Treatment of ulcerative colitis with germinated barley foodstuff feeding: a pilot study

Background

Germinated barley foodstuff (GBF) has been shown to attenuate intestinal injury in animal models, largely by increasing luminal short-chain fatty acid production.

Aim

To investigate the safety and efficacy of GBF in the treatment of ulcerative colitis (UC).

Methods

Ten patients with active UC received 30 g of GBF daily for 4 weeks in an open-label treatment protocol while the baseline anti-inflammatory therapy was continued. The response to treatment was evaluated clinically and endoscopically. Pre- and post-treatment stool concentrations of short-chain fatty acids were measured by gas-liquid chromatography.

Results

Patients showed improvement in their clinical activity index scores, with a significant decrease in the score from 6.9 ± 1.4 to 2.8 ± 1.5 (mean ± S.E.M., P < 0.05). The endoscopic index score fell from 6.1 ± 2.3 to 3.8 ± 2.3 (P < 0.0001). Patients showed an increase in stool butyrate concentrations after GBF treatment (P < 0.05). No side-effects were observed.

Conclusions

Oral GBF therapy may have a place in management of ulcerative colitis, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

     

Bone turnover during short-term therapy with methylprednisolone or budesonide in Crohn's disease

Background:

Glucocorticosteroids are used frequently for the treatment of relapses of Crohn’s disease.

Aim:

To investigate the influence of the new topically active glucocorticosteroid budesonide in comparison with methylprednisolone on bone turnover in a randomized open trial.

Methods:

Twenty-nine patients received either budesonide (controlled ileal release formulation) 9 mg for 10 weeks, or methylprednisolone 32 mg (equivalent to 40 mg prednisone) orally for 3 weeks with subsequent tapering.

Results:

Patients who completed the trial with methylprednisolone (n = 8) had suppression of serum osteocalcin (30.2 ± 2.6 to 20.4 ± 2.0 ng/mL, P < 0.01), whereas no changes in this parameter of bone synthesis were observed during budesonide treatment (n = 11) (34.8 ± 3.1 to 33.0 ± 3.5 ng/mL). Urinary pyridinolines and deoxypyridinolines, highly sensitive markers of bone degradation, did not change in either group.

Conclusion:

Short-term methylprednisolone therapy impairs osteoblast activity in patients with Crohn’s disease whereas budesonide does not.

     

Efficacy and safety of bisacodyl in the acute treatment of constipation: a double-blind, randomized, placebo-controlled study

Summary

Background

Although laxatives are a first‐line treatment for constipation, there are few randomized placebo‐controlled trials assessing their efficacy.

Aim

To determine the effect and safety of oral bisacodyl on stool frequency and consistency in patients with idiopathic constipation.

Methods

55 patients (age 19–89 years) with idiopathic constipation were recruited from eight primary care practices and randomized to receive bisacodyl, 10 mg once daily, or placebo, on three successive days following a 3‐day run‐in period. Patients recorded stool frequency and consistency and adverse events.

Results

In each treatment group, 27 patients were evaluable for efficacy. The mean number of stools per day was significantly greater in the bisacodyl‐treated group (1.8/day) compared with placebo (0.95/day) over the treatment phase (P = 0.0061). Mean stool consistency score improved from ‘hard’ (run‐in) to between ‘soft’ and ‘well‐formed’ during bisacodyl treatment, remaining between ‘moderately hard’ and ‘hard’ for placebo treatment (P < 0.0001). The investigator's global efficacy score was superior for the bisacodyl group compared with placebo. Both treatments were well tolerated. Serum electrolyte levels and incidence of adverse events were comparable between treatment groups.

Conclusions

Bisacodyl is effective and safe in improving stool frequency and consistency in acute treatment of idiopathic constipation.

     

Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C

Summary

Background

The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC).

Aim

To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC.

Methods

Ninety‐eight consecutive treatment‐naïve CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM‐IV, at baseline and both during and after treatment.

Results

Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti‐viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one).

Conclusion

Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy.

     

Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial

Summary

Background

Enteric viruses including noroviruses and rotavirus are leading causes of diarrhoeal disease and gastroenteritis worldwide, and there is no effective treatment.

Aim

To evaluate nitazoxanide, a thiazolide anti‐infective agent, in treating viral gastroenteritis in adults and adolescents.

Methods

50 out‐patients at least 12 years of age (mean 33.5 years) presenting with diarrhoea and stool‐positive by enzyme‐linked immunosorbent assay for norovirus, rotavirus or adenovirus were enrolled in a double‐blind, placebo‐controlled clinical trial. Patients were randomly assigned either nitazoxanide 500 mg or placebo twice daily for 3 days. The primary end point was time from first dose to resolution of symptoms. Analysis was modified intent‐to‐treat for 45 patients, excluding five patients with other identified enteropathogens at baseline.

Results

The median time from first dose to resolution of symptoms was 1.5 days (IQR: 0.5–2.5) for nitazoxanide‐treated patients and 2.5 days (IQR: 1.5–4.5) for the placebo group. Significant reductions in time to resolution of symptoms were observed for all patients analysed (P < 0.0001) and for subsets of patients with rotavirus (P = 0.0052) and norovirus (P = 0.0295). The number of patients with adenovirus (n = 5) was too small to draw any conclusion. No significant adverse events were reported.

Conclusions

Nitazoxanide may play an important role in managing viral gastroenteritis in adults.

     

Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety

Summary

Background

Lubiprostone, a locally acting type‐2 chloride channel activator, induces intestinal fluid secretion.

Aim

To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation.

Methods

A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked.

Results

Over the double‐blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1–6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P ≤ 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P ≤ 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P ≤ 0.009). The most common AEs were nausea, headache and diarrhoea.

Conclusions

Lubiprostone improved SBM rates in a dose‐dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk‐to‐benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.

     

Dialysis of the rectum for sampling drug concentrations in the luminal extracellular fluid of the gut: technique and precision

Background:

It is useful to measure the luminal concentration of drugs which act in the gut. Dialysis of the rectum has not previously been used or validated for this purpose.

Aim:

To determine the precision of rectal dialysis for measuring rectal drug concentrations.

Methods:

To establish the duration of dialysis required to approach equilibrium, the rate of methotrexate diffusion into dialysis bags was first determined in vitro. The precision of rectal dialysis for sampling the methotrexate concentration of colonic lumen extracellular fluid was determined in seven subjects who underwent two consecutive dialysis procedures. Subjects treated with subcutaneous methotrexate for refractory inflammatory bowel disease were studied.

Results:

Methotrexate crossed the dialysis membrane by a first-order process, and after a 2 h in vitro dialysis, equilibration was 74 ± 2% (mean ± s.d.) complete. Rectal dialysis was well tolerated by all subjects. The mean ± s.e. methotrexate concentration of 3.6 ± 1.1 nmol/L in the first dialysate was not significantly different from 3.6 ± 0.9 nmol/L in the second dialysate, P = 0.99 (paired two-tailed t-test). Similar precision was obtained for an endogenous molecule, potassium, secreted by the rectal mucosa.

Conclusions:

Dialysis of the rectum is a well tolerated and precise technique for sampling the colonic lumen extracellular fluid for quantitative analyses of exogenous and endogenous substances.

     

Effect of hiatal hernia on proximal oesophageal acid clearance in gastro-oesophageal reflux disease patients

Summary

Background

Proximal acid reflux is common in gastro‐oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton‐pump inhibitors.

Aim

To evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux.

Methods

Thirty seven consecutive gastro‐oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24‐h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis.

Results

At videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non‐hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: Δ + 2.5 min (95% confidence interval: 0.4–4.5); P < 0.02].

Conclusions

The presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro‐oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease.

     

Delta-9-tetrahydrocannabinol delays the gastric emptying of solid food in humans: a double-blind, randomized study

Background:

Delta-9-tetrahydrocannabinol (THC), the active constituent of marijuana, is an effective agent in the prevention of chemotherapy-induced nausea and vomiting.

Aim:

To determine the effect of THC on gastric emptying of a radiolabelled solid food in humans.

Methods:

Thirteen healthy volunteers underwent gastric emptying studies after receiving THC and placebo in a randomized double-blind fashion on 2 separate days. THC, at a dose of 10 mg/m² of body surface area, or placebo were administered.

Results:

Gastric emptying after THC was slower than placebo in all subjects. Mean percentage of isotope remaining in the stomach was significantly greater than after placebo from 30 min (85.5 ± 4.3% vs. 94.2 ± 1.4% placebo and THC, respectively, P < 0.05) to 120 min (45.6 ± 7.2% vs. 73.9 ± 7.1% placebo and THC, respectively, P < 0.001) after the test meal. No correlation was found between plasma THC levels and the delay in gastric emptying.

Conclusions:

THC at a dose used for preventing chemotherapy-induced nausea and vomiting significantly delays gastric emptying of solid food in humans. Therefore, the anti-emetic property of THC may be mediated through the central nervous system.

     

Effectiveness of interferon plus ribavirin combination in the treatment of naive patients with hepatitis C virus type 5. A French multicentre retrospective study

Summary

Aim

To assess the rate of sustained virological response in naïve hepatitis C virus‐type 5 patients treated by standard interferon or percutaneous endoscopic gastrostomy‐interferon (peg‐interferon) and ribavirin combination for 48 weeks.

Patients and methods

A total of 87 hepatitis C virus patients were included from 12 centres in France; 28 patients received interferon plus ribavirin and 59 were treated with peg‐interferon plus ribavirin.

Results

Baseline characteristics were: mean age 58 ± 11 years, sex ratio 1, 66% had metavir fibrosis score ≥F2, 21% were cirrhotics and 53% had pretherapeutic viral load ≥800 000 IU/mL. Sustained virological response was achieved in 64% and 58% of hepatitis C virus‐5 patients treated with interferon and peg‐interferon, respectively (NS). In adherent patients, sustained virological response was obtained in 75% of patients. Sustained virological response in hepatitis C virus‐5 patients (60%) was significantly higher than sustained virological response in hepatitis C virus‐1 patients (37%) (P = 0.0499) and not significantly different from sustained virological response in hepatitis C virus‐2–3 patients (63%) (P = 0.8098).

Conclusions

Combination therapy is effective in 60% of hepatitis C virus‐5‐infected patients. Sustained virological response seems better in hepatitis C virus‐5 patients than in hepatitis C virus‐1 patients, and is similar to that of hepatitis C virus‐2–3 patients. More studies are needed to determine optimal duration of treatment in hepatitis C virus‐5 patients.

     

Sustained virological response to peginterferon plus ribavirin in chronic hepatitis C genotype 1 patients is associated with a persistent Th1 immune response

Summary

Background

An impairment of cellular immune response may contribute to the persistency of hepatitis C virus infection.

Aim

To analyse the Th1/Th2 cytokine profile in peripheral blood CD4+ and CD8+ T cells from patients with chronic hepatitis C (CHC) during treatment with pegylated interferon‐α2a plus ribavirin and to correlate the Th1/Th2 balance with virological response (SVR).

Methods

Prospective longitudinal study: 44 naïve genotype 1 CHC patients received PEG‐IFNα2a plus ribavirin for 48 weeks: 26 (59.1%) achieved a SVR, 13 relapsed (29.5%) and 5 (11.4%) were non‐responders. Sixteen healthy controls were analysed. The production of IL‐4, IFNγ and TNFα by CD4+ and CD8+ T cells was measured using flow cytometry, both in resting and phorbol‐ester‐stimulated cells.

Results

First three months of treatment: the synthesis of TNFα by phorbol‐ester‐stimulated‐CD4+ T cells was higher in patients with SVR (P < 0.01). At the end of treatment, SVR was associated with higher intracellular expression of IFNγ by stimulated‐CD4+ and CD8+ T cells (P < 0.05). At the end of follow‐up, a higher intracellular expression of IFNγ by CD4+ T cells was associated with a SVR.

Conclusions

A Th1‐type immune response was associated with achievement of a SVR, as indicated by the persistent elevation of intracellular IFNγ and TNFα.

     

Evaluating the cost of sustained virologic response in naïve chronic hepatitis C patients treated à la carte

Summary

Background

There is a tendency to individualize treatment in chronic hepatitis C patients depending on viral load and rapid clearance of HCV‐RNA.

Aim

To evaluate the cost (€, 2006) per sustained virologic response in naïve patients with therapy à la carte compared with standard combination therapy.

Methods

A decision analysis model was used to compare standard therapy with peginterferon alpha and ribavirin for 24 weeks for genotype (G) 2/3, and 48 weeks for G1 and therapy à la carte with the same drugs but different durations: G1 high viral load for 48 weeks, G1 low viral load with rapid virologic response for 24 weeks, and without rapid virologic response for 48 weeks, and G2/3 with rapid virologic response for 12 weeks, and without rapid virologic response for 24 weeks.

Results

Sustained virologic response was similar in both strategies. The cost per successfully treated patient for standard therapy is €17 812 and for therapy à la carte€12 313. Assuming that 13 309 patients with standard therapy and 14 450 patients with therapy à la carte achieve sustained virologic response, therapy à la carte has an overall cost‐saving of €59.13 million.

Conclusion

Therapy à la carte is a cost‐saving strategy for chronic hepatitis C infection compared to standard therapy, with lower investment requirement per patient to achieve sustained virologic response.

     

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias

Summary

Background

Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes.

Aim

To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro‐oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms.

Methods

Thirty‐two patients (13 females and 19 males; age: 20–69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43–58 years) with GERD only, underwent simultaneous 24‐h pH‐metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full‐dosage PPI therapy (esomeprazole 40 mg/day) was prescribed.

Results

In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus–heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01).

Conclusions

This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms.

     

A randomized trial in primary biliary cirrhosis comparing ursodeoxycholic acid in daily doses of either 10 mg/kg or 20 mg/kg

Background:

Ursodeoxycholic acid (UDCA) prolongs transplantation-free survival in primary biliary cirrhosis (PBC). However, the optimal therapeutic dose has not been established.

Aim:

To compare the effects of UDCA administered in daily doses of 10 vs. 20 mg/kg on symptoms, liver biochemistry and biliary UDCA enrichment.

Methods:

A 6-month multicentre randomized open controlled trial was conducted to assess the effects of an increase in the dose of UDCA to 20 mg/kg/day vs. continuation of 10 mg/kg/day for patients who had not achieved biochemical normalization during treatment for at least 6 months with the 10 mg/kg dose. Clinical and laboratory evaluations were performed at entry and at 3-month intervals. The percentage UDCA in duodenal bile was assessed at entry and at 6 months.

Results:

Sixty-one patients were enrolled. No side-effects of UDCA were observed. Within the 20 mg/kg/day group significant decreases were found for alkaline phosphatase (? 8%; P = 0.003), aspartate aminotransferase (? 11%; P = 0.01), alanine aminotransferase (? 17%; P < 0.001), γ-glutamyl transferase?(? 34%; P < 0.001), immunoglobulin M (? 11%; P = 0.002) and cholesterol (? 8.1%; P < 0.001). In the 10 mg/kg group none of these parameters differed significantly from baseline. No significant differences between dose groups for symptom scores or serum bilirubin were found. Biliary enrichment with UDCA increased from 37% to 46% in the 20 mg/kg group (P = 0.02) while remaining stable in the 10 mg/kg group.

Conclusions:

Liver biochemistry improved in PBC patients receiving UDCA 20 mg/kg/day compared to a dose of 10 mg/kg/day. Both doses were equally well tolerated. These results indicate that UDCA 10 mg/kg/day is a suboptimal dose for treating PBC.

     

Comparison between theophylline and spironolactone in the management of cirrhotic ascites: a randomized controlled study

Background:

It has been suggested that adenosine is involved in the renal haemodynamic and tubular abnormalities observed in cirrhosis. Low-dose theophylline is an adenosine antagonist and recent studies have shown that this drug can improve renal blood flow and sodium excretion in cirrhotic patients.

Methods:

Fifteen patients with newly diagnosed cirrhotic ascites were randomized to receive either 100 mg spironolactone daily for 7 days or 250 mg theophylline on days 1, 2, 4 and 6. Baseline clinical and urinary and serum biochemical data were collected and compared following therapy.

Results:

After 7 days of spironolactone there were increases in urinary sodium excretion (43.5 ± 15.6 vs. 106.8 ± 34.7 mmol/day; P < 0.05) and urine volume (769.1 ± 206.5 vs. 1541.6 ± 342.6 mL/day; P < 0.05). No changes in the patients’ weight, creatinine clearance or serum electrolytes were observed. No change was detected in any of these parameters following theophylline therapy.

Conclusion:

Adenosine antagonism in the form of low-dose theophylline is less efficacious than spironolactone in the management of cirrhotic ascites.

     

The influence of cisapride on gastric tone and the perception of gastric distension

Background:

Delayed gastric emptying, impaired gastric accommodation to a meal and hypersensitivity to gastric distension have been implied in the pathophysiology of functional dyspepsia. Dyspeptic patients are often treated with the prokinetic drug cisapride.

Aim:

To assess the effects of cisapride on perception of gastric distension and gastric accommodation to a meal.

Methods:

Eighteen healthy volunteers underwent a gastric barostat study on two occasions, after pre-treatment with placebo or cisapride 10 mg q.d.s. Graded isobaric and isovolumetric distensions were performed until the subjects reported discomfort. Volume and pressure changes were recorded and perception was scored by a questionnaire. In 10 volunteers, the amplitude of the gastric accommodation to a mixed liquid meal was also measured.

Results:

Pre-treatment with cisapride significantly lowered thresholds for perception and for discomfort, both during isobaric (4.3 ± 0.7 vs. 3.2 ± 0.7 and 12.2 ± 1.2 vs. 9.2 ± 0.9 mmHg above minimal distending pressure (MDP), respectively, P < 0.05) and isovolumetric (256 ± 46 vs. 200 ± 35 and 644 ± 36 vs. 511 ± 40 mL, respectively, P < 0.05) distensions. Cisapride significantly enhanced the size of the meal-induced fundus relaxation (143 ± 37 vs. 270 ± 50 mL, P < 0.05).

Conclusions:

Cisapride enhances both the perception of gastric distension and the gastric accommodation to a meal. These data suggest that cisapride may provide benefit to patients with impaired postprandial relaxation of the fundus.

     

Patterns of gastritis and the effect of eradicating Helicobacter pylori on gastro-oesophageal reflux disease in Western patients with non-ulcer dyspepsia

Summary

Background

The effect of Helicobacter pylori eradication on the development of gastro‐oesophageal reflux disease is controversial.

Aim

To determine the incidence of symptoms of reflux disease and of erosive oesophagitis, and the relationship to changes in histological gastritis, in patients with non‐ulcer dyspepsia over 12 months.

Methods

Six hundred and ninety‐three patients in two similar randomized placebo controlled trials of H. pylori eradication in non‐ulcer dyspepsia were studied. Symptoms were assessed using the validated Gastrointestinal Symptom Rating Scale during a 1‐week run‐in period, at 6 months and 12 months. Endoscopy was performed at baseline to exclude patients with pathology and at 3 months and 12 months to determine if oesophagitis was present. Gastric biopsies were scored using the modified Sydney Classification.

Results

Patients without predominant heartburn, oesophagitis or ulcers at endoscopy were randomized to active (n = 297, omeprazole, amoxicillin and clarithromycin) treatment or to placebo/omeprazole (n = 306) for 1 week. The eradication rate was 82% in the active treatment group. Antrum‐predominant gastritis (55%) was more frequently found than corpus‐predominant gastritis (6%). In patients with antrum‐predominant gastritis, heartburn and regurgitation scores improved significantly 12 months after eradication. Erosive oesophagitis developed in 15/232 patients in the eradication group (7%) compared with 2/227 (2%) in the control group, but there was no significant difference when adjusted for oesophagitis present at baseline.

Conclusions

Antrum‐predominant gastritis is the most common pattern of gastritis seen in non‐ulcer dyspepsia in Western populations. Heartburn and regurgitation improve after eradication therapy or placebo in patients with non‐ulcer dyspepsia; the development of oesophagitis is uncommon.

     

Interdigestive antroduodenal motility and gastric acid secretion

Background:

In humans, interdigestive acid secretion and antroduodenal motility are closely related with cyclic variations in acid secretion, synchronous with the various phases of the migrating motor complex (MMC). Duodenal acidification inhibits antral motility, but little is known about the effect of acute acid inhibition on antroduodenal motility.

Aim:

To study the effect of acute acid inhibition on antroduodenal motility.

Subjects:

Ten healthy volunteers (four men and six women; age range 20–31 years).

Methods:

Antroduodenal motility (perfusion manometry) and gastric acid secretion (continuous aspiration with recovery marker) were measured simultaneously. Each subject was studied twice in random order during (1) intravenous infusion of saline for one–two complete MMC cycles and (2) during acute acid inhibition with intravenous famotidine (bolus 20 mg, continuous infusion 4 mg/h) for one–two complete MMC cycles or at least 240 min.

Results:

In the saline study, acid output in phase III (2.1 ± 0.3 mmol/10 min) and late phase II (1.7 ± 0.2 mmol/10 min) was significantly (P < 0.05) increased over early phase II and phase I (1.2 ± 0.2 and 1.2 ± 0.2 mmol/10 min, respectively). Famotidine increased gastric pH to above pH 6 within 30 min. After acid inhibition, duration of MMC cycle during famotidine (106 ± 8 min) was not significantly different from the saline experiment (133 ± 14 min). Phase distribution of the MMC cycle was not significantly different between famotidine (I, II and III: 12 ± 3, 82 ± 3 and 5 ± 1%) and saline (I, II and III: 13 ± 3, 83 ± 3 and 4 ± 1%).

Conclusions:

Gastric acid secretion varies cyclically with interdigestive antroduodenal motility. Acute acid inhibition with intravenous famotidine does not significantly affect interdigestive antroduodenal motility.

     

Meta-analysis: the adjuvant role of thymopentin on immunological response to hepatitis B virus vaccine in end-stage renal disease

Summary

Background

It has been calculated that 30–40% of dialysis patients fail to produce antibodies to HBsAg antigen after vaccination towards hepatitis B virus. Several authors have reported on the benefit of thymopentin (TP5) as adjuvant to vaccine against hepatitis B virus in patients receiving regular dialysis. However, consistent information on this issue is still lacking.

Aims

To evaluate efficacy and safety of thymopentin as adjuvant to hepatitis B vaccine in dialysis patients by performing a systematic review with a meta‐analysis of clinical trials.

Methods

We used the random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses.

Results

We identified 11 studies involving 272 unique patients with end‐stage renal disease. Only prospective, controlled trials were included. Pooling of study results did not show a significant increase in seroresponse rate among study (thymopentin plus hepatitis B virus vaccine) vs. control (hepatitis B virus vaccine alone) patients; the pooled odds ratio of failure to respond to hepatitis B virus vaccine was 0.677 (95% confidence intervals: 0.285–1.605); no heterogeneity was found (P = 0.0001). Thymopentin significantly improved the seroresponse rate in the subgroup of trials based on greater thymopentin doses (OR: 0.184; 95% CI: 0.085–0.398).

Conclusions

Our meta‐analysis showed that thymopentin significantly improved the seroresponse rate towards hepatitis B vaccine only in dialysis patients treated with higher thymopentin doses. The limited number of patients precluded definitive conclusions.

     

There are some benefits for eradicating Helicobacter pylori in patients with non-ulcer dyspepsia

Background

: The relationship between Helicobacter pylori infection and non‐ulcer dyspepsia is not established.

Aim

: To determine whether eradication of H. pylori might be of benefit in non‐ulcer dyspepsia patients.

Methods

: We randomly assigned 129 H. pylori infected patients with severe epigastric pain, without gastro‐oesophageal reflux symptoms, to receive twice daily treatment with 300 mg of ranitidine, 1000 mg of amoxicillin, and 500 mg of clarithromycin for 7 days and 124 such patients to receive identical‐appearing placebos.

Results

: Treatment was successful (decrease of symptoms at 12 months) in 62% of patients in the active‐treatment group and in 60% of the placebo group (N.S.). At 12 months, the rate of eradication of H. pylori was 69% in the active‐treatment group and 18% in the placebo group (P < 0.001). Complete relief of symptoms occurred significantly more frequently in patients on the active treatment (43%) than in placebo‐treated patients (31%, P=0.048). Within the active‐treatment group, therapeutic success was significantly more frequent in the non‐infected patients (84% vs. 64%, P=0.04).

Conclusions

: Although eradicating H. pylori is not likely to relieve symptoms in the majority of patients with non‐ulcer dyspepsia, a small proportion of H. pylori‐infected patients may benefit from eradication treatment.