bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of diaphragmatic paralysis following supraclavicular brachial plexus block and its effect on pulmonary function
Authors: Mak P. H. K. , Irwin M. G. , Ooi C. G. C. , Chow B. F. M. 
Published: March 2003

Thirty unpremedicated ASA physical status 1–3 patients aged between 18 and 69 years, scheduled for upper limb surgery, received a conventional supraclavicular brachial plexus block using a nerve stimulator and bupivacaine 0.375% 0.5 ml.kg−1. Spirometric measurements of pulmonary function and ultrasonographic assessments of diaphragmatic function were made before the block and at 10‐min intervals after injection until full motor block of the brachial plexus had developed. Complete paralysis of the ipsilateral hemidiaphragm occurred in 50% of patients. Seventeen per cent of patients had reduced diaphragmatic movement and the rest (33%) had no change in diaphragmatic movement. Those with complete paralysis all showed significant decreases in pulmonary function, whereas those with reduced or normal movement had minimal change. All patients remained asymptomatic throughout, with normal oxygen saturation on room air.
Circulatory, respiratory and metabolic changes after thigh tourniquet release in combined epidural‐propofol anaesthesia with preservation of spontaneous respiration
Authors: Iwama H. , Kaneko T. , Ohmizo H. , Furuta S. , Ohmori S. , Watanabe K. 
Published: March 2003

SummaryTwelve elderly patients undergoing total knee arthroplasty received lumbar epidural anaesthesia and propofol infusion at 5 mg.kg−1.h−1 following a 1.5–2.0 mg.kg−1 bolus dose with preservation of spontaneous respiration via a laryngeal mask airway. Circulatory, respiratory and metabolic variables were measured before and 1, 3, 5, 15 and 30 min after release of a pneumatic thigh tourniquet. The blood pressure was decreased at all time‐points and the respiratory rate increased at 1 min. The Paco2 was increased only at 1 min. Arterial blood pH and base excess were decreased at 1 and 3 min and 1, 3 and 5 min, respectively. Arterial blood lactate levels were increased at all times. These characteristics were considered to be identical to those under regional anaesthesia with conscious spontaneous respiration, showing that spontaneous respiration under this anaesthetic regimen has a similar respiratory capacity to that of conscious spontaneous respiration.
ESSAY PAPER The interaction between geological structure and global tectonics in multistoreyed landscape development: a denudation chronology of the South Indian shield
Authors: Gunnell Yanni 
Published: March 2003

This study constitutes a comprehensive attempt to interpret the multistoreyed benchland scenery of the South Indian shield. In South India, two rifted margins (and now competing base levels), a low‐elevation margin facing the Bay of Bengal, in existence since ≈130 Ma, and a younger (65 Ma) high‐elevation margin facing the Arabian Sea, together with a high‐standing backbone of extremely resistant granulitic rocks known as charnockites, have influenced the long‐term erosional response to rock uplift and to the eustatic shift of shorelines in a complex way.Several tiers of flat‐lying, denudational topographic surfaces, which are indifferent to stratification, schistosity or foliation and highlighted by a characteristic weathering mantle, are identified and the conditions of their genesis discussed. General definitions and assumptions concerning the evolution of planation surfaces are presented. A major key issue is the nature of crustal uplift in cratonic regions: its relation to global tectonics, its role in the redistribution in time and space of available relief and in the deformation of pre‐existing planation surfaces, and its bearing on denudational signals which may be recorded both by isotopic measurement techniques and offshore sedimentary sequences. The proposed denudation chronology considers all these aspects, and the analysis sets out to establish a thread of geodynamic events that can account for the observed morphology. Drainage, weathering and crustal uplift patterns, geological structures and chronostratigraphic data are examined in relation to their possible connections with the migration of drainage divides and surface lowering patterns. The high number of degrees of freedom involved when considering the long‐term interplay between gravity‐driven and radiation‐driven denudation systems is one of the many problems facing this analysis, and is extensively addressed in the discussion.
Late Jurassic subsidence and passive margin evolution in the Vulcan Sub‐basin, north‐west Australia: constraints from basin modelling
Authors: Baxter  , Cooper  , Hill  , O’Brien  
Published: March 2003

The Vulcan Sub‐basin, located in the Timor Sea, north‐west Australia, developed during the Late Jurassic extension which ultimately led to Gondwanan plate breakup and the development of the present‐day passive continental margin. This paper describes the evolution of upper crustal extension and the development of Late Jurassic depocentres in this subbasin, via the use of forward modelling techniques. The results suggest that a lateral variation in structural style exists. The south of the basin is characterized by relatively large, discrete normal faults which have generated deep sub‐basins, whereas more distributed, small‐scale faulting further north reflects a collapse of the early basin margin, with the development of a broader, ‘sagged’ basin geometry. By combining forward and reverse modelling techniques, the degree of associated lithosphere stretching can be quantified. Upper crustal faulting, which represents up to 10% extension, is not balanced by extension in the deeper, ductile lithosphere; the magnitude of this deeper extension is evidenced by the amount of post‐Valanginian thermal subsidence. Reverse modelling shows that the lithosphere stretchingfactor has a magnitude of up to β=1.55 in the southern Vulcan Sub‐basin, decreasing to β=1.2 in the northern Vulcan Sub‐basin. It is proposed that during plate breakup, deformation in the Vulcan Sub‐basin consisted of depth‐dependent lithosphere extension. This additional component of lower crustal and lithosphere stretching is considered to reflect long‐wavelength partitioning of strain associated with continental breakup, which may have extended 300–500 km landward of the continent–ocean boundary.
Roll‐back controlled vertical movements of outer‐arc basins of the Hellenic subduction zone (Crete, Greece)
Authors: Ten Veen  , Postma  
Published: March 2003

Crustal thickening north of the Hellenic subduction zone continued in the most external zones (e.g. Crete) probably until the late middle Miocene. The following period of predominant extension has been related by various workers to a number of causes such as: (1) trench retreat (roll back) driven by the pull of the African slab and (2) gravitational body forces associated with the thickened crust, both in combination with NNE motion of the African plate combined with westward extrusion of the Anatolian block along the North Anatolian Fault. To verify these hypotheses an inventory of fault orientations and fault‐block kinematics was carried out for central and eastern Crete and adjoining offshore areas by combining satellite imagery, digital terrain models, and structural, seismic, sedimentary and stratigraphical field data, all set up in a GIS. The GIS data set enabled easy visualization and combination of data, which resulted in a relatively objective analysis. The geological results are discussed in the light of a numerical model that investigated the intraplate stresses resulting from the above mentioned forces.Our tectonostratigraphic results for the late Neogene of central and eastern Crete show three episodes of basin extension following a period of approximately N–S compression. In the earliest Tortonian, N130E‐ to N100E‐trending normal faults developed, resulting in a roughly planar, arc‐parallel fault system aligning strongly asymmetric half‐grabens. The early Tortonian to early Messinian period was characterized by an orthogonal fault system of N100E and N020E faults resulting in rectangular grabens and half‐grabens. From the late Tortonian to early Pleistocene, deformation occurred along a pattern of closely spaced, left‐lateral oblique N075E faults, orientated parallel to the south Cretan trenches. Deformation phases younger than early Pleistocene are dominated by normal to oblique faulting along WSW–ENE (N050E) faults and dextral, oblique motions along NNW–SSE (N160E) faults. Many faults that were generated during previous deformational episodes appear to be reactivated in later periods.Our tectonostratigraphy points to a three step anticlockwise rotation of active fault systems since the late middle Miocene compressional phase. We suggest here that the rotation is associated with a reorganization of the stress field going from SSW–NNE tension in the early late Miocene to NE–SW left‐lateral shear in the Quaternary. The rotation is likely to be a response to arc‐normal pull forces combined with a progressive increase of the curvature of the arc. During the Pliocene to Recent period, the SSW‐ward retreat of the arc and trench system relative to the African plate was accomplished by transform motions in the eastern (Levantine) segment of the Hellenic Arc, resulting in, respectively, NNW–SSE and NE–SW left‐lateral shear on Crete.
Chronostratigraphic framework and evolution of the Fortuna basin (Eastern Betics) since the Late Miocene
Authors: Garcés M. , Krijgsman W. , Agusti J. 
Published: March 2003

ABSTRACT A Tortonian to Pliocene magnetostratigraphy of the Fortuna basin supports a new chronostratigraphic framework, which is significant for the palaeogeographical and geodynamic evolution of the Eastern Betics in SE Spain.The Neogene Fortuna basin is an elongated trough which formed over a left‐lateral strike‐slip zone in the Eastern Betics in the context of the convergence between the African and Iberian plates. Coeval with other basins in the Alicante–Cartagena area (Eastern Betics), rapid initial subsidence in the Fortuna basin started in the Tortonian as a result of WNW–ESE stretching. This led to transgression and deposition of marine sediments over extensive areas in open connection with the neighbouring basins. Since the late Tortonian, N–S to NW–SE compression led to inversion of older extensional structures. The transpressional tectonics along the NE–SW‐trending Alhama de Murcia Fault is related to the rising of a structural high which isolated the Fortuna basin from the open Mediterranean basin. The progression of basin confinement is indicated by the development of restricted marine environments and deposition of evaporites (7.8–7.6 Ma). The new basin configuration favoured rapid sediment accumulation and marine regression. The basin subsided rapidly during the Messinian, leading to the accumulation of thick continental sequences. During the Pliocene, left‐lateral shear along the Alhama de Murcia Fault caused synsedimentary folding, vertical axis block rotations and uplift of both the basin and its margins. The overall sedimentary evolution of the Fortuna basin can be regarded as a developing pull‐apart basin controlled by NE–SW strike‐slip faults. This resembles the evolution that has taken place in some areas of the Eastern Alboran basin since the late Tortonian.
Seismic reflection imaging of active offshore faults in the Gulf of Corinth: their seismotectonic significance
Authors: Stefatos A. , Papatheodorou G. , Ferentinos G. , Leeder M. , Collier R. 
Published: March 2003

ABSTRACTHigh resolution seismic reflection surveys over one of the most active and rapidly extending regions in the world, the Gulf of Corinth, have revealed that the gulf is a complex asymmetric graben whose geometry varies significantly along its length. A detailed map of the offshore faults in the gulf shows that a major fault system of nine distinct faults limits the basin to the south. The northern Gulf appears to be undergoing regional subsidence and is affected by an antithetic major fault system consisting of eight faults. All these major faults have been active during the Quaternary. Uplifted coastlines along their footwalls, growth fault patterns and thickening of sediment strata toward the fault planes indicate that some of these offshore faults on both sides of the graben are active up to present.Our data ground‐truth recent models and provides actual observations of the distribution of variable deformation rates in the Gulf of Corinth. Furthermore they suggest that the offshore faults should be taken into consideration in explaining the high extension rates and the uplift scenarios of the northern Peloponnesos coast. The observed coastal uplift appears to be the result of the cumulative effect of deformation accommodated by more than one fault and therefore, average uplift rates deduced from raised fossil shorelines, should be treated with caution when used to infer individual fault slip rates.Seismic reflection profiling is a vital tool in assessing seismic hazard and basin‐formation in areas of active extension.
A fossilized Opal A to Opal C/T transformation on the northeast Atlantic margin: support for a significantly elevated Palaeogeothermal gradient during the Neogene?
Authors: Davies R. J. , Cartwright J. 
Published: March 2003

ABSTRACTRock samples – collected from a recent deep‐water exploration well drilled in the Faeroe‐Shetland Channel, northwest of the UK – confirm that a distinctive high‐amplitude seismic reflector that cross‐cuts the Upper Palaeogene and Neogene succession and covers an area of 10 000 km2 is an example of a fossilized Opal A to Opal C/T (Cristobalite/Tridymite) transition. Analysis of these rock fragments tied to an extensive two‐dimensional and three‐dimensional seismic database constrains the time at which the boundary was fossilized and in addition reveals the unusual geometrical characteristics of a relict bottom‐simulating reflector.The diagenetic transformation of biogenic silica (Opal A) to Opal C/T is predominantly temperature‐controlled and requires sediments that contain biogenic silica. The reflector (termed as Horizon E) probably initially represented a biosiliceous ooze or a siltstone that contained a component of biogenic silica that underwent transformation as the diagenetic front migrated upsection during burial. The parallelism it shows with a shallower early Pliocene reflector and its apparent upsection migration during a compressional episode in the basin indicate that it was active during the middle and late Miocene and ceased activity during the early Pliocene when there was between 200 and 400 m of overburden. The present‐day burial depth of the boundary is ca. 700 m and the temperature at the inactive diagenetic front at the well location is 24 °C. Given these temperature and depth constraints, we hypothesize that even if this is an example of a relatively low‐temperature Opal A to Opal C/T transformation, a temporarily elevated geothermal gradient of ca. 60 °C km−1 would have been required to initiate and arrest upsection migration of the boundary during the middle and late Miocene. Factors such as climatic deterioration and the onset of cold deep‐water circulation are likely to only have had a contributory role in arresting the upward migration of the boundary.
Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery
Authors: Mather Laurence E. , Woodhouse Annie , Ward M. Elizabeth , Farr Stephen J. , Rubsamen Reid A. , Eltherington Lorne G. 
Published: March 2003

Aims
Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath‐actuated, microprocessor‐controlled metered dose oral inhaler (SmartMistTM, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain.
Methods
Aersolised pulmonary fentanyl base 100–300 μg was administered to healthy volunteers using SmartMistTM and the resultant plasma concentration‐time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects.
Results
Plasma concentrations from SmartMistTM were similar to those from i.v. injection. Time‐averaged bioavailability based upon nominal doses averaged 100%, and was >50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose‐dependence from either route. Side‐effects (e.g. sedation, lightheadedness) were the same from both routes.
Conclusions
Fentanyl delivery using SmartMistTM can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae.
Involvement of CYP1A2 in mexiletine metabolism
Authors: Nakajima M. , Kobayashi K. , Shimada N. , Tokudome S. , Yamamoto T. , Kuroiwa Y. 
Published: March 2003

Aims
Mexiletine has been reported to be hydroxylated by cytochrome P450 2D6 (CYP2D6) in humans. However, the involvement of CYP1A2 in the metabolism of mexiletine has been proposed based on the interaction with theophylline which is mainly metabolized by CYP1A2. The aim of this study was to clarify the role of human CYP1A2 in mexiletine metabolism.
Methods
Human CYP isoforms involved in mexiletine metabolism were investigated using microsomes from human liver and B‐lymphoblastoid cells expressing human CYPs. The contributions of CYP1A2 and CYP2D6 to mexiletine metabolism were estimated by the relative activity factor (RAF).
Results
Mexiletine p‐ and 2‐hydroxylase activities in human liver microsomes were inhibited by ethoxyresorufin and furafylline as well as quinidine. Mexiletine p‐ and 2‐hydroxylase activities in microsomes from nine human livers correlated significantly with bufuralol 1′‐hydroxylase activity (r=0.907, P<0.001 and r=0.886, P<0.01, respectively). Microsomes of B‐lymphoblastoid cells expressing human CYP1A2 exhibited lower mexiletine p‐ and 2‐hydroxylase activities than those expressing human CYP2D6. It was estimated by RAF that the major isoform involved in mexiletine metabolism was CYP2D6, and the contribution of CYP1A2 to both mexiletine p‐ and 2‐hydroxylase activities was 7–30% in human liver microsomes. However, the Km values of the expressed CYP1A2 (∼15 μm ) were almost identical with those of the expressed CYP2D6 (∼22 μm ) and human liver microsomes.
Conclusions
Mexiletine is a substrate of CYP1A2. The data obtained in this study suggest that the interaction of mexiletine with theophylline might be due to competitive inhibition of CYP1A2.
Lack of interaction between valaciclovir, the L‐valyl ester of aciclovir, and digoxin
Authors: Soul‐Lawton J. H. , Weatherley B. C. , Posner J. , Layton G. , Peck R. W. 
Published: March 2003

Aims
Changes in both digoxin and aciclovir renal clearance following coadministration with some other renally eliminated drugs have been reported. The potential interaction of valaciclovir, with its antiherpetic metabolite aciclovir, and digoxin was investigated.
Methods
Twelve healthy volunteers (seven males, five females) participated in an open, randomized, four‐period crossover study. Valaciclovir, 1000 mg, was given alone on one occasion, and on another, after the second of two 0.75 mg digoxin doses administered 12 h apart. Blood samples and all urine were collected up to 12 h following the valaciclovir dose for aciclovir radioimmunoassay. On a third occasion, digoxin was given alone and on a fourth, with 1000 mg valaciclovir three times/day for 8 days starting 12 h before the first digoxin dose. Blood samples were taken up to 168 h and all urine collected up to 24 h following the second dose for digoxin radioimmunoassay.
Results
There were no clinically significant differences in digoxin or aciclovir pharmacokinetic parameters when digoxin or valaciclovir was given alone or in combination.
Conclusions
No dosage adjustment is required when valaciclovir and digoxin are coadministered.
New active substances authorized in the United Kingdom between 1972 and 1994
Authors: Jefferys David B. , Leakey Diane , Lewis John A. , Payne Sandra , Rawlins Michael D. 
Published: March 2003

Aims
The study was undertaken to assemble a list of all new active medicinal substances authorised in the United Kingdom between 1972 and 1994; to assess whether the pattern of introductions had changed; and to examine withdrawal rates and the reasons for withdrawal.
Methods
The identities of those new active substances whose manufacturers had obtained Product Licences between 1972 and 1994 were sought from the Medicines Control Agency's product data‐base. For each substance relevant information was retrieved including the year of granting the Product Licence, its therapeutic class, whether currently authorised (and, if not, reason for withdrawal), and its nature (chemical, biological etc.).
Results
The Medicines Control Agency's data‐base was cross‐checked against two other data‐bases for completeness. A total of 583 new active substances (in 579 products) were found to have been authorised over the study period. The annual rates of authorisation varied widely (9 to 40 per year). Whilst there was no evidence for any overall change in the annual rates of authorising new chemical entities, there has been a trend for increasing numbers of new products of biological origin to be authorised in recent years. Fifty‐nine of the 583 new active substances have been withdrawn (1 each for quality and efficacy, 22 for safety, and 35 for commercial reasons).
Conclusions
For reasons that are unclear there is marked heterogeneity in the annual rates of authorisation of new active substances. Their 10 year survival is approximately 88% with withdrawals being, predominantly, for commercial or safety reasons. This confirms the provisional nature of assessments about safety at the time when a new active substance is introduced into routine clinical practice, and emphasises the importance of pharmacovigilance.
Frequency and cost of serious adverse drug reactions in a department of general medicine
Authors: Moore Nicholas , Lecointre Dominique , Noblet Catherine , Mabille Michel 
Published: March 2003

Aims
To assess the frequency and cost of drug reactions causing or prolonging hospitalization.
Methods
All patients admitted to an internal medicine ward over 6 months were evaluated to identify serious adverse reactions. The number of drug classes on admission or at the time of the adverse drug reaction (ADR) was counted. Excess ADR‐related hospital stay was computed using a) raw excess duration of hospital stay, b) correction of duration of hospital stay by age, sex, and number of drug classes, and c) estimation by investigator of excess hospital stay.
Results
Three hundred and twenty‐nine patients were evaluated: 212 male, 117 female, mean age 57.2 (males: 52.2, females: 66.2 (P<0.05)), range 17–95 years. They stayed a total of 3720 hospital days (mean stay 11.3 days). 298 had no ADR (mean age 55.8, taking a mean of 2.7 drug classes, 10.7 days hospital stay); 31 had ADRs: in 10, the ADR caused admission in patients with a mean age of 84 (P<0.01 vs the two other groups), taking 6.3 drug classes, who stayed a mean of 15.1 days; 21 occurred in hospital in patients with a mean age of 63.6, taking 4.2 drug classes (P<0.01), who stayed a mean of 19.2 days (P<0.01 vs patients without ADRs). In four the ADR was fatal (13% of ADRs, 40% of deaths). Raw ADR‐related excess hospital stay was 318 days (8.6% of all hospital days), after multivariate correction 282 days (7.6% of all hospital days), and with investigator estimation 197 days (5.3% of all hospital days). Point prevalence of ADRs at admission was 3%, incidence rate in hospital was 5.6/1000 patient‐days.
Conclusions
3% of the admissions were related to ADRs. In addition, 6.6% of hospitalized patients had significant ADRs. Between 5 and 9% of hospital costs were related to ADRs. In 24 of the 31 patients with ADRs (77%), these were related to the pharmacological properties of the involved drugs, and may possibly have been avoidable.