Jerome B. Simon

Predictive value of the rome criteria for diagnosing the irritable bowel syndrome

Objective:Our aim was to examine the predictive value of the Rome criteria and absence of so-called “red flags” of clinical practice for diagnosing irritable bowel syndrome. Red flags were relevant abnormalities on physical examination, documented weight loss, nocturnal symptoms, blood in stools, history of antibiotic use, and family history of colon cancer.Methods:In retrospective studies, 98 patients who had one or more Rome criteria and lacked red flags were identified by chart review of a 1-yr period. In prospective studies, 95 patients were identified who met the Rome criteria and lacked red flags. Sensitivity, specificity, predictive value of Rome criteria, and absence of red flags were determined. Consultants final diagnosis was the gold standard. Investigations before and after referral were recorded and reason for referral was determined in prospective studies.Results:In the retrospective series, the Rome criteria and absence of red flags had a sensitivity of 65%, specificity of 100%, and positive predictive value of 100%. None of these patients required revision of their diagnosis during a 2-yr follow-up. In the prospective study, the positive predictive value was 98%. More than 50% of the patients in this group had been referred because of diagnostic uncertainty and 24% had had an abdominal ultrasound; 66% of those <45 yr old underwent at least partial colonic evaluation.Conclusion:These findings suggest that the Rome criteria combined with a lack of red flags have a very high predictive value for diagnosing irritable bowel syndrome. Application of these diagnostic criteria has the potential to alter utilization of health care resources.

The IBS-36: A new Quality of Life measure for irritable bowel syndrome

OBJECTIVE:We aimed to develop and validate a quality of life instrument for patients with irritable bowel syndrome (IBS).METHODS:Using focus groups, existing questionnaires, and literature reviews, five IBS patients and nine gastroenterologists compiled and pilot tested for content validity a 70-item questionnaire. The questionnaire was then administered to 107 IBS patients, and using these data, the 70-item questionnaire was reduced to 36 questions through statistical and consensus methodology. The IBS-36 questionnaire was tested for construct validity, reliability, reproducibility, and responsiveness using a gold standard of structured interviews by three gastroenterologists, the Medical Outcomes Study Short Form Quality of Life Questionnaire, and the Coping Resource Inventory.RESULTS:The IBS-36 consists of 36 questions scored on a 7-point Likert scale. It has a very high internal consistency (Cronbachs α= 0.95) and a high test-retest reliability (Spearmans r= 0.92) and correlates as hypothesized with the Medical Outcomes Study Short Form Quality of Life Questionnaire (p < 0.001), McGill pain scores (p < 0.001), and IBS patient-reported sleep, symptom, and pain scores (ps = 0.030, <0.001, and <0.001, respectively).CONCLUSIONS:The IBS-36 addresses all areas of quality of life affected by IBS and is easy to administer and score. The IBS-36 is a well-validated, condition-specific quality of life measure for IBS patients that is sensitive to clinical intervention and highly correlated with established quality of life measures and patient-reported symptom scores.

Lecithin:cholesterol acyltransferase in human liver disease.

Serum cholesterol esterification in vitro is usually impaired in patients with parenchymal liver disease. This abnormality roughly parallels the severity of the hepatic disorder and appears due to decreased synthesis or release of LCAT by the damaged liver. The extent to which this explains the cholesterol ester derangements observed in vivo is still unclear. but it probably plays a significant role. In contrast, cholesterol esterification in patients with cholestatic hepatobiliary disease has been variably reported as low, normal. or high. Conflicting data may partly be due to the influence of substrate on apparent LCAT activity. Further studies are needed to sort out complex interactions among LCAT, lipoprotein-X, and other factors which probably contribute to the serum lipid abnormalities of cholestasis.

Liver Disease in Asymptomatic Carriers of Hepatitis B Antigen

The hepatic status of apparently healthy hepatitis B antigen (HB Ag) carriers is controversial. To help clarify this issue we did a prospective study of 6277 Red Cross blood donors in Canada. Of these, nine were chronic HB Ag carriers, with neither symptoms nor signs of hepatic or other disease. All were young adults who either abused drugs or had lived abroad where antigenemia is more prevalent than in North America. Liver function tests were mildly or moderately deranged in seven of the nine. Liver biopsy from each carrier was coded, randomly mixed with dummy biopsies, and read blindly by both authors. All biopsies were abnormal: nonspecific focal or reactive hepatitis was present in six, active lobular inflammation typical of acute viral hepatitis was present in one, and chronic aggressive hepatitis was present in two. Serial biopsies in a tenth asymptomatic HB Ag carrier, who was not part of the above prospective series, showed transition from active lobular hepatitis to chronic persistent hepatitis during a 13-mo period. We conclude that a wide spectrum of subclinical hepatic disease regularly accompanies the asymptomatic HB Ag carrier state in Canada.

The pros and cons of fecal occult blood testing for colorectal neoplasms

Testing feces for occult blood is widely recommended as a means of detecting subclinical colorectal tumors. Guaiac tests such as Hemoccult® are the most widely used, but chemical sensitivity is relatively low and the tests are affected by dietary peroxidases, the state of fecal hydration, and certain drugs. The newly devised HemoQuant® and immunologic techniques appear more sensitive and specific, but they require further evaluation before widespread clinical usage can be recommended.Occult blood screening has both merits and weaknesses. Testing does uncover subclinical colorectal cancer, often at a relatively early stage, but whether this actually improves the prognosis remains to be proven. Benign neoplastic polyps are also detected, although it is debatable whether this is a valid rationale for screening. Test sensitivity for malignancy varies from good to moderate, but is poor for benign polyps. Specificity is usually around 97%–98%, yet the predictive value of a positive test for cancer is only about 10%: hence most test-positive individuals are needlessly subjected to invasive colonic investigations. Reported figures on public compliance with occult blood testing vary widely from excellent to poor. Published costs of screening are usually quite low, but these overlook important indirect and hidden expenses and are therefore misleading.On balance, the problems of occult blood testing currently appear to outweight the merits. This could change, however, with the newer testing techniques and with awaited mortality data from controlled clinical trials now underway.

Cholesterol ester hydrolase in human red blood cells.

1. Cholesterol ester hydrolytic activity (sterol-ester hydrolase EC 3.1.1.13) was detected in human red blood cells. Enzyme activity appeared confined to the cell membrane and was most marked in washed preparations of red cell ghosts. 2. Hydrolytic activity was stimulated by the anti-oxidants D-alpha-tocopherol and butylated hydroxytoluene. Marked inhibition was produced by erythrocyte hemolysate, sodium taurocholate, and Triton X-100. 3. Optimal pH for the reaction was 5.4--5.7. 4. Because red cell cholesterol is all unesterified, it is speculated that the hydrolase serves to maintain the erythrocyte membrane free of esterified cholesterol.

Serum Cholesterol Esterification in Human Liver Disease: Role of Lecithin-Cholesterol Acyltransferase and Cholesterol Ester Hydrolase

Serum cholesterol esters in man are largely formed intravascularly by lecithin-cholesterol acyltransferase (LCAT), a circulating enzyme of hepatic origin. Esterification of serum cholesterol in vitro is normally equatable with LCAT activity, but in patients with liver disease it has been suggested that the damaged liver releases cholesterol ester hydrolase into the circulation, so that serum net cholesterol-esterifying activity reflects a balance between LCAT and hydrolase activities rather than LCAT alone. To assess the validity of this hypothesis, we simultaneously assayed net cholesterol-esterifying activity and LCAT in sera from 25 patients with parenchymal liver disease, the former by a colorimetric method and the latter by a 14 C-isotopic assay. There was close agreement between the two esterification rates ( r = 0.89, P P r ≅ 0.7, P 14 C cholesterol linoleate into autologous serum substrate. Electrophoretic and radiochromatographic analysis of substrate sera suggested that most of the 14 C-ester was incorporated into lipoproteins, and validity of the assay was confirmed by its ability to detect known cholesterol ester hydrolase activity in dog serum and hog pancreatic extract. Serum hydrolytic activity was sought in 13 of the patients, but none was detected even in those with severe hepatic disease. These studies, therefore, revealed neither direct nor indirect evidence of circulating cholesterol ester hydrolase in patients with parenchymal liver disease, although its rare occurrence has not been completely excluded. Low LCAT activity can entirely account for the impaired in vitro cholesterol esterification of hepatic disease and probably contributes to the cholesterol ester derangements seen in vivo.

Motion - Computerized tomographic colography is a better method for screening for polyps: Arguments against the motion

Computerized tomographic (CT) colography is an exciting technique whereby images of the colonic wall and lumen can be obtained without colonoscopy. It is not as good as conventional colonoscopy, however, because of both inherent and performance limitations. Among the former is the inability to visualize subtle mucosal lesions, such as alterations in colour or pliability. More importantly, CT colography is strictly a diagnostic technique, and does not allow biopsy or removal of polyps. The vigorous bowel preparation required for this procedure can be very unpleasant for the patient, and includes purgatives followed by distension of the colon with air. Unlike with colonoscopy, adherent stool can be difficult to distinguish radiologically from polyps or cancers; as a result, many patients require colonoscopy anyway. The major performance limitations of CT colography are poor sensitivity and specificity compared with conventional colonoscopy. Rectal lesions, flat adenomas and diminutive adenomas are especially difficult to detect, and false-positive results are also common. In addition, the procedure is expensive and less cost effective than colonoscopy. CT colography takes relatively little patient time, but a substantial amount of time is needed for the radiologist to interpret the images. Interobserver variability is high. For all of these reasons, CT colography cannot be recommended as a screening test for colorectal neoplasia.

Costs of Finding an Advanced Adenoma in Colorectal Screening

The authors used computerized decision analysis to estimate the costs of finding and removing an advanced colonic adenoma in patients referred because of a positive fecal occult blood test. An advanced adenoma was defined as a villous adenoma, a tubular adenoma 10 mm or more in size, or a lesion that harboured highgrade dysplasia or cancer. Four strategies were compared: flexible sigmoidoscopy, flexible sigmoidoscopy plus air contrast barium enema, virtual colonoscopy (CT colography) and colonoscopy. Colonoscopy with polypectomy was undertaken if any of the methods detected a polyp. Probabilities and test characteristics were determined from the literature, and costs were estimated from the provincial fee schedule (Ontario) and local hospital sources. With an assumed 17% probability of an advanced adenoma being present, sigmoidoscopy was the most cost effective strategy at

Occult blood screening for colorectal carcinoma: A critical review

1930 to find and clear an advanced lesion, but the procredure missed between one-third and almost one-half of the lesions, depending on the depth of insertion. At