Colonic cancer induced by 1,2-dimethylhydrazine: promotion by experimental colitis.
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Biomedical subjects
Publications and source records attributed to J F Chester.
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Because cholecystectomy stimulates hypertrophy and hyperplasia in the hamster pancreas, its effect on experimental pancreatic carcinogenesis was studied in this animal model. Forty female Syrian hamsters underwent cholecystectomy, while 40 others underwent sham operations. Two weeks later, 30 hamsters undergoing cholecystectomy and 30 hamsters undergoing sham operations received 4 weekly subcutaneous injections of N-nitroso-bis (2-oxopropyl) amine (BOP) (10 mg/kg). Remaining hamsters (n = 20) received equal volumes of 0.9% saline solution. A further 10 hamsters (controls) underwent no surgery and received no injections. Thirty weeks after the first BOP or saline injection the pancreas of hamsters that had undergone cholecystectomy was only 3% heavier than that of sham-operated animals, and there was no difference in the incidence of pancreatic cancer between BOP-treated hamsters that had undergone cholecystectomy and those that had undergone sham operations. In this study, cholecystectomy had no influence on BOP-induced pancreatic carcinogenesis in the Syrian hamster.
Conflicting reports exist for the efficacy of intermittent wound perfusion with bupivacaine in the relief of postoperative pain. A study was devised to assess postoperative pain relief objectively using a Patient Controlled Analgesic Device (PCAD) during continuous wound perfusion with bupivacaine or saline. Thirty consecutive patients undergoing cholecystectomy were randomised to receive continuous postoperative wound perfusion with 0.5% bupivacaine for 24 h followed by normal saline for a further 24 h or vice versa. During the study period, conventional analgesia was provided using a PCAD set to deliver (and record the number of) on-demand bolus doses of intravenous pethidine 0.2 mg/kg at half-hourly intervals as required. Pethidine requirements were higher on the first postoperative day, regardless of which solution was given, but bupivacaine perfusion almost halved mean linear analogue pain scores compared to those recorded with saline. Likewise, the number of bolus doses of pethidine demanded was reduced by an average of 68% compared to those recorded during saline perfusion on day 1 (P = 0.01) and by 82% on day 2 (P = 0.01). When assessed by objective criteria, perfusion of surgical wounds with bupivacaine after cholecystectomy produces better pain relief than wound perfusion with saline.
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The availability of an endoscopic support brace for use during gastrointestinal endoscopy is described.
We studied the binding of tritium-labeled deferoxamine, a strong iron chelator, to crocidolite asbestos fibers in vitro and in vivo. In aqueous suspension of asbestos, deferoxamine binding was rapid and strong, suggesting specific binding to iron. For the in vivo experiments, diffusion chambers containing native asbestos fibers or deferoxamine-washed asbestos were implanted in the peritoneal cavities of mice. Five days after parenteral injection of tritiated deferoxamine chambers were removed and the asbestos counted. More than twice as much label (2206 +/- 348 c.p.m./100 mg asbestos) was bound to the native asbestos as compared to the deferoxamine-washed asbestos (1080 +/- 201 c.p.m./100 mg asbestos), suggesting specific binding in vivo. Since deferoxamine can inhibit asbestos toxicity in vitro, these experiments suggest the feasibility of testing whether deferoxamine can prevent asbestos-related disease in vivo.
Over a 5-year period 68 diabetic patients underwent 102 primary partial amputations of the foot for infected diabetic gangrene. Seventy (69%) of these operations healed without further local surgery, but five patients needed seven femoropopliteal bypass grafts (two bilateral) to achieve healing. In total, 32 primary operations needed revision by further surgery to the foot or by leg amputation. Of the original operations 31% were carried out by a consultant surgeon; the rest (69%) were performed by a junior surgeon. By contrast, only four of the 32 operations needing revision (12%) had originally been done by a consultant, whereas 28/32 (88%) had been carried out by a junior surgeon. Of limbs at risk 65/80 (81%) were salvaged. Five patients died during their hospital admission, giving an overall mortality of 7%.
The augmenting effect of chronic inflammation on bladder cancer was studied in female Swiss mice treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT), 0.15% by weight of diet for 20 weeks. To produce chronic inflammation one silk suture and one catgut suture were placed through the bladder wall of 63 mice to receive FANFT and 18 to receive normal diet. In remaining mice (no. = 62) the bladder was simply touched without suture insertion. Thirty-two animals treated with FANFT and 33 treated with FANFT + sutures also received supplements to their drinking water throughout the experiment of the sulfhydryl-reducing agent N-acetylcysteine (500 mg./kg. body weight/day). Seven weeks following FANFT treatment, bladder cancers developed in 12% of mice with sutures and FANFT and in 19% of those with sutures, FANFT, and N-acetylcysteine. No cancers developed in mice receiving FANFT alone or FANFT with N-acetylcysteine and none in mice treated with sutures only. Placement of silk sutures through the bladder wall of mice augments FANFT-induced bladder cancer. N-acetylcysteine at these doses does not influence the incidence.
The incidence of Syrian golden hamsters with pancreatic cancer induced by subcutaneous injections of N-nitroso-bis(2-oxopropyl)amine for 19 weeks (each 10 mg/kg) increased from 44% to 75% (p=0.016) when epidermal growth factor was also administered from week 5 through week 8 (5 mug energy three days for injections). Epidermal growth factor increased pancreatic weight and body weight. The incidence of animals with bronchial cancer doubled. Epidermal growth factor could be a cocarcinogen as a result of its mitogenic activity.
Immunofluorescence studies have demonstrated the presence of fib (a group of fibrinogen- and fibrin-related proteins that react with antibodies raised against fibrinogen) in the stroma of several transplantable animal and autochthonous human tumors. Acceptance of these reports was tempered by the possibility of artifactual clotting and fibrinolysis associated with tumor removal or tumor transplantation and by the relatively poor histology inevitable when immunofluorescence is performed on frozen tissue sections. An immunoperoxidase study therefore was undertaken of the ductal pancreatic carcinomas induced in female LGV Syrian hamsters by N-nitroso-bis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4]. Artifactual clotting and fibrinolysis associated with tumor removal were avoided by systemic anticoagulation and antifibrinolysis. Fibronectin and residual fib were prominent components of tumor stroma. Prominent fib deposits also were found in a new location: the basement membrane zones of atypical pancreatic ducts and invasive carcinomas. In contrast, fib deposits were never found in the basement membranes of blood vessels, nerves, or pancreatic acini of BOP-treated or normal animals, or in the ductal basement membranes in the normal pancreas. Ducts with marked atypicality and invasive pancreatic carcinomas frequently exhibited discontinuous basement membrane staining for fib, which often paralleled loss of staining for the integral basement membrane proteins--type IV collagen and laminin. Loss of acquired fib basement membrane staining with malignant disease progression may serve as a new marker for local tumor invasion.
The alpha-adrenergic blocker phenoxybenzamine has been shown to be useful in the treatment of prostatism. To assess the place of phenoxybenzamine in the management of acute retention, 43 patients presenting with acute urinary retention secondary to benign prostatic hyperplasia were catheterized suprapubically. They were then randomized to receive either oral phenoxybenzamine (10 mg b.i.d.; n = 21), or placebo tablets (n = 22). Forty-eight hours later, the bladder of each patient was filled through the catheter with 300 ml sterile saline, the catheter was clamped, and the patient encouraged to void. Only 2 of 21 (10%) patients receiving phenoxybenzamine and 3 of 22 (14%) receiving placebo were able to void satisfactorily (p = NS). In this study phenoxybenzamine had no place in the management of acute retention of urine secondary to benign prostatic hyperplasia.
Because epidermal growth factor (EGF) is rapidly bound and internalized into rat pancreas, stimulates uptake of tritiated thymidine, and increases pancreatic weight, a cocarcinogenic effect on pancreatic cancer seemed likely. Pancreatic adenocarcinomas were induced in 70 female Syrian hamsters by 19 weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine (BOP) (10 mg/kg). From Wk 5 through Wk 8 of BOP injections, additional s.c. injections of EGF (5 micrograms every 3 days for 10 injections) were given to 45 animals, while 25 received saline solution. An additional group of 10 received EGF alone, and another 10 animals received saline solution alone (controls). Eleven wk later, the mean body weight of EGF-treated animals increased by 29% as compared with that of controls, and their mean pancreatic weight relative to body weight increased by 44% as compared with controls. The mean body weight of EGF + BOP-treated animals increased by 10%, and their pancreatic weight relative to body weight increased by 22% as compared with that of animals treated with BOP alone. The incidence of pancreatic cancer in the EGF + BOP-treated animals was 75% versus 44% in those treated with BOP alone (P = 0.016). No tumors developed in either animals treated with EGF alone or control animals. EGF augments pancreatic carcinogenesis induced by BOP. The incidence of bronchial carcinomas doubles.
Because ulcerative colitis predisposes to colonic cancer, for determination of the effect of colitis on experimental colon carcinogenesis, rectal instillations of peptides that attract and activate neutrophils were used to induce colitis in CD-1 (ICR) BR mice receiving 20 weekly injections of the carcinogen 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8]. From week 4 through week 15 of DMH injections, twice-weekly enemas of formyl-norleucyl-leucyl-phenylalanine were given to DMH-treated mice. The effect of the antioxidant vitamin E in the diet (1,750 IU/kg diet) was studied in another group of mice treated with DMH and having colitis. Four weeks after DMH was discontinued, cancer occurred in 9 of 28 (32%) animals with DMH plus control enemas, in 22 of 29 (76%) animals with DMH plus colitis (P = .001), and in 16 of 28 (57%) animals with DMH plus colitis plus supplemental vitamin E (P = .11 compared with the group with DMH and colitis). Colitis enhances DMH-induced colonic carcinogenesis.
A simple, inexpensive method for one-way collection and measurement of secretions is described. This method has been used successfully in surgical practice in Bath for more than 20 years (1).
An implantable drug-delivery and venous sampling device is described that is constructed from a polyvinyl chloride catheter and a rubber intravenous catheter plug coated with Silastic. The implant was used for repeated venous sampling and for both administration of parenteral solutions and injections into the right colon of the rat for periods to 1 mo.