bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of midazolam co‐induction with propofol predosing for induction of anaesthesia
Authors: Anderson L. , Robb H.
Published: March 2003

In a double‐blind, placebo‐controlled study of 90 ASA 1 and 2 patients scheduled for elective surgery we compared the effect of pre‐administering midazolam 2 mg or propofol 30 mg on the dose of propofol subsequently required to induce anaesthesia. Using loss of response to verbal command and tolerance to placement of a facemask as end‐points, the dose of propofol required to induce anaesthesia was significantly smaller in the patients given propofol (1.87 mgkg−1) or midazolam (1.71 mgkg−1) when compared to the control group (2.38 mgkg−1). Although the decrease in blood pressure following induction was significantly greater in the propofol group when compared to the control group, there was no difference between the two study groups and the decrease was felt not to be of clinical significance in this group of patients. As propofol is presented ‘… for use in a single patient only’ and the technique of predosing with propofol allowed induction of all patients with less than 200 mg (a single ampoule), we question on a cost basis whether midazolam co‐induction is necessary to reduce propofol induction doses.
Controlled ventilation using isoflurane with an in‐circle vaporiser
Authors: Wright D. , Brosnan S. , Royston B. , White D.
Published: March 2003

We studied 19 patients anaesthetised for routine surgery using isoflurane delivered from a Komesaroff vaporiser mounted within a circle system. Their lungs were ventilated using a Penlon Nuffield ventilator attached to the circle system by a trunk of tubing. Fresh gas flow rates of 1, 2 or 3 l.min−1 were used. The inspired agent concentration was measured using a Datex Ultima multigas analyser and was found to be stable and easily controlled.
Extent and practicalities of filter use in anaesthetic breathing circuits and attitudes towards their use: a postal survey of UK hospitals
Authors: Atkinson M. C. , Girgis Y. , Broome I. J.
Published: March 2003

A postal survey of 120 UK hospitals was conducted to assess the current use of filters in anaesthetic breathing systems and consultant anaesthetists' opinion of their value; 76% of the questionnaires were returned complete. The survey showed that 77.2% of anaesthetic departments use a new filter for every case, a variety of different filter types being used. A connector distal to the filter was used in 78.3% of patients, providing a possible route for cross infection. Anaesthetists rated the prevention of bacterial infection and gross contamination as being higher priorities than the prevention of viral infection. Of those surveyed, 66.3% believed filters were worthwhile whereas only 35.9% thought they were cost effective. Only 34.8% of anaesthetists believed that the supposed extra efficiency of pleated hydrophobic membrane filters over electrostatic filters merited their extra cost.
The effect of aprotinin on interleukin‐8 concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system
Authors: Gilliland H. E. , Armstrong M. A. , Uprichard S. , Clarke G. , McMurray T. J.
Published: March 2003

We examined the effect of aprotinin on the production of interleukin‐8 and the expression of leukocyte adhesion molecules in an isolated cardiopulmonary bypass circuit. Five healthy volunteers each donated 500 ml blood which was divided into equal portions (A) and (B). Portion A was treated with aprotinin 250 000 kallikrein inactivator units and added to a circuit primed with a further 250 000 kallikrein inactivator units. Portion B was simultaneously treated with 25 ml normal saline and added to an aprotinin‐free circuit. Samples of blood were taken at donation, after addition of a drug and at 30‐min intervals throughout isolated cardiopulmonary bypass. The interleukin‐8 increase was smaller in the aprotinin group but the difference between groups was not statistically significant (p > 0.05). In contrast, aprotinin inhibited the cardiopulmonary bypass‐induced increase in monocyte (p < 0.05) and granulocyte (p < 0.01) CD18 and the increase in granulocyte, but not monocyte, CD11b (p < 0.05). Cardiopulmonary bypass had little effect on expression of L‐selectin. These results confirm that aprotinin attenuates leukocyte activation during isolated cardiopulmonary bypass.
Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role
Authors: Khan Z. P. , Ferguson C. N. , Jones R. M.
Published: March 2003

Clonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic‐sparing activity. The more selective alpha‐2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri‐operative ischaemia. The side‐effects of hypotension and bradycardia have limited the routine use of alpha‐2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha‐2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha‐2 adrenoceptors and their therapeutic role in this review. The alpha‐2 adrenoceptor agonists are agonists at imidazoline receptors which are involved in central blood pressure control. Selective imidazoline agonists are now available for clinical use as antihypertensive agents and their pharmacology is discussed.
Effect of nitric oxide predilution on inhaled nitrogen dioxide concentrations
Authors: Foubert L. , Mareels K. , den Blauwen N. , Herregods L. , Rolly G.
Published: March 2003

We examined the possibility that predilution of a concentrated nitric oxide (NO) source with nitrogen, before contact with oxygen, can reduce the inspired nitrogen dioxide (NO2) concentration during administration of nitric oxide. A Manley Blease and a Siemens Servo 900 C ventilator delivered 10, 20, 40, 60 and 80 parts per million (ppm) NO using an NO source of 1000, 400 and 200 ppm. With the Manley Blease system, predilution from 1000 to 200 ppm NO reduced the inhaled NO2 concentration from 0.14 to 0.05 ppm (p < 0.01) at 10 ppm inhaled NO, and from 1.20 to 1.00 ppm (p < 0.01) at 40 ppm inhaled NO. With the Siemens Servo 900 C ventilator, inspiratory NO2 concentrations decreased from 0.21 to 0.11 ppm (p < 0.01) at 10 ppm inhaled NO, and from 1.49 to 1.16 ppm (p < 0.01) at 40 ppm NO. Predilution from 1000 to 400 ppm NO reduced the inspired NO2 concentrations by < 3% using either ventilator when the inspirated NO concentration was 80 ppm. Predilution of NO with nitrogen significantly reduced the inspired NO2 concentrations for nitric oxide concentrations between 10 and 40 ppm, but offered no clinically relevant advantage at higher NO concentrations.
Rapid sequence induction: a questionnaire survey of its routine conduct and continued management during a failed intubation
Authors: Thwaites A. J. , Rice C. P. , Smith I.
Published: March 2003

Two hundred and ten obstetric anaesthetists completed a questionnaire assessing how they would perform a rapid sequence induction of anaesthesia for a Caesarean section and their continued management during a failed tracheal intubation. The survey revealed considerable variation in the timing and application of cricoid pressure, the choice and dose of drugs used and the timing of their administration. The management of a difficult intubation also varied. This variability was independent of both grade of anaesthetist and frequency of practice. There appear to be at least two distinct techniques in current practice, characterised by ‘fast’ or ‘slow’ rapid sequence induction. Rapid sequence induction is clearly not a standard technique and debate is necessary to clarify the risks and benefits of its components. In particular, the rapidity of the technique and the application of cricoid pressure may contribute to the increased incidence of difficult tracheal intubation in obstetric anaesthesia.
The effect of oxygen on propofol‐induced inhibition of microsomal cytochrome P450 3A4
Authors: Miller E. , Park G. R.
Published: March 2003

We have shown previously that both hypoxia and propofol may inhibit the metabolism of midazolam. We now wished to see whether there was any additive or synergistic effect when they occurred together. Microsomes were incubated with 20 μm midazolam for 60 min, and propofol 0, 50, 100 or 1000 μM was added. Incubates were further subdivided so that the environment contained 0, 10, 21 or 70% oxygen. The results confirmed our earlier study showing that propofol only had a significant inhibitory effect at a concentration greater than that seen clinically (1000 μM). Anoxia was the only environment in which significant depression of the metabolism of midazolam occurred at all concentrations of propofol. This reduced it to almost zero. Post hoc analysis of the data showed that, with the greatest concentration of propofol (1000 μM), there was increasing inhibition of metabolism of midazolam with increases of oxygen from 10 to 70%.
Spinal anaesthesia for Caesarean section in a patient with systemic sclerosis
Authors: Bailey A. R. , Wolmarans M. , Rhodes S.
Published: March 2003

We describe the management of a diabetic primigravid woman with systemic sclerosis and thrombocytopaenia who required Caesarean section for pre‐eclampsia. This was performed successfully under spinal anaesthesia.
Acromegaly and papillomatosis: difficult intubation and use of the airway exchange catheter
Authors: Hulme G. J. , Blues C. M.
Published: March 2003

We describe the anaesthetic management of a patient with acromegaly scheduled for transsphenoidal resection of a pituitary tumour who was found at intubation to have coexisting laryngeal papillomatosis. Oral intubation was impossible using both direct and fibreoptic techniques. Nasal fibreoptic intubation was successful but precluded the transsphenoidal approach to surgery. A Cook Airway Exchange Catheter [Cook (UK) Ltd, Monroe House, Letchworth SG6 1LN] was used with a Negus bronchoscope to convert to oral intubation and allow completion of surgery without resort to tracheostomy.
The cardiorespiratory effects of laparoscopic procedures in infants
Authors: Bozkurt  , Kaya  , Yeker  , Tunali  , Altintaş
Published: March 2003

We assessed the cardiorespiratory effects of laparoscopic procedures in 27 infants aged between 36 and 365 days. Infants were monitored and anaesthetised in a standardised manner. Heart rate, mean arterial pressure, end‐tidal carbon dioxide and oxygen saturation were recorded, and blood gases were measured at 5 min after intubation, 15 and 30 min after carbon dioxide pneumoperitoneum, 5 min after desufflation and after extubation. The pH, Pao2, base excess, Sao2 and Spo2 decreased, and Pco2 increased by insufflation of carbon dioxide intraperitoneally, and improved following deflation. Changes in pH and Pao2 during the study were statistically significant (p < 0.0001). The increase in Paco2 30 min after pneumoperitoneum was statistically significant when compared with initial values. Transient arrhythmias were observed in 10 infants 1 min after pneumoperitoneum. There were no statistically significant alterations in heart rate and systolic blood pressure.
Fibre‐optically lit laryngoscope
Authors: Arthurs
Published: March 2003

The light from a battery‐powered laryngoscope with a fibreoptic blade is limited by the 3‐V battery and deteriorates with use, as the optic fibres break. A laryngoscope handle is described in which the bulb is replaced by a fibreoptic cable connecting to a mains, halogen light source. This laryngoscope gives 6000 Cd.m−2 light at the centre of the field compared with 800 Cd.m−2 for the battery. The field of illumination is also improved from 1600 Cd.m−2 20 mm from the centre compared with 120 Cd.m−2 for the battery handle. The fibre optic cable is attached at the side of the handle and does not interfere with intubation. The mains‐powered light source has the advantages of being reliable with the ability to switch immediately to a second bulb; low running costs; improved light for intubation and it makes it possible to use a dental mirror for indirect laryngoscopy in difficult intubations.
Failure of insertion of a laryngeal mask airway caused by a variation in the anatomy of the thyroid cartilage
Authors: Browning  , Whittet  , Williams
Published: March 2003

We report the failure of insertion of a laryngeal mask airway in a patient with a pre‐operative diagnosis of an abnormality of the superior cornua of the thyroid cartilage. We believe that this is the first time that this reason for failure has been reported.
Profound motor blockade with epidural ropivacaine following spinal bupivacaine
Authors: Buggy  , Allsager  , Coley
Published: March 2003

Ropivacaine, a relatively new amide local anaesthetic, reputedly produces less motor block than equivalent doses of bupivacaine, potentially combining high‐quality analgesia with the ability to ambulate. We report two cases of prolonged, profound motor block with patient‐controlled epidural analgesia using 0.1% ropivacaine, following spinal bupivacaine for Caesarean section. As there was no evidence of inadvertent intrathecal ropivacaine administration or of any neurological injury, we hypothesise that epidural ropivacaine may interact with intrathecal bupivacaine to prolong its effect.
An environmental survey of compliance with Occupational Exposure Standards (OES) for anaesthetic gases
Authors: Henderson K. A. , Matthews I. P.
Published: March 2003

Environmental monitoring of nitrous oxide and volatile agents was carried out between August 1996 and October 1997 within operating theatre areas in eight hospitals within the Bro Taf Health Authority. Static monitoring and personal sampling were undertaken to assess compliance with the Occupational Exposure Standards introduced in January 1996 by the Health and Safety Executive for anaesthetic agents. The monitoring concentrated on nitrous oxide with the results showing that compliance was being achieved. Limited monitoring was carried out of the volatile agents, which again were well below the Occupational Exposure Limits. Monitoring was also carried out in nontheatre areas in which anaesthetic agents were used. The results show that many of these locations, such as delivery suites and radiology units, have inadequate ventilation and no anaesthetic gas scavenging, both of which combined to produce levels that exceeded the standards.
The effect of rectal diclofenac on pruritus in patients receiving intrathecal morphine
Authors: Colbert S. , O'hanlon D. M. , Galvin S. , Chambers F. , Moriarty D. C.
Published: March 2003

In this prospective randomised study, pruritus and pain were evaluated in patients undergoing abdominal surgery in which intrathecal morphine was administered. Each patient received intrathecal morphine 0.3 mg prior to induction, followed by a standard anaesthetic. The patients were randomly allocated to one of two groups. One group received 100 mg of rectal diclofenac immediately post‐induction. Patients receiving diclofenac had significantly lower pruritus scores at 30 min (p = 0.0076), 2, 4, 8 and 24 h postoperatively, as well as significantly reduced pain scores at each time point (p < 0.0001 at each study interval). Morphine consumption in the first 24 h was also significantly lower in this group. In conclusion, rectal administration of diclofenac significantly reduces the incidence and severity of postoperative pruritus. It also significantly reduces pain and further analgesic requirements postoperatively.
A comparison of 1% ropivacaine with a mixture of 0.75% bupivacaine and 2% lignocaine for peribulbar anaesthesia
Authors: McLure H. A. , Rubin A. P. , Westcott M. , Henderson H.
Published: March 2003

In a single centre, randomised, double‐blind study, 54 patients underwent intraocular surgery under peribulbar anaesthesia with either ropivacaine 1% or a mixture of bupivacaine 0.75% and lignocaine 2%, both with hyaluronidase 7.5 iu.ml−1. There were no significant differences in volume of anaesthetic required, time to onset of block, peri‐operative pain scores or frequency of adverse events between the ropivacaine group and the lignocaine and bupivacaine group.
‘Near‐miss’ hyperkalaemic cardiac arrest associated with rapid blood transfusion
Authors: Carvalho B. , Quiney N. F.
Published: March 2003

A case is presented in which a relatively modest blood transfusion resulted in acute hyperkalaemia with a ‘near‐miss’ cardiac arrest. While transfusion‐related hyperkalaemia usually occurs in association with massive transfusions, several factors may have increased the risk of such an acute reaction. A high index of suspicion is required, especially in patients with risk factors. Anaesthetists should not be lulled into a false sense of security simply because modest volumes of blood are being transfused.
Visible and occult blood contamination of laryngeal mask airways and tracheal tubes used in adult anaesthesia
Authors: Parker M. R. J. , Day C. J. E.
Published: March 2003

The purpose of this study was to compare visible and occult blood contamination of 50 laryngeal mask airways and 50 tracheal tubes following routine anaesthesia for procedures not involving the oropharyngeal or nasal cavities. All airway devices were examined visually for the presence of blood before washing in 100 ml of water. A semiquantitative dipstick was used to test for the presence of blood in the washings. Laryngeal mask airways were examined visually by both authors to test agreement. The results show that occult blood contamination occurred in 78% of tracheal tubes and 76% of laryngeal mask airways, while visible blood contamination was 16% and 12%, respectively. Other studies reporting visible blood contamination of airway devices probably underestimate the true incidence of blood contamination. Oral secretions following the use of these devices should be considered as high risk for transmission of blood‐born viruses. Anaesthetic and recovery staff should be protected against the risks of occupational exposure to oral secretions following the use of airway devices.
Intrathecal alfentanil with and without bupivacaine for analgesia in labour
Authors: Hughes D. A. , Hill D. A.
Published: March 2003

Combined spinal–epidural (CSE) for analgesia in labour is widely used as a method of providing pain relief while minimising motor blockade. Aiming to further reduce the associated motor weakness, we investigated the use of alfentanil alone as the initial intrathecal injection in a double‐blind study. Thirty women were randomly allocated to receive either alfentanil 0.25 mg with bupivacaine 2.5 mg intrathecally, or alfentanil 0.25 mg in the same volume. Onset of analgesia did not differ significantly between groups but duration was significantly longer in those receiving alfentanil–bupivacaine (mean 55 min vs. 40 min; p < 0.05). Quality of analgesia was satisfactory for all women, although the cumulative analgesia scores were significantly lower in the women receiving the alfentanil–bupivacaine mixture (p = 0.003). More women in the alfentanil–bupivacaine group developed both a sensory level (15/15 vs. 6/15; p < 0.01) and sympathetic block (12/15 vs. 4/15; p < 0.01). Sixty per cent of women receiving the alfentanil–bupivacaine mixture demonstrated an impaired ability to straight leg raise compared with none of the women in the alfentanil–saline group (p < 0.01). The incidence of adverse effects in mother and fetus was similar in both groups. We conclude that intrathecal alfentanil 0.25 mg alone as part of a CSE technique provides rapid analgesia of satisfactory quality without detectable motor blockade.
End‐tidal oxygraphy during pre‐oxygenation in patients with severe diffuse emphysema
Authors: Samain E. , Farah E. , Delefosse D. , Marty J.
Published: March 2003

We hypothetised that the rate of pre‐oxygenation could be altered by the increase in lung volume and airflow obstruction observed in emphysema. End‐tidal oxygen concentration was monitored, using a paramagnetic oxygen analyser, during 10‐min pre‐oxygenation (tidal breathing of 100% oxygen) in 10 normal patients and in 10 patients with severe diffuse emphysema documented by computerised tomography. Emphysema was characterised by an important increase in functional residual capacity of the lungs [190 (23)% of predicted values] and a decrease in expiratory flow. The increase in end‐tidal oxygen concentration was slower in the emphysema group than in the control group (p = 0.0024). After 3 and 5 min of pre‐oxygenation, the end‐tidal fractional oxygen concentration was significantly lower in the emphysema group than the control group [mean (SD); value at 3 min: emphysema: 0.83 (0.06) vs. control: 0.91 (0.02), p = 0.0005]. Individual values of end‐tidal oxygen concentration measured after 3, 5 and 10 min of pre‐oxygenation were negatively correlated with functional residual capacity in the emphysema group, whereas no such correlation was found in the control group. These results suggest that pre‐oxygenation should be monitored in patients with diffuse emphysema to ensure that adequate pre‐oxygenation is achieved.
Menstrual cycle irregularity and the incidence of nausea and vomiting after laparoscopy
Authors: Harmon D. , O'Connor P. , Gleasa O. , Gardiner J.
Published: March 2003

Gender is an important risk factor for postoperative nausea and vomiting. Menstrual cycle phase has also been implicated as a further variable in female patients. It is not clear whether a history of an irregular menstrual cycle is a significant variable and studies to date have not examined this. The influence of an irregular menstrual cycle on nausea and vomiting after laparoscopy was evaluated in a blinded, prospective, observational study. One hundred and fifty‐nine patients scheduled for laparoscopy and dye investigation were included. Anaesthetic technique and postoperative analgesia were standardised. In comparison with patients who had a regular cycle, an irregular menstrual cycle increased the incidence of nausea or vomiting from 20.5% to 40.5% (absolute difference 20%; 95% CI 0.03–0.37, p = 0.01). Other variables were similar between the groups. An irregular menstrual cycle appears to increase the risk of postoperative nausea and vomiting.
A new method of predicting pulmonary capillary wedge pressure: the arterial pressure ratio
Authors: Uehara H. , Takenaka I. , Aoyama K. , Kadoya T. , Sata T. , Shigematsu A.
Published: March 2003

The response of arterial blood pressure to an increase in intrathoracic pressure has been shown to be predictive of pulmonary capillary wedge pressure. We devised a new method, which we termed the arterial pressure ratio. We defined arterial pressure ratio as the ratio of systolic blood pressure of the final beat during the strain phase of the Valsalva manoeuvre to that during apnoea before the manoeuvre, and tested the accuracy of arterial pressure ratio in predicting pulmonary capillary wedge pressure. In 30 patients scheduled for elective abdominal aortic reconstruction, following induction of general anaesthesia and tracheal intubation, a 20‐G catheter and pulmonary artery catheter were inserted through the radial artery and right internal jugular vein, respectively. Pulmonary capillary wedge pressure was then measured during a brief period of apnoea and the Valsalva manoeuvre was performed by application of pressure to the reservoir bag. Airway pressure was maintained at 30 cmH2O for 10 s and then released. Radial arterial pressure and airway pressure were recorded simultaneously, and arterial pressure ratio was calculated. There was a close linear correlation between arterial pressure ratio and pulmonary capillary wedge pressure (r = 0.88, p < 0.0001).
Gorham syndrome: anaesthetic management
Authors: Szabo C. , Habre W.
Published: March 2003

Gorham syndrome is a rare chronic disease of children and young adults, featuring massive osteolysis with pathological fractures and complicated by respiratory and neurological deficits. To date, 175 cases have been reported in the literature but information on anaesthetic management is sparse. We present a child with Gorham syndrome who underwent urgent surgical medullary decompression and who subsequently developed bilateral pleural effusions.
A comparison of two techniques for manual ventilation of the lungs by non‐anaesthetists: the bag–valve–facemask and the cuffed oropharyngeal airway (COPA)
Authors: Clayton T. J. , Pittman J. A. L. , Gabbott D. A.
Published: March 2003

In order to evaluate the possible role of the cuffed oropharyngeal airway during cardiopulmonary resuscitation, we compared its use by non‐anaesthetists with the bag–valve–facemask technique of providing ventilation. A group of anaesthetic nurses and operating department practitioners were asked to manually ventilate the lungs of 40 patients undergoing elective surgery following the induction of general anaesthesia with neuromuscular blockade. Ventilation was first attempted using the bag–valve–facemask technique and then using the appropriate size cuffed oropharyngeal airway and self‐inflating bag. Ventilation was clinically adequate in 32/40 (80%) patients using the bag–valve–facemask and in 38/40 (95%) patients using the cuffed oropharyngeal airway. Measured expired tidal volumes were greater using the cuffed oropharyngeal airway than with bag–valve–facemask ventilation in two‐thirds of patients, despite a higher incidence of audible air leak. Successful ventilation was achieved using the cuffed oropharyngeal airway in seven of the eight patients in whom bag–valve–facemask ventilation was inadequate. The cuffed oropharyngeal airway may offer an effective method of providing ventilation during cardiopulmonary resuscitation by non‐anaesthetic hospital staff, particularly when attempted ventilation using a bag–valve–facemask technique is proving ineffective.
Use of the common gas outlet for the administration of supplemental oxygen during Caesarean section under regional anaesthesia*
Authors: Stone A. G. H. , Howell P. R.
Published: March 2003

Summary A postal survey investigating the administration of supplemental oxygen to women undergoing Caesarean section under regional anaesthesia was sent to 262 lead consultant obstetric anaesthetists in the UK. Two hundred and fifteen (82%) completed questionnaires were returned. In 139 units (65%) supplemental oxygen was administered routinely to all Caesarean sections under regional techniques, while in 71 (33%), supplemental oxygen was given only if the procedure is an emergency or if there was evidence of fetal or maternal compromise. In 196 units (91%), the common gas outlet was used as the source of supplemental oxygen, with the standard anaesthetic breathing circuit disconnected in 194 (90%) and the vaporisers left on the back bar in 191 (89%). Critical incidents had occurred in 39 (18%) of units using the common gas outlet as a source of supplemental oxygen and 63 (30%) had experience of critical incidents with this practice in a non‐obstetric setting. We suggest that supplemental oxygen is more safely administered from a separate and dedicated source.
Cp50 of propofol for laryngeal mask airway insertion using predicted concentrations with and without nitrous oxide
Authors: Kodaka M. , Handa F. , Kawasaki J. , Miyao H.
Published: March 2003

This study sought to determine the predicted Cp50 of propofol required for laryngeal mask airway insertion (Cp50LMA) and to investigate whether nitrous oxide reduces these required concentrations. Using target‐controlled infusion and incorporating the standard Diprifusor™ pharmacokinetic model, 46 unpremedicated patients were randomly assigned to one of two groups. The patients received either 40% oxygen in air (control group: n = 23), or 60% nitrous oxide in oxygen (nitrous oxide group: n = 23). The target concentration for each patient was determined using the up and down method. Following equilibration between the predetermined blood and effect site concentrations, had been established for > 10 min, laryngeal mask airway insertion was attempted without neuromuscular relaxants. The data were analysed using a probit analysis to obtain Cp50LMA levels. The values for Cp50LMA were 3.24 µg.ml−1 in the control group and 1.93 µg.ml−1 in the nitrous oxide group.
White cell count and intensive care unit outcome
Authors: Waheed U. , Williams P. , Brett S. , Baldock G. , Soni N.
Published: March 2003

Summary A high white cell count on admission to the intensive care unit (ICU) is generally perceived to be associated with severe illness and poor outcome, but the implications of a low white cell count are less well recognised. We retrospectively analysed data on 4165 patients. The white cell count on admission was split into four categories, leucopenic (< 4.0 × 109.l−1), normal (4.001–10.0 × 109. l−1), leucemoid (10.001–25.0 × 109.l−1) and an exaggerated leucemoid response (> 25.001 × 109.l−1). The mortality of patients with leucopenia on admission to the intensive care unit was higher than those with normal or moderately raised white cell count (37.5% vs. 18.9% and 23.9%, respectively). A leucopenic response, as well as an exaggerated leucemoid response, is associated with an increased mortality.
Late Quaternary sedimentation and palaeohydrology in the Acre foreland basin, SW Amazonia
Authors: Kronberg  , Fralick  , Benchimol
Published: March 2003

Our study explores the geohydraulic history of the Acre retroarc foreland basin by gathering both spatial and temporal information from the upper 400 m of sediments. We also inquire into controls on sediment accommodation space as well as on stream vs. lacustrine domination.

The Acre basin is located in south‐west Amazonia, proximal to the Serra do Divisor which demarcates the eastern edge of the Andean fold–thrust belt. Radiocarbon ages from a range of materials indicate that the upper 50–250 m of the Solimôes Formation accumulated during the past 50 000 years. Both surficial and drill‐core sediment records show lacustrine–fluvial transitions throughout the Late Quaternary. These shifts in depositional environments are in response to episodic changes in hydrological conditions as well as to geodynamic activity, such as subsidence. Juxtaposition of lacustrine and fluvial systems in the vertical Acre basin record mimics the regional‐scale trends in the modern, upper and middle Solimôes–Amazon floodplains.

In the Acre basin record lacustrine successions are characterized by increasing calcium contents up‐section. This is also manifested, in the upper portions of lacustrine sequences outcropping at the surface, as alternating clastic and calcareous layers. The up‐section increase in carbonate content is related to increasing salinities brought about by drier hydrodynamic conditions. Desiccation cracks are typically infilled with gypsum as are cavities of fossils in bone‐beds. The latter represent isolated ponds in which the original fauna died as aridity intensified and waters became increasingly saline.

Modern trunk river systems in the Acre basin flow from south‐west to north‐east with tributaries entering from the south‐west, suggesting the influence of a domino‐style, basement, fault regime. Fault or, at least, fracture control on stream channels is also suggested throughout the greater Amazon basin in the orthogonal dispositions and asymmetric terrace systems of trunk rivers as well as of major tributaries.
Late Archaean to Palaeoproterozoic geotherms in the Kaapvaal craton, South Africa: constraints on the thermal evolution of the Witwatersrand Basin
Authors: Gibson R. L. , Jones M. Q. W.
Published: March 2003

The c. 2.97–2.71 Ga Witwatersrand Basin located in the Kaapvaal craton of South Africa represents a remnant of a large Late Archaean sedimentary basin that hosts the world's premier gold deposit within a series of conglomerate horizons. Evidence of postdepositional gold mobility within these conglomerates associated with hydrothermal–metamorphic activity has led to speculation about the Late Archaean to Palaeoproterozoic geothermal gradients in the basin. We use surface heat flow and heat production data from rocks in the basin and its environs in order to calculate detailed temperature profiles for the central Kaapvaal craton that show that the steady state crustal geotherm during the Late Archaean and Palaeoproterozoic was relatively cool at 15–20 K km−1. The geotherm in the upper crustal strata is also largely unaffected by substantial increases in the heat flow into the base of the crust. Consequently, regional greenschist facies metamorphism of the basin sediments could only have been achieved during a transient thermal event that advected heat into the upper crust. The most likely candidate for this is the Bushveld magmatic event at 2.06 Ga.
Interactions between onshore bedrock‐channel incision and nearshore wave‐base erosion forced by eustasy and tectonics
Authors: Snyder N.P. , Whipple K.X. , Tucker G.E. , Merritts D.J.
Published: March 2003

We explore the response of bedrock streams to eustatic and tectonically induced fluctuations in base level. A numerical model coupling onshore fluvial erosion with offshore wave‐base erosion is developed. The results of a series of simulations for simple transgressions with constant rate of sea‐level change (SLR) show that response depends on the relative rates of rock uplift (U) and wave‐base erosion (ɛw). Simple regression runs highlight the importance of nearshore bathymetry. Shoreline position during sea‐level fall is set by the relative rate of base‐level fall (U‐SLR) and ɛw, and is constant horizontally when these two quantities are equal. The results of models forced by a realistic Late Quaternary sea‐level curve are presented. These runs show that a stable shoreline position cannot be obtained if offshore uplift rates exceed ɛw. Only in the presence of a relatively stable shoreline position, fluvial profiles can begin to approximate a steady‐state condition, with U balanced by fluvial erosion rate (ɛf). In the presence of a rapid offshore decrease in rock‐uplift rate (U), short (∼5 km) fluvial channels respond to significant changes in rock‐uplift rate in just a few eustatic cycles. The results of the model are compared to real stream‐profile data from the Mendocino triple junction region of northern California. The late Holocene sea‐level stillstand response exhibited by the simulated channels is similar to the low‐gradient mouths seen in the California streams.
The time of maximum effect for model selection in pharmacokinetic– pharmacodynamic analysis applied to frusemide
Authors: Wakelkamp Monique , Alván Gunnar , Paintaud Gilles
Published: March 2003

Aims
 Both indirect‐response models and effect‐compartment models are used to describe the pharmacodynamics of drugs when there is a delay in the time course of the pharmacological effect in relation to the concentration of the drug. The aim of this study was to investigate whether the time of maximum response after single‐dose administration at different dose levels could be used to distinguish between these models and to select the most appropriate pharmacokinetic‐pharmacodynamic model for frusemide.

Methods
 Three doses of frusemide, 10, 25 and 40 mg were given as rapid intravenous infusions to five healthy volunteers. Urine samples were collected for 5 h after dosing. Volume and sodium losses were isovolumetrically replaced with an intravenous rehydration fluid. Diuresis and natriuresis were modelled for all three doses simultaneously, applying both an indirect‐response model and an effect‐compartment model with the frusemide excretion rate as the pharmacokinetic input.

Results
 The observed time of maximum diuretic and natriuretic response significantly increased with dose. This increase was well predicted by the indirect‐response model, whereas the modelling with the effect‐compartment model led to a poor prediction of the peaks. There was no difference between the observed and predicted time of maximum diuretic and natriuretic response using the indirect‐response model, whereas the time of maximum response predicted by the effect‐compartment model was significantly earlier than the time observed for the 25 mg (P<0.05) and 40 mg (P<0.05) doses.

Conclusions
 The time of maximum response to frusemide was better described using an indirect‐response model than an effect‐compartment model. Studying the time of maximum response after administration of different single doses of a drug may be used as a selective tool during pharmacokinetic‐pharmacodynamic modelling.
Results of single and repeat dose studies of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers
Authors: Millar Andrew W. , Brown Peter D. , Moore Jeff , Galloway W. Alan , Cornish Alan G. , Lenehan Terence J. , Lynch Kevin P.
Published: March 2003

Aims
 To assess the tolerability and pharmacokinetic profile of single and repeat doses of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers.

Methods
 A total of 31 subjects participated in two placebo‐controlled, rising‐dose studies. The first study assessed the pharmacokinetics and tolerability of single doses of marimastat of 25, 50, 100, 200, 400 and 800 mg. In the second study, continuous dosing over 6.5 days with three incremental dose levels of 50, 100 and 200 mg twice daily was assessed. Full pharmacokinetic profiles were obtained on days 0 and 6, and trough concentrations were measured on all days. For each pharmacokinetic profile in the studies, summary measures including Cmax, tmax, elimination half‐life and AUC were calculated. Urinary drug weights were also measured. All adverse events were documented, and haematological and biochemical variables, vital signs and ECGs were monitored throughout the study.

Results
 Peak plasma concentrations were observed at 1.5–3 h for all subjects at all doses. Peak levels were approximately proportional to dose, as was drug exposure as calculated by AUC. Data from both studies indicate that the terminal elimination half‐life is of the order of 8–10 h, and that there is no unexpected drug accumulation. Marimastat was well‐tolerated, with adverse effects being mild and occurring with similar frequency to placebo. Small but reversible elevations in liver transaminases were noted with repeat dosing of marimastat, the most significant of these occurring at a dose of 200 mg twice daily.

Conclusion
 Single and repeat oral doses of marimastat in healthy male subjects appear to be well‐tolerated. The drug is rapidly absorbed with high peak levels achieved. It has a terminal elimination half‐life of 8–10 h which would support twice daily dosing in further clinical trials.
Antioxidant power of angiotensin‐converting enzyme inhibitors in vitro
Authors: Benzie Iris F. F. , Tomlinson Brian
Published: March 2003

Aims
 There is controversy regarding the potential antioxidant effect of captopril, therefore this study was performed to compare the in vitro antioxidant power of captopril with other angiotensin‐converting enzyme (ACE) inhibitors.

Methods
 Antioxidant power of captopril, enalapril, fosinopril, perindopril, quinapril and ramipril in aqueous solution was measured using the ferric reducing (antioxidant) power (FRAP) assay; captopril was also measured in ethanolic solution.

Results
 Only captopril showed significant antioxidant power, demonstrating a stoichiometric factor of 1.0 in this assay. Concentration‐related antioxidant power was seen in both aqueous and ethanolic solutions.

Conclusions
 Captopril shows antioxidant activity in vitro. This property could be relevant in vivo if captopril is concentrated in membranes, lipoproteins or at other important sites.
Lipoprotein composition and oxidative modification during therapy with gemfibrozil and lovastatin in patients with combined hyperlipidaemia
Authors: Vázquez M. , Zambón D. , Hernández Y. , Adzet T. , Merlos M. , Ros E. , Laguna J. C.
Published: March 2003

Aims
 To evaluate the resistance to oxidation of human lipoproteins after hypolipidaemic therapy.

Methods
 VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a randomized, double‐blind, cross‐over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice daily, or lovastatin, 40 mg daily) and a 4‐week wash‐out period. Oxidation related analytes after Cu‐induced oxidation of VLDL and LDL have been investigated. Further, in order to relate possible changes in oxidative behaviour to lipoprotein composition, the proportion of the lipid species transported by lipoproteins (triglycerides, phospholipids, and cholesteryl esters), the molar composition of fatty acids for each lipoprotein lipid, and the content of antioxidant vitamins in plasma (vitamin C) and lipoproteins (vitamin E) have been studied.

Results
 Both drugs reduced the plasma concentration of apo‐B lipoproteins (−23% gemfibrozil, −26% lovastatin), but whereas lovastatin affected mainly LDL‐cholesterol (−30%), gemfibrozil reduced triglycerides (−49%) and VLDL‐cholesterol (−48%). Lovastatin treatment had no effect on the lipid and protein composition, the fatty acid profile, or the vitamin E content of either VLDL or LDL; likewise, lipoprotein oxidation markers (Cu‐induced conjugated dienes, thiobarbituric acid reactive substances formation, and lysine residues) were similar before and after lovastatin treatment. Gemfibrozil therapy also had no effect on lipoprotein oxidation; nevertheless, it consistently: a) decreased the proportion of LDL‐triglycerides (−32%), and b) increased the proportion (molar%) of 18:3 n‐6 in VLDL triglycerides (+140%), phospholipids (+363%) and cholesteryl esters (+53%).

Conclusions
 Based on these results, lovastatin and gemfibrozil do not adversely affect lipoprotein oxidation in patients with mixed dyslipidaemia. In the case of gemfibrozil, this occurs in spite of an increased proportion of some polyunsaturated fatty acids in VLDL. In the context of a fixed dietary intake, such modifications suggest that the drug influences liver enzyme activities involved in fatty acid chain synthesis (elongases and desaturases).
Computerized surveillance of adverse drug reactions in hospital: pilot study
Authors: Azaz‐Livshits Tatyana , Levy Micha , Sadan Batami , Shalit Meir , Geisslinger Gerd , Brune Kay
Published: March 2003

Aims
 To develop and assess the use of computerized laboratory data as a detection support tool of adverse drug reactions (ADRs) in hospital.

Methods
 This was a retrospective observational study of 153 sequential medical admissions during a 2‐month period to the 34‐bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. Measurements made were 1) Retrospective chart review for recognized and unrecognized adverse drug reactions (ADRs) and 2) Analysis of computerized laboratory data according to defined automatic laboratory signals (ALS) for adverse reactions.

Results
 Forty ADRs have been detected in 38 out of the 153 hospital admissions (24.8%). Nine reactions were considered severe. Altogether 212 ALS were generated involving 86 admissions. In 25 (65.8%) of the ADR‐positive admissions ADRs were detected through automatic signals generated from the laboratory data. ALS were detected in 56 out of the 115 (48.7%) ADR‐negative admissions. Twenty‐four (60%) of the ADRs were not recognized as such by the attending physicians. Two of these reactions were severe. ALS could have generated an alert for 19 (79.2%) of the unrecognized reactions.

Conclusions
 Application of automatic laboratory signals can increase the rate of recognition of ADRs and thereby improve medical care. The sensitivity and specificity of the method might be increased by refinement and redefinition of the signals.
Cytochrome P4502C9: an enzyme of major importance in human drug metabolism
Authors: Miners John O. , Birkett Donald J.
Published: March 2003

Accumulating evidence indicates that CYP2C9 ranks amongst the most important drug metabolizing enzymes in humans. Substrates for CYP2C9 include fluoxetine, losartan, phenytoin, tolbutamide, torsemide, S‐warfarin, and numerous NSAIDs. CYP2C9 activityin vivois inducible by rifampicin. Evidence suggests that CYP2C9 substrates may also be induced variably by carbamazepine, ethanol and phenobarbitone. Apart from the mutual competitive inhibition which may occur between alternate substrates, numerous other drugs have been shown to inhibit CYP2C9 activityin vivoand/orin vitro. Clinically significant inhibition may occur with coadministration of amiodarone, fluconazole, phenylbutazone, sulphinpyrazone, sulphaphenazole and certain other sulphonamides. Polymorphisms in the coding region of theCYP2C9gene produce variants at amino acid residues 144 (Arg144Cys) and 359 (Ile359Leu) of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly diminished metabolic capacities for most CYP2C9 substrates, although the frequency of this allele is relatively low. Consistent with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. Individualisation of dose is essential for those CYP2C9 substrates with a narrow therapeutic index.
Constant rate infusion of vancomycin in premature neonates: a new dosage schedule
Authors: Pawlotsky F. , Thomas A. , Kergueris M. F. , Debillon T. , Roze J. C.
Published: March 2003

Aims
 Since vancomycin's bactericidal action has been shown to be time‐dependent, a constant rate infusion over 24 h might result in a better bactericidal efficacy. The purpose of this study was to define a new dosage schedule in prematures.

Methods
 Two vancomycin 24 h constant rate infusion schedules were tested in two groups of neonates. Postconceptional age (PCA) was 27 to 41 weeks in group 1 (n=24) and 28 to 51.5 weeks in group 2 (n=29). Group 1 neonates received continuous infusion of 10 to 30 mg kg−1 day−1, adjusted for PCA and weight. Group 2 was designed to take into account the significant relationship observed in group 1 between vancomycin clearance standardized on weight and PCA and consisted of a constant loading dose of 7 mg kg−1 followed by continuous infusion of 10 to 40 mg kg−1 day−1 adjusted for PCA and weight.

Results
 Mean vancomycin serum concentration at steady state was 11±3.1 mg l−1 in group 1 and 15.4±6.2 mg l−1 in group 2. Fifty‐six percent of group 1 values vs 88% of group 2 values were between 10 and 30 mg l−1 at steady state (P<0.01). Both regimens were well tolerated.

Conclusion
 A loading dose of vancomycin followed by constant rate infusion of the appropriate dose adjusted for PCA and weight might improve vancomycin concentrations in neonates.
Chloroquine modulation of specific metabolizing enzymes activities: investigation with selective five drug cocktail
Authors: Adedoyin Adedayo , Frye Reginald F. , Mauro Kelly , Branch Robert A.
Published: March 2003

Aims
 The aim of this study was to investigate whether chloroquine can inhibit drug metabolism in humans, if such inhibition is general or selective for certain enzymes and evaluate the potential for and clinical significance of any drug‐drug interactions when chloroquine is co‐administered with other drugs.

Methods
 The study was conducted in fourteen normal non‐smoking healthy male volunteers using a cocktail of five drugs consisting of caffeine, mephenytoin, debrisoquine, chlorzoxazone and dapsone to assess activities of cytochromes P450 (CYP) 1A2, 2C19, 2D6, 2E1 and 3A4 respectively. Dapsone was also used to assess N‐acetyltransferase activity. The activities were assessed at baseline, after one and seven daily doses (250 mg daily) of chloroquine and 7 and 14 days after stopping chloroquine dosing.

Results
 Chloroquine caused a progressive and significant decrease in CYP2D6 activity as measured by debrisoquine metabolism from first to seventh dose and the activity returned to baseline gradually over 14 days after stopping administration. There was no effect on the metabolism of any of the other probe drugs.

Conclusions
 Chloroquine has been shown to be capable of inhibiting the activity of CYP2D6 in vivo in humans. This effect is selective as activities of other enzymes investigated were not affected. The effect was modest but suggests a potential for drug‐drug interactions when co‐administered with other drugs that are substrates for this enzyme. The clinical significance of such an interaction will depend on the therapeutic index of any drug involved.