bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient participation
Authors: Zhang Wei
Published: July 2010

This study analyses patient questions in prenatal genetic counselling (PGC) in a Hong Kong hospital. The focus is on the kinds of questions asked by the patients and the sequential environments in which the questions are asked. The ten patients in the study are pregnant women at or above 38 years of age, four local Cantonese-speaking Chinese, and six of Filipina or Thai origin. The PGC is conducted by a nurse who communicates with the Chinese patients in Cantonese and with the non-Chinese patients in English. Two broad types of questions, medical and administrative, in line with the purpose of PGC, are found in both groups. While both groups share a concern on the accuracy of the test, the Chinese group asks more questions on medical details beyond the issue of accuracy. With regard to sequential environments, questions may be either ‘occasioned’ by the nurse’s prior talk or ‘self-motivated’; both may occur in the positions for minimal responses in extended information delivery sequences. Self-motivated questions also occur as a second or later component in the patient’s extended turn. While the two groups of patients ask questions from either of the sequential positions, a qualitative difference lies in the turn design of the self-motivated questions.
Mandatory Influenza Vaccination of Healthcare Workers: A 5-Year Study
Authors: Rakita Robert M. , Hagar Beverly A. , Crome Patricia , Lammert Joyce K.
Published: July 2010

Background.

The rate of influenza vaccination among healthcare workers (HCWs) is low, despite a good rationale and strong recommendations for vaccination from many health organizations.

Objective.

To increase influenza vaccination rates by instituting the first mandatory influenza vaccination program for HCWs.

Design and Setting.

A 5-year study (from 2005 to 2010) at Virginia Mason Medical Center, a tertiary care, multispecialty medical center in Seattle, Washington, with approximately 5,000 employees.

Methods.

All HCWs of the medical center were required to receive influenza vaccination. HCWs who were granted an accommodation for medical or religious reasons were required to wear a mask at work during influenza season. The main outcome measure was rate of influenza vaccination among HCWs.

Results.

In the first year of the program, there were a total of 4,703 HCWs, of whom 4,588 (97.6%) were vaccinated, and influenza vaccination rates of more than 98% were sustained over the subsequent 4 years of our study. Less than 0.7% of HCWs were granted an accommodation for medical or religious reasons and were required to wear a mask at work during influenza season, and less than 0.2% of HCWs refused vaccination and left Virginia Mason Medical Center.

Conclusion.

A mandatory influenza vaccination program for HCWs is feasible, results in extremely high vaccination rates, and can be sustained over the course of several years.
Ubc4 and Not4 Regulate Steady-State Levels of DNA Polymerase-α to Promote Efficient and Accurate DNA Replication
Authors: Haworth Justin , Alver Robert C. , Anderson Melissa , Bielinsky Anja-Katrin
Published: July 2010

The accurate duplication of chromosomal DNA is required to maintain genomic integrity. However, from an evolutionary point of view, a low mutation rate during DNA replication is desirable. One way to strike the right balance between accuracy and limited mutagenesis is to use a DNA polymerase that lacks proofreading activity but contributes to DNA replication in a very restricted manner. DNA polymerase-α fits this purpose exactly, but little is known about its regulation at the replication fork. Minichromosome maintenance protein (Mcm) 10 regulates the stability of the catalytic subunit of pol-α in budding yeast and human cells. Cdc17, the catalytic subunit of pol-α in yeast, is rapidly degraded after depletion of Mcm10. Here we show that Ubc4 and Not4 are required for Cdc17 destabilization. Disruption of Cdc17 turnover resulted in sensitivity to hydroxyurea, suggesting that this pathway is important for DNA replication. Furthermore, overexpression of Cdc17 in ubc4 and not4 mutants caused slow growth and synthetic dosage lethality, respectively. Our data suggest that Cdc17 levels are very tightly regulated through the opposing forces of Ubc4 and Not4 (destabilization) and Mcm10 (stabilization). We conclude that regular turnover of Cdc17 via Ubc4 and Not4 is required for proper cell proliferation.
Affluence and Food: A Simple Way to Infer Incomes
Authors: Clements Kenneth W. , Chen Dongling
Published: July 2010

Accurate and timely measures of cross‐country real incomes are still a rarity. As the share of expenditure devoted to food is readily available, we use Engel's law in reciprocal form to measure affluence. Analysis of real income data for over 100 countries indicates that this approach is viable. To recognize the role of uncertainty in the analysis, we present the results in the form of stochastic cross‐country income comparisons.
Stem Rust Spores Elicit Rapid RPG1 Phosphorylation
Authors: Nirmala Jayaveeramuthu , Drader Tom , Chen Xianming , Steffenson Brian , Kleinhofs Andris
Published: July 2010

Stem rust threatens cereal production worldwide. Understanding the mechanism by which durable resistance genes, such as Rpg1, function is critical. We show that the RPG1 protein is phosphorylated within 5 min by exposure to spores from avirulent but not virulent races of stem rust. Transgenic mutants encoding an RPG1 protein with an in vitro inactive kinase domain fail to phosphorylate RPG1 in vivo and are susceptible to stem rust, demonstrating that phosphorylation is a prerequisite for disease resistance. Protein kinase inhibitors prevent RPG1 phosphorylation and result in susceptibility to stem rust, providing further evidence for the importance of phosphorylation in disease resistance. We conclude that phosphorylation of the RPG1 protein by the kinase activity of the pK2 domain induced by the interaction with an unknown pathogen spore product is required for resistance to the avirulent stem rust races. The pseudokinase pK1 domain is required for disease resistance but not phosphorylation. The very rapid phosphorylation of RPG1 suggests that an effector is already present in or on the stem rust urediniospores when they are placed on the leaf surface. However, spores must be alive, as determined by their ability to germinate, in order to elicit RPG1 phosphorylation.
Distribution of Four Viruses in Single and Mixed Infections Within Infected Watermelon Plants in Florida
Authors: Turechek William W. , Kousik Chandrasekar S. , Adkins Scott
Published: July 2010

Whitefly-transmitted Squash vein yellowing virus (SqVYV) and Cucurbit leaf crumple virus (CuLCrV) and aphid-transmitted Papaya ringspot virus type W (PRSV-W) have had serious impact on watermelon production in southwest and west-central Florida in the past 5 years. Tissue-blot nucleic acid hybridization assays were developed for simple, high-throughput detection of these three viruses as well as Cucurbit yellow stunting disorder virus (CYSDV), which was first reported in Florida in 2008. To determine virus distribution within plants, we collected 80 entire plants just before or during the harvest period in a systematic sample, 20 each on 11 April, 18 April, 26 April, and 3 May 2007, from a fruiting commercial watermelon field near Immokalee, FL showing symptoms of infection by SqVYV, CuLCrV, and PRSV-W and, possibly, CYSDV. This was followed by a sampling of five plants collected at harvest showing symptoms of virus infection on 11 October 2007 in a different commercial planting located in Duette, FL. Tissue prints were made from cross sections of watermelon plants from the crowns through the tips at 0.6-m intervals on nylon membranes and nucleic acid hybridization assays were used for virus detection. Results from testing crown tissue showed that SqVYV, CuLCrV, and PRSV-W were present in ≈37, 44, and 54%, respectively, of the 80 plants collected over the four sampling dates from the first field. For individual vines diagnosed with SqVYV, the distribution of SqVYV in vine tissue decreased proportionately with distance from the crown. The probability of detecting SqVYV was 70% at the base of the vine compared with 23% at the tip of the vine. In contrast, CuLCrV tended to be more evenly distributed throughout the plant, with ≈10% higher probability of detection at the growing tip relative to the crown of the plant. The distribution of PRSV-W resembled that of SqVYV but with ≈20% higher probability of detection at the tip of the vine. Similar trends were detected in the smaller sampling; however, CYSDV was also detected in three of the plants. Overall, the results indicated that SqVYV and PRSV-W were distributed differently than CuLCrV in watermelon plants, and this difference has implications on how samples should be collected and may affect vector acquisition and transmission of these viruses.
Effect of different modes of viral spread on the dynamics of multiply infected cells in human immunodeficiency virus infection
Authors: Wodarz Dominik , Levy David N.
Published: July 2010

Infection of individual cells with more than one HIV particle is an important feature of HIV replication, which may contribute to HIV pathogenesis via the occurrence of recombination, viral complementation and other outcomes that influence HIV replication and evolutionary dynamics. A previous mathematical model of co-infection has shown that the number of cells infected with
i
viruses correlates with the
i
th power of the singly infected cell population, and this has partly been observed in experiments. This model, however, assumed that virus spread from cell to cell occurs only via free virus particles, and that viruses and cells mix perfectly. Here, we introduce a cellular automaton model that takes into account different modes of virus spread among cells, including cell to cell transmission via the virological synapse, and spatially constrained virus spread. In these scenarios, it is found that the number of multiply infected cells correlates linearly with the number of singly infected cells, meaning that co-infection plays a greater role at lower virus loads. The model further indicates that current experimental systems that are used to study co-infection dynamics fail to reflect the true dynamics of multiply infected cells under these specific assumptions, and that new experimental techniques need to be designed to distinguish between the different assumptions.
High‐Temperature Properties of Mixed α′/β′‐SiAlON Materials
Authors: Klemm Hagen , Herrmann Mathias , Reich Thomas , Schubert Christian , Frassek Lutz , Wötting Gerhard , Gugel Ernst , Nietfeld Georg
Published: July 2010

The mechanical behavior of mixed α′/β′‐SiAlON materials was studied at elevated temperatures. Two different α′/β′‐SiAlON compositions along the Si3N4‐Y2O39AlN composition line in the Si3N4‐Al2O3AlN‐YN3AlN plane (α′‐SiAlON plane) were prepared using three different raw‐material mixtures. Six different materials were obtained with significantly lower values in α′‐SiAlON than expected. The high‐temperature properties of the materials studied were influenced strongly by the chemical composition (α′ content and grain‐boundary phase) of the SiAlONs. A high content of α′‐SiAlON was beneficial in terms of creep behavior of the materials. The same materials, however, were characterized by a considerably degradated fracture behavior at elevated temperatures in air because of a crack‐growth process enhanced by the poor oxidation resistance of these materials. It was concluded that, despite some superior features of the materials studied, a long‐term application of mixed α′/β′‐SiAlON materials at 1400°C in air is problematical. A combination of all properties required for such applications was not observed. For that reason, it is suggested that the real high‐temperature potential of these materials in air should be limited to temperatures <1300°C.
Superfast Densification of Oxide/Oxide Ceramic Composites
Authors: Gao Lian , Shen Zhijian , Miyamoto Hiroki , Nygren Mats
Published: July 2010

Superfast densification of ceramic composites in the pseudobinary system Al2O3‐Y3Al5O12 was carried out by using a new technique called spark plasma sintering (SPS). Dense ceramic composites were obtained by heating appropriate powder mixtures to 1573 K in an SPS unit at a rate of 600 K/min. No holding time at 1573 K was applied. Scanning electron microscopy studies showed the compacted materials to contain submicrometer‐sized grains of the same sizes as the precursor powder mixtures; i.e., no significant grain growth had occurred.
Conversion of a Precursor Derived from Cage‐Type and Cyclic Molecular Building Blocks into Al‐Si‐N‐C Ceramic Composites
Authors: Nakashima Hiroaki , Koyama Seiichi , Kuroda Kazuyuki , Sugahara Yoshiyuki
Published: July 2010

A precursor derived from (HAlNiPr)m and [MeSi(H)NH]n, which mainly consisted of cage‐type compounds and cyclic compounds, respectively, was converted into Al‐Si‐N‐C ceramic composites via pyrolysis. A dehydrocoupling reaction between AlH groups and NH groups occurred at low temperatures (≤∼250°C), which mainly accounts for its high ceramic yield (69% up to 900°C). At high temperatures (≥∼250°C), the organic groups were decomposed. The product pyrolyzed at 1350° and 1500°C under Ar contained a 2H wurtzite‐type compound and a β‐Si3N4‐type compound, while β‐SiC was clearly detected in addition to these compounds in the product pyrolyzed at 1600°C under Ar. On the other hand, the product pyrolyzed at 800°C under NH3 and subsequently at 1350°C under N2 consisted of AlN and β‐Sialon.
Successful treatment of combination therapy with tacalcitol lotion associated with sunscreen for localized Darier’s disease
Authors: ABE Masatoshi , YASUDA Masato , YOKOYAMA Yoko , ISHIKAWA Osamu
Published: July 2010

We herein report a sporadic case of Darier’s disease localized to the bilateral side of the neck in a 39‐year‐old Japanese woman. Several clinical variants of Darier’s disease have so far been recognized including unilateral Darier’s disease, localized Darier’s disease, segmental Darier’s disease and acral Darier’s disease. Few cases of Darier’s disease, restricted to sun‐exposed areas such as the bilateral side of the neck, have been described in the published work. It remains controversial, however, whether ultraviolet exposure can induce the onset of Darier’s disease. Our patient’s skin lesions, which were resistant to previous treatment with corticosteroid, improved substantially with high‐concentration tacalcitol lotion and sunscreen. This is the first report on the efficacy of topical tacalcitol lotion associated with sunscreen for the treatment of localized Darier’s disease.
Review: clinical trials in peptic ulcer disease—problems of methodology and interpretation
Authors: LAURITSEN K. , RASK‐MADSEN J.
Published: July 2010

This review focuses on the methodology and interpretation of drug trials in peptic ulcer disease. The problems of planning and conduct that are discussed include the ethics of using placebo, eligibility criteria, estimations of sample size, stopping rules, randomization, blinding, and efficacy criteria, that is, ulcer healing and pain relief in the short term and prevention of relapse and complications in the long term. Statistical topics covered include confidence intervals, evaluation of survival type data, post‐stratification, and sub‐group analysis. The difference between clinical and statistical significance is discussed, major problems being overemphasis onP‐value, type II errors, andpost hocpower determinations. Explanatory and pragmatic questions are based on compliance‐to‐protocol and intention‐to‐treat cohorts, respectively, and involve problems of compliance testing, evaluation of withdrawals, and the use of fixed‐dose regimens. The rather slow process for clinical trials to gain acceptance is described, and it is proposed to rely on disease‐related and behavioural barriers, lack of knowledge of the inherent limitations of methodology, and overemphasis on the subject of peptic ulcer healing, in addition to some concern at the relevance of assessing long‐term drug intervention by repeated endoscopies rather than by studying symptoms and the incidence of complications. We foresee an increased impact of clinical trials on ulcer research and therapeutic decision making, provided physicians are able to develop the proper methodology to answer the relevant questions.
Effect of naloxone, domperidone and idazoxan on the delay in gastric emptying induced by ileal lipid
Authors: WELCH I. McL. , BAXTER A. J. , READ N. W.
Published: July 2010

Studies were carried out on 22 healthy male volunteers to investigate whether intravenous administration of either the opiate antagonist, naloxone, or the dopamine antagonist, domperidone, or the α2‐adrenoreceptor antagonist, idazoxan, could reverse the delay in gastric emptying induced by ileal infusion of lipid emulsion. Ileal infusion of 50% lipid emulsion signficantly delayed the rate of gastric emptying compared with ileal infusion of isotonic saline (P< 0.01). Intravenous infusion of naloxone (20 μg kg−1hour−1) or prior administration of either intravenous domperidone (20 mg) or idazoxan (0.2 mg kg−1) did not inhibit the delay in gastric emptying induced by ileal infusion of lipid emulsion. These observations indicate that feedback regulation of gastric emptying by ileal lipid does not appear to be mediated by either dopaminergic or enkephalinergic neurons, nor by α2‐adrenoreceptors.
What are the current possibilities in treating peptic ulcer disease?
Authors: DAMMANN H. G. , WALTER TH. A. , DREYER M. , DAU B. , MÜLLER P. , SIMON B.
Published: July 2010

There are two major principles of ulcer therapy. Today, the most widely accepted drugs are those which substantially reduce aggressive factors (i.e. acid and pepsin), namely histamine H2‐receptor antagonists, antimuscarinics and antacids. Less frequently applied are mucoprotective agents like colloidal bismuth compounds and sucralfate. Prostaglandins both reduce acid secretion substantially and are believed to enhance mucosal resistance. Their anti‐ulcer efficacy, however, is solely explicable by their antisecretory activity. Although mucosa‐strengthening agents and H2‐receptor blockers have nearly identical healing rates, mucosa‐strengthening agents have inconvenient dosage regimens (four times or twice daily) and are probably less effective in relieving pain. The same holds true for antacids. Prostaglandins, antimuscarinics and antacids have dose related side effects. In contrast, H2‐receptor blockers are characterized by a clear mechanism of action, convenient dosage regimes, good tolerance and a low incidence of side‐effects. H2‐receptor antagonists are the most effective anti‐ulcer drugs presently available.
When should endoscopy (or radiology) be used in dyspepsia and peptic ulcer disease?
Authors: COLIN‐JONES D.G.
Published: July 2010

It is now possible readily to investigate dyspeptic symptoms using either a double‐contrast barium meal or upper gastrointestinal endoscopy. The accuracy of endoscopy makes it preferable for routine use. As oesophagogastro‐duodenoscopy (OGD) is invasive, some risks (albeit very small) are involved. Moreover, this technique has some weaknesses. For these reasons, selection of patients is important. Organic disease is most likely to occur in older patients: anyone presenting with dyspepsia for the first time over the age of 40 years should be investigated automatically. In individuals under 40 years of age, organic disease is less common and some selection criteria should be applied to reduce the number of negative investigations. After age, smoking is probably the single most important adverse factor. For gastric ulcer, endoscopy with biopsy, repeated after a course of therapy, is routine, but for duodenal ulcer repeat examination need not normally be undertaken owing to the effectiveness of modern healing drugs. Methods for improving the diagnostic accuracy of patient histories and clinical examinations need to be developed in order to utilize diagnostic investigations more efficiently for the patients’benefit.
Double‐blind comparison of 5‐aminosalicylic acid and acetyl‐5‐aminosalicylic acid suppositories in patients with idiopathic proctitis
Authors: HOGEZAND R. A. VAN , HEES P. A. M. VAN , GORP J. P. W. M. VAN , LIER H. J. J. VAN , BAKKER J. H. , WESSELING P. , HAELST U. J. G. M. VAN , TONGEREN J. H. M. VAN
Published: July 2010

Suppositories containing 300 mg 5‐aminosalicylic acid (1.96 mmol) or 425 mg acety1‐5‐aminosalicylic acid (1.96 mmol) were used in 40 patients with idiopathic proctitis to determine the efficacy of acetyl‐5‐aminosalicylic acid in treating this bowel inflammation. Each patient was treated with 5‐aminosalicylic acid or acetyl‐5‐aminosalicylic acid suppositories twice daily for 4 weeks in a double‐blind trial. Four patients were included twice in the trial. The second time they were treated with the alternative regimen. Six patients in the acetyl‐5‐aminoscylic acid group did not complete the trial, four of them because of diarrhoea. Complete clinical remission with normal rectal mucosa on sigmoidoscopy was achieved in 10 out of 18 patients on 5‐aminosalicylic acid and in only two out of 15 in the acetyl‐5‐aminosalicylic acid group (P= 0.03). A favourable histological improvement was demonstrated with 5‐aminosalicylic acid suppositories, but the difference with acetyl‐5‐aminosalicylic acid was not significant (P= 0.059). Three of the four patients who received both drugs recovered with 5‐aminosalicylic acid; in none of them was acetyl‐5‐aminosalicylic acid effective. The results from this study and from previous investigations show that acetyl‐5‐aminosalicylic acid is not superior to placebo.
The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations
Authors: HAWTHORN M. , FERRANTE J. , LUCHOWSKI E. , RUTLEDGE A. , WEI X. Y. , TRIGGLE D. J.
Published: July 2010

The activities of menthol and peppermint oil were determined in guinea‐pig ileal smooth muscle, in rat and guinea‐pig atrial and papillary muscle, in rat brain synaptosomes and in chick retinal neurones by pharmacological45Ca2+uptake and radioligand binding assays. Menthol is a major constituent of peppermint oil and is approximately twice as potent as peppermint oil as an inhibitor of K+depolarization‐induced and electrically stimulated responses in ileum and electrically stimulated atrial and papillary muscles. IC50values in the ileal preparation ranged from 7.7 to 28.1 μg ml−1and in the cardiac preparations from 10.1 to 68.5 μg ml−1. Similar potencies were demonstrated against K+depolarization‐induced45Ca2+uptake in synaptosomes and against K+depolarization and Bay K 8644‐induced uptake in chick retinal neurons. IC50values for menthol inhibition of K+and Bay K 8644 responses in the retinal neurons were 1.1 × 10−4M (17.2 μg ml−1) and 1.75 × 10−4M (26.6 μg ml−I), respectively, and for peppermint oil were 20.3 and 41.7 μg ml−1respectively. Both menthol and peppermint oil inhibited specific [3H]nitrendipine and [3H]PN 200–110 binding to smooth and cardiac muscle and neuronal preparations with potencies comparable to, but slightly lower than, those measured in the pharmacological and45Ca2+uptake experiments. Binding of menthol and peppermint oil, studied at 78 μg ml−1, was competitive against [3H]nitrendipine in both smooth muscle and synaptosome preparations. The data indicate that both menthol and peppermint oil exert Ca2+channel blocking properties which may underlie their use in irritable bowel syndrome. Ca2+channel antagonism may not be the only pharmacological effect of menthol and peppermint oil contributing to intestinal smooth muscle relaxation.
Prophylaxis of aspirin‐induced gastric mucosal bleeding with ranitidine
Authors: HAWKEY C. J. , SOMERVILLE K. W. , MARSHALL S.
Published: July 2010

The ability of ranitidine to protect the human gastric mucosa against aspirin‐induced damage was investigated by timed measurements of blood loss collected by gastric washing. Ranitidine (150 mg) 1 h or 5 h before 900 mg aspirin (5 doses of each) over 48 h reduced subsequent mean bleeding from 7.7 μi/10 min to 2.6 μl/10 min or 3.4 μl/10 min, respectively. Both regimens were antisecretory at the time of aspirin administration, as judged by a rise in the pH of the aspirated washings. The prolonged protection against aspirin‐induced bleeding achieved with twice daily dosing with ranitidine has dinical potential in the management of patients taking anti‐inflammatory drugs.
Review: new aminosalicylic acid derivatives for the treatment of inflammatory bowel disease
Authors: ARVIND A. S. , FARTHING M. J. G.
Published: July 2010

Up to 20–30% of patients treated with sulphasalazine experience a variety of adverse effects, principally due to the carrier moiety sulphapyridine. In the last decade there has been a major drive to develop a new generation of 5‐aminosalicylic acid (5‐ASA) and 5‐ASA‐related drugs which not only have a high efficacy but are also devoid of the unwanted side‐effects of sulphapyridine. Various forms of 5‐ASA have been evaluated in ulcerative colitis and appear to be effective orally in preventing relapse and topically in the treatment of active distal colitis. More recently, topical 4‐ASA has been found to be useful for the treatment of distal colitis with the advantage of better stability and lower cost compared with 5‐ASA. In the foreseeable future it seems likely that these new aminosalicylic acid derivatives will become the drugs of choice in the treatment of inflammatory bowel disease and largely replace sulphasalazine.
Enprostil inhibits post‐prandial gastrin release: a dose—response study
Authors: LANZON‐MILLER S. , ALLISON M. C. , POUNDER R. E. , BALL S. , HAMILTON M. R. , CHRONOS N. A. F.
Published: July 2010

In a double‐blind placebo‐controlled study in nine healthy volunteers, the effects of single doses of oral enprostil (8.75, 17.5, 35 and 70 μg), taken before a standard breakfast, were assessed on the post‐prandial release of gastrin into the plasma. All doses of enprostil caused a significant dose‐related decrease in median post‐prandial plasma gastrin concentration (range from — 29 to — 44%). In the same subjects, two doses of 25 mg indomethacin caused a significant (38%) increase in median post‐prandial plasma gastrin concentration.
A double‐blind crossover comparison of lidamidine, loperamide and placebo for the control of chronic diarrhoea
Authors: ALLISON M. C. , SERCOMBE J. , POUNDER R. E.
Published: July 2010

Fourteen patients with chronic diarrhoea, but no evidence of active organic disease, completed a double‐blind crossover comparison of the anti‐diarrhoeal effects of loperamide, placebo and the clonidine analogue, lidamidine. Failure of diarrhoea control led to early withdrawals from seven placebo‐ and six lidamidine‐treatment periods, but there was only one early withdrawal during treatment with loperamide. Loperamide was found to be superior to lidamidine or placebo for the control of stool consistency in patients with chronic diarrhoea.
A model of an ‘artificial stomach’ for assessing the characteristics of an antacid
Authors: VATIER J. , LIONNET F. , VITRÉ M. T. , MIGNON M.
Published: July 2010

A model of an ‘artificial stomach’ has been constructed in order to take into account some of the parameters lacking in conventional in vitro antacid evaluation, namely the interaction between secretory flux and variation in emptying fluxes, the presence of proteins, and the use of human gastric juice instead of an aqueous solution of hydrochloric acid.

The ‘artificial stomach’ has two elements, the ‘stomach’ and the pH recording system. The ‘stomach’ includes a ‘gastric’ reservoir receiving secretory flux and is emptied by variable fluxes.

Aluminium phosphate gel has been studied in 100 ml of 0.1 n HCl, without and with 1 or 5% meat extracts and also in 100 ml of human gastric juice. The antacid effect of 1 or 5% meat extracts has also been assessed.

The antacid effect of aluminium phosphate was characterized by the pH rise of the ‘gastric’ contents, the buffering capacity, and the dilution of gastric contents. These factors were modulated by emptying fluxes. The same characteristics were found when antacid was studied in gastric juice. Proteins exerted a neutralizing effect and modified aluminium phosphate's antacid capacity. A mechanism for buffering capacity by cation aluminium is suggested.
The effect of food on ranitidine‐induced inhibition of nocturnal gastric secretion
Authors: JOHNSTON D. A. , WORMSLEY K. G.
Published: July 2010

Overnight gastric secretion of acid and pepsin was studied in nine, healthy, male volunteers on two separate occasions, in randomized order. On one day, each individual received a standard meal at 18.00 hours, followed by an oral dose of 300 mg ranitidine at 18.15 hours. During the second study, 300 mg ranitidine was again taken at 18.15 hours, but the meal was consumed at 22.00 hours.

Gastric juice was sampled hourly from 19.00 to 24.00 hours and then aspirated completely and continuously until 08.00 hours the next morning. Median pH values were significantly lower and median acidity was significantly higher, when the meal was eaten at 22.00 hours. The outputs of acid and pepsin after midnight were also significantly greater following the late night meal.

It seems that food interferes with the gastric inhibitory effects of the currently used H2‐receptor antagonists, such as ranitidine. We conclude that H2‐receptor antagonists must be taken after the last meal of the day in order to ensure maximal therapeutic efficacy.
Double‐blind study of an α2agonist in the treatment of irritable bowel syndrome
Authors: PRIOR A. , WILSON K. M. , WHORWELL P. J.
Published: July 2010

A double‐blind crossover trial of the α2agonist lidamidine hydrochloride in 72 patients with irritable bowel syndrome is reported. Lidamidine was found to have no significant effect on frequency and severity of abdominal pain or abdominal bloating. It did cause a statistically significant reduction in frequency of defaecation (P= 0.005), but this was of a degree unlikely to be of clinical importance. Although α2agonists inhibit gastrointestinal motility in animals this study suggests that lidamidine hydrochloride does not have a useful therapeutic role in irritable bowel syndrome.
Diagnosis of gastrointestinal lesions during treatment with non‐steroidal anti‐inflammatory drugs
Authors: FESTEN H. P. M.
Published: July 2010

Probably all non‐steroidal anti‐inflammatory drugs (NSAIDs) increase the risk of gastrointestinal (GI) mucosal injury. The most frequent lesions are gastric erosions in the pre‐pyloric region. Non‐steroidal anti‐inflammatory drugs also increase the incidence of peptic ulcers, although it is not yet clear whether more gastric ulcers or more duodenal ulcers are produced. Gastrointestinal symptoms are prevalent during NSAID treatment, but there is no correlation between symptoms and lesions. Clinical presentation may therefore vary considerably: many symptomatic patients will have no lesions, whereas others will present with complications but no symptoms. Blood loss is the most frequent complication of NSAID‐induced GI lesions. Bleeding is usually 'silent’and occult. Overt haemorrhage, though rare, is more frequent in patients taking NSAIDs. Other complications, such as penetration and perforation, may also occur. Endoscopy is the diagnostic method of choice, as this method can detect even superficial mucosal lesions. However, because of the lack of correlation between symptoms and lesions, it is difficult to ascertain which patients are at risk and thus to avoid unnecessary diagnostic procedures. Future efforts should therefore be directed towards the prevention of NSAID‐induced GI lesions.
The effect of secretin on sodium ion absorption by the isolated human gallbladder
Authors: JACYNA M. R. , ROSS P. E. , HOPWOOD D. , BOUCHIER I. A. D.
Published: July 2010

Sodium ion (Na+) transport, a principal function of the gallbladder epithelium, was studied by measuring the flux of22Na across isolated human gallbladder mucosa maintained in a modified‘Ussing’flux chamber. Tissue was obtained from cholecystectomy specimens in symptomatic patients with cholelithiasis. Out of 26 gallbladders studied, 13 had a net Na+flux from mucosa to serosa which indicated active Na+absorption. The hormone secretin, when added to the serosal fluid, reversed the direction of net flux in these gallbladders and caused a secretion of Na+from serosa to mucosa. These results suggest that secretin may be involved in the physiological regulation of fluid transport in the human gallbladder, and also suggest a possible role for this hormone in gallbladder emptying.
The effect of a new selective a2‐adrenoreceptor antagonist, idazoxan, and the agonist, clonidine, on fasting antroduodenal motility in healthy volunteers
Authors: GREGERSEN H. , KRAGLUND K. , RITTIG S. , TØTTRUP A.
Published: July 2010

Studies were carried out on 16 healthy male volunteers to investigate whether intravenous administration of the α2‐adrenoreceptor antagonist, idazoxan, could affect fasting antroduodenal motility with and without administration of the agonist, clonidine. Contractile activity was recorded using an oral tube with perfused side holes positioned in the stomach and duodenum.

Clonidine decreased antral contractile activity, an effect that idazoxan did not restore. Idazoxan alone did not affect antral motility. In the duodenum, clonidine decreased the number of contractions significantly and idazoxan restored them. Idazoxan alone did not increase duodenal motility but clonidine induced phase‐III activity within the first 15 min after administration.

The observations indicate that regulation of antroduodenal motility is influenced by α2‐adrenoreceptor drugs. Idazoxan may have potential as a motility restoring drug, for example, in postoperative ileus.
Mesalazine in childhood inflammatory bowel disease
Authors: BARDEN L. , LIPSON A. , PERT P. , WALKER‐SMITH J. A.
Published: July 2010

A study was undertaken in paediatric patients suffering from ulcerative, Crohn's or indeterminate colitis. This aimed to compare the occurrence and tolerance of side‐effects arising during treatment with position‐release mesalazine (Asacol) with those occurring during previous treatment with sulphasalazine (Salazopyrin). The drugs were used to maintain remission from colitis. The occurrence of adverse reactions was also monitored.

Sixty‐seven children were assessed for a period of 6 months; 45 of these children received mesalazine after previous treatment with sulphasalazine.

The results show that the majority of patients were maintained in remission with either drug, but they reported a preference for position‐release mesalazine with respect to ease and frequency of administration when compared to sulphasalazine.

No serious adverse reactions arose during mesalazine treatment, compared with three such events during previous sulphasalazine treatment.
Review article: hypoxia and hepatic drug metabolism—clinical implications
Authors: ANGUS P. W. , MORGAN D. J. , SMALLWOOD R. A.
Published: July 2010

Most major pathways of hepatic drug metabolism are dependent on oxygen. Hepatic mixed‐function oxidases use oxygen directly as a substrate, while many other enzyme systems are indirectly dependent on oxygen for the generation of essential co‐factors, such as NAD‐and ATP. Studiesin vitroshow that many of these oxygen‐dependent reactions are impaired by relatively minor reductions in oxygen supply, of a magnitude likely to be encounteredin vivo.Phase I metabolism by mixed‐function oxidases appears to be more sensitive to hypoxia than phase II drug conjugation, although the oxygen requirements of conjugation reactions, such as glucuronidation, may be greatly enhanced by poor nutrition or fasting. Studies in humans are few, but in general they affirm the potential importance of the effects of hypoxaemic states on hepatic drug elimination. On present evidence, special care should be taken in hypoxic patients with drugs extensively metabolized by the liver, particularly those which have a low therapeutic ratio.
Effect of propranolol on secretin‐induced gastrin release and secretin‐induced tachycardia in patients with the Zollinger‐Ellison syndrome
Authors: GOLDSCHMIEDT M. , REDFERN J. S. , FELDMAN M.
Published: July 2010

The mechanism for secretin‐induced gastrin release in the Zollinger‐Ellison syndrome is uncertain. We evaluated whether the stimulatory effect of intravenous secretin on gastrin release was partly mediated through a beta‐adrenergic stimulatory mechanism. Serum gastrin concentrations and heart rate were monitored in six patients with the Zollinger‐Ellison syndrome. Secretin (2 clinical units/kg) increased mean serum gastrin concentrations from 1558 pg/ml basally to a peak of 3683 pg/ml (136% above baseline). This increase was not altered by pretreatment with 2 mg of propranolol intravenously, a dose which in previous studies blocked terbutaline‐induced gastrin release. Secretin increased heart rate by 14 beats/min (20% above base‐line) and this also was not altered by propranolol pretreatment. Thus, the stimulatory effects of secretin on gastrinoma cells and the heart do not appear to be mediated by beta‐adrenergic receptors.
Long‐term maintenance treatment of gastric ulcers with ranitidine
Authors: PENSTON J. G. , WORMSLEY K. G.
Published: July 2010

One hundred and twenty patients with gastric ulcer disease, who had been receiving maintenance treatment with ranitidine (150 or 300 mg/day) for periods up to 7 years, were studied retrospectively. The proportion of patients remaining free from symptomatic recurrence of ulcer during maintenance treatment was 97% after 1 year; 90% after 3 years; and 79% after 5 years. No patient developed haemorrhage or perforation during maintenance treatment. None of the demographic features was shown to be associated with a significantly increased risk of ulcer recurrence during maintenance treatment.

Comparison of the recurrence rates during maintenance treatment with those during periods without active anti‐ulcer therapy, using life table and incidence density analysis, showed a significant difference in favour of maintenance treatment.

We conclude that maintenance treatment with ranitidine for 5 years significantly reduces the risk of symptomatic ulcer recurrence in patients with gastric ulcer.
Review article: asymptomatic duodenal ulcers—implications of heterogeneity
Authors: PENSTON J. G. , WORMSLEY K. G.
Published: July 2010

The present review examines the evidence for the existence of an asymptomatic variant of duodenal ulcer disease, as well as its clinical significance and therapeutic implications. Asymptomatic duodenal ulcers have definitely been shown to occur only in patients treated with nonsteroidal anti‐inflammatory drugs (NSAIDs) and in patients who have previously suffered from ulcer disease, especially if the latter have been subjected to gastric surgery or are receiving long‐term continuous (maintenance) treatment with drugs. It seems likely (although conclusive evidence is not yet available) that NSAID‐associated asymptomatic duodenal ulcers are predisposed to haemorrhage or perforation and should therefore be healed and kept in remission. Asymptomatic duodenal ulcers discovered during maintenance treatment appear to be clinically innocuous and do not therefore indicate therapeutic failure, nor require modification of therapy.
Tripotassium dicitrato bismuthate enemas in the treatment of ulcerative proctitis
Authors: SRIVASTAVA E. D. , SWIFT G. L. , WILKINSON S. , WILLIAMS G. T. , EVANS B. K. , RHODES J.
Published: July 2010

Eleven patients with active proctitis or proctosigmoiditis completed one month's treatment with tripotassium dicitrato bismuthate enemas administered at night. Symptoms, sigmoidoscopic appearances, and the histological grade of acute inflammation were assessed at the commencement of therapy and after one month. An overall score of these features showed improvement in 9 of 11 patients, which encourages further investigation of bismuth in controlled trials for patients with inflammatory bowel disease.
Review article: the pharmacological implications of leucocyte–endothelial cell interactions in Crohn's disease
Authors: SAWYERR A. M. , WAKEFIELD A. J. , HUDSON M. , DHILLON A. P. , POUNDER R.E.
Published: July 2010

The importance of leucocyte–endothelial cell interactions in the inflammatory process is now recognized. In Crohn's disease, we have proposed that these interactions mediate not only the development of the parenchymal cell infiltrate, but also initiate a process (multifocal gastrointestinal infarction) that leads to ischaemic damage to the bowel wall. We review data on the actions of drugs in the treatment of Crohn's disease and, where known, we highlight their effects on leucocyte adhesion to the endothelium. Corticosteroids inhibit adhesion by inhibiting production of interleukin‐1, tumour necrosis factor, interferon gamma, leukotrienes and platelet activating factor. Drugs liberating 5‐aminosalicylate inhibit leukotriene production. Cyclosporin inhibits T‐cell activation, and amplification of the immune response. Inhibition of leucocyte–endothelial cell interactions probably accounts for some of the beneficial effects of these drugs in Crohn's disease.
Evaluation of an enteric‐coated naproxen pellet formulation
Authors: HARDY J. G. , LAMONT G. L. , EVANS D. F. , HAGA A. K. , GAMST O. N.
Published: July 2010

An enteric‐coated, pellet formulation of naproxen has been evaluated in eight healthy subjects. Each volunteer was dosed with 153Sm‐labelled, enteric‐coated pellets on two occasions, once whilst fasted and once after breakfast. Gastrointestinal transit was followed using gamma scintigraphy and drug absorption compared with that from uncoated naproxen pellets dosed on a separate occasion. The pH in the stomach and intestines was monitored using radiotelemetry capsules. Gastric emptying was delayed by dosing after breakfast, but small intestinal transit of the enteric‐coated formulation was the same on both occasions. The highest pH recorded from the stomach was 4.0 and in all subjects the pH rose to at least 7.3 in the small intestine. The onset of drug absorption was fastest from the uncoated formulation and slowest from the coated pellets taken after breakfast. The total amount of drug absorbed was the same on all three occasions.
Ranitidine prevents duodenal ulcers associated with non‐steroidal anti‐inflammatory drug therapy
Authors: ROBINSON M. , MILLS R. J. , EULER A. R.
Published: July 2010

The results of four similarly designed, randomized, double‐blind, placebo‐controlled studies conducted to evaluate ranitidine as prophylaxis for NSAID‐associated damage are reviewed. A total of 673 patients receiving therapeutic dosages of NSAIDs for arthritic or musculoskeletal conditions also received either ranitidine 150 mg twice daily (n= 343) or placebo (n= 330) for four weeks (two studies) or eight weeks (two studies). Endoscopic grading of mucosal lesions was based on a modified Lanza scoring system. All patients had normal baseline endoscopies. After four weeks of treatment a significant protective effect against duodenal mucosal lesions including duodenal ulcers (three studies) and gastric mucosal lesions including gastric ulcers (one study) was observed in patients who received ranitidine compared with those who received placebo. A meta‐analysis of the four studies confirmed that significantly fewer patients receiving ranitidine than placebo developed duodenal ulcers (1%vs. 6%, P= 0.01). Endoscopic data at eight weeks from the two longer‐term studies showed that duodenal ulcers occurred in ranitidine‐ and placebo‐treated patients at a rate of 1% (2/137) vs. 8% (10/126) (P= 0.02), respectively, in one trial, and 0% (0/57) vs. 8% (4/49) (P= 0.02), respectively, in the other trial. No protective effect in the stomach was evident at eight weeks. We conclude that ranitidine is effective in preventing NSAID‐associated duodenal ulcers and may be appropriate prophylaxis for certain high‐risk patients.
Cimetidine suspension in patients with Stage 0 gastro‐oesophageal reflux disease
Authors: RIEMANN J. F. , HÖBEL W.
Published: July 2010

One hundred and twenty‐five patients with symptoms of heartburn and acid regurgitation but without endoscopic abnormalities were randomized to receive 200 mg cimetidine suspension four times daily or placebo for two weeks. Daily diary cards were kept to evaluate the frequency and degree of symptoms. At two weeks cimetidine was significantly more effective than placebo. It is concluded that placebo suspension has a considerable effect on gastro‐oesophageal reflux disease symptoms, but cimetidine suspension provides significantly better relief.
Fluconazole for oropharyngeal candidiasis in anti‐HIV positive haemophiliacs
Authors: LIM S. G. , LEE C. A. , HALES M. , O'DOHERTY M. , WINTER M. , KERNOFF P. B. A.
Published: July 2010

Candidiasis of the oropharynx and oesophagus is one of the most common problems encountered in patients with HIV disease. Fluconazole is a bis‐triazole antifungal agent with a long serum half‐life. Sixteen anti‐HIV positive patients (15 haemophiliacs and one blood transfusion recipient) with a clinical diagnosis of oropharyngeal candidiasis were treated with 50 mg fluconazole daily for 14–28 days and then either 150 mg fluconazole or placebo weekly for 6 months in a prophylactic phase. Clinical cure occurred in all patients, and mycological cure occurred in 13/16 (81%) patients. In the prophylactic phase, there were 2/5 (40%) relapses in the placebo arm compared with 1/8 (12.5%) in the fluconazole arm, but this was not statistically significant by Fisher's onesided exact test (P= 0.31). It is concluded that fluconazole is an effective treatment of oropharyngeal candidiasis and has potential for prophylactic use.
Dose‐related healing of duodenal ulcer with the proton pump inhibitor lansoprazole
Authors: LONDONG W. , BARTH H. , DAMMANN H. G. , HENGELS K. J. , KLEINERT R. , MÜLLER P. , ROHDE H. , SIMON B.
Published: July 2010

Lansoprazole (AG 1749) is a novel substituted benzimidazole which inhibits gastric acid secretion by blocking H+, K+‐ATPase. This randomized, double‐blind multicentre trial studied the dose–response relationship of lansoprazole on ulcer healing and compared it with ranitidine in 314 out‐patients with endoscopically assessed, symptomatic duodenal ulcer. Cumulative healing rates with Lansoprazole 7.5, 15, and 30 mg o.m. were 48, 59, and 74% at 2 weeks and 75, 84, and 95 % at 4 weeks, respectively (intention‐to‐treat); the difference of the healing rates between 7.5 and 30 mg groups was significant (P< 0.001).

Corresponding healing rates for 300 mg ranitidine nocte were 51 and 89 %. Pain relief was similar in all treatment groups. Lansoprazole was well tolerated. During a follow‐up of 6 months relapse rates after lansoprazole 7.5, 15, and 30 mg were 21, 29, and 22%, respectively; the relapse rate after ranitidine 300 mg was 20%. In conclusion, lansoprazole provides faster healing of duodenal ulcer than ranitidine and a similar relapse pattern. For further trials in peptic ulcer disease a daily dose of lansoprazole 30 mg o.m. is recommended.