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Biomedical subjects

C G Clark

Publications and source records attributed to C G Clark.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1983

The effect of enteral nutritional support on skeletal muscle protein synthesis and whole-body protein turnover in fasted surgical patients.

Whole-body and muscle protein turnover have been studied in surgical patients, before abdominal surgery after an 18-h fast, using infusion of 1-[13C]leucine. Four patients received an unmodified hospital diet and four received extra nutritional support (1800 kcal, 70 g protein) by naso-jejunal tube for 7-10 d previously. In patients who received nutritional support there were significantly greater values of whole-body protein synthesis (+42 per cent, P less than 0.05) and breakdown (+45 per cent, P less than 0.01) and muscle protein synthesis (+36 per cent, P less than 0.05) than in those who received the unmodified hospital diet.

Aged↗
PubMed1982

Treatment of persistent perineal sinus with vaginal fistula following proctocolectomy for Crohn's disease.

The utilization of a myocutaneous flap based on the gracilis muscle is described in two patients who had a persistent perineal sinus following proctocolectomy for Crohn's disease. In each case the posterior vaginal wall had eroded to form a fistula. This flap provided a cutaneous surface with good sensation to replace the posterior vaginal wall and tissue bulk to fill the excised cavity. A good functional result was obtained in each patient. This technique provides a useful contribution to the management of this unusual complication.

Adolescent↗
PubMed1982

Polya gastrectomy for recurrent ulceration following vagotomy.

Thirty-seven patients with recurrent ulceration after vagotomy were treated by Polya gastrectomy and have been followed up for a minimum of 3 years (median 5 years). The diagnosis of recurrent ulcer was made by endoscopy or at operation. Nine patients were initially treated with cimetidine and either failed to respond or relapsed on maintenance dosage. There were 2 operative deaths and 2 patients were lost to follow-up. The results of Polya gastrectomy were Visick grade I: 61 per cent, Visick grade II: 15 per cent, Visick grade III: 9 per cent and Visick grade IV: 15 per cent, Two patients had further recurrent ulceration.

Adult↗
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

Proximal gastric vagotomy after five years.

A follow-up of 93 patients with chronic duodenal ulceration treated by proximal gastric vagotomy without drainage five to nine years previously shows a high incidence of confirmed recurrent ulceration of 16.1%. In addition, there have been patients with transient recurrent ulceration, and a small group with persistent dyspeptic symptoms but in whom no ulcer has been demonstrated. The operation is commendable for its lack of side-effects, but the high incidence of recurrent or persistent symptoms may lead to some reservations about its general application in the treatment of chronic duodenal ulceration.

Adult↗
PubMed1981

The diagnosis of Ménétrier's disease.

Two cases of Ménétrier's disease are reported to illustrate the clinical presentation and diagnosis of this unusual condition. The literature has been reviewed of all the reported cases to establish the relative importance of the individual symptomatology, the value of the diagnostic methods, and to highlight the diagnostic pitfalls. Recognition of the barium meal appearances and snare biopsy at gastroscopy may avoid the necessity of diagnostic laparotomy.

Adolescent↗
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↗
PubMed1981

Constipation--a simple approach to treatment.

A simple method of treating patients with constipation is outlined and has been used successfully in 40 patients with severe primary constipation or constipation associated with diverticular disease.

Adult↗