bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance characteristics of scintigraphic transit measurements for studies of experimental therapies
Authors: Cremonini F. , Mullan B. P. , Camilleri M. , Burton D. D. , Rank M. R. 
Published: March 2003

SummaryBackground : The intra‐ and inter‐individual reproducibility of gastrointestinal and colonic transit tests require full characterization.Aims : (i) To characterize the normal values and reproducibility effects of age and gender on the scintigraphic transit of solids in health. (ii) To compare scintigraphic and radio‐opaque marker measurements of colonic transit. (iii) To estimate demonstrable effect sizes for different transit end‐points based on observed variations.Methods : A scintigraphic gastrointestinal and colonic transit study and the mean colonic transit time were measured using radio‐opaque markers in 37 healthy volunteers; 21 subjects had a repeat scintigraphic test 3 weeks later.Results : Gastric emptying at 4 h was highly reproducible (coefficient of variation, 4%) on repeat testing. The colonic measurement varied by more than 1 geometric centre unit in 37% of subjects at 24 h and in 26% of subjects at 48 h. There were no age‐ or gender‐related differences in transit. Effect sizes demonstrable with 14 subjects per group were in the range previously shown to be clinically relevant: 25% change in gastric emptying at 4 h; 1.5 geometric centre unit change in colonic transit at 48 h.Conclusions : These data demonstrate the reproducibility and performance to be expected of transit measurements and are essential for designing studies in experimental therapeutics.
Gut mucosal response to food antigens in Crohn's disease
Authors: Van Den Bogaerde J. , Cahill J. , Emmanuel A. V. , Vaizey C. J. , Talbot I. C. , Knight S. C. , Kamm M. A. 
Published: March 2003

SummaryBackground : Food antigens may contribute to gut inflammation in Crohn's disease.Aim : To assess in vivo sensitization to food antigens, ascertain whether sensitivity is gut specific, assess food sensitization in vitro, and correlate in vivo changes with histological and blood changes.Methods : Skin testing and rectal exposure to six food antigens (cereal, cabbage, citrus, milk, yeast and peanut) and control saline were assessed double‐blind by immediate and 3.5‐h laser Doppler blood flowmetry, and rectal biopsies were taken. Peripheral blood lymphocyte proliferation was measured in response to the same antigens.Results : Ten patients with Crohn's disease and 10 healthy controls were studied. Blood flow increased in 24 of 60 antigen sites in Crohn's disease patients and six of 60 antigen sites in controls (P < 0.0001) after 3.5 h. The Crohn's disease group demonstrated higher rectal blood flow than controls in response to all food antigens, and this was significantly different for the responses to yeast (P = 0.036) and citrus fruits (P = 0.038). Lymphocyte proliferation occurred in 32 of 60 tests in Crohn's disease patients and eight of 60 tests in controls (P < 0.0001). There were no skin responses. Submucosal oedema corresponded to increased mucosal flow.Conclusions : Crohn's disease patients demonstrate in vivo and in vitro sensitization to food antigens, which is gut specific. Mucosal flowmetry allows the identification of sensitization to gut antigens.
Is your patient taking the medicine? A simple assay to measure compliance with 5‐aminosalicylic acid‐containing compounds
Authors: Shaw I. S. , Jobson B. A. , Silverman D. , Ford J. , Hearing S. D. , Ball D. , Johnson E. , Day A. , Probert C. S. J. 
Published: March 2003

SummaryBackground : Poor compliance with 5‐aminosalicylic acid therapy has been reported amongst patients with inflammatory bowel disease. Currently, there is no easy method to monitor 5‐aminosalicylic acid; however, the chemical similarity between 5‐aminosalicylic acid and salicylate might provide a solution.Aim : To determine the feasibility of using salicylate levels to monitor compliance with 5‐aminosalicylic acid medication.Methods : Thirty‐six patients with inflammatory bowel disease, taking maintenance 5‐aminosalicylic acid, provided either a paired serum and urine sample or an intestinal biopsy. Samples were split into two: half were sent to the hospital biochemistry department for salicylate measurement, and half were analysed for 5‐aminosalicylic acid and its metabolite, N‐acetyl‐5‐aminosalicylic acid, using high performance liquid chromatography. Correlation between the results was calculated.Results : Serum and urine were available for 25 patients. Serum salicylate was undetectable, but urinary salicylate ranged from 31 to 3254 µg/mL. The correlations between urinary salicylate and 5‐aminosalicylic acid and N‐acetyl‐5‐aminosalicylic acid were 0.96 (95% confidence interval, 0.91–0.98) and 0.9 (95% confidence interval, 0.77–0.96), respectively. Sixteen biopsies were available from 13 patients. The 5‐aminosalicylic acid and N‐acetyl‐5‐aminosalicylic acid concentrations were 0.2–657 ng/mg and 1.6–1598 ng/mg, respectively; there was no correlation with bowel salicylate.Conclusions : The close correlation between 5‐aminosalicylic acid and salicylate levels offers a simple method to assess compliance with 5‐aminosalicylic acid therapy.
Is there an optimal therapeutic regimen for antimitochondrial antibody‐negative primary biliary cirrhosis (autoimmune cholangitis)?
Authors: Gisbert J. P. , Jones E. A. , Pajares J. M. , Moreno‐Otero R. 
Published: March 2003

SummaryTesting for antimitochondrial antibodies is the most useful laboratory procedure in the diagnosis of primary biliary cirrhosis; nevertheless, 5–10% of patients with typical features of primary biliary cirrhosis do not have detectable antimitochondrial antibodies, their condition being referred to as antimitochondrial antibody‐negative primary biliary cirrhosis or ‘autoimmune cholangitis’. Uncertainty exists whether antimitochondrial antibody‐positive and ‐negative primary biliary cirrhosis represent distinct entities.We reviewed studies that compared: (i) the clinical, laboratory and histological characteristics of antimitochondrial antibody‐positive and ‐negative primary biliary cirrhosis; (ii) the response to treatment of both conditions; and (iii) the response of autoimmune cholangitis to ursodeoxycholic acid and immunosuppressive therapy. Antimitochondrial antibody‐positive and ‐negative primary biliary cirrhosis were characterized by similar clinical, laboratory and histological abnormalities, clinical course and survival.Antimitochondrial antibody status did not seem to affect the response to ursodeoxycholic acid. At present, the efficacy of therapies for autoimmune cholangitis has not been established in controlled trials. Of 52 patients with autoimmune cholangitis treated with ursodeoxycholic acid in 13 uncontrolled studies, 83% had serum biochemical improvement. Also, a favourable effect of immunosuppressive drugs occurred in 57% of 54 patients with autoimmune cholangitis in 17 uncontrolled studies. Each of these trials included very few patients and most evaluated the effects of treatment on surrogate markers of disease only.No marker that consistently distinguished patients who would respond favourably to ursodeoxycholic acid or immunosuppression was apparent. Consequently, treatment is, at present, empirical. However, ursodeoxycholic acid may be given when histology reveals bile duct lesions, whereas immunosuppressive therapy should probably be reserved for patients exhibiting interface hepatitis.
Cp50 of propofol for laryngeal mask airway insertion using predicted concentrations with and without nitrous oxide
Authors: Kodaka M. , Handa F. , Kawasaki J. , Miyao H. 
Published: March 2003

SummaryThis study sought to determine the predicted Cp50 of propofol required for laryngeal mask airway insertion (Cp50LMA) and to investigate whether nitrous oxide reduces these required concentrations. Using target‐controlled infusion and incorporating the standard Diprifusor™ pharmacokinetic model, 46 unpremedicated patients were randomly assigned to one of two groups. The patients received either 40% oxygen in air (control group: n = 23), or 60% nitrous oxide in oxygen (nitrous oxide group: n = 23). The target concentration for each patient was determined using the up and down method. Following equilibration between the predetermined blood and effect site concentrations, had been established for > 10 min, laryngeal mask airway insertion was attempted without neuromuscular relaxants. The data were analysed using a probit analysis to obtain Cp50LMA levels. The values for Cp50LMA were 3.24 µg.ml−1 in the control group and 1.93 µg.ml−1 in the nitrous oxide group.
Late Quaternary sedimentation and palaeohydrology in the Acre foreland basin, SW Amazonia
Authors: Kronberg  , Fralick  , Benchimol  
Published: March 2003

Our study explores the geohydraulic history of the Acre retroarc foreland basin by gathering both spatial and temporal information from the upper 400 m of sediments. We also inquire into controls on sediment accommodation space as well as on stream vs. lacustrine domination.The Acre basin is located in south‐west Amazonia, proximal to the Serra do Divisor which demarcates the eastern edge of the Andean fold–thrust belt. Radiocarbon ages from a range of materials indicate that the upper 50–250 m of the Solimôes Formation accumulated during the past 50 000 years. Both surficial and drill‐core sediment records show lacustrine–fluvial transitions throughout the Late Quaternary. These shifts in depositional environments are in response to episodic changes in hydrological conditions as well as to geodynamic activity, such as subsidence. Juxtaposition of lacustrine and fluvial systems in the vertical Acre basin record mimics the regional‐scale trends in the modern, upper and middle Solimôes–Amazon floodplains.In the Acre basin record lacustrine successions are characterized by increasing calcium contents up‐section. This is also manifested, in the upper portions of lacustrine sequences outcropping at the surface, as alternating clastic and calcareous layers. The up‐section increase in carbonate content is related to increasing salinities brought about by drier hydrodynamic conditions. Desiccation cracks are typically infilled with gypsum as are cavities of fossils in bone‐beds. The latter represent isolated ponds in which the original fauna died as aridity intensified and waters became increasingly saline.Modern trunk river systems in the Acre basin flow from south‐west to north‐east with tributaries entering from the south‐west, suggesting the influence of a domino‐style, basement, fault regime. Fault or, at least, fracture control on stream channels is also suggested throughout the greater Amazon basin in the orthogonal dispositions and asymmetric terrace systems of trunk rivers as well as of major tributaries.
Late Archaean to Palaeoproterozoic geotherms in the Kaapvaal craton, South Africa: constraints on the thermal evolution of the Witwatersrand Basin
Authors: Gibson R. L. , Jones M. Q. W. 
Published: March 2003

ABSTRACTThe c. 2.97–2.71 Ga Witwatersrand Basin located in the Kaapvaal craton of South Africa represents a remnant of a large Late Archaean sedimentary basin that hosts the world's premier gold deposit within a series of conglomerate horizons. Evidence of postdepositional gold mobility within these conglomerates associated with hydrothermal–metamorphic activity has led to speculation about the Late Archaean to Palaeoproterozoic geothermal gradients in the basin. We use surface heat flow and heat production data from rocks in the basin and its environs in order to calculate detailed temperature profiles for the central Kaapvaal craton that show that the steady state crustal geotherm during the Late Archaean and Palaeoproterozoic was relatively cool at 15–20 K km−1. The geotherm in the upper crustal strata is also largely unaffected by substantial increases in the heat flow into the base of the crust. Consequently, regional greenschist facies metamorphism of the basin sediments could only have been achieved during a transient thermal event that advected heat into the upper crust. The most likely candidate for this is the Bushveld magmatic event at 2.06 Ga.
Interactions between onshore bedrock‐channel incision and nearshore wave‐base erosion forced by eustasy and tectonics
Authors: Snyder N.P. , Whipple K.X. , Tucker G.E. , Merritts D.J. 
Published: March 2003

AbstractWe explore the response of bedrock streams to eustatic and tectonically induced fluctuations in base level. A numerical model coupling onshore fluvial erosion with offshore wave‐base erosion is developed. The results of a series of simulations for simple transgressions with constant rate of sea‐level change (SLR) show that response depends on the relative rates of rock uplift (U) and wave‐base erosion (ɛw). Simple regression runs highlight the importance of nearshore bathymetry. Shoreline position during sea‐level fall is set by the relative rate of base‐level fall (U‐SLR) and ɛw, and is constant horizontally when these two quantities are equal. The results of models forced by a realistic Late Quaternary sea‐level curve are presented. These runs show that a stable shoreline position cannot be obtained if offshore uplift rates exceed ɛw. Only in the presence of a relatively stable shoreline position, fluvial profiles can begin to approximate a steady‐state condition, with U balanced by fluvial erosion rate (ɛf). In the presence of a rapid offshore decrease in rock‐uplift rate (U), short (∼5 km) fluvial channels respond to significant changes in rock‐uplift rate in just a few eustatic cycles. The results of the model are compared to real stream‐profile data from the Mendocino triple junction region of northern California. The late Holocene sea‐level stillstand response exhibited by the simulated channels is similar to the low‐gradient mouths seen in the California streams.
The time of maximum effect for model selection in pharmacokinetic– pharmacodynamic analysis applied to frusemide
Authors: Wakelkamp Monique , Alván Gunnar , Paintaud Gilles 
Published: March 2003

Aims
Both indirect‐response models and effect‐compartment models are used to describe the pharmacodynamics of drugs when there is a delay in the time course of the pharmacological effect in relation to the concentration of the drug. The aim of this study was to investigate whether the time of maximum response after single‐dose administration at different dose levels could be used to distinguish between these models and to select the most appropriate pharmacokinetic‐pharmacodynamic model for frusemide.
Methods
Three doses of frusemide, 10, 25 and 40 mg were given as rapid intravenous infusions to five healthy volunteers. Urine samples were collected for 5 h after dosing. Volume and sodium losses were isovolumetrically replaced with an intravenous rehydration fluid. Diuresis and natriuresis were modelled for all three doses simultaneously, applying both an indirect‐response model and an effect‐compartment model with the frusemide excretion rate as the pharmacokinetic input.
Results
The observed time of maximum diuretic and natriuretic response significantly increased with dose. This increase was well predicted by the indirect‐response model, whereas the modelling with the effect‐compartment model led to a poor prediction of the peaks. There was no difference between the observed and predicted time of maximum diuretic and natriuretic response using the indirect‐response model, whereas the time of maximum response predicted by the effect‐compartment model was significantly earlier than the time observed for the 25 mg (P<0.05) and 40 mg (P<0.05) doses.
Conclusions
The time of maximum response to frusemide was better described using an indirect‐response model than an effect‐compartment model. Studying the time of maximum response after administration of different single doses of a drug may be used as a selective tool during pharmacokinetic‐pharmacodynamic modelling.
Results of single and repeat dose studies of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers
Authors: Millar Andrew W. , Brown Peter D. , Moore Jeff , Galloway W. Alan , Cornish Alan G. , Lenehan Terence J. , Lynch Kevin P. 
Published: March 2003

Aims
To assess the tolerability and pharmacokinetic profile of single and repeat doses of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers.
Methods
A total of 31 subjects participated in two placebo‐controlled, rising‐dose studies. The first study assessed the pharmacokinetics and tolerability of single doses of marimastat of 25, 50, 100, 200, 400 and 800 mg. In the second study, continuous dosing over 6.5 days with three incremental dose levels of 50, 100 and 200 mg twice daily was assessed. Full pharmacokinetic profiles were obtained on days 0 and 6, and trough concentrations were measured on all days. For each pharmacokinetic profile in the studies, summary measures including Cmax, tmax, elimination half‐life and AUC were calculated. Urinary drug weights were also measured. All adverse events were documented, and haematological and biochemical variables, vital signs and ECGs were monitored throughout the study.
Results
Peak plasma concentrations were observed at 1.5–3 h for all subjects at all doses. Peak levels were approximately proportional to dose, as was drug exposure as calculated by AUC. Data from both studies indicate that the terminal elimination half‐life is of the order of 8–10 h, and that there is no unexpected drug accumulation. Marimastat was well‐tolerated, with adverse effects being mild and occurring with similar frequency to placebo. Small but reversible elevations in liver transaminases were noted with repeat dosing of marimastat, the most significant of these occurring at a dose of 200 mg twice daily.
Conclusion
Single and repeat oral doses of marimastat in healthy male subjects appear to be well‐tolerated. The drug is rapidly absorbed with high peak levels achieved. It has a terminal elimination half‐life of 8–10 h which would support twice daily dosing in further clinical trials.
Antioxidant power of angiotensin‐converting enzyme inhibitors in vitro
Authors: Benzie Iris F. F. , Tomlinson Brian 
Published: March 2003

Aims
There is controversy regarding the potential antioxidant effect of captopril, therefore this study was performed to compare the in vitro antioxidant power of captopril with other angiotensin‐converting enzyme (ACE) inhibitors.
Methods
Antioxidant power of captopril, enalapril, fosinopril, perindopril, quinapril and ramipril in aqueous solution was measured using the ferric reducing (antioxidant) power (FRAP) assay; captopril was also measured in ethanolic solution.
Results
Only captopril showed significant antioxidant power, demonstrating a stoichiometric factor of 1.0 in this assay. Concentration‐related antioxidant power was seen in both aqueous and ethanolic solutions.
Conclusions
Captopril shows antioxidant activity in vitro. This property could be relevant in vivo if captopril is concentrated in membranes, lipoproteins or at other important sites.
Lipoprotein composition and oxidative modification during therapy with gemfibrozil and lovastatin in patients with combined hyperlipidaemia
Authors: Vázquez M. , Zambón D. , Hernández Y. , Adzet T. , Merlos M. , Ros E. , Laguna J. C. 
Published: March 2003

Aims
To evaluate the resistance to oxidation of human lipoproteins after hypolipidaemic therapy.
Methods
VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a randomized, double‐blind, cross‐over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice daily, or lovastatin, 40 mg daily) and a 4‐week wash‐out period. Oxidation related analytes after Cu‐induced oxidation of VLDL and LDL have been investigated. Further, in order to relate possible changes in oxidative behaviour to lipoprotein composition, the proportion of the lipid species transported by lipoproteins (triglycerides, phospholipids, and cholesteryl esters), the molar composition of fatty acids for each lipoprotein lipid, and the content of antioxidant vitamins in plasma (vitamin C) and lipoproteins (vitamin E) have been studied.
Results
Both drugs reduced the plasma concentration of apo‐B lipoproteins (−23% gemfibrozil, −26% lovastatin), but whereas lovastatin affected mainly LDL‐cholesterol (−30%), gemfibrozil reduced triglycerides (−49%) and VLDL‐cholesterol (−48%). Lovastatin treatment had no effect on the lipid and protein composition, the fatty acid profile, or the vitamin E content of either VLDL or LDL; likewise, lipoprotein oxidation markers (Cu‐induced conjugated dienes, thiobarbituric acid reactive substances formation, and lysine residues) were similar before and after lovastatin treatment. Gemfibrozil therapy also had no effect on lipoprotein oxidation; nevertheless, it consistently: a) decreased the proportion of LDL‐triglycerides (−32%), and b) increased the proportion (molar%) of 18:3 n‐6 in VLDL triglycerides (+140%), phospholipids (+363%) and cholesteryl esters (+53%).
Conclusions
Based on these results, lovastatin and gemfibrozil do not adversely affect lipoprotein oxidation in patients with mixed dyslipidaemia. In the case of gemfibrozil, this occurs in spite of an increased proportion of some polyunsaturated fatty acids in VLDL. In the context of a fixed dietary intake, such modifications suggest that the drug influences liver enzyme activities involved in fatty acid chain synthesis (elongases and desaturases).
Computerized surveillance of adverse drug reactions in hospital: pilot study
Authors: Azaz‐Livshits Tatyana , Levy Micha , Sadan Batami , Shalit Meir , Geisslinger Gerd , Brune Kay 
Published: March 2003

Aims
To develop and assess the use of computerized laboratory data as a detection support tool of adverse drug reactions (ADRs) in hospital.
Methods
This was a retrospective observational study of 153 sequential medical admissions during a 2‐month period to the 34‐bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. Measurements made were 1) Retrospective chart review for recognized and unrecognized adverse drug reactions (ADRs) and 2) Analysis of computerized laboratory data according to defined automatic laboratory signals (ALS) for adverse reactions.
Results
Forty ADRs have been detected in 38 out of the 153 hospital admissions (24.8%). Nine reactions were considered severe. Altogether 212 ALS were generated involving 86 admissions. In 25 (65.8%) of the ADR‐positive admissions ADRs were detected through automatic signals generated from the laboratory data. ALS were detected in 56 out of the 115 (48.7%) ADR‐negative admissions. Twenty‐four (60%) of the ADRs were not recognized as such by the attending physicians. Two of these reactions were severe. ALS could have generated an alert for 19 (79.2%) of the unrecognized reactions.
Conclusions
Application of automatic laboratory signals can increase the rate of recognition of ADRs and thereby improve medical care. The sensitivity and specificity of the method might be increased by refinement and redefinition of the signals.