoring of energy deposition and their efficacy and safety was tested in a randomised study in 140 experimental canine gastric ulcers. At optimal pulse settings 20J (M), 70J (L), 17J (B), 15J (H), effective haemostasis was achieved in all ulcers, the mean number of pulses being M5, L6, H6 and B11, the first three requiring significantly (p less than 0.01) less pulse than B. Relative safety of the electrodes was assessed by comparing the incidence of full thickness damage at histology: B24%, H20%, L58% and M69%; B and H proving significantly (p less than 0.01) safer than L and M. Sticking was assessed as H greater than B greater than M much greater than L. Insensitivity to extreme angulation and force of application was assessed as L greater than B greater than M (H is preset). Of the two safer electrodes the heater probe was more effective than the bipolar probe. Despite its greater tendency to stick than the other devices, the heater probe appeared the most promising of the endoscopic electrodes tested.

Animals↗
PubMed1984

An investigation into the mechanism of co-carcinogenesis of dietary cholesterol during the induction of colon cancer in rats by 1,2 dimethylhydrazine.

The mechanism by which dietary cholesterol facilities colon carcinogenesis was investigated in the dimethylhydrazine-induced rat colon cancer model. Fifty female Wistar rats received a standard course of dimethylhydrazine (DMH) injections (40 mg/kg/week subcutaneously for ten weeks) while being fed Vivonex, a cholesterol-free elemental diet. Animals were allocated to one of five dietary regimens. One control group received Vivonex with added cholesterol (10 mg/100 ml Vivonex/rat/day) throughout the experiment, while another group received Vivonex alone. The remaining three groups received added cholesterol exclusively before, during or after the ten week DMH induction period. The experiment continued for over 500 days, and was evaluated by comparing, between groups, the time taken for the development of objective signs of colonic disease (time to tumour presentation or TTP). Animals either died spontaneously or were killed and autopsied. Colon cancers were confirmed histologically in every animal. The results showed that cholesterol feeding throughout the experiment or during the DMH induction period reduced the TTP compared to controls (p less than 0.05). Cholesterol prefeeding had no such effect. In the after group, the TTP was correspondingly delayed (p less than 0.05). Cholesterol-fed controls and groups receiving cholesterol during or after the DMH induction had more colon tumours and/or a greater incidence of metastases than cholesterol-free controls or those pre-fed cholesterol. The findings indicate a direct relationship between timing of cholesterol exposure and signs of colon cancer, and demonstrate that dietary cholesterol has promoter-like characteristics.

1,2-Dimethylhydrazine↗
PubMed1984

Comparative study of the safety and efficacy of liquid and dry monopolar electrocoagulation in experimental canine bleeding ulcers using computerized energy monitoring.

The drawbacks of monopolar electrocoagulation in the control of gastrointestinal bleeding include tissue adherence, unpredictable energy deposition, and a high incidence of tissue damage. Introduction of a conductive interfacial film of liquid between the monopolar electrode and the bleeding point during electrocoagulation may overcome these drawbacks. A prospective, controlled study was undertaken to evaluate the efficacy and safety of a monopolar electrode in liquid and dry modes when used to coagulate experimental canine bleeding ulcers. All experiments were done in open fashion via a gastrotomy with hand-held electrodes. An analog computer, which could be connected between a standard electrosurgical generator and the electrode, was designed and built to monitor and control the energy delivered to the tissue. Both liquid and dry electrodes were highly effective in stopping bleeding. The liquid electrode was found to be superior to the dry electrode in that tissue adherence was eliminated and energy deposition was more predictable, varying less with angle of incidence. The liquid electrode caused less macroscopic serosal damage and less full-thickness histologic damage if the total energy or number of pulses was limited; however, both caused microscopic full-thickness damage in one-half of the experimental ulcers treated, although no perforations occurred.

Animals↗
PubMed1983

Effect of sodium taurocholate on gastric secretion in patients with duodenal ulceration.

The effect of sodium taurocholate instillation on the stimulated stomachs of patients with duodenal ulceration has been investigated. Instillation into the stomach of sodium taurocholate significantly reduced pentagastrin stimulated volume and outputs of both acid and sodium, with no change in the calculated volume of duodenogastric reflux. These observations are not consistent with the back-diffusion theory, but suggest direct parietal cell inhibition of gastric secretion by sodium taurocholate.

Duodenal Ulcer↗
PubMed1983

Combination chemotherapy with 5-fluorouracil (5FU) and 1,3-bis(2-chloro-ethyl)-1-nitrosourea (BCNU) prolongs survival of rats with dimethylhydrazine-induced colon cancer.

The effects of combination chemotherapy with 5FU and BCNU on rats with dimethylhydrazine (DMH)-induced colon cancer were investigated in a long term survival study. Eighty Wistar rats received a colon cancer producing regimen on DMH (40 mg/kg body weight/week, subcutaneously for 10 weeks). After presenting with signs of colonic disease, all rats underwent diagnostic laparotomy and colonoscopy when colon tumours were located, measured and the extent of the disease staged. Only animals with tumours (n = 63) were included and allocated to one of three tumour stages. Stage A (n = 17), had colonic tumours without serosal involvement; stage B (n = 28) had serosal involvement without metastases; stage C (n = 18) had serosal involvement with lymphadenopathy and/or metastases. Each group was randomly allocated into two subgroups, one serving as untreated controls while the other received 5FU (300 mg/m2 weekly intragastrically for life) together with BCNU (40 mg/m2 intraperitoneally on days 0, 42 and 84). The effect of chemotherapy on tumour growth was measured sequentially by colonoscopy. Animals were observed until death and necropsied, when colon carcinoma was histologically confirmed and survival analysed. The results indicate that chemotherapy significantly prolongs the survival of rats with the least advanced disease (stage A) but was of no benefit to rats with locally advanced or metastatic disease (stages B and C). Furthermore, chemotherapy was associated with a significant reduction in tumour size. Survival analyses in untreated animals show that the laparotomy staging system adopted provides accurate prognostic information. This study shows that DMH-induced colon tumours are chemosensitive, and suggests that this animal model may be a valuable testing ground for new chemotherapeutic agents.

1,2-Dimethylhydrazine↗
PubMed1982

The effects of subclinical malnutrition and refeeding on the healing of experimental colonic anastomoses.

The effects of dietary protein deprivation on he healing of colonic anastomosis in the rat have been investigated. Nutritional status was assessed both before and after operation using body weight, nitrogen balance studies and serum albumin estimations. Healing of colonic anastomosis was assessed by bursting pressure measurements. Rats fed a protein-depleted diet throughout the study were compared both with rats restored to a full diet after surgery and rats receiving a full diet throughout. Although protein depletion caused a 12.5 per cent weight loss and a negative nitrogen balance, serum albumin remained normal in all rats at the time of operation. After operation, all rats were in negative nitrogen balance, although this was greater in the protein-depleted group. Similarly, in comparison to control animals, the protein-depleted group had significantly lower colonic bursting pressures and significantly lower serum albumin concentrations. Rats returned to a full diet after operation had smaller losses of nitrogen and normal colonic bursting pressures. The results indicate that a commonly encountered degree of malnutrition, insufficient to affect nutritional indices used in clinical assessment, may interfere with colonic healing. Early re-introduction of nutrition in the postoperative period may be able to reverse this effect.

Animals↗
PubMed1982

Dietary cholesterol deprivation improves survival and reduces incidence of metastatic colon cancer in dimethylhydrazine-pretreated rats.

Cholesterol feeding of rats with colon cancer induced by dimethylhydrazine results in reduced survival and an increased incidence of metastatic colon cancer. As cholesterol may be implicated in the induction or maintenance of the metastatic process, an experiment was designed to determine whether rats with colon cancer would benefit from the removal of cholesterol from the diet. Female Wistar rats were treated with a colon cancer-inducing regimen of dimethylhydrazine (40 mg/kg/week for 10 weeks) while being fed on a standard cholesterol-containing rat pellet diet. After two rats had died spontaneously of histologically proven adenocarcinoma of the colon at 24 weeks, the remaining rats were randomly allocated in groups of 15 to one of three dietary regimens. Group S continued to receive standard pellet diet, group V were fed on Vivonex alone and group VC were fed Vivonex plus cholesterol (10 mg/100 ml Vivonex). Each group was assessed for survival and incidence of histologically proven metastatic disease. There were no differences in either survival or incidence of metastases when groups S and VC were compared. In the cholesterol deprived group V, however, there was a significant increase in survival compared with groups S and VC (p less than 0.02) and this was due to a significant reduction in the incidence of metastases (p less than 0.05). Cholesterol deprivation therefore benefits rats with established colon cancer induced by dimethylhydrazine by improving survival and reducing the incidence of metastases.

1,2-Dimethylhydrazine↗
PubMed1982

Subtotal colectomy in the dimethylhydrazine-treated rat. A surgical model of colorectal cancer.

The effects of subtotal colectomy on the survival of rats with established colon cancer induced by 1,2-dimethylhydrazine (DMH) have been investigated in an attempt to assess whether it might provide a suitable model of surgical treatment of this disease. 40 female Wistar rats received a regimen of DMH injections (40 mg/kg body weight s.c. every 14 days for 10 weeks) known to produce colon cancer. An additional 10 rats received no DMH, serving as controls (group 1). After presenting with signs of colonic disease at 25 weeks, all DMH-treated rats had diagnostic colonoscopy under general anaesthesia, only those with visible neoplasms (n = 34) being included in the study. These were randomised into two groups: group 2 (n = 13) animals were unoperated controls while group 3 (n = 21) animals had a therapeutic subtotal colectomy with histological confirmation of cancer in the resected colon. The animals were observed until death, the postoperative survival and cause of death at necropsy being compared between groups. The results showed that overall survival (p less than 0.013) and survival from death due to colon cancer (p less than 0.001) were significantly increased in the colectomised group 3 animals compared to unoperated controls (group 2). While 91% of the unoperated controls died of colon cancer, only 8% of the colectomised group died of this cause (p less than 0.001), the remainder dying from unrelated causes, predominantly DMH-induced primary extracolonic cancers. Subtotal colectomy in rats with DMH-induced colon cancer reduces mortality from this disease, providing a suitable model of surgical treatment. However, the high incidence of DMH-induced extracolonic cancers may make the model unsuitable for studies of adjuvant therapy.

1,2-Dimethylhydrazine↗
PubMed1981

Experimental colon carcinogenesis is facilitated by endogenous factors in the intestinal contents.

The theory that endogenous factors in the intestinal contents may be pathogenic during large bowel carcinogenesis was tested in the dimethylhydrazine (DMH)-induced rat colon cancer model. Thirty female Wistar rats, each serving as their own control, had a surgical transection of the proximal colon with reanastomosis to the rectum, thereby excluding part of the colon from faecal contact. All rats then received a course of DMH (40 mg/kg body wt/wk s.c. for 10 weeks) while fed on Vivonex. This diet was selected because it lacks known exogenous (dietary) cocarcinogens. It also produces mucosal atrophy in functioning (proximal) colon, to parallel the disuse atrophy induced in the defunctioned (distal) colon. Animals remained on the diet throughout the experiment and were killed when moribund or at 40 weeks. At necropsy, the anatomical distribution, number, size and histological type of colon tumours were compared between functioning and defunctioned colonic segments within the same animal. At autopsy, there were significantly fewer colon tumours in the defunctioned segment (P less than 0.005). Furthermore, there were significantly fewer carcinomas (P less than 0.005) and fewer tumours greater than 1 cm diameter (P less than 0.01) in this segment. The data indicate that endogenous factors in the intestinal contents facilitate chemically-induced colon carcinogenesis. Luminal nutrition may be implicated.

Adenoma↗
PubMed1981

The effects of cholic acid and bile salt binding agents on 1,2-dimethylhydrazine-induced colon carcinogenesis in the rat.

The theory that bile salts may be colon tumour promoters was tested in the dimethylhydrazine (DMH)-induced rat colon cancer model. Fifty Wistar rats were randomly allocated to one of five experimental group (n = 10), all fed the same standard diet. One group served as saline-injected controls, while the other four groups received DMH (20 mg/kg body weight/rat/week s.c.) for 20 weeks. In addition, each of the DMH-injected groups concurrently received 20 weekly i.g. instillations of one of the following: cholic acid (a bile acid); cholestyramine or aluminium hydroxide (both bile acid binding agents), or water. After a years observation period, all the controls were alive and tumour-free, while all the DMH-injected rats had died of histologically proven colon cancer. Irrespective of the type of gastric instillate, there were no significant differences between the groups in terms of time to tumour presentation, survival, in the necropsy incidence of primary or metastatic colon cancer, or in the numbers of colon tumours per group. The data suggest that bile salts and bile salt binding agents are not colon tumour promoters in the rat. The bile salt theory of colon carcinogenesis may need reappraisal.

1,2-Dimethylhydrazine↗
PubMed1981

Experimental evidence against the bile salt theory of colon carcinogenesis.

According to the bile salt theory of colon carcinogenesis, therapeutic agents which increase the delivery of bile salts to the large intestine may promote colon cancer. The possibility that aluminium hydroxide (Aludrox), a bile salt binding agent, might facilitate colon carcinogenesis in vivo was tested experimentally, using the dimethylhydrazine (DMH)-induced rat colon cancer model. 48 Wistar rats were randomly allocated to 1 of 3 groups, all fed the same standard diet. Two groups received a course of ten weekly DMH injections. One was allowed fresh drinking water ad libitum whilst the other received Aludrox in their drinking water. A third group received weekly saline injections plus Aludrox in their drinking water. After 1 year's observation, there were no significant differences between the groups of DMH-injected rats given drinking water with or without Aludrox in respect of survival, necropsy incidence of primary or metastatic colon cancer, or in the total number of colon tumours per group. The results provide reassurance that Aludrox does not promote colon cancer and tend to contradict the bile salt theory of colon carcinogenesis.

Aluminum Hydroxide↗