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Deoxyribonucleic acid amplification and hybridisation in Crohn's disease using a chlamydial plasmid probe.

The possibility that Crohn's disease is caused by infection with Chlamydia trachomatis was examined by probing for chlamydial plasmid deoxyribonucleic acid (DNA) in DNA extracts from Crohn's disease tissue and by means of a serological study. Gut DNA extracts were obtained from 10 patients with Crohn's disease and four control subjects and were probed with a chlamydial plasmid probe after Southern blotting. The polymerase chain reaction was also used to amplify any chlamydial plasmid DNA present in tissue DNA extracts, before Southern blotting and probing. Chlamydial proctitis control specimens were not available: gut DNA extracts mixed with traces of chlamydia plasmid served as positive controls. Using these techniques, no chlamydial plasmid DNA sequences were found in Crohn's disease tissue. An enzyme linked immunosorbent assay for C trachomatis LI was performed on 48 patients with Crohn's disease and 48 control subjects. Seropositivity was present in 14.6% of patients and 29% of control subjects and was not statistically significant (p greater than 0.05). The failure to show chlamydial DNA and the lack of serological response to chlamydia make C trachomatis infection a very unlikely factor in the pathogenesis of Crohn's disease.

Adult↗

Pathology of the defunctioned rectum in ulcerative colitis.

Faecal stream diversion may induce inflammatory changes in the defunctioned segment of the large intestine. These changes are predominantly mucosal, although confusing histological features including granulomas may be present. The pathology of 15 defunctioned rectal stumps has been studied. All patients had previously undergone urgent total colectomy for ulcerative colitis and rectal stumps had been left in situ while they awaited pelvic ileal reservoir construction. All rectal stumps showed predominantly mucosal disease but there were additional features such as florid lymphoid follicular hyperplasia (12 cases), transmural inflammation (nine cases), granulomas (four cases), fissures (eight cases), and changes akin to ischaemia or to pseudomembraneous colitis (four cases). These changes may result from a combination of defunctioning and of active ulcerative proctitis. Some induce a histological appearance that may mimic Crohn's disease. Nevertheless review of all 15 colectomy specimens showed unequivocal ulcerative colitis and none of the patients has subsequently shown any clinical, radiological, or pathological evidence to support a diagnosis of Crohn's disease. Histology of the rectal stump in ulcerative colitis may lead to an erroneous diagnosis of Crohn's disease and the patient may subsequently be denied the advantage of a pelvic ileal reservoir.

Adult↗

Failure of colonoscopic surveillance in ulcerative colitis.

A prospective surveillance programme for patients with longstanding (> = 8 years), extensive (> = splenic flexure) ulcerative colitis was undertaken between 1978 and 1990. It comprised annual colonoscopy with pancolonic biopsy. One hundred and sixty patients were entered into the programme and had 739 colonoscopies (4.6 colonoscopies per patient; 709 patient years follow up). Eight eight per cent of examinations reached the right colon. There was no procedure related death. One Dukes's A cancer was detected. Forty one patients (25%) defaulted. Of these 25 remain well; 13 are unaccounted for, and one died from colonic cancer. One patient had colectomy for medical reasons, and another died of carcinoma of the pancreas. Retrospectively an additional 16 eligible patients were identified who had not been recruited. Of these, 14 remain well, two are unaccounted for. None developed colonic cancer. Four patients refused colonoscopy. All remain well. Over the same period seven other cases of colonic cancer were found in association with ulcerative colitis, two in patients who had erroneously been diagnosed as having only proctitis and were therefore not entered into the programme, but were found at operation to have total colitis, one in a patient with colitis of seven years duration, and four patients who had previously attended the clinic but had been lost to follow up before 1978 and then had represented with new symptoms during the surveillance period. Thus, of the nine colitis related cancers diagnosed in this centre during the study period only one was detected by the surveillance programme. The results of this large study, a a review of published works, cast doubts on the effectiveness of colonoscopic surveillance programmes in detecting colorectal cancer in patients with ulcerative colitis.

Adult↗

Morphometric analysis of intestinal mucosa. V. Quantitative histological and immunocytochemical studies of rectal mucosae in gluten sensitivity.

To study changes in rectal mucosa that might be attributable to the effects of gluten, rectal biopsy specimens from untreated and treated gluten sensitised subjects were analysed morphometrically and by immunohistochemical techniques and were compared with a series of disease control mucosae. Although morphometry showed increased populations of plasma cells, lymphocytes, and mast cells in the mucosae of untreated patients, which were reduced (except for mast cells) by dietary gluten restriction, immunohistochemical techniques were far more sensitive in defining these changes. There were highly significant increases in CD3+ and gamma delta+ lymphocytes within both the lamina propria and the epithelium while neutrophils (CD15+ cells) were not at all prominent. Activated (CD25+) lymphocytes expressing interleukin (IL)-2 receptors were increased in lamina propria, usually subjacent to basal lamina, although a few IL-2R+ intraepithelial lymphocytes were found: other IL-2R+ cells were deemed to be macrophages (CD68+). These results clearly indicate that in untreated, gluten sensitised subjects the rectal mucosa shows a lymphoplasmacytoid reaction that is responsive to gluten restriction. The absence of neutrophilia suggests that this lesion is not a conventional inflammatory type proctitis, but rather one presumed to be induced by gluten antigen(s) present in the faecal stream--that is, a cell mediated form of response.

CD3 Complex↗

Lower gastrointestinal malignancy in Crohn's disease.

An increased incidence of carcinoma of the small bowel and colon has been described in patients with Crohn's disease. Tumours arising in the rectum and anus are reported less often. Between 1940 and 1992, of some 2500 patients with Crohn's disease seen at this hospital, 15 are known to have developed carcinoma of the lower gastrointestinal tract. Malignancy occurred in the colon in two patients, in the upper two thirds of rectum in one, in the lower third of rectum in seven, and in the anus in five. The 12 patients with carcinoma arising in the anus or lower rectum had longstanding severe anorectal Crohn's disease, which included a stricture in four, fistula in four, proctitis in one, abscess in two, and enlarged anal skin tags in one. The development of malignancy in patients with Crohn's disease may apply particularly to those with chronic complicated anorectal disease.

Adenocarcinoma↗

Incidence of inflammatory bowel disease in north west Greece: rarity of Crohn's disease in an area where ulcerative colitis is common.

Ulcerative colitis (UC) and Crohn's disease (CD) are generally regarded as diseases of affluent societies of the Western World, although their frequency in less affluent areas is not well established. This retrospective study therefore, assesses the incidence of UC and CD in a semirural area of north west Greece during the 10 year period 1982-1991. By the 31 December 1991, 61 patients had met standard diagnostic criteria for UC (annual incidence 4.0/10(5), 95% confidence intervals 3.0 to 5.0/10(5)) and only five patients met the diagnostic criteria for CD (annual incidence 0.3/10(5), 95% confidence intervals 0.1 to 0.8/10(5)) in this area of 157,214 inhabitants. UC incidence was lowest in the first three years at 1.8/10(5) per annum and subsequently increased to 4.8 and 5.1/10(5) per annum for the successive four and three year periods respectively. UC incidence was slightly higher in men. A third of all cases of UC had pancolitis while a quarter had only proctitis. More than one half were categorised as having moderate or severe colitis. Three quarters of the patients resided in urban areas. The incidence of CD was a twelfth of the UC incidence, which is in considerable contrast with most Western countries where the incidence of CD is usually no less than a third that for UC. The rarity of CD points to the absence of aetiological environmental factors specific for CD.

Adult↗

Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD).

BACKGROUND: It has been suggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is three or more times higher in northern than in southern Europe. The aim of this EC funded study was to investigate this apparent variation by ascertaining the incidence of IBD across Europe. METHODS: For the period 1 October 1991 to 30 September 1993 all new patients diagnosed with IBD were prospectively identified in 20 European centres according to a standard protocol for case ascertainment and definition. FINDINGS: Altogether 2201 patients aged 15 years or more were identified, of whom 1379 were diagnosed as UC (including proctitis), 706 as CD, and 116 as indeterminate. The overall incidence per 100,000 at ages 15-64 years (standardised for age and sex) of UC was 10.4 (95% confidence interval (95% CI) 7.6 to 13.1) and that of CD was 5.6 (95% CI 2.8 to 8.3). Rates of UC in northern centres were 40% higher than those in the south (rate ratio (RR) = 1.4 (95% CI 1.2 to 1.5)) and for CD they were 80% higher (RR = 1.8 (95% CI 1.5 to 2.1)). For UC the highest reported incidence was in Iceland (24.5, 95% CI 17.4 to 31.5) and for CD, Maastricht (The Netherlands; 9.2, 95% CI 6.5 to 11.8) and Amiens (north west France; 9.2, 95% CI 6.3 to 12.2). The lowest incidence of UC was in Almada (southern Portugal) (1.6, 95% CI 0.0 to 3.2) and of CD in Ioannina (north west Greece) (0.9, 95% CI 0.0 to 2.2). An unexpected finding was a difference in the age specific incidence of UC in men and women with the incidence in women but not men declining with age. INTERPRETATION: The higher overall incidence rates in northern centres did not seem to be explained by differences in tobacco consumption or education. Nevertheless, the magnitude of the observed excess for both conditions is less than expected on the basis of previous studies. This may reflect recent increases in the incidence of IBD in southern Europe whereas those in the north may have stabilised.

Adolescent↗

High Fas ligand expression on lymphocytes in lesions of ulcerative colitis.

BACKGROUND: The pathogenesis of ulcerative colitis is unclear, but cytotoxic T lymphocytes infiltrating the mucosa have been implicated in mucosal damage. The Fas ligand (FasL), expressed on cytotoxic T lymphocytes, induces apoptosis in cells expressing Fas. AIM: To analyse FasL expression in affected colonic mucosa to ascertain Fas-FasL interaction in ulcerative colitis. METHODS: FasL mRNA was quantified in colonic mucosal specimens from healthy subjects and patients with ulcerative colitis or Crohn's disease, using the competitive reverse transcription polymerase chain reaction. FasL mRNA localisation was determined by in situ hybridisation. Expression of Fas in colonic mucosa was analysed immunohistochemically. Phenotypes of lamina propria lymphocytes that expressed FasL were analysed by flow cytometry. RESULTS: FasL mRNA was strongly expressed in active ulcerative colitis lesions, but not in those associated with active Crohn's disease or active proctitis-type ulcerative colitis. In situ hybridisation showed that FasL mRNA expression occurred in mononuclear cells infiltrating lesions. Fas was expressed in epithelial cells in ulcerative colitis and Crohn's disease, and in normal subjects. Cytometry showed that FasL was expressed in CD3 lymphocytes infiltrating the lamina propria in active lesions. CONCLUSIONS: FasL is expressed in CD3 lymphocytes infiltrating into ulcerative colitis but not Crohn's disease lesions, suggesting that Fas-FasL induced apoptosis participates in the mucosal damage of ulcerative colitis.

Acute Disease↗

Irritable bowel syndrome in general practice: prevalence, characteristics, and referral.

BACKGROUND AND AIMS: Little is known about the prevalence, symptoms, diagnosis, attitude, and referral to specialists of patients with irritable bowel syndrome (IBS) in general practice. This study aimed to determine these characteristics. METHODS: 3111 patients attending 36 general practitioners (GPs) at six varied locations in and near Bristol, UK, were screened to identify those with a gastrointestinal problem. These patients (n=255) and their doctors were given questionnaires. Six months later the case notes were examined to reach criteria based diagnoses of functional bowel disorders. RESULTS: Of 255 patients with a gastrointestinal complaint, 30% were judged to have IBS and 14% other functional disorders. Compared with 100 patients with an "organic" diagnoses, those with IBS were more often women and more often judged by their GP to be polysymptomatic and to have unexplained symptoms. The majority of patients with IBS (58%) were diagnosed as such by the GP; 22% had other functional diagnoses. Conversely, among 54 patients diagnosed as having IBS by the GPs, the criteria based diagnosis was indeed functional in 91%; only one patient had organic disease (proctitis). More patients with IBS than those with organic disease feared cancer. In most some fear remained after the visit to the doctor. On logistic regression analysis, predictors of referral to a specialist (29% referred) were denial of a role for stress, multiple tests, and frequent bowel movements. CONCLUSIONS: Half the patients with gut complaints seen by GPs have functional disorders. These are usually recognised, and few patients are referred. In IBS, cancer fears often remain, suggesting unconfident diagnosis or inadequate explanation.

Adolescent↗

Thiol methyltransferase activity in inflammatory bowel disease.

BACKGROUND: Luminal anionic sulphide may contribute to epithelial damage in ulcerative colitis. Thiol methyltransferase (TMT) governs sulphide detoxification by the colonic mucosa and circulating erythrocytes. AIMS: To measure levels of TMT activity in erythrocytes of surgically treated cases of colitis or in rectal biopsies of defined groups of colitis. PATIENTS: Venepuncture blood was obtained from 37 blood donors and 27 subjects who had previously undergone a proctocolectomy for colitis: 18 for ulcerative colitis and nine for Crohn's colitis. Rectal biopsies from 122 cases were obtained: 47 without mucosal disease, 33 post-colon resection for cancer, 14 with moderate to severe ulcerative colitis, 15 with quiescent ulcerative colitis, seven with acute Crohn's colitis, and six with radiation proctitis. METHODS: TMT activity was measured by high performance liquid chromatography with radioactive detection to measure (14)C methylmercaptoethanol formation, the reaction product of cell extracts incubated with mercaptoethanol and (14)C S-adenosylmethionine. RESULTS: Erythrocyte TMT activity of surgically treated cases of colitis was significantly elevated (p<0. 001) compared with control cases. TMT activity of rectal biopsies was significantly decreased (p<0.02) in acute but not quiescent ulcerative colitis, Crohn's colitis, or radiation colitis. CONCLUSIONS: Erythrocyte TMT activity was persistently elevated after proctocolectomy for Crohn's disease and ulcerative colitis. No primary defect of TMT activity was found in any case of unoperated colitis but mucosal activity was diminished with disease progression of ulcerative colitis. Studies of genetic control of TMT activity of erythrocytes in inflammatory bowel disease appear worthwhile.

Adult↗

Pseudomembranous colitis.

Three basic histopathological patterns which may be seen in rectal biopsies from patients with pseudomembranous colitis are described, based on a study of 29 cases. The spectrum of change is illustrated and the problems of differential diagnosis are discussed--from a non-diagnostic proctitis at one extreme to acute ischaemia at the other. In the differential diagnosis of the acute colitic, the importance of urgent rectal biopsy and a carefully taken drug history is stressed. The association of pseudomembranous colitis with pre-existing disease and antibiotic therapy is confirmed. It is suggested that these cause local mucosal damage and may trigger the first part of a local Shwartzman reaction. Capillary microthrombosis may then paly a part in producing the mucosal necrosis seen later in the disease.

Adolescent↗

Granulomatous disease in the vermiform appendix.

In a twenty-year period 19 appendicectomy specimens were diagnosed as primary Crohn's disease. This represents 4.9% of the total number of both resection specimens and mucosal biopsies diagnosed as Crohn's disease during that time. This is a review of the main histopathological features found in these appendices and their subsequent clinical outcome. The predominant feature is transmural inflammation characterised by fibrosis and giant cell epithelioid granulomata. An accompanying spectrum of acute inflammatory changes is also seen. One patient progressed to more widespread ileal and caecal disease 17 months later. One patient developed perianal fistulae and chronic non-specific proctitis 24 months later. This represents a proven recurrence of one case in a study population of 19. The conclusion is that primary Crohn's disease of the appendix is usually an isolated phenomenon but rarely it may forewarn of more widespread bowel disease in the future. A discussion regarding the differential diagnosis of granulomatous appendiceal lesions is included.

Adolescent↗

Lymphogranuloma venereum as a cause of rectal strictures.

Rectal strictures are uncommon in young patients without a history of malignancy, inflammatory bowel disease or previous surgery. Lymphogranuloma venereum of the rectum has been described as a rare cause of rectal strictures in the western world, mainly in homosexual men and in blacks. It presents with nonspecific symptoms, rectal ulcer, proctitis, anal fissures, abscesses and rectal strictures. Clinical and endoscopic findings as well as histology resemble Crohn's disease, which may be misdiagnosed. Serology is often positive for Chlamydia trachomatis but negative serology is not uncommon. We present two young black women who suffered from chronic diarrhoea, abdominal pain and weight loss. There was no previous history and investigations showed in both cases a long rectal stricture. Serology was positive in one patient. They were treated with erythromycin and azithromycin and they both underwent an anterior resection of the rectum. Postoperative histology confirmed the presence of lymphogranuloma venereum of the rectum. We conclude that rectal lymphogranuloma venereum is a rare cause of rectal strictures but surgeons should be aware of its existence and include it in the differential diagnosis of unexplained strictures in high-risk patients.

Adult↗

Sigmoidoscopy--a necessary procedure in the routine investigation of homosexual men?

In a study to assess the value of sigmoidoscopy in the routine investigation of homosexual men, this procedure was undertaken on 1118 men who attended a sexually transmitted diseases clinic as "new" or "return new" patients. Serious rectal disease was not identified in any of the 557 men who were symptomless at the initial attendance. Though the extent of the proctitis diagnosed in 166 men would not have been defined, 99% (465) of 470 anorectal lesions would have been identified if proctoscopy alone had been performed. It is concluded that sigmoidoscopy does not have a role in the routine investigation of homosexual men.

Diagnostic Tests, Routine↗

Prevalence of Chlamydia trachomatis in young men in north west London.

BACKGROUND: Chlamydia trachomatis is the most common, treatable, bacterial sexually transmitted infection in England and Wales. Among men, chlamydial infection is an important cause of non-gonococcal urethritis, epididymitis, and proctitis. The case for wider screening among women has been accepted by an expert advisory group. In the absence of estimates of the prevalence of infection in men, its potential impact at the population level is difficult to assess. OBJECTIVE: To estimate the prevalence of Chlamydia trachomatis in young men in clinic and community based samples in north west London. METHOD: Cross sectional survey in healthcare centres and general practices in north west London. 1002 males aged 18-35 years, living in north west London, were recruited by staff in occupational health departments, general practices, student health services, and a "well man" clinic and by postal recruitment in four GP practices. The men were tested for C trachomatis using the ligase chain reaction assay on urine samples. The main outcome measure was prevalence of C trachomatis infection in men aged 18-35 years. RESULTS: The overall response rate was 51%. Prevalence of confirmed infection was 1.9% (95% CI: 1.14% to 2.96%) in all men. Best estimated minimum prevalence of infection was 1% (95% CI: 0.58% to 1.50%). Estimated prevalence was highest among men aged over 30 years. CONCLUSIONS: The estimated prevalence among men is commensurate with that described for female populations in London. The results suggest that recruitment of men to screening programmes would be difficult. However, a higher proportion of chlamydial infection may be detected in men than in women by existing approaches to control through genitourinary medicine clinic based case finding and contact tracing. Screening of young women and the contact tracing of the male partners of positive females may be an efficient approach to improving chlamydia control.

Adolescent↗

Kaposi sarcoma and lymphadenopathy syndrome: limitations of abdominal CT in acquired immunodeficiency syndrome.

Abdominal computed tomography (CT) was performed in 31 patients with Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS), three patients with classic KS, and 12 patients with the newly described lymphadenopathy syndrome (LNS). The frequency, distribution, and appearance of lymphadenopathy and splenomegaly were similar in the AIDS-related KS and LNS groups. Rectal and perirectal disease was identified in 86% of the homosexual men studied; rectal KS could not be distinguished from proctitis on CT criteria alone. No CT abnormalities were seen in patients with classic KS. The CT demonstration of retroperitoneal, mesenteric, or pelvic adenopathy or of rectal or perirectal disease in patients with AIDS-related KS is not necessarily indicative of widespread involvement with the disease.

Acquired Immunodeficiency Syndrome↗

Internal hemorrhoids: diagnosis with double-contrast barium enema examinations.

The authors retrospectively studied 43 patients suspected of having internal hemorrhoids at double-contrast barium enema examination. At endoscopy, 24 patients (56%) had internal hemorrhoids, four (9%) had other pathologic lesions in the rectum without evidence of hemorrhoids, and 15 (35%) had no reported abnormalities in the rectum. Internal hemorrhoids were found at endoscopy in 10 of 20 patients (50%) with lobulated folds extending 3 cm or less from the anorectal junction and 10 of 13 patients (77%) with multiple submucosal nodules. However, no patients with these characteristic radiographic findings were found to have other pathologic lesions in the rectum that had been mistaken for hemorrhoids at barium enema examination. Conversely, three of four patients with lobulated folds extending more than 3 cm from the anorectal junction and one of six patients with solitary nodules had proctitis or rectal neoplasms. Thus, specific criteria are suggested for the diagnosis of internal hemorrhoids on double-contrast barium enema examinations. Suspected hemorrhoids that do not fulfill these criteria should be evaluated endoscopically to rule out other more serious pathologic lesions in the rectum.

Barium Sulfate↗

Complications of prostate cancer treatment: spectrum of imaging findings.

The imaging appearances of prostate cancer are well described in the radiology literature, but little has been written about the detection and appearance of the complications of therapy for this disease. The most frequently used treatments for prostate cancer are surgical therapy (eg, radical retropubic prostatectomy, radical perineal prostatectomy), radiation therapy (eg, brachytherapy, external-beam radiation therapy, three-dimensional conformal radiation therapy, intensity-modulated radiation therapy), and cryoablative therapy, each of which may lead to complications with characteristic imaging appearances. Possible complications include lymphocele formation; injuries to the ureter, rectum, and urethra; prostatic necrosis; vesicourethral anastomotic leak and stricture; urethral stricture, necrosis, and fistula; radiation proctitis; transient bladder outlet obstruction; radiation-induced urethritis; urinary incontinence; and erectile dysfunction. With improvements in surgical techniques and advances in technology, complications of therapy for prostate cancer are decreasing but still occur with sufficient frequency to warrant familiarity on the part of radiologists. Knowledge of the diverse spectrum of these complications and their characteristic radiologic features facilitates prompt diagnosis and treatment.

Humans↗