bluuebunny/crossref_metadata_2025 huggingface dataset:
Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection*
Authors: Mimoz O. , Incagnoli P. , Josse C. , Gillon M‐C. , Kuhlman L. , Mirand A. , Soilleux H. , Fletcher D.
Published: March 2003

In order to compare the morphine‐sparing effect, analgesic efficacy and tolerance of nefopam and propacetamol given at their highest recommended doses, 120 patients undergoing elective hepatic resection were randomly assigned to receive postoperative intravenous patient‐controlled analgesia with morphine alone, or in combination with nefopam (20 mg.4 h‐1) or propacetamol (2 g.6 h‐1). Compared with the control group (43 [7–92] mg), median [range] cumulative morphine consumption for 24 h after the study started was halved in the nefopam group (21 [3–78] mg, p <0.001) and 20% lower in the propacetamol group (35 [6–84] mg, p = 0.15). Analgesia was superior in the nefopam group despite the lower morphine consumption. Adverse effects were comparable in the three groups, except for significantly more nausea in the control group (39% vs. 17 and 26% in the nefopam and propacetamol groups, respectively) and more sweating in the nefopam group (17% vs. 0 and 3% in the control and propacetamol groups, respectively). Overall patient satisfaction was better (p < 0.001) in patients given nefopam (97%) than those receiving morphine alone (82%) or propacetamol (74%).
Extension of epidural blockade in labour for emergency Caesarean section using 2% lidocaine with epinephrine and fentanyl, with or without alkalinisation*
Authors: Lam D. T. C. , Ngan Kee W. D. , Khaw K. S.
Published: March 2003

In a randomised, double‐blind study, we investigated rapid extension of epidural analgesia to surgical anaesthesia for emergency Caesarean section. Parturients receiving epidural analgesia in labour who subsequently required Caesarean section were given a test dose of 3 ml lidocaine 2% with epinephrine 1 : 200 000, followed 3 min later by 12 ml lidocaine 2% with epinephrine 1 : 200 000 and fentanyl 75 µg, to which was added 1.2 ml sodium bicarbonate 8.4% (bicarbonate group; n = 20) or saline (saline group; n = 20). Mean (SD [range]) time to surgical anaesthesia was less in the bicarbonate group (5.2 (1.5) [2–8] min) than the saline group (9.7 (1.6) [6–12] min; mean difference 4.5 min (95% CI 3.5–5.5) min; p < 0.001). Maternal side‐effects and neonatal outcome were similar between groups. We conclude that pH‐adjusted lidocaine 2% with epinephrine and fentanyl is effective for rapidly establishing surgical anaesthesia in patients with a functioning epidural catheter for labour who require emergency Caesarean section.
Monitoring pollution by proton‐transfer‐reaction mass spectrometry during paediatric anaesthesia with positive pressure ventilation via the laryngeal mask airway or uncuffed tracheal tube
Authors: Rieder J. , Keller C. , Brimacombe J. , Gruber G. , Lirk P. , Summer G. , Amann A.
Published: March 2003

Summary Twenty children aged 2–66 months were randomly allocated for airway management with either the laryngeal mask airway or uncuffed tracheal tube using intermittent positive pressure ventilation with a tidal volume of 8 ml.kg−1 and a respiratory rate adjusted to maintain end‐expiratory carbon dioxide concentration at 5.3 kPa. Induction was with fentanyl/propofol and maintenance was with sevoflurane 2.5% in oxygen/air. The airway device was removed when the patients were awake and the patients were transferred to the postanaesthesia care unit 10 min later. Air was sampled from a point 1.5 m above the floor at a location remote from the ventilation outlet and analysed using a proton‐transfer‐reaction mass spectrometer capable of continuous trace gas analysis at the parts per billion volume (ppbv) level. The concentration of sevoflurane was recorded every minute during three consecutive phases: for 5 min before the introduction of sevoflurane (background); after introduction of sevoflurane until removal of the airway device (intra‐operative); and every minute after removal until the concentration returned to background levels. Median (interquartile range [range]) intra‐operative sevoflurane concentrations were 200–400 times higher than background values for the laryngeal mask airway 1 (1–2 [0–3]) ppbv vs. 404 (278–523 [83–983]) ppbv, respectively, and the tracheal tube 2 (1–3 [0–5]) ppbv vs. 396 (204–589 [107–1735]) ppbv (both p < 0.0001), and returned to background values within 5 min of removal. There were no differences in sevoflurane concentration between devices intra‐operatively or after removal. The performance of the proton‐transfer‐reaction mass spectrometer was identical at the start and end of the 30‐day study. We conclude that peri‐operative sevoflurane concentration in a modern operating theatre is similar for the laryngeal mask airway and the uncuffed tracheal tube in paediatric patients receiving intermittent positive pressure ventilation. Intra‐operative sevoflurane concentrations are five times lower than occupational safety limit requirements, and 1000 times lower 5 min after removal of the airway device with the patient awake. The proton‐transfer‐reaction mass spectrometer has potential for monitoring air quality in the operating theatre.
Training in airway management
Authors: Stringer K. R. , Bajenov S. , Yentis S. M.
Published: March 2003

Management of the airway is central to the practice of anaesthesia, yet trainees frequently feel poorly trained in this area. A large range of skills needs to be acquired, but there are often problems providing training on live patients. We review the different modalities available for training and assessment in airway management.
Spinal anaesthesia for inguinal herniotomy in preterm infants sedated with nitrous oxide: a comparison of lumbar puncture in the lateral or sitting position
Authors: Vilà R. , Lloret J. , Munar F. , Vinzo J.
Published: March 2003

This study compares spinal anaesthesia for inguinal herniotomy in preterm infants in the lateral or sitting position. Thirty patients were randomly divided into two equal groups. One hour before spinal anaesthesia, a eutetic mixture of local anaesthetic cream was applied to the lower lumbar spine. Sedation with nitrous oxide 50% in oxygen was given to all patients before and during induction of spinal anaesthesia, and throughout surgery. Lumbar punctures were performed at the L4−5 interspace using a 2.5 cm 22 G needle. Isobaric bupivacaine 0.5% with epinephrine 1 : 200 000 at a bupivacaine dose of 1 mg.kg−1 was injected in the lateral or sitting position. Measurements included heart rate, blood pressure, oxygen saturation, maximum sensory block height and duration of motor block and analgesia. There were no statistically significant differences between the groups in any measured parameters. Median [range] maximum block height was T5[T4−T7] in the lateral group and T5[T4−T5] in the sitting group. The median [range] duration of motor blockade was 67 [50–85] min in the lateral group and 63 [50–80] min in the sitting group. Our results indicate that in preterm infants sedated with nitrous oxide, spinal anaesthesia for inguinal herniotomy performed with isobaric bupivacaine 0.5% at a dose 1.0 mg.kg−1 in the lateral or sitting position is equally effective and is associated with minimal side effects.
Anaesthetists' attitudes towards awareness and depth‐of‐anaesthesia monitoring
Authors: Myles P. S. , Symons J. A. , Leslie K.
Published: March 2003

Summary Advances in technology have resulted in the development of several depth‐of‐anaesthesia monitors. Whether any of these monitors can reduce the incidence of awareness is an important issue for anaesthetists and their patients. We therefore surveyed a random selection of anaesthetists, asking for their opinions of awareness and depth‐of‐anaesthesia monitoring in current clinical practice. Approximately half (52%) of the anaesthetists surveyed had experienced a patient with awareness. Anaesthetists considered that they had a lower incidence of awareness in their own practice when compared with others, 1:5000 vs. 1:10 000 (p < 0.001). Anaesthetists rated awareness on an11‐point scale as only a moderate problem, median (interquartile range) 5 (2–7). Older anaesthetists were less likely to rate the importance of awareness highly (p = 0.009) and to use awareness monitoring (p = 0.001). Anaesthetists are prepared to use depth‐of‐anaesthesia monitoring more widely if it can be shown to prevent most cases of awareness in routine practice.
THIS ARTICLE HAS BEEN RETRACTED Prevention of propofol‐induced injection pain by remifentanil: a placebo‐controlled comparison with lidocaine*
Authors: Roehm K. D. , Piper S. N. , Maleck W. H. , Boldt J.
Published: March 2003

Summary In a randomised, double‐blind study we compared the efficacy of continuous remifentanil infusion (0.25 µg.kg−1.min−1) with 40 mg lidocaine and placebo in the prevention of injection pain due to intravenous propofol administration (1.5–2 mg.kg−1) in 155 patients scheduled for elective surgery. Pain severity was evaluated using a four‐point scale. The incidence of injection pain was 62% in the placebo group and could be reduced significantly by using remifentanil (30%; p < 0.0015) or lidocaine (33%; p < 0.005). Analysis of the pain scores showed a significant difference between remifentanil and placebo (p < 0.00005) as well as between lidocaine and placebo (p < 0.0002). There was no significant difference between remifentanil and lidocaine. Remifentanil provided effective pain relief, comparable with lidocaine, and is an alternative as part of an intravenous anaesthesia regimen to using another concomitant drug.
A comparison of total intravenous with balanced anaesthesia for middle ear surgery: effects on postoperative nausea and vomiting, pain and conditions of surgery*
Authors: Mukherjee K. , Seavell C. , Rawlings E. , Weiss A.
Published: March 2003

Summary We compared postoperative nausea and vomiting (PONV), pain and conditions for surgery in patients scheduled for middle ear surgery. In a double‐blind study, 100 patients were randomly allocated to receive either balanced anaesthesia (group A) using fentanyl, propofol and isoflurane, or total intravenous anaesthesia (group B) using propofol and remifentanil infusions. Pain scores, nausea/vomiting scores, conditions for surgery and analgesic requirements were recorded for 18 h post operatively. In the recovery ward, patients in group B suffered significantly less PONV (p = 0.026) with a reduced requirement for anti‐emetic medication (p = 0.023); however, this difference was not maintained on the ward. The overall incidence of PONV was 34% and 17% in groups A and B, respectively. Initial pain scores were higher in group B in the recovery ward (p = 0.003) and patients required more morphine administration (p = 0.002); however, pain scores were similar on the ward. Conditions for surgery were found to be better in group B.
Probable dystonic reaction after a single dose of cyclizine in a patient with a history of encephalitis
Authors: King H. , Corry P. , Wauchob T. , Barclay P.
Published: March 2003

Summary A patient underwent an emergency Caesarean section under general anaesthesia for an antepartum haemorrhage. Following delivery of a live infant, cyclizine was administered in accordance with departmental anti‐emetic protocol. On awakening she was confused, slow to articulate and had slurred speech. A computed tomography (CT) scan, which was performed to exclude an intracranial event, was normal. Her symptoms were suggestive of a lingual–facial–buccal dyskinesia as seen with dopamine antagonists. A presumptive diagnosis of a dystonic reaction to cyclizine was made. She received two doses of procyclidine before her symptoms completely resolved. Cyclizine has had a resurgence in popularity owing to the recent withdrawal of droperidol and anaesthetists should be aware that, although extremely rare, dystonic reactions may occur with this agent.
Stratigraphic inversion of siliciclastic basin fills: a note on the distinction between supply signals resulting from tectonic and climatic forcing
Authors: Weltje* Gert Jan , Meijer Xander D. , De Boer Poppe L.
Published: March 2003

Rates of accommodation and sediment supply are the principal controls on stacking patterns in siliciclastic basin fills. Stratigraphic inversion is aimed at reconstruction of these controls from the detrital record. Efforts to ‘explain’ siliciclastic basin fills have been focused on analysis and numerical modelling of sequence geometry in response to changes in accommodation, whereas comparatively few studies have attempted to address the role of sediment supply. The compositional and textural properties of siliciclastic basin fills are linked with the evolution of drainage basins through the principle of climatic–physiographic control of sediment production and supply. Application of this principle leads to a method of compositional analysis for distinguishing sequences controlled by high‐frequency changes in the rate of accommodation from sequences controlled by high‐frequency variations in the rate of sediment supply (order of 10 kyr). This method does not require detailed time control. Changes in rate and type of sediment supplied to depositional systems in response to environmental perturbations in drainage basins are explored in greater detail by means of a numerical model of sediment production under various scenarios of climatic and tectonic forcing. Simulation experiments suggest that drainage basins respond differently to high‐frequency tectonic and climatic perturbations. Synthetic time series of cyclically forced sediment production display different types of asymmetric variations in grain size, accumulation rate and residence time of sediments in response to tectonic and climatic forcing. The results also highlight the role of vegetation as the principal modulator of climate forcing, and show that the nonlinear response to climate change may frustrate any attempts at providing broad generalizations of the system's responses. The modelling results confirm the usefulness of a combined analysis of sediment composition and sequence geometry, and the mathematically rich behaviour of the system suggests that further development of this approach is likely to increase our ability to reconstruct forcing mechanisms and initial boundary conditions from the detrital record.
Grain‐size trends, basin subsidence and sediment supply in the Campanian Castlegate Sandstone and equivalent conglomerates of central Utah
Authors: Robinson Ruth A. J. , Slingerl Rudy L.
Published: March 2003

Reconstructions of grain‐size trends in alluvial deposits can be used to understand the dominant controls on stratal architecture in a foreland basin. Different initial values of sediment supply, tectonic subsidence and base‐level rise are investigated to constrain their influence on stratal geometry using the observed grain‐size trends as a proxy of the goodness of fit of the numerical results to the observed data. Detailed measurements of grain‐size trends, palaeocurrent indicators, facies and thickness trends, channel geometries and palynological analyses were compiled for the middle Campanian Castlegate Sandstone of the Book Cliffs and its conglomerate units in the Gunnison and Wasatch plateaus of central Utah. They define the initial conditions for a numerical study of the interactions between large‐scale foreland basin and small‐scale sediment transport processes. From previous studies, the proximal foreland deposits are interpreted as recording a middle Campanian thrusting event along the Sevier orogenic belt, while the stratal architecture in the Book Cliffs region is interpreted to be controlled by eustatic fluctuation with local tectonic influence. Model results of stratal geometry, using a subsidence curve with a maximum rate of ≈45 m Myr−1 for the northern Wasatch Plateau region predict the observed grain‐size trends through the northern Book Cliffs. A subsidence curve with a maximum rate of ≈30 m Myr−1 in the Gunnison–Wasatch Plateaus best reproduces the observed grain‐size trends in the southern transect through the southern Wasatch Plateau. Eustasy is commonly cited as controlling Castlegate deposition east of the Book Cliffs region. A eustatic rise of 45 m Myr−1 produces grain‐size patterns that are similar to the observed, but a rate of eustatic rise based on Haq et al. (1988) will not produce the observed stratal architecture or grain‐size trends. Tectonic subsidence alone, or a combined rate of tectonic subsidence and a Haq et al. (1988) eustatic rise, can explain the stratal and grain‐size variations in the proximal and downstream regions.
Tectonic geomorphology in the Hexi Corridor, north‐west China
Authors: Li Youli , Yang Jingchun
Published: March 2003

The Hexi Corridor is a Cenozoic foreland basin system at the north‐eastern margin of the Qinghai–Tibet Plateau. Active faults, having clear geomorphological expression, are mainly NW‐trending reverse‐sinistral faults and NNW‐trending reverse‐dextral faults. From the south‐west to the north‐east, landforms can be divided into three parallel zones arranged along the WNW faults. Longitudinally, three transverse uplifted blocks divide the Hexi Corridor into four subbasins. North‐eastward motion of the Qinghai–Tibet Plateau and eastward motion of the north‐east part of the Plateau resulted in compressive and shear deformations and controlled the geomorphological pattern in the Hexi Corridor.
Minimum work, fault activity and the growth of critical wedges in fold and thrust belts
Authors: Hardy Stuart , Duncan Chris , Masek Jeff , Brown Dennis
Published: March 2003

Many studies of critical wedges treat the interior of the wedge as continuous and do not address the manner in which it grows from the undeformed state to a typical imbricate wedge. In this paper we present a 2D kinematic–mechanical model which attempts to explain the development of a critical wedge in a fold and thrust belt in terms of both gravitational and frictional work. In the undeformed model a series of thrust faults are defined which have the potential to take up an external displacement. The active fault at a given time is that which minimizes gravitational and frictional work as a result of displacement. Displacement on the active fault causes a change in topography and deformation of other faults which may favour an alternative fault at the next time step. The model is a mixed Lagrangian–Eulerian scheme in which the upper surface, in addition to being deformed, is also subject to erosion, transport and sedimentation.

The model predicts propagation of thrust fault activity towards the foreland through time as a result of increasing topographic (gravitational) loads and frictional work on deformed hinterland faults. As the zone of fault activity progresses through the developing critical wedge several faults are active over time‐scales of ≈1 Myr. However, a simple chronology or sequence of fault activity cannot be assumed as out‐of‐sequence thrusting occurs during this overall foreland propagation. The detailed spatial and temporal activity of faults is complex and reflects the interaction between the development of topography, the contrast between basal (décollement) and internal coefficients of friction and the effects of erosion and sedimentation. In particular, rates of erosion and sedimentation are found to be important controls on fault activity both spatially and temporally. Erosion, by locally removing topography above a fault, reduces gravitational and frictional work enabling continued fault activity or reactivation. Sedimentation, conversely, acts to increase gravitational and frictional work on a fault, and therefore has the potential to blanket faults and render them inactive. Model results illustrate the complex feedbacks that can exist between tectonic and surficial mass transport processes.
Gravity anomalies, subsidence history and the tectonic evolution of the Malay and Penyu Basins (offshore Peninsular Malaysia)
Authors: Madon* Mazlan B. , Watts
Published: March 2003

The tectonic subsidence and gravity anomalies in the Malay and Penyu Basins, offshore Peninsular Malaysia, were analysed to determine the isostatic compensation mechanism in order to investigate their origin. These continental extensional basins contain up to 14 km of sediment fill which implies that the crust had been thinned significantly during basin development. Our results suggest, however, that the tectonic subsidence in the basins cannot be explained simply by crustal thinning and Airy isostatic compensation.

The Malay and Penyu Basins are characterized by broad negative free‐air gravity anomalies of between −20 and −30 mGal. To determine the cause of the anomaly, we modelled four gravity profiles across the basins using a method that combines two‐dimensional flexural backstripping and gravity modelling techniques. We assumed a model of uniform lithospheric stretching and Airy isostasy in the analysis of tectonic subsidence. Our study shows that the basins are probably underlain by relatively thinned crust, indicating that some form of crustal stretching was involved. To explain the observed gravity anomalies, however, the Moho depth that we calculated based on the free‐air gravity data is about 25% deeper than the Moho predicted by assuming Airy isostasy (Backstrip Moho). This suggests that the Airy model overestimates the compensation and that the basins are probably undercompensated isostatically. In other words, there is an extra amount of tectonic subsidence that is not compensated by crustal thinning, which has resulted in the discrepancy between the gravity‐derived Moho and the Backstrip Moho. We attribute this uncompensated or anomalous tectonic subsidence to thin‐skinned crustal extension that did not involve the mantle lithosphere. The Malay and Penyu Basins are interpreted therefore as basins that formed by a combination of whole‐lithosphere stretching and thin‐skinned crustal extension.
Reciprocal flexural behaviour and contrasting stratigraphies: a new basin development model for the Karoo retroarc foreland system, South Africa
Authors: Catuneanu  , Hancox  , Rubidge
Published: March 2003

The main Karoo Basin of South Africa is a Late Carboniferous–Middle Jurassic retroarc foreland fill, developed in front of the Cape Fold Belt (CFB) in relation to subduction of the palaeo‐Pacific plate underneath the Gondwana plate. The Karoo sedimentary fill corresponds to a first‐order sequence, with the basal and top contacts marking profound changes in the tectonic setting, i.e. from extensional to foreland and from foreland to extensional, respectively.

Sedimentation within the Karoo Foreland Basin was closely controlled by orogenic cycles of loading and unloading in the CFB. During orogenic loading, episodes of subsidence and increase in accommodation adjacent to the orogen correlate to episodes of uplift and decrease in accommodation away from the thrust‐fold belt. During orogenic unloading the reverse occurred. As a consequence, the depocentre of the Karoo Basin alternated between the proximal region, during orogenic loading, and the distal region, during orogenic unloading. Orogenic loading dominated during the Late Carboniferous–Middle Triassic interval, leading to the accumulation of thick foredeep sequences with much thinner forebulge correlatives. The Late Triassic–Middle Jurassic interval was dominated by orogenic unloading, with deposition taking place in the distal region of the foreland system and coeval bypass and reworking of the older foredeep sequences.

The out of phase history of base‐level changes generated contrasting stratigraphies between the proximal and distal regions of the foreland system separated by a stratigraphic hinge line. The patterns of hinge line migration show the flexural peripheral bulge advancing towards the craton during the Late Carboniferous–Permian interval in response to the progradation of the orogenic front. The orogenward migration of the foreland system recorded during the Triassic–Middle Jurassic may be attributed to piggyback thrusting accompanied by a retrogradation of the centre of weight within the orogenic belt during orogenic loading (Early Middle Triassic) or to the retrogradation of the orogenic load through the erosion of the orogenic front during times of orogenic unloading (Late Triassic–Middle Jurassic).
Neogene tectonics and basin fill patterns in the Hellenic outer‐arc (Crete, Greece)
Authors: Ten Veen  , Postma
Published: March 2003

Six time‐slice reconstructions in the form of palaeogeographical maps show the large‐scale tectonic and sedimentary evolution of the Hellenic outer‐arc basins in central and eastern Crete for the middle and late Miocene. The reconstructions are based on extensive field mapping and a detailed chronostratigraphy.

Latest compressional features related to subduction and associated crustal thickening are poorly dated and assigned a middle Miocene age. These are possibly contemporaneous with widespread occurrence of breccia deposits all over Crete. The precise date for the onset of extension, possibly controlled by the roll‐back of the subsiding African lithosphere, remains at this point a discussion. We present circumstantial evidence to place the beginning of the roll back in the middle Miocene, during the accumulation of an arc‐parallel, westward‐draining fluvial complex. The continental succession is transgressed steadily until it is interrupted by an important tectonic event at the boundary of the middle and late Miocene (normally seen as the onset of slab roll‐back). In the earliest late Miocene a few large‐sized fault blocks along arc‐parallel normal faults subsided rapidly causing a deepening of the half‐graben basins up to approximately 900 m. About 1 Myr later, a new N020E and N100E fault system developed fragmenting the existing half‐grabens into orthogonal horst and graben structure. The development of the new fault system caused original continental regions to subside and original deep basins to emerge, which is not easy to reconcile with roll back controlled extensional processes alone. Underplating and inherited basement structure may have played here an additional role, although evidence for firm conclusions is lacking. In late Miocene times (late Tortonian, ≈7.2 Ma), the extensional outer arc basins become deformed by N075E‐orientated strike‐slip. The new tectonic regime begins with strong uplift along existing N100E fault zones, which developed about E–W‐striking topographical highs (e.g. Central Iraklion Ridge and Anatoli anticline) in about 0.4 Myr. The strong uplift is contemporaneous with abundant landsliding observed along an important N075E fault zone crossing eastern Crete and with renewed volcanic activity of the arc. The origin of the ridges may be due to active folding related to the sinistral slip.
Ebro Basin continental sedimentation associated with late compressional Pyrenean tectonics(north‐eastern Iberia): controls on basin margin fans and fluvial systems
Authors: Arenas C. , Millán H. , Pardo G. , Pocoví A.
Published: March 2003

ABSTRACT This contribution deals with the External Sierras and a part of the foreland Ebro Basin related to the southern Pyrenean thrust front. The structure of the External Sierras consists of a south‐verging thrust system developed from middle Eocene to early Miocene times. Since the end of the early Oligocene, a regional‐scale detachment anticline (the Santo Domingo anticline) developed, folding the original thrust system and creating new thrust units.

The molassic fill in this part of the Ebro Basin (Uncastillo Formation) mainly corresponds to an extensive, composite distributary fluvial system, termed the Luna system, which drained the uplifted Gavarnie Unit to the north. Small, marginal alluvial fans originated along the External Sierras and coalesced in the proximal‐middle portions of the Luna system.

Three tecto‐sedimentary units (TSU), late Oligocene to early Miocene in age, comprise the Uncastillo Formation. Lateral relationships and areal distribution of lithofacies through time have been used to establish sedimentary models for the marginal alluvial fans and the Luna fluvial system. Their sedimentary evolution was controlled by tectonics affecting the drainage basins, and based on mapping and stratigraphic relationships of the TSU, the temporal succession of the marginal alluvial fans and their relationships with each thrust system in the south Pyrenean front can be shown. Alluvial fan formation evolved through time from west to east, in accord with the progressive eastward growth of the Santo Domingo anticline as a conical fold.

The fluvial network of the Luna system appears to have been mainly radial, but near the basin margin its architecture was influenced by the syndepositional Fuencalderas and Uncastillo anticlines developed within the Ebro Basin. These low‐amplitude folds originated by layer‐parallel shearing caused by rotation of the southern flank of the Santo Domingo anticline. Progressive uplift of these anticlines constrained part of the fluvial discharge to synclinal areas parallel to the basin margin; these areas where characterized by meandering sandy channels. At the peripheral tips of the anticlines the channel system flowed basinward.
Quantitative analogue flume‐model study of river–shelf systems: principles and verification exemplified by the Late Quaternary Colorado river–delta evolution
Authors: Van Heijst M. W. I. M. , Postma G. , Meijer X. D. , Snow J. N. , Anderson J. B.
Published: March 2003

ABSTRACT Physical modelling of clastic sedimentary systems over geological time spans has to resort to analogue modelling since full scaling cannot be achieved within the spatial and temporal restrictions that are imposed by a laboratory set‐up. Such analogue models are suitable for systematic investigation of a sedimentary system's sensitivity to allocyclic changes by isolating governing parameters. Until now, analogue models of landscape evolution were mainly qualitative in nature. In this paper, we present a quantitative approach. The quantitative experimental results are verified and discussed by comparison with high‐resolution data from the Colorado river–shelf system of the Texas shelf that we used as a prototype.

The model's dimensions are proportionally scaled to the prototype, except for a vertical exaggeration. Time is scaled using a Basin Response factor to maintain a similar ratio between the period of change and the system's equilibrium time for model and prototype. A Basin Fill factor was used to compare the ratio between the time‐averaged sedimentation rate and the rate of change in accommodation space of model and prototype. The flume‐model results are in the form of sediment budgets that are related to shelf cannibalism and fluvial supply, which are compared with the ancestral Colorado river–delta evolution of the last 40 kyr.

Model and prototype have similarities in delta evolution in response to one cycle of sea‐level change. With sea‐level change as the isolated variable, the flume model generates a significant supply pulse caused by headward erosion of the shelf in response to the sea‐level fall. This pulse adds to the yield of the hinterland. The supply induced by sea‐level change persists during the early rise, although its rate declines. A similar trend is observed on the east Texas shelf. We argue that shelfal and fluvial degradation cycles induced by sea‐level changes can significantly influence the timing and amount of sediment supply to basins and must therefore be taken into consideration.
Tectono‐sedimentary processes along an active marine/lacustrine half‐graben margin: Alkyonides Gulf, E. Gulf of Corinth, Greece
Authors: Leeder M. R. , Collier R. E. Ll. , Abdul Aziz L. H. , Trout M. , Ferentinos G. , Papatheodorou G. , Lyberis E.
Published: March 2003

ABSTRACT The Alkyonides half‐graben is separated from the Gerania Range to the south by active faults whose offshore traces are mapped in detail. The East Alkyonides and Psatha Faults have well‐defined, Holocene‐active tip zones and cannot be extrapolated from the onshore Skinos Fault into a single continuous surface trace. During the late Quaternary, catchments draining the step‐faulted range front have supplied sediment to alluvial fans along a subsiding marine ramp margin in the hangingwall of the Skinos Fault, to shelf ledge fans on the uplifting footwall to the East Alkyonides Fault and to the Alepochori submarine fan in the hangingwall of the latter. During late Pleistocene lowstand times (c. 70–12 ka), sediment was deposited in Lake Corinth as fan deltas on the subsiding Skinos shelf ramp which acted as a sediment trap for the adjacent 360 m deep submarine basin plain. At the same time, the uplifting eastern shelf ledge was exposed, eroded and bypassed in favour of deposition on the Alepochori submarine fan. During Holocene times, the Skinos bajada was first the site of stability and soil formation, and then of substantial deposition before modern marine erosion cut a prominent cliffline. The uplifting eastern shelf ledge has developed substantial Holocene fan lobe depositional sequences as sediment‐laden underflows have traversed it via outlet channels. We estimate mean Holocene displacement rates towards the tip of the Psatha Fault in the range 0.7–0.8 mm year−1. Raised Holocene coastal notches indicate that this may be further partitioned into about 0.2 mm year−1 of footwall uplift and hence 0.5–0.6 mm year−1 of hangingwall subsidence. Holocene displacement rates towards the tip of the active East Alkyonides Fault are in the range 0.2–0.3 mm year−1. Any uplift of the West Alkyonides Fault footwall is not keeping pace with subsidence of the Skinos Fault hangingwall, as revealed by lowstand shelf fan deltas which show internal clinoforms indicative of aggradational deposition in response to relative base‐level rise due to active hangingwall subsidence along the Skinos Fault. Total subsidence here during the last 58 kyr lowstand interval of Lake Corinth was some 20 m, indicating a reduced net displacement rate compared to estimates of late Holocene (< 2000 bp) activity from onshore palaeoseismology. This discrepancy may be due to the competition between uplift on the West Alkyonides Fault and subsidence on the onshore Skinos Fault, or may reflect unsteady rates of Skinos Fault displacement over tens of thousands of years.
The physical scale modelling of braided alluvial architecture and estimation of subsurface permeability
Authors: Moreton D. J. , Ashworth P. J. , Best J. L.
Published: March 2003

The quantitative modelling of fluvial reservoirs, especially in the stages of enhanced oil recovery, requires detailed three‐dimensional data at both the scale of the channel belt and within‐channel. Although studies from core, analogue outcrop and modern environments may partially meet these needs, they often cannot provide detail on the smaller‐scale (i.e. channel‐scale) heterogeneity, frequently suffer from limited three‐dimensional exposure and cannot be used to examine the influence of different variables on the process–deposit relationship. Physical modelling offers a complementary technique that can address many of these quantitative requirements and holds great future potential for integration with reservoir modelling. Physical modelling provides the potential to upscale results and derive reservoir information on three‐dimensional facies geometry, connectivity and permeability.

This paper describes the development and use of physical modelling, which employs generic Froude‐scaling principles, in an experimental basin that permits aggradation in order to model the morphology and subsurface depositional stratigraphy of coarse‐grained braided rivers. An example is presented of a 1:50 scale model based on the braided Ashburton River, Canterbury Plains, New Zealand and the adjacent late Quaternary braided alluvium exposed in the coastal cliffs. Critically, a full, bimodal grain size distribution (20% sand and 80% gravel) was used to replicate the prototype, which allows the realistic reproduction of the surface morphology and importantly permits grain size sorting during deposition. Uncertainties associated with the compression of time, sediment mass balance and the hydrodynamics of the finest particle sizes do not appear to affect the reproducibility of stratigraphy between experimental and natural environments.

Sectioning of the preserved sedimentary sequence in the physical model allows quantification of the geometry, shape, spatial distribution and internal sedimentary structure of the coarse‐ and fine‐grained facies. A six‐fold facies scheme is proposed for the model braided alluvium and a direct link is established between the grain size distribution and facies type: this allows permeability to be estimated for each facies, which can be mapped onto two‐dimensional vertical cross‐sections of the preserved stratigraphy. Results demonstrate the dominance of four facies based on permeability that range over three orders of magnitude in hydraulic conductivity. Quantification of such variability, and linkage to both vertical proportion curves for facies distribution and connectivity presents significant advantages over other methodologies and offers great potential for the modelling of heterogeneous braided river sediments at the within channel‐belt scale. This paper outlines how physical models may be used to develop high‐resolution, geologically‐accurate, object‐based reservoir simulation models.
Subsidence analyses from the Betic Cordillera, southeast Spain
Authors: Hanne D. , White N. , Lonergan L.
Published: March 2003

Fifty‐four Mesozoic–Cenozoic stratigraphic sections from the Betic Cordillera of southeast Spain have been analysed in order to estimate the timing and amount of lithospheric stretching that occurred at the western end of the Tethyan Ocean since the Hercynian Orogeny. The standard backstripping technique has been used in order to calculate the water‐loaded subsidence of basement for each section. Water‐loaded subsidence curves were then inverted in order to determine the variation of lithospheric strain rate as a function of time, which yields estimates of timing, magnitude and intensity of stretching.

Rifting commenced during the Late Permian/Early Triassic times and continued intermittently throughout the Mesozoic in response to the opening of the Tethyan Ocean to the east and the opening of the Atlantic Ocean to the west. Two major events in the Permo‐Triassic/Early Jurassic and the Late Jurassic/Early Cretaceous can be clearly identified. Stretching factors are generally small (1.1–1.25) probably because the Betic Cordillera was located at the westernmost end of the Tethys.

Peak strain rates of ∼10−15 s−1 were obtained for Mesozoic rift events and these values are in broad agreement with those obtained throughout the Tethyan Realm. We have also analysed the Neogene extensional event, which played an important role in forming the existing Mediterranean Sea. A combination of well‐log information and calibrated seismic reflection data was modelled. Peak strain rates in these younger basins are almost one order of magnitude faster than those estimated for the Mesozoic basins. These higher values appear to be typical of back‐arc extensional basins elsewhere. To the west and north of the Betic Cordillera, the Guadalquivir foreland basin developed as extension took place further east. Backstripped sections from this basin clearly record the northward migration of foreland basin subsidence through time.
Early lung absorption profile of non‐CFC salbutamol via small and large volume plastic spacer devices
Authors: Lipworth B. J. , Clark D. J.
Published: March 2003

Aims
 To evaluate the lung dose of a non‐CFC salbutamol metered dose inhaler (MDI) formulation via three commonly used plastic spacer devices, of both large and small volume, compared with the MDI used on its own.

Methods
 Ten healthy volunteers were studied in a randomized single (investigator) blind crossover design. Single 1200 μg nominal doses of salbutamol from a non‐CFC MDI (Airomir), as 12 sequential 100 μg puffs over 6 min, were delivered from the MDI alone and via two large volume spacer devices (Nebuhaler, Volumatic), and a small volume spacer (Aerochamber). All spacers were prewashed prior to each study day and mouth rinsing was performed after each drug sequence. Plasma salbutamol was measured at 5, 10, 15 and 20 min, with calculation of maximum (Cmax ) and average (Cav ) concentrations. This lung dose was assessed using the early lung absorption profile of salbutamol in the first 20 min after inhalation.

Results
 Both of the large volume spacers, the Nebuhaler and the Volumatic, delivered significantly more salbutamol than the MDI alone. For Cav this amounted to a 2.07‐fold difference (95% CI 1.48–2.90) between Nebuhaler vs MDI, and a 1.49‐fold difference (95%CI 1.19–1.87) between Volumatic vs MDI. The Nebuhaler also produced greater deposition than either the Volumatic or the Aerochamber spacers; Nebuhaler vs Volumatic: 1.39‐fold difference (95% CI 1.09–1.76), Nebuhaler vs Aerochamber: 1.63‐fold difference (95% CI 1.20–2.21). There were no significant differences between the Aerochamber and the MDI alone.

Conclusions
 Using the early lung absorption profile, for administration of the same nominal dose, both of the large volume spacers (Nebuhaler and Volumatic) but not the small volume spacer (Aerochamber) delivered significantly more salbutamol than the MDI alone. The Nebuhaler also produced greater delivery than either the Volumatic or the Aerochamber spacer devices. Our results show that whilst lung delivery of non‐CFC salbutamol MDI is improved by the use of a plastic spacer, there may be appreciable differences in performance, particularly between large and small volume devices.
Pharmacokinetic analysis of subcutaneous erythropoietin administration with nonlinear mixed effect model including endogenous production
Authors: Hayashi Naoto , Kinoshita Haruki , Yukawa Eiji , Higuchi Shun
Published: March 2003

Aims
 Erythropoietin, a glycoprotein hormone is produced by the kidney and targeted to erythrocyte precursors. Recombinant human erythropoietin (Epoetin β) has been utilized for therapeutic purposes in renal anaemia or anaemia occurring after auto blood donation or chemotherapy. The administration routes for erythropoietin are normally subcutaneous or intravenous. No population pharmacokinetic analysis, however, has been performed following subcutaneous administration with consideration given for endogenous production.

Methods
 In the present study, we have attempted to analyze the pharmacokinetics of erythropoietin after subcutaneous administration in healthy adult male volunteers by using the Nonlinear Mixed Effect Model program (NONMEM) with a model including endogenous erythropoietin production.

Results
 It has been established that the final estimation of the population mean values of the absorption rate constant (ka ), the elimination rate constant (ke ), the distribution volume (V  ) and the endogenous production are 0.0430 h−1, 0.206 h−1, 3.14 l and 15.7IU h−1, respectively. For the circadian rhythm of endogenous production, the amplitude was calculated as 9.86% and the peak appeared around 24.00 h.

Conclusions
 The values for ke and V  are very similar to those previously reported for intravenous administration. The circadian rhythm of endogenous production are also able to be substantiated. The factors influencing ke were found to be serum creatinine and age.
Suppression of tumour development by substances derived from the diet—mechanisms and clinical implications
Authors: Gescher Andreas , Pastorino Ugo , Plummer Simon M. , Manson Margaret M.
Published: March 2003

The concept that cancer can be prevented, or its onset postponed, by certain diet‐derived substances is currently eliciting considerable interest. Agents which interfere with tumour development at the stage of promotion and progression in particular are of potential clinical value. As chemopreventive agents have to be administered over a long period of time in order to establish whether they possess efficacy in humans, it is of paramount importance to establish their lack of toxicity. The desire to select the best chemopreventive drug candidates for clinical trial, and the necessity to monitor efficacy in the short and intermediate term, render the identification of specific mechanism‐based in vivo markers of biological activity a high priority. Antioxidation, inhibition of arachidonic acid metabolism, modulation of cellular signal transduction pathways, inhibition of hormone and growth factor activity and inhibition of oncogene activity are discussed as mechanisms by which the soya constituent genistein, the curry ingredient curcumin and the vitamin A analogue 13‐cis retinoic acid exert tumour suppression. A better understanding of these mechanisms will help the establishment of screens for the discovery of new and better chemopreventive agents and the identification of surrogate markers to assess the outcome of clinical chemoprevention trials.
Halofantrine and chloroquine inhibit CYP2D6 activity in healthy Zambians
Authors: Simooya O. O. , Sijumbil G. , Lennard M. S. , Tucker G. T.
Published: March 2003

Aims
 To determine the effect of therapeutic loading doses of halofantrine and chloroquine on CYP2D6 activity in healthy black Zambians.

Methods
 Twenty healthy black male Zambians were phenotyped for CYP2D6 activity by measuring the debrisoquine/4‐hydroxydebrisoquine ratio in a 0–8 h urine sample after a 10 mg oral dose of debrisoquine hemi‐sulphate. The subjects (all ‘extensive metabolizer’ phenotype with respect to CYP2D6) were randomized into two groups of 10, and 24 h later one group received 1500 mg halofantrine hydrochloride and the other group 1500 mg chloroquine phosphate both orally in divided doses. All subjects were given further 10 mg doses of debrisoquine at 2 h, 1 week and 2 weeks after the last dose of the antimalarial drug, and phenotyped as described above.

Results
 The median debrisoquine/4‐hydroxydebrisoquine 0–8 h urinary ratio was increased by halofantrine (1.39 to 6.05; P<0.01; 95% confidence intervals 4.00–11.7) and chloroquine (1.96 to 3.91; P<0.01; 95% confidence intervals 1.34–2.66) when debrisoquine was given 2 h after treatment. The decrease in CYP2D6 activity remained statistically significant for 1 week after both drugs. Halofantrine was a significantly more potent inhibitor of CYP2D6 than chloroquine (P=0.037). Phenocopying occurred in two subjects taking halofantrine and one taking chloroquine (i.e. the debrisoquine/4‐hydroxydebrisoquine ratios became consistent with the poor metabolizer phenotype).

Conclusions
 Given in therapeutic loading doses, both halofantrine and chloroquine caused significant inhibition of CYP2D6 activity in healthy black Zambians. With respect to halofantrine, this finding reinforces the recommendation that its combination with other drugs known to prolong the QT interval should be avoided, especially those that are metabolized significantly by CYP2D6.
Characteristics of indirect pharmacodynamic models and applications to clinical drug responses
Authors: Sharma Amarnath , Jusko William J.
Published: March 2003

This review describes four basic physiologic indirect pharmacodynamic response (IDR) models which have been proposed to characterize the pharmacodynamics of drugs that act by indirect mechanisms such as inhibition or stimulation of the production or dissipation of factors controlling the measured effect. The principles underlying IDR models and their response patterns are described. The applicability of these basic IDR models to characterize pharmacodynamic responses of diverse drugs such as inhibition of gastric acid secretion by nizatidine and stimulation of MX protein synthesis by interferon α‐2a is demonstrated. A list of other uses of these models is provided. These models can be readily extended to accommodate additional complexities such as nonstationary or circadian baselines, equilibration delay, depletion or accumulation of a precursor pool, sigmoidicity, or other mechanisms. Indirect response models which have a logical mechanistic basis account for time‐delays in many responses and are widely applicable in clinical pharmacology.