bluuebunny/crossref_metadata_2025 huggingface dataset:
Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects
Authors: Coulie B. , Camilleri M. , Bharucha A. E. , Sandborn W. J. , Burton D.
Published: March 2003

Background:

Nicotine decreases diarrhoea and pain in ulcerative colitis without reducing inflammation.

Aims:

(i) To evaluate the effect of ulcerative proctosigmoiditis on motor functions of an uninflamed segment of descending colon; and (ii) to assess nicotine’s effects on colonic motor functions in patients and healthy subjects.

Methods:

In healthy subjects (n=30) and patients with ulcerative colitis (13; 11 active, two quiescent colitis), we studied the effects of intravenous nicotine on colonic transit of solid residue by scintigraphy (healthy subjects) and on colonic motility in healthy subjects and 11 patients.

Results:

In ulcerative colitis, fasting colonic motility was increased, whereas motor response to a meal was significantly reduced; compliance was unchanged. In healthy subjects, high‐dose nicotine induced transient high amplitude propagated contractions and relaxation of the descending colon followed by decreased phasic contractions. This dose also accelerated colonic transit. Low‐dose nicotine (mimicking a transdermal nicotine patch) reduced colonic compliance in healthy subjects, but did not affect motor function in ulcerative colitis.

Conclusions:

Ulcerative proctosigmoiditis increases fasting colonic motility and reduces tone response to a meal in the descending colon without affecting colonic compliance, suggesting changes in physiological responses but not intrinsic wall properties. Nicotine has dose‐dependent effects on colonic motor activity in healthy subjects.
Polaprezinc attenuates the Helicobacter pylori‐induced gastric mucosal leucocyte activation in Mongolian gerbils—a study using intravital videomicroscopy
Authors: Suzuki H. , Mori M. , Seto K. , Miyazawa M. , Kai A. , Suematsu M. , Yoneta T. , Miura S. , Ishii H.
Published: March 2003

Background:

We previously demonstrated that Helicobacter pylori colonization evokes gastric mucosal inflammation and an extensive increase in lipid peroxides and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have been reported to be potent antioxidants in gastric mucosa.

Aim:

To examine the effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori‐colonized Mongolian gerbils.

Methods:

Sixty‐eight male Mongolian gerbils were orally inoculated with H. pylori (ATCC43504, 5 × 108 CFUs/gerbil; H. pylori group) and 35 gerbils were inoculated with the culture media (control group). Twenty‐two gerbils in the H. pylori and 13 gerbils in the control group were fed with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils were fed a standard laboratory chow diet. Neutrophil infiltration, assessed histologically and by the activity of myeloperoxidase, the contents of CXC‐chemokine (GRO/CINC‐1‐like protein) and the contents of thiobarbituric acid‐reactive substances, was evaluated in each group 12 weeks after the inoculation. Separately, gastric mucosal leucocyte activation and capillary perfusion were also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the inoculation.

Results:

In all H. pylori‐inoculated animals, the bacterial infection persisted throughout the experimental period. Gastric mucosal lesion formation in the H. pylori group was significantly inhibited in the H. pylori + polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC‐1 and thiobarbituric acid‐reactive substances in the H. pylori group at 12 weeks were attenuated significantly by polaprezinc treatment. Enhanced levels of venular leucocyte activation observed in the H. pylori group were attenuated significantly in the H. pylori + polaprezinc group during both the early phase (2 weeks) and late phase (12 weeks).

Conclusion:

Polaprezinc inhibited H. pylori‐associated gastric mucosal oxidative inflammation, including initial micro‐vascular leucocyte activation, in Mongolian gerbils.
Erythromycin as a prokinetic agent in infants and children
Authors: Curry J. I. , Lander T. D. , Stringer M. D.
Published: March 2003

Erythromycin has been used as an antibiotic for more than four decades, but only in the last 10 years have other therapeutic benefits of this agent been exploited. Animal and human studies have demonstrated a prokinetic effect on the gastrointestinal tract at sub‐antimicrobial doses (typically a quarter or less of the antibiotic dose). A limited number of studies have been performed in children to investigate this action. A review of this literature is particularly pertinent given the frequency of clinical problems related to gastrointestinal dysmotility in children and the limited availability of prokinetic agents in paediatric practice, compounded by the recent withdrawal of cisapride.

The prokinetic effects of erythromycin have been investigated in infants with dysmotility associated with prematurity, in low birth‐weight infants recovering from abdominal surgery, and in older children with a variety of other gastrointestinal disorders. Only one randomized placebo‐controlled trial has been conducted. All except one of these studies have shown a beneficial effect of erythromycin in either promoting tolerance of enteral feeds or enhancing a measured index of gastrointestinal motility. Erythromycin appears to be equally effective when given orally (as ethylsuccinate or estolate) or intravenously (as lactobionate). Significantly, no serious adverse effects have been reported in studies in which erythromycin has been used for its prokinetic effects, although fatal reactions have followed the intravenous administration of erythromycin to neonates in antibiotic doses.
Colon cleansing preparation for gastrointestinal procedures
Authors: Toledo T. K. , Dipalma J. A.
Published: March 2003

Adequate cleansing is essential for reliable diagnostic and surgical colon procedures. Accuracy and safety depend on good preparation. Patient compliance is enhanced by simplicity and well‐tolerated methods.

Several methods are available. Diet and cathartic regimens utilize clear liquids or diets designed to leave a minimal colonic residue. Laxatives, cathartics and enemas are employed. Gut lavage solutions are osmotically balanced electrolyte lavage products. Oral sodium phosphate solutions and tablets are available and are attractive because of good efficacy with a small volume of administration.

For colonoscopy and colon surgery preparation, these methods have been proven safe and effective. For barium enema X‐ray, lavage requires an adjunctive agent such as bisacodyl to enhance barium coating. Overall, all regimens are well‐tolerated.

This review discusses the development and clinical experience with various colon cleansing regimens.
Control of intragastric pH with omeprazole 20 mg, omeprazole 40 mg and lansoprazole 30 mg
Authors: Katz P. O. , Xue S. , Castell D. O.
Published: March 2003

Background:

Single daily doses of proton pump inhibitors, omeprazole and lansoprazole provide effective acid suppression and equal healing and symptom relief in patients with GERD. Despite this, controversy exists as to the efficacy of available proton pump inhibitors in the control of gastric acidity.

Aim:

To assess the efficacy of omeprazole 20 mg vs. lansoprazole 30 mg and omeprazole 40 mg vs. lansoprazole 30 mg in intragastric pH control.

Methods:

Study I: 12 Helicobacter pylori‐negative volunteers (mean age 33 years) were treated with omeprazole 20 mg and lansoprazole 30 mg in random order before breakfast for 7 days. Study II: 24 subjects (mean age 36 years) were similarly treated with omeprazole 40 mg and lansoprazole 30 mg for 7 days after a baseline pH study. One week washout was allowed between studies. Subjects had the same meal on each study day. On day seven, a 24‐h intragastric pH study was performed. The percentage time for which gastric pH > 4 was analysed (Gastrosoft, Synectics Medical Inc.) and expressed as mean ± s.d.

Results:

(1) Omeprazole 20 mg and lansoprazole 30 mg showed no significant difference in the percentage time for which gastric pH > 4 in the daytime and night‐time periods. (2) The percentage time for which pH > 4 with omeprazole 40 mg was significantly greater than lansoprazole 30 mg in both daytime (61 ± 19% vs. 48 ± 14%, P < 0.001), and night‐time periods (34 ± 21% vs. 26 ± 14%, P < 0.05). (3) A large inter‐subject variation existed in both studies. (4) In 10 subjects who participated in both studies, omeprazole 40 mg showed a significantly higher percentage time for which pH > 4 in the daytime (69 ± 18% vs. 51 ± 15%, P=0.015) than omeprazole 20 mg.

Conclusion:

These pH data support the therapeutic equivalency of FDA approved doses of omeprazole and lansoprazole.
The therapy of constipation
Authors: Schiller L. R.
Published: March 2003

Constipation is a common symptom that may be idiopathic or due to various identifiable disease processes. Laxatives are agents that add bulk to intestinal contents, that retain water within the bowel lumen by virtue of osmotic effects, or that stimulate intestinal secretion or motility, thereby increasing the frequency and ease of defecation. Drugs which improve constipation by stimulating gastrointestinal motility by direct actions on the enteric nervous system are under development. Other modalities used to treat constipation include biofeedback and surgery. Laxatives and lavage solutions are also used for colon preparation and evacuation of the bowels after toxic ingestions.
The effect of Helicobacter pylori eradication therapy on dyspepsia symptoms in industrial workers in Japan
Authors: Azuma T. , Ito Y. , Suto H. , Ohtani M. , Dojo M. , Muramatsu A. , Kuriyama M. , Kato T.
Published: March 2003

Background:

The relationship between Helicobacter pylori infection and non‐ulcer dyspepsia is still controversial. The potential benefits and risks of the treatment could depend on local conditions, such as the prevalence of the infection and the local rates of gastric cancer.

Aim:

To evaluate the effects of H. pylori eradication therapy on non‐ulcer dyspepsia symptoms in industrial workers in Japan.

Methods:

A total of 615 employees of an industrial corporation were examined for H. pylori infection and symptom scores; 215 H. pylori‐positive non‐ulcer dyspepsia cases underwent eradication therapy. Symptom scores were also analysed 12 months after the eradication therapy. Serum pepsinogen A and pepsinogen C levels were analysed and chronic atrophic gastritis was serologically diagnosed on the basis of the criteria of a pepsinogen A < 70 ng/mL and pepsinogen A : pepsinogen C ratio < 3.0.

Results:

The symptom score improved significantly in the cured cases, but not in the non‐cured cases. The effect of the cure of H. pylori infection on symptoms was analysed according to the serological diagnosis of chronic atrophic gastritis. In both groups, cases with atrophic gastritis and cases with chronic gastritis only, the cure of infection was effective in improving symptoms.

Conclusion:

The cure of H. pylori infection was effective in reducing non‐ulcer dyspepsia symptoms in industrial workers in Japan.
Impaired bioavailability of vitamin A in adults and children with persistent diarrhoea in Zambia
Authors: Kelly P. , Musuku J. , Kafwembe E. , Libby G. , Zulu I. , Murphy J. , Farthing M. J. G.
Published: March 2003

Background:

We have previously demonstrated a strong relationship between low serum retinol concentration and mortality in Zambian AIDS patients with diarrhoea, but were unable to detect any benefit from oral micronutrient supplementation.

Aim:

To test the hypothesis that this is related to impaired availability of vitamin A, we analysed serum retinol concentration changes over 6 h following oral mega‐dose therapy (60, 120 or 180 mg retinol).

Methods:

Twenty‐four men without diarrhoea, 15 adults with persistent diarrhoea and 11 children (six girls, five boys) with persistent diarrhoea were studied.

Results:

Men with persistent diarrhoea had lower baseline serum retinol concentrations (median 0.39 μmol/L, interquartile range 0.21–0.56) than controls (median 1.16 μmol/L, interquartile range 0.84–1.47; P=0.0003). After 60 mg retinol, the rise in serum retinol in HIV seropositive controls (median 0.63 μmol/L, interquartile range 0.35–0.77) did not differ significantly from that observed in HIV seronegative controls (median 0.35 μmol/L, interquartile range – 0.04–0.56; P=0.20). Increasing the dose to 120 mg or 180 mg retinol did not enhance the increase in serum retinol concentration. The increase in serum retinol was less in adults with persistent diarrhoea (median 0.25 μmol/L, interquartile range 0.04–0.35) and in children (median 0.11 μmol/L, interquartile range 0.04–0.46) than in men without diarrhoea (median 0.44 μmol/L, interquartile range 0.26–0.74; P=0.03). Adults and children with diarrhoea had greater losses of retinol in urine over a 24‐h period than controls, but less than 1% of the ingested dose was excreted.

Conclusions:

These results suggest that persistent diarrhoea in this population is associated with reduced bioavailability of retinol. Further work is required to determine the metabolic fate of therapeutic doses of retinol and to determine appropriate replacement strategies for HIV infected individuals.
The effect of cholecystokinin antagonism on postprandial lower oesophageal sphincter function in asymptomatic volunteers and patients with reflux disease
Authors: Trudgill N. J. , Hussain F. N. , Moustafa M. , Ajjan R. , D'Amato M. , Riley S. A.
Published: March 2003

Background:

Postprandial acid reflux is thought to be mediated by the increase in transient lower oesophageal sphincter relaxations (TLOSR) frequency and fall in lower oesophageal sphincter (LOS) pressure seen after ingestion of a meal. Studies in animals and healthy volunteers suggest that cholecystokinin (CCK) may play a role.

Aim:

To study the role of CCK in postprandial LOS function using the CCK antagonist loxiglumide.

Subjects:

10 asymptomatic volunteers (7 male, 20–29 years) and 9 patients with symptomatic gastro‐oesophageal reflux (4 male, 33–66 years).

Methods:

Oesophageal, LOS and gastric pressure and oesophageal pH readings were recorded for 1 h before and 2 h after intragastric infusion of a 200 kCal, 300 mL long chain triglyceride meal. Each subject underwent two studies and received intravenous loxiglumide or placebo infusion in randomized order.

Results:

During placebo infusion, postprandial LOS pressure fell [volunteers: 17 (9–31) to 7 (1–19) mmHg (P < 0.01), patients: 15 (6–26) to 9 (2–21) mmHg (P=0.02)] and TLOSR frequency increased [volunteers: 0 (0–1) to 2 (0–7) per hour (P=0.01), patients: 0 (0–3) to 2 (0–10) per hour (P=0.03)]. Loxiglumide infusion attenuated the postprandial fall in LOS pressure and the postprandial increase in TLOSR frequency [volunteers: 0 (0–3) per hour (P=0.04 vs. placebo), patients: 0 (0–2) per hour (P=0.03 vs. placebo)], but it had only modest effects on postprandial acid exposure [volunteers: placebo 45 (0–1725) vs. loxiglumide 0 (0–443) seconds (N.S.), patients: placebo 60 (0–3442) seconds vs. loxiglumide 31 (0–1472) seconds (N.S.)].

Conclusions:

Loxiglumide inhibits TLOSR and attenuates the fall in LOS pressure following a meal, but has only modest effects on postprandial gastro‐oesophageal acid reflux.
Citric acid‐enhanced Helicobacter pylori urease activity in vivo is unrelated to gastric emptying
Authors: Shiotani A. , Saeed A. , Yamaoka Y. , Osato M. S. , Klein P. D. , Graham D. Y.
Published: March 2003

Background:

In a previous study, the use of a citric acid test meal produced a rapid dose‐dependent increase in urease activity that was significantly greater than that resulting from a pudding meal, ascorbic acid or sodium citrate. The mechanism was hypothesized to be related to the ability of citric acid to delay gastric emptying and possibly to enhance intragastric distribution of the urea.

Objective:

To compare the effects of sodium citrate, two doses of citric acid and a pudding meal on gastric motor function.

Method:

Eleven normal healthy volunteers were investigated using non‐invasive techniques to measure gastric emptying and gastric motility. We evaluated gastric emptying using the Meretek 13Ceebiscuit solid phase gastric emptying breath test, which employs a 340‐calorie biscuit containing 200 mg of the edible 13C‐blue–green alga Spirulina platensis, after the administration of test meals of pudding, 2 g and 4 g of citric acid and 2 g of sodium citrate. Electrogastrograms (Digitrapper EGG) were also recorded for 30 min before and 180 min after the test meal.

Results:

Gastric emptying, as assessed by the half‐time (T1/2), was delayed similarly with the pudding (136.8 ± 9 min) and with 4 g of citric acid (144.5 ± 7 min) (P > 0.7). Sodium citrate (108.7 ± 6 min) and 2 g of citric acid (110.1 ± 6 min) had similar effects on gastric emptying (P=0.986), and were significantly less effective in delaying gastric emptying (P < 0.01) compared to pudding or 4 g of citric acid. The electrogastrograms remained normal and there were no differences among meals and no relation with the gastric emptying results.

Conclusions:

The increased intragastric urea hydrolysis associated with citric acid test meals cannot be attributed to delayed gastric emptying. Changes in the intragastric distribution of urea or a direct effect of citric acid on the bacteria (e.g. via the cytoplasmic protein, UreI) are more likely to be responsible.
Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced colitis
Authors: Carrier J. , Aghdassi E. , Platt I. , Cullen J. , Allard J. P.
Published: March 2003

Background:

Iron supplementation may increase disease activity in ulcerative colitis, possibly through the production of reactive oxygen species from the Fenton reaction.

Aim:

To assess the effects of two doses of oral iron on intestinal inflammation and oxidative stress in experimental colitis.

Methods:

Colitis was induced in rats by giving 5% dextran sulphate sodium in drinking water for 7 days. First, using a 2 × 2 factorial design, rats with or without dextran sulphate sodium received the regular diet or a diet containing iron 3%/kg diet. Second, rats with dextran sulphate sodium‐induced colitis were supplemented with iron 0.3%/kg diet and compared with rats on dextran sulphate sodium and regular diet. The body weight change, histological scores, colon length, rectal bleeding, plasma and colonic lipid peroxides, colonic glutathione peroxidase and plasma vitamin E and C were measured. Faecal analysis for haem and total, free and ethylenediaminetetra‐acetic acid‐chelatable iron was also performed.

Results:

Iron 3% and iron 0.3% increased the activity of dextran sulphate sodium‐induced colitis, as demonstrated by higher histological scores, heavier rectal bleeding and further shortening of the colon. This was associated with increased lipid peroxidation and decreased antioxidant vitamins. Faecal iron available to the Fenton reaction was increased in a dose‐dependent manner.

Conclusions:

Iron supplementation taken orally enhanced the activity of dextran sulphate sodium‐induced colitis and is associated with an increase in oxidative stress.
Helicobacter pylori eradication is superior to ulcer healing with or without maintenance therapy to prevent further ulcer haemorrhage
Authors: Sharma V. K. , Sahai A. V. , Corder F. A. , Howden C. W.
Published: March 2003

Background:

Helicobacter pylori eradication decreases ulcer recurrence and should prevent recurrent ulcer haemorrhage.

Aim:

By meta‐analysis, to compare treatment of H. pylori infection with other approaches to prevent recurrent ulcer haemorrhage and, by cost minimization analysis, to determine the least costly strategy.

Methods:

We searched for randomized, controlled trials comparing treatment of H. pylori infection with ulcer healing alone or with maintenance therapy in preventing recurrent ulcer haemorrhage. We calculated the relative and absolute risk reductions and numbers needed to treat.

Results:

Treatment of H. pylori infection decreased recurrent bleeding by 17% (numbers needed to treat=6) compared with ulcer healing treatment alone. Compared with ulcer healing treatment followed by maintenance therapy, recurrent bleeding was decreased by 4% (numbers needed to treat=25). Decision model‐based cost minimization analysis demonstrated that treatment of H. pylori infection was the least costly strategy unless the incidence of complicated recurrences after treatment was over 6%, or the cost of confirming eradication was over $741.

Conclusions:

Treatment of H. pylori infection is superior to ulcer healing treatment with or without maintenance therapy in preventing recurrent ulcer haemorrhage. All patients with ulcer bleeding should be tested for H. pylori infection and appropriately treated if positive.
Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?
Authors: Netzer P. , Gaia C. , Lourens S. T. , Reber P. , Wildi S. , Noelpp U. , Ritter E. P. , Ledermann H. , Lüscher D. , Varga L. , Kinser J. A. , Büchler M. W. , Scheurer U.
Published: March 2003

Background:

In previous studies, tropisetron has been shown to accelerate gastric emptying of a solid meal. However, it is uncertain whether other specific 5‐hydroxytryptamine‐3 receptor antagonists, such as ondansetron, also have a gastroprokinetic effect in humans.

Aim:

To evaluate the effect of ondansetron on gastric half‐emptying time (T1/2) of a solid meal, gastric myoelectrical activity and hormone levels in 14 healthy volunteers.

Methods:

In a placebo‐controlled, randomized, crossover study, we investigated the effects of ondansetron (8 mg intravenously) on the gastric emptying of solids (by scintigraphy), gastric myoelectrical activity (by electrogastrography) and the post‐prandial release of cholecystokinin, gastrin, human pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, substance P and galanin.

Results:

The average T1/2 values were 86 min and 85.5 min without lag time (P=0.082) and 92 min and 93 min with lag time (P=0.158) for the placebo and ondansetron treatments, respectively. The average T1/2 of female volunteers was significantly longer than that of male volunteers. The dominant gastric electrical frequency and hormone plasma concentrations were not altered by ondansetron.

Conclusions:

Ondansetron did not affect the gastric emptying of solids, the dominant gastric electrical frequency or the plasma concentrations of the analysed gastrointestinal peptides.
The complexity of drug development for irritable bowel syndrome
Authors: Kamm M. A.
Published: March 2003

Drug development for functional gastrointestinal disorders is complex. These conditions involve central and peripheral physiological changes, together with psychological factors. Methodological problems have included a poor appreciation of the physiological and psychological correlates of patients' symptoms, a lack of animal models of proven relevance, and safety issues. Government, patient pressure groups and the Internet can also influence a drug's success. Most recent interest has focused on the serotonin (5‐HT) modifying drugs. Cisapride has been withdrawn in some countries because of concerns related to QT prolongation and cardiac arrhythmias. The 5‐HT3 antagonists, developed to modify visceral sensation, have caused constipation; alosetron, also withdrawn, caused ischaemic colitis. The 5‐HT4 agonists induce peristalsis; tegaserod and prucalopride, both delayed in their development due to issues of safety and efficacy, benefit patients with `constipation‐predominant' irritable bowel syndrome or idiopathic constipation. 5‐HT1 agonists improve impaired gastric accommodation and symptoms in patients with functional dyspepsia. Antidepressants also affect serotonin metabolism. Previous examples of success in this area involved drugs targeted at peripheral receptors mediating motor function or secretion. Modification of sensory function is a much more challenging objective. The experience with serotonin modifying drugs has been mixed, and some important lessons are there to be learnt.
Haemodynamic effects of acute and chronic administration of low‐dose carvedilol, a vasodilating β‐blocker, in patients with cirrhosis and portal hypertension
Authors: Tripathi D. , Therapondos G. , Lui H. F. , Stanley A. J. , Hayes P. C.
Published: March 2003

Background:

Carvedilol is a non‐selective vasodilating β‐blocker with weak α1 receptor antagonism. Recent studies have demonstrated its potential as a portal hypotensive agent.

Aim:

To assess the haemodynamic effects and patient tolerability of the acute and chronic administration of low‐dose carvedilol.

Methods:

Haemodynamic measurements were performed in ten cirrhotic patients before and 1 h after the administration of 12.5 mg oral carvedilol. The study was repeated 4 weeks after daily administration of 12.5 mg carvedilol.

Results:

After acute administration of carvedilol, there was a 23% reduction in the hepatic venous pressure gradient from 16.37 ± 2.14 to 12.56 ± 3.91 mmHg (P < 0.05), with significant falls in the heart rate, mean arterial pressure and cardiac output. Chronic administration resulted in a further fall in the hepatic venous pressure gradient from a baseline of 16.37 ± 0.71 to 9.27 ± 1.40 mmHg (P < 0.001) with the mean arterial pressure being unaffected. The drug was well tolerated with only one patient experiencing asymptomatic hypotension.

Conclusions:

The results show that low‐dose carvedilol is an extremely potent portal hypotensive pharmacological agent, and is worthy of further investigation in large randomized trials to assess its effect in preventing variceal haemorrhage.
The effect of regular medication on the outcome of paracetamol poisoning
Authors: Schmidt L. E. , Dalhoff K.
Published: March 2003

Background : Patients admitted with paracetamol overdose frequently receive one or more types of regular medication that may affect the outcome of the paracetamol intoxication.

Aim : To describe the use of regular medication in patients with paracetamol poisoning and to evaluate its effects on morbidity and mortality.

Methods : Seven hundred and thirty‐seven consecutive patients admitted with paracetamol poisoning were studied and the use of regular medication was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, severe hepatic dysfunction and severe hepatocellular injury was evaluated by multivariate analysis.

Results : Regular medication was received by 332 patients (45%). Medication with benzodiazepines (105 cases), antidepressants (100 cases), neuroleptics (75 cases), paracetamol (58 cases), oral contraceptives (51 cases), beta‐agonists (40 cases), opioid analgesics (32 cases) and anticonvulsants (27 cases) predominated. Regular medication with opioid analgesics was associated with a high incidence of hepatic dysfunction (odds ratio, 5.39; 95% confidence interval, 1.13–25.8). No significant findings were demonstrated for benzodiazepines, antidepressants, neuroleptics, paracetamol, oral contraceptives, beta‐agonists or anticonvulsants in the multivariate analysis.

Conclusions : Regular medication with psychotropic medication, analgesics, oral contraceptives, beta‐agonists or anticonvulsants was frequent in patients admitted with paracetamol poisoning. Medication with opioid analgesics was associated with a significantly increased incidence of hepatic dysfunction, whereas the other medications did not appear to affect the outcome of the paracetamol intoxication.
Octreotide enhances the accelerating effect of erythromycin on gastric emptying in healthy subjects
Authors: Athanasakis E. , Chrysos E. , Zoras O. J. , Tsiaoussis J. , Karkavitsas N. , Xynos E.
Published: March 2003

Background : Erythromycin exhibits gastrokinetic properties through cholinergic pathways. Reports regarding the action of octreotide on gastric emptying are conflicting.

Aim : To assess: (i) the hypothesis that serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying; and (ii) any modification of the gastrokinetic action of erythromycin induced by octreotide.

Subjects and methods : Gastric emptying of a standard meal was estimated in 20 healthy subjects by scintigraphy on three different occasions in a double‐blind, placebo‐controlled manner and in random order: (i) after placebo; (ii) after 200 mg of intravenous erythromycin; and (iii) after 200 mg of intravenous erythromycin following pre‐treatment with either 4 mg of intravenous ondansetron (10 subjects) or 50 µg octreotide.

Results : Erythromycin significantly accelerated gastric emptying in all subjects by abolishing the lag phase. Pre‐treatment with ondansetron abolished the accelerating effect of erythromycin by restoring the emptying times to placebo levels. Octreotide significantly enhanced the accelerating effect of erythromycin by reducing both the lag and post‐lag phases of gastric emptying.

Conclusions : Serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying. This effect seems to be enhanced by pre‐treatment with octreotide, possibly as a result of the modification of the gastrointestinal hormonal environment.
Biological agents in the treatment of Crohn's disease
Authors: Caprilli R. , Viscido A. , Guagnozzi D.
Published: March 2003

The main aim of the management of Crohn's disease is to reduce inflammation. Current approaches with corticosteroids, immunosuppressive agents, mesalazine and antibiotics have limited therapeutic benefit for many patients. Considerable progress has been made with regard to our knowledge of the basic mechanisms of the disease, which is associated with immunological imbalance characterized by an excess of pro‐inflammatory cytokines.

Recent advances in bio‐technology have led to the development of many new therapeutic agents, so‐called biological agents, which selectively target single key processes involved in the pathogenesis of the disease. A growing number of biological agents are under investigation in both randomized controlled trials and uncontrolled studies. The aim of this review is to provide the clinician with an insight into the randomized controlled trials published in the literature on the use of biological agents in the treatment of Crohn's disease.
Azathioprine or methotrexate in the treatment of patients with steroid‐dependent or steroid‐resistant ulcerative colitis: results of an open‐label study on efficacy and tolerability in inducing and maintaining remission
Authors: Paoluzi O. A. , Pica R. , Marcheggiano A. , Crispino P. , Iacopini F. , Iannoni C. , Rivera M. , Paoluzi P.
Published: March 2003

Background : The role of azathioprine and methotrexate in inducing and maintaining remission in patients with ulcerative colitis is still controversial.

Aim : To evaluate the efficacy and tolerability of these two drugs in a series of patients with steroid‐dependent or steroid‐resistant active ulcerative colitis.

Methods : Forty‐two patients were treated with a daily dose of azathioprine (2 mg/kg) and, if intolerant or not responding, with methotrexate (12.5 mg/week intramuscularly), and their efficacy was established by clinical, endoscopic and histological examinations at 6 months. Patients achieving clinical remission continued with treatment and were followed up.

Results : Of the 42 patients on azathioprine, 10 experienced early side‐effects requiring withdrawal from treatment, 22 (69%) achieved complete remission, six (19%) achieved improvement and four (12%) obtained no substantial benefit. Methotrexate, administered to eight patients intolerant to and two patients resistant to azathioprine, induced complete remission in six patients (60%) and improvement in four (40%). During follow‐up, a larger number of patients on azathioprine relapsed in comparison with patients on methotrexate [16/28 (57%) vs. 2/10 (20%), respectively; P < 0.05]. Only minor side‐effects wereobserved on both treatments.

Conclusions : Azathioprine is effective in patients with steroid‐dependent or steroid‐resistant ulcerative colitis. Methotrexate seems to be a good alternative in patients intolerant to or not responding to azathioprine.
Racial differences in the frequency of symptoms and complications of gastro‐oesophageal reflux disease
Authors: Spechler S. J. , Jain S. K. , Tendler D. A. , Parker R. A.
Published: March 2003

Background : A number of reports have suggested that there are substantial racial differences in the frequency of gastro‐oesophageal reflux disease and its complications, but few studies have compared directly the frequency of this disorder amongst different racial groups.

Aim : To explore the racial differences in the frequency of gastro‐oesophageal reflux disease and its complications.

Methods : We reviewed endoscopy reports and medical records for data on race and complications of gastro‐oesophageal reflux disease in 2477 consecutive patients who had endoscopic examinations at the general endoscopy unit of an academic hospital. In addition, we prospectively interviewed 129 out‐patients attending general medical clinics in the hospital and in an Asian community health centre in Boston to obtain data on race and gastro‐oesophageal reflux disease symptoms.

Results : One or more gastro‐oesophageal reflux disease complications (peptic oesophageal ulcer, stricture or Barrett's oesophagus) were observed in 267 of 2174 white patients (12.3%), seven of 249 black patients (2.8%), one of 21 West Asian patients (4.8%) and none of 33 East Asian patients seen at the general endoscopy unit (P < 0.001); 34.6% of whites, 46.1% of blacks and 2.6% of East Asian patients interviewed claimed that they had heartburn (P < 0.01), but the term ‘heartburn’ was understood by only 34.6%, 53.8% and 13.2% of whites, blacks and East Asians, respectively (P < 0.01).

Conclusions : Asian patients in Boston infrequently complain of heartburn, whereas heartburn is commonly reported by both white and black patients. Many patients do not understand the meaning of the term heartburn, however, and so physicians should be cautious when using the term during patient interviews. Complicated gastro‐oesophageal reflux disease appears to be predominantly a disorder of whites.
Fluorescence in situ hybridization vs. epsilometer test for detection of clarithromycin‐susceptible and clarithromycin‐resistant Helicobacter pylori strains in gastric biopsies from children
Authors: Feydt‐Schmidt A. , Rüssmann H. , Lehn N. , Fischer A. , Antoni I. , Störk D. , Koletzko S.
Published: March 2003

Aim : To compare the results of culture and epsilometer test with fluorescence in situ hybridization for the detection of Helicobacter pylori and the presence of clarithromycin‐susceptible and clarithromycin‐resistant strains in antral biopsies from children.

Methods : Antral biopsies from 149 unselected children were investigated prospectively; 15 had previously received anti‐H. pylori therapy. H. pylori status was defined by histology, rapid urease test and 13C‐urea breath test. Fluorescence in situ hybridization was applied on fresh tissue with probes specific for the clarithromycin‐susceptible wild type and three clarithromycin‐resistant mutants. Susceptibility to clarithromycin was tested by epsilometer test in two laboratories.

Results : Culture and fluorescence in situ hybridization gave negative results in all 66 H. pylori‐negative children (specificity, 100%). Of 83 infected children, cultures were successful in 75 (90%), epsilometer test in 71 (86%) and fluorescence in situ hybridization in 77 (93%). Eleven children (13%) showed discrepant results between the applied methods, indicating mixed infection. Clarithromycin‐resistant isolates were identified in 16 of 73 previously untreated children.

Conclusions : Primary resistance to clarithromycin is common (22%) in H. pylori isolates from children living in Germany. Fluorescence in situ hybridization is an excellent, fast method for the detection of H. pylori and clarithromycin‐resistant mutants in gastric biopsies. Multiple biopsies identify mixed infections, indicating that clarithromycin‐resistant and clarithromycin‐ susceptible strains are not evenly distributed within the stomach.
Azathioprine without oral ciclosporin in the long‐term maintenance of remission induced by intravenous ciclosporin in severe, steroid‐refractory ulcerative colitis
Authors: Domènech E. , Garcia‐Planella E. , Bernal I. , Rosinach M. , Cabré E. , Fluvià L. , Boix J. , Gassull M. A.
Published: March 2003

Background : Intravenous ciclosporin is considered to be the only alternative to avoid surgery in severe, steroid‐refractory ulcerative colitis. In responders, some authors recommend a switch to oral ciclosporin to act as a ‘bridge’ until the therapeutic action of azathioprine is achieved for maintenance treatment.

Aim : To report the short‐ and long‐term outcome of intravenous ciclosporin‐responsive ulcerative colitis patients treated with oral azathioprine without oral ciclosporin.

Methods : The records of all patients treated with intravenous ciclosporin for severe, steroid‐refractory ulcerative colitis were reviewed. Responders following treatment with azathioprine but without oral ciclosporin as maintenance therapy were included. Patients with colonic cytomegalovirus infection and/or follow‐up of less than 1 year were excluded.

Results : Twenty‐seven patients were included. Steroids were discontinued in 24 (89%). The median follow‐up was 36 months. Eighteen (75%) patients presented mild or moderate relapses, which were easily managed with salicylates or steroids. Cumulative probabilities of relapse were 42%, 72% and 77% at 1, 3 and 5 years, respectively. Eleven (40.7%) patients underwent elective colectomy. Cumulative probabilities of colectomy were 29%, 35% and 42% at 1, 3 and 5 years, respectively. No opportunistic infections were observed.

Conclusions : Oral azathioprine seems to be enough to maintain long‐term remission induced by intravenous ciclosporin in patients with steroid‐refractory ulcerative colitis. The ‘bridging step’ with oral ciclosporin may not be necessary in this subset of patients, although a randomized controlled trial is warranted to confirm this hypothesis.
NSAIDs, gastroprotection and cyclo‐oxygenase‐II‐selective inhibitors*
Authors: Micklewright R. , Lane S. , Linley W. , McQuade C. , Thompson F. , Maskrey N.
Published: March 2003

In patients at high risk of NSAID‐associated serious upper gastrointestinal complications, gastroprotection with misoprostol or a proton pump inhibitor should be considered. Only misoprostol, 800 µg/day, has been shown to reduce serious upper gastrointestinal complications in a large clinical outcome trial. The benefit of Helicobacter pylori eradication in reducing NSAID‐associated gastrointestinal toxicity is controversial, and routine testing for and eradication of H. pylori in NSAID users are not currently advised.

The gastrointestinal safety of rofecoxib and celecoxib has been assessed in large clinical outcome trials which, on first analysis, show benefits over non‐selective NSAIDs in the incidence of serious upper gastrointestinal complications. However, longer term gastrointestinal data from the celecoxib study (CLASS) and cardiovascular adverse event data from the rofecoxib study (VIGOR) have questioned the risk–benefit profile of these new drugs and, until they are better understood, it seems sensible not to use them routinely in large numbers of individuals. The gastrointestinal safety of meloxicam and etodolac has not been adequately assessed in such trials. Therefore, evidence for their use instead of non‐selective NSAIDs, or instead of celecoxib or rofecoxib, is not robust.
Neuromuscular interactions between mivacurium and esmolol in rabbits
Authors: Kim K. S. , Kim K. H. , Shin W. J. , Yoo H. K.
Published: March 2003

We compared the dose–response relationship and the neuromuscular blocking effects of mivacurium during infusions of esmolol in 40 anaesthetised rabbits. Train‐of‐four stimuli were applied every 10 s to the common peroneal nerve and the force of contraction of the tibialis anterior muscle was measured. Plasma cholinesterase activity decreased by 13% after esmolol infusion. The ED95 of mivacurium increased significantly from 29 (4.8) μgkg−1 with placebo to 61 (9.8) μgkg−1 during esmolol 100 μgkg−1.min−1, 49 (8.2) μgkg−1 during esmolol 300 μgkg−1.min−1 and 54 (7.3) μgkg−1 during esmolol 500 μgkg−1.min−1, respectively (p < 0.001). The duration of neuromuscular block with mivacurium 0.16 mgkg−1 was prolonged by 30% with esmolol due to diminished plasma cholinesterase activity (p < 0.05). Heart rate and mean arterial blood pressure decreased by 15% with esmolol (p < 0.05). The results of this study show that, in rabbits, esmolol decreased plasma cholinesterase activity, antagonised the neuromuscular blocking potency of mivacurium and prolonged its neuromuscular blocking effect.
Body posture during simulated tracheal intubation
Authors: Matthews A. J. , Johnson C. J. H. , Goodman N. W.
Published: March 2003

Seventeen experienced anaesthetists and 15 novices were filmed intubating the trachea of a training manikin. Measurements were made of the distance from manikin's chin to subject's nose and of the angles at the elbow, the shoulder and of the forearm with the horizontal. Trained subjects stood further back (trained: median 43 cm, interquartile range 41–56 cm; novices 35 cm, 26–38 cm; Mann–Whitney U, p < 0.01), with a straighter arm (trained elbow angle: 108°, 99–121°; novices': 92°, 88–102°; Mann–Whitney U, p < 0.01). Trained subjects tended to hold the laryngoscope closer to the hinge, with a pincer grip; novices were more likely to use a full grip of the handle. Trainers should consider giving novices explicit intructions on how to stand and how to hold the laryngoscope.
Pain on injection of propofol
Authors: Tan C. H. , Onsiong M. K.
Published: March 2003

Pain on injection of propofol is a common problem, the cause of which remains unknown. The chemical properties and preparation of propofol, proposed mechanisms for the cause of the pain and clinical strategies to prevent pain on injection of propofol are reviewed in the hope of shedding some light on the subject.
Anaesthesia for video‐assisted thoracoscopic patent ductus arteriosus ligation
Authors: Shaw A. D. S. , Mitchell J. B.
Published: March 2003

The case notes of children undergoing video‐assisted thoracoscopic ligation of a patent ductus arteriosus were reviewed with particular emphasis on the anaesthetic management. All children were managed using one‐lung ventilation with no serious adverse sequelae. The lungs could be isolated easily in all cases and no special equipment was required. We describe our initial series of 13 cases and discuss the anaesthetic implications arising from this surgical technique. We also discuss the different ways of monitoring duct closure.
Phosphate poisoning by ingestion of clothes washing liquid and fabric conditioner
Authors: Vincent J. C. , Sheikh A.
Published: March 2003

A case of deliberate ingestion of clothes washing liquid and fabric conditioner is described. Tracheal intubation and controlled ventilation became necessary because of respiratory muscle dysfunction associated with hypocalcaemia. We suggest that the phosphate component of the clothes washing liquid was responsible for the dramatic metabolic upset and subsequent need for admission to the Intensive Care Unit.
Impedance cardiographyThe impact of new technology
Authors: Critchley L. A. H.
Published: March 2003

The 1990s have witnessed major advances in impedance cardiography technology. Problems existed with the methods used to calculate cardiac output. Excessive lung fluid, as often found in critically ill patients, may also invalidate measurements. The signal processing and measurement techniques used in older systems were deficient. The newer systems, of which there are at least six, incorporate novel and improved signal processing techniques. They also offer analog visual displays, personal computer interfacing, sophisticated analytical software and haemodynamic patient management systems. Evaluation of these systems is difficult because no true ‘gold standard’ method of cardiac output measurement exists. When compared with thermodilution techniques, limits of agreement of ± 20–30% seem acceptable. These limits can be achieved in normal subjects but not in critically ill patients. Validation data are available for only half of the new systems. Until recently, the main application for impedance cardiography has been research but improved accuracy should lead to increased clinical usage.
Reasons for withdrawing treatment in patients receiving intensive care
Authors: Manara A. R. , Pittman J. A. L. , Braddon F. E. M.
Published: March 2003

We studied the frequency with which treatment was withdrawn in intensive care patients and the primary reason for reaching this decision. The medical records of patients having had active treatment withdrawn between August 1992 and February 1996 inclusive were reviewed. Patients were classified into an imminent death group consisting of those expected to die, a qualitative group who had treatment withdrawn on quality of life considerations and a lethal conditions group who had associated disease that precluded long‐term survival. There were 1745 patients admitted, of whom 338 (19.4%) died in ICU. In 220 patients death followed the withdrawal of treatment (12.6% of all ICU admissions), 203 dying on ICU (60% of ICU deaths) and a further 17 soon after discharge to a ward. The primary reason for treatment withdrawal was imminent death in 45% of patients, qualitative considerations in 50% and lethal conditions in 5%. The reason varied significantly depending on the patient's age. Treatment is withdrawn commonly in ICU, the primary reason being quality of life considerations as often as because death is the expected outcome.
Use of the flexible intubating fibrescope for tracheal re‐intubation in a patient with difficult extubation
Authors: Popat M. T. , Dravid R. M. , Watt‐Smith S. R.
Published: March 2003

Difficulty in tracheal extubation was experienced in a patient following major maxillofacial surgery for reconstruction of the maxilla using bone grafts and a microvascular free flap. With the aid of an intubating flexible fibrescope, the cause of the difficulty was identified as a stitch accidentally transfixed through the tracheal tube. Tracheal re‐intubation was required to facilitate surgical exploration to remove the stitch and the proximal end of the tube. The tip of an Olympus LF‐2 intubating fibrescope was successfully negotiated in the trachea alongside the original tube with its cuff deflated. This allowed safe and speedy railroading of a new tube immediately after the distal end of the original tube was removed.
Epidural placement in a patient with undiagnosed acquired haemophilia from factor VIII inhibitor
Authors: Christie‐Taylor G. A. , McAuliffe G. L.
Published: March 2003

We report a case of acquired haemophilia that presented as continuous bleeding from an epidural insertion site in a previously asymptomatic parturient. Peripartum anaesthetic management of this rare medical emergency has not previously been reported and the difficulties associated with its treatment are discussed.