Alimentary Pharmacology & Therapeutics

Orr, W. C.; Goodrich, S.; Robert, J.

doi: 10.1111/j.1365-2036.2005.02310.xpmid: 15679759

Summary Background : Several studies have demonstrated that night‐time gastro‐oesophageal reflux affects sleep quality, and thereby impairs daytime functioning. Aim : To determine whether treatment with a proton‐pump inhibitor (rabeprazole) would improve both objective and subjective measures of sleep. Methods : Individuals with complaints of significant gastro‐oesophageal reflux disease were studied by polysomnography and 24‐h pH monitoring on two separate nights. On one occasion, participants received 20 mg rabeprazole b.d., and on another they received placebo. Both study conditions were preceded by a week of treatment with either rabeprazole or placebo. The order of treatments was randomized. Results : Rabeprazole significantly reduced overall acid reflux, but it did not significantly reduce night‐time acid contact. Rabeprazole treatment significantly improved subjective indices of sleep quality. There were no significant differences on objective measures of sleep between placebo and rabeprazole treatment. Conclusions : Consistent with other studies of pharmacological treatments for gastro‐oesophageal reflux, subjective measures of sleep improved with heartburn medication but objective measures were not affected.

Puleston, J.; Cooper, M.; Murch, S.; Bid, K.; Makh, S.; Ashwood, P.; Bingham, A. H.; Green, H.; Moss, P.; Dhillon, A.; Morris, R.; Strobel, S.; Gelinas, R.; Pounder, R. E.; Platt, A.

Getliffe, K. M.; Al Dulaimi, D.; Martin‐Ruiz, C.; Holder, R. L.; Von Zglinicki, T.; Morris, A.; Nwokolo, C. U.

doi: 10.1111/j.1365-2036.2005.02311.xpmid: 15679761

Summary Background : The chromosome instability observed in peripheral blood lymphocytes in ulcerative colitis could be a biomarker of cancer susceptibility. Aim : To determine whether accelerated telomere shortening could explain chromosome instability and assess the effect of drugs and smoking on telomere dynamics in these cells. Methods : Peripheral blood lymphocytes were isolated from ulcerative colitis, Crohn's disease and non‐inflammatory bowel disease control patients. Telomere lengths were measured by quantitative real‐time polymerase chain reaction. After activation and cell separation, telomerase activity and human telomerase reverse transcriptase messenger ribonucleic acid were measured by telomerase repeat amplification protocol enzyme‐linked immunosorbent serological assay and quantitative real‐time polymerase chain reaction, respectively. Results : Age‐related telomere loss in peripheral blood lymphocytes was similar in ulcerative colitis, Crohn's disease and control patients. Telomerase activity decreased with age in all groups and correlated positively with telomere length (r = 0.489, P =0.006). Among Crohn's disease patients, azathioprine was associated with decreased telomerase activity (0.66 vs. 1.54, P = 0.026, P < 0.05) and smoking was associated with decreased human telomerase reverse transcriptase mRNA expression (10.5 vs. 33.3, P =0.036, P < 0.05). Conclusions : Telomere shortening is not accelerated and therefore cannot be the cause of the chromosome instability observed in ulcerative colitis peripheral blood lymphocytes. Azathioprine and cigarette smoking modify telomerase expression in these cells.

Marakhouski, Y.; Fixa, B.; Holomán, J.; Hulek, P.; Lukas, M.; Bátovský, M.; Rumyantsev, V. G.; Grigoryeva, G.; Stolte, M.; Vieth, M.; Greinwald, R.; Greinwald, R.

doi: 10.1111/j.1365-2036.2005.02312.x

Barratt, H. S.; Kalantzis, C.; Polymeros, D.; Forbes, A.

doi: 10.1111/j.1365-2036.2005.02314.xpmid: 15679763

Summary Background : Functional symptoms occur in inflammatory bowel disease probably more than in the general population. Existing disease indices rely heavily on symptoms that may be organic or functional. This may explain inconsistencies between recent therapeutic trials in inflammatory bowel disease. Clinically, misinterpretation can lead to over‐treatment of functional symptoms with potent agents, and to under‐treatment of inflammatory bowel disease when inflammatory features are more subtle. Aim : To assess functional symptoms in inflammatory bowel disease and to devise simple means of their evaluation. Methods : Patients with Crohn's disease, ulcerative colitis, and irritable bowel syndrome completed questionnaires, generating inflammatory bowel disease and irritable bowel syndrome indices. Data from outliers selected as exemplars were employed to create a new index. Results : One hundred and ninety patients completed questionnaires. Overall, Crohn's and irritable bowel syndrome patients had similar functional features. The new scoring system was based on the eight apparently discriminant symptoms. Prospective evaluation in a separate cohort of 180 inflammatory bowel disease patients yielded scores that are independent of established indices, inflammatory markers and psychometric scores. Conclusions : Patients with Crohn's report comparable rates of apparently functional symptoms to those with irritable bowel syndrome. A new score has been developed to help in their identification. This has the potential to guide therapeutic decisions and optimize future trial recruitment.

Fossmark, R.; Johnsen, G.; Johanessen, E.; Waldum, H. L.

doi: 10.1111/j.1365-2036.2004.02271.xpmid: 15679764

Summary Background : Rebound acid hypersecretion develops after the use of acid inhibitors. Aim : To estimate the duration of hypersecretion and to elucidate the role of the enterochromaffin‐like (ECL) cell in rebound acid hypersecretion. Methods : Patients waiting for anti‐reflux surgery who had used a proton pump inhibitor daily > 1 year were included. All patients discontinued taking acid inhibiting drugs after the operation. Basal and pentagastrin stimulated acid output was measured at 4, 8, 16 and 26 weeks postoperatively. Oxyntic mucosal biopsies were collected before and 26 weeks after the operation for counting of histidine decarboxylase (HDC) immunoreactive cells. Serum chromogranin A (CgA) and gastrin were measured before and at 4, 8, 16 and 26 weeks after the operation. Results : Pentagastrin stimulated acid secretion was higher at 4 and 8 weeks than at 26 weeks after the operation. Gastrin and CgA were significantly reduced at 4 and 8 weeks, respectively. The number of HDC immunoreactive cells was reduced by 60% at 26 weeks postoperative. Discussion : Rebound acid hypersecretion lasts more than 8 weeks, but less than 26 weeks after long‐term proton pump inhibition. Conclusion : The findings indicate that not only the parietal cell mass, but also ECL cell mass and activity are involved in the mechanism of acid hypersecretion.

Wong, W.‐M.; Bautista, J.; Dekel, R.; Malagon, I. B.; Tuchinsky, I.; Green, C.; Dickman, R.; Esquivel, R.; Fass, R.

doi: 10.1111/j.1365-2036.2005.02313.xpmid: 15679765

Background : The wireless pH is a new technique to monitor oesophageal acid exposure. Aim : To compare the feasibility and tolerability of the wireless pH capsule vs. the traditional pH probe. Methods : Consecutive patients referred for a pH test were enrolled into the study. Patients were randomized to traditional pH probe, or wireless pH capsule. Patients recorded their activities, food consumption, symptoms, satisfaction with the test and completed a quality of life questionnaire. Results : Of the 50 patients recruited, 25 patients underwent placement of the traditional pH probe, and 25 the wireless pH capsule. Patients with the wireless pH capsule had less nose pain, runny nose, throat pain, throat discomfort and headache as compared with those with the traditional pH probe (P = 0.047, P = 0.001, P = 0.032, P = 0.001, P = 0.009, respectively). Patients in the wireless pH capsule group had more chest discomfort during the pH test (P = 0.037). Patients in the wireless pH capsule group perceived the test as interfering less with their overall daily activities, eating and sleep (P =0.001, P = 0.003, P = 0.025, respectively), and had overall satisfaction with the test (P = 0.023). Conclusions : Transnasal/per‐oral placement of the wireless pH capsule is significantly better tolerated then the traditional pH probe.

Graham, D. Y.; Opekun, A. R.; Belson, G.; El‐Zimaity, H. M. T.; Carlson, M. R.

doi: 10.1111/j.1365-2036.2005.02322.xpmid: 15679766

Summary Background: Current anti‐Helicobacter pylori treatment regimens are costly and because of the increasing antibiotic resistance, are becoming ineffective. Aim: To evaluate a triple‐layer tablet containing 100 mg bismuth subcitrate, 250 mg metronidazole, and 250 mg tetracycline in a single triple‐layer tablet. Methods: H. pylori‐infected adult patients received bismuth–metronidazole–tetracycline (two tablets, t.d.s.) and ranitidine (300 mg) once daily for 14 days. Efficacy was determined using 13C‐urea breath testing. Results: Thirty‐three of 35 enrolled patients were available for evaluation; using the protocol‐specified modified intention‐to‐treat analysis, five failed treatment, two were lost to follow‐up (cure rate per‐protocol = 85.7%, intention‐to‐treat = 78.7%). The cure rate among metronidazole‐susceptible strains was 100% (22 of 22) (95% confidence interval 84–100%) compared with 55% (five of nine intention‐to‐treat) (95% confidence interval 21–86%) among metronidazole‐resistant strains. In four cases, therapy was truncated at 4–7 days because of side‐effects; yet the treatment was effective in three. The three metronidazole‐susceptible but clarithromycin‐resistant infections were cured. Conclusion: This novel triple‐layer tablet combination therapy was effective in all patients with metronidazole‐susceptible H. pylori and many of those with resistant organisms. A greater degree of acid suppression may further improve effectiveness.

Kanwal, F.; Dulai, G. S.; Spiegel, B. M. R.; Yee, H. F.; Gralnek, I. M.

doi: 10.1111/j.1365-2036.2005.02321.xpmid: 15679767

Summary Background: The model for end stage liver disease (MELD)‐based organ allocation system is designed to prioritize orthotopic liver transplantation (OLT) for patients with the most severe liver disease. However, there are no published data to confirm whether this goal has been achieved or whether the policy has affected long‐term post‐OLT survival. Aim: To compare pre‐OLT liver disease severity and long‐term (1 year) post‐OLT survival between the pre‐ and post‐MELD eras. Methods: Using the United Network of Organ Sharing database, we compared two cohorts of adult patients undergoing cadaveric liver transplant in the pre‐MELD (n = 3857) and post‐MELD (n = 4245) eras. We created multivariable models to determine differences in: (i) pre‐OLT liver disease severity as measured by MELD; and (ii) 1‐year post‐OLT outcomes. Results: Patients undergoing OLT in the post‐MELD era had more severe liver disease at the time of transplantation (mean MELD = 20.5) vs. those in the pre‐MELD era (mean MELD = 17.0). There were no differences in the unadjusted patient or graft survival at 1 year post‐OLT. This difference remained insignificant after adjusting for a range of prespecified recipient, donor, and transplant centre‐related factors in multivariable survival analysis. Conclusions: Although liver disease severity is higher in the post‐ vs. pre‐MELD era, there has been no change in long‐term post‐OLT patient or graft survival. These results indicate that the MELD era has achieved its primary goals by allocating cadaveric livers to the sickest patients without compromising post‐OLT survival.

Braden, B.; Faust, D.; Sarrazin, U.; Zeuzem, S.; Dietrich, C. F.; Caspary, W. F.; Sarrazin, C.

doi: 10.1111/j.1365-2036.2005.02317.xpmid: 15679768

Summary Background : The 13C‐methacetin breath test enables the quantitative evaluation of the cytochrome P450‐dependent liver function. Aim : To find out whether this breath test is sensitive in noncirrhotic patients also with chronic hepatitis C in early stages of fibrosis. Methods : Sixty‐one healthy controls and 81 patients with chronic hepatitis C underwent a 13C‐methacetin breath test. In all patients, a liver biopsy was performed. The liver histology was classified according to the histology activity index–Knodell score. Results : Delta over baseline values of the patients at 15 min significantly differed from controls (19.2 ± 9.2‰ vs. 24.1 ± 5.7‰; P < 0.003). The cumulative recovery after 30 min in patients was 11.4 ± 4.8% and in healthy controls 13.8 ± 2.8% (P < 0.002). However, patients with early fibrosis (histology activity index IVB) did not differ in delta over baseline values of the patients at 15 min (23.2 ± 7.9‰ vs. 22.6 ± 7.2‰; P = 0.61) or cumulative recovery (13.6 ± 3.7% vs. 13.2 ± 3.8%; P = 0.45) from patients with more advanced fibrosis (histology activity index IVC). Patients with clinically nonsymptomatic cirrhosis (histology activity index IVD; Child A) metabolized 13C‐methacetin to a significantly lesser extent (delta over baseline values of the patients at 15 min: 8.3 ± 4.9‰; P < 0.005 and cumulative recovery after 30 min: 5.6 ± 3.2%; P < 0.003). The 13C‐methacetin breath test identified cirrhotic patients with 95.0% sensitivity and 96.7% specificity. Conclusion : The non‐invasive 13C‐methacetin breath test reliably distinguishes between early cirrhotic (Child A) and noncirrhotic patients, but fails to detect early stages of fibrosis in patients with chronic hepatitis C.