bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of treadmill training on the arteriolar and venular portions of capillary in soleus muscle of young and middle‐aged rats
Authors: SUZUKI J. , GAO M. , BATRA S. , KOYAMA T.
Published: October 2003

The effects of a 6‐week programme of endurance training on soleus muscle capillarity were examined, in terms particularly of the proportions of arteriolar and venular capillaries and their capillary domain area, in young (3‐week‐old) and middle‐aged (54‐week‐old) Wistar rats. Exercise protocols for the young training group were: 10–22.5 m min−1, 60 min day−1 for 6 days a week, with a gradient of 7 degrees during the final 2 weeks; for the middle‐aged training group, the protocols were: 10–20 m min−1, 50 min day−1 for 6 days a week. In both young and middle‐aged training groups, the density of arteriolar capillaries was significantly increased (P<0.05), but that of venular and intermediate capillaries was decreased slightly. The proportion of arteriolar capillaries therefore was significantly (P<0.05) increased, from 63.9 to 73.1%, in young rats and from 33.0 to 48.4%, in middle‐aged rats after training. The increase in the proportion of arteriolar capillaries is an advantageous adaptation to exercise‐induced increases in oxygen demand. In both young and middle‐aged rats, capillary domain area and Krogh's tissue cylinder radii in all capillary portions decreased after training. These results suggest that adaptive changes in oxygen transport system, identified as an increase in the arteriolar capillary and a reduction in diffusion distance for oxygen, were observed in middle‐aged as well as in young rats. However, capillary angiogenesis induced by exercise appeared to be greater in young than in middle‐aged rats.
Cardiovascular and renal effects of endothelin receptor blockade with PD 145065 and interaction with urodilatin
Authors: DOBROWOLSKI L. , ENDLICH K. , SADOWSKI J. , STEINHAUSEN M.
Published: October 2003

Role of endogenous endothelins (ET) in the control of cardiovascular system and renal function, and ET interaction with urodilatin (URO) were studied in anaesthetized rats. Activity of ET was blocked using PD 145065 (5 mg kg‐1 body wt i.v.), a non‐selective antagonist of ETA and ETB receptors. PD 145065 decreased mean arterial blood pressure (MBP) from 114±4 to 109±4 mmHg and the renal blood flow (RBF) from 6.6±0.3 to 5.8±0.4 mL min‐1 (P<0.02) and increased renal vascular resistance (RVR) from 17.7±1.2 to 20.1±2.1 mmHg min mL‐1. Heart rate (HR) and renal function were not affected. URO was infused i.v. at 0.1 nmol min‐1  kg‐1 body wt without or with previous ET receptor blockade. After pre‐treatment with PD 145065, infusion of URO decreased MBP more than did URO alone: 15±3% vs. 7±2% (P<0.05). RVR and HR did not change after URO alone but decreased with URO given to PD 145065 treated rats (19±5% and 14±3%, respectively, P<0.01). It is concluded that in anaesthetized surgically prepared rats endogenous ET can cause renal vasodilation, in contrast to constriction of systemic vasculature. Enhancement by ET blockade of vascular systemic and renal effects of URO supports ET interaction with natriuretic peptides in the control of cardiovascular and renal function.
Brain natriuretic peptide (BNP) gene expression in the heart of vasopressin‐deficient Brattleboro rats
Authors: ARJAMAA O. , TASKINEN T. , VUOLTEENAHO O. , LEPPÄLUOTO J.
Published: October 2003

Brain natriuretic peptide (BNP) messenger RNA was measured with a semiquantitative method from heart auricles and ventricles of vasopressin‐deficient Brattleboro rats (DI) and from desmopressin treated Brattleboro rats (DI+DDAVP). Desmopressin had been injected peripherally and Long‐Evans rats (LE) served as controls. The 3‐day substitution treatment had shifted the fluid balance of DI almost to that of LE. In the present study, the amount of BNP mRNA, normalized to the glyceraldehyde‐3‐phosphate‐dehydrogenase mRNA content, was constant in all three groups in the right auricle. No changes were seen when the right auricular and left auricular mRNA levels were compared within each group. In the left auricle, desmopressin treatment increased significantly (P<0.05) the amount of BNP mRNA compared with that of LE rats (from 1.09±0.21, n=7 to 1.72±0.17, n=8, arbitrary units). In all groups, the left ventricle had significantly (P<0.05) higher mRNA content than the right ventricle (LE: 2.24±0.23 vs. 0.67±0.13, n=6; DI: 2.30±0.60 vs. 0.33±0.05, n=8; DI+DDAVP: 2.36±0.29 vs. 0.37±0.07, n=10). In the right ventricle, both DI and DI+DDAVP rats had significantly (P<0.05) lower mRNA content than LE rats (0.33±0.5 vs. 0.67±0.13 and 0.37±0.07 vs. 0.67±0.13, respectively).

To conclude, these findings suggest that brain natriuretic peptide gene expression dissociates from, or rapidly adapts to, the chronic effects of peripheral desmopressin treatment which have shifted the fluid balance to almost normal in Brattleboro rats. The left ventricular pressure appears to regulate the brain natriuretic peptide gene expression.
Heavy physical exercise decreases nitric oxide levels in the nasal airways in humans
Authors: LUNDBERG J. O. N. , RINDER J. , WEITZBERG E. , ALVING K. , LUNDBERG J. M.
Published: October 2003

A continuous production of nitric oxide (NO) takes place in human nasal airways. NO in the nasal airways is mainly derived from the paranasal sinuses. The factors that regulate NO synthesis in the upper airways are presently not known. We have investigated the effects of physical exercise on NO levels in the nasal airways. Nasal cavity NO levels were measured by chemiluminescence technique in five healthy non‐smoking male subjects before, during and after 5 min of maximal exercise (245 W) on an ergometer cycle. In addition, in one subject NO levels were measured directly in the maxillary sinus during exercise. Nasal cavity NO levels were decreased by 47% after only 1 min of exercise compared with the control situation. A maximal 76% reduction was found at the end of the exercise period and thereafter NO levels slowly increased, reaching basal levels again in about 15–20 min. NO levels in the sinus decreased in a similar manner during exercise. The decrease in nasal cavity NO levels cannot be explained merely by dilution of nasal air due to changes in nasal cavity volume or increased ventilation. We conclude that the excretion of NO in the nasal airways is decreased acutely during heavy short term physical exercise.
Influence of picrotoxin and strychnine on the spectral sensitivity of the turtle ERG b‐ and d‐wave: I. Dark adaptation
Authors: KUPENOVA P. , VITANOVA L. , POPOVA E. , MITOVA L.
Published: October 2003

The ERG ON‐ (b‐wave) and OFF‐response (d‐wave) to differently coloured stimuli was studied using a wide range of stimulus intensities in dark adapted turtle retina. The intensity–response curve of the b‐wave showed saturation but that of the d‐wave, decline in the high‐intensity stimulus range. The curves of the relative spectral sensitivity of the ERG ON‐ and OFF‐response were similar and showed a maximum in the longwave part of the spectrum. GABAergic blockade by 50 μmol L−1 picrotoxin caused an increase of the sensitivity, contrast sensitivity and the amplitude range of both ON‐ and OFF‐responses without narrowing of the response dynamic range. In the range of lower stimulus intensities the ON‐responses to blue stimuli and the OFF‐responses to red stimuli were affected to a greater extent. An increased ERG b‐ and d‐wave sensitivity was also observed during glycinergic blockade by 50 μmol L−1 strychnine. In the low intensity stimulus range the effect was maximal on the ON‐responses to blue stimuli and on the OFF‐responses to 570 nm stimuli. It was concluded that the GABA‐ and glycinergic systems in the retina equalize rather than make different the relative spectral sensitivities of the ON‐ and OFF‐responses.
The future of Helicobacter pylori eradication: a personal perspective
Authors: MARSHALL B. J.
Published: October 2003

Future changes in the use of Helicobacter pylori eradication therapy first will involve a decision‐making process to determine which individuals require testing. Clearly, only persons who require therapy need to be diagnosed and, at present, the indications for therapy are constantly expanding. The author takes the view that everyone with H. pylori would be better off without the bacterium, but accepts that in many countries resources are inadequate to achieve this goal.

Where antibiotic therapy for H. pylori fails due to a resistant organism, second treatment must include a different class of antibiotic. When a third therapy is contemplated, antibiotic sensitivity studies are usually necessary.

In developing counties where reinfection with H. pylori is common, lesser goals than permanent cure might be appropriate. Thus, selected patients could have H. pylori suppressive therapy to prevent full expression of H. pylori‐associated disease, or to prevent reinfection after an initial eradicative therapy.

After considering all these alternatives, one must conclude that a vaccination strategy, if safe and cost effective, is the ideal future therapy.
Non‐endoscopic tests in the diagnosis of Helicobacter pylori infection
Authors: ATHERTON J. C.
Published: October 2003

The urea breath test (UBT) and serological antibody detection are simpler and less expensive than endoscopic tests for the diagnosis of Helicobacter pylori. For the UBT, either non‐radioactive 13C or radioactive 14C is used as an isotopic marker. 14C‐UBTs are cheaper and are safe, but licensing regulations may make them inconvenient. Some UBTs have been simplified by omitting the normal test meal and encapsulating the urea to avoid metabolism by oral bacteria. These modified tests need further validation, especially when used for assessing H. pylori status after treatment. Serological tests detect circulating IgG or IgA. They are of variable accuracy, the best performing as well as UBTs. Paired serum samples pre‐treatment and 6 months post‐treatment accurately assess treatment success. Rapid in‐office tests appear less accurate and cannot be used for post‐treatment assessment. In practice, for primary diagnosis of H. pylori infection, endoscopic tests are best because endoscopy allows assessment of treatment indications. Where indications already exist or taking biopsies is dangerous, UBTs or serology are suitable, but serology is cheaper and more convenient. After treatment, endoscopy is usually unnecessary and UBTs accurately assess H. pylori status at 4 weeks. Serology is an alternative only if results are not required before 6 months.
Outcomes research in Helicobacter pylori infection
Authors: FENDRICK A. M.
Published: October 2003

While the medical community has accepted the role of H. pylori in the pathogenesis of peptic ulcer disease, confusion persists among clinicians regarding when and on which patients to attempt H. pylori eradication. Thus, the objective for outcomes research in H. pylori is to help clinicians identify which patients benefit from H. pylori eradication and to determine the cost‐effective strategies for their diagnosis, treatment and follow‐up care.

Economic evaluation of the impact of H. pylori infection has focused primarily on assessment of patient with documented peptic ulcer disease, with particular attention to costs of pharmaceuticals. However, drug costs are only one portion of the total costs of management for patients with acid‐related disorders and therefore must be put in the appropriate context. Additional aspects of patient benefit (e.g. patient satisfaction) and health‐care expenditures (e.g. over‐the‐counter medications, specialist visits, hospitalizations) must be included in an evaluation of the value of a particular diagnostic test, treatment, clinical guideline or disease management strategy.

As a result of the high quality and quantity of data emerging, it can be safely said that H. pylori eradication is cost‐effective in selected patient populations: newly documented peptic ulcer disease; history of peptic ulcer disease and taking maintenance therapy; and suspected peptic ulcer disease using a serological test to guide initial treatment. The role of eradication in other areas, for example, patients with non‐ulcer dyspepsia and screening to prevent gastric cancer, remains to be seen. In addition to the performance of rigorous studies, researchers must respond to the ‘information overload’ on busy clinicians, by effectively disseminating their findings. If data generated from outcomes research are not integrated into everyday clinical practice, the enormous benefits associated with H. pylori eradication will not be achieved.
Helicobacter pylori eradication and its implications for the future
Authors: BLASER M. J.
Published: October 2003

It has become evident that at least some strains of Helicobacter pylori are pathogenic for humans. However, H. pylori are highly diverse and at least part of this variation involves characteristics related to pathogenicity. A large amount of evidence suggests that H. pylori infection of humans is ancient, and in general, the interaction is not terribly destructive. However, we should try to understand better the risks associated with infection with particular H. pylori strains, and limit treatment to those situations in which the indications for eradicating H. pylori are clear‐cut. It is entirely possible that some H. pylori strains are commensals, and that others are symbionts. Eradicating those infections could ultimately cause more harm than good. It is too early to reach firm conclusions about whether all H. pylori infections need to be eradicated.
The treatment of Helicobacter pylori infection
Authors: POUNDER R. E. , WILLIAMS M. P.
Published: October 2003

Indications for eradication of Helicobacter pylori infection have widened since the National Institutes of Health consensus conference in 1994. It is argued that they should now include infected patients with non‐ulcer dyspepsia, those concerned about the risk of gastric cancer, patients with gastric lymphoma, and those requiring long‐term treatment with a proton pump inhibitor. Problems with existing clinical trials are discussed, and the results of different treatment regimens are discussed. It is proposed that future eradication trials should investigate H. pylori‐infected subjects identified by serology, rather than ulcer patients, and that eradication is proved only by a pair of 13C‐urea breath tests.
Randomized comparison of differing periods of twice‐a‐day triple therapy for the eradication of Helicobacter pylori
Authors: LAINE L. , ESTRADA R. , TRUJILLO M. , FUKANAGA K. , NEIL G.
Published: October 2003

Background: We assessed the efficacy, compliance, and tolerability of the twice‐a‐day triple therapy, amoxycillin, omeprazole, and clarithromycin, for Helicobacter pylori and studied the effect of treatment duration (7, 10 or 14 days) on these factors.

Methods: One‐hundred and fifty subjects with H. pylori infection documented by 13C‐urea breath test were randomly assigned to a 7, 10 or 14‐day course of amoxycillin 1 g b.d., omeprazole 20 mg b.d. and clarithromycin 500 mg b.d. Subjects returned at the end of therapy for pill count and assessment of side‐effects. Subjects returned for a repeat 13C‐urea breath test 4 weeks after the end of therapy.

Results: Poor compliance (<80% of medications taken) was seen in 0 subjects at 7 days, 6% at 10 days, and 10% at 14 days (P=0.03 by χ2 test for trend; difference for 7 vs. 14 days=10%; 95% CI, −2% to 18%; P=0.056). Intention‐to‐treat eradication rates were 86% at 7 days, 90% at 10 days and 92% at 14 days. Per‐protocol eradication rates were 86% at 7 days, 91% at 10 days, and 95% at 14 days (P=0.11; difference for 7 vs. 14 days=9%; 95% CI, −2% to 21%; P=0.17).

Conclusions: One week of twice‐a‐day amoxycillin, omeprazole and clarithromycin is well tolerated and provides a good rate of H. pylori eradication. Increasing the duration of therapy decreases compliance but has the potential to modestly improve efficacy if the patient takes the full complement of medication.
Long‐term treatment with lansoprazole of patients with duodenal ulcer and basal acid output of more than 15mmol/h
Authors: HIRSCHOWITZ B. I. , MOHNEN J. , SHAW S.
Published: October 2003

Background: About 10% of patients with duodenal ulcers have marked gastric acid hypersecretion with basal acid output (BAO) of more than 15 mmol/h, which is in the range found in Zollinger–Ellison syndrome.

Patients and study design: We report long‐term, up to 4 years, prospective treatment using lansoprazole in nine male patients with duodenal ulcers and a BAO of more than 15 mmol/h whose results are compared with those in 10 male Zollinger–Ellison syndrome patients with intact stomachs reported in detail in an accompanying paper.

Results: All 19 subjects, except one Zollinger–Ellison syndrome patient who had gastric and oesophageal ulcers, had a history of duodenal ulcers; 22% of those with gastric acid hypersecretion had oesophagitis compared with 60% of those with Zollinger–Ellison syndrome. Each subject had the dose of lansoprazole adjusted to give a BAO of less than 5 mmol/h. At 3‐month intervals to 1 year, and then at 6‐monthly intervals, basal and pentagastrin stimulated secretions were studied, in addition to gastroscopy with biopsy for gastric mucosal morphology. Basal and maximal acid and pepsin secretions were not different between gastric acid hypersecretion and Zollinger–Ellison syndrome patients before treatment. During treatment, BAO was reduced by over 90% to less than 2 mmol/h, while peak acid output was reduced by 70% in those with gastric acid hypersecretion and 90% in Zollinger–Ellison syndrome patients. Four gastric acid hypersecretion patients had relapses during treatment, three times in one patient and twice in another patient, but all responded to continued treatment with lansoprazole. Of the seven ulcer‐related relapses in the gastric acid hypersecretion patients, four occurred with a BAO of less than 2 mmol/h and three with a BAO of 7.1–7.3 mmol/h; five of the seven relapses occurred in the absence of Helicobacter pylori. Lansoprazole remained effective at an average dose of ≈70 mg/day, without causing any side‐effects.

Conclusion: Lansoprazole is apparently safe and effective for treating hypersecretion, whether due to hypergastrinaemia (Zollinger–Ellison syndrome) or not (non‐Zollinger–Ellison syndrome hypersecretors).
Prescriptions for mesalazine and sulphasalazine: a prevalence estimate of patients treated for inflammatory bowel disease in Rome
Authors: TEBANO M. T. , TRAVERSA G. , DA CAS R. , LOIZZO A.
Published: October 2003

Background: Sulphasalazine and 5‐amino salicyclic acid drugs are specifically indicated for the treatment of inflammatory bowel disease.

Aim: To use drug consumption by a given population as a marker to estimate the number of patients with inflammatory bowel disease.

Methods: Prescriptions for sulphasalazine and mesalazine were identified for the 133000 inhabitants of a local health unit in Rome. Other prescriptions received by the patients, who were users of sulphasalazine or mesalazine, were also studied.

Results: 99465 patients received at least one prescription for any drug in 1991. Three hundred and seventy‐six patients were prescribed sulphasalazine and/or mesalazine, an average of 3.8 prescriptions per patient. These patients were exposed more frequently than the general population to other drugs often used in inflammatory bowel disease treatment, for example, corticosteroids, anti‐diarrhoeal drugs and intestinal anti‐infectives. We identified that 258 of 100000 inhabitants were prescribed either sulphasalazine or mesalazine; 127 of 100000 inhabitants received full‐dose treatment for at least 30 days, and 42.8 of 100000 inhabitants received prescriptions of either drug, also associated with systemic corticosteroids.

Conclusion: The consumption of drugs used specifically for inflammatory bowel disease may act as a marker for the prevalence of the condition in a community.
Systemic availability of 5‐aminosalicylic acid: comparison of delayed release and an azo‐bond preparation
Authors: GIONCHETTI P. , CAMPIERI M. , VENTURI A. , RIZZELLO F. , FERRETTI M. , BRIGNOLA C. , MIGLIOLI M.
Published: October 2003

Aim: To determine the systemic uptake of 5‐aminosalicylic acid (5‐ASA) and acetyl‐5‐ASA (Ac‐5‐ASA) at steady state during treatment with either an azo‐bond preparation, olsalazine, or a delayed‐release mesalazine.

Methods: In an open cross‐over trial with randomized sequence, 15 patients with ulcerative colitis in remission were given 7‐day courses of olsalazine (Dipentum 1.0 g daily) and of mesalazine (Asacol 1.6 g daily). Plasma and urine were collected on days 6 and 7 of each course and concentrations of 5‐ASA and Ac‐5‐ASA were determined by high‐performance liquid chromatography (HPLC).

Results: Mean steady‐state plasma concentrations of 5‐ASA and Ac‐5‐ASA were significantly higher after treatment with mesalazine than with olsalazine (P< 0.0001). Total urinary excretion of 5‐ASA and Ac‐5‐ASA as a percentage of the given dose was significantly higher on mesalazine than on olsalazine (P<0.01).

Only two patients experienced, during the first 3 days of treatment with olsalazine, transient watery diarrhoea which resolved spontaneously. No unexpected or major changes in haematology or biochemistry were detected during the study.

Conclusion: As 5‐ASA acts locally, the lower systemic load provided by olsalazine may increase efficacy and reduce the potential risk of nephrotoxicity during long‐term maintenance treatment of ulcerative colitis.
Antral gastrin cell hyperfunction and Helicobacter pylori infection
Authors: ANNIBALE B. , RINDI G. , D'AMBRA G. , MARIGNANI M. , SOLCIA E. , BORDI C. , DELLE FAVE G.
Published: October 2003

Background: Antral gastrin cell hyperfunction (AGCH), is a rare cause of duodenal ulcer associated with non‐tumour hypergastrinaemia and acid hypersecretion.

Aim: To investigate the role of Helicobacter pylori in AGCH.

Patients: Twelve AGCH patients and eight H. pylori‐positive non‐hypergastrinaemic duodenal ulcer patients were compared.

Methods: Basal and peak acid outputs, gastrin‐stimulation (meal and bombesin) tests, and immunohistochemistry for antral G and D cells were performed. One year after H. pylori eradication, six AGCH patients were again investigated with the same tests.

Results: Significantly more basal, and stimulated gastrin and acid secretion, were found in AGCH compared to the H. pylori‐positive duodenal ulcer patients (P<0.01). G cell counts were significantly higher in AGCH than in duodenal ulcer patients (118.8, range 58–192.4, vs. 86.1, range 49–184; P<0.05), and the resulting G/D cell ratio was also higher in AGCH patients (4.2, range 2.6–5.6, vs. 3.3, range 1.9–4.3; P<0.05). H. pylori was present in the gastric mucosa of all 12 AGCH patients. Cure of infection in six AGCH individuals resulted in marked a decrease of gastrin levels associated with a significant (23.7%; P<0.05) decrease of G cell count and an increase (12%; P<0.05) of D cell count.

Conclusions: The results indicate that AGCH may result from H. pylori overstimulation of gastrin cell function in patients with some presently undefined, familial predisposition and that an imbalance of the G/D cell ratio may have a role in the genesis of hypergastrinaemia.
Morning versus evening dosing of lansoprazole 30 mg daily on twenty‐four‐hour intragastric acidity in healthy subjects
Authors: FRASER A. G. , SAWYERR A. M. , HUDSON M. , SMITH M. S. H. , POUNDER R. E.
Published: October 2003

Background: Morning dosing is usually recommended with proton pump inhibitors, but there are few data from 24‐h intragastric acidity studies comparing times of dosing.

Methods: A double‐blind, placebo‐controlled study was performed on the seventh day of dosing to compare the effects of lansoprazole 30 mg given either in the morning or evening on 24‐h intragastric acidity in 32 healthy volunteers.

Results: The median integrated 24‐h intragastric acidity on the seventh day of morning dosing with lansoprazole 30 mg was decreased to 36% of the placebo value, compared with 42% for evening dosing. For each daytime meal‐related interval, morning dosing was significantly more effective for controlling acidity, but there was no significant difference between the regimens during the night interval (23.00–08.00 h).

Conclusions: These data favour morning dosing of lansoprazole 30 mg for routine use, but patients with mainly nocturnal symptoms may be best treated by evening dosing.
clinical aspects of Helicobacter pylori eradication therapy in peptic ulcer disease
Authors: PENSTON J. G.
Published: October 2003

Background and aims: Although the role of H. pylori in peptic ulcer disease is no longer in dispute, certain aspects of eradication therapy in this condition have yet to be settled. Uncertainties still surround the relationship between Helicobacter pylori status and ulcer healing, the efficacy of eradication therapy in alleviating acute symptoms and healing ulcers, and the prognosis after eradication with respect to recurrence of symptoms, ulcers and complications. The present literature review, encompassing studies published up to October 1995, specifically addresses these issues.

Results: Pooled data show that eradication therapy heals 90% of duodenal ulcers and 85% of gastric ulcers, while individual studies repeatedly confirm that it is more effective at healing ulcers than conventional treatment with anti‐secretory drugs. Recent reports indicate that triple therapy regimens for 1 week, provided they include an anti‐secretory drug, are sufficient to achieve high rates of healing and rapid symptom relief. A detailed analysis of the data, particularly those from studies reporting healing rates in relation to H. pylori status after eradication therapy, provides strong evidence that eradication of H. pylori produces ulcer healing. Follow‐up studies show that ulcer recurrence and complications are rare after eradication treatment in patients with either gastric or duodenal ulcer disease. However, while ulcer symptoms are infrequent during follow‐up, a proportion of patients appear to develop gastrooesophageal reflux after eradication.

Conclusions: H. pylori eradication is highly effective in promoting ulcer healing and preventing subsequent ulcer recurrence. These beneficial effects of eradication therapy are observed in patients with either gastric or duodenal ulcers which are associated with H. pylori infection.
Omeprazole versus ranitidine: short‐term triple‐therapy in patients with Helicobacter pylori‐positive duodenal ulcers
Authors: SPADACCINI A. , DE FANIS C. , SCIAMPA G , MASCIULLI V , PANTALEONE U , DI VIRGILI M. , MAGNARINI C. , PIZZICANNELLA G.
Published: October 2003

Aim: To compare the results of two short triple‐therapy regimens, different only in the antisecretory drugs used, in patients with active duodenal ulcer and Helicobacter pylori infection.

Methods: All patients received a combination of clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 1 week, in addition to an antisecretory drug: omeprazole 20 mg (50 patients) or ranitidine 300 mg (50 patients) twice daily for 1 week, followed by a single daily dose for a further 3 weeks. Upper gastrointestinal endoscopy, with rapid urease test and histological examination of antral and corpus biopsies, was performed prior to the treatment and at least 2 months after the discontinuation of the antisecretory therapy.

Results: Duodenal ulcer healing was documented in all patients at the endoscopic examination after therapy. H. pylori eradication was achieved in 46 of 50 patients (92%, 95% CI=85–99%) in the omeprazole group and in 43 of 50 patients (86%, 95% CI=76–96%) in the ranitidine group; the difference is not significant.

Conclusion: Omeprazole or ranitidine, in combination with clarithromycin and tinidazole, are equally effective in the eradication of H. pylori infection and healing of duodenal ulcers.
pathogenesis and treatment of chronic hepatic encephalopathy
Authors: JALAN R. , SEERY J. P. , TAYLOR‐ROBINSON S. D.
Published: October 2003

The various treatment strategies for hepatic encephalopathy are compared in the light of the available body of scientific work on the pathogenesis of the syndrome. Data on animal models of hepatic encephalopathy and in vitro studies on brain slices are discussed. Difficulties in extrapolating the results obtained to the human situation are highlighted, while results of human positron emission tomography and magnetic resonance spectroscopy studies are outlined on the background of the potential weaknesses of these non‐invasive techniques.
Differing actions of the acute administration of propranolol and isosorbide‐5‐mononitrate on the portal circulation
Authors: FORREST E. H. , JALAN R. , REDHEAD D. N. , HAYES P. C.
Published: October 2003

Background: The aim of this study was to clarify the actions of propranolol and isosorbide‐5‐mononitrate upon the portal circulation.

Methods: Portal haemodynamics were assessed in 16 patients with transjugular intrahepatic portosystemic stent shunts. A reverse thermodilution catheter was positioned in the portal vein, and portal vein pressure and portal vein flow were measured directly. The effects of propranolol 80 mg and isosorbide‐5‐mononitrate 20 mg over 1 h were determined independently.

Results: This demonstrated that propranolol reduced both portal pressure gradient (7.7±2.3 to 5.5±2.1 mmHg, P<0.01) and portal vein flow (925±123 to 597±99 mL/min, P=0.01) significantly, implying a reduction in splanchnic inflow as its main effect. In contrast, isosorbide‐5‐mononitrate tended to increase portal vein flow (814±186 to 911±211 mL/min; P=0.06) whilst reducing portal pressure significantly (108±12 to 92±10 mmHg P=0.014). This suggests a fall in intrahepatic resistance and provides no evidence for baroreceptor‐mediated reflex splanchnic vasoconstriction.

Conclusions: These drugs act upon different variables contributing to portal hypertension and so they may have a powerful synergistic effect in combination. Direct measurement of portal vein flow is a valuable method for assessing the pharmacological modulation of portal venous inflow.
Factors affecting dose selection and outcome of cisapride treatment for dyspepsia in primary care
Authors: BRUNNER H. ,   THE AUSTRO‐CIS STUDY GROUP
Published: October 2003

Background: Little is known about the prescribing habits and impact of life style or disease factors on the outcome of cisapride treatment for dyspepsia in primary care.

Method: In this large‐scale open, multi‐centre study in Austria, primary care physicians were asked to prescribe cisapride according to the current prescribing guidelines (standard dose, 5 mg t.d.s.; in case of severe symptoms, 10 mg t.d.s.). Symptom severity was rated by the physicians, after 4 weeks of treatment and after another 4 weeks of follow‐up without medication. The global therapeutic result was given by both the physicians and patients.

Results: Among the 3912 recruited patients, 60.0% received cisapride 5 mg t.d.s. and 38.5% received 10 mg t.d.s. The dose selection by the physicians was not only influenced by severity of the symptoms (significantly more patients with severe symptoms receiving the higher dosage when compared to those with milder symptoms (P<0.001)), but also other factors were associated with prescription of the higher dose, including heavy smoking, longer pre‐existence of complaints and failing previous treatment. After 4 weeks of treatment, the dyspeptic symptoms improved in about 80% of patients, in both dosage groups. Four weeks after discontinuation of medication, 21% of patients still further improved, while 10% relapsed. The overall therapeutic outcome defined as the percentage of patients with good or excellent results was comparable in both dosage groups and appeared independent of the patient's characteristics, life style or disease factors. However, when only the proportion of ‘excellent’ responders was analysed, this rate significantly decreased the longer the duration of symptoms, the heavier the smoking and with failing previous therapy. This effect was particularly seen with the patients' ratings.

Conclusions: Although the open‐study design does not allow evaluation of the contribution of placebo‐effect and calls for cautious interpretation, the data suggest that the use of flexible cisapride doses for management of dyspepsia in primary care results in a good acute and medium‐term outcome, with apparently little dependence on life style and disease factors, at least when assessed by physicians.
Intravenous midazolam as a sedative for colonoscopy: a randomized, double‐blind clinical trial
Authors: YUNO K. , IISHI H. , TATSUTA M. , HIFUMI K. , OMORI M.
Published: October 2003

Methods: Forty patients, aged between 36 and 60 years, scheduled to undergo colonoscopic removal of colorectal polyps were randomly assigned to receive 0.9% saline solution (n=20) or 0.05 mg/kg body weight of midazolam (n=20) intravenously.

Results: Midazolam significantly (P<0.001) increased the tolerance of patients to colonoscopy. It had no significant effect on pulse or systolic blood pressure during endoscopy. Arterial oxygen saturation decreased significantly (P<0.01) during endoscopy in patients pre‐treated with midazolam, but it did not decrease by more than 5%.

Conclusions: Intravenous midazolam is useful as a sedative for colonoscopy, but we recommend continuous oxygen saturation monitoring during endoscopy.
Effects of ranitidine bismuth citrate on gastric acid secretion and gastrin release in subjects with and without Helicobacter pylori infection
Authors: CIOCIOLA A. A. , WEBB D. D. , HEATH A. , WALSH J. H.
Published: October 2003

Background: Ranitidine bismuth citrate is a novel antiulcerant that provides the antisecretory activity of ranitidine and the gastric mucosal protection and antibacterial properties of bismuth.

Methods: This randomized, double‐blind, placebo‐controlled study evaluated the effects of single doses of ranitidine bismuth citrate 200 mg, 400 mg and 800 mg and ranitidine hydrochloride 150 mg on gastrin release and suppression of gastric acid secretion, and compared acid secretory profiles and gastrin release between Helicobacter pylori‐negative and‐positive patients. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and in response to peptone meal stimulation. Acid secretion was measured under basal conditions and in response to peptone meal stimulation. Presence of H. pylori was determined by both 14C‐urea breath test and ELISA serology.

Results: Inhibition of gastric acid output by ranitidine bismuth citrate was both time‐ and dose‐dependent over the 9‐h post‐dose study period. Doses of ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg, which are equimolar, produced similar suppression of acid output regardless of H. pylori status. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations regardless of H. pylori status. All doses of ranitidine bismuth citrate were well tolerated.

Conclusions: Ranitidine bismuth citrate caused time‐and dose‐dependent reductions in meal‐stimulated and between‐meal gastric acid output regardless of H. pylori status. The magnitude of decreased acid secretion was similar with ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations.
A double‐blind randomized trial of low‐dose versus high‐dose topical anaesthesia in unsedated upper gastrointestinal endoscopy
Authors: MULCAHY H. E. , GREAVES R. R. S. H. , BALLINGER A. , PATCHETT S. E. , RICHES A. , FAIRCLOUGH P. D. , FARTHING M. J. G.
Published: October 2003

Background: Upper gastrointestinal endoscopy is frequently performed on unsedated subjects. Pharyngeal anaesthesia is thought to improve patient tolerance to the procedure but the optimum dose of anaesthesia is not known. The aim of this study was to assess the benefits of low‐dose vs. high‐dose topical anaesthesia in unsedated gastroscopy.

Methods: One hundred and fourteen subjects attending for diagnostic gastroscopy were studied. Patients were randomized to receive either 30 mg or 100 mg of topical pharyngeal lidocaine spray prior to endoscopy in a double‐blind fashion. Subjects completed a questionnaire before and after endoscopy.

Results: A similar proportion of patients in each group required intravenous sedation because of discomfort or anxiety during the procedure (P=0.48). The high‐dose group experienced less discomfort during endoscope insertion (P=0.002) and throughout the examination (P=0.01). Overall satisfaction was almost identical in the two groups (P=0.85) and a similar percentage of the high‐dose and low‐dose groups stated that they would request sedation prior to future endoscopy (37 vs. 44%; P=0.48). Further analysis showed that apprehensive patients and younger patients reported relatively high levels of discomfort, and that female subjects were more likely to express a preference for sedation at any future gastroscopy.

Conclusion: High‐dose pharyngeal anaesthesia reduces patient discomfort during unsedated upper gastrointestinal endoscopy. However, patient tolerance is also influenced by clinical features, which might be useful in deciding which patients are suitable for this procedure.
A prospective randomized trial of colchicine in prevention of liver cirrhosis in chronic hepatitis B patients
Authors: LIN D.‐Y. , SHEEN I.‐S. , CHU C.‐M. , LIAW Y.‐F.
Published: October 2003

Background: The clinical course of chronic hepatitis B is variable. Patients with hepatic decompensation, bridging necrosis or an alpha‐fetoprotein level greater than 100 ng/mL during an exacerbation of hepatitis have a high risk of developing cirrhosis. This study was conducted to evaluate the effect of colchicine in the prevention of cirrhosis in such patients.

Methods: Patients with risk factor(s) were randomized to receive either colchicine 5 mg/week or no specific treatment, the end point being development of cirrhosis.

Results: After a follow up period of 4 years, the treatment group had a marked reduction in exacerbations of acute hepatitis (32% vs. 63%/patient/year, P<0.005). Seven out of 38 patients in the treatment group and 10 out of 27 patients in the control group developed cirrhosis. The calculated cumulative incidence of cirrhosis by the end of first, second, third and fourth years in the treatment group was 8.7, 18.6, 32 and 32%, respectively. The corresponding figures in the control group were 30, 35.5, 46.3 and 73.2%, respectively, with a P‐value of 0.057.

Conclusions: The results suggest that colchicine may prevent cirrhosis in chronic hepatitis B patients with risk factor(s), possibly by suppressing exacerbations of hepatitis through an anti‐inflammatory effect.
Feasibility of analysing [13C]urea breath tests for Helicobacter pylori by gas chromatography‐mass spectrometry in the selected ion monitoring mode
Authors: KASHO V. N. , CHENG S. , JENSEN D. M. , AJIE H. , LEE W‐N. P. , FALLER L. D.
Published: October 2003

Background: The [13C]urea breath test for Helicobacter pylori is nonradioactive, as well as noninvasive, but few clinical laboratories have the expensive isotope ratio mass spectrometer used for analysis.

Methods: To demonstrate the feasibility of analysing [13C]urea breath tests with a gas chromatograph‐mass spectrometer routinely used for drug testing, 13CO2 standards for breath tests and breath samples from patients in a multiple‐blind study were analysed. The breath samples were also analysed by isotope ratio mass spectrometry, and the diagnoses were compared with biopsy results.

Results: The precision of the enrichment measurements by gas chromatography–mass spectrometry was 1.1 parts per thousand, and the calculated differences in enrichment between standard gases equaled the certified values. The sensitivity (94%), specificity (94%), and percentage agreement (94%) for diagnosis of Helicobacter pylori (n=34) were as high or higher than for analysis of replicate breath samples by isotope ratio mass spectrometry and comparable to the values reported for diagnosis of the bacterium by other currently accepted tests.

Conclusions: The study demonstrates that a gas chromatograph–mass spectrometer can be used to analyse [13C]urea breath tests, thus potentially lowering the cost of the test and increasing the number of laboratories that can perform the test.
Altered bowel function and duodenal bacterial overgrowth in patients treated with omeprazole
Authors: LEWIS S. J. , FRANCO S. , YOUNG G. , O'KEEFE S. J. D.
Published: October 2003

Background: The dramatic inhibitory effect of proton pump inhibitors on acid secretion has raised concern about possible side‐effects, such as small bowel bacterial overgrowth, which may result in further gut dysfunction. The aim of this study was to assess the effect of proton pump inhibitors on duodenal bacteriology, carbohydrate absorption and bowel habit.

Methods: Small bowel bacterial overgrowth and xylose absorption were measured by culture of aspirated duodenal fluid and a combined 1 g 14C‐d‐xylose absorption–metabolism test in 20 patients with peptic ulcer disease. Tests were repeated after 4 weeks of treatment with omeprazole 20 mg daily. Intestinal transit was assessed by recording interdefecatory intervals and stool form.

Results: All patients showed an increase in duodenal bacterial counts following treatment, geometric mean counts increasing from 330 to 95000 CFU/mL. The geometric mean of the difference was 290 CFU/mL (95% CI, 110–720 CFU/mL; P<0.0001). No changes were noted in the xylose absorption or metabolism tests. Mean interdefecatory intervals decreased by 32% from 31.7 to 21.6 h, the mean difference being 10.1 h (95% CI, 1.6–18.5 h; P=0.01). The mean stool form index increased from 2.95 to 4.70, mean difference 1.75 (95% CI, 1.10–2.40; P<0.0001), with four patients reporting diarrhoea.

Conclusion: The results indicate that conventional treatment for duodenal ulcers with a proton pump inhibitor significantly increases bacterial colonization of the duodenum and the speed of intestinal transit.
Helicobacter pylori eradication using one‐week low‐dose lansoprazole plus amoxycillin and either clarithromycin or azithromycin
Authors: CAMMAROTA G. , TURSI A. , PAPA A. , MONTALTO M. , VENETO G. , CUOCO L. , FEDELI G. , GASBARRINI G.
Published: October 2003

Aim: To evaluate and compare two 1‐week low‐dose triple therapies based on lansoprazole, amoxycillin and a macrolide in eradicating Helicobacter pylori.

Methods: Seventy consecutive patients, suffering from dyspeptic symptoms with H. pylori infection, were randomly allocated to one of two treatment groups: (A) (LAC; n=35) lansoprazole 30 mg once daily, amoxycillin 1000 mg b.d., clarithromycin 250 mg b.d., all for 7 days; and (B) (LAA; n=35) lansoprazole 30 mg once daily and amoxycillin 1000 mg b.d., both for 7 days, plus azithromycin 500 mg once daily for only 3 days. The H. pylori status was evaluated by means of histology and rapid urease test at entry and 8 weeks after treatment.

Results: Three patients did not complete the treatment: one in the LAC group was withdrawn owing to severe side‐effects; two patients in the LAA group stopped the treatment prematurely. H. pylori eradication was obtained in 28 of 34 (82%; 95% CI=66–93%) patients in the LAC group and in 20 of 33 (61%; 95% CI=42–77%) patients in the LAA group. The difference is significant (P<0.029). On intention‐to‐treat analysis, the rates of eradication were (28 of 35 patients, 80% in the LAC group and 20 of 35 patients, 57% in the LAA group. Side‐effects occurred in nine (26%) and six (18%) patients in the LAC and LAA groups, respectively.

Conclusions: Low‐dose lansoprazole plus amoxycillin and clarithromycin is more effective than low‐dose lansoprazole plus amoxycillin and azithromycin, but it gave a greater incidence of side‐effects.
Tilidine does not affect human sphincter of Oddi motility—a randomized, controlled study
Authors: WEHRMANN T. , RAUSCH D. , SEILER K. U. , BRENNSCHEIDT U. , CASPARY W. F.
Published: October 2003

Aim:

To investigate the effects of intravenous pentazocine and tilidine on sphincter of Oddi motility.

Methods:

Twenty patients with suspected sphincter of Oddi dysfunction were enrolled in a prospective, double‐blind study. Sphincter of Oddi motility was assessed by means of endoscopic manometry after injection of 0.9% saline, as well as after randomized dosing with either 30 mg pentazocine i.v. (n = 10) or 50 mg tilidine i.v. (n = 10).

Results:

Pentazocine significantly increased the sphincter of Oddi baseline pressure from 32 ± 21 mmHg (saline) to 41 ± 19 mmHg (P = 0.002), whereas tilidine did not alter the sphincter baseline pressure (34 ± 15 mmHg saline vs. 36 ± 16 mmHg tilidine, P = 0.16). Furthermore, pentazocine increased the phasic sphincter contraction amplitude (108 ± 16 mmHg saline vs. 121 ± 18 mmHg pentazocine, P = 0.004), but tilidine was without any effect (125 ± 24 mmHg saline vs. 125 ± 21 mmHg tilidine, P = 0.93). The phasic sphincter of Oddi contraction frequency and duration were not influenced either by pentazocine or by tilidine.

Conclusion:

In contrast to 30 mg of pentazocine, 50 mg of tilidine does not affect sphincter of Oddi motility. Therefore, tilidine can be used during endoscopic manometry and for analgesia in pancreatobiliary disease.
The influence of age, gender, Helicobacter pylori and smoking on gastric mucosal adaptation to non‐steroidal anti‐inflammatory drugs
Authors: LIPSCOMB G. R. , CAMPBELL F. , REES W. D. W.
Published: October 2003

Introduction:

Oral NSAIDs cause acute gastric injury that resolves, despite continued administration, by a process known as adaptation. Little is known about the factors that influence this process.

Methods:

Sixty‐two healthy volunteers were given a 28‐day course of either etodolac 300 mg b.d. (13 subjects), naproxen 500 mg b.d. (23), enteric‐coated diclofenac (10) or effervescent diclofenac 50 mg b.d. (16). All subjects were gastroscoped before and on days 1, 7 and 28 during drug administration, to assess gastric mucosal damage using a modified Lanza scale. Subjects were then divided into three categories: those who adapted completely, those who adapted incompletely and those who showed no adaptation. The proportion of subjects in each group was compared with respect to age, gender, smoking, the presence of Helicobacter pylori, and the NSAID prescribed.

Results:

Fifty‐nine subjects (median age 25.0 years, range 18–70) developed initial gastric injury to NSAIDs of whom 42 adapted completely, 13 adapted incompletely and four showed no evidence of adaptation. The mean age of subjects was lower in those who adapted (26.8 ± 9.8 years) than those who adapted incompletely (32.5 ± 10.3 years) and those who did not adapt (42.0 ± 15.7 years, P = 0.01). There was no evidence of gender influencing adaptation. Of 17 H. pylori‐positive subjects, a higher proportion had incomplete adaptation, with only nine subjects adapting completely (53% vs. 81%, P = 0.04). Sixteen subjects were smokers, of whom a greater proportion showed no evidence of adaptation (19% vs. 2%, P = 0.03). A smaller proportion of those who took naproxen (48%) adapted completely than those who took enteric‐coated diclofenac (89%), effervescent diclofenac (75%) or etodolac (91%, P = 0.03).

Conclusion:

Some adaptation occurred in over 90% of subjects after 4 weeks dosing with an NSAID, but adaptation was less frequent in older subjects and in smokers. Complete adaptation occurred less frequently in H. pylori‐positive subjects and in those who were given naproxen.