bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of the effects of desflurane and isoflurane on arterial oxygenation during one‐lung ventilation
Authors: Wang J. Y. Y. , Russell G. N. , Page R. D. , Oo A. , Pennefather S. H.
Published: March 2003

In a randomised prospective cross‐over study, we compared the effects of desflurane and isoflurane on arterial oxygenation, heart rate and mean arterial pressure during one‐lung anaesthesia. Thirty patients scheduled for oesophagogastrectomy were randomly assigned to one of two groups. One group of 15 patients received desflurane to an end‐tidal concentration of 6% in oxygen from induction until the end of 30 min of open chest one‐lung ventilation in the lateral position. This was followed by isoflurane to an end‐tidal concentration of 1.1% in oxygen for the next 30 min of one‐lung ventilation. The other group of 15 patients received the two anaesthetic agents in the reverse order. We found no significant difference in arterial oxygenation, heart rate or mean arterial pressure between the two inhalational agents. In the subgroup of 10 patients with pulmonary artery catheters, we found no significant differences in mixed venous saturation, derived shunt or cardiac output. We conclude that during one‐lung ventilation, the choice between desflurane and isoflurane does not significantly influence arterial oxygenation.
Entonox equipment as a potential source of cross‐infection
Authors: Chilvers R. J. , Weisz M.
Published: March 2003

A survey of the hospitals with obstetric units within the Anglia and Oxford Region was performed to assess current practices regarding the cleaning of, and use of filters with, Entonox apparatus. The survey revealed that there was no consensus regarding the cleaning of the equipment and, in contrast to anaesthetic machines in which microbiological filters are recommended and in widespread use, only 10% of the hospitals surveyed were using such filters with the Entonox apparatus in their units. Cleaning procedures were changed in 75% of hospitals when dealing with known ‘high‐risk’ patients, the remaining hospitals treating all patients as ‘high‐risk’ or denied caring for such patients. All patients should be protected from potential cross‐infection, and the recommendation that a microbiological filter should be placed between patients and the breathing system should be extended to Entonox equipment.
Non‐invasive ventilation in the treatment of ventilatory failure following corrective spinal surgery
Authors: Doherty M. J. , Millner P. A. , Latham M. , Dickson R. A. , Elliott M. W.
Published: March 2003

Non‐invasive positive pressure ventilation has previously been used successfully to treat both acute and chronic ventilatory failure secondary to a number of conditions, including scoliosis. We report two patients in whom it was used, on three separate occasions, to treat acute ventilatory failure following corrective spinal surgery. Non‐invasive positive pressure ventilation may be useful postoperatively in high‐risk patients undergoing major spinal surgery in an attempt to prevent intubation and its attendant complications.
A comparison of the intubating and standard laryngeal mask airways for airway management by inexperienced personnel
Authors: Choyce A. , Avidan M. S. , Shariff A. , Del Aguila M. , Radcliffe J. J. , Chan T.
Published: March 2003

Twenty‐four inexperienced participants were timed inserting the intubating laryngeal mask airway and the laryngeal mask airway in 75 anaesthetised subjects. Adequacy of ventilation was assessed on a three‐point scale. The pressure at which a leak first developed around the device's cuff was also measured. There was no significant difference in insertion time or the likelihood of achieving adequate ventilation between devices. However, the intubating laryngeal mask airway was better at providing adequate ventilation without audible leak (58/75 (77%) vs. 42/75 (56%); p = 0.009). The median (range [IQR]) pressure at which an audible leak developed was higher for the intubating laryngeal mask airway, 34.5 (14–40 [29–40]) cmH2O, than for the laryngeal mask airway, 27.5 (14–40 [22–33]) cmH2O (p < 0.001). The intubating laryngeal mask airway is worthy of further consideration as a tool for emergency airway management for inexperienced personnel.
Working patterns of trainee anaesthetists in the UK: results of a national postal survey
Authors: McGill A. , Hutchinson S. P. , Andrzejowski J. C. , Francis G. A.
Published: March 2003

The ‘New Deal’ restrictions on junior doctors' hours have major implications for the staffing of anaesthetic departments and the provision of adequate training. The results of a national postal survey demonstrate a decline in traditional on‐call arrangements, especially in hard‐pressed work sectors such as intensive care. A substantial number of anaesthetic departments have still completely to satisfy the hours restrictions in many work sectors. Many departments experience recruitment difficulties and express concern about both service and training issues.
Fatal subdural haemorrhage following lumbar spinal drainage during repair of thoraco‐abdominal aneurysm
Authors: McHardy F. E. , Bayly P. J. M. , Wyatt M. G.
Published: March 2003

A 63‐year‐old male patient collapsed and died from a major subdural haemorrhage 5 days after elective repair of a Type III thoraco‐abdominal aortic aneurysm. The anaesthetic technique had included the use of a lumbar cerebrospinal fluid drain. The management of the patient is described, and the association between subdural haemorrhage and cerebrospinal fluid drainage is discussed.
Effect of smoking on induction of anaesthesia with sevoflurane
Authors: Mendonca C. , Thorpe C. M.
Published: March 2003

Inhalational induction with sevoflurane has been shown to be a viable alternative to intravenous induction; however, studies have focused mainly on healthy patients or volunteers. Airway complications in patients with potential airway irritability have not been studied. Sixty smokers undergoing general anaesthesia were randomly assigned to one of three groups: group 1, vital capacity breathing with 8% sevoflurane; group 2, tidal breathing with 8% sevoflurane; and group 3, tidal breathing with step‐up of sevoflurane (sevoflurane concentration increased by increments of 2% every 10 s until 8%). Step‐up induction was significantly slower to induce loss of consciousness than a vital capacity breath or tidal breathing at 8% (p < 0.05). Step‐up induction produced more complications than tidal breathing at 8% (p = 0.05). All patients had acceptable induction of anaesthesia with no patient having an oxygen saturation below 96% at any time. Blood pressure and heart rate decreased gradually over time in all groups (p < 0.001), but there were no significant differences between groups. Patient satisfaction with the techniques was high with 59 of 60 patients willing to have the same technique again. Inhalational induction with sevoflurane can be used safely as an induction technique in smokers. In common with other patient groups, use of a high initial concentration reduces induction time without causing additional airway or cardiovascular complications.
Intra‐operative blood salvage in abdominal trauma
Authors: Gwynne Hughes L. , Thomas D. W. , Wareham K. , Jones J. E. , John A. , Rees M.
Published: March 2003

We performed a retrospective audit of 1235 patients presenting between 1992 and 1997, following the introduction of intra‐operative blood salvage at our hospital. Twenty‐two cases of severe abdominal trauma requiring emergency laparotomy and intra‐operative blood salvage were identified. The impact of intra‐operative blood salvage in aiding resuscitation and reducing demand on allogeneic blood supplies is discussed.
Renal and respiratory failure in Scottish ICUs
Authors: Noble J. S. , MacKirdy F. N. , Donaldson S. I. , Howie J. C.
Published: March 2003

The purpose of this study was to define the outcome of patients receiving both renal replacement therapy and mechanical ventilation in 16 Scottish intensive care units over a 2‐year period. Patients were identified from the Scottish Intensive Care Society's database. Survivors developing end‐stage renal failure were identified after examination of the Scottish Renal Registry's database. Mortality was 64.2% (392/612) for all patients receiving renal replacement therapy and mechanical ventilation. End‐stage renal failure developed in 1.6% (3/188) of the survivors of acute renal failure and in 33% (4/11) of the survivors with pre‐existing chronic renal failure. Mortality has not improved when compared with earlier studies. End‐stage renal failure rarely develops following acute renal failure in the intensive care unit.
Anaesthetic management of 27 cases of boron neutron capture therapy for glioblastoma
Authors: Shinomura T. , Furutani H. , Osawa M. , Ono K. , Fukuda K.
Published: March 2003

Twenty‐seven patients received boron neutron capture therapy during craniotomy at our research reactor from 1991 to 1999. This is a form of intra‐operative radiation therapy, which uses neutrons from a nuclear reactor. There are three additional major problems to anaesthetists: boron neutron capture therapy must be given beside the nuclear reactor, with no hospital facilities; neutrons cannot be shielded effectively by ordinary protectors; and neutrons are detrimental to metal devices and especially to electrical appliances. Boron neutron capture therapy has been adopted as an effective therapy for glioblastoma/astrocytoma, but special considerations are required for anaesthesia.
Arterial blood sampling practices in intensive care units in England and Wales
Authors: O'Hare D. , Chilvers R. J.
Published: March 2003

A postal survey of arterial blood sampling practices in 280 intensive care units throughout England and Wales found that very few measures are taken to reduce diagnostic blood loss in adult intensive care patients from arterial sampling. The average volume of blood withdrawn to clear the arterial line before sampling is 3.2 ml; subsequently returned to the patient in only 18.4% of intensive care units.

Specific measures to reduce the blood sample size by the routine use of paediatric sample tubes in adult patients occurs in only 9.3% of intensive care units. In paediatric units, the average volume withdrawn was 1.9 ml and this was routinely returned in 67% of units. Some aspects of arterial blood sampling practices identified in this survey may contribute to iatrogenic anaemia in intensive care patients.
The use of spectral measures of heart rate variability to differentiate between male snorers and patients with sleep apnoea syndrome
Authors: Dworschak M. , Maurer J. T. , Haschemian T. , Rapp H.‐J. , Waschke K. F.
Published: March 2003

Snoring is a characteristic feature of habitual snorers and patients with sleep apnoea syndrome. However, unlike snorers, sleep apnoea patients have an increased peri‐operative morbidity. Presently available methods to differentiate between these two groups are either expensive, invasive or time consuming. As cardiac reflexes are impaired in sleep apnoea syndrome, we tested whether heart rate variability could discriminate between snorers and patients with sleep apnoea syndrome. Heart rate variability measurement detects cardiac autonomic dysfunction non‐invasively in an ambulatory setting. We studied 32 male patients undergoing polysomnography for suspected sleep apnoea. Total, low‐ and high‐frequency power were measured using a Holter electrocardiogram. Differences in night‐ and daytime variability were then calculated. Differences between day and night values were more pronounced in the sleep apnoea group and related to the apnoea‐hypopnoea‐index and low oxygen saturation. Higher values in sleep apnoea patients resulted from increasing variability at night. Heart rate variability might thus help to differentiate between snorers and patients with severe sleep apnoea syndrome.
Quantitative physical chemistry analysis of acid−base disorders in critically ill patients
Authors: Story D. A. , Poustie S. , Bellomo R.
Published: March 2003

Compared with the Henderson−Hasselbalch approach, the Stewart approach may better describe the mechanisms of acid−base physiology and disorders. We prospectively examined the acid−base disorders of 100 routine blood samples from critically ill patients using Stewart's physical chemistry analysis. The median results were pH 7.45, Paco2 5.5 kPa, bicarbonate 27.2 mmol.l−1 and base excess 3 mmol.l−1. The median reference strong ion difference was 46.0 meq.l−1 and the measured median was 45.5 meq.l−1. The median reference total weak‐acid concentration was 11.1 mmol.l−1. The measured median total weak‐acid concentration was 6.8 mmol.l−1. From Stewart's approach, the most likely explanation for the overall alkalosis was decreased total weak‐acid concentration resulting from decreased plasma albumin concentration.
Effects of shivering prevention on haemodynamic and metabolic demands in hypothermic postoperative neurosurgical patients
Authors: Bilotta F. , Pietropaoli P. , La Rosa I. , Spinelli F. , Rosa G.
Published: March 2003

We evaluated the haemodynamic and metabolic effects of prevention of shivering after prophylactic nefopam administration in neurosurgical patients undergoing craniotomy and mild systemic hypothermia (33–35 °C). Forty patients were enrolled in a randomised, double‐blind study. Before extubation, patients received intravenously either nefopam 0.12 mg.kg−1 or an equal volume of saline 0.9%. Left ventricular systolic work index, oxygen consumption index and systemic lactate concentration were recorded before, immediately after and every 20 min for 2 h after extubation. Shivering appeared in two patients treated with nefopam and in all control patients (p < 0.001). Both left ventricular systolic work index and oxygen consumption index were similar in the two groups before extubation, increased after extubation, and further increased in control patients showing a statistical difference compared to patients treated with nefopam. Our results suggest that nefopam is effective in preventing postoperative shivering in patients undergoing neurosurgery and mild hypothermia and attenuates the haemodynamic effects of shivering during rewarming.
Disappearance of intraperitoneal gas following gynaecological laparoscopy
Authors: Stanley I. R. , Laurence A. S. , Hill J. C.
Published: March 2003

We investigated 25 day case gynaecological laparoscopy patients to determine the duration of the pneumoperitoneum, the rate at which residual gas disappeared and the relative contribution of this gas to pain in the early postoperative period. The volume of gas was calculated from measurements of the subdiaphragmatic gas bubble obtained from an erect chest X‐ray. Each patient was X‐rayed twice, either immediately prior to discharge and at 24 h post laparoscopy, or at 24 h and 48 h post surgery. Patients were contacted by telephone at 24 and 48 h to confirm fitness to return for the X‐ray and at the same time verbal pain and activity scores were recorded. We found that residual gas was almost entirely gone by 48 h following surgery and that it appeared to reduce in an exponential manner. The contribution of this gas to postoperative pain was significant in the first 24 h, but by 48 h it was considerably reduced. We conclude that in day case gynaecological laparoscopy patients, postoperative pneumoperitoneum is short‐lived, and that by 48 h its volume and contribution to postoperative pain should be minimal.
A combined technique utilising regional anaesthesia and target‐controlled sedation in a patient with myotonic dystrophy
Authors: Aquilina A. , Groves J.
Published: March 2003

Summary Myotonic dystrophy presents several problems to the anaesthetist. We describe what we believe to␣be the first report of target‐controlled sedation combined with regional anaesthesia in a patient with myotonic dystrophy. Precise control of propofol levels and titration to patient satisfaction avoided the problem of delayed recovery which has been described with propofol anaesthesia.
Pulmonary artery blood temperature and the measurement of cardiac output by thermodilution
Authors: Moise S. F. , Sinclair C. J. , Scott D. H. T.
Published: March 2003

Summary Thermodilution cardiac output measurement assumes that the temperature within the pulmonary artery is stable during the measurement period. This may not be achieved in clinical practice because of temperature changes that are not solely produced by the thermal indicator. Such temperature changes constitute thermal noise. Thermal noise and how it may interfere with measurement is discussed with reference to both the injectate and the thermal filament methods of thermodilution cardiac output measurement.
The value of risk scores for predicting postoperative nausea and vomiting when used to compare patient groups in a randomised controlled trial
Authors: Thomas R. , Jones N. A. , Strike P.
Published: March 2003

Summary Whilst conducting a randomised controlled trial into the effects of combination anti‐emetics, we endeavoured to confirm that our patient groups were matched using the predictive scoring systems for postoperative nausea and vomiting (PONV) and postoperative vomiting (POV) reported in the literature. One hundred and seventy‐seven female patients attending for day case gynaecological surgery were studied and their individual risks of PONV and POV were calculated using four predictive models for PONV and two predictive models for POV. The scoring systems were then evaluated to see if agreement existed between them using the method described by Bland and Altman. Bias and 95% limits of agreement were calculated for each combination. Agreement between scoring systems was poor. As the scoring systems gave widely divergent predictions, we concluded that the predictive risk for PONV or POV would be dependent upon the scoring system chosen, thus limiting their usefulness in this role.
Pharmacological agents as cerebral protectants during deep hypothermic circulatory arrest in adult thoracic aortic surgery
Authors: Dewhurst A. T. , Moore S. J. , Liban J. B.
Published: March 2003

A postal survey was sent to members of the Association of Cardiothoracic Anaesthetists to ascertain current practice in the use of pharmacological agents as cerebral protectants during deep hypothermic circulatory arrest. The response rate was 60%. Eighty‐three per cent of respondents used some form of pharmacological agent specifically for cerebral protection. Fifty‐nine per cent of respondents used thiopental, 29% used propofol and 48% used a variety of other agents, the most common of these being a steroid. There were variations in the dose and timing of administration of drugs. Few respondents believed that there was a body of evidence to support this use of pharmacological agents. Only 35% of respondents believed there to be sufficient evidence to support the use of thiopental. Similarly, only 11% of respondents believe that there is evidence supporting the use of propofol, and 16% the use of steroids. The above findings demonstrate that it would not be possible to create a ‘best practice’ set of guidelines at present. A national database of all cases of adult thoracic surgery involving deep hypothermic cardiac arrest, with methodology and outcome, could probably establish such guidelines, evidence based.
The Sister Anaesthetists of Norwich
Authors: Woollam C. H. M.
Published: March 2003

The administration of general anaesthesia in the UK has generally been carried out by medically qualified staff but there have been instances where this has not been the case. This article describes the role of the ‘Sister Anaesthetists’ who made a significant contribution to the delivery of anaesthesia services at the Norfolk and Norwich Hospital from the end of the First World War until the introduction of the National Health Service in 1948.
Use of intrathecal morphine for postoperative pain relief after elective laparoscopic colorectal surgery
Authors: Kong S‐K. , Onsiong S. M. K. , Chiu W. K. Y. , Li M. K. W.
Published: March 2003

Laparoscopic surgery has become popular in recent years, but few studies have addressed analgesia for this type of surgery. We conducted a prospective double‐blind randomised trial on 36 cases of laparoscopic colorectal surgery to determine the influence of intrathecal morphine on postoperative pain relief. All patients received a subarachnoid block with local anaesthetic in addition to general anaesthesia. One group also received intrathecal morphine. A patient‐controlled analgesic (PCA) device was prescribed for pain control postoperatively and the visual analogue score (VAS) was used for pain assessment. The group who received intrathecal morphine used significantly less morphine. There were no adverse cardiovascular effects of the combined anaesthetic technique. Nausea and vomiting remained the main side‐effect of intrathecal morphine but this was easily treated with anti‐emetics.
Adverse airway events during brief nasal inhalations of volatile anaesthetics: the effect of humidity and repeated exposure on incidence in volunteers preselected by response to desflurane*
Authors: Wilkes A. R. , Raj N. , Hall J. E.
Published: March 2003

Summary Twelve volunteers known to have airways that responded adversely to 2.0 MAC desflurane were recruited. Each volunteer inhaled three single breaths of each of 0.5, 1.0 and 2.0 MAC of sevoflurane, halothane, isoflurane, desflurane and balance air, with breaths of air between, whilst breathing nasally through a face mask attached to one of three filters that provided three different levels of humidification. The incidence of any adverse airway events was recorded. The anaesthetic inhaled significantly affected the incidence of adverse airway events (p < 0.001), with the least to most irritant being sevoflurane, halothane, isoflurane and desflurane. Increasing the concentration of anaesthetic also significantly increased the incidence of adverse airway events (p < 0.001). The filter used, and hence the level of humidification, did not affect the incidence of adverse airway events (p = 0.09), but repeated exposure caused a significant reduction in the incidence of adverse airway events (p < 0.001).
Multimethod (K–Ar, Rb–Sr, Sm–Nd) dating of bentonite minerals from the eastern United States
Authors: Toulkeridis Theofilos , Clauer Norbert , Chaudhuri Sam , Goldstein Steve L.
Published: March 2003

Isotopic determinations (K–Ar, Rb–Sr and Sm–Nd), and trace and rare‐earth elemental analyses were made on a few biotite and clay fractions of Palaeozoic bentonite units from the eastern United States. The clay fractions were gently leached with dilute hydrochloric acid to study separately the acid‐soluble minerals intimately associated with the extracted clay particles. The data highlight interesting potentials for this integrated approach to decipher complex tectonothermal evolutions of sedimentary basins. Biotite K–Ar ages are consistent with a Middle Ordovician stratigraphic age for the bentonite units with a mean age of 459±10 Ma. The clay residues give a Sm–Nd isochron age of 397±44 Ma, indicative of their crystallization during Acadian tectonothermal activity at about 200 °C. The clay leachates, which are considered to represent mineral phases different from clay material, yield a distinct Sm–Nd isochron age of 285±18 Ma which is indistinguishable from K–Ar ages obtained previously on the clays, suggesting a thermally induced diffusion of radiogenic 40Ar from clay particles during Alleghenian–Ouachita orogenic activity. The Rb–Sr system of the clay material seems to have been variably disturbed, except for the sample taken near the Allegheny Front for which an age of 179±4 Ma suggests a further localized activity of the thrust system at about 130–150 °C.

Clearly the limited number of samples does not allow us to perfectly constrain an evolutionary model. However, analysis of the soluble minerals for their contents in metal and rare‐earth elements suggests that metal‐carrying fluids migrated during the Alleghenian–Ouachita orogenic activity in the eastern North American continent. Consequently, they could have contributed to the concentration of ore deposits in the region, but this possibility needs to be tested with a larger data base.
Structural and topographic evolution of the central Transverse Ranges, California, from apatite fission‐track, (U–Th)/He and digital elevation model analyses
Authors: Blythe  , Burbank  , Farley  , Fielding
Published: March 2003

Apatite fission‐track (FT) and (U–Th)/He analyses are used to constrain the low‐temperature thermal history of the San Gabriel and San Bernardino Mountains (SGM and SBM), which are part of the southern California Transverse Ranges. FT ages from 33 SGM samples range from 3 to 64 Ma. Helium ages, ranging from 3 to 43 Ma, were obtained from 13 of these samples: all of the He ages are the same or younger than their respective FT ages. FT ages from 10 SBM samples were older, ranging from 45 to 90 Ma. The FT and He data document at least three phases of cooling in the SGM, but only two in the SBM. Prior to ~7 Ma, the thermal history of the SGM appears to have been nearly identical to many of the core complexes in the Basin and Range of south‐eastern California: a major phase of cooling is indicated from ~60 to 40 Ma, with a more recent phase beginning at ~23 Ma and continuing until ~10 Ma. The similarity of this timing to that of core complexes suggests that the SGM also originated as a core complex, when the rocks were adjacent to the Chocolate–Orocopia Mountains, and that some of the range‐bounding faults were initially extensional. In the SBM, the two phases of cooling documented by the FT data occurred from ~65 to 55 Ma, and from ~18 Ma to the present. The timing on the second phase is very poorly constrained and, therefore, we do not speculate on the origin of the SBM.

The most recent phase of cooling appears to have begun at ~7 Ma in the SGM, as the result of the onset of contractional deformation. A more accelerated phase of cooling may have begun at ~3 Ma. Distinct variations in the total amounts and rates of cooling between different fault‐bounded blocks within the SGM are documented since 7 Ma. We use these variations in cooling rates to calculate denudation rates, which are then compared to topographic characteristics for each structural block. These comparisons suggest that more rapid bedrock uplift in the eastern and southern part of the range has strongly affected the present‐day physiography. Despite a higher mean elevation, the SBM are much less dissected than the SGM, suggesting that the most recent phase of cooling and bedrock uplift began in the last 3 Myr, much later than the initiation of recent bedrock uplift in the SGM.
Polyphase Tectonics through subsidence analysis: the Oligo‐Miocene Venetian and Friuli Basin, north‐east Italy
Authors: Mellere  , Stefani  , Angevine
Published: March 2003

Subsidence and provenance analysis has been used as a tool to quantify and discriminate the role of tectonics and eustasy in the Veneto and Friuli Basin, north‐east Italy, using 17 sections distributed along east–west‐trending outcrops of Oligo‐Miocene deposits. The basin can be considered a two‐phase foreland; first, during late Oligocene to Langhian with respect to the NW–SE‐trending Dinaric Chain, and then with respect to the south‐vergent South‐Alpine Chain.The clastic succession is up to 4000 m thick, and was deposited in a generally shallow‐marine to nonmarine environment. Subsidence diagrams reconstructed for each section and E–W subsidence profiles indicate a compound effect of the Dinaric and South‐Alpine tectonics as well as interference with eustatic sea‐level changes.During the Oligocene and the early Miocene, the cycles recognized within the basin approximately match sea‐level curves, the inferred cyclicity being primarily eustatic. However, the westward migration of the sedimentary depocentre during the same interval of time indicates activity of Dinaric thrusts.From Burdigalian (20 Ma) onwards, differential subsidence between the northernmost and the southernmost sectors of the basin suggests initiation of South‐Alpine uplift in the frontal parts. During Tortonian and early Messinian uplift, erosion and southward migration of the thrust system was associated with the progressive closure of the basin from open marine influence. During Messinian sea‐level drop, up to 2500 m of alluvial sediments were deposited at the same time as the South‐Alpine thrusts were emerging, as confirmed by progressive angular unconformities within the continental succession.
Morphology and origin of major Cenozoic sequence boundaries in the eastern North Sea Basin: top Eocene, near‐top Oligocene and the mid‐Miocene unconformity
Authors: Huuse M. , Clausen O. R.
Published: March 2003

Unconformities in sedimentary successions (i.e. sequence boundaries) form in response to the interplay between a variety of factors such as eustasy, climate, tectonics and basin physiography. Unravelling the origin of sequence boundaries is thus one of the most pertinent questions in the analysis of sedimentary basins. We address this question by focusing on three of the most marked physical discontinuities (sequence boundaries) in the Cenozoic North Sea Basin: top Eocene, near‐top Oligocene and the mid‐Miocene unconformity.

The Eocene/Oligocene transition is characterized by an abrupt increase in sediment supply from southern Norway and by minor erosion of the basin floor. The near‐top Oligocene and the mid‐Miocene unconformity are characterized by major changes in sediment input directions and by widespread erosion along their clinoform breakpoints. The mid‐Miocene shift in input direction was followed by a marked increase in sediment supply to the southern and central North Sea Basin.

Correlation with global δ18O records suggests that top Eocene correlates with a major long‐term δ18O increase (inferred climatic cooling and eustatic fall). Near‐top Oligocene does not correlate with any major δ18O events, while the mid‐Miocene unconformity correlates with a gradual decrease followed by a major long‐term increase in δ18O values The abrupt increases in sediment supply in post‐Eocene and post‐middle Miocene time correlate with similar changes worldwide and with major δ18O increases, suggesting a global control (i.e. climate and eustasy) of the post‐Eocene sedimentation in the North Sea Basin.

Erosional features observed at near‐top Oligocene and at the mid‐Miocene unconformity are parallel to the clinoform breakpoints and resemble scarps formed by mass wasting. Incised valleys have not been observed, indicating that sea level never fell significantly below the clinoform breakpoint during the Oligocene to middle Miocene.
A study of the relation of exposure to quinolones and suicidal behaviour
Authors: Jick Susan S. , Vasilakis Catherine , Martinez Carlos , Jick Hershel
Published: March 2003

Aims
 To investigate the concern, raised by spontaneous reports received by the German regulatory authorities, that use of quinolone antibiotics may increase the risk for suicide and other suicidal behaviours.

Methods
 We carried out a nested case‐control study using the General Practice Research Database (GPRD). We compared the risk of suicidal behaviours among users of quinolones, other antibiotics and no antibiotics.

Results
 From January 1, 1991 through April 30, 1995 we identified 348 cases of suicide, attempted suicide, or suicidal ideation and 808 controls. Compared with controls, cases who had received a prescription for a quinolone in the 30 days prior to the event had an adjusted relative risk (RR) estimate of 1.5 (95% CI 0.4–6.3) for any suicidal behaviour. Cases who had filled a prescription for a quinolone in the 31 to 180 days prior to their event had an adjusted RR estimate of 0.8 (95% CI 0.4–1.7) compared with controls. Cases who used other antibiotics in the 30 days prior to the event conferred an adjusted RR estimate of 1.1 (95% CI 0.6–2.2), and 0.9 (95% CI 0.6–1.3) for exposure in the 31 to 180 days prior to the event. The results were not materially different when suicide, suicide attempt, and suicidal ideation were analyzed separately.

Conclusions
 We conclude that there is no material increased risk of suicidal behaviours for use of quinolone antibiotics compared with non‐use or use of other antibiotics.
Fenoterol increases erythropoietin concentrations during tocolysis
Authors: Gleiter C. H. , Schreeb K. H. , Goldbach S. , Herzog S. , Cunze T. , Kuhn W.
Published: March 2003

Aims
 The present study was carried out to assess the effect of the selective β2‐ adrenoceptor agonists on erythropoietin (EPO) production.

Methods
 Routine tocolysis with fenoterol (using the regular rate of 2 μg min−1 ) was used as a clinically easily accessible model.

Results
 EPO concentrations had doubled 24 h after the start of tocolysis (P<0.001). This increase lasted over the entire observation period of 48 h. Potassium concentrations fell significantly during the first hours of fenoterol infusion. There was no increase of human placenta lactogen during the period of EPO increase.

Conclusions
 The data confirm our earlier results that fenoterol increases EPO concentrations following haemorrhage. In this model it was not necessary to stimulate EPO production prior to pharmacological treatment.
Effect of food on the bioavailability of triclabendazole in patients with fascioliasis
Authors: Lecaillon J. B. , Godbillon J. , Campestrini J. , Naquira C. , Miranda L. , Pacheco R. , Mull R. , Poltera A. A.
Published: March 2003

Aims
 Preliminary results indicate higher absorption of triclabendazole (TCBZ) administered postprandially. Therefore, the influence of food on the pharmacokinetics of TCBZ and its active sulphoxide (TCBZ‐SO) and sulphone (TCBZ‐SO2) metabolites was investigated.

Methods
 Two single doses (10 mg kg−1 ) of TCBZ were administered to 20 patients with fascioliasis. Ten patients were first given the drug after a high energy breakfast and then, 48 h later, after an overnight fast. The other 10 patients first received the drug in fasting state and then, 48 h later, after breakfast. A low energy breakfast was served 2 h after drug administration for fasting state.

Results
 Compared with the fasting state, an increased AUC and Cmax after food intake (significant, P<0.0001) was shown from the values of TCBZ, TCBZ‐SO and TCBZ‐SO2. The mean AUC for TCBZ (fasting: 1.55, fed: 5.72 μmol l−1 h), TCBZ‐SO (fasting: 177, fed: 386 μmol l−1 h) and TCBZ‐SO2 (fasting: 13.9, fed: 30.5 μmol l−1 h) indicated a large availability increase with food and the strong systemic predominance of the active sulphoxide metabolite over the unchanged drug. (All patients were cured at the end of the trial except one who required a second course of two postprandial doses of triclabendazole (10 mg kg−1 each). Tolerability to the treatment among the patients was good.

Conclusions
 The administration of triclabendazole with food is recommended for improved systemic availability in patients with fascioliasis or paragonimiasis.
Plasma hydroxy metronidazole/metronidazole ratio in anti‐HCV carriers with and without apparent liver disease
Authors: Da Silva C. M. F. , David F. L. , Muscará M. N. , Sousa S. S. , Ferraz J. G. P. , De Nucci G. , Polimeno N. C. , Pedrazzoli Jr J.
Published: March 2003

Aims
 To evaluate plasma hydroxy‐metronidazole/metronidazole ratio as a dynamic liver function test in HCV‐infected individuals with/without liver disease, in the absence of liver cirrhosis.

Methods
 Metronidazole was administered intravenously in healthy volunteers, asymptomatic anti‐HCV‐positive blood donors, and in chronic hepatitis C patients. Serology to HCV was determined by a second generation assay and confirmed by gelatin particle agglutination test using recombinant antigens C22‐3 and C200. Plasma concentration of metronidazole and hydroxy‐metronidazole was measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min following the end of metronidazole infusion.

Results
 Chronic hepatitis C patients had abnormal liver enzymes, while healthy volunteers and anti‐HCV‐positive blood donors had normal liver biochemistry tests. Plasma metronidazole concentration was similar in all groups studied. Plasma hydroxy‐metronidazole/metronidazole ratio was significantly reduced in HCV‐infected subjects, an effect observed 10 min after the end of drug infusion.

Conclusions
 Metronidazole clearance is impaired in anti‐HCV‐positive blood donors and chronic hepatitis C patients, indicating that HCV is capable of affecting liver function at early stages of the disease. The metronidazole clearance test can detect impaired liver function in HCV‐infected individuals even in the absence of liver cirrhosis.
Therapeutic drug monitoring—antiepileptic drugs
Authors: Eadie M. J.
Published: March 2003

Aims
 To provide a brief critical review of the basis and contemporary practice of monitoring the concentrations of antiepileptic drugs in biological fluids.

Methods
 The review is based on literature data and observations from clinical practice.

Results
 As experience has accumulated, monitoring of antiepileptic drug concentrations has come to be applied mainly to certain of the drugs when present in whole plasma. For these drugs there is a reasonably established relationship between drug concentrations and biological effects, but attention still needs to be paid to issues such as the timing of the measurements in relation to drug intake, the presence or absence of steady‐state conditions, the presence in plasma of active metabolites and possible nonlinear pharmacokinetics of particular agents e.g. phenytoin.

Conclusions
 Plasma antiepileptic drug concentration monitoring is coming to be used in a more thoughtful and critical manner. Lack of adequate knowledge of matters such as the relationship between the plasma concentrations and antiepileptic and toxic effects of the drugs, not only the newer, but also the longer established ones, in particular clinical situations, remains more important than deficiencies in analytical methodology in limiting the clinical usefulness of antiepileptic drug concentration monitoring.
Pharmacokinetic‐pharmacodynamic model relating zabiciprilat plasma concentrations to brachial and femoral haemodynamic effects in normotensive volunteers
Authors: Bellissant Eric , Giudicelli Jean‐François
Published: March 2003

Aims
 To investigate, in healthy volunteers, the relationships between the plasma concentrations (C, ng ml−1 ) of zabiciprilat, the active metabolite of the angiotensin I‐converting enzyme inhibitor (ACEI) zabicipril, and the effects (E) induced on plasma converting enzyme activity (PCEA, nmol ml−1 min−1 ), brachial and femoral artery flows (BAF, FAF, ml min−1 ), and brachial and femoral vascular resistances (BVR, FVR, mmHg.s ml−1 ) after a single oral administration of two doses (0.5 and 2.5 mg) of zabicipril.

Methods
 The study was placebo‐controlled, randomized, double‐blind and crossover. E was related to C by the Hill model, E=Emax.Cγ/(CEγ50+Cγ ), fitted to the data of both doses simultaneously.

Results
 We obtained (mean±s.d.) Emax=−99±1%, CE50=2.2±1.0 ng ml−1 and γ=1.0±0.4 for PCEA, Emax=55±26 ml min−1, CE50=5.1±4.0 ng ml−1 and γ=2.4±1.6 for BAF, and Emax=−45±10%, CE50=2.0±1.3 ng ml−1 and γ=2.3±1.4 for BVR. The parameters obtained for FAF and FVR were similar to those obtained for BAF and BVR, respectively. The CE95 (C required to induce 95% of Emax ) varies from 7 to 17 ng ml−1 for haemodynamic effects.

Conclusions
 As zabiciprilat peak plasma concentrations average 20 ng ml−1 after the 2.5 mg dose of zabicipril, this dose of the drug should be sufficient to induce optimal haemodynamic effects.
The lignocaine metabolite (MEGX) liver function test and P‐450 induction in humans
Authors: Reichel Christoph , Skodra Thorsten , Nacke Axel , Spengler Ulrich , Sauerbruch Tilman
Published: March 2003

Aims The N‐deethylation of lignocaine to monoethylglycinexylidide (MEGX) is partially catalysed by the rifampicin inducible P‐450 isoenzyme CYP3A4. This has led to the use of the MEGX test (MEGX plasma concentrations after i.v. lignocaine) as a marker of CYP3A4 activity. To test this hypothesis, we studied lignocaine and MEGX plasma pharmacokinetics.

Methods Ten healthy volunteers received rifampicin (600 mg day−1 ) for 6 days, resulting in a four‐ to sixfold increase in urinary 6β‐hydroxycortisol output. On days 1 and 7 (pretreatment), day 11 (treatment), and day 14 (48 h after rifampicin), 50 mg lignocaine i.v. was administered. MEGX concentrations at 30 min [MEGX30min] were assessed and normalised to MEGX test results after 1 mg kg−1 lignocaine. On days 7 and 14 the lignocaine and MEGX plasma concentrations were measured over a 300 min period. MEGX test results and lignocaine and MEGX plasma pharmacokinetics before and after induction with rifampicin were compared.

Results The lignocaine plasma clearance increased from 7.5±1.2 ml min−1 kg−1 before to 8.6±2 ml min−1 kg−1 (P=0.026) after induction. The normalised MEGX30min concentrations increased from 61±14 (day 7) to 82±34 μg l−1 (day 14) by a mean of 21 μg l−1 (95% confidence interval: −3 to 44 μg l−1 ) (P=0.055).

Conclusion An insignificant increase of MEGX plasma concentrations was found in 10 volunteers after induction of CYP3A4 activity by rifampicin. Therefore, the MEGX test is not a sensitive marker of P‐450 induction in healthy human liver.
Attenuation by ACE inhibitor drugs of α‐adrenoceptor sensitivity in human vessels: possible differences related to drug lipophilicity
Authors: Kimura Masahiko , Umemura Kazuo , Kosuge Kazuhiro , Nishimoto Masahiko , Ohashi Kyoichi , Nakashima Mitsuyoshi
Published: March 2003

Aims We investigated the effect of angiotensin converting enzyme inhibitors (ACEIs) on postsynaptic adrenoceptor sensitivity and compared the effect of the lipophilic ACEI, quinapril, and that of hydrophilic agent, enalapril in human vessels.

Methods α‐adrenoceptor sensitivity was evaluated using the dorsal hand vein compliance technique. The dose–response curves of vasoconstriction to phenylephrine and prostaglandin F2α were obtained in healthy male volunteers.

Results The ACEIs shifted the dose–response curve of phenylephrine to the right and raised the median effective dose (ED50; 189.3 (57.6 ng min−1 ) of phenylephrine. Following quinapril administration, ED50 increased to 481.1 (101.8 ng min−1 compared with 266.8 (55.8 ng min−1 after enalapril (95% CI for differences; 31.1–397.5 ng min−1 ). Quinapril administration had no effect on the dose–response curve of PGF2α.

Conclusions ACE inhibition attenuates α‐adrenoceptor sensitivity in human vessels. The effect of quinapril, a lipophilic ACEI, was greater than that of enalapril, a hydrophilic ACEI. Lipophilic ACEIs may be more potent in vasodilating effect than hydrophilic ACEIs. Angiotensin II concentration in tissue rather than that in plasma may contribute to the α‐adrenoceptor sensitivity of the vessels.
The effects of age and gender on the pharmacokinetics of irbesartan
Authors: Vachharajani Nimish N. , Shyu Wen Chyi , Smith Robert A. , Greene Douglas S.
Published: March 2003

Aims Single dose pharmacokinetics and safety of irbesartan, an angiotensin II receptor antagonist, were evaluated in healthy young and elderly male and female subjects.

Methods Irbesartan was administered as two 25 mg capsules after a 10 h fast to 12 young men, 12 young women, 12 elderly men and 12 elderly women. Serial blood and urine sample were collected up to 96 h after the dose. Plasma and urine samples were analysed for irbesartan by h.p.l.c./fluorescence methods.

Results No statistically significant gender effects were observed in peak plasma concentration (Cmax ), area under the curve (AUC), and terminal elimination half‐life (t1/2 ) of irbesartan. The geometric mean AUC and Cmax increased by about 43% and 49%, respectively, in the elderly subjects. Also the time to peak was significantly shorter in the elderly subjects compared with that observed in the young subjects. Renal clearance of irbesartan was significantly reduced in the elderly females but this reduction is not likely to be of any clinical relevance since less than 3% of the administered dose of irbesartan is excreted unchanged in the urine.

Conclusions Although there was an effect of age on the pharmacokinetics of irbesartan, based on the safety and efficacy profile, no adjustment in irbesartan dosage is necessary with respect to age or gender.
Pharmacokinetic and pharmacodynamic profile of donepezil HCl following multiple oral doses
Authors: Rogers  , Cooper  , Sukovaty  , Pederson  , Lee  , Friedhoff
Published: March 2003

Aim The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of donepezil HCl, a new, chemically distinct and specific acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer’s disease, following multiple‐dose administration.

Methods This was a double‐blind, randomized, placebo‐controlled, multiple‐dose study in healthy male volunteers (n=27). Three dose levels were investigated in sequential order: 1, 3 and 5 mg. Each dose was administered orally, once a day, for 21 consecutive days. Donepezil concentrations in plasma were quantified by HPLC. Pharmacodynamic activity was determined by the radioenzymatic measurement of erythrocyte membrane acetylcholinesterase (rbc‐AChE) inhibition.

Results The pharmacokinetic disposition of donepezil was observed to be dose proportional. The mean terminal disposition half‐life was 79.5±19.0 h which resulted in a slow approach to steady state (14–21 days). A four‐ to sixfold increase in donepezil plasma concentration was observed during this time; however, no further increase was evident after achievement of steady state. The mean donepezil plasma concentration at steady state (Css ) was 14.2 ng ml−1. Neither the rate of accumulation nor the rate of clearance was dose dependent. Inhibition of rbc‐AChE was directly correlated with donepezil concentration over a wide concentration range, with the higher concentrations showing the expected hyperbolic relationship. Donepezil was well tolerated by all subjects with no clinically significant changes in laboratory or physical parameters observed at any dose.

Conclusions The pharmacokinetics of donepezil were found to be dose proportional following the administration of multiple doses to healthy volunteers. A predictable relationship was also observed between plasma donepezil concentrations and rbc‐AChE inhibition. The half‐life of donepezil makes it suitable for once‐daily dosing.
Acarbose is an effective adjunct to dietary therapy in the treatment of hypertriglyceridaemias
Authors: Malaguarnera  , Giugno  , Ruello  , Rizzo  , Motta  , Mazzoleni
Published: March 2003

Aims In diabetics, acarbose causes a reduction of blood glucose and triglyceride levels. The aim of this study was to assess the effect of this drug in non diabetic subjects with hypertriglyceridaemia.

Methods Thirty non diabetic patients with hypertriglyceridaemia type IIb or IV (24 males, six females; mean age 51.1±10.2 years) were studied. They were stratified into two groups depending on their basal triglyceride concentration (group A: triglyceride values ≤4.5 mmol l−1; group B triglyceride values >4.5 mmol l−1 ). Treatment consisted of 4 week courses of diet plus acarbose (50 mg twice daily) alternating with 4 weeks of diet alone for a total period of 16 weeks.

Results Mean triglyceride values decreased significantly during the first and third cycles of therapy, i.e. diet plus acarbose treatment cycles in both patient groups. Group A also had significant reductions in total cholesterol and HDL cholesterol concentrations after completion of the acarbose treatment. Reduction of triglyceride levels was observed after both acarbose courses in patients affected by hypertriglyceridaemia type IIb. A marked reduction of triglyceride concentrations was achieved by patients affected by hypertriglyceridaemia type IV after the second acarbose course only.

Conclusions Diet alone did not reduce triglyceride concentrations to normal values in our patients. The data suggest that acarbose is a useful adjunct to dietary control in non‐diabetic patients affected by severe hypertriglyceridaemia.