bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cisapride inhibits meal‐stimulated gastric acid secretion and post‐prandial gastric acidity in subjects with gastro‐oesophageal reflux disease
Authors: Gardner J. D. , Rodriguez‐Stanley S. , Robinson M. , Miner P. B. 
Published: March 2003

SummaryBackground and aims : KCNQ1 potassium channels in human gastric parietal cells are thought to be involved in gastric acid secretion. As cisapride can inhibit similar channels in other tissues and is an effective treatment for nocturnal heartburn, we examined the effects of cisapride on gastric and oesophageal acidity, gastric emptying and heartburn severity in subjects with gastro‐oesophageal reflux disease.Methods : Subjects (n=11) had suffered from heartburn four times or more per week for at least 6 months. Gastric pH and oesophageal pH were measured before, during and after a standard meal ingested over 15 min. Each subject received placebo or 10 mg cisapride orally, 30 min before the beginning of the meal. Meal‐stimulated gastric acid secretion was calculated from the amount of HCl required to titrate the homogenized standard meal to pH 2 in vitro and the time required for the pH of the ingested meal to decrease to pH 2 in vivo. Heartburn severity was assessed at 15‐min intervals beginning at the end of the meal. Gastric emptying of solids was measured using a [13C]‐octanoic acid breath test.Results : Cisapride significantly decreased meal‐stimulated gastric acid secretion by 20%, decreased integrated gastric and oesophageal acidity by 50–60% and transiently increased the expiration of 13CO2. Cisapride did not significantly alter heartburn severity.Conclusions : The cisapride‐induced decreases in meal‐stimulated gastric acid secretion, gastric acidity and oesophageal acidity in subjects with gastro‐oesophageal reflux disease can account for its beneficial clinical effects. These results also raise the possibility that gastric KCNQ1 potassium channels are important in meal‐stimulated gastric acid secretion and possibly in the pathophysiology of gastro‐oesophageal reflux disease.
Efficacy of triple therapy comprising rabeprazole, amoxicillin and metronidazole for second‐line Helicobacter pylori eradication in Japan, and the influence of metronidazole resistance
Authors: Murakami K. , Sato R. , Okimoto T. , Nasu M. , Fujioka T. , Kodama M. , Kagawa J. 
Published: March 2003

SummaryBackground : The widespread use of eradication therapy for Helicobacter pylori in Japan has led to an increase in antibiotic‐resistant strains and the problem of re‐treatment in cases of eradication failure.Aim : To perform drug sensitivity testing for metronidazole in 92 H. pylori‐positive patients who had failed eradication treatment with first‐line triple therapy, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, and were administered metronidazole‐containing second‐line therapy.Methods : Second‐line eradication therapy, consisting of rabeprazole (20 mg b.d.), amoxicillin (750 mg b.d.) and metronidazole (250 mg b.d.), was administered for 1 week and the eradication rates and influence of metronidazole resistance were determined.Results : The eradication rates for rabeprazole–amoxicillin–metronidazole were 88% (81/92) using intention‐to‐treat analysis and 91% (81/89) using per protocol analysis. The eradication rates were 97% (61/63) for metronidazole‐sensitive strains and 82% (18/22) for metronidazole‐resistant strains.Conclusions : As second‐line H. pylori eradication treatment in Japan, rabeprazole–amoxicillin–metronidazole triple therapy is effective, even with metronidazole‐resistant strains.
Effect of peppermint oil and caraway oil on gastrointestinal motility in healthy volunteers: a pharmacodynamic study using simultaneous determination of gastric and gall‐bladder emptying and orocaecal transit time
Authors: Goerg K. J. , Spilker TH. 
Published: March 2003

SummaryBackground : Although peppermint oil and caraway oil are frequently used in herbal drugs for abdominal discomfort and pain, the pharmacological insights into their effects on the gastrointestinal tract are poor.Methods : The pharmacodynamic effects of 90 mg peppermint oil (WS 1340) and 50 mg caraway oil (WS 1520) on the motility of the stomach and gall‐bladder, and on the orocaecal transit time, in comparison with placebo, 10 mg cisapride and 10 mg n‐butylscopolamine, were studied in 12 healthy volunteers. The study involved simultaneous ultrasonic determination of gastric and gall‐bladder emptying, together with assessment of the orocaecal transit time using the lactulose H2 breath test. The combination of these methods allows three gastrointestinal organs to be studied in one subject simultaneously.Results : The antral filling time was comparable with placebo, peppermint oil, caraway oil and cisapride, whereas it was significantly shortened (P = 0.04, two‐sided paired t‐test) with n‐butylscopolamine. The gastric emptying time did not differ significantly between placebo, peppermint oil, caraway oil and cisapride, but was significantly prolonged by n‐butylscopolamine (P = 0.04, two‐sided paired t‐test). Complete inhibition of gall‐bladder emptying was caused by both oils and n‐butylscopolamine. Cisapride significantly shortened gall‐bladder emptying compared with placebo (P = 0.02, two‐sided signed rank test). The orocaecal transit time was significantly prolonged by peppermint oil (P = 0.004) and n‐butylscopolamine (P = 0.002), but not significantly prolonged by caraway oil (P = 0.06); it was significantly shortened by cisapride (P = 0.04, all two‐sided paired t‐test).Conclusions : Peppermint oil and caraway oil show a relaxing effect on the gall‐bladder and the former slows small intestinal transit. Further studies should investigate the effects of both oils on a maximal contraction stimulus on the gall‐bladder, and in patients suffering from motility disorders.
The cardiovascular response to insertion of the intubating laryngeal mask airway
Authors: Choyce A. , Avidan M. S. , Harvey A. , Patel C. , Timberlake C. , Sarang K. , Tilbrook L. 
Published: March 2003

SummarySixty‐one patients received a standardised anaesthetic and were randomly assigned to three groups: tracheal intubation via direct laryngoscopy, tracheal intubation via an intubating laryngeal mask airway with immediate removal of the device, and tracheal intubation via an intubating laryngeal mask airway with delayed removal. The cardiovascular response to intubation was of a similar magnitude in all groups, although delayed removal of the intubating laryngeal mask airway was associated with a second pressor response. Norepinephrine changed significantly over time following direct laryngoscopy and following immediate removal of the intubating laryngeal mask airway, but not after delayed removal. The findings of this study do not support using the intubating laryngeal mask instead of direct laryngoscopy purely to decrease the response to intubation.
Nasotracheal intubation for head and neck surgery
Authors: Hall C. E. J. , Shutt L. E. 
Published: March 2003

SummaryNasotracheal intubation offers the head and neck surgeon more scope for surgical manoeuvre in operations of the mouth, pharynx, larynx and also the neck. Concern over the complications of using this route of intubation and lack of training may be limiting its use. A thorough knowledge of the anatomy, benefits of using nasal vasoconstrictors and attention to technique are prerequisites to maintaining the skill. This article reviews each of these topics and aims to encourage the appropriate use of nasotracheal intubation in current practice.
Normal faulting, extension and uplift in the outer thrust belt of the central Apennines (Italy): role of the Caramanico fault
Authors: Ghisetti F. , Vezzani L. 
Published: March 2003

AbstractThe outer Adriatic zones of the central Apennines (Italy) provide good conditions for analysing geometry and kinematics of the earliest normal faults, superposed onto the thrust belt. During the latest stages of thrusting onto the Adriatic foreland (late Pliocene–early Pleistocene), the outermost imbricates of the thrust belt were subjected to normal faulting, coeval with differential uplift. Crosscutting normal faults get younger towards the foreland, thus the easternmost normal faults record the latest stages of fault propagation and growth. The Caramanico fault, on the western flank of Mt. Maiella, is the largest outcropping normal fault of the outer zones. This high‐angle fault (dip > 70°) has cumulative offsets ≤ €4.2 km, and propagated with slip rates of 2.6 mm/year in a short time interval (≤ 1.6 Ma), concomitant with intense uplift of Mt. Maiella. In contrast with normal faults in a more internal position, the Caramanico fault maintains a high‐angle planar geometry, and does not reach the major basal detachment of the thrust belt. Thus the fault did not cause large extensional displacements; its major role was rather to accommodate ongoing components of vertical uplift of the overthickened thrust wedge. Downfaulting of the thrust belt on the western flank of Mt. Maiella represents the youngest end member of the same processes that have operated since 11 Ma in the Tyrrhenian hinterland, where large extensional strains and crustal thinning of the orogenic belt were achieved by long‐lasting activity of listric normal faults detached at lower crustal depths.
Insulating effect of coals and organic rich shales: implications for topography‐driven fluid flow, heat transport, and genesis of ore deposits in the Arkoma Basin and Ozark Plateau
Authors: Nunn J.A. , Lin G. 
Published: March 2003

ABSTRACT Sedimentary rocks rich in organic matter, such as coal and carbonaceous shales, are characterized by remarkably low thermal conductivities in the range of 0.2–1.0 W m−1 °C−1, lower by a factor of 2 or more than other common rock types. As a result of this natural insulating effect, temperature gradients in organic rich, fine‐grained sediments may become elevated even with a typical continental basal heat flow of 60 mW m−2. Underlying rocks will attain higher temperatures and higher thermal maturities than would otherwise occur. A two‐dimensional finite element model of fluid flow and heat transport has been used to study the insulating effect of low thermal conductivity carbonaceous sediments in an uplifted foreland basin. Topography‐driven recharge is assumed to be the major driving force for regional groundwater flow. Our model section cuts through the Arkoma Basin to Ozark Plateau and terminates near the Missouri River, west of St. Louis. Fluid inclusions, organic maturation, and fission track evidence show that large areas of upper Cambrian rocks in southern Missouri have experienced high temperatures (100–140 °C) at shallow depths (< 1.5 km). Low thermal conductivity sediments, such as coal and organic rich mudstone were deposited over the Arkoma Basin and Ozark Plateau, as well as most of the mid‐continent of North America, during the Late Palaeozoic. Much of these Late Palaeozoic sediments were subsequently removed by erosion. Our model results are consistent with high temperatures (100–130 °C) in the groundwater discharge region at shallow depths (< 1.5 km) even with a typical continental basal heat flow of 60 mW m−2. Higher heat energy retention in basin sediments and underlying basement rocks prior to basin‐scale fluid flow and higher rates of advective heat transport along basal aquifers owing to lower fluid viscosity (more efficient heat transport) contribute to higher temperatures in the discharge region. Thermal insulation by organic rich sediments which traps heat transported by upward fluid advection is the dominant mechanism for elevated temperatures in the discharge region. This suggests localized formation of ore deposits within a basin‐scale fluid flow system may be caused by the juxtaposition of upward fluid discharge with overlying areas of insulating organic rich sediments. The additional temperature increment contributed to underlying rocks by this insulating effect may help to explain anomalous thermal maturity of the Arkoma Basin and Ozark Plateau, reducing the need to call upon excessive burial or high basal heat flow (80–100 mW m−2) in the past. After subsequent uplift and erosion remove the insulating carbonaceous layer, the model slowly returns to a normal geothermal gradient of about 30 °C km−1.
Icehouse world sea‐level behaviour and resulting stratal patterns in late Visean (Mississippian) carbonate platforms: integration of numerical forward modelling and outcrop studies
Authors: Barnett A. J. , Burgess P. M. , Wright V. P. 
Published: March 2003

ABSTRACTLate Visean (Asbian–Brigantian) platform carbonates in the British Isles show a pronounced cyclicity marked by the alternation of mainly subtidal carbonates and subaerial exposure surfaces. Whereas the cyclicity of shallow‐water limestones of this age has been well‐documented, there has been little attempt to understand the controls on larger‐scale patterns such as those recognized in Pennsylvanian successions in the U.S.A. The principal aim of this study is to test two contrasting theories of cycle stacking via numerical forward modelling. Earlier studies of Pennsylvanian‐early Permian platform carbonates in south‐west U.S.A. suggest that cycle stacking patterns were controlled by the interaction of third‐ and fourth‐order sea‐level oscillations, with relatively uniform fourth‐order oscillations altered mainly by the harmonic effect of lower‐order sea‐level changes. An alternative model is based on an insolation curve for the Carboniferous calculated using Milankovitch parameters. This model predicts a considerable variability in levels of solar insolation that would have affected the amplitude of fourth‐order sea‐level changes and cycle composition. Both of these ideas were examined via numerous model runs using CARBONATE 6.0 and a new program, CARBOSMUT. Model results were evaluated through the use of 3 key criteria derived from well‐documented outcropping stratigraphies in the U.K.: (1) cycle stacking patterns and the stratigraphic position of major transgressions, (2) stratigraphic position of major faunal changes, (3) degree of development of subaerial exposure surfaces. Computer simulations and comparison with outcrop data suggest that a model invoking the interaction of relatively uniform fourth‐ (c.100 Kyr) and third‐order sea‐level oscillations is most appropriate for much of the late Visean, with major lowstands occurring at the mid‐Asbian and Asbian–Brigantian boundary. Late Visean cycles are important exploration targets in the Pri‐Caspian Basin, Kazakhstan and understanding the controls on stratal patterns is important as a potential exploration tool.
Adverse effects of a single dose of (+)‐sotalol in patients with mild stable asthma
Authors: Devereux G. , Fishwick K. , Aiken T. C. , Bourke S. J. , Hendrick D. J. 
Published: March 2003

Aims
To investigate the effect of (+)‐sotalol, which is not thought to possess clinically significant β‐adrenoceptor blocking activity, on airway responsiveness in subjects with mild asthma.
Methods
A placebo controlled, double‐blind, single dose, cross over study, evaluating the effects of oral (+)‐sotalol 300 mg and oral (±)‐sotalol 240 mg, on airway responsiveness, FEV1, and heart rate in 18 asthmatic volunteers with quantifiable levels of airway responsiveness.
Results
Compared with placebo, (+)‐sotalol induced a significant increase in airway responsiveness, and a significant decrease in FEV1, but there was no significant change in heart rate. Following (±)‐sotalol there was no significant effect on airway responsiveness, but there were significant decreases in FEV1 and heart rate. In one subject both (+)‐sotalol and (±)‐sotalol provoked a 49% decrement in FEV1, and in another there were decrements of 20% and 18%, respectively.
Conclusions
Despite theoretical considerations, it cannot be assumed that (+)‐sotalol is safe in patients with asthma.
Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjects
Authors: Ridge Susan A. , Sludden Julieann , Brown Oliver , Robertson Leigh , Wei Xiaoxiong , Sapone Andrea , Fernandez‐Salguero Pedro M. , Gonzalez Frank J. , Vreken Peter , Van Kuilenburg Andre BP , Van Gennip Albert H. , McLeod Howard L. 
Published: March 2003

Aims
Dihydropyrimidine dehydrogenase (DPD) catalyses the reduction of pyrimidines, including the anticancer agent 5‐fluorouracil (5FU). Impaired 5FU degradation, through low DPD activity, has led to severe, life‐threatening or fatal toxicity after administration of 5FU. Complete DPD deficiency is associated with the inherited metabolic disease thymine uraciluria. Several mutations in the gene encoding DPD have recently been identified, but the phenotype‐genotype concordance of these alterations in the general population has not been reported.
Methods
Mononuclear cells were isolated from whole blood and DPD activity was determined after ex vivo incubation with 14C‐5FU followed by h.p.l.c. analysis of 5FU metabolites. Analysis of mutations in the DPD gene at an exon splice site, codons 534, 543, and 732, and a deletion at base 1897 (ΔC1897) were performed in 30 subjects with the lowest and 30 subjects with the highest enzyme activity using PCR‐RFLP.
Results
DPD activity was measured in 226 Caucasian subjects and was highly variable (range 19.1–401.4 pmol min−1 mg−1 protein). Mutations were frequently observed at codons 543 (allele frequency 28%), 732 (allele frequency 5.8%), and 534 (allele frequency 0.8%), but were not associated with low DPD activity. There were no splice site or ΔC1897 mutations found in this population.
Conclusions
The five mutations analysed in this study are insufficient for identification of patients at risk for 5FU toxicity or thymine uraciluria. Both the splice site mutation and ΔC1897 are relatively rare in the general Caucasian population. Therefore, identification of further molecular alterations is required to facilitate the use of DPD analysis in genetic diagnosis and cancer therapeutics.
Impaired β‐adrenoceptor mediated venodilation in patients with diabetes mellitus
Authors: Harada Kazuhiro , Ohmori Masami , Kitoh Yasuhiko , Sugimoto Koh‐ichi , Fujimura Akio 
Published: March 2003

Aims We investigated whether venoconstriction by α‐adrenoceptor stimulation, and venodilation by β‐adrenoceptor stimulation and nitroglycerin are altered in patients with diabetes mellitus (DM).Methods Eight male patients with non insulin‐dependent DM and eight age‐matched control subjects were included. The patients had neither hypertension nor hyperlipidaemia. Noradrenaline (1 to 512 ng min−1 ), isoprenaline (1 to 256 ng min−1 ) and nitroglycerin (0.5 to 128 ng min−1 ) were infused into a dorsal hand vein and its diameter was measured using a linear variable differential transformer.Results The venoconstricting response to noradrenaline and the venodilating response to nitroglycerin in DM patients were similar to those in control subjects, while the venodilation by isoprenaline was significantly (P<0.05) smaller in DM patients than in control subjects at the dose of 32 ng min−1 or more [32 ng min−1: 11.5%vs 29.8% (DM vs control subjects), 64 ng min−1: 19.0%vs 40.1%, 128 ng min−1: 25.2%vs 49.0%, 256 ng min−1: 34.3%vs 56.7%].Conclusions These data suggested that venoconstriction by α‐adrenoceptor stimulation and venodilation by nitroglycerin are not altered, whereas venodilation by β‐adrenoceptor stimulation might be impaired in patients with DM.
Effect of cimetidine and ranitidine on pharmacokinetics and pharmacodynamics of a single dose of dofetilide
Authors: Abel Samantha , Nichols Donald J. , Brearley Christopher J. , Eve Malcolm D. 
Published: March 2003

Aims The aim of this open‐label, placebo‐controlled, randomized, four‐period crossover study was to determine the effects of cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of a single dose of dofetilide. Methods Twenty healthy male subjects received 100 or 400 mg twice daily of cimetidine, 150 mg twice daily of ranitidine, or placebo for 4 days. On the second day, a single oral 500 μg dose of dofetilide was administered immediately after the morning doses of cimetidine, ranitidine, or placebo. Treatment periods were separated by 1–2 weeks. Pharmacokinetic parameters were determined from plasma and urinary dofetilide concentrations; prolongation of the QTc interval was determined from three‐lead electrocardiograms. Results Ranitidine did not significantly affect the pharmacokinetics or pharmacodynamics of dofetilide; however, a dose‐dependent increase in exposure to dofetilide was observed with cimetidine. When dofetilide was administered with 100 and 400 mg of cimetidine, the area under the plasma concentration‐time curve of dofetilide increased by 11% and 48% and the maximum plasma dofetilide concentration increased by 11% and 29%, respectively. The respective cimetidine doses reduced renal clearance of dofetilide by 13% and 33% and nonrenal clearance by 5% and 21%. Dofetilide‐induced prolongation of the QTc interval was enhanced by cimetidine; the mean maximum change in QTc interval from baseline was increased by 22% and 33% with 100 and 400 mg of cimetidine, respectively. However, the relationship between the prolongation of the QTc interval and plasma dofetilide concentrations was unaffected by cimetidine or ranitidine; a 1 ng ml−1 increase in plasma dofetilide concentration produced a 17–19 ms prolongation of the QTc interval. Dofetilide was well tolerated, with no treatment‐related adverse events or laboratory abnormalities. Conclusions These results suggest that cimetidine increased dofetilide exposure by inhibiting renal tubular dofetilide secretion, whereas ranitidine did not. This effect is not an H2‐receptor antagonist class effect but is specific to cimetidine. If therapy with an H2‐receptor antagonist is required, it is recommended that cimetidine at all doses be avoided; since ranitidine has no effect on dofetilide pharmacokinetics or prolongation of the QTc interval, it can be seen as a suitable alternative.