bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Miocene tectono‐sedimentary evolution of the southern Tyrrhenian Sea: stratigraphy, structural and palaeomagnetic data from the on‐shore Amantea basin (Calabrian Arc, Italy)
Authors: Mattei M. , Cipollari P. , Cosentino D. , Argentieri A. , Rossetti F. , Speranza F. ,   and, Di Bella L. 
Published: March 2003

AbstractWe report on new stratigraphic, palaeomagnetic and anisotropy of magnetic susceptibility (AMS) results from the Amantea basin, located on‐shore along the Tyrrhenian coast of the Calabrian Arc (Italy). The Miocene Amantea Basin formed on the top of a brittlely extended upper plate, separated from a blueschist lower plate by a low‐angle top‐to‐the‐west extensional detachment fault. The stratigraphic architecture of the basin is mainly controlled by the geometry of the detachment fault and is organized in several depositional sequences, separated by major unconformities. The first sequence (DS1) directly overlaps the basement units, and is constituted by Serravallian coarse‐grained conglomerates and sandstones. The upper boundary of this sequence is a major angular unconformity locally marked by a thick palaeosol (type 1 sequence boundary). The second depositional sequence DS2 (middle Tortonian‐early Messinian) is mainly formed by conglomerates, passing upwards to calcarenites, sandstones, claystones and diatomites. Finally, Messinian limestones and evaporites form the third depositional sequence (DS3). Our new biostratigraphic data on the Neogene deposits of the Amantea basin indicate a hiatus of 3 Ma separating sequences DS1 and DS2.The structural architecture of the basin is characterized by faulted homoclines, generally westward dipping, dissected by eastward dipping normal faults. Strike‐slip faults are also present along the margins of the intrabasinal structural highs. Several episodes of syn‐depositional tectonic activity are marked by well‐exposed progressive unconformities, folds and capped normal faults. Three main stages of extensional tectonics affected the area during Neogene‐Quaternary times: (1) Serravallian low‐angle normal faulting; (2) middle Tortonian high‐angle syn‐sedimentary normal faulting; (3) Messinian‐Quaternary high‐angle normal faulting.Extensional tectonics controlled the exhumation of high‐P/low‐T metamorphic rocks and later the foundering of the Amantea basin, with a constant WNW‐ESE stretching direction (present‐day coordinates), defined by means of structural analyses and by AMS data. Palaeomagnetic analyses performed mainly on the claystone deposits of DS1 show a post‐Serravallian clockwise rotation of the Amantea basin.The data presented in this paper constrain better the overall timing, structure and kinematics of the early stages of extensional tectonics of the southern Tyrrhenian Sea. In particular, extensional basins in the southern Tyrrhenian Sea opened during Serravallian and evolved during late Miocene. These data confirm that, at that time, the Amantea basin represented the conjugate extensional margin of the Sardinian border, and that it later drifted south‐eastward and rotated clockwise as a part of the Calabria‐Peloritani terrane.
Digital rocks: linking forward modelling to carbonate facies
Authors: Boylan A. L. , Waltham D. A. , Bosence D. W. J. , Badenas B. , Aurell M. 
Published: March 2003

ABSTRACTForward stratigraphic models usually display sediment types on simulated stratigraphic profiles as ‘facies’ defined only by their depth of deposition. More recently, ‘facies’ have been defined and displayed in terms of the dominant processes of deposition (e.g. in situ growth, pelagic production, turbidite deposition). Standard carbonate facies; that is, the Dunham classification, are defined by rock textures and grain composition that imply that a combination of processes acted together to generate a facies. For example, a bioclastic wackestone is a matrix‐supported rock containing up to 90% matrix and > 10% shelly grains. In terms of modelled processes, the muddy matrix could be generated by: (i) reworking of the shallow platform sediments, (ii) from pelagic deposition, or (iii) in situ production. A traditional depth of deposition process display would not be able to distinguish such a wackestone from any other facies deposited at this water depth and a majority process display would not combine reworked, pelagic muds and in situ contribution in one simulated ‘facies’. This paper introduces a new scheme that enables forward models to output simulated facies defined by a range of values for each of the controlling processes and thereby predicts rock textures within simulated stratigraphies. This approach has been applied to the Jurassic carbonate ramps of the Iberian Basin in northeastern Spain. It is shown to provide more accurate information about the processes that are being simulated, allowing more direct comparisons to be made with the facies observed in the field and providing potential for a more rigorous method for assessing the ‘goodness of fit’ of a simulated stratigraphy.
Evolution of the Longmen Shan Foreland Basin (Western Sichuan, China) during the Late Triassic Indosinian Orogeny
Authors: Yong L. , Allen P. A. , Densmore A. L. , Qiang X. 
Published: March 2003

ABSTRACTThe Longmen Shan Foreland Basin developed as a flexural foredeep during the Late Triassic Indosinian orogeny, spanning the time period c. 227–206 Ma. The basin fill can be divided into three tectonostratigraphic units overlying a basal megasequence boundary, and is superimposed on the Palaeozoic–Middle Triassic (Anisian) carbonate‐dominated margin of the South China Block. The remains of the load system responsible for flexure of the South China foreland can be seen in the Songpan‐Ganzi Fold Belt and Longmen Shan Thrust Belt. Early in its history the Longmen Shan Foreland Basin extended well beyond its present northwestern boundary along the trace of the Pengguan Fault, to at least the palinspastically restored position of the Beichuan Fault.The basal boundary of the foreland basin megasequence is a good candidate for a flexural forebulge unconformity, passing from conformity close to the present trace of the Beichuan Fault to a karstified surface towards the southeast. The overlying tectonostratigraphic unit shows establishment and drowning of a distal margin carbonate ramp and sponge build‐up, deepening into offshore marine muds, followed by progradation of marginal marine siliciclastics, collectively reminiscent of the Alpine underfilled trinity of Sinclair (1997). Tectonostratigraphic unit 2 is marked by the severing of the basin's oceanic connection, a major lake flooding and the gradual establishment of major deltaic‐paralic systems that prograded from the eroding Longmen Shan orogen. The third tectonostratigraphic unit is typified by coarse, proximal conglomerates, commonly truncating underlying rocks, which fine upwards into lacustrine shales.The foreland basin stratigraphy has been further investigated using a simple analytical model based on the deflection by supracrustal loads of a continuous elastic plate overlying a fluid substratum. Load configurations have been partly informed by field geology and constrained by maximum elevations and topographic profiles of present‐day mountain belts. The closest match between model predictions and stratigraphic observations is for a relatively rigid plate with flexural rigidity on the order of 5 × 1023 to 5 × 1024 N m (equivalent elastic thickness of c. 43–54 km). The orogenic load system initially (c. 227–220 Ma) advanced rapidly (>15 mm yr−1) towards the South China Block in the Carnian, associated with the rapid closure of the Songpan‐Ganzi ocean, before slowing to < 5 mm yr−1 during the sedimentation of the upper two tectonostratigraphic units (c. 220–206 Ma).
Risk factors for mortality in users of ibopamine
Authors: Feenstra J. , In′t Veld B. A. , Van Der Linden P. D. , Grobbee D. E. , Stricker B. H. Ch. 
Published: March 2003

Aims
In September 1995, the indication for the oral dopamine agonist ibopamine was restricted in the Netherlands and in several other European countries to patients with NYHA‐class II heart failure as a result of an interim analysis of the PRIME‐II trial. This trial demonstrated an increased risk of mortality in patients with NYHA‐class III/IV heart failure on ibopamine. In September 1995, we initiated an assessment of the effects of ibopamine under everyday circumstances in a cohort of users of ibopamine in all NYHA‐classes.
Methods
In a nationwide retrospective cohort study all 2147 community pharmacies and drug dispensing general practitioners received a request to list all patients to whom they had dispensed ibopamine in the preceding years. All responding drug dispensing outlets (DDO) received a questionnaire on cardiovascular risk factors and mortality for the general practitioner of a random sample of these patients. DDO were also requested to send an anonymised printout of the complete medication record. On the end‐date of follow‐up, February 15th 1996, mortality rates were compared across categories of ibopamine use, adjusted for potential confounders. To assess medication use, drug exposure was compared in a 3 months’ period before date of death in the deceased, and before a random date in those patients who were still alive.
Results
In patients with NYHA‐class III/IV heart failure, multivariate analysis indicated that current use of ibopamine was significantly associated with mortality (RR 1.37;95% CI: 1.15–1.64). In patients with NYHA‐class I/II heart failure, however, multivariate analysis showed a 2.03 (95% CI: 1.10–3.72) risk of mortality in current users of ibopamine. Apart from current use of ibopamine, male gender and increased serum creatinine were also independent risk factors for mortality in all NYHA‐classes. No statistically significant association was found between mortality and current use of amiodarone or use of amiodarone at baseline.
Conclusions
The increased risk of mortality in patients with NYHA‐class III and IV heart failure on ibopamine seems to confirm the main finding of the recently published PRIME‐II trial. However, our results indicate that also patients with NYHA‐class I/II heart failure may be at an increased risk of mortality when using ibopamine. Additional research on the effects of ibopamine in these patients is warranted and the use of ibopamine in NYHA‐class II heart failure patients may have to be reconsidered.
Radioreceptor assay analysis of tamsulosin and terazosin pharmacokinetics
Authors: Taguchi Katsunari , Schäfers Rafael F. , Michel Martin C. 
Published: March 2003

Aims
A radioreceptor assay has been developed for α1‐adrenoceptor subtypes and applied to a pharmacokinetic analysis of tamsulosin and terazosin.
Methods
Young, male, healthy volunteers received 0.4 mg tamsulosin (as Omnic® modified release capsules) or 5 mg terazosin (as Flotrin® tablets) in a randomized, cross‐over design. Before and after 1, 3, 5, 7, 10 and 23.5 h plasma was analyzed by radioreceptor assay using cloned human α1A‐, α1B‐ and α1D‐adrenoceptors and specific h.p.l.c. analysis.
Results
Following ingestion of tamsulosin median peak plasma levels of 16 ng ml−1 were reached after 5 h and declined to 2 ng ml−1 at 23.5 h. The time course in the radioreceptor assay was similar, and at most time points binding to α1A‐adrenoceptors was significantly greater than to α1B‐ and α1D‐adrenoceptors. Following ingestion of terazosin median peak plasma levels of 91 ng ml−1 were reached after 1 h and declined to 11 ng ml−1 at 23.5 h. In the radioreceptor assay binding also peaked at 1 h and declined thereafter, but even after 23.5 h considerable binding activity remained detectable at all three subtypes. At most time points binding to the α1A‐ and α1D‐adrenoceptor was significantly greater than to the α1B‐adrenoceptor.
Conclusions
We conclude that α1‐adrenoceptor antagonist pharmacokinetics can be monitored by radioreceptor assays in a subtype‐selective manner. Tamsulosin and terazosin exhibit subtype selective receptor binding ex vivo. The discordance between terazosin blood levels as determined by h.p.l.c. and radioreceptor assay at late time points indicates the possible involvement of metabolites in in vivo terazosin effects.
A limited sampling method for the estimation of AUC and Cmax of carbamazepine and carbamazepine epoxide following a single and multiple dose of a sustained‐release product
Authors: Mahmood Iftekhar , Chamberlin Nancy 
Published: March 2003

Aims
The objectives of this study are to develop a model to predict area under the curve (AUC) and maximum plasma concentration (Cmax ) of carbamazepine (CBZ) and its active metabolite carbamazepine epoxide (CBZE) following single and multiple dose of CBZ using one or two samples in volunteers.
Methods
Limited sampling models (LSM) were developed for CBZ and CBZE following 200–800 mg single oral dose and 400–800 mg twice daily dose for 14 days of a sustained‐release product (CBZ‐SR) to estimate AUC and Cmax. The LSM was developed from a training data set of 15 subjects using one blood sample taken at 48 h following a single dose. The model was validated on 60 subjects who received different doses of CBZ. Following multiple dosing, the LSM was developed from a training data set of 10 subjects using the steady state Cmin (plasma concentration obtained 5 min before the last CBZ‐SR dose).
Results
The model provided good estimates of AUC and Cmax for CBZ and CBZE. The bias and the precision of the predicted AUC and Cmax for CBZ and CBZE were less than 10% and 15%, respectively. Similar results were obtained when CBZ was given as multiple dose.
Conclusions
The method described here may be used to estimate AUC and Cmax for CBZ and CBZE without detailed pharmacokinetic studies following single or multiple dose of CBZ.
Induction of CYP1A2 activity by carbamazepine in children using the caffeine breath test
Authors: Parker A. C. , Pritchard P. , Preston T. , Choonara I. 
Published: March 2003

Aims
Carbamazepine is a known enzyme inducer. The aim of this study was to determine whether carbamazepine induces the metabolism of caffeine in children.
Methods
Children due to receive carbamazepine for epilepsy were recruited into the study. The caffeine breath test was carried out prior to the administration of carbamazepine and after a minimum of 2–3 weeks therapy. Five children were studied and they received 200–600 mg carbamazepine daily.
Results
The mean values of the 2 h cumulative labelled carbon dioxide were 3.47% before and 7.65% during carbamazepine. There was a significant increase in the percentage labelled caffeine exhaled as carbon dioxide during the administration of carbamazepine (Student's paired t‐test, P<0.05).
Conclusions
The results suggest that carbamazepine induces the metabolism of caffeine by the CYP1A2 pathway in the children studied.
Agreement between the pharmacy medication history and patient interview for cardiovascular drugs: the Rotterdam elderly study
Authors: Sjahid Suzy I. , Van Der Linden Paul D. , Stricker Bruno H. Ch. 
Published: March 2003

Aims
To study whether there is agreement between cardiovascular drugs presented at patient interview and pharmacy records in an elderly population.
Setting
The Rotterdam Elderly Study, a prospective population based cohort study of people older than 55 years of age.
Methods
We compared cardiovascular drug use as presented during patient interview with the computerized pharmacy medication history. Concordance of cardiovascular drug use in patient interview and pharmacy data was measured by merging the two data sets and assessed in two episodes: in a period of 6 months before patient interview and within the legend duration of each cardiovascular drug.
Results
We found 2706 concordant pairs in a total of 3365 prescriptions (80.4%) in the merged data. There were 195 prescriptions presented at patient interview which had not been filled at the pharmacy, and 464 which had been filled but were not presented by the patient. The percentage of concordant pairs slightly increased to 80.6% (2275 of a total of 2824) for prescriptions of which the legend duration included the date of patient interview. The highest agreement was noted with β‐adrenoceptor blocking agents with Kappa statistics of 0.97 for atenolol and metoprolol. The lowest Kappa statistic was found for organo‐heparinoid, mainly as ointments against haemorrhoids (0.26).
Conclusion
The agreement between patient interview and pharmacy records is good for prescription only drugs, and pharmacy records are a useful resource for pharmacoepidemiological studies on cardiovascular agents.
Determinants of the blood pressure response to the first dose of ACE inhibitor in mild to moderate congestive heart failure
Authors: Murray Lilian , Squire Iain B. , Reid John L. , Lees Kennedy R. 
Published: March 2003

Aims
To investigate the relationship in patients with heart failure between BP response to the first dose of ACE inhibitor and (1) plasma drug concentration and (2) baseline clinical and laboratory variables.
Methods
We studied individual placebo‐corrected BP responses to initiation of treatment with one of a number ACE inhibitor preparations in 132 patients with mild to moderate CHF. Various pharmacokinetic/pharmacodynamic models were compared. We assessed the strength of association between baseline physiological and laboratory variables and the BP response as assessed directly from the AUC(0,10 h) and indirectly from the slope of the PK/PD relationship. Predictive models for response variables were developing using regression analysis.
Results
BP response was primarily related to plasma drug concentration. The association between the fall in BP and baseline variables was weak. The strongest single predictor of BP response was baseline mean arterial pressure (r2=5.8%, P=0.02). The best combinations of predictor variables contained mean arterial pressure, plasma renin activity, creatinine concentration and age (r2=14.4%, P=0.37). When the choice of ACE inhibitor was added, the predictive power of the model increased (r2=23.6%, P<0.01) but left the majority of the variability in response unexplained.
Conclusions
The first‐dose blood pressure response to ACE inhibition cannot be accurately predicted from baseline pathophysiological variables in patients with mild to moderate CHF. The choice of ACE inhibitor accounts for a small proportion of the variability in response but wide inter‐individual variability exists in the response to each treatment.
Concurrent administration of donepezil HCl and cimetidine: assessment of pharmacokinetic changes following single and multiple doses
Authors: Tiseo  , Perdomo  , Friedhoff  
Published: March 2003

Aim The aim of this study was to examine the pharmacokinetics of donepezil HCl and cimetidine separately, and in combination, following administration of multiple oral doses.

Methods This was an open‐label, randomized, three‐period crossover study in healthy male volunteers (n=19). During each treatment period, subjects received single daily doses of either donepezil HCl (5 mg), cimetidine (800 mg), or a combination of both drugs for 7 consecutive days. Pharmacokinetic comparisons were made between groups for the day 1 and day 7 profiles. Each treatment period was followed by a 3‐week, drug‐free washout period.

Results On both day 1 and day 7, a statistically significant difference was observed between the donepezil and the donepezil+cimetidine groups in terms of the Cmax and AUC(0–24) values for donepezil. The combination group had an 11–13% greater Cmax and a 10% greater AUC(0–24) than the donepezil‐only group. No significant difference was observed between the tmax of the two treatment groups on day 1, and no significant differences in tmax, t½ or the rate of drug accumulation (RA ) were observed between the groups on day 7.Cimetidine pharmacokinetics were essentially unchanged by co‐administration of the two drugs. The donepezil+cimetidine treatment group had a 20% greater maximum cimetidine concentration (Cmax ) than the cimetidine‐only group (P=0.001) on day 1, but not on day 7, and no difference was observed in any of the other pharmacokinetic parameters examined.

Conclusions Co‐administration of donepezil HCl (5 mg) and cimetidine (800 mg) did not produce clinically significant changes in the pharmacokinetic profiles of either drug.
Concurrent administration of donepezil HCl and ketoconazole: assessment of pharmacokinetic changes following single and multiple doses
Authors: Tiseo  , Perdomo  , Friedhoff  
Published: March 2003

The aim of this study was to examine the pharmacokinetics of donepezil HCl and ketoconazole separately, and in combination, following administration of single and multiple oral doses.  This was an open‐label, randomized, three‐period crossover study in healthy volunteers (n=21). During each treatment period, subjects received single daily doses of either donepezil HCl (5 mg), ketoconazole (200 mg), or a combination of both drugs for 7 consecutive days. Pharmacokinetic comparisons were made between treatment groups for the day 1 and day 7 profiles. Each treatment period was followed by a 3‐week, drug‐free washout period.  On both day 1 and day 7, a statistically significant difference was observed between the donepezil and the donepezil+ketoconazole treatment groups in terms of Cmax and AUC(0–24) of donepezil. The concurrent administration of both drugs resulted in a 12% greater Cmax (9.5 ng ml−1 versus 8.4 ng ml−1; P=0.01) and a 12% greater AUC(0–24) (135.2 ng h ml−1 versus 118.7 ng h ml−1; P=0.001) than donepezil alone on day 1, and a 26.8% greater Cmax (37.7 ng ml−1 versus 27.6 ng ml−1; P<0.0001) and a 26.4% greater AUC(0–24) (680.9 ng h ml−1 versus 501.0 ng h ml−1; P<0.0001) than donepezil alone on day 7.In contrast, ketoconazole plasma concentrations were unaffected by the concurrent administration of donepezil, and there were no statistically significant differences in ketoconazole pharmacokinetics when ketoconazole administered alone was compared with ketoconazole administered with donepezil. The concurrent administration of ketoconazole and donepezil produces no change in ketoconazole plasma concentrations, but a statistically significant change in donepezil plasma concentrations. These observed changes, which are smaller than those produced by ketoconazole for other agents sharing the CYP‐3A4 pathway, are most likely the result of donepezil also being metabolized by CYP‐2D6, as well as its slow rate of clearance from plasma.
A comparative analysis of the particle size output of beclomethasone diproprionate, salmeterol xinafoate and fluticasone propionate metered dose inhalers used with the Babyhaler, Volumatic and Aerochamber spacer devices
Authors: Barry  , O’Callaghan  
Published: March 2003

Aims To determine in vitro the effect of delay, inspiratory flow, and spacer washing on the drug output of metered dose inhalers (MDIs) used with different spacer devices.Methods The amount of drug in particles <5 μm diameter from MDI+spacer, sampling after a delay of up to 20 s, was measured using a Multistage Liquid Impinger. Drug output was also measured at different flow rates, and after washing the Babyhaler in household detergent.Results More fluticasone in small particles was recovered from the Babyhaler than the Volumatic or the Aerochamber spacers, and more beclomethasone and salmeterol was recovered from the Babyhaler and Volumatic spacers than from the Aerochamber. Washing the Babyhaler reduced the recovery of salmeterol, and did not alter the recovery of the other drugs tested.Conclusions Spacer devices need to be fully evaluated for each drug prescribed for them.