Ola Ghaith

Alcohol consumption is a risk factor for colonic diverticulosis.

Background and Aim: The exact factors predisposing to colonic diverticulosis other than age are unknown. Methods: Cross-sectional study of asymptomatic subjects undergoing screening colonoscopy. A detailed dietary and social questionnaire was completed on all participants. A worldwide review of the literature was performed to further investigate any association between identified risk factors and diverticulosis. Results: Seven hundred forty-six consecutive individuals were enrolled (mean age, 61.1±8.3 y; female: male=0.98). Overall, the prevalence of diverticulosis was 32.8% (95% CI, 29.5-36.2). Diverticula were left-sided, right-sided, or both in 71.5%, 5.8%, and 22.7% of affected subjects, respectively. On univariate analysis, age, sex, adenomatous polyps, advanced neoplasia (adenoma≥1 cm, villous histology, or cancer), aspirin, and alcohol use were significantly associated with diverticulosis. Diet, body mass index, physical activity, and bowel habits were not associated with the disease. On multivariate analysis, increasing age (P<0.001), advanced neoplasia (P=0.021), and alcohol consumption (P<0.001) were significantly associated with diverticulosis. The adjusted odds ratio for diverticulosis in alcohol users was 1.91 (1.36 to 2.69), with increasing prevalence with higher alcohol consumption (P-value for trend=0.001). When the prevalence of diverticulosis reported from 18 countries was analyzed against alcohol use, there was a strong correlation with national per-capita alcohol consumption rates (Pearson correlation coefficient r=0.68; P=0.002). Conclusions: Alcohol use is a significant risk factor for colonic diverticulosis and may offer a partial explanation for the existing East-West paradox in disease prevalence and phenotype. Further studies are needed to investigate this association and its putative pathophysiological mechanisms.

Proton pump inhibitors have no measurable effect on calcium and bone metabolism in healthy young males: A prospective matched controlled study

OBJECTIVES Proton pump inhibitors (PPIs) are associated with an increased risk of bone fractures. This study sought to evaluate the effect of PPIs on biochemical markers of calcium and bone metabolism. METHODS Prospective matched controlled study involving healthy adult males (age 18-50years) suffering from frequent heartburn. Patients received standard-dose PPI for 12weeks and were matched by age with healthy controls. Blood studies were taken at 0, 1 and 3months for biochemical markers of mineral and bone metabolism. Two-way (time and PPI treatment) repeated measures analysis of variance (RM-ANOVA) and multiple linear regression were used for analysis. RESULTS A total of 58 participants (29 per group) completed the study. Mean age of participants was 33.2±7.5years. Baseline characteristics and biomarkers were similar for both groups except for higher BMI (28.6 vs. 25.6kg/m(2), p=0.008) and serum C-terminal cross linked telopeptides of type I collagen [CrossLaps, (300 vs. 228pg/ml, p=0.028)] in the PPI group. There was no difference in parathormone (PTH), ionized calcium, vitamin D, osteocalcin and CrossLaps between the PPI and control subjects (all non-significant; 2-way RM-ANOVA). Multiple linear regression modeling showed no effect of PPIs on any of the studied calcium or bone metabolism biomarkers. CONCLUSION PPI intake for 12weeks has no measurable effect on calcium or bone metabolism in healthy young males.

Association of Streptococcus bovis endocarditis and advanced colorectal neoplasia: a case-control study.

To study the association between Streptococcus bovis (S. bovis) endocarditis and advanced colorectal neoplasia.

Investigational agents for the irritable bowel syndrome

Importance of the field: Irritable bowel syndrome (IBS) is a common disorder with significant health and economic consequences. The etiology of IBS is complex and appears to be multifactorial. Traditional IBS therapies have been directed primarily at the relief of individual symptoms but have been largely disappointing. This has triggered the search for newer treatment strategies with improved patient outcomes. Areas covered in this review: Enhanced knowledge about the putative pathophysiology of IBS has allowed the identification of new mechanistic targets for treatment. Our aim is to review emerging and promising drugs in the treatment of IBS based on disease pathophysiology. Data were extracted using Medline and PubMed search engines until January 2010. Abstracts were identified through ‘Web of Science’ and abstract supplements of major gastrointestinal scientific meetings. Drugs were classified according to mechanism of action and those with efficacy in trials involving human subjects examined. What the reader will gain: Additional insight into the pathophysiology as well as current and prospective treatments of IBS. Take home message: A multitude of putative drug targets have been identified and some novel treatments have progressed through to human clinical trials, but very few will be approved for the market in the near future. Moreover, and in keeping with the complex and multifactorial nature of this syndrome, it is unlikely that there will be one dominant and universally effective form of therapy for all IBS patients.

Duration of Pain Is Correlated With Elevation in Liver Function Tests in Patients With Symptomatic Choledocholithiasis

BACKGROUND & AIMS We assessed the temporal relationship between abdominal pain and elevation in liver function tests (LFTs) in patients with acute symptomatic choledocholithiasis. METHODS Retrospective study of patients that presented within 12 hours of pain onset and were subsequently found to have choledocholithiasis. RESULTS We identified 40 patients with complete medical records. Levels of aspartate and alanine aminotransferases (AST and ALT) correlated with duration of pain (Pearson correlation, r = 0.633 and 0.622 respectively, P < .001 for both); the correlation was not as strong for γ-glutamyl transpeptidase (GGT) (r = 0.326, P = .046) and was not significant for alkaline phosphatase or bilirubin. This temporal association was stronger in patients that had undergone cholecystectomy versus those with intact gallbladders (for ALT, r = 0.603 vs r = 0.311, respectively). Eighteen patients, evaluated within 6 hours of pain, had normal or minimal alterations in LFTs; transabdominal ultrasound was abnormal in 6 (sensitivity 33.3%). All had repeat LFTs within 24 hours (mean 10.3 ± 6.9 hours later) and large increases in ALT and aspartate aminotransferase levels (mean 10.5- and 6.8-fold respectively; P < .01 for both), intermediate increases in glutamyl transpeptidase levels, (mean 4-fold, P < .05), and no changes in alkaline phosphatase levels. This significant increase in LFTs was the only indication of biliary pathology before endoscopy in 11/18 patients. CONCLUSIONS Increasing duration of pain is associated with increasing LFTs (particularly transaminases) in patients with acute symptomatic choledocholithiasis. Patients with normal LFTs and ultrasound upon presentation should have repeat LFTs if biliary pain is suspected. The absence of significant biochemical abnormalities within the first 24 hours makes the diagnosis of symptomatic choledocholithiasis unlikely.

A Prospective Randomized Trial of Mosapride vs. Placebo in Constipation-Predominant Irritable Bowel Syndrome

To the Editor: Irritable bowel syndrome (IBS) is a common disorder affecting ~5% of adults and comprising 28% of gastroenterology practice (1,2). Treatment of IBS remains a challenge because of its poorly defined pathophysiology, high placebo response, and variable symptomatology (3). Mosapride citrate, a selective partial 5–HT4 receptor agonist, which enhances gastrointestinal motility after accelerating the release of acetylcholine from nerves in the gastrointestinal tract (4), has been shown to accelerate colonic motility in animals (5). A small Japanese study (6) involving 11 patients with constipation-predominant IBS (C-IBS) showed that mosapride reduced abdominal pain and distention, decreased flatus, shortened bowel transit time, and produced looser stools, suggesting that mosapride may be useful in C-IBS.

CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the antiplatelet action of clopidogrel.

Abstract: The aim of this study is to investigate the effect of CYP2C19 polymorphism and cotherapy with rabeprazole or esomeprazole on the antiplatelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and CYP2C19*3, and vasodilator-stimulated phosphoprotein testing to measure platelet reactivity index (PRI). Two hundred thirty-nine consecutive patients were enrolled as follows: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). Forty-five patients had loss of function (LOF) polymorphism (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean PRI was 20.7% ± 21.9% in the C group, 19.1% ± 20.9% in the CR group, and 24.5% ± 22.9% in the CE group (P = NS). High on-treatment platelet reactivity (HPR), defined as PRI >50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, and CE, respectively (P = NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor proton pump inhibitor cotherapy were associated with HPR. The use of proton pump inhibitors was indicated in 30.6% of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel.

Peripheral vascular tumors and vascular malformations: imaging (magnetic resonance imaging and conventional angiography), pathologic correlation and treatment options

Vascular anomalies are classified into vascular tumors (infantile hemangioma) and vascular malformations. Vascular malformations are divided into slow flow and high flow subtypes. Magnetic resonance imaging helps in classification and assessing extent and distribution. Conventional angiography also known as digital subtraction angiography is pivotal in assessment of fine vascular details and treatment planning. Imaging correlates well with histopathology. We review recent development in imaging techniques of various vascular anomalies most of which are affecting the peripheral system which potentially may broaden understanding of their diagnosis, classification and treatment.

A randomized trial of standard-dose versus half-dose rabeprazole, clarithromycin, and amoxicillin in the treatment of Helicobacter pylori infection.

Objectives To evaluate the efficacy and safety of a standard-dose versus half-dose 10-day triple regimen for the eradication of Helicobacter pylori infection. Methods A total of 115 consecutive patients with documented infection were enrolled in this open-label trial. Group A (standard dose) received rabeprazole (20 mg), amoxicillin (1 g), and clarithromycin (500 mg), all twice daily for 10 days. Group B (half dose) received rabeprazole (10 mg), amoxicillin (500 mg), and clarithromycin (250 mg), all twice daily for 10 days. 14C urea breath tests were performed a minimum of 4 weeks after treatment and a minimum of 2 weeks off any acid-suppressive therapy. Compliance and adverse effects were evaluated throughout the treatment period. Results A total of 115 patients were enrolled (59 women and 56 men; mean age 47.1±14.0 years). Eradication occurred in 45 of 58 patients [77.6%; 95% confidence interval (CI): 66.9–88.3%] in the standard-dose group versus 44 of 57 in the half-dose group (77.2%; 95% CI: 66.3–88.1%) on an intent-to-treat (ITT) analysis (P=1.00). Per protocol eradication rates were 45 of 57 (78.9%; 95% CI: 68.4–85.9%) and 44 of 54 (81.5%; 95% CI: 71.1–91.8%), respectively (P=0.81). The number of patients reporting any adverse effect was significantly higher in the standard-dose group (64.9 vs. 40.4%; P=0.014). The cost of treatment was significantly less in patients receiving the half-dose regimen (ITT analysis; P<0.05). The number needed to harm to suffer one additional failure in the half-dose over the standard-dose arm was 250 (ITT analysis). Conclusion A half-dose 10-day regimen of rabeprazole, amoxicillin, and clarithromycin is equally effective but cheaper and better tolerated than its standard-dose regimen in the treatment of Helicobacter pylori. Eradication rates of both regimens are, however, suboptimal compared with accepted standards.

Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole.

Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially - available combination of two antibiotics - spiramycin and metronidazole - commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis.