bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral budesonide for treatment of autoimmune chronic active hepatitis
Authors: DANIELSSON Å. , PRYTZ H.
Published: July 2010

Objectives: To see if budesonide, a second generation glucocorticosteroid with a high topical effect and a high first‐pass metabolism of 90% in the healthy liver, can induce biochemical remission in autoimmune chronic active hepatitis before being metabolized, and further to study the effect on endogenous plasma cortisol levels and corticosteroid‐related side effects. Patients and design: Thirteen patients with autoimmune chronic active hepatitis (11 females) were treated openly for up to 9 months by oral budesonide capsules. The initial dose was 6–8 mg (mean 6.3 mg) daily for 6–10 weeks, and then the dose was individualized.

Results: The pre‐treatment values of alanine aminotransferase and immunoglobulin (IgG) were 7.1 ± 1.2,μkat/L (mean ± S.E.M.) and 26.4 ± 3.9 g/L, respectively. After 6 weeks of treatment, significant decreases in alanine aminotransferase (to 2.1 ± 0.9 μkat/L) and immunoglobulin (to 18.4 ± 2.4 g/L) were recorded. After 9 months the corresponding values (n= 9) were 1.2 ± 0.9 μkat/L and 15.9 ± 1.3 g/L, respectively. The mean value of plasma cortisol remained within normal ranges or was only slightly subnormal for the whole group (364 ± 44 nmol/L at start, 165 ± 46 after 6 weeks and 138 ± 44 after 9 months). However, significantly reduced plasma cortisol levels were found in patients with biopsy‐proven liver cirrhosis.

Conclusion: Oral budesonide appears to decrease liver inflammation in autoimmune chronic active hepatitis while causing a low frequency of systemic side effects and a marginal reduction in plasma cortisol in non‐cirrhotic patients over a study period of 9 months.
Review article: the hypersensitive gut—peripheral kappa agonists as a new pharmacological approach
Authors: JUNIEN J. L. , RIVIERE P.
Published: July 2010

Hypersensitivity to pain is a common component of functional bowel disorders. Hyperalgesia may be induced by various stimuli which produce a cocktail of inflammatory mediators that decrease the pain threshold. Drugs able to block these peripheral events within the gut may offer a new pharmacological approach for treating functional bowel disorders. Kappa opioids have been shown to inhibit somatic pain through a peripheral mechanism of action, acting directly on receptors located on peripheral sensory endings. They can block both the nociceptive messages as well as the release of sensory peptides. This paper reviews the effects of opioid agonists on gut visceral pain and motility anomalies induced by visceral pain. Kappa opioids have strong effects on all models tested, with a peripheral mechanism of action allowing the design of drugs acting only in the periphery and having no central nervous system side‐effects. This contrasts with mu agonists which are centrally active on pain and worsen the subsequent transit and motility anomalies.
factors protecting the oesophagus against acid‐mediated injury
Authors: BROWN C. M. , REES W. D. W.
Published: July 2010

Reflux of gastric acid and pepsins into the lower oesophagus causes symptoms such as heartburn and nausea, and tissue injury leading to erosive oesophagitis and stricture formation. This article reviews the mechanisms involved in protecting the oesophagus against acid‐mediated injury, including the role of the lower oesophageal sphincter, secondary oesophageal peristalsis and swallowed saliva. The oesophageal mucosa has inherent abilities to resist acid damage, and recent data from three laboratories suggest a secretory function with local production of bicarbonate and mucus responsive to local acidification. The evidence for these putative oesophageal defence mechanisms is discussed.
Ranitidine maintenance therapy in the prevention of duodenal ulceration; a comparison of 150 mg at night with 300 mg at night
Authors: McDOUGLE A. M. A. , LANCASTER‐SMITH† M. J. , HIGSON D. L.
Published: July 2010

Background: The purpose of this study was to investigate if the use of a higher night time dose of ranitidine (300 mg) could keep significantly more duodenal ulcer patients in remission than the usual maintenance dose (150 mg).

Methods: Double‐blind, multi‐centre, parallel group study of patients with proven healed duodenal ulcer randomized to ranitidine 150 mg or 300 mg daily for 1 year. The primary study end‐point was symptomatic, endoscopically proven ulcer relapse.

Results: A total of 489 patients were recruited into the study. The endoscopically proven relapse rates were 6.1% of ranitidine 150 mg daily (n= 250) and 6.9% on 300 mg daily (n= 239). These differences were not statistically significant.

Conclusion: This study provides further evidence that maintenance therapy with ranitidine 150 mg daily is highly effective at preventing duodenal ulcer relapse. The use of the higher dose of 300 mg daily does not appear to keep significantly more patients in remission.
A double‐blind study of pantoprazole and omeprazole in the treatment of reflux oesophagitis : a multicentre trial
Authors: MÖSSNER J. , HÖLSCHER† A. H. , HERZ R. , SCHNEIDER A.
Published: July 2010

Background: Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+,K+‐ATPase.

Aim:To compare pantoprazole 40 mg with omeprazol 20 mg as once daily dosing in the treatment of reflux oesophagitis (grades II and III).

Methods: This double‐blind, randomized, multicentre study included 286 patients. Patients were reendoscoped after 4 weeks, and continued to receive a further 4 weeks of treatment if they were not healed a this time.

Results: After 4 weeks of treatment, complete healing occurred in 126/170 (74%) patients in the pantoprazole group and in 67/86 (78%) patients in the omeprazole group (per‐protocol analysis). At 8 weeks, the corresponding healing rates were 153/170 (90%) and 81/86 (94%). The differences between the treatment groups were not significant (P= 0.57 and 0.34). Improvement in the principal symptoms of reflux oesophagitis was also very similar between the treatment groups, with 59% and 69% at 2 weeks, and 83% and 86% at 4 weeks, respectively, being free from any individual symptom. Both treatments were well tolerated.

Conclusions: This study has shown pantoprazole and omeprazole to be similarly effective and well tolerated in the treatment of mild to moderate reflux oesophagitis.
Intestinal site‐dependent susceptibility to chronic indomethacin in the rat: a morphological and biochemical study
Authors: NYGÅRD G. , ANTHONY A. , KHAN K. , BOUNDS S. V. J. , CALDWELL J. , DHILLON A. P. , POUNDER R. E. , WAKEFIELD A. J.
Published: July 2010

Background: The cyclo‐oxygenase inhibitor indomethacin induces a pattern of gastrointestinal injury in the rat that is site‐dependent. This study compared the extent of injury to different regions of the rat intestine (small intestine, caecum and colon) with the corresponding changes in arachidonic acid metabolism in these areas, following long‐term, low‐dose indomethachin.

Methods: Rats (eight per group) received either indomethacin (3 mg.kg/day) or control diet for either 6 or 12 weeks. At termination animals were bled, examined both macroscopically and microscopically for ulcers, and assayed for blood thromboxane B2, intestinal tissue prostaglandin E2 content and production of leukotriene B4. In a further eight animals luminal indomethacin concentrations from the small intestine, caecum and colon were measured following 6 weeks of chronic drug ingestion.

Results: At 6 weeks, macroscopic ulcers were observed in 2/8 (small intestine), 3/8 (caecum) and 1/8 (colon) animals. The corresponding ratios at 12 weeks were 5/8, 8/8 and 0/8. In control animals, a site‐dependent gradient of the prostaglandin E2 concentration was found. In indomethacin‐dosed animals the intestinal prostaglandin E2 content was reduced significantly in the caecum at 6 weeks, and in all tissues at 12 weeks. An increased leukotriene B4 production was observed in the caecum only, at 12 weeks (P < 0.01), and the blood thromboxane B2 was reduced at both time points (P < 0.05).

Conclusion: There is a site‐dependent gradient of the prostaglandin E2 concentration in the rat intestine. The rat caecum is particularly sensitive to long‐term low‐dose indomethacin, both in terms of chronic intestinal inflammation and changes in prostanoid metabolism. This site‐dependent degree of injury may be associated with a local cyclo‐oxygenase inhibition.
Comparison of pantoprazole versus omeprazole in the treatment of acute duodenal ulceration—a multicentre study
Authors: REHNER M. , ROHNER H. G. , SCHEPP W.
Published: July 2010

Methods: In this randomized, double‐blind, multicentre study, the proton pump inhibitors pantoprazole and omeprazole were compared in patients with active duodenal ulcers. Two hundred and seventy‐six protocol‐correct patients received either pantoprazole 40 mg (n= 185) or omeprazole 20 mg (n= 91), once daily for 2 or 4 weeks, depending on the progress of ulcer healing.

Results: Rates of complete ulcer healing after 2 weeks were 71% in patients given pantoprazole and 74% in patients given omeprazole. After 4 weeks the figures were 96% and 91%, respectively. These differences were not significant. There was no significant difference in ulcer pain prior to treatment, and 85% of the pantoprazole group and 86% on omeprazole were pain‐free after 2 weeks (not significant). The time until complete pain relief with pantoprazole or omeprazole, based on data from diary cards, was not significantly different (P < 0.05, Uleman's U‐test). Both treatments were equally well tolerated. Changes in routine laboratory parameters were minimal in both groups.

Conclusion: Pantoprazole was shown to be a highly‐effective and well‐tolerated treatment for acute duodenal ulcer. Pantoprazole 40 mg and omeprazole 20 mg were equally effective with respect to ulcer healing and pain relief, and have similar adverse event profiles.
Pain and quality of life in patients with acute duodenal ulcer treated with ranitidine
Authors: RAMPAL P. , RUSZNIEWSKI P. , BOUREAU F. , RICHARD A. , SLAMA A.
Published: July 2010

Background: The various components of pain and quality of life in duodenal ulcer patients receiving antisecretory drugs have not been studied to date.

Methods: Ninety‐five patients with epigastric pain and duodenal ulcer at endoscopy completed this prospective, multicenter, open‐study. All were treated with effervescent ranitidine 300 mg daily for 4 weeks. The following parameters were assessed: (a) disappearance of duodenal ulcer pain by self‐evaluation and on a weekly visual analogue scale (VAS) from 0 to 100; (b) evolution of sensory and affective components of ulcer pain by the Validated French Version of the McGill Pain Questionnaire (Questionnaire Douleur de Saint‐Antoine, QDSA); (c) quality of life by the Nottingham Health Profile (NHP) which includes six criteria: pain, mobility, energy, emotions, sleep and social isolation.

Results: Forty‐nine, 66 and 87% of the patients were pain‐free during the day‐time after 7, 14 and 28 days, respectively. Corresponding figures for the night‐time were 80%, 88% and 97% respectively. Median time to disappearance of ulcer pain was 8 days. VAS self‐assessment showed a significant decrease each week throughout the treatment period (P= 0.001). Sensory and affective QDSA scores were significantly improved after the second day and at each assessment during the 28 days of treatment (P= 0.001). Physical as well as affective aspects of quality of life were significantly improved after 28 days for each of the six criteria explored (P= 0.001). The duodenal ulcer healing rate was 86% after 4 weeks of treatment.

Conclusions: Using complementary scales measuring different aspects of ulcer pain, sensory and affective components improved significantly from the second day of treatment with ranitidine 300 mg. A significant improvement in quality of life is observed after a 4‐week treatment.

QDSA and NHP appear to be useful evaluation tools of duodenal ulcer pain and quality of life.
Loperamide oxide in acute diarrhoea: a double‐blind, placebo‐controlled trial
Authors: DREVERMAN J. W. M. , VAN DER POEL A. J. M.
Published: July 2010

Background: Loperamide is an established treatment of acute diarrhoea with only rare adverse reactions. The pro‐drug loperamide oxide is converted to loperamide by anaerobic bacteria in the lower alimentary tract. With the use of loperamide oxide, it was expected to obtain similar antidiarrhoeal efficacy as with loperamide, but with a lower dose and a lower plasma concentration. The incidence of adverse reactions might be reduced with the use of loperamide oxide.Methods: Loperamide oxide (0.5 and 1 mg capsules) was compared with placebo in a double‐blind treatment of acute diarrhoea of 242 patients. Relief of diarrhoea was significantly more rapid for either dose of loperamide oxide than for placebo. Both the investigators’and the patients’global assessment of the treatment significantly favoured the loperamide oxide 1 mg capsule, but not 0.5 mg, over placebo. Adverse experiences were less frequent in the drug‐treated than in the placebo‐treated group.

Conclusion: These results suggest that loperamide oxide 1 mg produces effective relief of diarrhoeal symptoms.
the risks of malignancy from either immuno‐suppression or diagnostic radiation in inflammatory bowel disease
Authors: FORBES A. , READING N. G.
Published: July 2010

Inflammatory bowel disease is associated with an increased risk of gastrointestinal malignancy. There has been concern that either diagnostic medical radiation and long‐term drug therapy—particularly immunosuppression—might contribute to this increased cancer risk.

For the major drug groups (5‐aminosalicylates, steroids and immunosuppressants) data are scant but broadly reassuring. Only azathioprine (including 6‐mercaptopurine) has been investigated at all carefully. Short‐ to medium‐term therapy probably poses a very slightly increased risk of malignancy which is easily accepted given the current limitation of this agent to second‐line use. Continuous therapy for more than two years is much less well documented, and caution should be maintained.

A hypothetical model based on data from occupational radiation exposure has been constructed; this permits reasonable confidence that the medical use of ionising radiation contributes a negligibly increased risk of malignancy overall, and is particularly unlikely to add significantly to the incidence of gastrointestinal malignancy.
Pre‐ulcerative villous contraction and microvascular induced by indomethacin in the rat jejunum: a detailed morphological study
Authors: ANTHONY A. , DHILLON A. P. , THRASIVOULOU C. , POUNDER R. E. , WAKEFIELD A. J.
Published: July 2010

Background: In indomethacin‐induced jejunal ulceration in the rat, villi undergo both early microvascular injury and shortening that may involve activation of villous smooth muscle.

Aim: This study sought to substantiate light microscopic observations using three‐dimensional imaging of early villous architectural changes in response to indomethacin.

Methods: At both 2 and 6 h after oral indomethacin 15 mg/kg or vehicle to groups of rats, the vasculature of the small intestine was visualised by both carbon‐ink perfusion/confocal microscopy and injection casting. The mucosa was also examined for lesions by dissection microscopy and scanning electron microscopy.

Results: In indomethacin‐dosed rats examined by scanning electron microscopy and histology, the mucosa at 2 h showed villous shortening and wrinkling of the surface epithelium without epithelial loss: at 6 h, the mucosa was flattened, often with epithelial loss to expose a ‘contracted’ villous core. Examination of the vasculature in carbon‐injected tissues indicated significant reductions of both mucosal height and inter‐capillary distance at both 2 and 6 h post‐indomethacin. Scanning electron microscopy of injection casts at 2 and 6 h indicated similar changes. These changes were not seen in control tissues.

Conclusion: Histology, confocal microscopy and scanning electron microscopy support the proposal that villous shortening with disruption of surface capillary architecture are early changes in the ulcerative enteropathy induced by nonsteroidal anti‐inflammatory drugs.
Review article: Refractory distal colitis—explanations and options
Authors: GRIFFIN M. G. , MINER P. B.
Published: July 2010

Distal colitis refractory to standard therapy is a complex and challenging problem. Physiological differences between the right and left colon may be exploited for maximum therapeutic benefit. Overreliance on oral therapy should be seen as one of the reasons for treatment failure and delivery systems should target therapy to the distribution of the disease in doses proven to be therapeutically beneficial. The clinician should also be cognizant of potential adverse effects of standard therapies, particularly colitis due to mesalazine, which may mimic worsening disease. Numerous endogenous and exogenous factors that may exacerbate the underlying inflammatory bowel disease are discussed. This review explores the potential mechanisms why distal colitis may be refractory to therapy and addresses newer therapies that, while still in the investigatory stages, offer hope for a widening armamentarium of therapeutic modalities.
Prevention of water immersion stress‐induced gastric lesions through the enhancement of nitric oxide synthase activity in rats
Authors: TACHI K. , GOTO H. , HAYAKAWA T. , SUGIYAMA S.
Published: July 2010

Background: Gastric mucosal microcirculation is an important factor in the protection of gastric mucosa, and nitric oxide (NO) plays a crucial role in the regulation of regional blood flow. This study was designed to evaluate the effect of cetraxate, an anti‐ulcer drug, on water immersion stress‐induced gastric lesions in relation to the changes in NO synthase activity.

Methods: Gastric lesions were induced in rats by water immersion stress. The effects of cetraxate on NO synthase activity with or without stress was determined enzymatically. Changes in gastric mucosal prostaglandin (PG) contents with or without stress were also determined using high‐performance liquid chromatography. Gastric mucosal blood flow was measured by hydrogen gas clearance technique.

Results: Water immersion stress‐induced gastric lesions. Cetraxate significantly mitigated the lesions but NG‐monomethyl‐l‐arginine (l‐NMMA), a specific inhibitor of NO synthase, exacerbated the lesions. The favourable effect of cetraxate was remarkably diminished by administration ofl‐NMMA. NO synthase activity decreased significantly by 6 h after stress. Cetraxate treatment increased NO synthase activity throughout the experiment in rats with or without stress treatment. Water immersion stress decreased all PGs detected, i.e. 6‐keto‐PGF1α, PGF2αPGE2and PGD2. Cetraxate prevented stress‐induced decreases in PG contents.l‐NMMA showed no significant effect on PG contents. Cetraxate increased gastric mucosal blood flow significantly andl‐NMMA cancelled out cetraxate‐induced increase in blood flow.

Conclusions: The pharmacological efficacy of anti‐ulcer drugs such as cetraxate might be attributable to the enhancement of NO synthase activity resulting in an increase in gastric mucosal blood flow.
Metronidazole, ranitidine and clarithromycin combination for treatment of Helicobacter pylori infection (modified Bazzoli's triple therapy)
Authors: YOUSFI M. M. , EL‐ZIMAITY H. M. T. , COLE R. A. , GENTA R. M. , GRAHAM D. Y.
Published: July 2010

Background: Multi‐drug regimens are generally required to reliably cure Helicobarter pylori infection. Metronidazole, clarithromycin and omeprazole has proven to be an effective combination therapy with a cure rate of 90% or greater.

Methods: We evaluated a 14‐day combination regimen for H. pylori infection consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d. and ranitidine 300 mg b.d. (MRC) instead of omeprazole. Ranitidine alone was continued for an additional 4 weeks. H. pylori status was determined by rapid urease testing. histopathology using the Genta stain, and by culture at entry and 4 weeks after completing antimicrobial therapy.

Results: Twenty‐seven patients with documented peptic ulcer disease and H. pylori infection were treated. Five had previously failed macrolide‐based antimicrobial therapy: none had received metronidazole. All ulcers were healed at week 6 except one patient taking naproxen; his H. pylori infection was cured. Overall, H. pylori infection was cured in 78% (95% CI = 58–91%). In patients with clarithromycin‐sensitive isolates, the cure rate was 20 of 23 (87%, 95% C.I. = 66–97%); only one of four patients (25%) with clarithromycin‐resistant isolates was cured. In contrast, four of five patients with metronidazole‐resistant isolates were cured (80%). In patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18 (89% 95% C.I. = 65–99%). Mild side effects were reported by 27%, including diarrhoea and altered taste. Compliance averaged 98%.

Conclusion: These results suggest that the combination of metronidazole, ranitidine and clarithromycin results in high cure rates in patients with clarithromycin‐sensitive isolates. Omeprazole may not be required for Bazzoli's triple therapy; and large multicentre comparative trials are indicated.
Could frameshift mutations in the frxA and rdxA genes of Helicobacter pylori be a marker for metronidazole resistance?
Authors: MASAOKA T. , SUZUKI H. , KURABAYASHI K. , NOMOTO Y. , NISHIZAWA T. , MORI M. , HIBI T.
Published: July 2010

Background

Although resistance of Helicobacter pylori to metronidazole had been reported to be associated with mutations in the rdxA or the frxA gene, recent studies have indicated that they may contribute little to metronidazole resistance.

Aim

To clarify the roles of these genes in metronidazole resistance, we examined them in strains that were not eradicated by first‐line eradication therapy.

Patients and methods

A total of 132 patients (92 males, 40 females, average age: 53.8 years old) who underwent upper gastrointestinal endoscopy after unsuccessful first‐line H. pylori eradication were enrolled. Antibiotic susceptibility to metronidazole was investigated using the agar dilution method. The H. pylorirdxA and frxA genes were then sequenced.

Results

In the metronidazole‐resistant strains, the sensitivity of detection of frameshift mutations in the rdxA gene was 44%. A significant association between the presence of frameshift mutations in the rdxA gene and resistance to metronidazole was observed. No significant association between frameshift mutations in the frxA gene and resistance to metronidazole was observed.

Conclusion

Mutation in the rdxA gene was sufficient, but not necessary to confer resistance to metronidazole in H. pylori. Mutation in the frxA gene was not necessary for resistance to metronidazole in H. pylori.
Enhanced plasma ghrelin levels in patients with functional dyspepsia
Authors: NISHIZAWA T. , SUZUKI H. , NOMOTO Y. , MASAOKA T. , HOSODA H. , MORI M. , OHARA T. , MORISHITA T. , KANGAWA K. , HIBI T.
Published: July 2010

Background

Ghrelin, growth‐hormone‐releasing peptide, has been reported to accelerate food intake and gastrointestinal motility.

Aim

The present study was designed to investigate the plasma ghrelin levels in patients with functional dyspepsia (FD).

Patients and Methods

Ninety‐seven patients, who showed no evidence of peptic ulcer disease or gastrointestinal cancer on upper gastrointestinal endoscopy, were recruited. Seventeen patients who had no gastrointestinal symptoms were recruited as controls. Forty‐seven patients were diagnosed to be suffering from FD, based on the Rome II criteria. The FD patients were further subdivided into those with ulcer‐like FD, dysmotility‐like FD and non‐specific‐type FD, based on their Gastrointestinal Symptom Rating Scale (GSRS) scores. Fourteen patients were categorized as having gastro‐oesophageal reflux disease, and 19 patients were excluded as having the irritable bowel syndrome, based on the GSRS. The plasma ghrelin levels were measured by radioimmunoassay.

Results

The plasma ghrelin levels were significantly higher in FD patients, especially in those with dysmotility‐like FD, as compared with those in controls. The plasma ghrelin levels were also correlated well with the indigestion scores.

Conclusion

Plasma ghrelin levels are significantly higher in patients with dysmotility‐like FD, suggesting that this parameter could become useful as a novel supportive marker for the diagnosis of FD.
Interaction between Helicobacter pylori and immune response to CagA: CagA antibody may down‐regulate bacterial colonization and tyrosine phosphorylation
Authors: DEGUCHI R. , WATANABE K. , KOGA Y. , KIJIMA H. , TAKAGI A.
Published: July 2010

Background

CagA+Helicobacter pylori strains are associated with the development of gastroduodenal diseases. H. pylori possess a type IV secretion system that is responsible for the translocation of CagA into host cells.

Aim

To investigate the correlation between the CagA status and the severity of histological gastritis and to analyse the tyrosine phosphorylation of CagA.

Methods

A total of 149 H. pylori status was determined via urine antibody to H. pylori, histological examination and serum antibody against CagA. Histological gastritis was evaluated using the updated Sydney system and scored from 0 to 3. Tyrosine phosphorylation was analysed using immunoprecipitation and immunoblotting.

Results

Anti‐CagA titres were correlated with the severity of mononuclear cell infiltration. In contrast, mean anti‐CagA in patients with grade 2 bacterial density was significantly higher than those with grade 0 (P < 0.01). Mean anti‐titre in patients with grade 3 tended to be lower than that seen with grade 2. CagA tyrosine phosphorylation was significantly more common in bacteria isolated from CagA‐antibody‐negative patients (93%;13/14) than from CagA‐antibody‐positive patients (29%; 4/14, P = 0.0007).

Conclusions

Host–bacteria interaction is regarded as one of the important factors in the development of gastroduodenal diseases.
Neurokinin‐1 receptor antagonism in a human model of visceral hypersensitivity
Authors: WILLERT R. P. , HOBSON A. R. , DELANEY C. , HICKS K. J. , DEWIT O. E. , AZIZ Q.
Published: July 2010

Background

Substance P acting via the neurokinin‐1 receptor is involved in the development of hyperalgesia, although studies using neurokinin‐1 receptor antagonists (NK‐1RA) in human somatic pain have been disappointing.

Aim

To evaluate whether Substance P is involved in the development of human visceral pain/hyperalgesia using a selective NK‐1RA.

Methods

Using a validated human model of acid‐induced oesophageal allodynia, pain thresholds to electrical stimulation (mA) were measured in the proximal oesophagus and the foot (somatic control), pre‐ and for 4 h postdistal oesophageal acid in 14 healthy subjects, using a double‐blind, randomized, two‐period, crossover study. Measurements were taken on the third day of dosing with either an oral NK‐1RA or matching placebo, with 2 weeks washout between periods.

Results

Baseline pain threshold did not differ between treatments (proximal oesophagus 37 ± 7.4 mA NK‐1RA vs. 38 ± 10.1 placeboP = 0.81, foot 40 ± 15 mA NK‐1RA vs. 38 ± 14 placeboP = 0.68). NK‐1RA did not attenuate the reduction in pain threshold in the proximal oesophagus postacid infusion (AUC−394 ± 279 NK‐1RA vs. −262 ± 397 placeboP = 0.54).

Conclusions

The lack of effect of NK‐1RA on oesophageal pain threshold in our model does not support a role for Substance P in the development of acid‐induced oesophageal allodynia.
Predictors of inappropriate utilization of intravenous proton pump inhibitors
Authors: AFIF W. , ALSULAIMAN R. , MARTEL M. , BARKUN A. N.
Published: July 2010

Background  Inappropriate use of intravenous proton pump inhibitors is prevalent.

Aim  To assess appropriateness of intravenous proton pump inhibitor prescribing.

Methods  Retrospective review of in‐patient prescribing of intravenous pantoprazole over a 2‐month period in 2004, in an academic centre. Prescribing was deemed appropriate before and after endoscopic haemostasis, and in fasting individuals requiring a proton pump inhibitor.

Results  Amongst 107 patients, 49 (46%) had upper gastrointestinal bleeding. Overall, 33 (31%, 95% CI: 22–41%) received appropriate therapy (indication, dose and duration), 61 (57%, 95% CI: 47–67%) had an inappropriate indication, and 13 (12%, 95% CI: 7–20%) had an incorrect treatment dose or duration. Therapy was appropriate in 20 (41%, 95% CI: 27–55%) with upper gastrointestinal bleeding, and 13 (22%, 95% CI: 12–33%) in the non‐upper gastrointestinal bleeding group. Appropriate prescribing rates decreased (from 41% to 16%, 95% on difference CI: 14–38%) when considering intravenous proton pump inhibitor use while awaiting endoscopy as inappropriate. Significant predictors of inappropriate use were increasing age and decreasing mean daily dose, with a trend for prescriptions written during evening shifts.

Conclusion  Inappropriate intravenous proton pump inhibitor utilization was most frequent in the non‐upper gastrointestinal bleeding group, mostly for unrecognized indications. Educational interventions to optimize utilization should target prescribing in older patients, those receiving lower mean daily doses, and, perhaps, prescribing outside regular hours.
Sustained virological response to interferon reduces cirrhosis in chronic hepatitis C: a 1386‐patient study from Taiwan
Authors: HUANG J.‐F. , YU M.‐L. , LEE C.‐M. , DAI C.‐Y. , HOU N.‐J. , HSIEH M.‐Y. , WANG J.‐H. , LU S.‐N. , SHEEN I.‐S. , LIN S.‐M. , CHUANG W.‐L. , LIAW Y.‐F.
Published: July 2010

Background The long‐term benefits of interferon‐based therapy on preventing cirrhosis at non‐cirrhotic stage in chronic hepatitis C patients are not fully clarified.

Aim To evaluate the effectiveness of interferon‐based therapy regarding to cirrhosis prevention in non‐cirrhotic chronic hepatitis C patients.

Methods A total of 1386 biopsy‐proven, non‐cirrhotic chronic hepatitis C patients (892 received interferon‐based therapy and 494 untreated) were enrolled.

Results Fifty‐six untreated and 51 treated (24 sustained virologic responders and 27 non‐responders) patients developed cirrhosis during a mean follow‐up period of 5.0 (1–16) and 5.1 (1–15.3) years, respectively. The annual incidences of cirrhosis in untreated and treated groups were 2.26 and 1.11% (non‐responders: 1.99%, sustained responders: 0.74%), respectively. The 15‐year cumulative incidence of cirrhosis was significantly lower in treated (9.9%) than untreated patients (39.8%, P = 0.0008, log‐rank test). The 14.5‐year cumulative incidence of cirrhosis was significantly lower in sustained responders (4.8%) compared with non‐responders (21.6%, P = 0.0007) and untreated patients (36.6%, P < 0.0001). The difference was not significant between non‐responders and untreated controls. Cox proportional hazards regression showed sustained virologic responders and younger age were independent negative factors for cirrhosis development.

Conclusion A sustained virologic response secondary to IFN‐based therapy could reduce cirrhosis development in chronic hepatitis C patients.
Review article: drug hepatotoxicity
Authors: CHANG C. Y. , SCHIANO T. D.
Published: July 2010

BackgroundDrug toxicity is the leading cause of acute liver failure in the United States. Further understanding of hepatotoxicity is becoming increasingly important as more drugs come to market.

Aims(i) To provide an update on recent advances in our understanding of hepatotoxicity of select commonly used drug classes. (ii) To assess the safety of these medications in patients with pre‐existing liver disease and in the post‐liver transplant setting. (iii) To review relevant advances in toxicogenomics which contribute to the current understanding of hepatotoxic drugs.

MethodsA Medline search was performed to identify relevant literature using search terms including ‘drug toxicity, hepatotoxicity, statins, thiazolidinediones, antibiotics, antiretroviral drugs and toxicogenomics’.

ResultsAmoxicillin‐clavulanic acid is one of the most frequently implicated causes of drug‐induced liver injury worldwide. Statins rarely cause clinically significant liver injury, even in patients with underlying liver disease. Newer thiazolidinediones are not associated with the degree of liver toxicity observed with troglitazone. Careful monitoring for liver toxicity is warranted in patients who are taking antiretrovirals, especially patients who are co‐infected with hepatitis B and C. Genetic polymorphisms among enzymes involved in drug metabolism and HLA types may account for some of the differences in individual susceptibility to drug hepatotoxicity.

ConclusionsDrug‐induced hepatotoxicity will remain a problem that carries both clinical and regulatory significance as long as new drugs continue to enter the market. Future results from ongoing multicentre collaborative efforts may help contribute to our current understanding of hepatotoxicity associated with drugs.
First‐line triple therapy with levofloxacin for Helicobacter pylori eradication
Authors: GISBERT J. P. , FERNÁNDEZ‐BERMEJO M. , MOLINA‐INFANTE J. , PÉREZ‐GALLARDO B. , PRIETO‐BERMEJO A.‐B. , MATEOS‐RODRÍGUEZ J.‐M. , ROBLEDO‐ANDRÉS P. , GONZÁLEZ‐GARCÍA G.
Published: July 2010

Background At present, the efficacy of proton pump inhibitor‐clarithromycin‐amoxicillin regimen is relatively low.

Aim To evaluate the efficacy and tolerability of a first‐line triple clarithromycin‐free regimen including ranitidine bismuth citrate, levofloxacin and amoxicillin.

Methods Design: Prospective study. Patients: Helicobacter pylori‐positive patients complaining of dyspeptic symptoms referred for gastroscopy. Intervention: Levofloxacin (500 mg b.d.), amoxicillin (1 g b.d.) and ranitidine bismuth citrate (400 mg b.d.) was prescribed for 10 days. Outcome: Eradication was confirmed by a 13C‐urea breath test 8 weeks after therapy. Compliance with therapy was determined by questioning and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire.

Results Sixty‐four patients were included (30% peptic ulcer, 70% functional dyspepsia). Almost all (97%) patients took all the medications correctly. Per‐protocol and intention‐to‐treat eradication rates were 88.5% (95% CI =78–95%) and 84.4 (74–91%). Adverse effects were reported in 9.5% of the patients, mainly including diarrhoea (7.9%); none of them were severe.

Conclusion This new 10‐day levofloxacin‐based combination represents an alternative to clarithromycin‐based therapy, as it meets the criteria set for regimens used as primary H. pylori treatment: effectiveness (>80%), simplicity (twice‐daily dosing and excellent compliance) and safety (low incidence of adverse effects).
Eosinophilic oesophagitis and coeliac disease: is there an association?
Authors: QUAGLIETTA L. , COCCORULLO P. , MIELE E. , PASCARELLA F. , TRONCONE R. , STAIANO A.
Published: July 2010

Aim  To report a series of 17 children affected by eosinophilic oesophagitis. Six of them also received a diagnosis of coeliac disease.

Methods  Seventeen children with history of dyspeptic symptoms were investigated.

Results  Six patients (M/F:2/4; mean age ± s.d.: 5.6 ± 1.3 years, range: 4–7 years; Group A) affected by eosinophilic oesophagitis also received a diagnosis of coeliac disease. The other 11 children (M/F:10/1, mean age ± s.d.:7.5 ± 2.3 years, range: 4–10 years, Group B) were affected solely by eosinophilic oesophagitis. All children underwent a change in dietary regimen. Group A received a gluten‐free diet. Group B attempted dietary restriction based on the allergy testing results. After 6 months follow‐up, all patients in Group A showed a complete disappearance of symptoms and three of them, who underwent upper gastrointestinal endoscopy, showed histologic remission. Patients from Group B had moderate clinical improvement and in seven of them (64%) a repeated upper gastrointestinal endoscopy showed a statistically significant reduction in eosinophilic infiltration.

Conclusions  This is the first reported group of patients with an association between coeliac disease and eosinophilic oesophagitis. To date, it is not possible to exclude that in a subgroup of children with coeliac disease the oesophageal eosinophilic infiltration could be caused by coeliac disease itself.
Acute systemic, splanchnic and renal haemodynamic changes induced by molecular adsorbent recirculating system (MARS) treatment in patients with end‐stage cirrhosis
Authors: DONATI G. , PISCAGLIA F. , COLÌ L. , SILVAGNI E. , RIGHINI R. , DONATI G. , PINI P. , STEFONI S. , BOLONDI L.
Published: July 2010

Aim

To evaluate the acute effect of treatment with the molecular adsorbent recirculating system (MARS) on splanchnic, renal and systemic haemodynamics in patients with end‐stage cirrhosis.

Methods

Twelve patients with end‐stage cirrhosis, undergoing MARS treatment, were enrolled. The following haemodynamic parameters were measured by means of Doppler ultrasonography and thoracic electrical bioimpedance, before and after each session: portal velocity, renal and splenic resistance indices, cardiac output, cardiac stroke volume, heart rate, mean arterial pressure, systemic vascular resistance.

Results

Median portal velocity increased significantly after treatment (23.7 vs. 20.3 cm/s,P < 0.05) while renal resistance index (0.72 vs. 0.75,P < 0.05) and splenic resistance index (0.60 vs. 0.65,P < 0.05) decreased significantly. Mean arterial pressure (83 vs. 81 mmHg,P < 0.05) and vascular resistance (899 vs. 749 dyne. s/cm5,P < 0.05) increased significantly, while cardiac output and stroke volume showed no significant changes.

Conclusions

Data emerging from this investigation suggest that MARS treatment improves significantly various haemodynamic alterations in cirrhotic patients in the short term. The observed decrease in renal vascular resistance and improvement in splenic resistance index, a parameter related to portal resistance, which leads us to hypothesize that these haemodynamic effects are probably mediated by clearance of vasoactive substances during MARS treatment.
Meta‐analysis: a functional polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel syndrome
Authors: VAN KERKHOVEN L. A. S. , LAHEIJ R. J. F. , JANSEN J. B. M. J.
Published: July 2010

Background  Serotonin is associated with symptoms of the irritable bowel syndrome, its action is terminated by the serotonin transporter protein.

Aim  To assess the association between a functional polymorphism in the gene encoding for activity of the serotonin transporter protein and the irritable bowel syndrome.

Methods  Meta‐analysis of studies identified through a Medline, PubMed and Web of Science search, describing the prevalence of a polymorphism in the serotonin transporter gene creating long and short alleles.

Results  Eight eligible studies described a total of 1034 patients with the irritable bowel syndrome, and 1377 healthy controls. Presence of the short allele is not associated with an increased risk for the irritable bowel syndrome: OR 1.0; 95% CI: 0.7–1.4 for homozygous subjects, and OR 1.0; 95% CI: 0.8–1.2 for homozygous subjects and heterozygotes together. Although Caucasians and Asians had diverging genotypic frequencies, no association with the shot allele and irritable bowel syndrome was observed in subgroups: Asians OR 1.2; 95% CI: 0.9–1.6 and OR 1.1; 95% CI: 0.2–5.9; Caucasians OR 0.9; 95% CI: 0.5–1.7 and OR 0.9; 95% CI: 0.7–1.2, respectively, for homozygous subjects alone and for homozygous subjects and heterozygotes together.

Conclusion  A genetic polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel.
Clinical trial: switch to combined mycophenolate mofetil and minimal dose calcineurin inhibitor in stable liver transplant patients – assessment of renal and allograft function, cardiovascular risk factors and immune monitoring
Authors: CICINNATI V. R. , YU Z. , KLEIN C. G. , SOTIROPOULOS G. C. , SANER F. , MALAGÓ M. , FRILLING A. , GERKEN G. , BROELSCH C. E. , BECKEBAUM S.
Published: July 2010

Background Calcineurin inhibitor (CNI)‐related nephrotoxicity significantly contributes to chronic renal failure after liver transplantation.

Methods In this prospective study, liver transplantation patients with renal dysfunction were randomized either to receive mycophenolate mofetil (MMF) followed by stepwise reduction of CNI with defined minimal CNI‐trough levels (MMF group), or to continue their maintenance CNI dose (control group). Immune monitoring was performed in a subgroup of the patients.

Results In the MMF group (n = 50), renal function assessed by serum creatinine improved >10% in 62% of patients, was stable in 36% and deteriorated >10% in 2% after 12 months compared with baseline values. Mean serum creatinine levels (± s.d.) significantly decreased from 1.90 ± 0.44 mg/dL to 1.61 ± 0.39 mg/dL and the corresponding calculated glomerular filtration rate significantly increased from 38.8 ± 9.6 mL/min/1.73 m2to 47.0 ± 11.8 mL/min/1.73 m2over a 12‐month follow‐up period. Blood pressure and levels of liver enzymes significantly decreased. In the control group (n = 25), there were no significant changes with respect to the investigated parameters. The MMF group had significantly lower numbers of circulating cytotoxic T cells compared with the controls; whereas regulatory T cells significantly increased.

Conclusion Combined MMF and minimal dose CNI therapy after liver transplantation is nephroprotective and may promote allograft tolerance.
Clinical trial: knowledge of negative Helicobacter pylori status reduces subsequent dyspepsia‐related resource use
Authors: FORD A. C. , FORMAN D. , NATHAN J. , CROCOMBE W. D. , AXON A. T. R. , MOAYYEDI P.
Published: July 2010

Background  Screening for Helicobacter pylori reduces dyspepsia and dyspepsia‐related costs in positive individuals.

Aims  To assess effect of knowledge of H. pylori status on healthcare‐seeking in negative individuals.

Methods  H. pylori‐negative subjects in a community screening programme were randomized to placebo triple therapy or informed of their negative H. pylori status. Dyspepsia‐related resource data were extracted from primary care records at 2 years, and National Health Service reference costs were applied to calculate the total cost per subject. Proportions of individuals incurring any cost were compared using a relative risk (RR) and 95% confidence interval (CI). Differences in costs were compared using an independent sample t‐test.

Results  A total of 1353 H. pylori‐negative individuals were randomized to placebo whilst 1355 were informed of their infection status. In the placebo arm, 212 (16%) subsequently incurred any dyspepsia‐related cost compared to 172 (13%) informed of their infection status (RR of incurring cost = 0.81; 95% CI: 0.67–0.97). Those informed of their infection status incurred lower costs (mean saving per individual = £11.02; 95% CI: −£3.52 to 25.56).

Conclusions  H. pylori‐negative individuals informed of infection status sought health care for dyspepsia less often than those who were unaware. Population screening may reduce dyspepsia‐related costs in uninfected, as well as infected individuals.
Review article: thrombocytopenia in chronic liver disease
Authors: POORDAD F.
Published: July 2010

Background Thrombocytopenia is a common finding in advanced liver disease. It is predominantly a result of portal hypertension and platelet sequestration in the enlarged spleen, but other mechanisms may contribute. The liver is the site of thrombopoietin (TPO) synthesis, a hormone that leads to proliferation and differentiation of megakaryocytes and platelet formation. Reduced TPO production further reduces measurable serum platelet counts.

Aim This paper describes the scope of thrombocytopenia in chronic liver disease and assesses the clinical impact in this patient population.

Methods A medline review of the literature was performed pertaining to thrombocytopenia and advanced liver disease. This data is compiled into a review of the impact of low platelets in liver disease.

Results The incidence of thrombocytopenia, its impact on clinical decision making and the use of platelet transfusions are addressed. Emerging novel therapeutics for thrombocytopenia is also discussed.

Conclusions Thrombocytopenia is a common and challenging clinical disorder in patients with chronic liver disease. New therapeutic options are needed to safely increase platelet counts prior to invasive medical procedures as well as to counteract therapies that further exacerbate low platelets, such as interferon. An ideal compound would be orally available and safe, with rapid onset of action.
Systematic review and meta‐analysis: the clinical and physiological effects of fibre‐containing enteral formulae
Authors: ELIA M. , ENGFER M. B. , GREEN C. J. , SILK D. B. A.
Published: July 2010

Background Enteral nutrition can be associated with gastrointestinal side effects and fibre supplementation has been proposed as a means to normalize bowel function.

Aim To evaluate systematically the effects of fibre supplementation of enteral feeds in healthy volunteers and patients both in the hospital and community settings.

Methods Electronic and manual bibliographic searches were conducted. Controlled studies in adults or children, comparing fibre‐supplemented vs. fibre‐free formulae given as the sole source of nutrition for at least 3 days, were included.

Results Fifty‐one studies (including 43 randomized‐controlled trials), enrolling 1762 subjects (1591 patients and 171 healthy volunteers) met the inclusion criteria. Fibre supplementation was generally well tolerated. In the hospital setting, the incidence of diarrhoea was reduced as a result of fibre administration (OR 0.68, 95% CI: 0.48–0.96; 13 randomized‐controlled trials). Meta‐regression showed a more pronounced effect when the baseline incidence of diarrhoea was high. In both patients and healthy subjects, fibre significantly reduced bowel frequency when baseline frequency was high and increased it when it was low, revealing a significant moderating effect of fibre.

Conclusions The review indicates that the fibre‐supplemented enteral formulae have important physiological effects and clinical benefits. There is a need to use a consistent approach to undertake more studies on this issue in the community setting.
The utilization of parenteral nutrition during the in‐patient management of inflammatory bowel disease in the United States: a national survey
Authors: NGUYEN G. C. , LAVEIST T. A. , BRANT S. R.
Published: July 2010

Background  Parenteral nutrition has a limited role in the in‐patient management of inflammatory bowel disease.

Aim  To determine nationwide patterns of in‐patient parenteral nutrition utilization and its demographic determinants and impact on outcomes.

Methods  We identified inflammatory bowel disease discharges in the Nationwide Inpatient Sample between 1998 and 2003 and determined rates of parenteral nutrition utilization among US census regions, in‐hospital mortality and hospital resource utilization.

Results  The parenteral nutrition utilization rate among hospitalized inflammatory bowel disease patients was 6%. Only 64% of Crohn’s disease and 55% of ulcerative colitis discharges who received parenteral nutrition had malnutrition, fistulizing or obstructive Crohn’s disease, or surgery as an indication. The adjusted odds ratio of receiving parenteral nutrition were 0.36 (95% CI: 0.26–0.51) for the mid‐west, 0.47 (0.37–0.56) for the south and 0.70 (0.56–0.89) for the west, compared to the north‐east. Use of parenteral nutrition was associated with higher in‐hospital mortality (OR 2.5; 95% CI: 1.93–3.24), length of stay (13.7 vs. 5.7 days, P < 0.001) and hospital charges ($51 729 vs. $19 563, P < 0.001).

Conclusions  In‐patient utilization of parenteral nutrition for inflammatory bowel disease varies markedly by census region, expends significant resources, and leads to potentially significant adverse outcomes. These findings underscore the need for guidelines for judicious parenteral nutrition use in inflammatory bowel disease.