bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron‐Rich Sintered Glass‐Ceramics from Industrial Wastes
Authors: Karamanov Alexander , Taglieri Giuliana , Pelino Mario
Published: July 2010

In this study, sintered glass‐ceramics made up of jarosite (a hazardous industrial waste) have been obtained by sintering high‐iron‐content glasses. Thermal gravimetry and differential thermal analysis, carried out in different atmospheres, have been utilized to explain the phase formations in the volume and iron oxidation on the surface of the glass particles. Low‐angle XRD technique has been used to investigate the distribution of the phases formed on the surface of the glass during heating. The variation of density of the powder and bulk samples has been used to investigate the kinetics of phase transformation. The value of the Avrami constant, n, has been obtained as 1.33, which corresponds to the three‐dimensional diffusion growth on a fixed number of nuclei. The sinter‐crystallization process has been defined to yield a 40 wt% crystal phase. The results of this study have opened the possibility of preparing glass‐ceramics with an original appearance, somewhat similar to that of granite, by reevaluating industrial wastes.
Influence of Chemical Reactions in Magnesia‐Graphite Refractories: II, Effects of Aluminum and Graphite Contents in Generic Products
Authors: Baudín Carmen , Alvarez Carlos , Moore Robert E.
Published: July 2010

A group of magnesia‐graphite and magnesia‐graphite‐aluminum materials, the compositions of which represent a wide range of graphite contents (~10‐16.4 wt%), aluminum contents (0‐5.2 wt%), and MgO and graphite qualities, were fabricated, using standard commercial practices. Chemical analysis and determination of room‐temperature modulus of rupture (MOR) and Young's modulus, as well as a complete microstructural characterization of the as‐received materials, were performed. Mechanical characterization at high temperature (1000°, 1200°, and 1450°C) was done in terms of Young's modulus and MOR in an argon atmosphere (<1000 ppm oxygen at 1000°C). Modulus‐of‐elasticity values ranged from 4 to 16 GPa, and their evolution with temperature was determined by the evolution of the microstructure in the bulk of the specimens. A strong effect of aluminum‐metal concentration on Young's modulus overrode other microstructural differences among the materials. MOR values ranged from 6 to 20 MPa, and their evolution with temperature was determined by the evolution of the microstructure in the bulk of the specimens at the lower testing temperatures (T lessthan equal to 1200°C) and by phase assemblages in the surface regions of the specimens‐essentially by the presence of the dense MgO zone‐at 1450°C. The thickness of the dense MgO zone in the aluminum‐containing materials was determined by the amount of aluminum and the MgO aggregate size.
Formation of Novel ZSM‐5/Porous Mullite Composite from Sintered Kaolin Honeycomb by Hydrothermal Reaction
Authors: Katsuki Hiroaki , Furuta Sachiko , Komarneni Sridhar
Published: July 2010

The formation and properties of continuous ZSM‐5 film on a porous mullite honeycomb have been investigated. The porous mullite honeycomb coated with ZSM‐5 film provides a novel microporous (0.5 nm in diameter)–macroporous (0.5–0.6 μm in diameter) composite. Amorphous silica‐glass in the kaolin honeycomb sintered at 1650°C is used as a source for ZSM‐5 formation. The honeycomb is hydrothermally treated in NaOH, tetrapropylammonium bromide, and water to prepare a novel honeycomb–zeolite composite by in situ crystallization of ZSM‐5 film. This paper describes the effects of hydrothermal conditions—such as reaction temperature, time, and concentration of NaOH solution—on the formation of ZSM‐5 film on the honeycomb, and on the mechanical strength and porous properties of the honeycomb composite.
Strengthening of Porous Alumina by Pulse Electric Current Sintering and Nanocomposite Processing
Authors: Oh Sung‐Tag , Tajima Ken‐ichi , Ando Motohide , Ohji Tatsuki
Published: July 2010

Porous Al2O3 and SiC–dispersed‐Al2O3 (Al2O3/SiC) nanocomposites with improved mechanical properties were fabricated using pulse electric current sintering (PECS). Microstructures with fine grains and enhanced neck growth, as well as high fracture strength, could be achieved via PECS of Al2O3. The incorporation of fine SiC particles into an Al2O3 matrix significantly increased the fracture strength of porous Al2O3. Based on microstructural observations, it was revealed that the refinement of Al2O3 grains and neck growth occurred by PECS and nanocomposite processing.
Phase Evolution in Silicon Carbide–Whisker‐Reinforced Mullite/Zirconia Composite during Long‐Term Oxidation at 1000° to 1350°C
Authors: Lin Chien‐Cheng , Zangvil Avigdor , Ruh Robert
Published: July 2010

A composite consisting of 30 wt% SiC whiskers and a mullite‐based matrix (mullite–32.4 wt% ZrO2–2.2 wt% MgO) was isothermally exposed in air at 1000°–1350°C, for up to 1000 h. Microstructural evolution in the oxidized samples was investigated using X‐ray diffractometry and analytical transmission electron microscopy. Amorphous SiO2, formed through the oxidation of SiC whiskers, was devitrified into cristobalite at T≥ 1200°C and into quartz at 1000°C. At T≥ 1200°C, the reaction between ZrO2 and SiO2 resulted in zircon, and prismatic secondary mullite grains were formed via a solution–reprecipitation mechanism in severely oxidized regions. Ternary compounds, such as sapphirine and cordierite, also were found after long‐term exposure at T≥ 1200°C.
Hot Forging of Mullite‐Based Ceramics Prepared from Kaolin–Alumina
Authors: Ohashi Masayoshi , Iida Yasuo
Published: July 2010

Mullite‐based ceramics prepared from a mixture of kaolin and alumina were plastically deformed in uniaxial compression tests at high strain rates (= 10−2–10−3 s−1) at 1450° and 1500°C. Deformation occurred with barreling in tests that used SiC platens coated with h‐BN. This study shows that more‐suitable lubricants and molds (platens) must be found, to reduce friction between the mullite‐based ceramics and molds. However, this hot‐working method can be used to give a fine, textured surface to mullite‐based ceramic substrates for polycrystalline silicon thin‐film solar cells.
Effects of SiO2, CaO2, and MgO Additions on the Grain Growth of Alumina
Authors: Park Chan Woo , Yoon Duk Yong
Published: July 2010

When pure alumina is sintered at 1620°C, normal grain growth occurs with equiaxial grains and curved grain boundaries. When 100 ppm of SiO2 together with 50 ppm of CaO is added, abnormal grain growth (AGG) occurs with large grains elongated with straight grain‐boundary segments in the direction of the basal planes. Some of the fine matrix grains also have straight grain boundaries, and ∼10% of the grain boundaries of the matrix grains are faceted when observed by transmission electron microscopy (TEM). Some of these grain boundaries are expected to be singular with low‐energy structures corresponding to the cusps in the polar plot of the grain‐boundary energy against the inclination angle. No frozen liquid is found at the grain triple junctions and grain boundaries by TEM. When 600 ppm of MgO is added together with 100 ppm of SiO2 and 50 ppm of CaO normal growth occurs. The grain boundaries are curved when observed via optical microscopy and TEM and show that all the grain boundaries are defaceted, indicating that they become atomically rough. When sintered at 1900°C after adding 150, 300, or 500 ppm of SiO2, AGG occurs with straight and faceted grain boundaries, similar to the specimens sintered at 1620°C after CaO and SiO2 are added. When MgO is added together with SiO2 and sintered at 1900°C, normal grain growth occurs with rough grain boundaries. High‐resolution TEM observation shows no frozen liquid layer at a grain boundary. The results indicate that the occurrence of AGG in alumina with SiO2 or together with CaO is correlated with the formation of faceted and straight (on large and atomic scales) grain boundaries. It is proposed that these grain boundaries have singular ordered structures with low boundary energies and their growth by lateral step movement can cause the AGG. The addition of MgO causes grain‐boundary roughening and, thus, normal grain growth. The grain boundaries in pure alumina also appear to be rough, and, hence, normal grain growth occurs.
An Alternative Explanation for the Origin of the Resistivity Anomaly in La‐Doped BaTiO3
Authors: Morrison Finlay D. , Sinclair Derek C. , West Anthony R.
Published: July 2010

Semiconductivity in La‐doped BaTiO3 ceramics after high‐temperature firing, e.g., 1350°C in air, is attributed to oxygen nonstoichiometry. In more heavily doped compositions, the observed resistivity rise is attributed to surface oxidation of the grains during cooling.
A Simple and Cost‐Effective Approach to Fabrication of Dense Ceramic Membranes on Porous Substrates
Authors: Xia Changrong , Liu Meilin
Published: July 2010

A simple and elegant approach to fabrication of dense ceramic membranes on porous substrates, a traditional dry pressing of foam powders, has been developed to reduce the cost of fabrication. Gd‐doped ceria (GDC, Gd0.1Ce0.9O1.95) electrolyte membranes as thin as 8 μm are obtained by dry‐pressing highly porous GDC powders. The membrane thickness can be readily controlled by the amount of powder. The electrolyte membranes are studied in a solid‐oxide fuel cell (SOFC) with air as oxidant and humidified hydrogen (3% H2O) as fuel. Open‐circuit voltages of about 1.0 V are observed, implying that the permeability of the membranes to molecular gases is insignificant. Power densities of 140 and 380 mW/cm2 are demonstrated at 500° and 600°C, respectively, representing a significant progress in developing low‐temperature SOFCs.
Effects of Methane Concentration in the Deposition Process on the Crystal Structure and the Adhesive Fracture Toughness of CVD Diamond
Authors: Takahashi Hironori , Kamiya Shoji , Saka Masumi , Sato Futami , Tanaka Michiyoshi , Abé Hiroyuki
Published: July 2010

Crystal structures of CVD diamond particles were observed in detail by transmission electron microscopy. The particles were deposited on silicon substrates under various conditions and had different levels of adhesion. An interlayer of SiC was found along the interface obtained with low methane concentration in the source gas, but it disappeared when deposited with higher methane concentrations. On the other hand, the size of crystal grains became smaller with increasing methane concentrations. From the correspondence between the structures and the adhesive toughness of these particles, it was suggested that the effect of both the SiC interlayer and the variation of grain size resulted in the complicated trend of adhesion with respect to methane concentration.
Neogenesis and development of the high endothelial venules that mediate lymphocyte trafficking
Authors: Hayasaka Haruko , Taniguchi Kanako , Fukai Shoko , Miyasaka Masayuki
Published: July 2010

Physiological recruitment of lymphocytes from the blood into lymph nodes and Peyer’s patches is mediated by high endothelial venules (HEV), specialized blood vessels found in secondary lymphoid tissues except for the spleen. The HEV are distinguished from other types of blood vessels by their tall and plump endothelial cells, and by their expression of specific chemokines and adhesion molecules, which all contribute to the selective lymphocyte trafficking across these blood vessels. The development of HEV is ontogenically regulated, and they appear perinatally in the mouse. High endothelial venules can appear ectopically, for instance in chronically inflamed tissues. Given that HEV enable the efficient trafficking of lymphocytes into tissues, the induction of HEV at a tumor site could potentiate tumor‐specific immune responses, and the artificial manipulation of HEV neogenesis might thus provide a new tool for cancer immunotherapy. However, the process of HEV development and the mechanisms by which the unique features of HEV are maintained are incompletely understood. In this review, we discuss the process of HEV neogenesis and development during ontogeny, and their molecular requirements for maintaining their unique characteristics under physiological conditions. (Cancer Sci 2010; 101: 2302–2308)
Chronic administration of the somatostatin analogue SMS 201–995 does not lead to endogenous antibody formation
Authors: FUESSL H. S. , DOMIN J. , ANDERSON J. V. , BLOOM S. R.
Published: July 2010

Plasma samples of seven patients with gut and pancreatic endocrine tumours who have been on long‐term treatment with a long‐acting somatostatin analogue (SMS 201‐995) were investigated for endogenous antibodies to the peptide by incubation with radiolabelled SMS 201–995. The duration of treatment with the somatostatin analogue was between 9 and 26 months and the dose from 100 to 300μg day−1. In none of the patients could antibodies to SMS be detected. The effect of this somatostatin analogue is unlikely to be impaired by formation of endogenous antibodies, even after long‐term treatment.
The gastric proton pump, a target for neuroleptics and antidepressant drugs?
Authors: BEIL W. , STÜNKEL P. , PIEPER A. , SEWING K.‐Fr.
Published: July 2010

The antisecretory action of the antidepressant drugs trimipramine, doxepin and nortriptyline was studied in two different in‐vitro test systems; the isolated and enriched guinea‐pig parietal cell and the purified H+/K+‐ATPase preparation. The effect of the antidepressants was compared with that of the neuroleptic agents chlorpromazine, triflupromazine, trifluoperazine, haloperidol, fluspirilene and with that of the tricyclic anticholinergic agent pirenzepine. All neuroleptics and antidepressants inhibited acid formation in intact parietal cells with IC50 values in the nanomolar range. The inhibitory potency for each compound was identical regardless of whether histamine or db‐cAMP was used as stimulant. Isolated H+/K+‐ATPase, measured in the presence of 5 mmol litre−1 KCl, was inhibited by all psychotropic drugs with IC50 values in the micromolar range. EGTA did not affect the inhibitory potency at the H+/K+‐ATPase, indicating that the action of the drugs does not depend on their calmodulin blocking activity. Pirenzepine was ineffective in both test systems. Kinetic studies done with nortriptyline, chlorpromazine and haloperidol showed a competitive type of inhibition with respect to K+ at low inhibitor concentrations. This competitive type was changed to a mixed type of inhibition with increasing inhibitor concentrations, demonstrating cooperative effects between drug binding and K+ activation of the enzyme. From these data it is suggested that antidepressants and neuroleptics act by an allosteric mechanism of action, and that the lipid solubility is a significant factor to establish enzyme inhibition.
Review: loperamide—a potent antidiarrhoeal drug with actions along the alimentary tract
Authors: RUPPIN H.
Published: July 2010

The synthetic opioid, loperamide, reduces stool weight, frequency of bowel movements, urgency and faecal incontinence in acute and chronic diarrhoea. In man, the mechanism of action of loperamide is primarily the retardation of small‐intestinal transit, and the stimulation of anal sphincter pressure and of faecal continence. This mechanism increases mucosal contact time, allowing more complete absorption of electrolytes and water. Studies in animals have demonstrated inhibitory effects of opiates and opioids, including loperamide, on fluid and electrolyte secretion induced by various secretagogues. By comparison, opiates have smaller if any antisecretory or pro‐absorptive actions in man. The discrepancies between the results obtained in animal and human experiments are most certainly due to the large differences between drug doses used. Besides its opiate‐receptor binding and stimulating activity, loperamide also behaves as a calcium–calmodulin antagonist and as a calcium channel blocker. These two other mechanisms might contribute to loperamide's antidiarrhoeal activity. Loperamide is more effective and safer than other opiates or opioid drugs in the treatment of both infantile and adult diarrhoea of various causes, although adequate fluid and electrolyte replacement remain the prime need.
Comparison of ranitidine 300 mg twice daily, 300 mg at night and placebo on 24‐hour intragastric acidity of duodenal ulcer patients
Authors: MERKI H. S. , WITZEL L. , WALT R. P. , NEUMANN J. , SCHEURLE E. , KAUFMANN D. , MAPPES A. , HEIM J. , RÖHMEL J.
Published: July 2010

Continuous measurement of 24‐hour intragastric acidity was performed in 12 duodenal ulcer patients in remission during treatment with placebo, ranitidine 300 mg nocte and ranitidine 300 mg b.d. Median 24‐hour acidity was 79.4 mmol litre−1 during placebo treatment; it decreased to 28.2 mmol litre−1 during treatment with ranitidine 300 mg nocte and to 3.6 mmol litre−1 during treatment with ranitidine 300 mg b.d. The two regimens decreased intragastric acidity to a similar degree during the night, but significantly greater inhibition of daytime and 24‐hour acidity followed use of ranitidine 300 mg b.d.
Twenty‐four‐hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer, or pernicious anaemia
Authors: LANZON‐MILLER S. , POUNDER R. E. , HAMILTON M. R. , CHRONOS N. A. F. , BALL S. , MERCIECA J. E. , OLAUSSON M. , CEDERBERG C.
Published: July 2010

Twenty‐four‐hour intragastric acidity and plasma gastrin concentration were measured in healthy subjects (n= 16), and patients with duodenal (n= 12) or gastric (n= 10) ulceration, or pernicious anaemia (n= 8). Median integrated 24‐hour intragastric acidity was highest in duodenal ulcer patients and lowest in pernicious anaemia patients (1148 and 0 mmol. hour litre−1, respectively). Median integrated 24‐hour plasma gastrin was highest in pernicious anaemia and lowest in the healthy subjects (9886 and 238 pmol. hour litre−1, respectively). Pernicious anaemia patients have unremitting hypergastrinaemia throughout the 24 hours. The results of this study not only provide a reference range of acidity and plasma gastrin in health and disease, but also will act as a baseline for future studies using antisecretory drugs.
Twenty‐four‐hour intragastric acidity and plasma gastrin concentration before and during treatment with either ranitidine or omeprazole
Authors: LANZON‐MILLER S. , POUNDER R. E. , HAMILTON M. R. , BALL S. , CHRONOS N. A. F. , RAYMOND F. , OLAUSSON M. , CEDERBERG C.
Published: July 2010

Simultaneous 24‐hour intragastric acidity and plasma gastrin concentrations were measured in 12 duodenal ulcer patients before and on the twenty‐eighth day of treatment with either ranitidine 150 mg b.d. or omeprazole 20 mg o.m. Median integrated 24‐hour intragastric acidity was decreased significantly from 1148 to 490 and 36 mmol. hour litre−1 during treatment with ranitidine and omeprazole, respectively, whilst median intragastric 24‐hour plasma gastrin was raised significantly from 328 to 799 and 1519 pmol. hour litre−1 respectively. When the results of all 48 experiments were considered together, there was a significant inverse correlation between the 24‐hour integrated values for intragastric acidity and plasma gastrin concentration. Both drugs caused a significant elevation of plasma gastrin throughout the 24 hours, although ranitidine had no effect on intragastric acidity from 1900 to 2200 hours. When compared with similar profiles of acidity and gastrin in pernicious‐anaemia patients, the modest elevations of plasma gastrin observed in this study suggest that neither drug will be associated with clinically relevant enterochromaffin‐like cell proliferation in duodenal ulcer patients.
Gastric acid secretory capacity falls after repeated within‐day pentagastrin testing in fed subjects
Authors: BROOK C. W. , YEOMANS N. D. , HEWSON E. G. , SMALLWOOD R. A.
Published: July 2010

Between‐day pentagastrin testing yields highly reproducible stimulated gastric acid output values, but little is known of the reproducibility of repeated within‐day pentagastrin tests. We have performed three pentagastrin tests within the 1 day in nine healthy subjects. Within‐day tests were 6 hours apart; the first followed an overnight fast and the second and third were both 4 hours after a substantial meal. A further test was performed the following morning, again after an overnight fast, which allowed comparison of within‐day and between‐day testing. In the second and third within‐day tests there was a marked decrease of stimulated gastric acid output, with both maximal and peak acid output decreased to approximately half of the value of the first test (P< 0.01). By contrast there were no significant differences in the acid output values obtained in between‐day tests (both following an overnight fast). Possible mechanisms for the decreased output on repeated within‐day testing include alterations in the sensitivity of the gastrin receptor, or some neurohumoral influence secondary to the preceding meal. Future studies of the duration of action of drugs affecting acid secretion may need to take account of these findings.
Review: lipoxygenase inhibitors and the gut
Authors: KENNEDY N. P. , KEELING P. W. N.
Published: July 2010

Leukotriene synthesis is influenced by several drugs currently in use for the treatment of alimentary disease, including the corticosteroids, sulphasalazine and mesalazine. However, the use of selective lipoxygenase inhibitors in human gastrointestinal disease has not been investigated. The complexity of eicosanoid metabolism, and the incomplete knowledge of roles played by each metabolite in each tissue and disease condition, make rational pharmacological manipulation of arachidonate metabolism difficult. However, lipoxygenase inhibitors show promise in animal models of inflammation, including hepatitis, and studies in vitro suggest that therapeutic benefits may be achieved using inhibitors of leukotriene synthesis in other inflammatory disorders.
Comparison of two antimuscarinic drugs, pirenzepine and propantheline, on gastric acid secretion, serum gastrin concentration, salivary flow and heart rate in patients with duodenal ulcer disease
Authors: RICHARDSON C. T. , BARNETT C. C. , WALSH J. H. , FELDMAN M.
Published: July 2010

Effects of orally‐administered pirenzepine and propantheline bromide on food‐stimulated gastric acid secretion, serum gastrin concentration, salivary flow and heart rate were compared in 10 duodenal ulcer patients in a placebo‐controlled, double‐blind study. Pirenzepine inhibited acid secretion by 25, 36 and 44% at doses of 50, 100, and 150 mg, respectively, while propantheline inhibited acid secretion by 32 and 41% at doses of 15 and 45 mg, respectively. None of the doses of pirenzepine affected food‐stimulated serum gastrin concentrations, whereas 45 mg propantheline increased serum gastrin concentration significantly above placebo control. Enhancement of gastrin release by propantheline was not due to its antisecretory effect since intragastric pH after the meal was held constant at 5.0 by intragastric titrationin vivo.Pirenzepine had no significant effect on heart rate and little or no inhibitory effect on salivary volume, depending on the dose administered. By contrast, both doses of propantheline increased heart rate and reduced salivary volume significantly (P< 0.05). Thus, pirenzepine and propantheline in the doses administered inhibited acid secretion to approximately the same extent but pirenzepine had fewer effects on other organs.
The effect of oral cisapride on colonic transit
Authors: KREVSKY B. , MALMUD L. S. , MAURER A. H. , SOMERS M. B. , SIEGEL J. A. , FISHER R. S.
Published: July 2010

A prospective double‐blind cross‐over trial of oral cisapride 10 mg and placebo was performed to determine the effects of cisapride on the transit of colonic contents in normal humans. Six male volunteers were studied twice using Colonic transit scintigraphy. After passing a tube to the caecum, 50 μCi of 111Indium diethylene triamine pentaacetic acid were instilled into the bowel lumen. The movement of radiolabelled material was followed using a gamma camera interfaced to a digital computer. Cisapride decreased the half‐emptying of the caecum and ascending colon from 1.68 ± 0±4 hours to 0.72 ± 0.15 hours (P < 0.05). The total colon half‐emptying time was reduced from 38.5 ± 7.2 hours to 11.1 ± 2.9 hours on cisapride (P < 0.05). Cisapride accelerated transit through the transverse colon, but not the descending colon. The progression of the geometric centre was faster during cisapride administration than with placebo (P < 0.05). The number of bowel movements 48‐hours−1 increased after cisapride from 2.5 ± 0.8 to 5.0 ± 0.4 (P < 0.05). This study demonstrates that cisapride has a marked prokinetic effect on Colonic transit in normal subjects. Cisapride may be a useful agent in the treatment of constipation.
Marked suppression of stimulated gastric acid and pepsin secretion by enisoprost, a new PGE1 analogue
Authors: HOWDEN G W. , BURGET D. W. , SILLETTI C. , VAN EEDEN A. , TOMKINS K. B. , HUNT R. H.
Published: July 2010

The gastric antisecretory effects of three different doses of enisoprost, a new synthetic PGE1 analogue, were compared with placebo and misoprostol in 20 healthy male volunteers. Enisoprost 100, 200 and 400 μg all significantly (P < 0.0001; ANOVA) suppressed histamine‐stimulated acid and pepsin output when compared with placebo or misoprostol 200 μg. Misoprostol produced a significant decrease of stimulated acid output when compared with placebo (P= 0.0012). The concentration of pepsin in gastric juice was significantly (P < 0.0001) decreased by enisoprost at the commencement of histamine stimulation. This effect was short‐lived, and was maximal with enisoprost 400 μg. There was a significant dose‐response relationship for enisoprost for inhibition of stimulated acid output (P= 0.0065). Enisoprost was well tolerated, and no consistent drug‐related adverse effects were detected. The profile of antisecretory effect of enisoprost, producing marked suppersion of both acid and pepsin secretion independently, is unusual. This combination of activity along with any mucosal protective properties might be particular effective in the treatment of peptic ulcer disease.
Idiopathic slow‐transit constipation: whole gut transit times, measured by a new simplified method, are not shortened by opioid antagonists
Authors: FOTHERBY K. J. , HUNTER J. O.
Published: July 2010

A simplified method for measuring mean whole gut transit time has been validated which avoids stool collection and is suitable for out‐patients. Radio‐opaque markers are swallowed daily for 14 days and the mean whole gut transit time is derived directly from an abdominal X‐ray. Using this new technique, neither nalmefene (in a double‐blind study of six patients) nor naloxone (in an open study of four patients) shortened mean whole gut transit time in idiopathic slow‐transit constipation.
Review: first‐pass metabolism by the gastrointestinal mucosa
Authors: BACK D. J. , ROGERS S. M.
Published: July 2010

The bioavailability of orally administered drugs may be reduced due to presystemic elimination. The first‐pass effect can occur in the gastrointestinal tract, the liver and lung. Although the liver is the main drug metabolizing organ in the body, the gut wall can play an important role in the first‐pass metabolism of certain drugs. Both phase I (preconjugation) and phase II (conjugation) reactions have been described. However, while the oxidative metabolic capacity of the intestinal mucosa is considerably smaller than that of the liver, the activity of conjugation reactions in the gut may be close to that of the liver, and in some cases may exceed it. Sulphate conjugation is particularly important for steriod hormones such as ethinyloestradiol, and for the β‐adrenoceptor stimulants isoprenaline and isoetharine. Glucuronidation has been demonstrated to occur in man for morphine, paracetamol and oestrogens. Significant drug—drug interactions have been described involving drugs undergoing sulphate conjugation. The study of intestinal metabolismin vivois difficult in man since direct methods (for example, hepatic portal vein catheterization) is justified in only a small number of patients. Therefore, much of our present understanding has been derived from various in‐vitro studies involving intestinal sheets, mucosal biopsies, isolated enterocytes and microsomal preparations.
Review: gut sterilization in inflammatory bowel disease
Authors: HODGSON H. J. F.
Published: July 2010

Achieving a substantial reduction in the bacterial flora of the gut is a theoretically attractive means of treating inflammatory bowel disease, particularly colonic disease. There are practical difficulties in obtaining a sustained reduction of the colonic bacterial count, and the potential role of such a treatment regimen is therefore the initiation of remission. The data in the literature supporting such a suggestion are anecdotal, and a controlled study is indicated.
Ranitidine and cimetidine in the healing of duodenal ulcer: meta‐analysis of comparative clinical trials
Authors: McISAAC R. L. , McCANLESS I. , SUMMERS K. , WOOD J. R.
Published: July 2010

All available ranitidine and cimetidine comparative trials in acute duodenal ulcer disease were examined: of the 44 trials, 36 favoured ranitidine, and there was an overall difference in ulcer healing of 7%. Further stratification enabled examination of trials with common attributes: the most frequent endoscopic assessment was at 4 weeks to compare ranitidine 150 mg twice daily with cimetidine 1 g day−1 or 400 mg b.d. Twenty of these trials had sufficient data to permit pooling. Ranitidine was favoured in 18/20 trials and in three the differences achieved statistical significance. Results of the trials were combined using meta‐analysis to calculate differences in ulcer healing. Most studies had sample sizes that were insufficient to detect clinically‐important differences; the power to detect a 20% difference was less than 80% in 15/20 trials, and for a 10% difference was less than 80% in all but one trial. Fifteen trials compared ranitidine 150 mg b.d. with cimetidine 1 g day−1: healing after 4 weeks therapy was overall 6% greater for ranitidine. This was statistically significant (P < 0.05) and the combined total number of patients had a power of 83% to detect this difference. In five trials the dose of cimetidine used was 400 mg b.d.: the 12% difference in healing in favour of ranitidine 150 mg b.d. was statistically significant, and the combined trials had a power of 95% to detect this difference. Ranitidine 150 mg twice daily heals significantly more duodenal ulcers after 4 weeks of therapy than either cimetidine 400 mg b.d. or cimetidine 1 g day−1.
Comparison of the effectiveness of midazolam and diazepam in lipid emulsion as sedation during upper gastrointestinal endoscopy
Authors: BULLIMORE D. W. , MULLEY B. A. , COOKE P. , MILOSZEWSKI K. J. A.
Published: July 2010

In a study of 101 patients undergoing upper gastrointestinal endoscopy, 90% of patients had complete amnesia for the procedure after intravenous midazolam (average dose 10 mg), but only 61% had complete amnesia after intravenous diazepam in lipid emulsion (average dose 18.4 mg) (P= 0.0006). However, when assessed by two different tests, recovery within the first hour was significantly more rapid after diazepam (P < 0.0001). Prolonged sedation (over 20 hours after injection) was reported occasionally by patients who had received either drug. Thus, as with patients who have been sedated with diazepam, those who have been sedated with midazolam should also be advised to avoid driving or operating machinery for at least 24 hours after injection.
Contractility of human gallbladder muscle in vitro
Authors: FEELEY T. M. , CLANACHAN A. S. , SCOTT G. W.
Published: July 2010

This study examined the effects of transmural nerve stimulation, acetylcholine, adrenoceptor agonists and several peptides on the contractility of strips of human gallbladder in vitro. Acetylcholine caused concentration‐related contractions of the tissues and the sensitivity to acetylcholine was similar in gallbladders with mild and severe chronic cholecystitis. Noradrenaline and adrenaline relaxed gallbladder strips, probably via β2‐adrenoceptor stimulation. Transmural nerve stimulation always caused contractions, but in the presence of atropine inhibitory responses were demonstrable and these were antagonized by propranolol. There was no evidence of non‐adrenergic inhibitory neural responses. Of the peptides tested, only cholecystokinin octapeptide (CCK‐OP), gastrin, pentagastrin, substance P and caerulein caused contractions. Responses to CCK‐OP, gastrin and pentagastrin were antagonized by dibutyryl cyclic GMP. Hormones which had no effect upon human gallbladder strips included motilin, secretin, bombesin, neurotensin, glucagon, vasopressin, VIP and somatostatin. Considerable differences therefore exist between human tissues and those from experimental animals with respect to the direct actions of neural and hormonal stimuli on gallbladder contractility.
The effect of two α2‐adrenoreceptor agonists and an antagonist on gastric emptying and mouth to caecum transit time in humans
Authors: BAXTER A. J. , EDWARDS C. A. , HOLDEN S. , CUNNINGHAM K. M. , WELCH I. McL. , READ N. W.
Published: July 2010

Experiments were performed to investigate the effect of two α2‐adrenoreceptor agonists, clonidine and lidamidine, and a specific α2‐adrenoreceptor antagonist, idazoxan, on gastric emptying and mouth to caecum transit time (MCTT) of a radiolabelled meal in 27 healthy male subjects. Lidamidine (20 mg p.o.) and clonidine (0.3 mg p.o.), given alone had no significant effect on gastric emptying or MCTT suggesting that the anti‐diarrhoeal action of clonidine and lidamidine are unlikely to be explained by a slowing of small intestinal transit. Idazoxan (20 mg p.o.) reversed the effect of clonidine in 10 subjects, who showed a delay in MCTT after taking clonidine, but did not alter MCTT under basal conditions. These results suggest that although the sympathetic nervous system can influence upper gastrointestinal motility by an action on α2‐adrenoreceptors, this action does not exert a tonic influence on upper gastrointestinal motility under basal conditions.
Is it really more difficult to treat prepyloric ulcers?
Authors: HALTER F. , EIGENMANN F.
Published: July 2010

Prepyloric and duodenal ulcers have some common characteristics: gastric acid secretion is increased and there is an association with blood group O. Many, therefore, have considered prepyloric ulcers to be a variety of duodenal ulcer disease. From an anatomical point of view, however, prepyloric ulcers are clearly gastric ulcers. After proximal selective vagotomy, the recurrence rate is very high, amounting to more than 30% in 5 years; this is significantly higher than the rate for duodenal ulcers. Better results are obtained in prepyloric ulcers, if vagotomy is combined with a drainage procedure. In recent years, some evidence, primarily from Scandinavia, has accumulated indicating that prepyloric ulcers are more resistant to treatment with histamine H2‐receptor antagonists than duodenal ulcers or ulcers located in other parts of the stomach. In addition, the recurrence rate is particularly high in prepyloric ulcers. One must, however, consider that not only have all of these studies included relatively small numbers of patients, but also the prepyloric ulcer healing rates in other studies were similar to those observed for both duodenal ulcers and ulcers located elsewhere in the stomach. Prospective studies with large numbers of patients are, therefore, necessary before a clear‐cut conclusion can be reached.

There are several reasons why prepyloric ulcers could be more resistant to treatment. Impaired gastric emptying, duodeno‐gastric reflex or choric gastritis, especially in conjunction with Campylobacter pylori infection, must be considered. At present one can only speculate on the validity of any of these hypotheses.
When and why do ulcers bleed and what can be done about it?
Authors: SWAIN C P.
Published: July 2010

This article reviews the pathophysiology and management of bleeding peptic ulcer. Ulcers bleed when and because they erode into a blood vessel, and bleed massively when they erode into a medium‐ or large‐sized artery. Focal pathology at the bleeding point (such as arteritis, aneurysmal dilatation or recanalized thrombus) contributes to the timing and clinical pattern of ulcer bleeding. Big bleeds are probably associated with erosion into big arteries. The identification of a visible vessel in the floor of an ulcer that has recently bled is predictive of further bleeding, while the absence of a visible vessel or stigmata of recent haemorrhage is strongly predictive that further bleeding will not occur. Unfortunately, no conventional method of managing gastrointestinal bleeding from ulcers has been convincingly shown to be better than placebo in controlled clinical trials. The value of transfusion and surgery has never been tested in controlled trials, while many small studies of drug therapy, especially of H2‐receptor blocking agents, and a few small studies of early surgery afford generally negative or equivocal results. There is some evidence that new physical methods such as lasers or bipolar probes applied at endoscopy are superior to placebo though negative trials have also been reported. Studies randomizing larger numbers of patients with bleeding ulcers are required if therapeutic benefit of any aspect of management is to be demonstrated or refuted.
The place of famotidine in anti‐ulcer therapy
Authors: MANN S. G.
Published: July 2010

Famotidine now presents physicians in the USA and many European countries with a third option when considering H2‐antagonist therapy. A dose of 40 mg in the evening decreases nocturnal gastric acidity for 10–12 hours, leaving daytime‐stimulated acidity virtually unaffected. This single evening dosage regimen produces effective healing of gastric and duodenal ulceration; maintenance of healing can then be achieved satisfactorily with 20 mg in the evening. In extensive clinical studies, the adverse effect profile of famotidine is similar to placebo. Famotidine has no known drug interactions and there are no identified mechanisms by which it might be expected to produce them. Circulating plasma hormone concentrations in man are not affected by famotidine and no antiandrogenic properties have been observed in animal studies. Future potential uses of famotidine may include the treatment of haemorrhage from peptic ulcers and the healing of oesophageal ulceration.
Omeprazole in the treatment of Zollinger—Ellison syndrome: a 4‐year international study
Authors: LLOYD‐DAVIES K. A. , RUTGERSSON K. , SÖLVELL L.
Published: July 2010

The H+, K+‐ATPase inhibitor omeprazole has been made available on a compassionate basis for patients with Zollinger—Ellison syndrome considered resistant to, or with side‐effects on, histamine Hz ‐receptor antagonists. By December 1985, the first 80 patients, from 46 centres in 11 countries, had been treated for periods of 2 days to 4 years. Basal acid output was decreased to the desired level of less than 10 mmol · hour1, and symptoms were rapidly relieved. Acid secretion and laboratory variables were checked regularly and endoscopic examinations made at intervals. Dosage was adjusted primarily on the basis of basal acid output, but also if symptoms recurred. The starting dose was generally 60 mg daily and the median dose ranged between 60 and 70 mg daily over the study period. There was no evidence of tachyphylaxis. More than 90 % of the patients were successfully controlled on total daily doses of 120 mg or less; one‐third of patients required divided doses. Tolerance was good: there were no obvious drug‐related effects on laboratory variables, including fasting serum gastrin, and there were very few adverse events. Thirteen patients died (11 of the primary disease and two of other causes), four underwent successful tumour resection, six underwent total gastrectomy (though acid secretion was controlled in five), four patients’ treatment was changed to other medical therapy, and one was lost to follow‐up. Omeprazole thus appears to be both safe and very effective in controlling acid hypersecretion in this group of patients, and to provide a suitable alternative to total gastrectomy.
Effect of a slow‐release formula of trimoprostil on intragastric acidity in healthy volunteers
Authors: EMDE C. , CILLUFFO T. , BAUERFEIND P. , FIMMEL C. J. , BLUM A. L.
Published: July 2010

We investigated the effect of a slow‐release formula of trimoprostil, a prostaglandin E2 analogue, at a dose of 3 mg b.d. on circadian intragastric acidity in nine healthy volunteers using ambulatory pH‐metry in a placebo‐controlled study. The effect of trimoprostil was long lasting (8 hours during the night). However, it lowered gastric pH on average only by 0.4 pH units. In four of the six women severe side‐effects occurred in the form of abdominal cramping, metrorrhagia, and/or diarrhoea. These disadvantages may limit the clinical use of this drug.
Somatostatin compared with cimetidine in the treatment of bleeding peptic ulcer without visible vessel
Authors: SAPERAS E. , PIQUÉ J. M. , PÉREZ‐AYUSO R. , FUSTER F. , TERÉS J. , BORDAS J. M. , RODÉS J.
Published: July 2010

In a randomized double‐blind trial 100 patients with severe bleeding peptic ulcers were treated with an intravenous (i.v.) infusion of cimetidine or somatostatin. Only those patients in whom endoscopy performed within 6 h of admission showed non‐arterial bleeding or signs of recent haemorrhage without a visible vessel entered the trial. The two treatment groups were well matched for age, sex, presence of underlying disease, prior ingestion of ulcerogenic drugs, tobacco habits, type of bleeding, haematocrit at admission, presence of hypovolaemic shock, source of bleeding and endoscopic findings. Four patients in each group were excluded after randomization. Further haemorrhage occurred in eight (17.3%) patients in the somatostatin group and in 10 (21.7%) in the cimetidine group, but the difference was not statistically significant. The number of surgical procedures, blood transfusion requirement, duration of hospitalization and mortality rates were similar in the two treatment groups. These results suggest that somatostatin does not improve the results obtained with cimetidine in patients with bleeding peptic ulcer, in whom the endoscopy discloses non‐arterial bleeding or signs of recent haemorrhage without a visible vessel.
The effects of the 5‐hydroxytryptamine (5HT3) receptor antagonist ICS 205‐930 in the carcinoid syndrome
Authors: COUPE M. O. , ANDERSON J. V. , MORRIS J. A. , ALSTEAD E. M. , BLOOM S. R. , HODGSON H. J. F.
Published: July 2010

Therapy for diarrhoea associated with the carcinoid syndrome is often unsatisfactory. In an open study ICS 205‐930 (Sandoz Limited), a novel 5HT3‐antagonist, controlled diarrhoea in five of six patients studied. This drug may be a useful advance in the symptomatic treatment of the carcinoid syndrome.
Balsalazide in the maintenance treatment of patients with ulcerative colitis, a double‐blind comparison with sulphasalazine
Authors: McINTYRE P. B. , RODRIGUES C. A. , LENNARD‐JONES J. E. , BARRISON I. G. , WALKER J. G. , BARON J. H. , THORNTON P. C.
Published: July 2010

Balsalazide (BSZ) is a pro‐drug which releases 5‐aminosalicylic acid (5ASA) and 4‐aminobenzoyl‐β‐alanine (an inert carrier) in the colon of various species including man. BSZ was compared with sulphasalazine (SASP) (both 1 g b.d. orally) in the maintenance of remission in patients with ulcerative colitis (UC). Seventy‐nine patients (5.3 male, 26 female), mean age 49 years (range 19–79 years), with UC were randomly allocated to either treatment (41 BSZ, 38 SASP) for 6 months. The groups were similar in respect of age, sex, duration and extent of disease. Seven patients defaulted (3 BSZ, 4 SASP) leaving 38 on BSZ and 34 on SASP. Two male patients, both receiving SASP, were withdrawn because of severe side‐effects. One of these patients, with an exfoliative rash, was maintained satisfactorily on open BSZ. Remission rates at 6 months (51% BSZ, 63% SASP) were not significantly different (life‐table analysis P < 0.1). Twelve patients (15%) reported troublesome side‐effects (2 BSZ 5%, 10 SASP 26%, P= 0.017 Fisher Exact Test). Mean haemoglobin concentrations, similar on entry, increased after 6 months with BSZ (0.2 g/dl) but decreased with SASP (0.5 g/dl) (P < 0.0002). BSZ was not significantly different from SASP in maintaining remission in patients with UC but had fewer side‐effects.
Effect of low‐dose omeprazole on gastric acid secretion in duodenal ulcer patients
Authors: McLAUCHLAN G. , CREAN G. P. , McCOLL K. E. L.
Published: July 2010

The effect of 7 days of oral dosing with 5 mg day−1 and 20 mg day−1 omeprazole on basal and pentagastrin‐stimulated gastric acid output was studied in nine duodenal ulcer patients. Basal acid output measured 5–6 h post‐dosing was decreased by a mean of 75% on 5 mg omeprazole and by 90% on 20 mg omeprazole (P < 0.05 and P < 0.01, respectively). Peak acid output measured 6–7 h post‐dosing was decreased by a mean of 75% on 5 mg omeprazole and 90% on 20 mg omeprazole (P < 0.01 for each). There was a wide interindividual variation in response to the 5 mg dose, with five of the nine patients having more than 90% inhibition of peak acid output, but two patients having less than 40% inhibition. This unpredictable response to daily low‐dose omeprazole therapy makes it unsuitable for maintenance treatment.
Review: the enterochromaffin‐like cell, intragastric acidity and the trophic effect of plasma gastrin
Authors: POLAK J. M. , BLOOM S. R.
Published: July 2010

Although enterochromaffin‐like (ECL) cells form the major endocrine cell population of the non‐antral stomach, they have been largely overlooked in the study of gastric disease. In the human, their product and functions are unknown, but they are associated with histamine secretion in rodents. The cells are controlled by neural and hormonal factors, the most significant of the latter being gastrin. Interest in ECL cells has been stimulated by the observation that hyperplasia of these cells, sometimes leading to formation of gastric carcinoid tumours, occurs in conditions of persistent hypergastrinaemia — for example, in response to the achlorhydria of individuals with pernicious anaemia. The advent of new highly potent inhibitors of gastric acid secretion is allowing more information to be obtained on the physiology and functions of the ECL cell. However, there is clearly a great deal more to be discovered about this enigmatic endocrine cell type.
Gastro‐oesophageal reflux associated with nifedipine
Authors: JENKINSON L. R. , NORRIS T. L. , WATSON A.
Published: July 2010

A 57‐year‐old woman presented with a 3‐week history of dysphagia for solids, 6 months after starting treatment with nifedipine. Endoscopy demonstrated oesophagitis and a benign oesophageal stricture. Twenty‐four‐hour ambulatory pH monitoring demonstrated decreased acid reflux 8 weeks after withdrawal of nifedipine, with coincidental symptomatic and endoscopic improvement. Nifedipine may induce, or aggravate, pre‐existing, gastro‐oesophageal reflux.
The effect of a long‐acting somatostatin analogue on portal and systemic haemodynamics in cirrhosis
Authors: PRINGLE S. D. , McKEE R. F. , GARDEN O. J. , LORIMER A. R. , CARTER D. C.
Published: July 2010

Current interest in the pharmacological manipulation of portal pressure centres on the long‐acting somatostatin analogue SMS 201‐995. Nine haemodynamically stable cirrhotic patients who had previously bled from oesophageal varices had wedged and free hepatic venous pressures and cardiac index measured, using a Swan—Ganz catheter, before and at 60, 120 and 180 min after beginning a 60‐min infusion of 25 μg/h of SMS 201‐995. Seven clinically similar patients had the same measurements performed without SMS 201‐995. In all patients cardiac index was found to decrease and systemic vascular resistance increase at 60 min, although heart rates and arterial blood pressures were unchanged. The group given SMS 201‐995 was significantly different from the control group in sustaining a fall in wedged hepatic venous pressure and trans‐hepatic venous gradient at 60 min. SMS 201‐995 causes a fall in portal pressure without a significant systemic haemodynamic effect.