Alexandra Lavy

Budesonide versus prednisone in the treatment of active Crohn's disease

BACKGROUND & AIMS Budesonide (BUD) is a potent steroid that undergoes extensive first-pass metabolism. BUD incorporated in a pH-dependent formulation has been proposed as an alternative treatment for Crohns disease (CD). The aim of this study was to compare the efficacy and safety of BUD and prednisone (PRED) in the treatment of active CD involving the terminal ileum and/or the colon. METHODS Patients with mild to moderately active CD were included in a randomized, double-blind, double-dummy controlled trial. Patients received either 9 mg BUD once daily for 8 weeks or 40 mg PRED once daily for the first 2 weeks tapered gradually to 5 mg/day by the end of the study. Disease activity, quality of life, and laboratory parameters were recorded. RESULTS One hundred patients received BUD, and 101 patients received PRED. By intention-to-treat analysis, treatment efficacy defined as Crohns Disease Activity Index of <150 at completion was 51% and 52.5% for the BUD and PRED groups, respectively. Twice as many responded to treatment with no side effects in the BUD compared with the PRED group (30% vs. 14%) (P = 0.006). Most of the decrease in CDAI scores occurred during the first 2 weeks. CONCLUSIONS BUD is as effective as PRED in the treatment of CD involving the terminal ileum and right colon. BUD has significantly fewer steroid-related adverse reactions.

Is Traveler's Diarrhea a Significant Risk Factor for the Development of Irritable Bowel Syndrome? A Prospective Study

A total of 564 travelers were enrolled in a study aimed at investigating the influence of travelers diarrhea in the development of irritable bowel syndrome. At 6-7 months after repatriation, we found that an episode of travelers diarrhea was associated with a quintuple risk of developing irritable bowel syndrome.

Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis.

Cigarette smoking worsens Crohns disease (CD) but ameliorates ulcerative colitis (UC). In Israel, where there is no epidemiological association of smoking with CD, we examined the effects of current smoking on the course of CD and UC. Patients at nine public hospitals completed a questionnaire detailing their smoking history, disease course and treatments; subjects altering their smoking habit after the onset of disease were excluded. Sixty-four smokers and 144 nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were found between CD smokers and nonsmokers for hospitalizations, operations, and requirement for corticosteroid and immunosuppressive treatment. By contrast, UC smokers had less extensive disease than nonsmokers (P < 0.02) and fewer hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a minority of studies showing no adverse effect of smoking on the course of CD, and confirm the protective effect of smoking in UC.

Lack of association between smoking and Crohn's disease but the usual association with ulcerative colitis in Jewish patients in Israel: a multicenter study

OBJECTIVE:The association between smoking and inflammatory bowel disease (IBD) is well established, but data in Jewish patients in Israel were discrepant. The aim of this study was to examine the smoking habits of Jewish IBD patients in Israel in a large scale, multicenter study.METHODS:Patients with established IBD aged 18–70 yr were interviewed in relation to smoking and other habits. Two controls (one clinic and one neighborhood control matched by age, sex, community group, and education) were sought for each subject.RESULTS:A total of 534 patients (273 ulcerative colitis [UC], and 261 Crohns disease [CD]), along with 478 clinic controls and 430 neighborhood controls, were interviewed. There was no significant difference in the smoking habits between CD patients and their controls. Of patients with CD, 24.5% were current smokers, as compared to 19.9% of clinic controls and 25.2% of neighborhood controls (NS).The odds ratio for CD in current smokers was 1.30 (95% confidence interval 0.85–1.99) versus clinic controls, and 0.96 (0.63–1.46) versus neighborhood controls. There were also no significant differences in the proportion of ex-smokers between the groups. Only12.9% of UC patients were current smokers versus 21.9. % Clinic controls, and 26.4% community controls (p < 0.005). The proportions of ex-smokers were higher in UC patients 29.7%versus 25.9%, and 19.5% in their respective controls (p < 0.001vs community controls). No significant differences were found in the proportions of never-smokers between IBD patients and controls. All the above trends were similar in four different parts of the country. The proportion of current smokers in UC decreased with the extent of disease (19.7% in proctitis, 13.6% in left-sided, and 4.5% in total colitis) (p < 0.05). Patients with UC were more likely to be light smokers(1–10 cigarettes/day), whereas patients with CD were more likely to be moderate smokers (11–20 cigarettes/day) in comparison to their controls.CONCLUSIONS:The lack of association between smoking and CD has now been established in Jewish patients in Israel. The association was found in UC. The stronger genetic tendency in CD may contribute to this discrepancy.

Effect of Dietary Supplementation of Red or White Wine on Human Blood Chemistry, Hematology and Coagulation: Favorable Effect of Red Wine on Plasma High-Density Lipoprotein

Twenty healthy males were divided into two groups: 10 subjects were supplemented for 2 weeks with 400 ml of red wine (11% alcohol) per day and the other 10 subjects were given 400 ml of white wine (11% alcohol) per day for a similar period. Blood samples were drawn prior to wine supplementation, after 1 week and at the end of the study. No significant effects were found on plasma concentrations of urea, creatinine, bilirubin, creatine kinase, amylase, blood cell counts, platelet counts and platelet aggregation. Both red- and white-wine supplementation resulted in a transient minor reduction in plasma glucose concentration and in a minor elevation in blood coagulation properties such as prothrombin time and partial thromboplastin time. Red (but not white) wine resulted in an 11 and 26% increment in plasma triglyceride concentrations after 1 and 2 weeks of supplementation, respectively. Plasma cholesterol, as well as very-low- and low-density-lipoprotein levels did not change during the 2 weeks of red- or white-wine supplementation. The most impressive effect of red-wine intake was a significant (p < 0.01) increase in plasma high-density lipoprotein (HDL) cholesterol and in plasma apolipoprotein A-I concentrations by up to 26 and 12%, respectively. These effects were not observed after the intake of white wine. We conclude that the major effect of red-wine supplementation (about 40 g of alcohol per day for a period of 2 weeks) was a significant increase in plasma HDL concentration which may contribute to the reduced risk for cardiovascular diseases observed in red-wine drinkers.

Diagnosis and Treatment of Urinary Tract Complication in Crohn’s Disease: An Experience over 15 Years

BACKGROUD: Urinary tract complications in Crohn’s disease are common but treatable, and often present diagnostic and therapeutic dilemmas.

Preferential Inhibition of LDL Oxidation by the all-trans Isomer of β-Carotene in Comparison with 9-cis β-Carotene

| In the present study, the binding of the all-trans and the 9-cis isomers of s-carotene to plasma lipoproteins was investigated, and the effect of these isomers on the susceptibility of plasma lipoprotein to lipid peroxidation and on macrophage uptake of oxidized LDL were studied. Both the synthetic all-trans isomer of s-carotene and the natural s-carotene from the algae Dunaliella Bardawil [which is composed of the all-trans (70%) and 1 the 9-cis (30%) isomers], were found to bind similarly to all plasma lipoproteins, following the incubation of s-carotene with purified lipoproteins or with whole plasma. Incubation of the s-carotene isomers with whole plasma, followed by separation of the lipoproteins, revealed substantial carotene binding to very low density lipoprotein (VLDL) and to LDL and limited binding to high density lipoprotein (HDL). Lipid peroxidation of VLDL and LDL were significantly inhibited by s-carotene. The synthetic s-carotene, however, was twice as effective as the Dunaliella s-carotene in inhibiting LDL lipid | peroxidation (following LDL incubation with copper ions). Cellular degradation of oxidized lipoproteins | (mediated via the scavenger receptor) was decreased by 40% and 18%, respectively, when they were prepared by incubation in the presence of synthetic or natural s-carotene; the control oxidized LDL was prepared in the absence of s-carotene. s-Carotene probably binds to the cholesteryl ester moiety of LDL, and causes changes in the physicochemical properties of the lipoprotein. The synthetic all-trans isomer of s-carotene, but not the natural s-carotene, reduced LDL electrophoretic mobility and increased the availability of free amino groups of lysine residues. We conclude that altough both the all-trans and the 9-cis isomers of s-carotene can bind in vitro to plasma ! lipoproteins, they exert different effects of LDL atherogenicity; the all-trans isomer of s-carotene is more effective in inhibiting the susceptibility of lipoproteins to lipid peroxidation and in reducing the cellular uptake of oxidized LDL by macrophages.

Appendectomy is more frequent but not a risk factor in Crohn's disease while being protective in ulcerative colitis: a comparison of surgical procedures in inflammatory bowel disease.

OBJECTIVE:Appendectomy was shown to be protective in patients with ulcerative colitis (UC). There are fewer data in Crohns disease (CD). Other operations were less studied. The aim of this study was to investigate the prevalence of appendectomy, cholecystectomy, and tonsillectomy, including their timing, in patients with inflammatory bowel disease in comparison to controls.METHODS:Two hundred seventy-one patients with UC and 260 with CD, 475 clinic controls, and 428 community controls were interviewed.RESULTS:Appendectomy was found in 5.5% patients with UC, in 11% of clinic controls (p < 0.05), and 7.7% of community controls (p = not significant). The differences were more significant for appendectomy before onset of disease. Appendectomy was performed in 19.2% of patients with CD, in 10.9% of clinic controls, and in 10.1% of community controls (p < 0.01). However, there were no significant differences when only appendectomy before onset of disease was considered. Cholecystectomy was found in 1.5% of patients with UC, in 6.1% of clinic controls (p < 0.01), and in 4.5% of community controls (p = not significant). The difference remained significant when confined to operations performed before disease onset. No such difference was found in patients with CD. No significant difference was found in the prevalence of tonsillectomy between patients and controls.CONCLUSIONS:Appendectomy is protective in UC; it is more frequent, but not a risk factor in CD. The role of cholecystectomy should be investigated further.

Follow-Up of Exocrine Pancreatic Function in Type-1 Diabetes mellitus

In a previous study, mild to moderate exocrine pancreatic insufficiency, as measured by the secretin-pancreozymin test, was found in 23 (43%) of 53 patients with type-1 diabetes mellitus. Of these 53 patients, 20 (7 of whom initially had an abnormal secretin-pancreozymin test) were available for a follow-up examination 11 years later. Of the 7 patients with abnormal exocrine pancreatic function at the first test, 5 remained abnormal and 2 became normal, whereas of the 13 patients with initially normal pancreatic function the test result remained normal in 11 patients and became abnormal in 2. In these 2 groups the test result did not differ significantly between both tests. However, exocrine pancreatic function had returned to normal or had become abnormal in 2 patients, respectively, at the second test. In the 3 patients with exocrine pancreatic insufficiency at the first and second tests, the lipase level had not fallen below 10% or less than the normal level at which steatorrhea occurs and therapy is required. There was no significant correlation between the duration of the diabetes and the test results for both time points of investigation. The data suggest that mild to moderate exocrine pancreatic insufficiency found in type-1 diabetes is due to an early event in the course of the diabetes and does not progress. Therefore, this finding is of minor clinical importance and expensive pancreatic enzyme substitution will not be required.

Linear EUS for bile duct stones

BACKGROUND Radial scanning endoscopic ultrasonography (EUS) has been shown, in experienced hands, to be a safe and accurate means of detecting bile duct stones. We compared linear array EUS with endoscopic retrograde cholangiopancreatography (ERCP), in our first 50 cases, to evaluate efficacy of this examination as well as the learning curve for this indication. METHODS A retrospective study was conducted on 50 patients with suspected choledocholithiasis. We compared results of EUS with those of ERCP as a reference. First a linear EUS examination was performed followed by ERCP, at a median interval of 31 days (range 3 to 162 days). RESULTS The average age of patients was 56 years (range 26 to 76); 48% were women. Fifteen (30%) had undergone cholecystectomy, a mean of 8.5 years (range 1 to 22) before the EUS. EUS compared with ERCP had a 97% sensitivity, 77% specificity, and 90% accuracy. In 14% of patients EUS provided an additional or alternative diagnosis: chronic pancreatitis (n = 3), duodenitis (2), bile duct stricture (1), chronic gastritis (1). No complications were encountered due to EUS. CONCLUSIONS We found in this early experience that linear array EUS is a reasonably safe and accurate means of detecting choledocholithiasis. Linear array EUS, despite the learning curve, seems to be about equivalent to radial EUS in accuracy. Appropriate use of this less invasive technique may possibly replace the use of diagnostic ERCP.