bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical management of the short bowel
Authors: LENNARD‐JONES J. E.
Published: July 2010

A shortened small intestine may end at a stoma or be anastomosed to the colon. Patients with a jejunostomy, but not those with a colon, lose large amounts of sodium. The intake and absorption of sodium can be increased by sipping a sodium–glucose solution: stomal loss can be reduced by restricting water or low‐sodium drinks. If a stoma is situated less than 100 cm along the jejunum, a constant negative sodium balance may necessitate parenteral saline supplements. Gastric anti‐secretory drugs or a somatostatin analogue reduce jejunostomy losses in such patients but do not restore a positive sodium balance. Loperamide or codeine phosphate benefit some patients. Magnesium deficiency can usually be corrected by oral magnesium oxide supplements. An elemental or hydrolysed diet is not beneficial. Patients with a jejunostomy can maintain a normal diet without fat reduction.

When the colon is present, unabsorbed carbohydrate is fermented to absorbable short chain fatty acids. Unabsorbed long chain fatty acids and bile salts cause watery diarrhoea and increased colonic oxalate absorption with hyperoxaluria. Such patients benefit from a high carbohydrate, low‐fat and low‐oxalate diet.

Parenteral nutrition is needed only by the few patients unable to maintain health or avoid socially disabling diarrhoea despite these measures.
Review article: infective complications of therapeutic gastric acid inhibition
Authors: LARNER J. , HAMILTON M. I. R.
Published: July 2010

Gastric acid secretion has a non‐specific bactericidal action which contributes to gastrointestinal defence mechanisms against micro‐organisms. Therapeutic inhibition of acid secretion with histamine H2 receptor antagonists and proton pump inhibitors might therefore be expected to predispose to infection. This article reviews clinical reports of infection occurring during therapeutic gastric acid inhibition, and assesses the risk of infection incurred by such treatment. Non‐typhoid salmonelloses, Campylobacter infections, local candidiasis, and possibly Strongyloides hyperinfections may be more prevalent after acid inhibitory treatment, but concurrent impairment of other gastrointestinal defence mechanisms may be necessary to permit infection.
Dexamethasone promotes ulcer plugging in experimental enteritis
Authors: ANTHONY A. , DHILLON A. P. , SIM R. , POUNDER R. E. , WAKEFIELD A. J.
Published: July 2010

Aim: We investigated the effect of dexamethasone on indomethacin‐induced ulceration in the rat.

Methods: Groups of four rats received oral indomethacin (15 mg/kg) and the jejunal mucosa was examined 24 h later for mucosal ulceration. Three of the groups received oral dexamethasone (1,3 and 6 mg/kg) 0.5 h prior to indomethacin, while the fourth received vehicle. Haematological evaluation was performed and ulcers were assessed both histologically and immunohistochemically.

Results: Indomethacin caused multifocal jejunal ulceration that was reduced only by the highest dose of dexamethasone (6 mg/kg). Indomethacin caused a significant fall in the blood haemoglobin concentration that was prevented by dexamethasone at all doses. The ulcers induced by indomethacin alone were deep, punched‐out and haemorrhagic while the ulcers arising in rats pre‐treated with dexamethasone (all doses) were‘plugged‘ by a white fibrino‐purulent exudate. Histologically, the dexamethasone ulcer exudate was composed of bacteria, fibrin, mucus and a significant increase in the numbers of neutrophils. Dexamethasone alone had no significant pathological effect on the small intestine.

Conclusions: We report the observation that examethasone at high doses inhibits indomethacin‐induced jejunal ulceration in the rat while at low doses it promotes‘plugging‘ of ulcers with bacteria, fibrin, mucus and neutrophils that probably reduces haemorrhage from the ulcer base.
Pharmacokinetics and retrograde colonic spread of budesonide enemas in patients with distal ulcerative colitis
Authors: NYMAN‐PANTELIDIS M. , NILSSON Å. , G‐WAGNER Z. , BORGA O.
Published: July 2010

Methods: The retrograde spread of two budesonide enema formulations with different viscosities was investigated. The study design was open, randomized and two‐period crossover. Three female and two male patients (age range: 35–45 years) with distal ulcerative colitis or proctitis participated. Both enema formulations contained a dose of 2 mg budesonide/100 mL. An unabsorbable radioactive marker (99mTc‐labelled human serum albumin microcolloid) was added to the enema just before administration. All doses were given in the evening with the patients lying in a supine position during the whole investigation. The intestinal spread was followed for 8 h using scintigraphic imaging. Plasma samples for budesonide assay were taken during the 12 h after administration of the low viscosity enema.

Results: Budesonide plasma levels were measurable for up to 4–6 h. Cmax was 2.5 nmol/L (range:0.9–4.5 nmol/L) and was attained in 1.5 h (range 1–3 h). The patients had no difficulty in retaining the enemas. There was a statistically significant difference in spread between the low and high viscosity enema. The low viscosity enema spread over an area situated between the rectum and the splenic flexure. The spread occurred mainly in the first 15 min after administration. In contrast, the high viscosity enema, in most cases, spread only over a minor part of this area and the rate and extent of spreading was also more variable with this formulation.

Conclusion: The spread of a low viscosity enema appears to be well suited for the treatment of proctitis and distal colitis.
Omeprazole and the cytochrome P450 system
Authors: PETERSEN K.‐U.
Published: July 2010

Enzymes of the cytochrome P450 superfamily play a key role in xenobiotic metabolism. Their properties and significance are discussed with particular reference to interactions with the H+, K+‐ATPase blocker, omeprazole. Such interactions include both inhibitory (subfamily 2C) and inducing effects (subfamily 1A). Delayed metabolic elimination of diazepam, warfarin, carbamazepin and phenytoin is probably due to omeprazole competition for the concerned isoform of subfamily 2C; however, these effects are modest to negligible in magnitude and, for phenytoin, not consistently reproducible. Also, induction of subfamily 1A is only minor as assessed from the resultant changes inN‐3‐demethylation of caffeine, a reaction specific to this subfamily. Concerns about a possible activation of procarcinogens that might arise from subfamily 1A induction appear ill‐founded given the fact that cruciferous vegetables such as broccoli and Brussels sprouts are potent inducers, but rather seem to lower the incidence of certain types of cancer. Likewise, the idea that the toxicity of acetaminophen might increase upon subfamily 1A induction appears far‐fetched, mainly because much stronger inducers of subfamily 1A (cigarette smoke and charcoaled beef) are unable to alter acetaminophen metabolism.
Successful Helicobacter pylori eradication incorporating a one‐week antibiotic regimen
Authors: HUDSON N. , BRYDON W. G. , EASTWOOD M. A. , FERGUSON A. , PALMER K. R.
Published: July 2010

Background: The optimum regimen for the eradication of Helicobacter pylori remains unclear. The aim of this study was to determine the efficacy and tolerability of omeprazole 40 mg daily given for 2 weeks, plus amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. given for the first 7 days, in the treatment of H. pylori associated peptic ulcer disease.

Results: One hundred and thirty‐two consecutive patients with peptic ulcer disease were entered into the study (89 male, 41 female; median age 47 years; inter‐quartile range: 36–58 years). H. pylori was eradicated successfully in 109 of 130 patients (intention‐to‐treat: 83%; 95% confidence limits: 76–89%); per protocol: 85% (95% CI: 78–91%)). Ninety per cent of patients completed the full course of therapy. Only four patients (3%) stopped treatment as a result of side effects although these occurred in 41% of patients. One patient developed pseudomembranous colitis requiring hospital admission.

Conclusion: Omeprazole combined with one week of treatment of amoxycillin and metronidazole is an effective and well tolerated Helicobacter eradication regimen. Occasional severe side effects remain a risk, even when the duration of antibiotic exposure is reduced.
Review article: anti‐diarrhoeal pharmacology and therapeutics
Authors: SCHILLER L. R.
Published: July 2010

Anti‐diarrhoeal drugs reduce the symptoms of diarrhoea (loose stool consistency, frequency of defecation and excessive stool weight) by effects on intestinal transit, mucosal transport or luminal contents. Opiates and opioids are the most useful anti‐diarrhoeal agents. Opiates have major effects on intestinal transit; pro‐absorptive and anti‐secretory effects are less well documented, but may be important for some of these drugs. Alpha‐adrenergic agonists, somatostatin analogues and several other agents have had limited clinical use; these drugs may modify mucosal transport in addition to slowing transit. Adsorbents, bismuth and stool texture modifiers are used frequently by the public, but their efficacy is largely unproven. Oral rehydration solutions have had the greatest impact in saving lives and continue to be improved. Many new approaches to the treatment of diarrhoea are yet to be exploited.
Effect of D2‐dopamine receptor antagonist levosulpiride on diabetic cholecystoparesis : a double‐blind crossover study
Authors: MANSI C. , SAVARINO V. , VIGNERI S. , SCIABÀ L. , PERILLI D. , MELE M. R. , CELLE G.
Published: July 2010

Background: Abnormal gall‐bladder motility has been reported in diabetics. The objective was to evaluate the effect of chronic D2‐dopamine receptor inhibition on gall‐bladder emptying in diabetic patients.

Methods: Under double‐blind placebo‐controlled conditions and according to a crossover design, patients were randomly assigned to receive either 4 weeks treatment with levosulpiride 25 mg t.d.s. or 4 weeks treatment with placebo, with an interval of 15 days. Twenty‐three consecutive long‐standing, insulin‐treated diabetics with autonomic neuropathy were studied.

Measurements: At the beginning of the study and after levosulpiride or placebo treatment, gall‐bladder emptying was measured ultrasonically by evaluating the gall‐bladder volume in basal conditions and every 15 min for 90 min after the ingestion of a standard meal. Statistical analysis of the results was performed by means of analysis of variance.

Results: Levosulpiride treatment reduced the basal mean gall‐bladder volume from 21.6 ± 2.3 to 18.6 ± 2.3 mL (P < 0.05). Furthermore, the residual gall‐bladder volume (9.3 ± 1.4 mL) was significantly reduced compared to the corresponding pre‐treatment volume (14.6 ± 1.5 mL (P < 0.05)). In placebo‐treated patients, no significant differences were observed in gall‐bladder volumes before and after treatment.

Conclusion: These results show that chronic oral administration of the D2 dopamine antagonist levosulpiride has a significant effect on gall‐bladder motility in diabetic patients.
manipulation of cell death — the development of novel strategies for the treatment of gastrointestinal disease
Authors: WATSON A. J. M.
Published: July 2010

The mechanisms underlying cell death are reviewed in order to propose new targets for the therapy of gastrointestinal disease. Necrosis is a set of precise biochemical and cellular lesions which culminate in cell destruction. A number of potential targets for drug therapy are discussed which will inhibit necrosis, including preservation of cellular ATP by inhibition of poly(ADP‐ribose) polymerase. Such therapies may be useful either as adjuncts to other therapeutic modalities such as immunosuppressive agents for the treatment of inflammatory conditions or on their own for organ preservation prior to organ transplantation. Either excessive apoptosis or failure of apoptosis plays an important role in a variety of gastrointestinal diseases. Failure of apoptosis is of particular importance in the development of colorectal cancer. Mutations or deletions ofp53, bcl‐2andmycprevents the appropriate deletion of malignant cells and causes resistance to anti‐cancer drugs which act by the induction of apoptosis. Correction of these genetic defects or replacement of their function is a major strategy in cancer prevention and therapy. It is concluded that manipulation of cell death processes is an important new area for gastrointestinal research.
new insights into prostaglandins and mucosal defence
Authors: WALLACE J. L. , TIGLEY A. W.
Published: July 2010

A role for prostaglandins in maintaining mucosal integrity in the gastrointestinal tract is well documented. While traditionally the effects of prostaglandins on mucosal blood flow and epithelial function have been regarded as critical in the mechanism of action of these fatty acids, recent evidence that mucosal ulceration is almost invariably associated with mucosal inflammation has caused a reevaluation of the role of prostaglandins in mucosal defence. This review focuses on the ability of prostaglandins to exert anti‐inflammatory, and therefore anti‐ulcerogenic, effects in the gastrointestinal tract. These effects of prostaglandins are attributable to their ability to suppress the release of inflammatory mediators and reactive oxygen metabolites from a number of immunocytes, stromal cells and inflammatory cells. There is emerging evidence for cooperative interactions between prostaglandins and nitric oxide in maintaining mucosal integrity. Recent work on the inducible isoform of prostaglandin synthase as it pertains to mucosal defence is also reviewed.
osteoporosis, corticosteroids and inflammatory bowel disease
Authors: COMPSTON J. E.
Published: July 2010

Osteoporosis is a serious complication of inflammatory bowel disease which has not received adequate recognition despite its high prevalence and potentially devastating clinical effects. Its pathogenesis remains poorly defined although corticosteroid therapy and sex hormone deficiency are likely to play a major role.

Recent advances in the diagnosis and management of osteoporosis have facilitated early detection of bone loss and identified means by which this may be prevented. Bone density measurements to predict fracture risk and define thresholds for prevention and treatment should be performed routinely in patients with inflammatory disease. Hormone replacement therapy is effective in prevention of bone loss in peri‐ and post‐menopausal patients, but the treatment of younger women and men of all ages requires further study.
Prognostic factors for relapse and maintenance treatment with cisapride in gastro—oesophageal reflux disease
Authors: TYTGAT G. N. J. , BLUM† A. L. , VERLINDEN M.
Published: July 2010

Aim: To perform a further Cox proportional hazards logistic regression analysis of data from two large‐scale placebo‐controlled trials with cisapride as maintenance treatment in reflux disease.

Results: Analysis of each of the two databases, allowing the model to operate freely, led to the identification of a number of unexpected putative predictors of outcome in the 6 to 12 months following initial healing of oesophagitis with an H2‐receptor antagonist or omeprazole. This allowed us to delineate more accurately the patient population that is likely to respond to long‐term continuous treatment with low or standard dose cisapride.

The analysis revealed that symptom severity may be more useful than endoscopic severity in predicting relapse or in guiding therapy. Reflux oesophagitis outcome is particularly poor in the presence of treatment‐recalcitrant symptoms or severe mucosal damage.

Analysis showed cisapride to be effective in the maintenance treatment of patients with non‐refractory symptoms, irrespective of the initial severity of oesophagitis, the healing agent used, or a history of previous endoscopic relapses.
Gastrin releasing peptide and its value in assessing gastric secretory function
Authors: McCOLL K. E. L. , EL‐OMAR E.
Published: July 2010

Gastrin releasing peptide (GRP) has proved to be a particularly valuable tool in detecting disturbances of gastric secretory function associated with duodenal ulcer disease and Helicobacter pylori infection, and it has furthered understanding of the pathophysiology of these conditions. Its attractiveness lies in the fact that it simultaneously activates many physiological control processes, both stimulatory and inhibitory. This facilitates the detection of a defect in any of the many controls involved in regulating biological function. Other gastrointestinal functions such as gall‐bladder contraction, pancreatic secretion and gastrooesophageal motility are also subject to complex regulatory controls, and GRP may also be of value in investigating disturbances of these processes.
The relative effectiveness of somatostatin and octreotide therapy in pancreatic disease
Authors: JENKINS S. A. , BEREIN A.
Published: July 2010

Somatostatin and octreotide inhibit basal and stimulated pancreatic secretion, stimulate reticuloendothelial system activity, modulate the cytokine cascade and are cytoprotective with respect to the pancreas. These effects of somatostatin and octreotide suggest that both drugs may be useful either in the treatment of pancreatic disorders, or in preventing acute pancreatitis following procedures on the pancreas.

In recent years it has become clear that somatostatin is a useful and effective therapy for severe acute pancreatitis and in preventing complications following endoscopic retrograde cholangiopancreatography (ERCP), whereas octreotide has no beneficial effect and may be deleterious in both these indications. The differences in the therapeutic efficacy of somatostatin and octreotide in acute pancreatitis and ERCP appears to be related to their differential effects on sphincter of Oddi motility—the native hormone relaxing, and the analogue increasing, its contractility. Consequently, any beneficial effects of octreotide in both acute pancreatitis and ERCP are offset by the increased contractility of the sphincter of Oddi, which results in retention of activated enzymes within the pancreas and further autodigestion of the gland.

Somatostatin and octreotide are equally effective in promoting the closure of pancreatic fistulae. However, the time to closure after commencement of therapy is much more variable and longer in patients treated with subcutaneous octreotide than those receiving intravenous somatostatin, possibly as a result of fluctuations in pancreatic enzyme secretion between consecutive administrations of the hormone.

Furthermore, the initial potent inhibitory effect of octreotide on pancreatic secretion is lost after 7 days of continuous subcutaneous administration. Therefore, in terms of cost‐effectiveness, somatostatin would appear to be the treatment of choice for pancreatic fistulae.

Octreotide markedly reduces the complication rates after elective pancreatic surgery. It remains to be established whether somatostatin is as effective as octreotide in this indication.
Helicobacter pylorieradication in a clinical setting: success rates and the effect on the quality of life in peptic ulcer
Authors: REILLY T. G. , AYRES R. C. S. , POXON V. , WALT R. P.
Published: July 2010

Background: Helicobacter pylorieradication for peptic ulcer has been widely taken up. Evidence for the efficacy of different regimens is often derived from small series in clinical trials but there is little reporting of everyday practice with unselected patients. Freedom from ulcer relapse has been demonstrated, but not whether this equates with clinical success.

Methods: We report on a series of 706 patients withH. pyloriinfection who, between January 1991 and April 1995, received eradication therapy followed by assessment of H. pylori status. Two‐hundred and seven of these patients were followed‐up by postal questionnaire, validated by parallel questionnaires to their general practitioners, covering clinical outcome measures.

Results: The overall eradication rate was 81.7%, and a 1‐week course of omeprazole plus two antibiotics was significantly better than a 2‐week course of standard triple therapy (85.0% vs. 78.0%,P< 0.05). Amongst 21 first‐time failures, a 7‐day course of a clarithromycin‐containing triple therapy succeeded in 18. The questionnaire replies indicate that, following successfulH. pylorieradication, ulcer patients are less likely to consult with ulcer symptoms (P< 0.0005), take medication (P< 0.0005), require further prescription (P< 0.0005), or lose work‐time because of their ulcer (P< 0.005). They are more likely to have a subjective sense of ulcer cure (P< 0.0005).

Conclusions: In addition to clear cost savings, social benefits are now demonstrated whenH. pyloriis eradicated. A well‐tolerated 1 week regimen is genuinely effective in everyday practice.
Addition of metronidazole to omeprazole/amoxycillin dual therapy increases the rate of Helicobacter pylori eradication: a double‐blind, randomized trial
Authors: BELL G. D. , BATE C. M. , AXON A. T. R. , TILDESLEY G. , KERR G. D. , GREEN J. R. B. , EMMAS C. E. , TAYLOR M. D.
Published: July 2010

Aims: To compare the efficacy, safety and tolerability of an omeprazole/amoxycillin (OA) dual therapy Helicobacter pylori eradication regimen with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen.

Methods: In this double‐blind trial, conducted in 19 hospitals, 119 patients with symptomatic duodenal ulcer disease were randomized to receive either 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 59) or 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s., followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 60). H. pylori status was assessed by 13C‐urea breath test at entry and at 4 weeks post‐treatment.

Results: H. pylori infection was eradicated in 46% of the OA treated patients and in 92% of the OAM treated patients, a mean difference of 46% (P < 0.0001, 95% CI for the difference: + 30 to + 62). In only one patient was the duodenal ulcer not endoscopically healed after 4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant differences in speed of symptom relief or improvement in symptoms between the two groups. Both regimens were well tolerated, with 96% of patients completing the course, and only one patient withdrawing due to an adverse event. The only side‐effect with a significantly higher incidence in the OAM group was diarrhoea, which occurred in 36% of patients compared to 16% of patients in the OA group (P < 0.05).

Conclusions: A regimen consisting of omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably higher H. pylori eradication rate than omeprazole and amoxycillin alone, with acceptable tolerability.
Prospective study of fluconazole suspension for the treatment of oesophageal candidiasis in patients with AIDS
Authors: LAINE L. , RABENECK L.
Published: July 2010

Background: Oesophageal candidiasis is the most common cause of oesophageal symptoms in patients with AIDS. Antifungal therapy, given as a suspension, may be better tolerated than capsules or tablets in children or patients with oesophageal symptoms. We performed a prospective study of the safety and efficacy of fluconazole suspension.

Methods: Patients with HIV infection; odynophagia, dysphagia, or retrosternal pain; endoscopic evidence of white plaques or exudate in the oesophagus; and microscopic confirmation of fungal infection on biopsy or brushing specimens were eligible. Patients received fluconazole oral suspension (200 mg loading dose followed by 100 mg q.d.s.). Therapy was continued for 2 weeks after symptom resolution. Repeat endoscopy was performed after completion of therapy.

Results: Forty‐two patients enrolled in the study: 40 were male, mean (± s.e.) age was 37 ± 2 years and mean CD4 cell count was 67 ± 14/mm3. One patient was not evaluable because he received amphotericin during the first week of therapy. Symptoms resolved in all 41 evaluable patients; 17 (41%) had resolution by 1 week, 37 (90%) by 2 weeks, and 40 (98%) by 3 weeks. Endoscopic resolution occurred in 35 (95%) of 37 patients who underwent repeat endoscopy. Adverse events (skin rash in 1, nausea/vomiting in 2, elevated liver tests in 2) Ied to early termination of therapy in 5 patients, all of whom had clinical and endoscopic cure.

Conclusions: Symptoms resolved in 100% of patients with AIDS and oesophageal candidiasis receiving an oral suspension of fluconazole, and 90% of patients had symptom resolution within 2 weeks. Determining whether the more rapid clinical cure in this study, compared with a previous trial which employed capsules, is related to an additional topical antifungal effect of the suspension, will require further study.
The effects of lintopride, a 5HT‐4 antagonist, on oesophageal motility
Authors: DELVAUX M. , MAISIN J.‐M. , ARANY Y. , ATLAN P. , PRIETO‐CABANIS M.‐J. , CANAL M. , FREXINOS J.
Published: July 2010

Aim: To evaluate the effects of various doses of lintopride, a new 5HT‐4 antagonist with moderate 5HT‐3 antagonist properties, on oesophageal body and lower oesophageal sphincter (LOS) motility in humans.

Methods: Eight healthy male volunteers, mean age 22 (19–28) years, without any history of digestive disease or chest pain, were randomized to three doses of lintopride (0.1, 0.3 and 0.5 mg/kg i.v.) and a placebo at 1‐week intervals in a double‐blind, crossover study. Oesophageal motility was recorded continuously for 4 h after each dose, using perfused catheters inserted at the level of the LOS and in the body of the oesophagus, at 5, 10 and 15 cm from the LOS. Peristalsis was studied during 10 wet swallows, at 30‐min intervals (T0–T240min).

Results: The LOS basal pressure (23.3 ± 2.0 cmH2O; mean ± s.d.) remained stable after dosing with placebo toT240After lintopride, LOS basal pressure increased significantly vs. placebo (AUCcomparison: 0.1 mg/kg,P= 0.036; 0.3 mg/kg,P= 0.027; 0.5 mg/kg,P= 0.052). In contrast, the duration and extent of LOS relaxation after swallowing was not affected by any of the three doses of lintopride. The amplitude of peristaltic waves in the oesophagus increased significantly atT30after lintopride 0.3 mg/kg (34.5 cmH2O,P= 0.020) and 0.5 mg/kg (32.5 cmH2O,P=‐0.027), atT60after 0.3 mg/kg (48.8 cmH2O,P= 0.0009) and 0.5 mg kg (29.1 cmH2O,P= 0.029) and atT60after 0.3 mg/kg (34.5 cmH2O,P= 0.0018).

Conclusions: Lintopride significantly increased the LOS basal tone without affecting LOS physiological relaxation after swallowing. Peristaltic waves were also enhanced by lintopride.
Review article The treatment of lactose intolerance
Authors: SUAREZ F. L. , SAVAIANO D. A. , LEVITT M. D.
Published: July 2010

While about 50 million Americans malabsorb lactose, the colonic metabolism of this disaccharide may prevent the symptomatic state known as lactose intolerance. Elucidation of the clinical importance of lactose malabsorption requires comparison of symptoms after ingestion of lactose with those following an identical appearing lactose‐free control. This paper reviews the extensive literature concerning lactose‐induced symptoms and the value of lactose digestive aids. Poorly controlled studies have suggested that a cup of milk results in appreciable symptoms in the majority of lactase‐deficient subjects. In contrast, controlled trials in unselected lactose malabsorbers of subjects claiming severe lactose intolerance indicate that symptoms from a cup of milk are no greater than that with a lactose‐hydrolyzed control. An increasing fraction of subjects experience symptoms as the lactose load is increased, with the majority having symptoms when the equivalent of 1 L of milk is ingested as a single dose. Further studies are required to determine the tolerance to several cups of milk taken throughout the day. Available digestive aids include pre‐hydrolyzed milk and lactase preparations that can be added to milk (which is then incubated) or ingested with milk. While these products are effective in reducing symptoms, it should be emphasized that there appears to be no need for these preparations when the dosage of milk is limited to one cup per day.
Review article The use of botulinum toxin in the alimentary tract
Authors: ALBANESE A. , BENTIVOGLIO A. R. , CASSETTA E. , VIGGIANO A. , MARIA G. , GUI D.
Published: July 2010

New and future indications for the treatment of disorders of the alimentary tract using local injections of botulinum toxin are reviewed. Clinical experience shows that overactive smooth muscle sphincters may be weakened to treat disorders such as achalasia or chronic anal fissure. By contrast, injections placed into the sphincter of Oddi have proven less effective for post‐cholecystectomy pain syndrome. Experimental evidence suggests that food intake may be reduced by weakening the distal stomach with botulinum toxin. This approach may possibly lead to the treatment of obesity. There are some new possible indications for the use of botulinum toxin on the alimentary tract, and infantile hypertrophic pyloric stenosis seems to be the most promising new development.
The efect of indornethacin‐induced gastric rnucosal injury on 24‐h intragastric acidity and plasma gastrin concentration in healthy volunteers
Authors: RADEMAKER J. W. , RAINSFORD K. D. , STETSKO P. I. , JOHNSON D. M. , CHIBA N. , MCDONALD T. M. , HUNT R. H.
Published: July 2010

Aims: To determine the influences of prostaglandin inhibition by indomethacin on 24‐h intragastric acidity and plasma gastrin concentration, related to gastric mucosal injury.

Methods:A pre‐ and post‐treatment study design was employed in 10Helicobacter pylorinegative healthy male subjects. All subjects underwent upper gastrointestinal endoscopy at least 3 days before and after 7 days dosing with indomethacin 50 mg t.d.s. Mucosal damage was scored according to the Lanza method, and biopsies were taken forH. pyloristatus and assay of mucosal concentrations of prostaglandin (PG)E2and leukotriene (LT)B4. Before and on the last day of dosing, intragastric acidity was measured by continuous 24‐h pH monitoring, and plasma gastrin levels determined by radioimmunoassay in blood samples collected over the same period.

Results:All subjects completed the study and no serious adverse events were reported. The mucosal injury score increased significantly from 0 (0–2) to 3.4 (0–8) (mean and range of values, P < 0.05) after dosing with indomethacin. No differences were observed in 24‐h mean pH or meal stimulated plasma gastrin concentrations. Mucosal PGE2and LTB4were unchanged 8–10 h after the last indomethacin dose.

Conclusions: Endogenous prostaglandins do not appear to alter intragastric acidity or gastrin secretion, in contrast to the PGE analogues, whose effects must be more pharmacological than physiological.
Effects of psyllium therapy on stool characteristics, colon transit and anorectal function in chronic idiopathic constipation
Authors: ASHRAF W. , PARK F. , LOF J. , QUIGLEY E. M. M.
Published: July 2010

Background: Psyllium is widely used in the symptomatic therapy of constipation. Its effects on colonic function and their correlation with symptomatic response have not been defined.

Methods: After a 4‐week baseline, placebo, run‐in phase, 22 subjects with idiopathic constipation confirmed by prospectively administered stool diaries were randomly assigned to receive either psyllium (5 g b.d., 11 patients) or placebo (11 patients) for 8 weeks, followed by another 4‐week wash‐out, placebo phase. A colon transit study and anorectal manometry were performed at the beginning and at the end of each study phase. Subjects recorded, in diaries, their daily stool frequency, difficulty with defecation and weekly stool weight.

Results: Stool frequency increased significantly after 8 weeks of psyllium treatment (3.8 ± 0.4 vs. 2.9 ± 0.1 stools/week,P< 0.05) as did stool weight (665.3 ± 95.8 g vs. 405.2 ± 75.9 g,P< 0.05). Subjects also reported an improvement in stool consistency (stool consistency score: 3.2 ± 0.2 vs. 3.8 ± 0.2,P< 0.05) and pain on defecation (pain score: 2.0 ± 0.4 vs. 2.6. ± 0.5,P< 0.05) on psyllium. Colon transit and anorectal manometry parameters were unchanged on psyllium. Subjects treated with placebo did not show any change in either subjective or objective measures of constipation.

Conclusions: Psyllium increases stool frequency and weight and improves stool consistency in idiopathic constipation. These effects are not associated with significant changes in either colonic or rectal motor function. We suggest that the beneficial effects of psyllium in constipation are primarily related to a facilitation of the defecatory process.
Pantoprazole and omeprazole in the treatment of reflux oesophagitis: a European multicentre study
Authors: CORINALDESI R. , VALENTINI M. , BELAÏCHE J. , COLIN R. , GELDOF H. , MAIER C. ,   THE EUROPEAN PANTOPRAZOLE STUDY GROUP
Published: July 2010

Background: Pantoprazole is a new substituted benzimidazole which inhibits gastric H+,K+‐ATPase.

Methods: In this double‐blind, multicentre study, pantoprazole 40 mg once daily was compared with omeprazole 20 mg once daily in the treatment of grade II and III (Savary–Miller) reflux oesophagitis. Endoscopy was repeated after 4 weeks of treatment, and also after 8 weeks in patients unhealed at 4 weeks.

Results: The primary efficacy variable was ulcer healing; after 4 weeks, 81/103 (78.6%) patients in the pantoprazole group and 83/105 (79.0%) patients in the omeprazole group had healed completely. After 8 weeks, the cumulative healing rates were 94.2% and 91.4 % in the pantoprazole and omeprazole groups, respectively (P> 0.05 at 4 weeks and 8 weeks). Both groups experienced rapid relief of the key symptoms: heartburn, acid regurgitation and pain on swallowing. The time course of relief of the individual symptoms was similar in both groups after 2 and 4 weeks (P> 0.05). Both treatments were well tolerated, with only three patients withdrawing owing to adverse events.

Conclusion: Pantoprazole has been shown to be as effective as omeprazole in the treatment of reflux oesophagitis.
The relationship between the control of pH and healing and symptom relief in gastro‐oesophageal reflux disease
Authors: HUNT R. H.
Published: July 2010

Gastro‐oesophageal reflux disease (GERD) is generally considered to be the result of a motility disorder which permits the abnormal and prolonged exposure of the lumen of the oesophagus to the acidic gastric contents.

This view is supported by experimental data, intraoesophageal pH measurement, and the dramatic results of symptom relief and healing seen with effective antisecretory treatment.

Oesophageal mucosal injury is determined by the pH of the refluxate and duration of acid exposure. Most patients experience meal‐stimulated reflux during the day and the more severe cases experience 24‐h acid exposure. In contrast to the H2‐receptor antagonists (H2RAs), the proton pump inhibitors (PPIs) are more effective at controlling meal‐stimulated acid secretion when each is given in standard doses. Therefore, the degree and duration of acid suppression throughout 24 h is greater.

Treatments which maintain intra‐oesophageal pH > 4 for 96% or more of the 24 h normalize acid exposure and are associated with the highest healing rates. Peptic activity is minimized at or above pH 4. The time above pH 4 is significantly longer with the PPIs than with the H2RAs. Thus, the healing‐time curves for GERD (grades II‐IV) are shifted to the left for the PPIs which heal a significantly greater proportion of patients earlier than the H2RAs or sucralfate.

Symptoms in GERD are related to the degree and duration of oesophageal acid exposure. Symptom relief is more rapid and complete with the PPIs than with the H2RAs or other treatments in standard doses.
The role and limitations of H2‐receptor antagonist in the treatment of gastro‐oesophageal refrux disease
Authors: COLIN‐JONES D. G.
Published: July 2010

Gastro‐oesophageal reflux disease (GERD) occurs in up to 44% of adults in the USA. Most individuals do not seek medical help, self‐medicating with antacids. Manifestations of GERD range from symptoms without oesophagitis, which constitute the bulk of patients who self‐medicate, to active oesophagitis and then to complications such as stricture and ulceration. It is the more severe cases who tend to come to the gastroenterologist, but it must be remembered that reflux symptoms are probably around 5–10 times more common than actual oesophagitis. Since acid in the refluxate is responsible for the bulk of the symptoms and mucosal damage, antacids are often used for quick relief—which of course may not be sustained. More prolonged suppression of acid secretion, such as by a histamine H2‐receptor antagonist (H2RA) or a proton pump inhibitor (PPI), is required to give long‐lasting symptomatic relief and heal any inflammatory change.

H2‐receptor antagonists inhibit acid secretion with an effect that lasts for 4–8 h with a single dose, decreasing stimulated acid secretion by around 70%. When treating oesophagitis, the H2RAs suffer from the disadvantage of their relatively short duration of action (compared with PPIs), development of tolerance, and incomplete inhibition of acid secretion in response to a meal. Therefore, it is not easy for the H2RAs to achieve optimum conditions for healing the more severe forms of oesophagitis—even very high doses may fail.

In mild GERD the H2RAs have been shown to be effective in relieving symptoms. In particular, when there is no oesophagitis, relief of reflux symptoms has been obtained after 4 weeks in almost all cases with a twice daily regimen: and it would seem that the sensitivity of the oesophageal mucosa may be reduced so that symptomatic remission is often obtained for a prolonged period after stopping therapy. In the milder forms of oesophagitis (grades I or II) healing can be achieved with all the H2RAs in 40–60% of cases in 8 weeks. This can be increased, by a substantial increase in dosage, to around 50–70%, but seldom higher than that. This higher dose has cost and compliance considerations. Proton pump inhibitors are required for higher percentage healing and especially for more severe disease.
The role of proton pump inhibitors in the treatment of gastro‐oesophageal reflux disease
Authors: BARDHAN K. D.
Published: July 2010

Efficacy (healing, symptom relief) and cost‐effectiveness are the principal reasons for the rapidly increasing use of proton pump inhibitors (PPIs) for the management of gastro‐oesophageal reflux disease.

Efficacy: Mean healing rates pooled from clinical trials are as follows: on omeprazole (OME) 20 mg vs. H2‐receptor antagonist, H2RA (cimetidine (CIM) 1.6 g or ranitidine (RAN) 300 mg) (eight studies) at 4 weeks, 67% vs. 37%; at 8 weeks, 81% vs. 49%; on lansoprazole (LAN) 30 mg vs. H2RA (three studies), 83% vs. 47% and 91% vs. 63% at 4 and 8 weeks, respectively. The benefit is greatest in severe disease because the H2RAs are disproportionately less effective. Heartburn is more rapidly relieved and in a higher proportion: at 4 weeks, on OME 20 mg vs. H2RA, 77% vs. 47% and on LAN 30 mg vs. H2RA, 81% vs. 46%. Both PPIs are effective in H2RA‐refractory disease, approximately 80% healing occurring in 8 weeks.

Relapse rates after healing vary from 2 5 % to 8 5 % at 6 months. Maintenance therapy sustains remissions: relapse at 1 year is, on OME 20 mg vs. RAN 300 mg (2 studies), 12% vs. 79% and 28% vs. 55% (and 38% on OME 10 mg); on LAN 30 mg vs. 10 mg vs. RAN 600 mg, 20% vs. 31% vs. 68%. The effectiveness of the lower dose allows for dose titration.

Cost effectiveness: The higher drug costs for the PPIs are offset by their higher efficacy, making their use cost effective, particularly in severe disease.

Efficacy and cost effectiveness are likely to further expand the use of PPIs at the expense of H2RAs as increasing numbers of patients with milder disease are treated.
The role of Helicobacter pylori in gastritis and its progression to peptic ulcer disease
Authors: BLASER M. J.
Published: July 2010

Helicobacter pylori infection is now recognized as the major cause of chronic gastritis throughout the world. A fraction of infected persons develop peptic ulcer disease or gastric cancer, accounting for its clinical significance. The pathophysiology of this infection can be better understood by considering five central concepts—heterogeneity of strains, persistence of infection, immunological down‐regulation, physiological consequences and variability in outcome. Microbial, host and environmental factors must each contribute to the outcome variation.
Ropivacaine gel in active distal ulcerative colitis and proctitis—a pharmacokinetic and exploratory clinical study
Authors: ARLANDER E. , ÓST Å. , STÅHLBERGS D. , LÓFBERG R.
Published: July 2010

Background: Local anaesthetics have anti‐inflammatory effects as indicated by preclinical and explorative clinical data.

Objective: To investigate the pharmacokinetics, tolerability and clinical efficacy of the new local anaesthetic ropivacaine in active distal ulcerative colitis.

Methods: Twelve patients were openly given 200 mg ropivacaine gel rectally twice daily for 2 weeks in this open study.

Results: Mean peak total plasma concentrations,Cmaxwere 1.37, 1.26, 1.03 and 0.99 mg/L on treatment days 1, 3, 7 and 14. The mean unbound plasma concentrations atCmaxwere 0.071, 0.058, 0.050 and 0.045 mg/L. The decrease inCmax(P< 0.01) as well as in the area under the plasma concentration‐time curve, AUC (P< 0.01), may be due to a decreased absorption but an increased metabolism cannot be excluded. The median time ofCmaxwas around 2 h and the mean terminal half‐life was around 2.7 h. Mucosal inflammation assessed endoscopically at the most severely affected site decreased after 2 weeks of treatment (P< 0.01: blinded) and there was also a trend towards histological improvement (P= 0.06). Clinical symptoms, including total number of stools, blood in stools and diarrhoea increased (P< 0.05) during the study. The treatment was, in general, well tolerated with few gastrointestinal complaints and there were no unequivocal signs of systemic effects.

Conclusions: Ropivacaine given rectally as a gel, 200 mg twice daily does not accumulate over a 2‐week treatment period and carries a low risk for systemic adverse effects. The results suggest a therapeutic efficacy in active distal ulcerative colitis.
The effect of omeprazole on gastric juice viscosity, pH and bacterial counts
Authors: GODDARD A. F. , SPILLER R. C.
Published: July 2010

Background: In vitro studies have shown that pH is an important determinant of mucus structure and function, but the relationshi P in vivo is unclear. Omeprazole increases intragastric pH and also allows bacterial overgrowth. In this study we have assessed the effect of omeprazole on gastric juice viscosity and examined the influence of pH and bacterial overgrowth on the resulting change.

Methods: Gastric juice specific viscosity, pH and total bacterial counts were measured in nine healthy male volunteers before and after omeprazole 20 mg twice daily for 1 week. The effect of incubation at pH 2 and 7 was also determined. Viscosity changes were compared with changes in pH and bacterial counts.

Results: Mean viscosity fell (P < 0.05) following treatment, though there was a wide range in viscosity both before and after treatment. The decrease was reproduced by incubation of pre‐treatment juice at pH 7 but not pH 2. The fall in viscosity was correlated (P < 0.05) with change in pH.

Conclusion: Omeprazole decreases gastric juice, and hence gastric mucus, viscosity by increasing intragastric pH. This could be important if it allows improved penetration of antimicrobials to Helicobacter pylori within the mucus layer.
The effects of omeprazole and famotidine on mucin and PGE2 release in the rat stomach
Authors: YOSHIMURA K. , DELBARRE S. G. , KRAUS E. , BOLAND C. R.
Published: July 2010

Background: Gastric antisecretory agents may inhibit the synthesis or secretion of gastric mucin during acid suppression, which would interfere with mucosal protection and limit the efficacy of the agents.

Methods: Rats were dosed with famotidine, omeprazole, or buffer control for 4 weeks. Mucin synthesis, mucin histochemistry, mucin carbohydrate composition and prostaglandin E2 (PGE2) release were measured during and after drug treatment.

Results: PGE2 release was maximally inhibited after 2 weeks of omeprazole or 4 weeks of famotidine. Total glycoprotein synthesis was inhibited at all times by omeprazole, but only after the cessation of dosing with famotidine. Sulphated glycoprotein synthesis was inhibited by both drugs at 2 weeks. PGE2 release and sulphated glycoprotein synthesis were restored to control values or more by the 5th day after the end of dosing, at which time total glycoprotein synthesis was significantly suppressed in both groups. Histologically, a reduction of PAS‐positive surface mucus was observed after 2 weeks of dosing in both groups. Both famotidine and omeprazole reduced the sialic acid content during and after treatment.

Conclusions: These results suggest that long‐term anti‐secretory therapy also affects the production of factors involved in primary gastric mucosal defence, which should be considered in the assessment of response to treatment in clinical trials.
Helicobacter pylori infection induces accumulation of Vδ1 T cells via CCR2 upregulation
Authors: FUTAGAMI S. , HIRATSUKA T. , SHINDO T. , HAMAMOTO T. , UEKI N. , SUZUKI K. , KUSUNOKI M. , WADA K. , MIYAKE K. , OHASHI K. , GUDIS K. , TSUKUI T. , SAKAMOTO C.
Published: July 2010

Background

We investigated factors that impact γδ T‐cell phenotype accumulation in Helicobacter pylori‐infected gastric mucosa and peripheral blood.

Aim

To determine whether H. pylori infection induces accumulation of Vδ1 T cells via CC chemokine receptor 2 (CCR2) upregulation.

Methods

Mucosal biopsy samples from 22 H. pylori‐free and 75 H. pylori‐infected patients were classified into grades I–III gastritis groups as per our previous study. The number of γδ, Vδ1 and Vδ2 T cells was evaluated by immunostaining and then compared with counts in 17 patients after H. pylori eradication. TGF‐β, IFN‐γ and CCR2 mRNA expression levels in Vδ1 T cells stimulated by H. pylori component were also evaluated.

Results

γδ T‐cell count was significantly higher in grade III gastritis patients, who exhibited strong IgA and IgG responses to H. pylori urease, than in other groups. Vδ1 T cells were found dominantly residing in H. pylori‐infected gastric mucosa, whereas Vδ2 T cells were mainly found in peripheral blood. Vδ1 T‐cell count was significantly reduced after H. pylori eradication therapy. In in vitro studies, H. pylori component stimulation significantly upregulated both TGF‐β and IFN‐γ production in supernatant from stimulated Vδ1 T cells. Moreover, CCR2 mRNA expression in Vδ1 T cells stimulated with H. pylori components was significantly increased.

Conclusion

Accumulation of Vδ1 T cells may occur through the upregulation of CCR2 expression.