bluuebunny/crossref_metadata_2025 huggingface dataset:
Delay of gastric emptying by duodenal intubation: sensitive measurement of gastric emptying by the paracetamol absorption test
Authors: MEDHUS  , SANDSTAD  , BREDESEN  , HUSEBYE
Published: March 2003

Aims

: To examine the influence of duodenal intubation on gastric emptying measured by the paracetamol absorption test using a new algorithm developed to estimate emptying parameters, and to determine the sensitivity of this test.

Methods

: A caloric liquid meal with paracetamol as marker of emptying was administered orally to eight healthy volunteers during phase I and phase II of the migrating motor complex (MMC) and without intubation on 3 separate days, and to 10 patients with partial gastrectomy.

Results

: Healthy subjects: With duodenal tube, time until 25% of the meal had emptied (t25%) was 24 ± 7 (phase I, P < 0.02) and 21 ± 6 min (phase II, P < 0.02) compared with 14 ± 4 min for meal intake without intubation. Time until 50% of the meal had emptied (t50%) was 45 ± 8 (phase I, P < 0.001) and 35 ± 8 min (phase II, P < 0.02) compared with 26 ± 9 min for meal intake without intubation. Intraduodenal instillation of 10–20 mL of the liquid meal was reliably detected. Patients: In 9 out of 10 patients with partial gastrectomy t25% was below the lower limit of the range for healthy controls, and t25% detected accelerated emptying with a higher degree of sensitivity than the commonly applied pharmacokinetic parameters Cmax and Tmax.

Conclusions

: A duodenal tube delays gastric emptying of a caloric liquid meal. The paracetamol absorption test emerges as a sensitive method suitable for detecting both delayed and accelerated gastric emptying of caloric liquid meals.
Survey on repeat prescribing for acid suppression drugs in primary care in Cornwall and the Isles of Scilly
Authors: Boutet R. , Wilcock M. , Mackenzie I.
Published: March 2003

Background

: Repeat prescriptions for acid suppression therapy represent an important burden on health care resources.

Aim

: To determine the prevalence of acid suppression therapy and its indications by general practitioners (GPs) in a larger sample of practices than previous studies.

Method

: Practices in Cornwall and the Isles of Scilly were invited to identify the number of patients on repeat prescription for acid suppression drugs in their practice, to review the indication for treatment in a sample of 50 patients, and to indicate the mode of review of these patients.

Results

: Out of 77 practices, 42 (55%) participated in the study. Overall, 5% of patients were authorized to receive a repeat prescription for acid suppression drugs. Repeat rates varied between practices, from 1.68% to 11.11%. Repeat rates increased with age and were higher in men than in women. Only 41% of patients had a proven diagnosis of gastro‐oesophageal reflux disease or peptic ulcer. A review of notes was the most frequent way (36%) stated by GPs to review acid suppression therapy.

Conclusion

: The repeat rate found in our study was higher than that found in previous studies. A high proportion of older patients in Cornwall, as well as a continuing increase in the prescription of acid suppression drugs, may account for these results.
Octreotide in refractory functional epigastric pain with nutritional impairment—an open study
Authors: Ducrotte  , Maillot  , Leroi  , Lalaude  , Colin  , Denis
Published: March 2003

Aim

: To test the therapeutic efficacy of octreotide administered subcutaneously for the relief of chronic refractory epigastric pain severe enough to provoke nutritional impairment.

Subjects and methods

: Seventeen patients were enrolled in an open trial. Epigastric pain had lasted from 1 to 8 years (median: 5 years), following anti‐reflux surgery in eight patients. Median weight loss was 10% (range 10–15). The initial dose of octreotide was 50 μg b.d, adjusted during the follow‐up visits which were scheduled for months 1, 3, 6, 8, 10, 12 and every 3 months. At each visit, overall symptomatic improvement, frequency and intensity of symptoms were checked on a 10‐cm visual analogic scale.

Results

: At month 1, a progressive improvement of pain intensity was reported in 15 of the 17 patients, while octreotide was a therapeutic failure in two. In four out of 15, the daily dose of octreotide was increased to 100 μg b.d. In these 15 patients, median follow‐up was 7 months (3–27). The symptomatic benefit was maintained in each patient at month 3, with a median weight gain of 3.5 kg.2–5 An attempt to stop octreotide led to recurrence of symptoms in 2–3 days which were as intense as before the treatment. The 11 patients followed‐up for at least 6 months reported persistent improvement of symptoms with octreotide and a median weight gain of 4 kg.3–7 Four patients were followed up for more 11–27 months: octreotide was withdrawn gradually in two who remained asymptomatic. Six of the 17 patients experienced minor side‐effects, but none developed biliary sludge.

Conclusions

: This open study suggests that octreotide could be a promising alternative treatment when all others fail in refractory chronic functional epigastric pain severe enough to limit food intake and to induce nutritional impairment. These results must be tested by a placebo‐controlled study.
The safety of proton pump inhibitors in pregnancy
Authors: Nielsen  , Sørensen  , Thulstrup  , Tage‐Jensen  , Olesen  , Ekbom
Published: March 2003

Aim

: To assess the safety of proton pump inhibitors during pregnancy.

Methods

: Fifty‐one pregnant women exposed to proton pump inhibitors around the time of conception or during pregnancy were compared with 13 327 controls without exposure to any prescribed drug in a population‐based study based on The Pharmaco‐Epidemiological Prescription Database of North Jutland and the Danish Hospital Discharge Registry.

Results

: Three babies with malformations were found among 38 women exposed to proton pump inhibitors from 30 days before conception to the end of the first trimester. No cases of stillbirth were recorded. Crude relative risks of malformation, low birth weight and preterm delivery were 1.6 (95% CI: 0.5–5.1), 1.8 (95% CI: 0.2–13.0) and 2.3 (95% CI: 0.9–6.0), respectively.

Conclusions

: In this population‐based follow‐up study, we found no substantially elevated risk in terms of malformations, low birth weight or number of preterm deliveries in pregnancies exposed to proton pump inhibitors. However, further monitoring is warranted in order to establish or rule out a potential association between the use of proton pump inhibitors and increased risk of either cardiac malformations or preterm birth.
The effects on intragastric acidity of per‐gastrostomy administration of an alkaline suspension of omeprazole
Authors: Sharma  , Vasudeva  , Howden
Published: March 2003

Background

: It may be difficult to administer proton pump inhibitors via gastrostomy. Previous studies have examined the effect of intact proton pump inhibitor granules in orange juice. This study examined the effect of an alkaline suspension of omeprazole (simplified omeprazole suspension (SOS)) on 24‐h intragastric acidity.

Methods

: Six men with an established gastrostomy had a baseline 24‐h intragastric pH study using methodology we have previously described. They then received 20 mg SOS o.d. for 7 days and had a repeat pH study at the end of this period. Four of the patients then received 20 mg SOS with 30 cc of liquid antacid (Mylanta, TM) per gastrostomy o.d. for a further 7 days and then underwent a third pH study.

Results

: SOS raised mean pH from 2.2 to 4.1. Intragastric pH was above 3, 4 and 5 for 35, 28 and 17% of the 24‐h period at baseline, respectively; corresponding values after SOS were 63, 51 and 39%, respectively. Addition of liquid antacid to SOS did not further increase its pH‐controlling effect.

Conclusions

: We found a statistically significant effect of o.d. SOS on intragastric pH when administered via gastrostomy. We found no additional benefit of administering SOS with liquid antacid.
Laser assisted ratio analyser 13C‐urea breath testing, for the detection of H. pylori: a prospective diagnostic European multicentre study
Authors: Van Der Hulst  , Lamouliatte  , Megraud  , Pounder  , Stolte  , Vaira  , Williams  , Tytgat
Published: March 2003

Background

: Novel technology based on laser optogalvanic spectroscopy called the LARA (Laser Assisted Ratio Analyser) system was developed to measure 12C/13C ratios in breath samples using stable 13C isotopes, to detect Helicobacter pylori infection.

Aim

: To determine the sensitivity and specificity of the 13C‐LARA‐urea breath test in the detection of H. pylori infection in a prospective European multicentre trial; FDA‐and EMEA‐approved.

Methods

: Consecutive dyspeptic patients underwent diagnostic gastroscopy with biopsies for culture and histopathology, to detect H. pylori infection (gold standard). Subsequently, the LARA‐urea breath test was performed using either a system without a cold trap (part I) or a system with a cold trap (part II). In both instances baseline, 30‐min and 60‐min breath samples were collected. The optimum cut‐off level for 12C/13C ratios was determined by Receiver Operator Characteristics analysis.

Results

: In part I, 544 out of 604 patients were evaluable (low CO2: 47; withdrawn: 13). 284 out of 544 patients (52%) were H. pylori‐positive according to the gold standard. The sensitivity of the LARA‐urea breath test was 95% and the specificity 94%. In part II, 257 out of 272 were evaluable (low CO2: 14; withdrawn: 1). Sensitivity and specificity were 93% and 96%, respectively.

Conclusion

: The LARA‐technology represents an accurate and non‐invasive testing system for the detection of H. pylori infection. Its major advantages are the use of stable 13C isotope, the high throughput of samples and the easy means of collecting, storing and transporting the samples, thus making the system convenient to both patient and clinician.
Comparison of two different formulations of botulinum toxin A for the treatment of oesophageal achalasia
Authors: Annese  , Bassotti  , Coccia  , D’Onofrio  , Gatto  , Repici  , Andriulli  ,   THE GISMAD ACHALASIA STUDY GROUP
Published: March 2003

Background

: Intrasphincteric injection of botulinum toxin has been reported as a safe and effective alternative treatment in oesophageal achalasia, especially in high‐risk and elderly patients.

Aim

: To compare two formulations of botulinum toxin in the management of achalasia.

Patients and methods

: We randomly compared the efficacy and safety of 100 U of Botox (Allergan, Irvine, USA) and 250 U of Dysport (Ipsen, Milan, Italy), injected through a sclerotherapy needle at the level of the lower oesophageal sphincter, in 78 consecutive patients with achalasia. Symptom score, oesophageal manometry and 24 h pH‐metry were recorded (before and 1 month after therapy). Symptom score was also obtained 6 months after treatment.

Results

: One month after treatment, the effects of the toxin on symptoms and oesophageal tests were similar for both formulations. Lower oesophageal sphincter pressure decreased from 31 ± 12 to 18 ± 5 mmHg after Botox, and from 35 ± 9 to 18 ± 10 after Dysport. At the end of the follow‐up period (6 months), symptom score decreased from 5 ± 1.2 to 1.2 ± 0.8 after Botox and from 5.2 ± 1.5 to 1.5 ± 1 after Dysport. Moreover, the percentages of patients who failed to respond to treatment (10% and 17.5%) and who relapsed during follow‐up (12% and 24%) did not differ significantly. No patient complained of reflux symptoms after treatment, although abnormal acid exposure was documented in two subjects.

Conclusions

: Both formulations of botulinum toxin have comparable efficacy in the treatment of oesophageal achalasia, for up to 6 months of follow‐up.
Plasma hydroxy‐metronidazole/metronidazole ratio can detect early changes in hepatic function in ethanol‐induced liver injury
Authors: Da Silva  , David  , Muscará  , Sousa  , Ferraz  , De Nucci  , Polimeno  , Pedrazzoli
Published: March 2003

Aims

: To evaluate the usefulness of plasma hydroxy‐metronidazole/metronidazole (OH‐MET/MET) ratios as a dynamic liver function test in ethanol abusers with or without liver cirrhosis.

Methods

: Metronidazole was administered intravenously for 20 min to healthy volunteers, and to patients with alcohol‐induced, non‐cirrhotic hepatopathy and liver cirrhosis. Plasma concentrations of metronidazole and hydroxy‐metronidazole were measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min after the metronidazole infusion.

Results

: Patients with non‐cirrhotic alcoholic hepatopathy had significantly elevated aminotransferase levels compared to healthy volunteers and Child A patients. Child‐Pugh C patients had significantly prolonged prothrombin times when compared to healthy volunteers and patients with non‐cirrhotic hepatopathy. Metronidazole metabolism, as measured by the OH‐MET/MET ratio following the intravenous administration of 500 mg of the drug, was significantly impaired in all ethanol‐abusing individuals, including patients with non‐cirrhotic alcoholic hepatopathy.

Conclusions

: Metronidazole metabolism was impaired in ethanol abusers, even in the absence of liver cirrhosis, indicating that ethanol was capable of affecting liver function in the early stages of alcohol‐induced liver disease.
Effect of basic fibroblast growth factor on gastric ulcer healing and its own mRNA expression
Authors: Pohle  , Shahin  , Domschke  , Konturek
Published: March 2003

Background

: The application of an acid‐stable mutein of basic fibroblast growth factor (bFGF) called CS23 results in acceleration of ulcer healing. The modes by which this cytokine exerts these effects are not yet completely understood.

Aim

: To describe the pattern of bFGF‐mRNA expression during ulcer healing and to examine the effects of exogenously applied CS23 on gastric ulcer healing in an animal model.

Methods

: The speed of healing of gastric ulcers, expression of extracellular matrix gene mRNAs such as pro α(I) collagen (by non‐radioactive in situ hybridization), cellular proliferation evidenced by the display of PCNA (by immunohistochemistry), angiogenesis, and the feedback of this growth factor on its own mRNA expression pattern were used to evaluate the effects of CS23 on rat gastric ulcer healing in an animal model.

Results

: CS23 accelerates gastric ulcer healing at 7, 14 and 21 days after ulcer induction. We found an increase in connective tissue beneath the ulcer bed in treated animals in comparison to controls. The expression of PCNA as well as pro α(I) collagen mRNA was markedly increased in ulcers, yet there was no distinct difference between treatment arms. In contrast, the density of microvessels was significantly increased in the submucosa of ulcers by CS23 application. bFGF‐mRNA expression is up‐regulated in the submucosa during early ulcer healing; this increase diminishes within days but can be restituted by the exogenous application of CS23.

Conclusions

: CS23 speeds gastric ulcer healing and significantly increases the density of microvessels in the ulcerated tissue without affecting the numbers of proliferating cells or the transcription of collagen mRNA. In addition, it augments the expression of bFGF‐mRNA during the later stages of healing, suggesting a positive feedback loop.
Review article: the treatment of acute biliary pancreatitis
Authors: Enns  , Baillie
Published: March 2003

World‐wide, gallstones are the commonest cause of acute pancreatitis (AP), a potentially life‐threatening condition. Scoring systems based on radiologic findings and serologic markers help predict which patients may have retained bile duct stones. Endoscopic decompression of the biliary tree (by sphincterotomy and stone extraction during ERCP) is safer than surgery, which carries high morbidity and mortality in AP. Four prospective, randomized clinical trials confirm the utility of this approach, however careful patient selection is necessary. Medical therapy for AP is supportive; no agent or medical intervention has been shown consistently to abort or ameliorate the course of AP. Drugs that inhibit inflammatory cytokine production, however, are showing promise.
Oesophageal motility defects associated with nocturnal gastro‐oesophageal reflux on proton pump inhibitors
Authors: Fouad  , Katz  , Castell
Published: March 2003

Background

: Recent studies from our laboratory reveal that 70% of patients with gastro‐oesophageal reflux disease (GERD) on proton pump inhibitors twice daily (b.d.) have nocturnal gastric acid breakthrough (gastric pH < 4 > 1 h) which is often accompanied by oesophageal acid exposure. The pathogenesis of GER during gastric acid breakthrough is not clear.

Aim

: To determine the prevalence of oesophageal motility abnormalities in patients with nocturnal GER associated with nocturnal acid breakthrough on proton pump inhibitor b.d.

Methods

: We reviewed the pH‐metry and manometric studies of 100 consecutive patients with GERD who were on proton pump inhibitor b.d. pH tracings were analysed for the nocturnal period (10.00 hours until 06.00 hours). Nocturnal GER was defined as>  0.5% time distal oesophageal pH < 4. Manometric tracings were reviewed for lower oesophageal sphincter (LES) pressure and oesophageal body motility. Chi‐squared and Fischer’s test were used for statistical analysis.

Results

: Of the 100 patients, 74 (74%) had nocturnal gastric acid breakthrough. Thirty‐one (42%) had concurrent abnormal nocturnal GER (refluxers) and 43 out of 74 (58%) had no GER (non‐refluxers). The prevalence of ineffective oesophageal motility, and low LES pressure was significantly higher in refluxers than in non‐refluxers (P < 0.05, P < 0.001, respectively). Ineffective‐oesophageal motility has a high specificity (91%), but low sensitivity (45%) as a diagnostic predictor for patients who are more likely to develop nocturnal GER on proton pump inhibitor b.d.

Conclusion

: Ineffective oesophageal motility is a risk factor for proton pump inhibitor refractory GER.
Behaviour ofSaccharomyces boulardiiin recurrentClostridium difficiledisease patients
Authors: Elmer  , McFarland  , Surawicz  , Danko  , Greenberg
Published: March 2003

Background:

Despite recent interest in therapeutic microorganisms taken orally, little is known about the pharmacodynamics of these agents in a target population of patients with disease. The present study reports the stool concentrations ofSaccharomyces boulardiiin a patient population withClostridium difficiledisease (CDD) and correlates stool concentrations with efficacy.

Methods:

Patients with recurrent CDD all received a 10‐day standard antibiotic regimen together with 28 days ofS. boulardiior placebo. Stool samples were collected from patients at various time points and assayed forS. boulardii.

Results:

The mean concentration ofS. boulardiiof patients who recurred was 2.5 × 104CFU/g compared to 1 × 106CFU/g in patients that did not recur (P=0.02). Patients with low yeast concentrations in their stools (<104/g) recurred more often (14/15, 93%) compared with patients with higher levels (19/35, 54%,P=0.007). Clearance ofS. boulardiiwas rapid; only 4% had positive stools 3 days after stopping dosing.

Conclusions:

After chronic dosing ofS. boulardii, patients with low stool concentrations had a higher likelihood of recurrence of CDD. Stool concentrations were also lower during periods of diarrhoea. These results show the importance of characterizing the dynamics of a therapeutic microorganism in patients with disease, as kinetic studies in healthy volunteers may not give a true reflection of the disturbed microecology in the disease state.
Characterization of M cell development during indomethacin‐induced ileitis in rats
Authors: Kucharzik  , Lügering  , Lügering  , Rautenberg  , Linnepe  , Cichon  , Reichelt  , Stoll  , Schmidt  , Domschke
Published: March 2003

Background

: M cells play an important role in the intestinal immune system as they have a high capacity for transcytosis of a wide range of microorganisms and macromolecules. However, little is known about the role of M cells during intestinal inflammation.

Aim

: We studied M cell development during indomethacin‐induced intestinal inflammation in rats.

Methods

: Ileitis in rats was induced by two subcutaneous injections with indomethacin (7.5 mg/kg) given 24 h apart. Rats were sacrificed after 14 days and tissue was analysed by fluorescence microscopy and electron microscopy. M cells could be visualized by using the FITC‐labelled mAb anti‐cytokeratin (CK)‐8 (clone 4.1.18), which was recently identified as specific M cell marker in rats. The number of cytokeratin‐8 positive M cells was related to the surface of the follicle associated epithelium. For morphological studies, we used both transmission electron microscopy (T.E.M.) and scanning electron microscopy (S.E.M.).

Results

: In non‐inflamed ileum M cells were scarce. Only 4% of the follicle associated epithelium were M cells, whereas an increase of M cells up to 11% was found in inflamed follicle associated epithelium (P < 0.001). The rate of M cell induction depended on the macroscopic degree of inflammation. T.E.M./S.E.M. studies showed that in inflamed tissue most M cells underwent apoptosis with typical morphological signs. In contrast to apoptotic M cells, the neighbouring enterocytes usually appeared intact. The number of mononuclear cells below the follicle associated epithelium was significantly increased. S.E.M. studies revealed that during induced ileitis mononuclear cells migrated from the lamina propria into the gut lumen by passing through apoptotic M cells.

Conclusions

: During indomethacin‐induced ileitis in rats the increase in M cell number in association with apoptosis of M cells may alter the intestinal barrier function. These observations may play a pivotal role in the pathogenesis of chronic intestinal inflammation, e.g. in inflammatory bowel disease.
Ibuprofen versus other non‐steroidal anti‐inflammatory drugs: use in general practice and patient perception
Authors: Hawkey  , Cullen  , Pearson  , Holmes  , Doherty  , Wilson  , Garrud  , Garner  , Maynard  , Logan
Published: March 2003

Objective:

To investigate whether ibuprofen was as well‐regarded by patients as other non‐steroidal anti‐inflammatory drugs (NSAIDs).

Design:

Questionnaire sent to 1137 consecutive recipients of an NSAID prescription from 21 doctors in six general practices with computerized records. Patient responses were subsequently linked to data held on the practice records.

Setting:

General practices in and around Nottingham, selected to reflect local variations in number of partners, list size, geographical location, deprivation, prescribing burden and prescribing rate.

Subjects:

Unselected patients receiving NSAIDs prescribed for all indications for use.

Main outcome measures:

Effectiveness of ibuprofen and other NSAIDs, possible drug related adverse events, patients’ overall satisfaction with ibuprofen and other NSAIDs, factors associated with choice of ibuprofen, drug costs of ibuprofen and other NSAIDs.

Results:

The main NSAIDs used were ibuprofen, diclofenac and naproxen. Ibuprofen use ranged from 1.0% of prescriptions in one practice to 69.1% in another. Although ibuprofen was generally prescribed in low doses, it was perceived by patients as being as effective as the other NSAIDs used, even after allowing for severity of the pre‐treatment condition. Overall, 50.5% of patients rated their NSAID the best treatment they had received for their condition with no differences between individual drugs.

Conclusions:

Ibuprofen is as highly regarded as other NSAIDs when used in similar circumstances. Switching patients to ibuprofen may be a realistic way of reducing financial and medical costs associated with NSAIDs.
Cure of Helicobacter pylori infection does not improve symptoms in non‐ulcer dyspepsia patients—a double‐blind placebo‐controlled study
Authors: Miwa  , Hirai  , Nagahara  , Murai  , Nishira  , Kikuchi  , Takei  , Watanabe  , Sato
Published: March 2003

Background:

It remains controversial whether the cure of H. pylori infection improves NUD symptoms.

Aim:

To conduct a double‐blind placebo‐controlled single centre study with concealed allocation to investigate this question.

Patients and methods:

Ninety NUD patients with H. pylori infection were randomly assigned to either the treatment group (50 patients) or placebo group (40 patients). The treatment group received omeprazole, amoxycillin, clarithromycin and the placebo group received omeprazole and placebos for 7 days. Symptoms were assessed every week for up to 12 weeks after completion of medication by a symptom questionnaire. Alteration of histological parameters for gastritis was also evaluated.

Results:

The infection was cured in 41 out of 48 patients in the treatment group and none in the placebo group. There was no significant difference in the mean symptom scores at any assessment point up to 12 weeks between the treatment and placebo groups. Regarding histological parameters, activity and inflammation, not atrophy or intestinal metaplasia, were significantly improved in the treatment group.

Conclusion:

Although histological parameters were significantly improved in the treatment group, there was no significant improvement in symptoms of NUD in the treatment group compared to placebo.
Fasting induces impairment of gastric mucosal integrity in non‐insulin‐dependent diabetic (db/db) mice
Authors: Kinoshita  , Igarashi  , Kume  , Saito  , Arakawa
Published: March 2003

Background:

Although diabetic patients often have gastrointestinal complications, the gastric mucosal function in diabetes has not been well documented.

Aim:

To investigate the effect of fasting on the gastric mucosa in C57BL/KsJ–db +/+ db (db/db) mice, genetically non‐insulin‐dependent diabetic animals.

Methods:

Blood glucose levels, gastric mucosal morphology, and the amount of gastric mucin were examined before and after 18 h of fasting with free access to water in db/db mice and their non‐diabetic littermates (db/m).

Results:

Although 18 h of fasting reduced the blood glucose levels of both db/db and db/m mice, fasting decreased the amount of gastric adherent mucin and caused haemorrhagic gastric lesions only in db/db mice. After fasting, oral administration of ethanol induced much more severe gastric damage in db/db than in db/m mice. The above fasting‐induced gastric damage such as haemorrhagic lesions, loss of the mucin, and the increased sensitivity to ethanol worsened as the duration of diabetes became longer. Glucose ingestion in drinking water during the fasting counteracted the fall in blood glucose and prevented the decrease in the amount of gastric mucin and the formation of gastric mucosal lesions in db/db mice.

Conclusion:

These findings indicate that fasting‐induced glucose deficit causes gastric mucosal lesions and increases the susceptibility of gastric mucosa to noxious agents owing to the loss of mucus glycoprotein in db/db mice. Prolonged diabetes is likely to augment the severity of fasting‐induced impairment of the gastric mucosal function.
Gastric myoelectric activity in older adults treated with cisapride for gastro‐oesophageal reflux disease
Authors: Orr  , Zhang  , Mcclanahan  , Sloan  , Chen
Published: March 2003

Background:

The incidence of both gastro‐oesophageal reflux disease (GERD) and upper gastrointestinal motility disorders appears to increase with age. However, there is a dearth of data concerning the utility of a prokinetic agent such as cisapride in the treatment of older adults with symptomatic GERD.

Aim:

To investigate the incidence of electrogastrographic abnormalities in older adults with and without GERD symptoms, as well as the effect of cisapride therapy on symptoms of GERD and electrogastrographic responses.

Methods:

We report on 18 older adults with symptomatic GERD and 10 older adult controls (mean ages 71 and 75 years, respectively). Subjects underwent electrogastrographic evaluation pre‐ and postprandially under baseline conditions and after 1 month of treatment with 10 mg q.d.s. of cisapride.

Results:

Heartburn frequency and postprandial fullness were both significantly (P < 0.05) reduced after cisapride treatment. Acid contact time was not significantly changed. The percentage of 2–4 cpm activity in the electrogastrographic analysis was significantly (P < 0.05) increased with cisapride treatment, and the instability coefficient was significantly (P < 0.05) diminished with cisapride treatment.

Conclusions:

Enhanced gastric functioning and reduction in heartburn suggest that cisapride is efficacious in the treatment of older adults with symptomatic GERD, and that gastric dysrhythmias and postprandial fullness are resolved with cisapride treatment.
The effects of meloxicam, indomethacin or NS‐398 on eicosanoid synthesis by fresh human gastric mucosa
Authors: Tavares
Published: March 2003

Background:

In the stomach, constitutive cyclooxygenase (COX‐1) synthesizes prostaglandins that maintain the integrity of the gastric mucosa, while their inhibition contributes to gastric mucosal damage. In contrast COX‐2, an inducible enzyme, forms prostanoids involved in pain and inflammation.

Aim:

To compare prostaglandin synthesis inhibition by meloxicam, a selective COX‐2 NSAID reported to have better gastric tolerability, with indomethacin and NS‐398 in human gastric mucosa and in whole blood assays.

Methods:

Meloxicam, indomethacin or NS‐398 were incubated with fresh human gastric mucosa pieces (100 mg in 1 mL phosphate buffered saline, pH 7.4, 37 °C, 30 min), clotting human blood (1 mL, 37 °C, 60 min) or with lipopolysaccharide‐stimulated heparinized blood (1 mL, 37 °C, 24 h). Prostanoids were analysed by radioimmunoassay.

Results:

Meloxicam was a less potent inhibitor of gastric mucosal eicosanoid compared to indomethacin, showing a sixfold difference in IC50 with gastric mucosal prostaglandin E (PGE) (11.8 and 1.8 μM, respectively). In the whole blood assays, the COX‐2/COX‐1 ratio for meloxicam was 0.2 compared to 0.9 for indomethacin confirming meloxicam’s COX‐2 selectivity.

Conclusion:

The results with human mucosa pieces would suggest that the better gastric tolerability of meloxicam compared to indomethacin is related to its relatively lower inhibition of gastric mucosal PGE synthesis by COX‐1.
The effectiveness of omeprazole, clarithromycin and tinidazole in eradicating Helicobacter pylori in a community screen and treat programme
Authors: Moayyedi  , Feltbower  , Crocombe  , Mason  , Atha  , Brown  , Dowell  , Richards  , Axon  ,   ON BEHALF OF THE LEEDS HELP STUDY
Published: March 2003

Introduction:

Helicobacter pylori screening and treatment has been proposed as a cost‐effective method of preventing gastric cancer.

Aim:

To assess, in a randomized controlled trial, the efficacy of therapy in eradicating H. pylori as part of a screening programme, and to report the adverse events associated with this strategy.

Methods:

Subjects between the ages of 40–49 years were randomly selected from the lists of 36 primary care centres. Participants attended their local practice and H. pylori status was determined by 13C‐urea breath test. Infected subjects were randomized to receive omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 7 days (OCT) or identical placebos. Eradication was determined by a 13C‐urea breath test 6 months and 2 years after the first visit. Successful eradication was defined as two negative 13C‐urea breath tests or one negative and one missing test. Adverse events and compliance were assessed at the 6‐month visit.

Results:

A total of 32 929 subjects were invited to attend, 8407 were evaluable, and 2329 (28%) of these were H. pylori‐positive. A total of 1161 subjects were randomized to OCT and 1163 to placebo; over 80% returned for a repeat 13C‐urea breath test on at least one occasion. The eradication rates in those allocated to OCT were as follows: intention‐to‐treat, 710 out of 1161 (61%; 95% confidence interval: 58–64%); evaluable 710 out of 967 (73%; 95% CI: 71–76%); took all medication 645 out of 769 (84%; 95% CI: 81–87%). Adverse events occurred in 45% of the treatment group and in 18% of the placebo group (relative risk 2.5; 95% CI: 2.1–2.9). Compliance, male gender, no antibiotic prescription in the subsequent 2 years and experiencing a bitter taste with the medication were independently associated with treatment success.

Conclusions:

The OCT regimen has an eradication rate of 61% in intention‐to‐treat analysis and is therefore less successful in treating H. pylori as part of a screening programme compared with hospital studies in dyspeptic patients.
Efficacy and tolerability of mesalazine foam enema (Salofalk foam) for distal ulcerative colitis: a double‐blind, randomized, placebo‐controlled study
Authors: Pokrotnieks  , Marlicz  , Paradowski  , Margus  , Zaborowski  , Greinwald
Published: March 2003

Background:

Rectal formulations of mesalazine are the treatment of choice in mildly to moderately active ulcerative colitis. A new foam formulation of mesalazine was developed to improve both drug delivery and patient acceptance.

Methods:

In this multicentre, randomized, double‐blind, parallel‐group study, 111 patients with mildly to moderately active proctitis, proctosigmoiditis, or left‐sided ulcerative colitis received mesalazine foam enema or placebo enema (2 g mesalazine per day) for 6 weeks. Disease activity was monitored on the basis of the Clinical Activity Index, Endoscopic Index, Histological Index, and global efficacy assessment by the investigators. Safety assessments included the recording of adverse events, laboratory variables and vital signs.

Results:

Clinical remission was more frequent in the mesalazine group than the placebo group (65% vs. 40%; P=0.0082), particularly in patients with mild disease and patients with proctosigmoiditis. The frequency of patients with an endoscopic remission was higher in the mesalazine group (57%) than in the placebo group (37%). Similarly, 59% of patients receiving mesalazine but only 41% of those receiving placebo showed an improved Histological Index. The foam enemas were generally well‐tolerated, and no treatment‐related changes on laboratory variables and vital signs were noted.

Conclusions:

Mesalazine foam enema was well‐tolerated and was more effective than placebo in the treatment of patients with distal ulcerative colitis.
Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors
Authors: Stedman C. A. M. , Barclay M. L.
Published: March 2003

Proton pump inhibitors have dramatically influenced the management of acid‐peptic disorders in recent years. They all have a broadly similar mechanism of action and are extensively metabolized in the liver via cytochromes P450 2C19 and 3A4. There is some variation in their potential for drug interactions due to differences in enzyme inhibition. Relatively few serious adverse effects have been reported for the proton pump inhibitors.

Comparative studies of acid suppression suggest that lansoprazole and pantoprazole have a potency similar to that of omeprazole on a mg for mg basis; however, rabeprazole may have a greater potency than omeprazole. Lansoprazole and rabeprazole display a more rapid onset of maximal acid suppression than the other proton pump inhibitors.

Comparative studies using proton pump inhibitors for the treatment of reflux oesophagitis, duodenal ulcer healing and Helicobacter pylori eradication show little overall difference in outcome between the proton pump inhibitors when used in their standard doses. Lansoprazole and rabeprazole provide earlier and better symptom relief than the other proton pump inhibitors in some studies of peptic ulcer treatment. The few studies of gastric ulcer treatment suggest that there is an advantage in using the proton pump inhibitors that have a higher standard daily dose.
Chemotactic properties of ICAM‐1 and PECAM‐1 on neutrophil granulocytes in ulcerative colitis: effects of prednisolone and mesalazine
Authors: Vainer B. , Nielsen O. H.
Published: March 2003

Background:

ICAM‐1 seems to exhibit effects other than passive leucocyte/endothelial interaction.

Aim:

To investigate the attracting properties of selected adhesion molecules, assessing the influence of the two major anti‐inflammatory drugs in ulcerative colitis, prednisolone and mesalazine.

Methods:

Circulating neutrophils (11 ulcerative colitis, 15 controls) were assessed in microchemotaxis chambers by the leading front technique, using physiologically relevant concentrations of ICAM‐1 (0.005–5000 p M), PECAM‐1 (0.001–1000 n
M), and P‐selectin (0.01–100 n
M). Neutrophils pre‐incubated with prednisolone (10–8–10–4 M) or mesalazine (0.65–10.4 n
M) were assessed towards ICAM‐1.

Results:

Migration of neutrophils towards ICAM‐1 showed a bell‐shaped curve with a maximum at 5 p M (migration: 37.7 μm; P < 0.001), whereas PECAM‐1 attracted neutrophils equally in the range of 0.1–10 n
M (25.0 μm; P < 0.001). P‐selectin had no cell‐attracting effect. No differences were detected between cells from ulcerative colitis patients and controls. Pre‐treatment with prednisolone decreased the cell attracting effect of ICAM‐1 in a dose‐dependent manner to 72% of the basal migration (P < 0.001). Conversely, prednisolone showed a pro‐chemokinetic effect by increasing the spontaneous locomotion of neutrophils by 40% (P < 0.001).

Conclusions:

Specific chemotactic properties were observed for ICAM‐1 and PECAM‐1. Prednisolone exhibited a dual effect in inhibiting the ICAM‐1‐mediated migration and stimulating the general locomotion of neutrophils.
Parkinsonism: differential age‐trend in Helicobacter pylori antibody
Authors: Dobbs  , Charlett  , Dobbs  , Weller  , Peterson
Published: March 2003

Background:

Parkinsonism is associated with prodromal peptic ulceration. Dopamine antagonists provoke experimental ulcer, dopaminergic agents protect, and might inhibit growth of Helicobacter pylori.

Objective:

To describe the relationship between H. pylori serology and parkinsonism.

Methods:

Serum H. pylori anti‐urease‐IgG antibody was measured in 105 people with (idiopathic) parkinsonism, 210 without, from same locality. None had received specific eradication therapy.

Results:

Controls showed a birth‐cohort effect: antibody titre rose from 30 to 90 years (P < 0.001). Parkinsonism obliterated this (disease status · age interaction, P < 0.05), the differential age trend not being attributable to social class. Those with diagnosed parkinsonism were more likely to be seropositive (odds ratio 2.04 (95% CI: 1.04, 4.22) P < 0.04) before 72.5 years. Overall, titre fell (P=0.01) by 5 (1, 9)% per unit increase in a global, 30‐point rating (median 14 (interquartile range 10.5, 17)) of disease severity. No individual category of anti‐parkinsonian medication (92% taking) had a differential lowering effect.

Conclusions:

Higher prevalence of seropositivity in parkinsonism, before 8th decade, may be due to host susceptibility/reaction, or, conversely, infection with particular H. pylori strain(s) lowering dopaminergic status. Absence of a birth cohort effect in parkinsonism, despite similar social class representation, may be consequent on eradication, spontaneous (gastric atrophy) or by anti‐parkinsonian medication.
Allopurinol in addition to 5‐aminosalicylic acid based drugs for the maintenance treatment of ulcerative colitis
Authors: Järnerot  , Ström  , Danielsson  , Kilander  , Lööf  , Hultcrantz  , Löfberg  , Florén  , Nilsson  , Broström  ,   FOR THE SWEDISH ORGANISATION FOR STUDY OF INFLAMMATORY BOWEL DISEASES (SOIBD)
Published: March 2003

Background:

To investigate the value of combined treatment with allopurinol and 5‐aminosalicylic (5‐ASA) based drugs as maintenance treatment for ulcerative colitis (UC).

Methods:

199 patients with UC in remission but with active disease during the preceding 3 years were included. Allopurinol 100 mg twice daily or placebo was added to the 5‐ASA based maintenance treatment. Clinical and endoscopic follow up was performed after 1, 6 and 12 months.

Results:

Intention‐to‐treat analysis after 6 and 12 months showed similar results in both groups. A log‐rank test showed that 77% in the allopurinol compared to 59% in the placebo group were still in remission after 6 months (P=0.0083) and 62% and 53% after 12 months, respectively (P=0.0936). This was mainly due to a higher than expected number of relapses during the first 3 months in the placebo group. After the first 3 months, the rate of relapse in each group was similar.

Conclusions:

It appears possible that allopurinol in combination with 5‐ASA is better than 5‐ASA alone for a 6‐month, but not a 12‐month period. This has to be verified in further dose‐ranging studies.
Role of inducible nitric oxide synthase in dextran sulphate sodium‐induced colitis
Authors: Yoshida Y. , Iwai A. , Itoh K. , Tanaka M. , Kato S. , Hokari R. , Miyahara T. , Koyama H. , Miura S. , Kobayashi M.
Published: March 2003

Background: Different authors have postulated both toxic and protective effects for nitric oxide (NO) in the pathophysiology of active inflammation.

Aim: To examine the role of NO, especially that produced by the inducible form of nitric oxide synthase (iNOS), by investigating the effects of NOS inhibitors and NO donors on inflammation in experimental acute colitis.

Methods: Acute colitis was induced in rats by dextran sulphate sodium (DSS). White blood cell counts and levels of thiobarbituric acid reactants in the portal blood were determined, as were histological changes in the colonic mucosa. We then evaluated the effects of NG‐nitro‐
l‐arginine methyl ester (
l‐NAME), aminoguanidine (AG) and an NO donor on DSS‐induced changes in these inflammatory parameters.

Results and Conclusions: Inhibition of NO production by either
l‐NAME or AG worsened DSS‐induced inflammation, suggesting a protective role for NO in acute colitis. On the other hand, a NO donor also exaggerated DSS‐induced inflammatory parameters, suggesting that acute colitis may be aggravated by either too much or too little NO. These results suggest that medical treatment of ulcerative colitis must aim for maintenance of appropriate NO levels in the intestinal mucosa.
The incidence of reflux oesophagitis after cure of Helicobacter pylori in a Japanese population
Authors: Murai T. , Miwa H. , Ohkura R. , Iwazaki R. , Nagahara A. , Sato K. , Yamada T. , Ota K. , Tanaka H. , Kawabe M. , Minowa T. , Takei Y. , Miyazaki A. , Sato N.
Published: March 2003

Aim: To investigate the incidence of reflux oesophagitis after antibacterial therapy for Helicobacter pylori infection in our patient population.

Methods: Subjects were 451 H. pylori‐infected patients (primary symptom: peptic ulcer disease in 347, nonulcer dyspepsia in 100, and reflux oesophagitis in four); 11 of these patients had reflux oesophagitis on study entry. H. pylori infection was treated by a proton pump inhibitor/amoxycillin‐clarithromycin regimen for either 7 or 14 days. Each patient was examined by endoscopy before treatment and more than 6 months after treatment to compare oesophageal findings. In addition, 227 patients were interviewed regarding reflux symptoms, using symptom questionnaires, before and more than 6 months after treatment.

Results: Among 440 patients who did not have reflux oesophagitis prior to antibacterial treatment (340 peptic ulcer patients and 100 nonulcer dyspepsia patients), 23 patients whose infection was eradicated developed reflux oesophagitis (5.4%). The 11 patients who had reflux oesophagitis prior to treatment were all successfully cured of infection. Six of these patients showed no change in their oesophagitis, while the condition improved in three and worsened in two. Symptom scores improved in 34 of the 36 patients who reported reflux symptoms. Among 19 patients who showed persistent infection, only one developed reflux oesophagitis (5.2%), while none complained of newly developed symptoms following treatment.

Conclusions: Development of reflux oesophagitis after treatment of H. pylori infection was observed in a Japanese population. However, the incidence of this condition was comparable between those with persistent H. pylori infection and those in whom the infection was eradicated.
Pharmacokinetics of clarithromycin in Helicobacter pylori eradication therapy in patients with liver cirrhosis
Authors: Azuma T. , Ito S. , Suto H. , Ito Y. , Miyaji H. , Yamazaki Y. , Kato T. , Kuriyama M.
Published: March 2003

Background: Proton pump inhibitor triple therapy with clarithromycin and metronidazole has been widely used for Helicobacter pylori eradication. However, the efficacy and the safety of this therapy in patients with liver cirrhosis have not been established.

Aim: To evaluate the effect of hepatic dysfunction on metabolism of clarithromycin as it is used for H. pylori eradication therapy in patients with liver cirrhosis, and the efficacy of eradication therapy in those patients.

Methods: Serum levels of clarithromycin and its meta‐bolite, 14‐(R)‐hydroxyclarithromycin, were examined in 18 subjects (five normal controls and 13 hospitalized patients with liver cirrhosis) on a selected day between days 7 and 10 of a 2‐week course of eradication therapy. This therapy consisted of lansoprazole (30 mg, once a day) together with clarithromycin (200 mg, twice a day) and metronidazole (250 mg, twice a day). In addition, 118 H. pylori‐positive out‐patients, 88 with peptic ulcer and 30 with liver cirrhosis, underwent the same eradication therapy.

Results: Values for the area under the 0–6 h concentration–time curve (AUC) for clarithromycin were not significantly different among the groups. However, the AUC (0–6 h) values of 14‐(R)‐hydroxyclarithromycin were significantly lower in the Child‐Pugh C group than in either the normal controls or the Child‐Pugh A/B group. The cure rate for the peptic ulcer patients was 84% on a per protocol analysis (95% CI: 80%−88%) and 81% on an intention‐to‐treat analysis (95% CI: 77%−85%), while in the liver cirrhosis patients it was 89% in a per protocol analysis (95% CI: 78%−99%) and 83% in an intention‐to‐treat analysis (95% CI: 70%−97%). Mild adverse effects were observed in 10% of the peptic ulcer patients and 13% of the liver cirrhosis patients, with none leading to premature withdrawal from the study.

Conclusion: The 2‐week low‐dose lansoprazole‐based triple therapy tested is a simple, effective and well‐tolerated regimen for H. pylori eradication in patients with liver cirrhosis.
Review article: defects in gall‐bladder motor function – role in gallstone formation and recurrence
Authors: Pauletzki J. , Paumgartner G.
Published: March 2003

The pathogenesis of cholesterol gallstones is now recognized as a multifactorial process, including saturation of bile with cholesterol, destabilization of bile leading to cholesterol crystals and hypomotility permitting crystal growth, and agglomeration and retention of microstones which then grow to macroscopic gallstones. In the last 15 years meticulous research has demonstrated convincing evidence that many patients with cholesterol gallstone disease have a distinct defect in gall‐bladder motor function that is induced by bile saturated with cholesterol.