bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Mixed Conducting Ceramic Oxides SrFeCo0.5Oy Powder by Hybrid Microwave Heating
Authors: Huo Di , Zhang Jinsong , Xu Zhijun , Yang Yongjin , Yang Hongcai
Published: July 2010

Mixed conducting ceramic oxide SrFeCo0.5Oy powders were prepared by a conventional solid‐state reaction method and two types of hybrid microwave heating methods. XRD, SEM/EDS (energy‐dispersive spectroscopy), and TEM/EDX (energy‐dispersive X‐ray microanalysis) were used to characterize the products. The conventional heated sample is a three‐phase mixture composed of a predominant orthorhombic Sr4(Fe1−xCox)6O13±δ phase, a cubic perovskite SrFe1−xCoxO3−δ phase, and a CoO phase. Phase components of the direct hybrid heated samples are similar to those of the conventional heated sample, except that its predominant phase is a cubic perovskite SrFe1−xCoxO3−δ phase other than the orthorhombic Sr4(Fe1−xCox)6O13±δ phase. The indirect hybrid heated sample is mainly composed of a cubic perovskite Sr(Fe,Co)1.5Oy phase, with a trace amount of orthorhombic phase and spinel (Fe,Co) oxides. The cobalt content of the Sr(Fe,Co)1.5Oy phase is much higher than that of the SrFe1−xCoxO3−δ phase. Particle size distribution of the conventional heated sample is very wide. The indirect hybrid heated sample has a relatively narrow particle size distribution, with an average particle size of 3–4 μm, but the particles stick to form agglomerates. The morphology of the direct hybrid heated sample is similar to that of the conventional heated sample, except that submicrometer grade particles were rarely observed.
Silicon Nitride Joining Using Silica and Yttria Ceramic Interlayers
Authors: Sainz Maria Antonia , Miranzo Pilar , Osendi Maria Isabel
Published: July 2010

Dense hot‐pressed β‐Si3N4 blocks were joined using both SiO2 and SiO2‐Y2O3 powder slurries as bonding interlayers. The assembled specimens (Si3N4/interlayer/Si3N4) were heated in a flowing N2 atmosphere in the temperature range of 1500°–1650°C. The joining interlayer was clearly distinguished from the Si3N4 bulk. The microstructure and the reaction products found in the bonding interlayer were very different in both compositions. Reactions occurring between the Si3N4 and the ceramic joining compositions have been explained based on existing diagrams of the YN–Si3N4‐Y2O3‐SiO2 system.
Spliceostatin A blocks angiogenesis by inhibiting global gene expression including VEGF
Authors: Furumai Ryohei , Uchida Kazuyo , Komi Yusuke , Yoneyama Misao , Ishigami Ken , Watanabe Hidenori , Kojima Soichi , Yoshida Minoru
Published: July 2010

Spliceostatin A (SSA) is a methylated derivative of an antitumor natural product FR901464, which specifically binds and inhibits the SF3b spliceosome sub‐complex. To investigate the selective antitumor activity of SSA, we focused on the regulation of vascular endothelial growth factor (VEGF) mRNA, since VEGF is a key regulatory component in tumor angiogenesis and known for the intricate regulation of mRNA processing, such as alternative splicing. We found that in HeLa cells SSA reduced the amount of both mRNA and protein of VEGF. Spliceostatin A not only inhibited the splicing reaction of VEGF pre‐mRNA but also reduced the total amount of VEGF’s transcripts, while SSA affected GAPDH mRNA to a lesser extent. Given a significant reduction in VEGF gene expression, SSA was expected to possess anti‐angiogenic activity in vivo. Indeed, SSA inhibited cancer cell‐derived angiogenesis in vivo in a chicken chorioallantoic membrane (CAM) assay. The inhibition of angiogenesis with SSA was abolished by addition of exogenous VEGF. We also performed global gene expression analyses of HeLa cells and found that the expression levels of 38% of total genes including VEGF decreased to <50% of the basal levels following 16 h of SSA treatment. These results suggest that the global interference of gene expression including VEGF in tumor cells is at least one of the mechanisms by which SSA (or FR901464) exhibits its strong antitumor activity. (Cancer Sci 2010; 101: 2483–2489)
Exogenous introduction of tissue inhibitor of metalloproteinase 2 reduces accelerated growth of TGF‐β‐disrupted diffuse‐type gastric carcinoma
Authors: Johansson Erik , Komuro Akiyoshi , Iwata Caname , Hagiwara Akifumi , Fuse Yuma , Watanabe Akira , Morishita Yasuyuki , Aburatani Hiroyuki , Funa Keiko , Kano Mitsunobu R. , Miyazono Kohei
Published: July 2010

Diffuse‐type gastric carcinoma is characterized by rapid progression and poor prognosis. High expression of transforming growth factor (TGF)‐β and thick stromal fibrosis are observed in this type of gastric carcinoma. We have previously shown that disruption of TGF‐β signaling via introduction of a dominant negative form of the TGF‐β type II receptor (dnTβRII) into diffuse‐type gastric cancer cell lines, including OCUM‐2MLN, caused accelerated tumor growth through induction of tumor angiogenesis in vivo. In the present study, we show that TGF‐β induces upregulation of expression of tissue inhibitor of metalloproteinase 2 (TIMP2) in the OCUM‐2MLN cell line in vitro, and that expression of TIMP2 is repressed by dnTβRII expression in vivo. Transplantation of the OCUM‐2MLN cells to nude mice exhibited accelerated tumor growth in response to dnTβRII expression, which was completely abolished when TIMP2 was coexpressed with dnTβRII. Although the blood vessel density of TIMP2‐expressing tumors was only slightly decreased, the degree of hypoxia in tumor tissues was significantly increased and pericytes covering tumor vasculature were decreased by TIMP2 expression in OCUM‐2MLN cells, suggesting that the function of tumor vasculatures was repressed by TIMP2 and consequently tumor growth was reduced. These findings provide evidence that one of the mechanisms of the increase in angiogenesis in diffuse‐type gastric carcinoma is the downregulation of the anti‐angiogenic protein TIMP2. (Cancer Sci 2010; 101: 2398–2403)
Intragastric pH monitoring in acute upper gastrointestinal bleeding and the effect of intravenous cimetidine and ranitidine
Authors: REYNOLDS J. R. , WALT R. P. , CLARK A. G. , HARDCASTLE J. D. , LANGMAN M. J. S.
Published: July 2010

Intragastric pH was measured continuously from 1800 to 1200 hours the following day in 22 duodenal ulcer patients and in eight gastric ulcer patients, all of whom had been admitted as emergencies with acute upper gastrointestinal haemorrhage. The effects of intravenous cimetidine or ranitidine were compared with no treatment. In patients with duodenal ulcer, median intragastric pH was 1.8 (range 1.0–4.9) in the group receiving no treatment. In the cimetidine group (400 mg, 6‐hourly, n= 8) median pH was 4.7 (range 1.5–7.7) and after ranitidine (50 mg, 6‐hourly, n= 10) it was 3.8 (range 1.2–7.8). The pH remained above 4.0 for 67% of the recording time with cimetidine, 47% with ranitidine and for only 3% with placebo. Intragastric pH in gastric ulcer patients without treatment was higher (median 3.4, range 1.0–6.9) than in duodenal ulcer patients with treatment. Both H2 antagonists raised intragastric pH in patients with gastric ulcer and maintained a gastric pH of > 4.0 for at least 50% of the time. Presently recommended i.v. doses of cimetidine and ranitidine do not consistently maintain gastric pH above 4.0 for long periods in patients with peptic ulcer bleeding.
Omeprazole in peptic ulcers resistant to histamine H2‐receptor antagonists
Authors: TYTGAT G. N. J. , LAMERS C. B. H. W. , HAMEETEMAN W. , JANSEN J. M. B. J. , WILSON J. A.
Published: July 2010

Eighteen patients with duodenal, gastric or jejunal ulcers, resistant to at least 3 months treatment with histamine H2‐receptor antagonists, singly or in combination with other anti‐ulcer drugs, were treated with 40 mg omeprazole once daily for up to 8 weeks. All ulcers healed, the majority within two weeks. After ulcer healing patients were given maintenance therapy with high doses of cimetidine or ranitidine. Of 15 patients on maintenance therapy with H2‐receptor antagonists, 12 (80%) developed a relapse after a period ranging from 3 to 52 weeks. Two patients were lost to follow‐up. After re‐healing on 40 mg omeprazole, two patients were given 20 mg omeprazole daily as maintenance therapy but relapses occurred again after 14 and 26 weeks respectively. After re‐healing on 40 mg omeprazole, these two patients and one additional patient received maintenance therapy with 40 mg omeprazole daily. At present these three patients have been relapse‐free for periods varying from 16 to 52 weeks. No side effects were registered during treatment with omeprazole. It is therefore concluded that omeprazole is highly effective in healing refractory peptic ulcers and that omeprazole maintenance therapy may be useful for prevention of relapse.
Cyclosporin for Crohn's disease
Authors: ALLISON M. G , POUNDER R. E.
Published: July 2010

Eight patients with active uncomplicated Crohn's disease, who were resistant to or intolerant of conventional treatment, were treated for 6 weeks with oral cyclosporin (mean dose 8.2 mg kg−1 day−1). Seven of the eight patients responded to treatment with cyclosporin by symptomatic improvement, weight gain and a return of serum C‐reactive protein concentration towards normal. All patients relapsed on stopping cyclosporin. No serious side‐effects were encountered. This favourable early experience justifies further trials using cyclosporin for active Crohn's disease.
The effects of cigarette smoking on plasma concentrations of gastric antisecretory drugs
Authors: BOYD E. J. S. , JOHNSTON D. A. , WORMSLEY K. G. , JENNER W. N. , SALANSON X.
Published: July 2010

Plasma concentrations of cimetidine and ranitidine were measured after oral administration (n= 5 for cimetidine, n= 5 for ranitidine) or intravenous administration (n= 6 for cimetidine, n= 4 for ranitidine) in habitual smokers, once when cigarettes were smoked and again on a separate day when cigarettes were prohibited. After oral administration plasma concentrations of both drugs rose more rapidly and peak plasma concentrations were achieved earlier when cigarettes were smoked. However, plasma concentrations of the drugs subsequent to the peak were significantly lower when cigarettes were smoked. Cigarette smoking had no effect on plasma blood concentrations of either drug when administered intravenously. In eight healthy smokers cigarette smoking increased the gastric emptying of a liquid test meal by 28% compared with non‐smoking control rates. In habitual smokers cigarette smoking alters the blood concentrations of antisecretory drugs in a manner which appears attributable to an increase in the rate of gastric emptying. The observed changes in drug disposition may contribute to the loss of gastric secretory inhibition observed in duodenal ulcer patients who are smokers.
Acid secretory capacity and plasma gastrin concentration after administration of omeprazole to normal subjects
Authors: SHARMA B. , AXELSON M. , POUNDER R. P. , LUNDBORG P. , ÖHMAN M. , SANTANA A. , TALBOT M. , CEDERBERG C.
Published: July 2010

In a randomized double‐blind study, two groups of eight healthy volunteers received either placebo or omeprazole 40 mg o.m. for 14 days. Fasting plasma gastrin concentration and peak acid output in response to a maximal intravenous dose of pentagastrin were measured before, during and after the 14 days of treatment. Omeprazole caused a 68% (mean) decrease in the peak acid output when measured 24 hours after the last dose, with a simultaneous increase in the fasting plasma gastrin concentration. When measured 1, 2, 3 and 8 weeks after cessation of treatment, there was no significant difference in the peak acid output between the two groups. The study demonstrates that there is no increase in the acid production capacity after 2 weeks of treatment with omeprazole. Thus it would appear that the rise in the plasma gastrin concentration during short‐term treatment with omeprazole does not induce parietal cell hypertrophy or hyperplasia.
SMS 201–995 treatment and advanced intestinal cancer: a pilot study
Authors: SAVAGE A. P. , CALAM J. , WOOD C. B. , BLOOM S. R.
Published: July 2010

The hypothesis that somatostatin, a compound with antitrophic effects on the gastrointestinal tract, may affect beneficially the progression of advanced intestinal cancer has been tested in a small pilot study. Ten patients, four with advanced pancreatic cancer, four with advanced colorectal cancer and two with gastric cancer, were treated with a long‐acting analogue of somatostatin, SMS 201–995, 50, 100 μg subcutaneously twice daily. There were no clinical, radiological or biochemical indicators of a response to this treatment. There are no indications from this study that hormonal manipulation alters the rate of growth of advanced gastrointestinal cancer.
Comparison of calcium channel blocking agents and an anticholinergic agent on oesophageal function
Authors: ALLEN M. , MELLOW M. , ROBINSON M. G. , ORR W. C.
Published: July 2010

The effects of oral doses of three calcium blockers and an anticholinergic drug on oesophageal function were compared. Nifedipine (20 mg) and hyoscyamine (0.25 mg) significantly reduced lower oesophageal sphincter (LES) pressure and oesophageal contractile pressure. Verapamil (120 mg) and diltiazem (60 mg) had no significant effect on any of the oesophageal variables measured. Oesophageal transit time and oesophageal contractile duration were not affected significantly by any of the agents. Only hyoscyamine significantly prolonged acid clearance time. The combination of nifedipine and hyoscyamine was no more effective in decreasing LES pressure or oesophageal contractile pressure than either agent alone. Either nifedipine or hyoscyamine would appear to be potentially effective for the treatment of oesophago‐spastic and other hypertensive motor disorders, but hyoscyamine may lead to prolongation of acid clearance from the oesophagus.
Twenty‐four‐hour intragastric acidity and clinical trial of bedtime enprostil 70 μg compared with ranitidine 300 mg in duodenal ulcer
Authors: WALT R. P. , POUNDER R. E. , HAWKEY C. J. , SANTANA I. A. , SOMERVILLE K. W. , LOGAN R. F. A. , LONG R. G. , LANGMAN M. J. S.
Published: July 2010

The effects of bedtime 70 μg and twice daily 35 μg doses of enprostil on 24‐hour intragastric acidity were investigated in nine duodenal ulcer patients in remission. Median nocturnal acidity decreased significantly by 30% with 35 μg twice daily, and by 48% with 70 μg at bedtime. In a clinical trial using bedtime dosing, 102 duodenal ulcer patients randomly received either ranitidine 300 mg or enprostil 70 μg. More ulcers healed after 4 and 8 weeks treatment with ranitidine than with enprostil (76% ranitidine vs 52% enprostil, at 4 weeks p= 0.0065 and 94%vs 68%, respectively at 8 weeks, P= 0.0007). However, 6 months after cessation of treatment there was no material difference in overall outcome. Despite combining mucosal protection with acid inhibition enprostil treatment conferred no advantage over simple acid inhibition.
Adverse reactions to sulphasalazine and 5‐amino salicylic acid in the same patient
Authors: BURKE D. A. , MANNING A. P. , WILLIAMSON J. M. S. , AXON A. T. R.
Published: July 2010

We report a patient who developed sulphasalazine‐related hepatitis with a subsequent adverse reaction to rectal 5‐amino salicylic acid, in the form of pain and fever without associated liver dysfunction, suggesting reactions to both components of sulphasalazine. Included is a review of the literature. Caution should be observed when prescribing 5‐amino salicylic acid to sulphasalazine‐intolerant patients.
Human lymphoblastoid interferon does not increase survival when added to mitozantrone in the treatment of hepatocellular carcinomas
Authors: BROOK M. G. , DUNK A. A. , McDONALD J. A. , LEVER A. M. L. , GOH C. , THOMAS H. C.
Published: July 2010

Human lymphoblastoid interferon, in an initial dose of 2.5 MU m−2 weekly i.m., was given with mitozantrone 12 mg m−2 i.v. every 3 weeks to 15 patients with hepatocellular carcinoma. The survival curve for these patients was worse than that of 15 patients previously treated with mitozantrone alone; there were more long‐term survivors in those not given interferon; more side‐effects were seen in the group given interferon. The addition of interferon to mitozantrone in the management of hepatocellular carcinoma is not recommended.
The impact of H2‐receptor antagonists on the complications, morbidity and mortality of peptic ulcer disease
Authors: ISENBERG J. I.
Published: July 2010

The epidemiology and character of peptic ulcer has changed over the last 20 years, with only some of the change being due to the introduction of H2‐receptor antagonists in the mid‐1970s. There is evidence that duodenal ulcer was declining before this change in therapeutics. H2‐receptor antagonists have, however, greatly reduced the morbidity and the time off work due to peptic ulcer disease. There is no strong evidence, however, that mortality due to peptic ulcer disease, which was already relatively small, has been reduced. The incidence of complications such as gastric haemorrhage, perforation and obstruction, may have increased in elderly patients. This may be associated with independent variables, such as increased use of non‐steroidal anti‐inflammatory drugs.
The effects of roxatidine acetate (HOE‐760) on 24‐hour intragastric acidity in healthy volunteers: comparison with ranitidine and placebo
Authors: MERKI H. S. , WITZEL L. , KAUFMANN D. , KEMPF M. , MÜSSIG V. , NEUMANN J. , SCHEURLE E. , RÖHMEL J. , WALT R. P.
Published: July 2010

In a series of double‐blind randomized studies in normal volunteers using continuous intragastric pH monitoring, the effects of different dosage regimens of roxatidine, a new H2‐receptor antagonist, were compared with placebo and ranitidine. Roxatidine acetate, 75 mg twice daily, decreased median 24 h gastric acidity from pH 1.6 to 3.2 and median nocturnal acidity from 1.5 to 3.0. Roxatidine acetate, 150 mg at bedtime, raised median 24 pH of the same 17 subjects to 2.4 and nocturnal pH to 5.9. In another series of experiments, 150 mg roxatidine acetate at bedtime was as effective as ranitidine 300 mg nocte raising median nocturnal pH (14 volunteers) from 1.4 to 6.65 compared to 6.7, respectively. However, when drugs were taken after the evening meal (post cenam nocte, pcn) roxatidine acetate 150 mg was less potent than ranitidine 300 mg with median night‐time pH rising from 1.3 to 3.2 and 4.0, respectively, in 28 volunteers. Roxatidine acetate 300 mg pcn raised the pH to 4.9 suggesting that roxatidine is 1–2 times as potent as ranitidine, on a milligram‐for‐milligram basis.
The effects of propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension
Authors: DUNK A. A. , MOORE J. , SYMON A. , DICKIE A. , SINCLAIR T. S. , MOWAT N. A. G. , BRUNT P. W.
Published: July 2010

Beta adrenoreceptor blocking drugs have been used for the prevention of haemorrhage from oesophageal varices. However, it is possible that these agents, by virtue of their effects on hepatic blood flow, may impair liver function and precipitate hepatic encephalopathy. We have therefore studied the effect of the beta blocking drug propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension. Twenty patients were randomly assigned to receive 4 weeks treatment with propranolol or an identical‐looking placebo, the former given in a dose sufficient to reduce resting pulse rate by ≥ 25%. Before and after treatment patients were assessed for the severity of liver disease and the presence of encephalopathy. EEG mean cycle frequency and fasting arterial ammonia concentrations were also measured, and in order to detect latent hepatic encephalopathy, each patient underwent a battery of psychometric tests. Patients were blinded as to their treatment, as were those assessing their responses. Neither propranolol nor placebo had any significant effect on the parameters measured. On propranolol median EEG mean cycle frequency fell from 9.08 ct s−1 (range 8.63–11.0 ct s−1) to 8.73 ct s−1 (range 8.27–11.44 ct s−1), and median fasting arterial ammonia concentration fell from 66 μmol litre−1 (range 40–329 μmol litre−1) to 49 μmol litre−1 (range 37–188 μmol litre−1). Psychometric test values, while initially abnormal and suggestive of latent hepatic encephalopathy in the majority of patients, did not change significantly during the study.
A comparison of the effects of treatment with either famotidine 40 mg or cimetidine 800 mg nocte on gastric acid secretion and serum gastrin
Authors: FULLARTON G. M. , LAFERLA G. , CREAN G. P. , McCOLL K. E. L.
Published: July 2010

The effects on gastric acid secretion and serum gastrin of 4 weeks treatment with famotidine 40 mg nocte or cimetidine 800 mg nocte (at 2200 h) were studied in 16 patients with previous duodenal ulcer. Patients were studied before commencing therapy, on days 5, 12 and 26 of treatment, and on days 3, 10 and 24 after completion of therapy. In contrast to cimetidine, basal and pentagastrin‐stimulated gastric acid secretion measured 12 h after dosing was significantly inhibited during treatment with famotidine. In addition, with famotidine there was inhibition of stimulated gastric acid secretion at 3 and 24 days after completion of treatment. Fasting serum gastrin measured 12 h after dosing was not significantly altered by either drug.
The effect of dietary fatty acids on the gastric production of prostaglandins and aspirininduced injury
Authors: PRICHARD P. , BROWN G. , BHASKAR N. , HAWKEY C.
Published: July 2010

We have investigated in man the effect of dietary supplementation with evening primrose oil (linoleic acid 72%, gamma‐linolenic acid 9%) on gastric immunoreactive PGE2 release and aspirin‐induced mucosal injury. Twenty healthy volunteers received in a randomized crossover evening primrose oil (2 g b.d.) and olive oil (control) for 2 weeks each. During the last 48 hours of each period, five doses of aspirin 900 mg were taken. In gastric washings on day 7, evening primrose oil had enhanced immunoreactive PGE2 release from a mean of 38 ng/30 min (olive oil) to 80 ng/30 min (P < 0.05). This, however, was not able to protect against aspirin‐induced gastric blood loss which rose from a mean (95% confidence limits) of 1.3 (0.7–2.1) μl 10 min—1 (evening primrose oil day 7) to 9.4 (5.4–16.5) μl 10 min—1 (day 14). Although not effective against aspirin, similar dietary supplementation might assist in preventing peptic ulcer recurrence.
The effects of omeprazole and ranitidine on 24‐hour pH in the distal oesophagus of patients with reflux oesophagitis
Authors: KLINKENBERG‐KNOL E. C. , FESTEN H. P. M. , MEUWISSEN S. G. M.
Published: July 2010

Ambulatory 24‐h pH monitoring in the distal oesophagus was performed in seven patients with erosive or ulcerative reflux oesophagitis to compare the effects of omeprazole and ranitidine in the management of gastro—oesophageal reflux disease. In a double‐blind, crossover study patients were treated with either 60 mg o.m. omeprazole or 150 mg b.d. ranitidine. The pH measurements were performed before treatment and on the fourteenth day of treatment with either regimen. The total acid exposure time (percentage total time pH < 4) was abnormal in six out of seven patients before treatment. During treatment with omeprazole the acid exposure time of five patients was normal in comparison with only two patients during ranitidine therapy. However, even with a rather high dose of omeprazole, pathological gastro‐oesophageal reflux may still occur.
The cost‐effectiveness of maintenance therapy for duodenal ulceration with an H2‐antagonist
Authors: FOX N. , MORTON R. E. , JACOBS J.
Published: July 2010

Data from several sources are used to quantify the expected direct medical costs of a recently healed duodenal ulcer patient prescribed an H2‐antagonist (famotidine) for a 6‐month period. These costs are compared to the expected direct medical costs associated with not using maintenance therapy.

Our results indicate that the estimated direct cost of patients prescribed a 6‐month regimen of an H2‐antagonist (famotidine) is 30.3% lower than patients who receive no H2‐antagonist therapy. Most of the savings result from a reduced risk of hospitalization and surgery. The results of the sensitivity analysis of four varying scenarios indicate that H2‐antagonist maintenance therapy remains less costly even when the assumptions underlying the model are varied enormously. We conclude that the decision to withhold maintenance therapy with H2‐antagonists should not be based on economics.
Involvement of M1 cholinergic receptors and enteric nerves in the spasmogenic activity of bacterial N‐formyl oligopeptides on guinea‐pig ileum
Authors: HOBSON C. H. , BROOM M. F. , FERRY D. , GRINDLEY R. , CHADWICK V. S.
Published: July 2010

Bacterial N‐formyl‐methionyl oligopeptides are spasmogenic for guineapig ileum in vitro but the mechanism of this effect is not understood. To investigate this phenomenon further, we have determined pA2 values (the negative logarithm of the concentration of an antagonist reducing a double‐dose agonist response to a single‐dose response) for a number of potential antagonists of N‐formyl‐met‐leu‐phe (F‐met‐leu‐phe) using histamine, acetylcholine, 5HT and substance P as control agonists. Atropine, pirenzepine and tetrodotoxin were potent inhibitors of F‐met‐leu‐phe induced contraction (pA2's 8.4, 8.0 and 7.9, respectively) suggesting involvement of neural and cholinergic pathways in the response. Sulphasalazine, known to block the F‐met‐leu‐phe receptor on neutrophil leucocytes, was also a potent inhibitor. Tachyphylaxis induced by either 5HT, or substance P, did not diminish the response to F‐met‐leu‐phe, suggesting that these potential mediators were not involved. These studies indicate that bacterially synthesized formyl—methionyl oligopeptides bind to cells bearing receptors in guinea‐pig ileum and produce muscle contraction via enteric cholinergic (M1) neural pathways.
Theophylline disposition—effects of cimetidine, mebendazole and albendazole
Authors: ADEBAYO G. I. , MABADEJE A. F. B.
Published: July 2010

On the basis of the report that benzimidazoles bind to and inhibit the hepatic cytochrome P‐450 enzyme system, the effect of mebendazole and albendazole on theophylline disposition was studied in 12 volunteers. Mebendazole at a dose of 100 mg b.d. for 3 days did not significantly alter the theophylline half‐life, volume of distribution or clearance in a group of six. In another group of six adult volunteers, albendazole (400 mg) pretreatment did not alter the same parameters. However, in this second group, pretreatment with cimetidine (400 mg t.d.s. for 5 days) significantly increased theophylline half life from 7.7 to 9.8 ± 1.5 h (P < 0.001) and reduced its clearance from 0.8 to 0.60 ± 0.1 ml min−1 kg−1 (P < 0.005). The volume of distribution was not altered significantly.

It is concluded that at therapeutic doses it is unlikely that mebendazole or albendazole will induce theophylline toxicity if co‐administered with the bronchodilator. Cimetidine‐induced impairment of theophylline metabolism is such that toxicity will be more likely in individuals with initial high theophylline clearance.
Haemodynamic responses to 1.25 and 2 mg of terlipressin intravenously in man
Authors: FREEMAN I. G. , BARTON J. R. , RECORD C. O.
Published: July 2010

The systemic and hepatic haemodynamic effects following terlipressin (Glypressin) administration were studied. Bolus intravenous injections of 1.25 and 2 mg significantly decreased wedged hepatic vein pressure gradient by 29% and 31%, respectively. With each dose there was a small increase in mean arterial blood pressure but after 1.25 mg of terlipressin, estimated hepatic blood flow fell by only 11% (not significant) compared to 24% after 2 mg, while the cardiac index fell by 12% compared to 29%. The adverse haemodynamic effects of terlipressin were diminished by a decrease in dosage, without any alteration in the beneficial effect of the drug upon portal pressure. Whether the smaller dose will be effective in arresting variceal haemorrhage remains to be determined.
Review: the pharmacological control of variceal bleeding
Authors: FREEMAN J. G. , RECORD C. O.
Published: July 2010

The haemodynamic effects and clinical uses of drugs used in the management of patients with oesophageal variceal bleeding are reviewed. Vasoconstrictor agents (vasopressin, teripressin) alone or in combination with nitrates continue to be used for acute bleeding episodes, while somatostatin is an alternative. Alpha‐ and beta‐adrenergic blocking drugs and vasodilators which lead to a sustained decrease in portal pressure can be used for the prevention of bleeding episodes, but despite numerous studies the pharmacological treatment of variceal bleeding remains controversial.
Three computer models for the calculation of prevalence of peptic ulcer disease during long‐term treatment
Authors: UNDERWOOD D. D. , AMOS J. C. , VENABLES C. W. , BARDHAN K. D. , BERESFORD J. , HALIBURN C. , McCARTHY C. F. , WEIR D. G.
Published: July 2010

At present the effects of maintenance treatment for peptic ulcer disease are usually calculated by using ‘life‐table’ analyses. Whilst these accurately demonstrate the speed with which an initial relapse occurs they make no allowance for the fact that, in clinical practice, a relapse often responds to a further course of full‐dose treatment and the patient then returns to maintenance therapy. A further compounding factor is that, in any long‐term study, patients will be lost to follow‐up for a variety of reasons not all related to failure of the treatment.

In this paper we describe the use of ‘prevalence rates’ to better reflect the outcome of peptic ulcer management. Three ‘computer models’, which have been developed to address the problems of patients leaving the study for any reason during such a long time‐period, are also described, as are the underlying assumptions made.

Using the results from a long‐term study of continuous treatment with cimetidine,1 the ‘prevalence rates’ of ulcer disease over 6 years were calculated. Observed relapse rates appeared to fall with time (from 2.7% for duodenal ulcer (DU) and 2.5% for gastric ulcer (GU) to 1% and 2% respectively). However, on applying the models to the data, prevalence rates tended to rise slowly with time for the first 3 years in each of the models tested. At 6 years, two of the models suggested that the prevalence rate for DU would be about 8%; this is not very different to the reported recurrence rate after surgical treatment by truncal vagotomy and pyloroplasty.

It is concluded that ‘prevalence rates’ should be used to assess long‐term medical treatments for ulcer disease. Similar methods could also be used to examine the medical treatment of any other disease where multiple relapses, capable of responding to re‐treatment, occur. The use of models proved beneficial in compensating for patients lost during the study.
Inhibitory effect of isoprenaline on gastric acid secretion in the rat. The role of endogenous histamine
Authors: HEYLINGS J. R. , REDFERN J. S. , FELDMAN M.
Published: July 2010

In dogs beta‐adrenoreceptor agonists inhibit gastric acid secretion stimulated by exogenous gastrin to a much greater extent than acid secretion stimulated by exogenous histamine. One possible explanation for this observation is that endogenous histamine is important in gastrin‐mediated acid secretion and that isoprenaline and related beta‐adrenoreceptor agonists block gastric mucosal histamine release. This possibility was tested in the present study in gastric lumen‐perfused anaesthetized rats. Intravenous infusion of isoprenaline (12 μg kg−1 h−1) inhibited maximal, pentagastrin‐stimulated acid output by 50–70% (P < 0.01), but had no significant inhibitory effect on the maximal acid secretory response to histamine. In contrast to its inhibitory effect on gastrin‐stimulated acid output, isoproterenol had no effect on gastric histamine output during pentagastrin infusion. We conclude that isoprenaline selectively inhibits gastrin‐stimulated acid secretion in the rat, as in the dog, and by a mechanism other than inhibiting gastric histamine release.
Effect of 10 mg and 20 mg omeprazole daily on duodenal ulcer: double‐blind comparative trial
Authors: LAURITSEN K. , ANDERSEN B. N. , HAVELUND T. , LAURSEN L. S. , HANSEN J. , ERIKSEN J. , JØRGENSEN T. , RASK‐MADSEN J.
Published: July 2010

One‐hundred and seventy‐one patients with endoscopically proven duodenal ulcers were allocated at random to double‐blind treatment with 10 or 20 mg of omeprazole in the morning for up to 4 weeks. Patients completed the study if ulcer healing and pain relief had occurred at 2 weeks. A total of 155 patients completed the trial. Patients treated with 20 mg of omeprazole daily responded significantly more rapidly than those treated with 10 mg of omeprazole daily (P < 0.001; Cochran‐Mantel‐Haenszel test covering both time points), cumulative healing rates at 2 and 4 weeks were 74% (58/78) and 91% (71/78), respectively. The corresponding rates in the group treated with 10 mg daily were 48% (39/81) and 75% (58/77). Pain relief was again more pronounced during treatment with the larger dose (P < 0.05; stratified Wilcoxon test). No major clinical or biochemical side effects were noted. An omeprazole dose of 20 mg daily is preferable to a lower dose for the treatment of duodenal ulcer disease in the short term.
Antroduodenal motility and gastric emptying. Gastroduodenal motility and pH following ingestion of paracetamol
Authors: SCHURIZEK B. A. , KRAGLUND K. , ANDREASEN F. , VINTER‐JENSEN L. , JUHL B.
Published: July 2010

The influence of paracetamol on antroduodenal motility and gastric pH was studied in 11 healthy subjects and the relationship between gastroduodenal motility and gastric emptying rate time, tmax, to peak concentration of serum paracetamol, Cmax, was evaluated. The incidence of antral phase III activity and the duration of phase III was diminished with paracetamol (P < 0.05). The other motility parameters assessed were unchanged.

Three patterns of motility and absorption were observed. One group (n= 5) were fast absorbers with a tmax of 1 h and a motility pattern characterized by antral activity, a high motility index and a short duration of phase II (33–60 min); the phase IIIs were complete except in one case. The second group (n= 4) had tmax at 1.5 h and their phase II motility was characterized by a longer duration (80–133 min) (P < 0.05), by antral activity, and by a high motility index; their phase IIIs were all incomplete. The last group (n= 2) were slow absorbers: Cmax was not reached in the investigation period, no antral contractions were seen, and the motility index was low. The area under the serum‐concentration curve of paracetamol differed between the groups at 90 and 180 min (P > 0.01).
Review article: a role for gastrointestinal prokinetic agents in the treatment of reflux oesophagitis?
Authors: VERLINDEN M.
Published: July 2010

Gastro‐oesophageal reflux disease may result from a host of factors. Medical therapy has largely been aimed at neutralizing acid or decreasing acid production but improvement of upper‐gastrointestinal motility may prove to be a valuable treatment modality as well. This paper reviews the current state of knowledge of the pathogenesis of reflux disease and concentrates upon promotility treatment with domperidone, metoclopramide and cisapride.
Low‐dose cyclosporin for Crohn's disease: implications for clinical trials
Authors: BRYNSKOV J. , BINDER V. , RIIS P. , LAURITSEN K. , DE MUCKADELL O. SCHAFFALITZKY , FREUND L. , FALLINGBORG J. , RASMUSSEN S. NØRBY , MATZEN P. , KRAG E. , TAGE‐JENSEN U. , JARNUMS S.
Published: July 2010

Cyclosporin is a potent immunosuppressant, which has gained recent interest as a possible treatment for Crohn's disease. Chronic nephrotoxicity, however, has recently been demonstrated as a result of early treatment with high initial cyclosporin doses. We report the effect of a 3‐month treatment with low‐dose cyclosporin (5–7.5 mg kg−1 day−1) in 11 chronically active, therapy‐resistant Crohn's disease patients. Eight of the 11 patients (72%) improved according to a clinical grading score and the Dutch Activity Index whereas 9/11 (82%) improved according to the Crohn's Disease Activity Index (P < 0.05) after 1 month. Three patients were withdrawn despite clinical improvement. One developed arterial hypertension, one dropped out and one required surgical treatment due to a small bowel stricture. Five patients (45%) completed the treatment period with improved clinical scores. After tapering‐off, two patients (18%) were better at follow‐up. No serious side‐effects were encountered and it is concluded that low‐dose cyclosporin treatment should be further investigated in Crohn's disease.
The effects of octreotide, soy polysaccharide, codeine and loperamide on nutrient, fluid and electrolyte absorption in the short‐bowel syndrome
Authors: RODRIGUES C. A. , LENNARD‐JONES J. E. , THOMPSON D. G. , FARTHING M. J. G.
Published: July 2010

Four agents, which could delay intestinal transit, were tested in six short‐bowel patients (jejunal length 30–120 cm) on long‐term nutritional/ electrolyte replacement therapy. Intestinal transit time of a liquid test meal and nutrient, water and sodium absorption were measured during a control study and with each test agent on separate days. Soy polysaccharide tended to increase transit time, but decreased the absorption of water, sodium and nutrients. Codeine phosphate and loperamide caused inconsistent and clinically unimportant changes. Octreotide, a long‐acting analogue of somatostatin, delayed transit and increased water, sodium and calorie absorption from the meal. Octreotide appears to have the potential to reduce the need for electrolyte and nutritional supplements in patients with the short‐bowel syndrome.
Effects of cimetropium bromide on gastrointestinal transit time in patients with irritable bowel syndrome
Authors: PASSARETTI S. , GUSLANDI M. , IMBIMBO B. P. , DANIOTTI S. , TITTOBELLO A.
Published: July 2010

Cimetropium bromide is a new antimuscarinic compound with strong antispasmodic activity. The aim of this study was to evaluate the effects of oral cimetropium bromide on total gut transit time in patients with irritable bowel syndrome. Forty patients, divided according to their initial total gastrointestinal transit times and presenting symptoms, were treated with cimetropium bromide 50 mg t.d.s. or placebo for 1 month according to a double‐blind, parallel group design. Before and after treatment all subjects ingested 24 radio‐opaque markers. The total intestinal transit time was determined by evaluating the rate of disappearance of markers from plain X‐ray films of the abdomen taken every 24 h for 4 days. Pain and bowel habits were also monitored. Seven patients did not complete the study. Cimetropium bromide significantly (P < 0.01) shortened the whole gut transit time in patients with prolonged transit time (80.8 ± 4.0 h before vs 60.8 ± 6.7 h after treatment) and improved the global clinical condition significantly compared with placebo (P= 0.029). In patients with a short total intestinal transit time, cimetropium bromide had no effect on whole gut transit time and did not significantly improve symptoms. The results of this study indicate that oral cimetropium bromide is effective both objectively and subjectively in a subgroup of irritable bowel syndrome patients with constipation.
Inappropriate use of metronidazole in gastrointestinal surgery
Authors: INGOLDBY C. J. H. , DEAN P. H. , VOWDEN P. , GILES G. R.
Published: July 2010

Pharmacokinetic data suggest that current treatment regimens of metronidazole in abdominal surgery are not always appropriate. We have examined antibiotic concentrations during emergency and elective surgery using a specific and sensitive high pressure liquid chromatography assay. Serum and tissue concentrations were measured after intravenous infusion during intra‐abdominal surgery and after suppositories given before appendicectomy. After intravenous dosage, bactericidal concentrations were reached in serum (13.6 ± 7.8 μ/ml), bowel (9.0 ± 6.6 μ/g), tumour (9.9 ± 7.1 μ/g) and subcutaneous fat (4.9 ± 3.2 μ/g). After suppositories the concentrations were: serum 4.6 ± 2.7 μ/ml, appendix 1.1 ± 0.6 μ/g, fat 1.5 ± 0.9 μ/g and peritoneal fluid 4.7 ± 4.3 μ/g. These values were obtained at a mean interval of 86.9 ± 27.5 min following administration of the drug.

Serum concentrations were measured during post‐surgical infusion of 500 mg i.v. 8 or 12 hourly. Mean concentrations after 8 hourly doses were 16.3 ± 4.85 μ/ml pre‐dose and 28.7 ± 6.76 μ/ml post‐dose, with evidence of drug accumulation by detection of metabolites. Twelve hourly infusions gave pre‐dose levels of 7.4 ± 3.86 μ/ml and post‐dose levels of 17.1 ± 3.69 μ/ml.

Metronidazole (500 mg) intravenously at induction of anaesthetic gives effective prophylactic concentrations in all tissues including tumour, but a metronidazole 1g suppository before appendicectomy does not provide reliable tissue concentrations. Metronidazole (500 mg) i.v. 12 hourly gives effective bactericidal concentrations of the drug and is more economical.
Natural history of Campylobacter pylori in duodenal ulceration treated with an H2‐antagonist
Authors: HO J. , HUI W.‐M. , NG I. , LAM S.‐K.
Published: July 2010

Campylobacter pylori has been associated closely with active antral gastritis and duodenal ulcer but its pathogenetic role remains uncertain. The present longitudinal study examined, prospectively, the endoscopic antral biopsies of 45 patients with duodenal ulceration, taken before and after healing of the duodenal ulcer, during remission and at relapse. The biopsies were examined for the activity and degree of chronic inflammation of the gastritis and for the occurrence and density of C. pylori by Warthin‐Starry stain. Before treatment the frequency of chronic active antral gastritis was 100% and the occurrence of C. pylori was 97%. Compared with the pre‐treatment state, there was no significant change in either the frequency and severity of antral gastritis, or in the occurrence and density of the bacteria in the antral mucosa at the time the duodenal ulcer healed, during remission, or at relapse. The occurrence of the bacteria was significantly more frequent during remission, than at the time when the ulcer had healed initially (P < 0.05). These results suggest that the bacterium may not play an important pathogenetic role in ulcer healing and relapse, when patients are managed using an H2‐blocker.
Therapeutic potential of fish oil in the treatment of ulcerative colitis
Authors: McCALL T. B. , O'LEARY D. , BLOOMFIELD J. , Ó'MORÁIN C. A.
Published: July 2010

In a pilot study six patients with active ulcerative colitis and six healthy controls were given fish oil (MaxEPA) containing 3–4 g of eicosapentaenoic acid daily for a period of 12 weeks. There was a significant improvement in the patients' symptoms and histological appearance of the rectal mucosa by the end of the treatment period. There was a significant fall in neutrophil chemiluminescence during treatment in patients, whereas no change was observed in the control group. Neutrophil leukotriene B4 levels fell significantly during treatment. Serum from patients receiving fish oil was significantly less chemotactic for neutrophils compared with control serum. Eicosapentaenoic acid inhibited neutrophil chemotaxis and chemiluminescence in vitro. The omega‐3 fatty acids, which occur naturally in fish oils, may exert a beneficial effect by decreasing the production of inflammatory mediators.
Comparison of 40 mg famotidine nightly and 150 mg ranitidine b.d.: ulcer healing and symptom relief in benign gastric ulcer
Authors: COCHRAN K. M. , COCKEL R. , CROWE J. , DICKINSON R. J. , GENT A. E. , KENNEDY N. P. , ROYSTON C. M. S. , CEDAR E. , MANN S. G.
Published: July 2010

Two hundred and eight patients with benign gastric ulcers seen on endoscopy were recruited by 13 hospitals in the United Kingdom and Ireland into this double‐blind study. Patients were assigned by prerandomized schedule to 8 weeks of treatment with either 40 mg famotidine at night or 150 mg ranitidine b.d. Repeat endoscopy confirmed complete ulcer healing in 62 of 77 evaluable patients in the famotidine group (81%) and 58 of 71 in the ranitidine group (82%). The treatments were equally effective in promptly relieving day and night pain. Adverse events were uncommon; dizziness and headaches were the most frequently reported in both groups. In conclusion, night‐time famotidine is as effective as twice daily ranitidine in healing benign gastric ulcers and provides similarly rapid symptomatic relief.
Ranitidine maintenance treatment of non‐steroidal anti‐inflammatory drug‐induced duodenal ulceration
Authors: PENSTON J. G. , WORMSLEY K. G.
Published: July 2010

Fifty‐six patients who presented with non‐steroidal anti‐inflammatory drug‐associated duodenal ulcers received maintenance treatment with ranitidine. Forty‐eight of these patients stopped treatment with nonsteroidal anti‐inflammatory drugs. The cumulative symptomatic remission at the end of 5 years of maintenance treatment was 97.7%. While half the patients had presented with haemorrhage from the ulcer, only one patient bled during maintenance treatment, giving a cumulative risk of 2.3% in 5 years of maintenance treatment.

We conclude that maintenance treatment with ranitidine effectively and safely keeps patients with non‐steroidal anti‐inflammatory drugassociated ulcers symptom‐ and risk‐free.
Single night‐time doses of 40 mg famotidine or 800 mg cimetidine in the treatment of duodenal ulcer
Authors: LEE F. I. , BOOTH S. N. , COCHRAN K. M. , CROWE J. , DICKINSONS R. J. , KENNEDY N. P. , COTTRELL J. , MANN S. G.
Published: July 2010

Famotidine (40 mg) and 800 mg cimetidine as single night‐time doses were compared in a randomized, double‐blind, multicentre study of acute treatment for duodenal ulceration. Fifteen centres recruited 304 patients into the study. Of these, 274 were included for analysis, with 136 receiving famotidine and 138 receiving cimetidine. After 4 weeks, 75% of the patients who received famotidine and 77% of the patients who received cimetidine were healed. At 6 weeks the cumulative healing rates were 91% with famotidine and 87% with cimetidine. Differences between the groups were not significant at 4 or 6 weeks. No significant difference in healing rates between smokers and non‐smokers was found. Day and night pain resolved rapidly in both groups. Both treatments were well‐tolerated; adverse events were reported in 17 patients on famotidine and 18 on cimetidine, with headache the most frequent event in both groups. Famotidine is effective and well‐tolerated in the shortterm treatment of duodenal ulcer.
Acute damage of gastroduodenal mucosa by acetylsalicylic acid: no prolonged protection by antacids
Authors: BERSTAD K. , HARAM E.‐M. , WEBERG R. , BERSTAD A.
Published: July 2010

Twenty healthy volunteers participated in a double‐blind, crossover study to evaluate endoscopically whether low‐dose antacids have any prolonged and pH‐independent protective capacity against gastroduodenal mucosal damage induced by acetylsalicylic acid. Antacid or placebo one tablet q.d.s. was given for 1.5 days. Acetylsalicylic acid (1.5 g) was administered 3 h after the last dose of antacid/placebo, and gastroscopy was performed 1 h thereafter. Thirteen of 20 subjects showed a decrease in total damage with antacids as compared with placebo, but the difference did not reach statistical significance. Thus, protection by antacids against acetylsalacylic acid‐induced gastric mucosal lesions could not be documented at a time when intragastric pH presumably had returned to normal.
Galanin: hydrokinetic action on salivary glands in man
Authors: BAUER F. E. , GHATEI M. A. , ZINTEL A. , BLOOM S. R.
Published: July 2010

Galanin was infused intravenously into eight healthy volunteers at a dose of 40 pmol kg−1 min−1 for 1 h to investigate the pharmacological effects of this peptide on the postprandial sialagogical response in man. Galanin significantly increased the salivary volume and the saliva output of sodium, chloride and bicarbonate compared to control saline infusion, but had no effect on the output of potassium and α‐amylase. An increase in salivary pH was also observed. The increase in salivary volume may indicate a physiological role of galanin in the control of salivary secretion.