bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helicobacter pylori and reflux disease
Authors: Sharma P. , Vakil N. 
Published: March 2003

SummaryThe falling prevalence of Helicobacter pylori infection and related diseases (peptic ulcer disease, gastric cancer) in developed countries has been paralleled by an increased recognition of gastro‐oesophageal reflux and its complications. These epidemiological data do not support a role for H. pylori in the pathogenesis of reflux disease, but suggest a negative association with the increasing incidence of oesophageal diseases. This has led some investigators to propose a ‘protective’ role of H. pylori infection against the development of oesophageal diseases. In these patients, pre‐existing lower oesophageal sphincter dysfunction, susceptibility to reflux, unmasking of latent reflux and the patterns and severity of gastritis are probably important factors contributing to the development of oesophageal diseases. The most likely mechanism by which H. pylori infection may protect against reflux is by decreasing the potency of the gastric refluxate in patients with corpus‐predominant gastritis. The prevalence of H. pylori infection in patients with reflux disease is probably no greater than that in those without reflux, and there are conflicting data indicating that reflux symptoms or erosive oesophagitis develop after H. pylori eradication. It is also unclear whether H. pylori augments the antisecretory effects of proton pump inhibitors or accelerates the development of atrophic gastritis.
6‐Thioguanine — efficacy and safety in chronic active Crohn's disease
Authors: Herrlinger K. R. , Kreisel W. , Schwab M. , Schoelmerich J. , Fleig W. E. , Ruhl A. , Reinshagen M. , Deibert P. , Fellermann K. , Greinwald R. , Stange E. F. 
Published: March 2003

SummaryBackground : Azathioprine and mercaptopurine are commonly used in chronic active Crohn's disease. They share the disadvantage of a delayed onset of action and potentially serious side‐effects, and are metabolized to thioguanine nucleotides which are thought to be the active metabolites. The direct use of 6‐thioguanine may offer a more rapid and safer alternative. We conducted an open prospective study to investigate the efficacy and safety of 6‐thioguanine in chronic active Crohn's disease.Methods : Thirty‐seven patients with chronic active Crohn's disease and a Crohn's disease activity index of > 150 were enrolled in this study. Inclusion criteria were steroid dependence (n = 19), steroid refractoriness (n = 9) and/or intolerance (n = 16) or refractoriness (n = 6) to azathioprine. Patients were treated with 40 mg/day of 6‐thioguanine for 24 weeks; a dose escalation to 80 mg was allowed at week 12. Remission was defined as a Crohn's disease activity index of < 150 associated with a decrease of > 70 points; response was defined as a decrease of > 70 points in the Crohn's disease activity index.Results : In the intention‐to‐treat analysis, 13 of 37 patients achieved remission (35%). Twelve of these 13 patients achieved remission after 4 weeks. Fifty‐seven per cent of patients (21/37) achieved a response. The mean Crohn's disease activity index decreased from 284 ± 74 to 153 ± 101. 6‐Thioguanine was more effective in azathioprine‐intolerant than in azathioprine‐refractory patients. Twelve of 16 patients intolerant to azathioprine tolerated 6‐thioguanine. Adverse events included phototoxicity, pancreatitis, headache, nausea, alopecia, arthralgia, minor infections and reversible elevation of transaminases. Six patients required discontinuation of medication, two because of leucopenia.Conclusions : In this patient group with chronic active Crohn's disease, 6‐thioguanine appeared to be effective with acceptable short‐term toxicity, but long‐term controlled trials are clearly needed to further define its role.
Oral desensitizing treatment in food allergy: clinical and immunological results
Authors: Patriarca G. , Nucera E. , Roncallo C. , Pollastrini E. , Bartolozzi F. , De Pasquale T. , Buonomo A. , Gasbarrini G. , Di Campli C. , Schiavino D. 
Published: March 2003

SummaryBackground : The possibility of inducing oral desensitization in patients with food allergy is still controversial and no standardized programmes are yet available.Aim : To evaluate the safety and efficacy of oral desensitization in patients with allergy induced by the most common food allergens.Methods : Fifty‐nine patients with food allergy underwent an oral desensitizing treatment according to standardized protocols. The control group consisted of age‐ and sex‐matched subjects, who followed a strict elimination diet. Specific immunoglobulin E and immunoglobulin G4 were assessed at baseline and after 6, 12 and 18 months.Results : The majority of patients (83.3%) successfully completed the treatment. During treatment, 51.1% of subjects experienced some mild side‐effects, easily controlled by the oral administration of antihistamines or sodium cromolyn. Specific immunoglobulin E showed a significant decrease, whilst specific immunoglobulin G4 showed a significant increase in all patients.Conclusions : The immunological findings induced by oral desensitization in food allergy allow us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory allergies. Moreover, the proposed standardized oral desensitization protocols may represent an effective alternative approach in the management of food‐allergic patients.
Measurement of tracheal tube cuff pressure in critical care
Authors: Vyas D. , Inweregbu K. , Pittard A. 
Published: March 2003

SummaryWe conducted an observational study to measure tracheal tube cuff pressures in the critical care environment, where prolonged intubation is common. Thirty‐two patients were studied. Sixty‐two per cent of all tracheal cuffs had intracuff pressures above the recommended value. We also conducted a telephone survey of 24 intensive care units within the Northern and Yorkshire Region, which showed that 75% of the intensive care units never checked tracheal tube cuff pressures. Critically ill patients are particularly vulnerable to tracheal injury due to prolonged intubation. We suggest that cuff pressures should be measured regularly.
Postanaesthetic shivering ‐ a new look at tramadol
Authors: Mathews S. , Al Mulla A. , Varghese P. K. , Radim K. , Mumtaz S. 
Published: March 2003

Summary We studied whether tramadol administered at the time of wound closure can prevent  postanaesthetic shivering. One hundred and fifty patients scheduled for general anaesthesia and surgery were randomly allocated and tramadol was administered intravenously at a dose of

2 mg.kg−1 in the high‐dose group, 1 mg.kg−1 in the low‐dose group and 0.9% saline in the control group. In the high‐dose group, 2% of patients had postanaesthetic shivering, compared to 4% in the low‐dose group and 48% in the control group (p < 0.001 vs. tramadol groups). There was no delay in tracheal extubation after reversal of neuromuscular blockade. The incidence of adverse side‐effects such as sedation and vomiting did not differ statistically and were clinically not significant. This study strongly supports the use of tramadol at wound closure for prevention of postanaesthetic shivering.
Thermal history during Mesozoic extension and Tertiary uplift in the Cameros Basin, northern Spain
Authors: Mata M. P. , Casas A. M. , Canals A. , Gil A. , Pocovi A. 
Published: March 2003

AbstractDetailed structural cross‐sections, analysis of extensional structures and palaeotemperatures obtained from primary fluid inclusions in quartz and calcite veins from the extensional Cameros Basin (N Spain) allow an interpretation of its thermal evolution and its geometric reconstruction to be constrained. The Cameros Basin underwent an extensional stage during the Late Jurassic to Early Cretaceous, with a maximum preserved thickness of Mesozoic deposits of about 9000 m. During the Tertiary, the basin was inverted, allowing a large part of the sedimentary sequence to be exposed. Extensional deformation in individual beds created N120E‐striking tension gashes in the synrift sequence, parallel to the master normal faults limiting the basin and dipping perpendicular to bedding. The extensional strain calculated from tension gashes varies between 4 and 12%. The number and thickness of veins increases the lower their position in the stratigraphic section. Palaeotemperatures were obtained from samples along a stratigraphic section comprising a thickness of 4000 m synrift deposits. Homogenization temperatures range from 107 to 225 °C. Palaeothermometric data and geometric reconstruction give a geothermal gradient of 27–41 °C km−1 during the extensional stage and allow an eroded section of at least 1500 m to be inferred. Low‐grade metamorphic assemblages in lutitic rocks of the deepest part of the basin presently exposed at surface imply P–T conditions of 350–400 °C and less than 2 kbar, which implies a geothermal gradient of about 70 °C km−1. Since the metamorphic thermal peak is dated at 100 Ma, the P–T path indicates a heating event during the late Albian, probably linked to the reaching of thermal equilibrium of the continental crust after extension. The results obtained support the hypothesis of a synclinal basin geometry, with vertical superposition of Lower Cretaceous sedimentary units rather than a model of laterally juxtaposed bodies onlapping the prerift sequence.
Chemostratigraphic correlation of carbonate successions in the Gariep and Saldania Belts, Namibia and South Africa
Authors: Fölling P. G. , Frimmel H. E. 
Published: March 2003

ABSTRACT Inter‐ and intrabasinal correlation of Neoproterozoic carbonate successions and associated glaciogenic deposits from the Pan‐African Gariep Belt and the Kango inlier in the Saldania Belt (Namibia and South Africa) is proposed on the basis of new δ13CCarb and 87Sr/86SrI data. Highly positive δ13CCarb values (as much as + 8.65‰) and low 87Sr/86SrI ratios (0.7071–0.7077) were obtained on carbonate successions of the Hilda Subgroup between an older and a younger diamictite in the Port Nolloth Group (Gariep Belt). These results are in agreement with data elsewhere that suggest deposition between the global ∼ 750 Ma Sturtian and ∼ 580 Ma Marinoan glaciations. Considerably lower, positive δ13CCarb values (up to + 1.01‰) and higher 87Sr/86SrI ratios (0.7082–0.7085) mark the carbonates (Bloeddrif Member, Holgat Formation) on top of the Numees Formation diamictite and support a correlation of this diamictite with the Marinoan glaciation.In the southern extension of the Gariep Belt, correlation of the Widouw Formation limestone (Gifberg Group) with the Bloeddrif Member carbonates is proposed based on similar isotopic characteristics. In the Kango inlier of the Saldania Belt, two carbonate‐bearing members exist in the Matjies River Formation. The lower one of these two (Nooitgedacht Member) compares well with the Hilda Subgroup, whereas the upper one (Kombuis Member) shows strong similarities to the Bloeddrif Member carbonates. This implies that all younger stratigraphic units of the Kango inlier are not correlatives of the Port Nolloth Group, as previously assumed, but syn‐ to post‐orogenic with respect to the 540–580 Ma Pan‐African orogeny.
Pharmacokinetics of intramuscular artemether in patients with severe falciparum malaria with or without acute renal failure
Authors: Karbwang J. , Na‐Bangchang K. , Tin T. , Sukontason K. , Rimchala W. , Harinasuta T. 
Published: March 2003

Aims
The pharmacokinetics of intramuscular artemether and its major plasma metabolite–dihydroartemisinin, were investigated in patients with severe manifestations of falciparum malaria.
Methods
Six severe falciparum malaria patients with acute renal failure (ARF) and 11 without ARF were recruited into the study. They were treated with intramuscular artemether at a loading dose of 160 mg, followed by daily doses of 80 mg for another 6 days (total dose 640 mg).
Results
Patients with and without ARF showed a good initial response to treatment; the parasite and fever clearance times were 66(30–164) and 76(36–140) h [median(range)], respectively. None had reappearance of parasitaemia in their peripheral blood smear within 7 days of initiation of treatment. In comatose patients, the time to recovery of consciousness was 51.6(22–144) h. Artemether was detected in plasma as early as 1 h after a 160 mg dose, and declined to undetectable levels within 24 h in most cases. Patients with ARF had significantly higher Cmax [2.38(1.89–3.95) vs 1.56(1.05–3.38) ng ml−1 mg−1 dose], AUC [35.4(22–52.9) vs 25.2(13.4–52.9) ng ml−1 h mg−1 dose], and lower Vz/F [5.45(3.2–6.9) vs 8.6(4.2–12.3) l kg−1] and CL/F [7.4(5.4–13.8) vs 19.1(8.5–25.1) ml min−1 kg−1] when compared with those without ARF. In addition, t1/2,z was significantly longer in ARF patients [7.0(5.5–10.0) vs 5.7(4.2–6.6) h]. The pharmacokinetics of dihydroartemisinin in the two groups of patients were comparable.
Conclusions
ARF significantly modified the pharmacokinetics of intramuscular artemether. The changes could be attributed to either improved absorption/ bioavailability, a reduction of systemic clearance, or a change in plasma protein binding of the drug.
A new regimen for starting warfarin therapy in out‐patients
Authors: Oates A. , Jackson P. R. , Austin C. A. , Channer K. S. 
Published: March 2003

Aims
Oral anticoagulation is increasingly used in elderly patients with atrial fibrillation to prevent embolic phenomena. The use of anticoagulants in this population is prophylactic rather than therapeutic and so there is no urgency to establish anticoagulation within the desired therapeutic range. The aim of the study was to develop an out‐patient regimen for initiation of oral anticoagulation with warfarin which requires only weekly monitoring of the International Normalized Ratio (INR).
Methods
The study was undertaken in two phases. In the first phase, factors which predict the final maintenance dosage of warfarin were defined and used to build a decision tree and dosage algorithm. In the second study the algorithm was tested. Patients were given 2 mg warfarin daily for 2 weeks and the INR at this time was used to predict the maintenance dose. Patients then attended for weekly measurements of the INR until steady state had been reached. Dosage adjustments were not made unless the INR was >4.0 or <1.5 for 2 consecutive weeks. The accuracy of the prediction was measured by calculating the mean INR of weeks 6–8 and the number of patients in the target range 2.0–3.0 was determined.
Results
One hundred and seven consecutive out‐patients (mean age 70 years range 64–86) completed the first study. The age, sex, height, weight, alcohol intake, number of cigarettes smoked, concomitant medication, clinical evidence of right heart failure, liver failure, abnormalities in liver enzyme estimations, baseline INR and INR after 2 weeks of 2 mg warfarin daily were used in a polytomous logistic regression analysis with stepwise inclusion of factors to determine which factors influenced the eventual maintenance dosage of warfarin. The INR after 2 weeks of 2 mg warfarin therapy predicted 70% of the variability of the maintenance dose. Of other factors only the sex of the patient had a large enough effect to be included in the prediction algorithm. One hundred and six patients (mean age 71 years range 50–85 years) completed the second study. Only one patient needed a dose adjustment in the first 2 weeks of warfarin 2 mg daily (INR 4.4). Overall, 60% patients were in the narrow target range (INR 2.0–3.0) at steady state. In five patients the INR was >4.0 at any visit after the second week and needed dosage adjustment. In four patients the INR was <1.5 at steady state.
Conclusions
We have developed a method of predicting the maintenance dose of warfarin in an elderly population based on the INR after 2 weeks of warfarin 2 mg daily, and the sex of the patient. This is a safe and convenient way of initiating warfarin therapy as an out‐patient which requires only weekly INR checks.
Pharmacokinetics and bioavailability of oral 5′‐deoxy‐5‐fluorouridine in cancer patients
Authors: Van Der Heyden  , Highley  , De Bruijn  , Tjaden  , Reeuwijk  , Van Slooten  , Van Oosterom  , Maes  
Published: March 2003

Aims Oral administration of 5‐fluorouracil (FUra), an important cytotoxic agent, is limited by a wide variation in bioavailability. 5′‐deoxy‐5‐fluorouridine (dFUrd), a masked form of FUra, has shown promise clinically when given intravenously or orally as a solution or tablet. This study investigates the efficacy of an oral capsule formulation of dFUrd in generating continuous systemic levels of this compound in cancer patients.Methods Six patients with advanced intestinal or ovarian malignancies were given three cycles of dFUrd, days 1–5, at intervals of 4 weeks. The doses of dFUrd were 600 mg m−2 three times daily, 800 mg m−2 three times daily, and 1000 mg m−2 three times daily, on cycles one, two and three, respectively (total dose 36 g m−2 ). The initial dose in each cycle was given as a slow intravenous injection over 10 min, and the remainder orally. Plasma and urine levels of dFUrd and two of its metabolites, FUra and 5,6‐dihydro‐5‐fluorouracil (FUraH2 ), were monitored in six patients at each dose level.Results All six patients completed the study, receiving three different doses over a 3 month period, following which one had achieved a partial response, one had stable disease, and four had developed progressive disease. Side‐effects were negligible, and only two instances of transient diarrhoea WHO grade 1 were seen. Total body clearance (CLtot) of intravenous dFUrd decreased with increasing dose; 2.7, 2.0 and 1.3 l min−1 m−2, following doses of 600, 800 and 1000 mg m−2, respectively. The mean elimination half‐life of intravenous dFUrd increased with the dose from 15 to 22 min. Oral dFUrd was rapidly absorbed with a lag time of less than 20 min. The mean elimination half‐life (t1/2, z ) of oral dFUrd was 32–45 min in the dose range 600–1000 mg m−2. The AUC of FUra and FUraH2 increased overproportionally with increasing intravenous doses of dFUrd. The mean systemic bioavailability of oral dFUrd was 34–47%.Conclusions dFUrd, which selectively releases the antimetabolite FUra in tumour cells, can be given orally at doses of 600–1000 mg m−2 three times daily for 5 days. The systemic levels achieved are equivalent to those seen following continuous infusions of dFUrd or FUra. Toxicity is tolerable, and further clinical investigation of oral dFUrd is warranted.
The rational use of β‐adrenoceptor blockers in the treatment of heart failure. The changing face of an old therapy
Authors: Squire Iain B. , Barnett David B. 
Published: March 2003

Heart failure is one of the commonest debilitating conditions of industrialized society, with mortality and morbidity comparable with that of the common neoplastic diseases. The role of antagonists of the adrenergic β‐receptor (β‐blockers) in heart failure has been the subject of debate for many years. Data from studies of the therapeutic use of β‐blockers in patients following acute myocardial infarction suggest that in this circumstance these agents confer at least as much benefit to patients with heart failure as they do to those without. Similarly retrospective analysis of a number of the studies of angiotensin converting enzyme (ACE) inhibitors in heart failure suggest a greater effect of the combination of β‐blocker with ACE inhibitor compared with ACE inhibitor alone.The results of recent prospective, placebo‐controlled studies of the addition of β‐blocker to standard therapy in patients with chronic heart failure have confirmed a significant beneficial effect. β‐blocker therapy in these studies was well tolerated and in addition to improved mortality, β‐blocker therapy is associated with improved morbidity in terms of progressive heart failure and numbers of hospitalizations.Initiation of β‐blocker therapy in heart failure may be associated with deterioration of cardiac function in the short term. Treatment should be started at a low dose of β‐blocker with slow up‐titration in a number of steps over several weeks. In spite of the established benefits of ACE inhibition in patients with heart failure, this treatment is under‐utilized. Part of this shortfall is due to physicians’ perceptions regarding potential unwanted effects of ACE inhibition. Perceptions regarding unwanted effects of β‐adrenoceptor blocker therapy are likely to be at least as great. While β‐blockade represents a welcome addition to the therapeutic armoury of physicians caring for patients with heart failure, initiation and stabilization of β‐adrenoceptor blocker therapy should be undertaken under specialist supervision.
Formation of omeprazole sulphone but not 5‐hydroxyomeprazole is inhibited by grapefruit juice
Authors: Tassaneeyakul Wichittra , Tassaneeyakul Wongwiwat , Vannaprasaht Suda , Yamazoe Yasushi 
Published: March 2003

Aims To determine the effect of grapefruit juice on omeprazole metabolism in vivo. Methods This was a randomized crossover study with a 2 week washout period. Omeprazole (20 mg) was taken orally by 13 healthy volunteers after an overnight fast with either grapefruit juice or water. Serial blood samples were obtained over 12 h and standardized meals were served 3 and 10 h after the administration of omeprazole. Plasma concentrations of omeprazole and its major metabolites, 5‐hydroxyomeprazole and omeprazole sulphone, were determined by high performance liquid chromatography (h.p.l.c.). Results Mean area under the plasma concentration vs time curve (AUC) between 0 and 12 h for omeprazole sulphone was approximately 20% lower (P<0.01) in the group receiving grapefruit juice. There was no significant difference in the mean AUC of 5‐hydroxyomeprazole or omeprazole. The AUC ratio of omeprazole sulphone to omeprazole, an index of CYP3A4 activity, was decreased by 33% (P<0.001) after administration of grapefruit juice whereas the AUC ratio of 5‐hydroxyomeprazole to omeprazole, an index of CYP2C19 activity, did not differ between the two phases of the study. Although the time to peak concentration (tmax ) and terminal half‐life (t1/2,z) of omeprazole and its two main metabolites were not altered, the peak concentration (Cmax ) of omeprazole sulphone was significantly reduced after administration of grapefruit juice. Conclusion Administration of grapefruit juice decreased the formation of omeprazole sulphone but not 5‐hydroxyomeprazole. These results indicate that activities of CYP3A4, but not of CYP2C19, are inhibited by the simultaneous administration of grapefruit juice.
Sleeping with the enemy? A randomized controlled trial of a collaborative health authority/industry intervention to influence prescribing practice
Authors: Freemantle Nick , Johnson Richard , Dennis Jane , Kennedy Andrew , Marchment Mike 
Published: March 2003

Aims To evaluate the effectiveness of a health authority/pharmaceutical company collaborative intervention to influence the choice of proton pump inhibitors Methods Randomized controlled trial, with general practices forming the unit of allocation and analysis. Results Constructive working relationships were achieved with five of six pharmaceutical companies involved. One hundred and two out of 140 practitioners in intervention group practices received at least one visit from an industry representative. There were no reports of representatives operating outside their agreed remit. Prescribing in both the intervention and control group moved towards that recommended by the guidelines but there was no difference between the groups in either the proportion of prescriptions in line with the guidelines or the overall cost. Conclusions Health authorities can achieve professional working relationships with the pharmaceutical industry although no changes in practice attributable to the intervention are achieved. Further work is required to develop effective means to influence prescribing in line with independent guidelines especially in the context of the development of Primary Care Groups.