The irritable bowel syndrome: a disease or a response? Discussion paper.
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Biomedical subjects
Publications and source records attributed to M J Ford.
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The clinical characteristics and putative pathogenetic mechanisms of the irritable bowel syndrome are described. The complex inter-relationships between stressful life situations, psychoneurotic and somatic factors involved in the production, maintenance and management of alimentary symptoms are discussed using a behavioural model and catastrophe theory.
Two cases of benign oesophageal stricture following the inadvertent ingestion of Steradent tablets are presented. We stress the particular risk of this problem occurring in the elderly population.
The Michigan alcoholism screening test was used to assess the prevalence of alcohol problems in 142 patients aged between 18 and 60 years consulting a general practitioner. Previous and/or current alcohol problems were identified in 33% of men and 4% of women. Unemployment was found to be significantly associated with alcohol problems in the men of the study group. The higher proportion of patients with alcohol problems requesting consultation compared with those without such problems did not appear to be associated with a specific presenting complaint.Screening for alcohol problems should be undertaken in all patients consulting a general practitioner if early detection and intervention are to be achieved.
The cause of intractable chronic diarrhoea was found to be malabsorption of bile acid in five out of 42 patients thought to have the irritable bowel syndrome, six out of 29 patients with persistent diarrhoea after surgery for peptic ulcer, 23 who had undergone small bowel resection, and two others. Specific treatment brought symptomatic relief. The diagnosis was established by measuring the proportion of SeHCAT, a synthetic bile salt, retained one week after oral administration of a tracer dose of less than 100 micrograms of the compound labelled with 40 kBq (1 microCi) of selenium-75. These results indicate that malabsorption of bile acid is a more common cause of chronic diarrhoea than is generally appreciated. Measurement of retention of SeHCAT is a simple, accurate, and acceptable means of establishing the diagnosis of this debilitating but treatable condition.
Significant levels of resistance against Schistosoma mansoni challenge were developed by mice exposed to highly irradiated (20 krad.) cercariae of the homologous species (53-67%), whereas vaccination with S. bovis, S. haematobium or S. japonicum failed to confer significant levels of resistance (-5-12%), thus confirming the specificity of the immunizing procedure. Attempts to transfer resistance to naive recipients by injection of serum and of spleen or lymph node cells from donor mice vaccinated with highly irradiated cercariae were largely unsuccessful. However, significant levels of resistance could be transferred to mice by injection of serum from rabbits exposed to irradiated cercariae. Comparable levels of resistance were conferred by injection of serum at the time of challenge (34-69%) or 5-6 days later (31-56%). In contrast, sera from rabbits injected with soluble egg antigen or homogenized cercariae failed to confer protection upon recipient mice. Sera from vaccinated mice, vaccinated rabbits and antigen-injected rabbits all caused cell adherence to skin-transformed schistosomula but neither the level of adherence nor the serum titre correlated with the ability to confer protection to mice.
The presenting features, clinical course and outcome of 19 patients with a diagnosis of CNS sarcoidosis are described. In two-thirds of the patients the initial features of sarcoidosis were neurological; half of them had an acute monophasic illness and half a chronic progressive or relapsing course. A favourable outcome was recorded unexpectedly during a study period of one to 16 years for two-thirds of the patients. The course of the disease in four patients suggested multiple sclerosis thus emphasising the importance of considering the possibility of CNS sarcoidosis in patients with suspected demyelinating disease.
In PVG rats a single immunizing infection with Schistosoma mansoni cercariae exposed to 0, 5, 10 or 20 krad. gamma radiation failed to induce more than minimal resistance (17-29%) to challenge 4 weeks later, whereas 4 immunizations with 20 krad.-irradiated cercariae, over several months, induced substantial resistance (75%). In contrast, significant protection was induced in Fischer rats by a single immunization with unirradiated cercariae or cercariae irradiated with up to 80 krad. Comparable resistance was induced by unirradiated and by 2, 5 and 20 krad.-irradiated cercariae (67-74%) and lower levels by 10, 40 and 80 krad.-irradiated infections (57, 48 and 33%, respectively). Although the resistance induced by a single dose of 1000 20 krad.-irradiated cercariae could be boosted by a second (88%), further immunizations failed to enhance this resistance. Also, increasing the number of immunizing cercariae in single or multiple vaccinations from 1000 to 3000 failed to increase the resistance. While the resistance induced by 20 krad.-irradiated cercariae persisted undiminished for at least 25 weeks (67%), the resistance induced by normal cercariae declined to insignificant levels by 25 weeks (21%). Comparison of the migration and survival of unirradiated and of 20 and 40 krad.-irradiated cercariae revealed dramatic differences in their fate: parasites exposed to 40 krad. remained in the skin, while the majority of 20 krad.-irradiated parasites died in the lungs after a sojourn of at least 14 days. Thus, although skin schistosomula alone could induce significant protection, optimal resistance was induced only by parasites which migrated to the lungs or beyond. The immunizing potential of these older parasites was investigated by exposing rats to lung- and liver-stage larvae injected into the tail and mesenteric veins, respectively. Irradiated 4-day lung schistosomula induced comparable resistance (79%) to that induced by a complete unattenuated cercarial infection (78%), whereas less resistance was induced by irradiated and unirradiated 11-day-old liver worms (30 and 27%) and by 25-day-old pre-adult worms (48%).
The immune-dependent elimination of a challenge infection in rats vaccinated with highly-irradiated cercariae of Schistosoma mansoni was analysed by passive transfer of serum, recovery of the challenge from the lungs and liver and by transferring lung-stage schistosomula. Recipients of serum from rats immunized with either unirradiated, 20 or 40 krad.-irradiated cercariae, most of which die in the liver, lungs and skin, respectively, were equally resistant if the serum was injected on the day of infection or 5-7 days after infection. In addition, vaccinated rat serum transferred to mice and vaccinated rabbit serum transferred to rats conferred comparable protection when injected on day 0 or 5 days after infection of the recipients. This apparent susceptibility of the lung schistosomula to immune attack was confirmed by challenging 20 or 40 krad.-irradiated cercariae vaccinated rats with lung-stage schistosomula derived either from mice or rats. All the detectable attrition of a cercarial challenge in vaccinated rats occurred between 7 and 10 days post-challenge, before the parasites reached the liver. Since there was no evidence of damage or attrition in the skin or lungs before day 7 it was concluded that immune-dependent elimination occurred rapidly following a 'window of sensitivity' coinciding with the migration of the parasites from the lungs to the liver.
Levels of antibody a binding to the schistosomulum surface and b mediating in vitro eosinophil-dependent cytotoxicity of schistosomula were studied and compared to the in vivo levels of resistance to cercarial challenge in mice infected with irradiated cercariae, unirradiated cercariae of single or mixed sex, or injected with eggs. Antibody-binding was assessed by counting the number of IgG-Fc-receptor bearing cells (P388D1 cells) adhering to mechanically-transformed schistosomula. Significant levels of adherence occurred with sera taken from 1--2 weeks following exposure to irradiated cercariae, the level increasing gradually thereafter and being enhanced by repeated exposure. Sera from the bisexual infection showed a dramatic increase in binding activity between weeks 5--8, and with the single sex infections there was a steady rise up to week 10 followed by a sharp rise between weeks 10--12. Weekly injections of eggs produced a steady rise in serum binding activity. Sera taken just before challenge were also tested for their ability to mediate killing of schistosomula by eosinophil-enriched preparations of heterologous rat peritoneal exudate cells in vitro. Significant levels of killing occurred with all sera, but the greatest lethal activity was found in sera from the egg-injected, chronically-infected and 200 male cercariae-infected groups. This ranking did not correlate with in vivo resistance against challenge as assessed by worm recovery, the egg-injected and single sex-infected groups failing to manifest significant resistance.
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A review of 40 patients with "solitary ulcer" of the rectum confirmed by rectal biopsy has provided information about the natural history of this unusual condition. At presentation, symptoms usually were the passage of blood and mucus per rectum, alteration in bowel habits, and anorectal pain. Solitary or multiple ulcers were found within 13 cm of the anal margin in 27 patients and were usually sited anteriorly; in 13 patients macroscopic ulceration was absent, though the histopathology of the rectal biopsy specimens was otherwise similar. Rectal mucosal prolapse was found in 25 of 29 patients examined specifically for this. Thirty-one patients were followed-up for a mean period of 4.8 yr (range 1-15 yr). In 22 patients, rectal ulceration was observed at presentation. In 14 of these patients, ulceration persisted despite treatment. In 9 patients presenting without macroscopic ulceration, rectal ulcers were not observed during follow-up; thus two patient groups were apparent. Neither medical nor local surgical treatment consistently achieved relief of symptoms or healing of the lesion.
Thirty-four acute exacerbations of chronic bronchitis were treated using a new formulation of trimethoprim and sulphadiazine. Significant bacterial isolates were obtained in 18 exacerbations of which 12 comprised Haemophilus influenzae. Adverse effects of treatment, principally nausea, occurred in 5 patients. A satisfactory clinical response in association with the achievement of mucoid sputum was obtained in 94% and the mean time for sputum conversion of 3.8 days compares favourably with other antibiotics.
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Changes in the surface antigenicity and susceptibility to in vitro killing during development of schistosomula of Schistosoma mansoni were studied using serum from chronically infected mice (CIS) and from mice vaccinated with highly irradiated (20 krad) cercariae (VS). Binding of these sera was quantitated by counting the number of P388D1 cells (a transformed, macrophage-like cell of mouse origin, bearing Fc receptors for IgG) binding to the parasite surface. Compared with schistosomula derived in vitro by mechanical transformation (MS), schistosomula recovered 3 hr after skin penetration in vitro (SS) showed a significant loss in surface binding of CIS. Schistosomula recovered 3 hr after skin penetration in vivo (SRS) showed even less binding, and this trend continued such that parasites recovered from the lungs 5 days after infection (LS) showed only minimal binding, and 10-day-old worms from the portal system showed no significant binding. In contrast, VS, which bound significantly less well to MS than CIS, showed enhanced binding to SS, and in the face of their declining antigenicity with respect to CIS, 3- to 24-hr SRS maintained this raised level of antigenicity. Although there appeared to be a decline in binding of VS thereafter, LS remained antigenic, still binding as many cells as MS did despite the fact that they also expressed host antigens detected using antisera raised against mouse RBC. In spite of this persistence of VS binding up to the lung stage, resistance to eosinophil-mediated killing in vitro had developed by 48 hr post-infection, and LS were totally resistant to both eosinophil- and C-mediated killing.
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