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Infectious causes of diarrhea in the differential diagnosis of inflammatory bowel disease.

The infectious causes of enteritis and colitis are numerous. However, the actual clinical differential diagnosis with either ulcerative colitis or Crohn's disease is usually not a significant problem, except, of course, in two circumstances: (1) acute onset of diarrhea with or without rectal bleeding, and (2) patients who have AIDS, are immunocompromised, or are male homosexuals. However, if one bears in mind that rectal bleeding and mucosal abnormalities which are diffuse and uniform are the hallmark of ulcerative colitis, that Crohn's disease has perianal and external manifestations as its significant clinical hallmark, and both diseases tend to be chronic and recurrent, the clinical distinction can usually be made. However, it is important to recognize that there is an increasing awareness of intestinal infections, partly as a result of study of male homosexuals or patients with AIDS, as well as increased recognition of other infectious causes of diarrhea, including traveler's diarrhea, that associated with C. difficile, and that found with infection due to Campylobacter. As is usually the case in clinical medicine, however, careful and accurate history, attention to detail on physical and sigmoidoscopic examination, and laboratory (usually stool culture) data will lead to the appropriate diagnosis.

Acquired Immunodeficiency Syndrome↗

Endoscopic screening and surveillance for gastrointestinal malignancy.

In the US, the cumulative lifetime risk of developing carcinoma of the upper gastrointestinal tract is less than 1 per cent, premalignant conditions are uncommon, and esophageal and gastric malignancies are rarely curable even when identified early. Endoscopic screening of the upper gastrointestinal tract in asymptomatic persons thus cannot be justified. Surveillance of persons with certain uncommon conditions associated with a higher risk of upper gastrointestinal cancer may be of benefit. These conditions include achalasia, Barrett's esophagus, chronic atrophic gastritis with intestinal metaplasia, familial polyposis coli, gastric polyps, lye stricture, Plummer-Vinson syndrome, and tylosis. In the lower gastrointestinal tract, however, the lifetime risk of developing carcinoma is 5 per cent, premalignant conditions and lesions are common, and carcinoma is curable when detected at an early stage. Sigmoidoscopic screening of asymptomatic adults has been advocated by the American Cancer Society but has not become widely practiced because of its cost, required physician effort, low overall yield, and poor patient compliance. Surveillance by flexible sigmoidoscopy is recommended for persons at slightly increased risk of colorectal carcinoma who have prior breast or gynecologic malignancy or a family history of colorectal malignancy. Colonoscopic surveillance is recommended for patients with high risk of colorectal cancer who have had prior colorectal carcinoma or adenoma or who have inflammatory bowel disease or a ureterosigmoidostomy.

Endoscopy↗

Colonic involvement in salmonellosis.

Although small intestine is generally regarded as the principal site involved in human salmonella infection of food-poisoning type, the pathophysiology of salmonella diarrhoea remains obscure. A sigmoidoscopic and biopsy study of 23 hospital inpatients with acute salmonella infection revealed presence of active colitis in 21. It is suggested that colonic involvement is common in human salmonellosis and probably plays an important role in the causation of diarrhoea.

Adolescent↗

An experiment to determine the active therapeutic moiety of sulphasalazine.

Sulphasalazine (S.A.S.P.) is of proven value in the treatment of ulcerative colitis, but its mode of action is unknown. When it is taken by mouth, nearly all the dose reaches the colon intact, where it is split by bacteria into sulphapyridine (S.P.) and 5-aminosalicylic acid (5-A.S.A.). An experiment was devised to determine whether the therapeutic property of S.A.S.P. is a function of the parent molecule or of these two principal metabolites. Retention enemas of S.A.S.P., S.P., and 5-A.S.A. were administered to volunteer patients with sigmoidoscopic evidence of active ulcerative colitis. The experiment was conducted as a blind controlled therapeutic trial, each patient having one of the test enemas daily for two weeks. Pronounced histological improvement was observed in approximately 30% of the patients receiving S.A.S.P. or 5-A.S.A., and in only 5% of those receiving S.P. It is concluded that the active therapeutic moiety of S.A.S.P. IS 5-A.S.A. and that the S.P. functions as a carrier ensuring that the 5-A.S.A. is liberated within the colon.

Administration, Topical↗

Oral vancomycin for antibiotic-associated pseudomembranous colitis.

Nine patients with antibiotic-associated pseudomembranous colitis were treated with oral vancomycin. All had severe diarrhoea, tissue-culture evidence of a clostridial toxin in stool, and typical lesions on sigmoidoscopic examination, despite discontinuation of all antimicrobials for periods of 10 days to 8 weeks. Oral vancomycin was given in doses of 2 g daily. All patients showed a good clinical response with gradual resolution of diarrhoea over 7 days and a rapid decrease in concentrations of the toxin in stools. Follow-up sigmoidoscopies in seven patients showed major improvement or complete clearing of lesions after 7-10 days of vancomycin treatment. The mean concentration of vancomycin in twenty-five stools obtained during treatment was 3100 microgram/g, levels in serum being very low. These results suggest a role for oral vancomycin treatment of antibiotic-associated pseudomembranous colitis which persists for extended periods despite discontinuation of the incriminated antimicrobial.

Administration, Oral↗

Acute colitis related to penicillin and penicillin derivatives.

5 cases of acute transient colitis associated with the ingestion of ampicillin, an ampicillin derivative, and penicillin are discussed. The clinical presentation, course, and radiographic and sigmoidoscopic findings are distinct from those in pseudomembranous colitis. The colonic changes may be related to an allergic reaction in the intestine which results primarily in transient ischaemia. The presenting symptom is blood diarrhoea, and barium enema is the most productive diagnostic examination.

Administration, Oral↗

Comparison of disodium cromoglycate and sulphasalazine as maintenance therapy for ulcerative colitis.

In a trial lasting six months disodium cromoglycate (800 mg daily), sulphasalazine (2 g daily), and these two agents in combination were compared in 120 patients as maintenance treatment for ulcerative colitis. Relapse was defined as recurrence of colitic symptoms accompanied by sigmoidoscopic evidence of inflammation. The patients receiving disodium cromoglycate had a much higher relapse-rate than those taking sulphasalazine and the results with the two agents combined were little different from those with sulphasalazine alone. Disodium cromoglycate in the dose employed is greatly inferior to sulphasalazine as maintenance treatment for the prevention of relapse in ulcerative colitis.

Administration, Oral↗

Beclomethasone dipropionate enemas for treating inflammatory bowel disease without producing Cushing's syndrome or hypothalamic pituitary adrenal suppression.

Since beclomethasone dipropionate (BDP) is a very potent glucocorticoid and since small oral doses (1 mg) seem to be metabolised (possibly in the gut wall or liver) before they reach the systemic circulation, a study was conducted to find out whether patients with inflammatory bowel disease could be treated with enemas containing small doses of BDP without their acquiring Cushing's syndrome or hypothalamic pituitary adrenal (HPA) suppression. The BDP in the 100 ml enemas used was stable and present in a concentration likely to be therapeutic (0.5 mg/dl). Single overnight BDP enemas, unlike conventional betamethasone (5 mg) enemas, did not interfere with the HPA axis in 6 healthy volunteers. In the double-blind randomised part of the study 2-week courses of BDP or betamethasone enemas were assessed in 9 patients having exacerbations of distal inflammatory bowel disease. The clinical and sigmoidoscopic responses as well as adrenocortical function (judged by the 'Cosyntropin' test) were evaluated on the morning after the last day of a course of enemas. Both types of enemas had similar beneficial effects, but only BDP enemas did not interfere with HPA function. Over a prolonged period, a patient with distal ulcerative colitis had been completely dependent on regular treatment with betamethasone enemas to control his symptoms. Substitution with BDP enemas successfully controlled his bowel symptoms, whilst his cushingoid features and HPA suppression regressed.

Adult↗

Colonoscopic diagnosis of minimal change colitis in patients with a normal sigmoidoscopy and normal air-contrast barium enema.

8 patients with normal sigmoidoscopic appearances and normal results by high-quality air contrast barium enema had substantial or total colitis diagnosed for the first time at colonoscopy performed within a month of the radiological examination. Colitis was confirmed in all 8 patients by histological examination of biopsy specimens. Barium enema radiographs were independently reviewed by three experienced observers who also reviewed other normal and abnormal radiographs. One observer regarded all 8 sets of radiographs from the patients with colitis as being of normal appearance, and 4 patients were reported as having normal radiographs by all three observers. All 7 of the rectal biopsy specimens taken showed histological features of inflammatory bowel disease. This emphasises the importance of performing a rectal biopsy in patients with gastrointestinal symptoms of unknown cause.

Adult↗

Retinal pigment epithelium lesions as a biomarker of disease in patients with familial adenomatous polyposis. A follow-up report.

BACKGROUND: The sensitivity of retinal pigment epithelium (RPE) lesions as a predictive congenital marker for the development of familial adenomatous polyposis (FAP) is evaluated. METHODS: In a prospective study, 34 patients at 50% risk of inheriting FAP were examined. Based on the presence or absence of four or more RPE lesions, patients were categorized as those who had inherited or those who lacked the FAP genes. All patients received dilated fundus examinations with binocular indirect ophthalmoscopy and all RPE lesions were documented with fundus photography. All patients underwent annual sigmoidoscopy to determine the presence or absence of polyps. RESULTS: A 3-year follow-up analysis showed that 8 of 14 patients who were positive for RPE lesions later developed polyps. Of the 20 patients considered negative for FAP based on normal fundus examination, none has developed polyps. CONCLUSION: The authors urge all patient at risk of inheriting FAP to undergo dilated fundus examination with binocular indirect ophthalmoscopy and wide-angle fundus photography at the earliest age possible. All patients with 4 or more RPE lesions should undergo annual sigmoidoscopic examinations beginning before 10 years of age.

Adenomatous Polyposis Coli↗

Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The objectives of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55-74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screening men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer. Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity, specificity, and positive predictive value; to assess incidence, stage, and survival of cancer cases; and to investigate biologic and/or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints. The design is a multicenter, two-armed, randomized trial with 37,000 females and 37,000 males in each of the two arms. In the intervention arm, the PSA and CA125 tests are performed at entry, then annually for 5 years. The DRE, TVU, and chest X-ray exams are performed at entry and then annually for 3 years. Sigmoidoscopy is performed at entry and then at the 5-year point. Participants in the control arm follow their usual medical care practices. Participants will be followed for at least 13 years from randomization to ascertain all cancers of the prostate, lung, colorectum, and ovary, as well as deaths from all causes. A pilot phase was undertaken to assess the randomization, screening, and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels. This paper describes eligibility, consent, and other design features of the trial, randomization and screening procedures, and an outline of the follow-up procedures. Sample-size calculations are reported, and a data analysis plan is presented.

Colorectal Neoplasms↗

The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial.

PURPOSE: Acute rectal complications occur in the majority of patients receiving external-beam radiotherapy for carcinoma of the prostate. Sucralfate has been proposed to reduce radiation-induced mucosal injury by forming a protective barrier on ulcer bases, binding local growth factors, and stimulating angiogenesis. However, there is conflicting clinical evidence as to whether sucralfate, taken prophylactically during radiotherapy, can ameliorate the symptoms of acute radiation proctitis. METHODS AND MATERIALS: A double-blind randomized trial was conducted at four Radiation Oncology Departments in Sydney, Australia, between February 1995 and June 1997. A total of 338 patients with clinically localized prostate cancer receiving small volume radiotherapy, of whom 335 were evaluable, were randomized to receive either 3 g of oral sucralfate suspension or placebo twice a day during radiotherapy. Patients kept a daily record of their bowel symptoms and were graded according to the RTOG/EORTC acute toxicity criteria. RESULTS: One hundred sixty-four patients received sucralfate and 171 received placebo. Both groups were well balanced with regard to patient, tumor, treatment factors, and baseline symptoms, except that the placebo group had a significantly more liquid baseline stool consistency score (p = 0.004). Patients kept a daily diary of symptoms during radiotherapy. After adjusting for baseline values, there was no significant difference between the two groups with regard to stool frequency (p = 0.41), consistency (p = 0.20), flatus (p = 0.25), mucus (p = 0.54), and pain (p = 0.73). However, there was more bleeding in the sucralfate group, with 64% of patients noticing rectal bleeding, compared with 47% in the placebo group (p = 0.001). There was no significant difference between the two groups with respect to RTOG/EORTC acute toxicity (p = 0.88; sucralfate 13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively). CONCLUSION: This study suggests that oral sucralfate taken prophylactically during radiotherapy does not ameliorate the symptoms of acute radiation proctitis and may increase acute bleeding. The cause of the increased bleeding in the sucralfate group is unclear. As the pathogenesis of acute and late reactions are different, late follow-up, which includes sigmoidoscopic evaluation, is currently being performed on this cohort of patients.

Administration, Oral↗

The optimum bowel preparation for flexible sigmoidoscopy.

With the proposed introduction of a flexible sigmoidoscopic screening programme for colorectal cancer, patient compliance is of paramount importance. Therefore, the bowel preparation providing optimum cleansing of the bowel with the least associated discomfort and inconvenience for the patient must be found. Patients were randomized to receive either Picolax the evening before the examination or self-administered Fleet enemas prior to the investigation. The endoscopist and nurse practitioner who collected data on a standard questionnaire were blinded to the preparation used. Bowel preparation was graded by the endoscopist as: excellent, good, adequate or poor. One hundred and two consecutive patients were randomized: 56 to the Fleet enema group and 46 to the Picolax group. Self-administered Fleet enemas provided a significantly superior bowel preparation with 52 (93%) being judged adequate or better, as opposed to 34 (74%) in the Picolax group. In addition, Fleet enemas were associated with significantly fewer adverse associated symptoms: 11 (20%) vs 24 (52%). Patients reported to be willing to receive Fleet enemas again in 53 (95%) vs 37 (80%) for the Picolax group. The self-administered Fleet enema is superior to Picolax in terms of bowel preparation for flexible sigmoidoscopy and the incidence of associated adverse symptoms.

Administration, Oral↗

Does provider prevention orientation influence female patients' preventive practices?

BACKGROUND: Health care provider encouragement for particular preventive behaviors is associated with patient adherence, but it is unclear whether a provider's overall prevention approach influences whether patients engage in recommended preventive measures. We examined whether older women who perceived that their health care provider encouraged a particular preventive behavior were more likely to follow that recommendation if they also perceived that the provider encouraged other preventive behaviors. DATA AND METHODS: The sample included 1119 women aged 50 to 79 enrolled in a health maintenance organization. We examined associations of reported provider encouragement for post-menopausal hormone use, physical activity, fecal occult blood testing (FOBT), and flexible sigmoidoscopy with one another and with adherence to these measures according to recommended guidelines. RESULTS: Among women reporting provider encouragement for physical activity, the likelihood of reporting regular physical activity was greater among women who reported encouragement for one other (odds ratio [OR]=1.99; confidence interval [CI]=1.35 to 2.95) and at least two other (OR=2. 38; 95% CI=1.62 to 3.48) preventive measures compared with women who reported no other encouragement. The likelihood of reporting adequate counseling for post-menopausal hormone use was greater among women reporting encouragement for at least two other preventive measures compared with those reporting no other encouragement. The likelihood of having had an FOBT or sigmoidoscopic examination was related to encouragement for those procedures, but not with greater encouragement for other preventive measures. CONCLUSIONS: Patient perceptions of a provider's overall preventive practice approach may influence whether patients engage in recommended preventive practices, particularly for lifestyle factors.

Aged↗

Colon cancer during pregnancy.

The medical community should become mobilized to diagnose colon cancer earlier in pregnancy to improve prognosis. The primary care physician or obstetrician should refer the pregnant patient with significant gastrointestinal complaints to the gastroenterologist for evaluation. Likewise, the gastroenterologist should be prepared to perform sigmoidoscopy, preferably without endoscopic medications, for significant lower gastrointestinal symptoms such as persistent rectal bleeding. Sigmoidoscopy is particularly sensitive in identifying colon cancer in pregnant patients because their cancers are usually distal and within reach of the sigmoidoscope.

Antineoplastic Agents↗

A novel form of ascertainment bias in case-control studies of cancer screening.

In case-control studies of cancer screening, some have generally admonished investigators against case definitions based on diagnosis dates because of lead-time bias. However, perhaps partly due to vagueness, the admonitions have been frequently ignored. A recurrence-time model simulates case ascertainment when diagnosis must occur within a specific calendar period. The model depends on screening test sensitivity and rate, age-specific preclinical incidence rates, and preclinical duration time and survival time distributions. For one study of sigmoidoscopic screening for colorectal cancer, when the true odds ratio is 1, its estimate is 0.50 to 0.75 under plausible assumptions. This bias can affect any observational study wherein case definition depends on diagnosis times (e.g., health-plan enrollment data). To avoid bias in observational investigations of cancer screening wherein the case definition depends on the diagnosis date, one must ensure that both screening and preclinical incidence do not occur before the case definition period.

Adult↗

Colonoscopy and biopsy.

The place of colonoscopy in the management of ulcerative colitis is restricted to clinical situations where the information provided will change clinical management. The information provided will be answers to the questions?inflammatory bowel disease, o r, in the patient with known colitis: inflammatory bowel disease?type?activity extent?dysplasia. Biopsy is pivotal to the diagnosis and provides the certainty of tissue diagnosis, assessment of activity and detection of dysplasia. Sigmoidoscopy is sufficient for providing information for clinical management in most circumstances, but colonoscopy is important where clinical features are disproportionate to sigmoidoscopic findings and systemic parameters of inflammatory activity; to determine type and extent of inflammatory bowel disease and when surveillance needs to start; and for biopsy to detect dysplasia. Ileoscopy is an important aspect of colonoscopy for differential diagnosis, and is the unique definer of total colonoscopy.

Biopsy↗

The value of endorectal ultrasonography in the follow-up of intracavitary radiation treated early rectal cancer.

In selected patients with early rectal cancer, intracavitary radiation is a successful treatment. Endorectal ultrasound has proved an accurate method for staging and selecting such cancers for treatment. The value of endorectal ultrasound in the follow-up of patients with intracavitary radiation has not been previously assessed. Between 1989 and 1991, 30 patients treated at the Hamilton Regional Cancer Centre with intracavitary radiation were assessed by endorectal ultrasound. The mean age was 65 +/- 12 years with a range of 37-78 years. There were 17 males and 13 females. All patients were treated with curative intent. The dose of radiation administered was 8963 +/- 1506 cGy over 3.5 +/- 0.7 fractions. No patient received supplemental iridium implantation. Thirty-seven endorectal ultrasounds were carried out in 30 of the intracavitary radiation treated patients. Clinical findings (digital, sigmoidoscopic, and histology) were compared with the radiologist's interpretation of the endorectal ultrasounds. Using a 2 x 2 table accepting the clinical findings as the 'Gold Standard', the sensitivity of endorectal ultrasound was 71%, the specificity 61%, the positive predictive value 53%, the negative predictive value 78% with an overall accuracy of 75%. We conclude that endorectal ultrasound in the routine follow-up of patients treated with intracavitary radiotherapy for carcinoma of the rectum is questionable.

Adult↗