Progress and frustration in inflammatory bowel disease.

Advances -- and lack of them -- in our understanding of the aetiology, nature, and treatment of ulcerative colitis and Crohn's disease during the past 30 years are reviewed with special reference to personal experience.

A search for persistent virus infection in Crohn's disease.

Cell cultures derived from Crohn's disease and control tissues were subjected to a series of tests designed to detect persistent, non-cytocidal virus infection. No evidence for any such infection was found, and it is concluded that persistent viral infection of gut tissues is unlikely to play a significant role in the pathogenesis of Crohn's disease.

Virus isolation studies in Crohn's disease: a negative report.

Homogenates of gut and mesenteric lymph node tissue from patients with Crohn's disease, ulcerative colitis, and control patients were tested for cytopathic effect (CPE) production in a series of cell lines including rabbit ileal and W138 cells. A CPE was produced in W138 cells by tissue homogenates from patients with Crohn's disease, ulcerative colitis, and control patients. Evidence was obtained to suggest that this effect, although superficially similar to a viral CPE, was due to toxic protein constituents of inflamed tissue homogenate.

Induction of granulomas in mice by Crohn's disease tissue.

Normal and immunodeficient CBA and A2G strain mice were inoculated with crude (100 to 20 to 30 micrometer), cell-free (0.2 micrometer) filtrates of Crohn's or noninflammatory bowel disease tissue homogenates, which were either fresh or frozen to -70 degree C. Mice of each strain developed epithelioid and giant cell granulomas both locally at the site of injection and systemically in response to crude and cell-free filtrates of Crohn's tissues. Control mice did not develop such changes. The granulomas evolved slowly, predominantly between 9 and 27 months. The granuloma-inciting agent has been shown to be present in ileum, colon, and mesenteric lymph nodes of patients with Crohn's disease and it withstands freezing to -70 degree C. The use of Crohn's tissues common to this study and one in rabbits previously reported, suggests that the induction of granulomas by this agent is not strain- or species-specific, and is independent of the immune status of CBA mice.

Sexual problems among married ileostomists. Survey conducted by The Ileostomy Association of Great Britain and Ireland.

The Ileostomy Association of Great Britain and Ireland has conducted a survey to assess the incidence and nature of sexual problems among a one in 10 sample of its membership. The analysis was restricted to married ileostomists; of those aged up to 45 years at the time of operation 16% had married and 23% had had children after the operation. The majority had adapted well to the ileostomy, and this appeared true also for the spouse. However, 12% of those who replied ascribed marital tension, unhappiness, or even separation, to the presence of the stoma. There was no evidence of sexual dysfunction from the construction of an ileostomy without rectal excision. After rectal excision nearly one-third of men reported sexual dysfunction, the frequency and severity of which was related to the age at operation. Up to the age of 45, one of 88 men developed complete erectile impotence and 17 partial dysfunction; over this age five of 30 men developed complete and 11 partial erectile impotence. One-third of women reported some dyspareunia after rectal excision.

Evidence of an agent transmissible from ulcerative colitis tissue.

Five New Zealand White rabbits were injected intracolonically with homogenates (100 mum) of ulcerative-colitis tissue. Histological changes closely similar to those seen in the human donors were present in the mucosa and submucosa of the large intestine of four of these rabbits 3-12 months later. Similar changes were seen in the large intestine of three of four rabbits 6-13 months after intravenous or intracolonic inoculation of homogenates of rabbit mesenteric lymph-nodes after passage of human ulcerative colitis tissue (100 mum or 0.2 mum). Three of thirty A2G strain mice injected with similar tissue homogenates (100 mum or 0.2 mum) from patients with ulcerative colitis into the footpad or intraperitoneally, had granulomatous changes in footpad, bowel, liver and/or spleen 3-22 months later. Such changes did not develop in rabbits or mice inoculated with tissue from normal controls. The results of these experiments suggest that a transmissible factor is involved in the aetiology of ulcerative colitis.

Place of azathioprine for Crohn's disease.

The clinical effects of azathioprine have been compared with those of corticosteroids in a group of 112 patients who have come under the care of a single unit between 1963 and 1975. There is no clear evidence that azathioprine alters the course of the disease in the long term; it is of value in obtaining a remission, particularly when the disease affects the large intestine.

A controlled trial of intraperitoneal noxytiolin in perforated appendicitis.

A controlled trial of intraperitoneal noxytiolin (Noxiflex) solution in patients with peritonitis due to perforated appendicitis is reported. No significant difference was found in the incidence of complications between the treated and a control group, raising doubts as to whether this substance is of value when used intraperitoneally in peritonitis.

Experimental animal studies of the etiology and pathogenesis of Crohn's disease.

Nineteen New Zealand White Rabbits were inoculated intramurally into the intestine with a 100- or 0.2-mu filtrate of homogenate of fresh ileum or colon from each of 6 patients with histologically confirmed Crohn's disease and compared with 22 animals injected with homogenates of normal ileum or colon from each of 5 patients; 4 sham controls were also included. The animals receiving Crohn's homogenates put on less weight than the controls; mucosal ulceration, ileal thickening, and abscess formation were seen in 8 animals and granulomatous changes evolved in 9. No significant macroscopic abnormalities or granulomatous changes were present in any of the 22 control inoculated rabbits. Successful first passage was achieved from 6 of 11 rabbits. The results of these experiments therefore confirm and extend those of our earlier reports and demonstrate that the transmissible agent or agents responsible must approximate to the size of a virus or be capable of being deformed to pass through a 0.2-mu filter.

A rabbit model of perforated appendicitis with peritonitis.

No satisfactory animal model simulating acute perforating appendicitis followed by peritonitis in man has hitherto been achieved. A technique has been developed in New Zealand White rabbits to fulfil these desiderata. The bacterial flora associated with the ensuing peritonitis is similar to that found in man both as regards aerobes and anaerobes and their concentrations. The method effectively produces the required model in 70 per cent of rabbits subjected to the experiment. Satisfactory postoperative survival is achieved enabling therapeutic studies.