bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of mini‐dose suxamethonium to facilitate the insertion of a laryngeal mask airway
Authors: Ho K. M. , Chui P. T.
Published: March 2003

The use of mini‐dose suxamethonium to facilitate the insertion of a laryngeal mask airway was investigated. Sixty patients were assigned randomly in a double‐blind manner to receive 0.9% sodium chloride or suxamethonium 0.1 mg.kg−1 intravenously, following intravenous induction with propofol 2.5 mg.kg−1. The laryngeal mask was inserted after the first attempt in 87% of patients. Mini‐dose suxamethonium improved the correct positioning of the laryngeal mask during the first attempt (93 vs. 67%, p < 0.02), decreased the incidence of swallowing (p < 0.001), gagging (p < 0.001) and head or limb movement (p < 0.05). Laryngeal mask insertion was graded as easy in 93% of patients who had mini‐dose suxamethonium, compared with 60% in the placebo group (p < 0.01). The duration of apnoea between the two groups was not significantly different (0.54 vs. 0.61 min, p = 0.46). The total dose of propofol needed to insert the laryngeal mask was lower in the suxamethonium group (2.57 vs. 3.25 mg.kg−1, p < 0.01) and was associated with less hypotension (p < 0.05). Fasciculation (17%) and mild myalgia (23%) were common despite the small dose of suxamethonium used. In conclusion, mini‐dose suxamethonium facilitates laryngeal mask insertion. Myalgia is common and the technique is not recommended for patients who are prone to suxamethonium myalgia.
Anterior mediastinal masses: an anaesthetic challenge
Authors: Goh M. H. , Liu X. Y. , Goh Y. S.
Published: March 2003

A patient with a large anterior mediastinal mass with minimal respiratory symptoms presented for a diagnostic biopsy of the mass. A pre‐operative thoracic computed tomographic scan demonstrated narrowing of the distal trachea, and right and left main stem bronchi. An awake intubation was done. Thiopentone and muscle relaxant were given and surgery commenced. High airway pressure developed and ventilation became difficult, although oxygenation remained satisfactory throughout. Anaesthetic implications are discussed. We recommend that patients with more than 50% obstruction of the airway at the level of the lower trachea and main bronchi have their femoral vessels cannulated in readiness for cardiopulmonary bypass.
Use of the cuffed oropharyngeal airway for manual ventilation by nonanaesthetists
Authors: Rees S. G. O. , Gabbott D. A.
Published: March 2003

We studied the use of the cuffed oropharyngeal airway in 100 ASA I and II anaesthetised patients. In the first 50 patients (group A), an experienced anaesthetist inserted the airway. The optimum sizes and cuff volumes for manual ventilation in adult males and females were found to be sizes 11 and 10 with up to 60 ml and 50 ml in each cuff, respectively. Manual ventilation was clinically successful in 49/50 (98%) of these patients. Using these recommendations and following a brief tutorial, a group of 50 nonanaesthetic, basic life‐support providers attempted to insert a cuffed oropharyngeal airway and manually ventilate the lungs of a subsequent 50 patients (group NA). Clinically adequate tidal volumes were achieved within 45 s in 47/50 (94%) patients in this group. A persistent leak was present in 21/49 (43%) and 24/47 (51%) of the successful insertions in each group, but this did not affect the ability to ventilate the lungs adequately. The cuffed oropharyngeal airway may offer an effective method of providing adequate ventilation during resuscitation by nonanaesthetic hospital staff.
Evoked potential monitoring in anaesthesia and analgesia
Authors: Kumar A. , Bhattacharya A. , Makhija N.
Published: March 2003

Electrophysiological monitoring of selected neural pathways of the brain, brainstem, spinal cord and peripheral nervous system has become mandatory in some surgery of the nervous system where preventable neural injury can occur. Evoked potentials are relatively simple methods of testing the integrity of various aspects of the nervous system. This review covers the variety of evoked potentials that can be monitored and outlines the principles of their measurement. Their use in specific situations and how factors such as anaesthesia might affect them is presented.
A comparison of the intubating laryngeal mask tracheal tube with a standard tracheal tube for fibreoptic intubation
Authors: Lucas D. N. , Yentis S. M.
Published: March 2003

We conducted a prospective randomised study to compare the intubating laryngeal mask tracheal tube with a standard tube, for ease of tracheal intubation over a fibrescope. Thirty‐six patients were investigated, using a sequential analysis technique. Ease of intubation was improved when the intubating laryngeal mask tracheal tube was used compared with the standard tube (p = 0.0009). Median (interquartile range [range]) intubation times (time from the tube's tip being level with the patient's teeth to successful placement) were 1.5 (1–2.3 [1–3]) s when the intubating laryngeal mask tracheal tube was used and 5 (3–7.3 [3–13]) s when the standard tube was used (p < 0.0001).
Single injection peribulbar anaesthesia
Authors: Frow M. W. , Miranda‐Caraballo J. I. , Akhtar T. M. , Hugkulstone C. E.
Published: March 2003

A prospective, observer blinded study on 51 patients undergoing cataract surgery was conducted to assess Total Upper Eyelid Drop as a new end‐point marker to single injection peribulbar block. At present, no such clinical marker exists to stop clinicians injecting more than necessary volumes of local anaesthetic and therefore to prevent dangerous increases in intra‐ocular pressure. Using this technique, satisfactory ocular akinesia was achieved in 90% of eyes 10 min after injection. Operating conditions were satisfactory in 98% of cases. The mean (range) volume injected was 9.1 (4–15) ml. The mean increase in intra‐ocular pressure immediately after injection was 6.9 mmHg, decreasing to 0.7 mmHg after 5 min without the application of ocular compression. We found a negative correlation between the increase in intra‐ocular pressure and the volume of injection (p < 0.002), which has never previously been reported. We conclude that Total Upper Eyelid Drop is a reliable endpoint marker for producing satisfactory operating conditions for cataract surgery while minimising increases in intra‐ocular pressure and its use may therefore avoid the risks associated with ocular compression.
Evaluation of a spinal needle locking device for use with the combined spinal epidural technique
Authors: Stocks G. M. , Hallworth S. P. , Fernando R.
Published: March 2003

Success of the ‘needle‐through‐needle’ technique for combined spinal epidural analgesia requires the immobilisation of the spinal needle during intrathecal injection. A device that achieves this was evaluated in 200 labouring women, randomly allocated to receive a combined spinal epidural using the CSEcure® (SIMS Portex, UK) locking needle or a conventional, non‐locking technique. Data collection included the incidence of dural click as the spinal needle penetrated the dura mater, presence of cerebrospinal fluid in the spinal needle hub and the number of technical failures with the spinal component. Successful dural punctures with the spinal needle were similar for locking and non‐locking needles (99.0 vs. 98.0%; p = 0.55), despite a small but significant reduction in dural click with the locking needle compared with the non‐locking technique (97.0 vs. 84.7%; p < 0.01). Although not statistically significant, there was a higher number of technical failures, mainly due to spinal needle movement, in the non‐locking group (9.1 vs. 3.1%; p = 0.08). The locking needle device may be a useful alternative to conventional methods for combined spinal epidural analgesia.
Reversing sevoflurane‐associated Q–Tc prolongation by changing to propofol
Authors: Kleinsasser A. , Loeckinger A. , Lindner K. H. , Keller C. , Boehler M. , Puehringer F.
Published: March 2003

Congenital or acquired forms of the long Q–T syndrome may result in ventricular tachycardia known as torsade de pointes. Many drugs including volatile anaesthetics modify the Q–T interval. Sevoflurane is known to prolong of the rate‐corrected Q–T interval (Q–Tc). The objective of this study was to determine whether the sevoflurane‐associated Q–Tc prolongation is rapidly reversible when propofol is substituted for sevoflurane. Thirty‐two female patients were allocated to two groups. All patients received sevoflurane induction and anaesthesia for 15 min. In one group, sevoflurane was then discontinued and anaesthesia maintained on propofol for another 15 min. The second group received sevoflurane anaesthesia for 30 min. Measurements were taken before, and 15, 20, 25 and 30 min after induction. Q–Tc prolongation was significantly reduced 5, 10 and 15 min after propofol had been substituted for sevoflurane. We conclude that the sevoflurane‐associated Q–Tc prolongation is fully reversible within 15 min when propofol is substituted for sevoflurane.
Undiagnosed adult diastematomyelia associated with neurological symptoms following spinal anaesthesia
Authors: Wenger M. , Hauswirth C. B. , Brodhage R. P.
Published: March 2003

Spinal anaesthesia is a safe, routinely performed procedure. However, in patients with lumbar cutaneous abnormities or deformities of the lower extremities, a previously undetected spinal anomaly may be present. In such patients, it may be prudent to avoid central neuraxial block to prevent neural damage. This instructive case presents such an adult patient in whom previously undiagnosed diastematomyelia, low conus and tethered cord was discovered only in the assessment of postspinal neurological symptoms.
The effects of rigid collar placement on intracranial and cerebral perfusion pressures
Authors: Hunt K. , Hallworth S. , Smith M.
Published: March 2003

Rigid collars are routinely used to immobilise the cervical spine during early management of trauma victims until spinal injury is excluded. Spinal injuries commonly coexist in patients with severe head injury, and there is still uncertainty as to whether application of a rigid collar may adversely affect intracranial pressure. The aim of this study was to examine this effect by applying rigid collars to patients with traumatic head injury. The results showed a significant rise from the baseline intracranial pressure when the collars were applied (mean rise = 4.6 mmHg, p < 0.0001). The mean rise in intracranial pressure was greater in those patients with a baseline intracranial pressure > 15 mmHg compared to those with a baseline intracranial pressure < 15 mmHg (p < 0.05). Since there was no significant change in cardiorespiratory parameters during this time, venous compression in the neck seems a likely explanation for the effect observed. These findings suggest that in head‐injured patients, rigid collars should be removed as soon as cervical spine injury has been excluded or, if this is delayed, an alternative method of spinal stabilisation considered.
The effect of phenylephrine and norepinephrine in patients with chronic pulmonary hypertension*
Authors: Kwak Y. L. , Lee C. S. , Park Y. H. , Hong Y. W.
Published: March 2003

In this study the effect of phenylephrine and norepinephrine for the treatment of systemic hypotension were evaluated in patients with chronic pulmonary hypertension. When systemic hypotension (systolic arterial pressure < 100 mmHg) occurred following induction of anaesthesia, either phenylephrine or norepinephrine were infused in a random manner to raise the systolic blood pressure by 30% and 50% above baseline values. Norepinephrine decreased the ratio of pulmonary arterial pressure to systemic blood pressure without a change in cardiac index. However, phenylephrine did not increase arterial blood pressure by more than 30% from baseline in one‐third of patients and decreased cardiac index without a significant decrease in ratio of pulmonary arterial pressure to systemic blood pressure. These vasoconstrictors showed different systemic and pulmonary haemodynamic effects in patients with chronic pulmonary hypertension as compared to acute pulmonary hypertension. Norepinephrine was considered to be preferable to phenylephrine for the treatment of hypotension in patients with chronic pulmonary hypertension.
Survey of the use of the gum elastic bougie in clinical practice
Authors: Latto I. P. , Stacey M. , Mecklenburgh J. , Vaughan R. S.
Published: March 2003

Summary Data were collected prospectively on the use of the gum elastic bougie in 200 patients. The bougie was successfully inserted into the trachea and tracheal intubation was accomplished in 199 cases. The bougie was inserted into the trachea at the first attempt in 178 cases. In nine cases (4.5%) a second, more experienced, clinician was required. In 173 cases, the grades of view were recorded before and after the application of laryngeal pressure; pressure improved the view in 80 cases (46%), had no effect in 89 (51%) and worsened the view in four cases (2%). Various recommendations for optimal external laryngeal pressure and use of the bougie were not followed on 15–64% of occasions. There is a need for better education in these techniques.
The peri‐operative implications of herbal medicines
Authors: Hodges P. J. , Kam P. C. A.
Published: March 2003

Summary An increasing number of patients are taking herbal medicines such as echinacea, garlic, ginkgo biloba, ginseng, St John's Wort, valerian, ephedra, kava, grapefruit juice and ginger. Although these herbal medications are considered ‘natural’ products that may have some benefits, adverse effects such as increased bleeding tendencies and drug interactions are associated with their use. Surgeonsand anaesthetists may be unaware of their patients' use of these medications because it is common for patients not to disclose their use of this form of medication, and both surgeons andanaesthetists often fail to enquire about their use. Anaesthetists and surgeons must be familiar with the effects of herbal medicines and should specifically enquire about the use of herbal medicines during pre‐operative assessment. Currently available data suggest that all herbal medicines should be ceased 2 weeks before surgery.
An assessment of the ability of impedance respirometry distinguish oesophageal from tracheal intubation
Authors: Mehta K. H. , Turley A. , Peyrasse P. , Janes J. , Hall J. E.
Published: March 2003

Summary Accidental oesophageal intubation is still an important cause of anaesthetic morbidity and mortality. This study investigated the use of impedance respirometry to determine the position of a tracheal tube. Seventy‐nine patients undergoing general anaesthesia requiring tracheal intubation with muscle relaxation were recruited to the study. After pre‐oxygenation, tracheal tubes were placed in both the oesophagus and trachea; a breathing system was attached to one tube chosen randomly. A blinded observer was required to correctly identify the position of the tube within six tidal ventilations. The position of every tube connected to the breathing system was correctly identified. The median time to correctly identify tracheal and oesophageal tubes was 3 and 5 s, respectively. The median number of breaths to identify tracheal and oesophageal tubes was two for both groups. Every tube position was identified within the required six breaths. Impedance respirometry is a reliable method for diagnosing tracheal tube position.
Effect of xenon on cerebral autoregulation in pigs
Authors: Schmidt M. , Marx T. , Papp‐Jambor C. , Schirmer U. , Reinelt H.
Published: March 2003

There are little data on the effect of anaesthetic concentrations of xenon on cerebral pressure autoregulation. In this study, we have investigated the effect of 79% xenon inhalation on cerebral pressure autoregulation and CO2 response in pigs. Ten pigs were randomly allocated to receive xenon 79% or halothane anaesthesia, respectively, in a crossover designed study. Halothane was used to validate the experimental set‐up. Transcranial Doppler was performed to determine the mean flow velocities in the middle cerebral artery (vMCA) during defined cerebral perfusion pressures and during normo‐, hyper‐ and hypoventilation. The results showed that the inhalation of 79% xenon preserved cerebral autoregulation during conditions of normo‐, hyper‐ and hypoventilation and at different cerebral perfusion pressures in pigs. These results suggest that with the inhalation of xenon, in the highest concentration suitable for a safe clinical use, cerebral autoregulation is preserved.
Assessment of the Ventrix parenchymal intracranial pressure monitoring probe (NL950‐P) and Monitor (NL950‐100) in a 3 Tesla magnetic resonance scanner
Authors: Coles J. P. , Steiner L. A. , Martin J. , Donovan T. , Hutchinson P. J. , Carpenter T. A. , Menon D. K.
Published: March 2003

Summary Magnetic resonance (MR) imaging and spectroscopy provide important information in patients with acute head injury. However, optimal patient management requires intracranial pressure (ICP) monitoring. There are few reports on the use of ICP sensors in an MR environment. We tested the Ventrix parenchymal intracranial pressure monitoring probe and monitor (Integra Neurosciences®, USA), modified by the use of a fibre‐optic extension cable, within a 3 Tesla MR system. The device performed well in the MR environment, but one element within the fibre‐optic extension was significantly ferromagnetic. The ICP probe produced a small susceptibility artefact on spin echo images, and a larger artefact on gradient echo images. The MR safety of the integrated system is probably acceptable, but could be easily improved with minor modifications. Although the system is MR compatible and produces generally acceptable imaging even at 3 Tesla, there is significant degradation of image quality during gradient echo sequences.
Anaesthetists' attitudes to teamwork and safety
Authors: Flin R. , Fletcher G. , McGeorge P. , Sutherland A. , Patey R.
Published: March 2003

Summary A questionnaire survey was conducted with 222 anaesthetists from 11 Scottish hospitals to measure their attitudes towards human and organisational factors that can have an impact on effective team performance and consequently on patient safety. A customised version of the Operating Room Management Attitude Questionnaire (ORMAQ) was used. This measures attitudes to leadership, communication, teamwork, stress and fatigue, work values, human error and organisational climate. The respondents generally demonstrated positive attitudes towards the interpersonal aspects of their work, such as team behaviours and they recognised the importance of communication skills, such as assertiveness. However, the results suggest that some anaesthetists do not fully appreciate the debilitating effects of stress and fatigue on performance. Their responses were comparable with (and slightly more favourable than) those reported in previous ORMAQ surveys of anaesthetists and surgeons in other countries.
Prospective randomised double‐blind comparative study of rocuronium and pancuronium in adult patients scheduled for elective ‘fast‐track’ cardiac surgery involving hypothermic cardiopulmonary bypass
Authors: Thomas R. , Smith D. , Strike P.
Published: March 2003

Summary The majority of cardiac anaesthetists in the UK use pancuronium for fast‐track cardiac surgery. We compared the duration of action of pancuronium and rocuronium in patients undergoing fast‐ track hypothermic cardiopulmonary bypass and cardiac surgery. We determined whether patients would have had residual neuromuscular blockade at extubation. Twenty patients were randomly allocated to receive either pancuronium 0.1 mg.kg−1 or rocuronium 1 mg.kg−1. Neuromuscular function was assessed by acceleromyography; spontaneous recovery was evaluated by the train‐of‐four ratio measured at the adductor pollicis longus muscle. Median times to recover train‐of‐four ratio of 0.9 were 3 h 38 min for rocuronium and 7 h 52 min for pancuronium. The median difference in recovery times was 4 h 15 min (95% CI 2 h 30 min to 6 h 20 min; p = 0.0003 by Mann–Whitney test). None of the patients in the rocuronium group and seven of 10 patients in the pancuronium group had their extubations delayed because of residual neuromuscular blockade. Unless fast‐track patients have neuromuscular function assessed before extubation, pancuronium should not be used.
The generation and degradation of marine terraces
Authors: Anderson  , Densmore  , Ellis
Published: March 2003

Marine terraces are ephemeral planar landforms. While tectonic and climatic forcings responsible for the generation of existing marine terraces have operated for at least 1 Myr, terraces have been completely removed by erosion above a given altitude (and hence above a given age). Above this altitude, the landscape has forgotten that it was once terraced. We ask what controls this characteristic time‐scale, which we term the ‘forget time’, in a landscape. We approach the problem with simple scaling arguments, and 1‐D numerical models of landscape evolution.

Using a simple cliff erosion model with a realistic sea‐level history, rock uplift and a cliff retreat rule, we find that the most important means of terrace removal is through the deeper transgression of a subsequent sea cliff into the landmass. The sequence of preserved terraces depends upon the history of sea cliff incursion into the landmass. The extent of sea cliff incursion depends on the duration of the sea‐level highstand, the far‐field wave energy input and the degree to which bathymetric drag dissipates wave energy. This portion of the marine terrace survival problem is an example of a common problem in geomorphology, in which the record of past tectonic or climatic events is rendered incomplete by the potential for younger events to wipe the topographic slate clean.

While sea cliffs decay through time, their form can still be recognized many hundreds of thousands of years after formation. This reflects the diffusive nature of their decay: early rapid evolution and lowering of maximum slopes yields to slower rates through time. Incision by streams, on the other hand, is rapid, as the streams respond to base‐level history driven by sea‐level changes. The rate of incision reflects the local climate conditions, and is limited by the rate of base‐level fall.

The principal means of vanquishing a marine terrace is by backwearing of slopes adjacent to these incising streams. The forget time should be proportional to the spacing between major incising streams and to the angle of hillslope stability, and should be inversely proportional to the rate of channel incision. This yields an overestimate of the forget time, as the terraced interfluves are reduced as well by the headward incision of tributary streams.

The resulting landscape may be viewed as a terraced fringe separating the sea from the fully channellized landscape. Over time‐scales corresponding to many glacial–interglacial sea‐level oscillations, this fringe can achieve a nearly steady width. The rate of generation of new terraced landscape, reflecting the uplift rate pattern, is then balanced by the rate at which the terraces are erased beyond recognition by channel and hillslope processes. The width of this fringe should depend upon the precipitation, and upon the distance to the nearest drainage divide, both of which limit the maximum power available to drive channel incision.
Contained turbidites used to track sea bed deformation and basin migration, Sorbas Basin, south‐east Spain
Authors: Haughton P.
Published: March 2003

ABSTRACT The mechanisms driving subsidence in late orogenic basins are often not easily resolved on account of later fault reactivation and a rapidly changing stress field. Contained turbidites in such basins provide a unique opportunity of monitoring sea bed deformation and evolving bathymetry and hence patterns of subsidence during basin filling. A variety of interpretations have been proposed to explain subsidence in Neogene basins in SE Spain, including extensional, strike‐slip and thrust top mechanisms. Ponded turbidite sheets on the floor of the Neogene Sorbas Basin (SE Spain) were deposited by sand‐bearing currents which ran into enclosed bathymetric deeps where they underwent rapid suspension collapse. The structure and distribution of these sheets (and the thick mudstone caps which overlie them) act as a proxy for the containing sea bed bathymetry at the time of deposition. An analysis of the sheet architecture helps identify a trough‐axial zone of syndepositional faulting and reveals a westwards stepping of the ponding depocentre with time. Fault breaks at the sea bed influenced the position of flow arrest and the distribution of sandstone beds on the basin floor. Westward stepping of the deeper bathymetry was episodic and probably controlled by transverse faults. Re‐locations of the depocentre were accompanied by the destabilization of carbonate sand stores on the margins of the basin, resulting in the repeated emplacement of large‐volume carbonate megabeds and calciturbidites. The fill to the Sorbas Basin was shingled by the onset of compression in the east attributed to transfer of slip between intersecting strike‐slip fault strands. A sinistral fault (a splay of the Carboneras Fault System) propagated through the evolving basin fill from the east as the eastern part of the basin became inverted and the locus of subsidence migrated into the Tabernas area 20 km area to the west. The sedimentological analysis of the basin fill helps see through a late dextral overprint which ultimately juxtaposed basement rocks to the south against the inverted and upended basin, along a late slip‐modified unconformity. Conventional palaeostress analysis of fractures along the basin margin fails to see past this late dextral shearing event. Basin migration parallel to the E–W‐orientated basin axis, slip‐reversal (sinistral to dextral) and the active involvement of strike‐slip faults are now identified as important aspects of the evolution of the Sorbas Basin during the latestTortonian.
Low‐amplitude, synsedimentary folding of a deltaic complex: Roda Sandstone (lower Eocene), South‐Pyrenean Foreland Basin
Authors: López‐Blanco M. , Marzo M. , Muñoz J.A.
Published: March 2003

The South‐Pyrenean Foreland Basin is a sedimentary trough developed during Palaeogene times in response Pyrenean orogenesis. The structural development of the chain progressively involved the foreland basin deposits resulting in synsedimentary thrusting and growth of folds through the basin. The lower Eocene Roda Sandstone was deposited in a shallow‐marine environment whose topography (bathymetry) was modified by a series of growing gentle folds. This synsedimentary folding is evidenced in the field (i) thickening of sedimentary units above synclinal structures and thinning over anticlines; (ii) carbonate platform deposits growing on top of anticlines; (iii) the areal distribution of benthic foraminifera in transgressive facies assemblages determined by an irregular, fold‐influenced palaeobathymetry; (iv) variation of sandstone palaeocurrents related to the presence of a sedimentary trough formed by the synsedimentary growth of a syncline. In addition, synsedimentary folding has been evidenced from seismic data. In the Roda Sandstone example, the growth of gentle folds occurred in an area with high sedimentation rates (∼0.21 ± 0.06 mm y−1). Due to the high sedimentation rates, exceeding the folds uplift rate (∼0.10 ± 0.01 mm y−1), there are no noticeable unconformities in the growth strata at outcrop scale. However, the effects on the sedimentation are very significant, because the sediments were deposited close to sea level, and thus were very sensitive to fauna and facies distribution.
The effect of duration of dose delivery with patient‐controlled analgesia on the incidence of nausea and vomiting after hysterectomy
Authors: Woodhouse Annie , Mather Laurence E.
Published: March 2003

Aims
 Postoperative nausea and vomiting (PONV) may be exacerbated by postoperative opioid analgesics and may limit patients’ successful use of these medications when used with patient controlled analgesia (PCA). We tested the hypothesis that the rapid change in blood morphine concentration associated with PCA bolus delivery contributed to PONV, and that prolonging its delivery to a brief infusion would result in decreased PONV.

Methods
 Patients, who were receiving morphine for pain relief via patient‐controlled analgesia (PCA) after total abdominal hysterectomy, received 1 mg morphine sulphate incremental doses either over 40 s with a 5 min lockout interval or over 5 min delivery with a 1 min lockout interval. Episodes of nausea, retching and vomiting, along with the use of morphine and the pain relief obtained, were recorded.

Results
 Data from 20 patients in each group were analysed. Contrary to expectations, most patients in both groups reported nausea postoperatively. Those patients receiving morphine over 5 min experienced more episodes of emesis (36) than those receiving the dose over 40 s (17). Most patients receiving the 40 s doses vomited in the first 12 h (median time 8 h), while those receiving the 5 min doses vomited between 12 and 24 h (median time 19 h) (P=0.01). There were no differences between groups in the visual analogue pain scores or use of morphine between groups.

Conclusions
 Reasons for these unexpected findings remain speculative. The high incidence of PONV appears to be inherently high in gynaecological surgery patients and standard antiemetic medication regimens appear to be poorly efficacious. Reasons for the differences in the time‐course of emetic episodes between the two groups may be related to differences in the time‐course of central opioid receptor occupancy.
Gastrointestinal tolerability of meloxicam and piroxicam: a double‐blind placebo‐controlled study
Authors: Lipscomb G. R. , Wallis N. , Armstrong G. , Rees W. D. W.
Published: March 2003

Aims
 The aim of the study was to compare the effects of meloxicam and piroxicam on the gastroduodenal mucosa in healthy adults.

Methods
 Forty‐four healthy volunteers were given a 28 day course of either meloxicam 15 mg, piroxicam 20 mg or placebo. Damage to the oesophageal, gastric and duodenal mucosa was assessed, mucosal blood flow (MBF) measured at endoscopy and biopsies taken for prostaglandin content and microscopic assessment of damage before NSAID administration and during days 1, 7 and 28 of continued intake.

Results
 Maximal macroscopic gastric mucosal damage (median grade+IQR) occurred within 24 h of piroxicam administration, the damage score increasing from 0 to 2.5 (0–3) (P=0.02) at day 1 before falling to 2.0 (0–2) at day 7 and 0 (0–1) at day 28 with resolution of damage observed in six out of the seven subjects who sustained acute injury. No significant macroscopic gastric damage occurred in either of the two other groups although some minor damage was observed in seven subjects taking placebo and five taking meloxicam. There was a trend towards piroxicam causing more acute gastric damage than meloxicam (P=0.06). Baseline antral, body and duodenal MBF were similar in all three groups. No significant changes occurred in any of the groups on any of the visits. There were also no changes in gastric mucosal prostaglandin content in any group.

Conclusions
 These observations suggest that meloxicam causes little acute damage to the upper gastrointestinal tract and piroxicam causes some acute gastric injury but such damage resolves in most subjects by 28 days.
Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service
Authors: Morris Raymond G. , Black Andrew B. , Harris Anne L. , Batty Andrew B. , Sallustio Benedetta C.
Published: March 2003

Aims To review (retrospectively) the relationships between lamotrigine (LTG) dosage and plasma concentrations based on data generated in a routine therapeutic drug monitoring laboratory from a heterogeneous sample of patients with epilepsy. To distinguish patients taking concomitant anti‐epileptic therapy which induced or inhibited drug metabolising enzymes, or a combination of both, together with LTG. To survey medical staff who use a routine LTG assay service with a view to establishing the utility of higher plasma LTG concentrations than those used in early clinical trials.

Methods All patient assays for LTG received over a 12 month period (339 requests from 149 patients) were reviewed and relationships between dosage and concentration calculated and grouped according to concomitant antiepileptic drug therapy. The doctors requesting the tests were surveyed by questionnaire (n=40 of 67 responded). They were asked for details about the patient’s seizure control, rationale used for LTG dosage adjustment and their acceptance of the proposed ‘therapeutic range’ adopted by the laboratory of 3–14 mg l−1.

Results Linear relationships were demonstrated between LTG dosage and concentration for the 3 treatment groups (LTG plus valproic acid (VPA), LTG plus enzyme inducing antiepileptic drugs, and LTG plus VPA and inducers), however, there were significant differences between groups (P<0.001) with a 4.4 fold difference in dosage:concentration ratios between the LTG plus VPA group and the LTG plus inducers group. The questionnaire showed that the therapeutic range was well accepted by 88% of responders, none of whom considered this higher range to be wrong.

Conclusions Metabolic inhibition by VPA was shown to have a marked effect on LTG kinetics, suggesting either a significant LTG dosage reduction is required if plasma LTG concentrations are elevated, or alternatively, higher plasma LTG concentrations could be attained from lower dosages. The higher therapeutic range adopted by the laboratory (3–14 mg l−1 ) was widely accepted and increasingly applied in clinical practice in the management of patients with epilepsy.
Relaxant effects of antidepressants on human isolated mesenteric arteries
Authors: Vila José M. , Medina Pascual , Segarra Gloria , Lluch Paloma , Pallardó Federico , Flor Blas , Lluch Salvador
Published: March 2003

Aims The therapeutic action of tricyclic agents may be accompanied by unwanted effects on the cardiovascular system. The evidence for the effects on vascular and nonvascular smooth muscle comes from animal studies. Whether these studies can be extrapolated to human vessels remains to be determined. Therefore, the present study was designed to investigate the influence of amitriptyline, nortriptyline and sertraline on the contractile responses of human isolated mesenteric arteries to electrical field stimulation, noradrenaline and potassium chloride.

Methods Arterial segments (lumen diameter 0.8–1.2 mm) were obtained from portions of the human omentum during the course of 41 abdominal operations (22 men and 19 women), and rings 3 mm long were mounted in organ baths for isometric recording of tension. In some artery rings the endothelium was removed mechanically.

Results In precontracted artery rings amitriptyline, nortriptyline and sertraline (3×10−7–10−4 m ) produced concentration‐dependent relaxation that was independent of the presence or absence of vascular endothelium. Incubation with indomethacin (3×10−6 m ) reduced the pD2 values thus indicating the participation of dilating prostanoid substances in this response. Amitriptyline and nortriptyline inhibited both the neurogenic‐and noradrenaline‐induced contractions. In contrast, only the highest concentration of sertraline reduced the adrenergic responses. Amitriptyline, nortriptyline and sertraline inhibited contractions elicited by KCl and produced rightward shifts of the concentration‐response curve to CaCl2 following incubation in calcium‐free solution.

Conclusions These results indicate that amitriptyline and nortriptyline could act as adrenoceptor antagonists and direct inhibitors of smooth muscle contraction of human mesenteric arteries, whereas sertraline might principally exert its action only as direct inhibitor of smooth muscle contraction. This relaxant mechanism involves an interference with the entry of calcium.
The antitussive effect of dextromethorphan in relation to CYP2D6 activity
Authors: Abdul Manap  , Wright  , Gregory  , Rostami‐Hodjegan  , Meller  , Kelm  , Lennard  , Tucker  , Morice
Published: March 2003

Aims To test the hypothesis that inhibition of cytochrome P450 2D6 (CYP2D6) by quinidine increases the antitussive effect of dextromethorphan (DEX) in an induced cough model.

Methods Twenty‐two healthy extensive metaboliser phenotypes for CYP2D6 were studied according to a double‐blind, randomised cross‐over design after administration of: (1) Placebo antitussive preceded at 1 h by placebo inhibitor; (2) 30 mg oral DEX preceded at 1 h by placebo inhibitor (DEX30); (3) 60 mg oral DEX preceded at 1 h by placebo inhibitor (DEX60); (4) 30 mg oral DEX preceded at 1 h by 50 mg oral quinidine sulphate (QDEX30). Cough frequency following inhalation of 10% citric acid was measured at baseline and at intervals up to 12 h. Plasma concentrations of DEX and its metabolites were measured up to 96 h by h.p.l.c.

Results Inhibition of CYP2D6 by quinidine caused a significant increase in the mean ratio of DEX to dextrorphan (DEX:DOR) plasma AUC(96) (0.04 vs 1.81, P<0.001). The mean (±s.d.) decrements in cough frequency below baseline over 12 h (AUEC) were: 8% (11), 17% (14.5), 25% (16.2) and 25% (16.9) for placebo, DEX30, DEX60 and QDEX30 treatments, respectively. Statistically significant differences in antitussive effect were detected for the contrasts between DEX60/placebo (P<0.001; 95% CI of difference +80, +327) and QDEX30/placebo (P<0.001, +88, +336), but not for DEX30/placebo, DEX30/DEX60 or DEX30/QDEX30 (P=0.071, −7, +241; P=0.254, −37, +211; P=0.187, −29, +219, respectively).

Conclusions A significant antitussive effect was demonstrated after 60 mg dextromethorphan and 30 mg dextromethorphan preceded by 50 mg quinidine using an induced cough model. However, although the study was powered to detect a 10% difference in cough response, the observed differences for other contrasts were less than 10%, such that it was possible only to imply a dose effect (30 vs 60 mg) in the antitussive activity of DEX and enhancement of this effect by CYP2D6 inhibition.
Thiopurine methyltransferase activity and its relationship to the occurrence of rejection episodes in paediatric renal transplant recipients treated with azathioprine
Authors: Dervieux  , Médard  , Baudouin  , Maisin  , Zhang  , Broly  , Loirat  , Jacqz‐Aigrain
Published: March 2003

Aims Azathioprine is a prodrug commonly used in combination therapy to prevent allograft rejection after renal transplantation. After conversion to 6‐mercaptopurine, the drug is metabolized into 6‐thioguanine nucleotides (6‐TGN) and catabolized by thiopurine methyltransferase (TPMT), an enzyme under monogenic control. The aim of this study was to evaluate the inter‐ and intraindividual variability of red blood cell thiopurine methyltransferase and 6‐TGN concentrations and their relationship to the clinical effects of azathioprine in paediatric patients.

Methods In the present study, the interand intraindividual variations in red blood cell TPMT activity and 6‐TGN concentrations and their relationship to the actions of azathioprine were evaluated during the first year after renal transplantation in 22 paediatric patients.

Results 6‐TGN concentration reached steady‐state values after 6 months and correlated negatively with TPMT activity (P=0.004). Initial TPMT activity (median: 20.8 nmol h−1 ml−1, range 7.8–34.6) and 6‐TGN concentration at steady‐state (median: 80 pmol 8×108–1 cells, range not detected to 366) were not related to the occurrence of rejection episodes during the period of the study. In contrast, TPMT activity and the percentage difference in TPMT activity from the day of transplantation determined at month 1 were higher in the patients with rejection episodes by comparison with those that did not reject during the first 3 months or the first year following transplantation (P<0.005).

Conclusions We report a relationship between TPMT activity and occurrence of rejection in paediatric kidney transplant patients undergoing azathioprine therapy. These data suggest a link between high red blood cell TPMT activity and poor clinical outcome probably caused by rapid azathioprine catabolism.
Nisoldipine improves the impaired erythrocyte deformability correlating with elevated intracellular free calcium‐ion concentration and poor glycaemic control in NIDDM
Authors: Fujita  , Tsuda  , Takeda  , Yu  , Fujimoto  , Kajikawa  , Nishimura  , Mizuno  , Hamamoto  , Mukai  , Adachi  , Seino
Published: March 2003

Aims To explore the mechanisms underlying the impaired erythrocyte deformability (RBC‐df) in diabetic patients, the relationship between erythrocyte intracellular free calcium‐ion concentration ([Ca2+]i) and RBC‐df, and the effects of Ca2+‐channel blocker on [Ca2+]i and RBC‐df were evaluated.

Methods Forty‐eight patients with NIDDM and 24 control subjects were enrolled in this study. [Ca2+]i was determined using fura‐2, and RBC‐df by filtration method expressed as Deformability Index (DI). Erythrocytes were treated with nisoldipine to evaluate the effects of a Ca2+‐channel blocker.

Results [Ca2+]i was significantly higher (82.6 (78.0–87.2) vs 76.6 (74.3–81.2) nmol lRBC−1, P<0.001), and DI was significantly lower (0.14 (0.09–0.28) vs 0.22 (0.16–0.28), P<0.01) in NIDDM than in controls. There was a significant correlation between HbA1c and [Ca2+]i (r=0.38, P<0.01), between HbA1c and DI (r=−0.51, P<0.01), and between [Ca2+]iand DI (r=−0.42, P<0.01). Stepwise multiple regression analysis revealed HbA1c and [Ca2+]i as independent determinants for the impaired RBC‐df. Nisoldipine treatment in vitro significantly decreased [Ca2+]i, and significantly improved RBC‐df.

Conclusions These data indicate that the impaired RBC‐df in NIDDM may at least partly be attributed to the elevated [Ca2+]i and poor glycaemic control. In addition, favorable effects of a Ca2+‐channel blocker on both [Ca2+]i and RBC‐df have been demonstrated.
A prospective study of adverse drug reactions in hospitalized children
Authors: Martínez‐Mir Inocencia , García‐López Mercedes , Palop Vicente , Ferrer José M. , Rubio Elena , Morales‐Olivas Francisco J.
Published: March 2003

Aims There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age.

Methods An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded.

Results A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR=1.66, 95% CI 1.03–2.52). The gastro‐intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti‐infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs.

Conclusions Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients.
Impaired cholinergic dilator response of resistance arteries isolated from patients with Raynaud’s disease
Authors: Smith Paula J. W. , Ferro Charles J. , McQueen Daniel S. , Webb David J.
Published: March 2003

Aims We examined the effect of cooling on the response to the endothelium‐dependent and ‐independent dilators, acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in human microvessels in vitro, and compared the responses between Raynaud’s disease (RD) patients and controls, in order to assess the pathogenic role of the endothelium in RD.

Methods Subcutaneous resistance arteries were dissected from gluteal fat biopsies taken from patients with RD (n=18) and from age‐and sex‐matched control subjects (n=17). Vessels were cannulated in a small vessel arteriograph, in which a pressure of 50 mmHg was maintained across the vessel wall. Cumulative concentration‐response curves for ACh (10−10–10−4 m ) and SNP (10−10–10−3 m ) were generated in vessels at either 37° C or 24° C, with endothelium intact for ACh and removed for SNP (n=6 per group).

Results Neither dilator showed significant differences in sensitivity when comparing responses between vessels from RD patients and controls, at either temperature, but the maximal relaxation to ACh was depressed in vessels from RD patients compared with controls at 37° C (Emax=45±13 in RD vs 89±4 in controls; P=0.004).

Conclusions These results support the hypothesis that impaired endothelium‐dependent vasodilatation is involved in the pathophysiology of RD.
Clinical pharmacy interventions by community pharmacists during the dispensing process
Authors: Hawksworth  , Corlett  , Wright  , Chrystyn
Published: March 2003

Aims To evaluate the professional contact between the community pharmacist and general practitioner during the dispensing process on issues other than the legality or simple clarification of the prescription.

Methods Fourteen community pharmacists from five adjacent localities completed details of each clinical pharmacy intervention during 1 week of each month for a period of 1 year. Each week of the month was randomly selected. When a community pharmacist had to contact the prescriber, during the dispensing of a prescription, the following data were recorded: brief patient details, the prescribed drug therapy, the reason for intervention, the outcome and the time taken. The main outcome measures were the type and nature of each intervention, the BNF category of the drug involved and the time taken. A multidisciplinary clinical panel assessed the potential of each intervention to alter the outcome of the patient’s clinical management and to prevent a drug related hospital admission. These assessments were ranked between 0 and 10 (100% confident).

Results During a period covering 1 week per month over 1 year, 1503 clinical pharmacy interventions were made out of 201 000 items dispensed. When normalized for the dispensing volume of each community pharmacy the lower the number of items dispensed then the greater was the percentage of interventions (P=0.013). The clinical panel decided that between 19 (0.01% of the total items dispensed) and 242 (0.12%) interventions may have prevented a drug‐related hospital admission, 71 (0.04%) to 483 (0.24%) could have prevented harm whilst 103 (0.05%) to 364 (0.18%) had the potential to improve the efficacy of the intended therapeutic plan. The panel also decided that 748 (0.37%) interventions improved the clinical outcome and could have saved a visit to or by the general practitioner.

Conclusion Clinical pharmacy provided by a community pharmacist during the dispensing process has the potential to provide a valuable contribution to health care.