bluuebunny/crossref_metadata_2025 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.
The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients
Authors: Helmy S. A. K. , Al‐Attiyah R. J.
Published: March 2003

Both propofol and midazolam are known to inhibit immune function. The aim of this study was to investigate cytokine production in critically ill surgical patients as early markers of immune response to prolonged infusion of propofol and midazolam. The study enrolled 40 elective patients who were to receive long‐term sedation for more than 2 days. Patients were randomly allocated to one of two equally sized groups. Central venous blood samples for measurement of interleukin‐1β (IL‐1β), interleukin‐2 (IL‐2), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), tumour necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ) were drawn prior to the start and after 48 h of infusion. After 48 h, propofol caused significant increases in IL‐1β (24%), IL‐6 (23%) and TNF‐α (4.8 times) levels, while midazolam caused significant decreases in IL‐1β (21%), IL‐6 (21%) and TNF‐α (19%). Both agents caused significant decreases in IL‐8 levels (propofol: 30%, midazolam: 48%, p < 0.05). Propofol caused significant decreases in IL‐2 levels (68%, p < 0.001) but increases in IFN‐γ (30%, p < 0.05), whereas there was no significant change with midazolam compared with the pre‐infusion level. In conclusion, during 48 h of continuous infusion, propofol stimulated, while midazolam suppressed, the production of the pro‐inflammatory cytokines IL‐1β, IL‐6 and TNF‐α, and both caused suppression of IL‐8 production. Propofol inhibited IL‐2 production and stimulated IFN‐γ production, whereas midazolam failed to do so. Therefore, sedative agents may have clinical implications in high‐risk and immunocompromised patients.
Variations in expenditure between adult general intensive care units in the UK
Authors: Edbrooke D. L. , Ridley S. A. , Hibbert C. L. , Corcoran M.
Published: March 2003

This paper presents the findings from the second pilot study of the cost block method in 21 adult general intensive care units (ICUs). The aim of this study was to explore the possible reasons for the variation in cost identified in a previous pilot study of 11 ICUs. Data were collected for the six cost blocks for the financial year 1996/97. Multivariate analysis showed that 93% of the variation in expenditure on disposable equipment could be explained by the number of ICU beds, the number of admissions and the presence of a high‐dependency unit (HDU). Ninety‐two per cent of the variation in nursing staff expenditure was explained by the number of ICU beds and the presence of an HDU. Hospital type and the number of patient days explained 76% of the variation in expenditure on consultant staff. Sixty‐four per cent of the variation in drug and fluid expenditure was explained by the number of patient days.
Randomised double‐blind comparison of ondansetron and droperidol to prevent postoperative nausea and vomiting associated with patient‐controlled analgesia
Authors: Millo J. , Siddons M. , Innes R. J. , Laurie P. S.
Published: March 2003

In a randomised, double‐blind trial, we compared the use of ondansetron and droperidol for the prevention of nausea and vomiting after total abdominal hysterectomy, during patient‐controlled analgesia with morphine. One hundred and forty‐two patients were randomly allocated to one of two groups. All patients received a standardised general anaesthetic and postoperative analgesic regimen. One group received ondansetron 4 mg at induction of anaesthesia, and ondansetron 0.13 mg with each 1‐mg bolus dose of morphine. The other group received droperidol 0.5 mg at induction and droperidol 0.05 mg per 1‐mg bolus dose of morphine. Results were available for 137 patients. During the first 24 h after surgery, prophylaxis was successful in 26 of 66 patients given ondansetron (39%) compared with 36 of 71 patients given droperidol (51%). This difference was not statistically significant (Chi‐squared = 1.766, p = 0.18). We conclude that in the regimens studied, ondansetron is not more effective than droperidol at preventing postoperative nausea and vomiting.
The effect of moderate hypovolaemia on microcirculation in healthy older blood donors
Authors: Janetzko K. , Klüter H. , Kirchner H. , Klotz K.‐F.
Published: March 2003

Compensation for acute blood loss requires cardiovascular integrity. In older people, asymptomatic cardiovascular impairment is common. In these subjects, even moderate blood loss is often treated by external volume replacement although its benefits are not clear. We investigated the effect of 450 ml of blood loss on the microcirculation and compensatory mechanisms in healthy older blood donors. Red blood cell count, plasma viscosity and protein concentration were measured. Plasma volume replacement was calculated using haematocrit. We measured microcirculation tissue perfusion by laser Doppler fluxmetry prior to, during and after blood donation. Blood loss was immediately accompanied by a median rapid water shift of 208 ml (interquartile range 134–298 ml). Haemodilution led to a decrease in haematocrit, protein and plasma viscosity. We observed no changes in cutaneous microcirculation. Moderate blood loss is tolerated in older cardiovascularly asymptomatic patients without having an impact on microcirculation. This may reduce the need for external volume replacement.
Arterial flow waveforms from pulse oximetry compared with measured Doppler flow waveforms
Authors: Wisely N. A. , Cook L. B.
Published: March 2003

This study compared derived arterial flow waveforms, extracted from pulse oximeter waveforms, with Doppler flow waveforms. Fingertip pulse oximeter waveforms and radial artery Doppler flow waveforms were measured simultaneously in volunteers. The pulse oximeter waveforms were processed to extract the arterial flow waveforms and these were compared with the measured Doppler waveforms. They were very similar.
Effect of ondansetron pretreatment on pain after rocuronium and propofol injection: a randomised, double‐blind controlled comparison with lidocaine
Authors: Reddy M. S. , Chen F.‐G. , Ng H.‐P.
Published: March 2003

In a randomised, controlled, double‐blinded trial to study the effect of ondansetron pretreatment on the pain produced after intravenous injection of rocuronium and propofol in comparison with lidocaine, 60 patients were randomly assigned to one of three groups. Group 1 received 5 ml of intravenous 0.9% sodium chloride solution pretreatment, group 2 received ondansetron 4 mg (2 mg.ml−1 solution) diluted into a 5‐ml solution, and group 3 received 50 mg lidocaine (5 ml 1% solution); this was followed 1 min later by rocuronium and propofol. Pain was reduced significantly in the ondansetron and lidocaine groups (p < 0.0001) compared with placebo, and significantly better with lidocaine than with ondansetron (p = 0.02). We conclude that ondansetron is effective in relieving the pain of rocuronium but is not as effective as lidocaine.
Status epilepticus
Authors: Chapman M. G. , Smith M. , Hirsch N. P.
Published: March 2003

Status epilepticus is a medical emergency that requires rapid and vigorous treatment to prevent neuronal damage and systemic complications. Failure to diagnose and treat status epilepticus accurately and effectively results in significant morbidity and mortality. Cerebral metabolic decompensation occurs after approximately 30 min of uncontrolled convulsive activity, and the window for treatment is therefore limited. Therapy should proceed simultaneously on four fronts: termination of seizures; prevention of seizure recurrence once status is controlled; management of precipitating causes of status epilepticus; management of the complications. This article reviews current opinions about the classification, aetiology and pathophysiology of adult generalised convulsive status epilepticus and details practical management strategies for treatment of this life‐threatening condition.
Anions and the anaesthetist
Authors: Maloney D. G. , Appadurai I. R. , Vaughan R. S.
Published: March 2003

Anions are the negative components of most chemical structures and play many important physiological and pharmacological roles that are of interest to the anaesthetist. Their relevance is reviewed with a particular emphasis on the inorganic anions (halides, bicarbonate, phosphate and sulphate) and the significance and limitations of the anion gap. Organic anions (albumin, lactate) are also discussed, albeit briefly. The suitability of anions for their role in neurotransmission and acid−base balance is outlined.
Comparison of cyclizine and ondansetron for the prevention of postoperative nausea and vomiting in laparoscopic day‐case gynaecological surgery
Authors: Grimsehl K. , Whiteside J. B. , Mackenzie Neil
Published: March 2003

Seventy‐four patients undergoing laparoscopic gynaecological surgery were randomly allocated to two groups receiving cyclizine 50 mg or ondansetron 4 mg at induction of anaesthesia. Anaesthetic and postoperative analgesia regimens were standardised. Approximately half of the patients in each group experienced some degree of postoperative nausea and vomiting (cyclizine, 56%; ondansetron, 54%). There was no difference between groups in respect of pre‐ and postdischarge incidence. Mean (SD) time to eye opening was significantly prolonged in the cyclizine group [10 (4) min vs. 8 (2) min; p < 0.001], but this had no influence on discharge times. Cyclizine and ondansetron appear equally effective in preventing postoperative nausea and vomiting but the 10‐fold price differential favours cyclizine.
Measuring the filtration performance of breathing system filters using sodium chloride particles*
Authors: Wilkes A. R.
Published: March 2003

The filtration performance of 33 breathing system filters (nine pleated hydrophobic and 24 electrostatic filters) was measured using sodium chloride particles. The particles had a size distribution with a count median diameter of 0.07 µm and a geometric standard deviation not exceeding 1.83. The geometric mean penetration values ranged from 0.002 to 0.67% for the nine pleated hydrophobic filters and from 0.25 to 35% for the 24 electrostatic filters (p < 0.0001 for the difference between the two filter types). The filtration performance obtained when filters are challenged with either sodium chloride particles or microbes is compared and discussed.
Tracheal intubation and sore throat: a mechanical explanation
Authors: Chandler M.
Published: March 2003

Although tracheal intubation remains a valuable tool, it may result in pressure trauma and sore throat. The evidence for an association between these sequelae is not conclusive and sore throat may be caused at the time of intubation. This hypothesis was tested in a mechanical model and the results from tracheal intubation compared with those from insertion of a laryngeal mask airway, which is associated with a lower incidence of sore throat. Use of the model suggests that the tracheal tube and laryngeal mask airway impinge on the pharyngeal wall in different manners and involve different mechanisms for their conformation to the upper airway, but that in a static situation, the forces exerted on the pharyngeal wall are low with both devices. It also suggests that the incidence of sore throat should be lower for softer and smaller tracheal tubes and that the standard ‘Magill’ curve (radius of curvature 140 ± 20 mm) is about optimum for the average airway.
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

Twelve 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.
Awareness during general anaesthesia: a review of 81 cases from the Anaesthetic Incident Monitoring Study
Authors: Bergman I. J. , Kluger M. T. , Short T. G.
Published: March 2003

Summary Because of recent studies suggesting that awareness is still a major issue in anaesthetic practice, we reviewed 8372 incidents reported to the Anaesthetic Incident Monitoring Study. There were 81 cases in which peri‐operative recall was consistent with awareness. There were 50 cases of definite awareness and 31 cases with a high probability of awareness. In 13 of the 81 incidents, the patients appeared to receive adequate doses of anaesthetic drugs. Where the cause could be determined, awareness was mainly due to drug error resulting in inadvertent paralysis of an awake patient (n = 32) and failure of delivery of volatile anaesthetic (n = 16). Less common causes included prolonged attempts at intubation of the trachea (n = 5), deliberate withdrawal of volatile anaesthetic (n = 4) or muscle relaxant apnoea with inadequate administration of hypnotic (n = 3). An objective central nervous system depth of anaesthesia monitor may have prevented 42 of these incidents and an improved drug administration system may have prevented 32. On the basis of these reports, we have developed guidelines that may have prevented the majority of these incidents.
Safer epidural and spinal connectors*
Authors: Lanigan C. J.
Published: March 2003

Summary Inadvertent cross‐connection of epidural local anaesthetic delivery systems with intravenous lines can cause significant morbidity and even death. Inadvertent intrathecal injection of toxic intravenous drugs has already led to many deaths. If epidural and spinal systems had the standard Luer lock connection reversed the problem would be prevented. The practical implications of this idea are explored. Patient safety would be enhanced if this system were adopted.
Uncertainty and scoring systems
Authors: Ridley S. A.
Published: March 2003

Summary Estimating risks for individual patients facilitates communication with patients, relatives and colleagues, and determines whether further treatment is futile. The process of estimating risks involves mathematics (i.e. scoring systems) and human experience and expertise. Understanding how risks are estimated is important because prognostication is an integral part of any medical specialty. In the USA, such treatment limitation or withdrawal decisions were made on only 7% of all intensive care unit patients but this represented 47% of all deaths on such units. In the UK, data reported by the Intensive Care National Audit and Research Centre suggest that although treatment limitation decisions are made on only 11.8% of patients, this accounts for over 50% of deaths on intensive care. Scoring systems offer a useful adjunct in identifying futility but there are important inherent weaknesses that limit their performance. This review aims to discuss some of these limitations.
Clinical results with a new acoustic device to identify the epidural space
Authors: Lechner T. J. M. , Van Wijk M. G. F. , Maas A. J. J.
Published: March 2003

Summary Fifty patients scheduled for surgery under lumbar epidural anaesthesia were included in a study toevaluate the possibility of localising the epidural space solely by means of an acoustic signal. With an experimental set‐up, the pressure generated during the epidural puncture procedure was translated into a corresponding acoustic signal. One anaesthetist held the epidural needle with both hands and detected the epidural space by means of this acoustic signal. At the same time, a second anaesthetist applied the loss of resistance technique and functioned as control. In all patients the epidural space was located with the acoustic signal. This was confirmed by conventional loss of resistance in 49 (98%) of the patients; in one patient (2%) it was not. We conclude that it is possible to locate the epidural space using an acoustic signal alone.
Matrix metalloproteinase‐9, tissue inhibitor of metalloproteinase‐1 and tumour necrosis factor α release during cardiopulmonary bypass*
Authors: Galley H. F. , Macaulay G. D. , Webster N. R.
Published: March 2003

Summary An inflammatory response occurs during cardiac surgery involving cardiopulmonary bypass. Matrix metalloproteinase‐9 is an enzyme involved in cytokine processing and leucocyte extravasation. It is secreted as a pro‐enzyme in response to several inflammatory mediators and is inhibited by endogenous tissue inhibitor of metalloproteinase‐1. The interaction between matrix metalloproteinase‐9 and its inhibitor during cardiopulmonary bypass is not known. We measured tumour necrosis factor α, and matrix metalloproteinase‐9 and its inhibitor using enzyme immunoassay at three time points in 20 patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass. Tumour necrosis factor and matrix metalloproteinase concentrations increased in all patients during bypass (both p < 0.0001), whereas the inhibitor in contrast, decreased (p < 0.0001). We conclude that matrix metalloproteinase‐9 is released as part of the inflammatory response during cardiac surgery. Levels of the endogenous inhibitor of metalloproteinase, however, show a different pattern of release, suggesting independent regulation.
Randomised controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery*
Authors: Conway D. H. , Mayall R. , Abdul‐Latif M. S. , Gilligan S. , Tackaberry C.
Published: March 2003

Summary Oesophageal Doppler monitoring allows non‐invasive estimation of stroke volume and cardiac output. We studied the impact of Doppler guided fluid optimisation on haemodynamic parameters, peri‐operative morbidity and hospital stay in patients undergoing major bowel surgery. Fifty‐seven patients were randomly assigned to Doppler (D) or control (C) groups. All patients received intra‐operative fluid therapy at the discretion of the non‐investigating anaesthetist. In addition, Group D were given fluid challenges (3 ml.kg−1) guided by oesophageal Doppler. Group D received significantly more intra‐operative colloid than Group C (mean 28 (SD 16) vs. 19.4 (SD 14.7) ml.kg−1, p = 0.02). Cardiac output increased significantly for Group D whilst that of controls remained unchanged. The mean difference between the groups in final cardiac output was 0.87 l.min−1 (95% confidence interval 0.31–1.43 l.min−1, p = 0.003). Five control patients required postoperative critical care admission. Fluid titration using oesophageal Doppler during bowel surgery can improve haemodynamic parameters and may reduce critical care admissions postoperatively.
Evaluation of an expired fraction carbon dioxide monitor
Authors: Ratnasabapathy U. , Allam S. , Souter M. J.
Published: March 2003

Summary Respiratory monitoring is an important aspect of critical care, especially in neurosurgery and neuro‐intensive care. Fixed capnographs are too cumbersome to allow monitoring during patient transport. Recently several portable expired fraction carbon dioxide devices have been developed, but no evaluation of their clinical peformance has been reported. We compared the Criticare POET LT Handheld expired fraction carbon dioxide monitor, in three different settings, to fixed capnographs and arterial blood gas analysis. A methodology for systematic appraisal of end‐tidal capnographs is proposed.
A comparison of propofol and sevoflurane anaesthesia: effects on aortic blood flow velocity and middle cerebral artery blood flow velocity*
Authors: Holzer A. , Winter W. , Greher M. , Reddy M. , Stark J. , Donner A. , Zimpfer M. , Illievich U. M.
Published: March 2003

Summary We compared systemic (aortic) blood flow and cerebral blood flow velocity in 30 patients randomly allocated to receive either propofol or sevoflurane anaesthesia. Cerebral blood flow velocity (CBFv) was measured in the middle cerebral artery using transcranial Doppler. Systemic blood flow velocity (SBFv) was measured in the aorta using transthoracic Doppler sonography at the level of the aortic valve. Bispectral index (BIS) was used to measure the depth of anaesthesia. Measurements were made in the awake patient and repeated during propofol or sevoflurane anaesthesia, with BIS measurements of 40–50. The effects of SBFv on CBFv were estimated by calculating the cerebral/systemic blood flow velocity‐index (CsvI). A CsvI value of 100 indicating a 1 : 1 relationship between CBFv and SBFv. The results demonstrated that propofol anaesthesia produced a significantly greater reduction in CsvI than did sevoflurane anaesthesia [propofol: 60 (19); sevoflurane: 83 (16), p = 0.009, t‐test]. This suggests a direct reduction in CBFv independent of SBFv during propofol anaesthesia. The greater reduction of CBFv occurring during propofol anaesthesia may be due to lower cerebral metabolic demand compared with sevoflurane anaesthesia at comparable depths of anaesthesia.
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.
Steady, balanced rates of uplift and erosion of the Santa Monica Mountains, California
Authors: Meigs  , Brozovic  , Johnson
Published: March 2003

Topographic change in regions of active deformation is a function of rates of uplift and denudation. The rate of topographic development and change of an actively uplifting mountain range, the Santa Monica Mountains, southern California, was assessed using landscape attributes of the present topography, uplift rates and denudation rates. Landscape features were characterized through analysis of a digital elevation model (DEM). Uplift rates at time scales ranging from 104to 106years were constrained with geological cross‐sections and published estimates. Denudation rate was determined from sediment yield data from debris basins in southern California and from the relief of rivers set into geomorphic surfaces of known age. First‐order morphology of the Santa Monica Mountains is set by large‐scale along‐strike variations in structural geometry. Drainage spacing, drainage geometry and to a lesser extent relief are controlled by bedrock strength. Dissection of the range flanks and position of the principal drainage divide are modulated by structural asymmetry and differences in structural relief across the range. Topographic and catchment‐scale relief are ≈300–900 m. Mean denudation rate derived from the sediment yield data and river incision is 0.5±0.3 mm yr−1. Uplift rate across the south flank of the range is ≈0.5±0.4 mm yr−1and across the north flank is 0.24±0.12 mm yr−1. At least 1.6–2.7 Myr is required to create either the present topographic or the catchment‐scale relief based on either the mean rates of denudation or uplift. Although the landscape has had sufficient time to achieve a steady‐state form, comparison of the time‐scale of uplift and denudation rate variation with probable landscape response times implies the present topography does not represent the steady‐state form.
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 stretching

factor 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.
Thermochronology, denudation and variations in palaeosurface temperature: a case study from the North Slope foreland basin, Alaska
Authors: O’Sullivan
Published: March 2003

Integration of vitrinite reflectance (Ro) and apatite fission track (AFT) data from well sequences can provide a direct estimate of the geothermal gradient at the time of maximum palaeotemperatures and the time at which sequences began to cool from maximum palaeotemperatures. These values, plus an understanding of the effects of cooling in response to long‐term climatic changes, are particularly important when estimating the amount of denudation experienced by the sequences during cooling from maximum palaeotemperatures. In this case study, AFT data have been generated for subsurface samples from eight wells drilled within the North Slope foreland basin of northern Alaska in an effort to study the thermal history of the basin. The combination of Ro and AFT data establish that maximum palaeotemperatures were attained within the North Slope foreland basin prior to cooling beginning in the Palaeocene. Furthermore, they indicate that palaeogeothermal gradients when cooling began were close to the present‐day values, and that Cenozoic surface cooling resulted in a significant amount of ‘apparent’ denudation. These results suggest that heating throughout the basin was largely due to deeper burial, and that cooling was due to both removal of section by denudation and a drop in the mean annual surface temperature.
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.
Tertiary foreland sedimentation in the Southern Subalpine Chains, SE France: a geodynamic appraisal
Authors: Ford  , Lickorish  , Kusznir
Published: March 2003

Tertiary foreland sedimentation in SE France occurred along the western sidewall of the Alpine orogen during collision of the Apulian indentor with the European passive margin. A detailed reappraisal of the stratigraphy and structure of the Southern Subalpine Chains (SSC) in SE France shows that Tertiary depocentres of differing character developed progressively toward the foreland during ongoing SW‐directed shortening. The geodynamic controls on each of four stages of basin development are evaluated using a flexural isostatic modelling package of thrust sheet emplacement and foreland basin formation. (1) The initial stage (mid to late Eocene) can be explained as a flexural basin that migrated toward the NW, closing off to the SW against the uplifting Maures–Esterel block. This broad, shallow basin can be reproduced in forward modelling by loading a lower lithospheric plate with an effective elastic thickness of 20 km. (2) The end of detectable flexural subsidence in the early Oligocene coincides with the emplacement of the internally derived Embrunais–Ubaye (E‐U) nappes, which caused 11 km of SW‐directed shortening in the underlying SSC. The lack of Oligocene flexural subsidence dictates that the E‐U units were emplaced as gravitational nappes. Within the SSC, Oligocene sedimentation was restricted to small thrust‐sheet‐top basins recording mainly continental conditions and ongoing folding. Further west, Oligocene to Aquitanian NNW–SSE extension generated the Manosque half‐graben as part of the European graben system that affected an area from the Gulf of Lion to the Rhine graben. (3) Following the Burdigalian breakup of the Gulf of Lion rift, a marine transgression migrated northward along the European graben system. Subsequent thermal subsidence allowed 1 km of marine sediments to be deposited across the Valensole and Manosque blocks, west of the active SSC thrust belt. (4) Mio‐Pliocene conglomeratic deposits (2 km thick) were trapped within the Valensole basin by the uplifting Vaucluse block to the west and the advancing Alpine thrust sheets to the east. Late Pliocene thrusting of the SSC across the Valensole basin (approx. 10.5 km) can be linked along a Triassic detachment to the hinterland uplift of the Argentera basement massif.
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

High 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

Rock 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.
Thermal history of the Cretaceous Sindong Group, Gyeongsang Basin, Korea based on fission track analysis
Authors: Lim Hyoun Soo , Lee Yong Il , Min Kyung Duck
Published: March 2003

ABSTRACT Apatite and zircon fission track (FT) analyses were carried out to reconstruct the thermal history of the Lower Cretaceous Sindong Group, which is the lowermost stratal unit of the Gyeongsang Basin, Korea. Zircon FT central ages show a wide range from 83 ± 5 to 157 ± 18 Ma, and single‐grain age spectra have multiple age populations, whereas all apatites have very consistent FT ages of c. 60 Ma, suggesting a totally reset cooling age. Co‐existence of both older and younger ages compared with the depositional age and relatively short mean track length indicate that the Sindong zircons were partially annealed. The Sindong Group was heated into the zircon partial annealing zone (ZPAZ) around 80 Ma, and cooled below the apatite closure temperature at c. 60 Ma. Based on the zircon FT results combined with vitrinite reflectance data, the maximum palaeotemperature to which the Sindong Group had been subjected can be inferred to be about 260 °C. Zircon FT data from a granite body that is in contact with the Sindong Group and sandstones close to the granite body indicate that thermal influence caused by Upper Cretaceous intrusive rocks was limited in close vicinity of the intrusion and that the major heat source of the Sindong Group was burial. The thickness of uplifted and eroded section is estimated to be about 7 km.
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.
Sorivudine and 5‐fluorouracil; a clinically significant drug‐drug interaction due to inhibition of dihydropyrimidine dehydrogenase
Authors: Diasio Robert B.
Published: March 2003

Sorivudine (1‐β‐d‐arabinofuranosyl‐E‐5‐[2‐bromovinyl] uracil; BV‐araU; SQ32,756) is an antimetabolite which is a synthetic analogue of thymidine. This drug has demonstrated antiviral activity against varicella zoster virus, herpes simplex type 1 virus, and Epstein‐Barr virus. Clinical studies in Japan and subsequently worldwide showed this drug to be a potent agent for treating varicella zoster infections. Although in general well tolerated, a fatal drug interaction with fluoropyrimidine drugs was subsequently observed. While three deaths resulting from this interaction were recognized to have occurred during the initial clinical evaluation in Japan, the full impact of the interaction was not recognized in Japan until post‐marketing when an additional 23 cases of severe toxicity were reported including 16 patients who subsequently died from fluoro‐pyrimidine toxicity. Worldwide recognition of this potentially fatal drug‐drug interaction led to subsequent disapproval in the US and elsewhere. The interaction has been shown to be due to suppression of 5‐fluorouracil (5‐FU) catabolism, resulting in higher levels of 5‐FU than would normally be observed. The mechanism of this interaction is mediated through inhibition of the 5‐FU rate‐limiting catabolizing enzyme dihydropyrimidine dehydrogenase (DPD) by the BV‐araU metabolite BVU. This drug‐drug interaction of sorivudine and 5‐FU further emphasizes the critical importance of DPD on the clinical pharmacology of 5‐FU.