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Non-neuronal cells may be pivotal in neurodegenerative disease, but the mechanistic basis of this effect remains ill-defined. In the polyglutamine disease spinocerebellar ataxia type 7 (SCA7), Purkinje cells undergo non-cell-autonomous degeneration in transgenic mice. We considered the possibility that glial dysfunction leads to Purkinje cell degeneration, and generated mice that express ataxin-7 in Bergmann glia of the cerebellum with the Gfa2 promoter. Bergmann glia-specific expression of mutant ataxin-7 was sufficient to produce ataxia and neurodegeneration. Expression of the Bergmann glia-specific glutamate transporter GLAST was reduced in Gfa2-SCA7 mice and was associated with impaired glutamate transport in cultured Bergmann glia, cerebellar slices and cerebellar synaptosomes. Ultrastructural analysis of Purkinje cells revealed findings of dark cell degeneration consistent with excitotoxic injury. Our studies indicate that impairment of glutamate transport secondary to glial dysfunction contributes to SCA7 neurodegeneration, and suggest a similar role for glial dysfunction in other polyglutamine diseases and SCAs.

CAG and CTG repeat expansions are the cause of at least a dozen inherited neurological disorders. In these so-called "dynamic mutation" diseases, the expanded repeats display dramatic genetic instability, changing in size when transmitted through the germline and within somatic tissues. As the molecular basis of the repeat instability process remains poorly understood, modeling of repeat instability in model organisms has provided some insights into potentially involved factors, implicating especially replication and repair pathways. Studies in mice have also shown that the genomic context of the repeat sequence is required for CAG/CTG repeat instability in the case of spinocerebellar ataxia type 7 (SCA7), one of the most unstable of all CAG/CTG repeat disease loci. While most studies of repeat instability have taken a candidate gene approach, unbiased screens for factors involved in trinucleotide repeat instability have been lacking. We therefore attempted to use Drosophila melanogaster to model expanded CAG repeat instability by creating transgenic flies carrying trinucleotide repeat expansions, deriving flies with SCA7 CAG90 repeats in cDNA and genomic context. We found that SCA7 CAG90 repeats are stable in Drosophila, regardless of context. To screen for genes whose reduced function might destabilize expanded CAG repeat tracts in Drosophila, we crossed the SCA7 CAG90 repeat flies with various deficiency stocks, including lines lacking genes encoding the orthologues of flap endonuclease-1, PCNA, and MutS. In all cases, perfect repeat stability was preserved, suggesting that Drosophila may not be a suitable system for determining the molecular basis of SCA7 CAG repeat instability.

Evaluative conditioning refers to the changes in liking of an evaluatively neutral stimulus (the conditional stimulus or CS) as a result of merely pairing it with another, already liked or disliked stimulus (the unconditional stimulus or US). We examined whether other, non-evaluative stimulus properties of a US can also be associatively transferred to a CS. In a series of experiments, we tried to transfer perceptions of the gender of children and the gender of first names. We found evidence for the associative transfer of these properties but only when participants were aware of the contingencies.

X-linked spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disorder characterized by lower motor neuron degeneration. SBMA is caused by polyglutamine repeat expansions in the androgen receptor (AR). To determine the basis of AR polyglutamine neurotoxicity, we introduced human AR yeast artificial chromosomes carrying either 20 or 100 CAGs into mouse embryonic stem cells. The AR100 transgenic mice developed a late-onset, gradually progressive neuromuscular phenotype accompanied by motor neuron degeneration, indicating striking recapitulation of the human disease. We then tested the hypothesis that polyglutamine-expanded AR interferes with CREB binding protein (CBP)-mediated transcription of vascular endothelial growth factor (VEGF) and observed altered CBP-AR binding and VEGF reduction in AR100 mice. We found that mutant AR-induced death of motor neuron-like cells could be rescued by VEGF. Our results suggest that SBMA motor neuronopathy involves altered expression of VEGF, consistent with a role for VEGF as a neurotrophic/survival factor in motor neuron disease.

Based on the hypothesis that information about the valence of words is encoded in a semantic system, we predicted that the match between the valence of a prime and the valence of a target word will influence the pronunciation of the target only if and to the extent that pronunciation is semantically mediated. In line with this prediction, we found affective priming effects (faster pronunciation when prime and target had the same valence than when they had a different valence) only when participants were instructed to read words but not nonwords (Experiment 1) or words that were not names of occupations (Experiment 2). Priming was not significant when participants were asked to read white but not red words (Experiment 1) or words that did not have a frame around them (Experiment 2).

Brain death was first defined in 1968, and since then laws on determining death have been implemented in all countries with active organ transplantation programs. As a prerequisite, the aetiology of brain death has to be known, and all reversible causes of coma have to be excluded. The regulations for the diagnosis of brain death are most commonly given by the national medical associations, and they vary between countries. Thus, the guidelines given in the medical textbooks are not universally applicable. The diagnosis is based on clinical examination, but confirmatory tests, such as angiography or EEG, are allowed on most occasions. Brain death is followed by cardiovascular and hormonal changes, which have implications in the management of a potential organ donor. Spinal reflexes are preserved, and motor and haemodynamic responses are frequently observed in brain dead patients.

Background: Paediatric studies have demonstrated that cardiopulmonary bypass is associated with a decline in thyroid hormone levels. Adult patients who undergo open heart surgery and receive triiodothyronine supplementation have demonstrated a dose-dependent increase in cardiac output which has been associated with an improved clinical outcome. Thyroid hormone supplementation in infants may also reduce post-operative morbidity and mortality., Objectives: To determine if peri-operative thyroid hormone supplementation or replacement in infants undergoing cardiac surgery on cardiopulmonary bypass improves post-operative and longer term morbidity and mortality., Search Strategy: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of The Oxford Database of Perinatal Trials, MEDLINE (1966 - December 2003), EMBASE (1980 - December 2003), CINAHL (1982 - December 2003), The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching in the English language., Selection Criteria: All trials using random allocation to peri-operative thyroid hormone therapy (supplementation or replacement) compared to control (placebo or no therapy) in infants (birth to one year of age) undergoing cardiac surgery requiring cardiopulmonary bypass. Thyroid hormone therapy must be tri-iodothyronine., Data Collection and Analysis: Primary clinical outcomes included measures of post-operative morbidity and mortality. The standard methods of the Cochrane Neonatal Review Group were used in the assessment of trial quality. Treatment effects were expressed using relative risk (RR) and mean difference (MD)., Main Results: Two very small studies were identified that tested peri-operative thyroid hormone supplementation or replacement in infants aged less than one year undergoing cardiac surgery (Chowdhury 2001; Portman 2000). In the Chowdhury 2001 study, a subgroup of nine neonates was eligible for this review. No deaths occurred during either study. Chowdhury 2001 found no significant effect of peri-operative thyroid hormone supplementation in neonates on either length of hospital stay or duration of mechanical ventilation. Portman 2000 found no significant difference in dopamine requirements for the treatment versus control groups for the first 24 hours post operatively, while in the Chowdhury neonatal subgroup, inotrope requirements were significantly lower in the treatment group. Portman 2000 reported significant differences between the two groups at 1 and 24 hours post operatively for free T3 and at 1 hour post operatively for total T3 levels. Total T4 levels showed no significant difference between groups, either pre-cardiopulmonary bypass or up to 72 hours post operatively., Reviewers' Conclusions: At present, there is a lack of evidence concerning the effects of tri-iodothyronine supplementation in infants undergoing cardiac surgery. Further randomised controlled trials which include sufficiently large subject numbers in a variety of different age strata (neonates, infants and older children) need to be undertaken.

Background: Buprenorphine is used as maintenance therapy for opioid-dependent patients. In comparison with other opioids it is thought to be safer because it is less likely to cause serious respiratory depression. However, concomitant use of psychotropics, especially benzodiazepines, and intravenous injection of dissolved buprenorphine tablets increase the risk of a serious overdose., Methods: As part of a larger retrospective study of opioid overdoses in Helsinki, the emergency medical services (EMS) records from January 1995 to April 2002 were reviewed for overdoses involving buprenorphine. Hospital records were reviewed when available., Results: We report 11 overdoses in which buprenorphine was involved. The classic symptoms and signs of an opioid overdose (respiratory depression, miosis and central nervous system depression) were present in most of the cases. At least eight of the patients had an overdose that was potentially fatal. One of the patients had a heroin overdose and was reportedly 'treated' by his friends with intravenously administered buprenorphine., Conclusion: The high-dosage formulation of buprenorphine used for opioid-dependent patients might have caused several dangerous and potentially fatal overdoses in Helsinki. However, it does cause considerably less serious overdoses than heroin. Drug abusers might be intravenously administering buprenorphine themselves to treat heroin overdoses.

Use of both l-epinephrine and racemic epinephrine (adrenaline) has improved clinical symptoms and composite respiratory scores in acute bronchiolitis. The objective of this randomized double-blind placebo-controlled study was to assess whether there was sufficient improvement in clinical state to reduce hospital admissions. Seventy-five infants aged 1 month to 1 year with a clinical diagnosis of acute bronchiolitis were treated with either 2 ml of 1:1000 nebulized adrenaline or 2 ml of nebulized normal saline administered after baseline assessment and 30 min later. Clinical respiratory parameters were recorded at 15-min intervals for a period of 2 h following the baseline assessment. Admission to hospital was the primary end-point and changes in respiratory parameters were secondary end-points. Fifty percent (19/38) of infants treated with adrenaline were discharged home compared with 38 percent (14/37) of those treated with saline. This 12 percent reduction in rate of admission is not statistically significant (95% CI of difference: -10% to 35%). There was no difference between treated and placebo groups in respiratory rate, oxygen saturation, heart rate or a composite respiratory distress score at 30, 60 or 120 min post-treatment. In this study, nebulized epinephrine did not confer a significant advantage over nebulized saline in the emergency room treatment of acute bronchiolitis.

Awake craniotomy is the cheapest and most reliable method to ensure neurological integrity in cerebral gliomas that infiltrate or come close to the eloquent areas of the brain, allowing (a) the localization of eloquent cortical areas by electrical stimulation and epileptic foci by cortical recording, and (b) the monitoring of the functional integrity of awake patients while aiming at subtotal removal of the gliomatous tissue. In addition, awake craniotomy opens a brief but unique window to the living brain for (a) basic neuroscience, including verification of preoperative functional imaging data and recording of electrophysiological correlates of mental processes, and for (b) applied research, including development of innovative instrumentation for brain recording and monitoring as well as screening for potential areas to be modulated in movement disorders and chronic pain.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the ataxin-7 gene. In humans, SCA7 is characterized by marked anticipation due to intergenerational repeat instability with a bias toward expansion, and is thus regarded as the most unstable of the polyglutamine diseases. To study the molecular basis of CAG/CTG repeat instability and its pathological significance, we generated lines of transgenic mice carrying either a SCA7 cDNA construct or a 13.5 kb SCA7 genomic fragment with 92 CAG repeats. While the cDNA transgenic mice showed little intergenerational repeat instability, the genomic fragment transgenic mice displayed marked intergenerational instability with an obvious expansion bias. We then went on to generate additional lines of genomic fragment transgenic mice, and observed that deletion of the 3' genomic region significantly stabilized intergenerational transmission of the SCA7 CAG92 repeat. These results suggest that cis-information present on the genomic fragment is driving the instability process. As the SCA7 genomic fragment contains a large number of replication-associated motifs, the presence of such sequence elements may make the SCA7 CAG repeat region more susceptible to instability. Small-pool and standard PCR analysis of tissues from genomic fragment mice revealed large repeat expansions in their brains and livers, but no such changes were found in any tissues from cDNA transgenic mice that have been shown to undergo neurodegeneration. As large somatic repeat expansions are absent from the brains of SCA7 cDNA mice, our results indicate that neurodegeneration can occur without marked somatic mosaicism, at least in these mice.

Background and Objective: Thiopental prolongs the QT interval more than propofol, and the two induction agents were compared in patients with subarachnoid haemorrhage predisposed to electrocardiographic abnormalities and cardiac dysrhythmias., Methods: Twenty-nine patients were studied randomly. Anaesthesia was induced with either thiopental or propofol and fentanyl; vecuronium was used as a neuromuscular blocking agent. The electrocardiogram and arterial blood pressure were monitored from before the induction of anaesthesia to 2 min after endotracheal intubation., Results: The median QT interval was at baseline 423 ms in the thiopental group and at 432 ms in the propofol group, and it increased in the thiopental group to 446 ms and decreased in the propofol group to 425 ms (P < 0.01 between groups). After induction and endotracheal intubation, the number of patients with increased QT dispersion was greater in the propofol group (P < 0.05). The incidence of cardiac dysrhythmias was similar in the study groups., Conclusions: Thiopental and propofol are equally suitable for the induction of anaesthesia in patients with subarachnoid haemorrhage.

Spinocerebellar ataxia (SCA) type 7 is an inherited neurodegenerative disorder caused by expansion of a polyglutamine tract within the ataxin-7 protein. To determine the molecular basis of polyglutamine neurotoxicity in this and other related disorders, we produced SCA7 transgenic mice that express ataxin-7 with 24 or 92 glutamines in all neurons of the CNS, except for Purkinje cells. Transgenic mice expressing ataxin-7 with 92 glutamines (92Q) developed a dramatic neurological phenotype presenting as a gait ataxia and culminating in premature death. Despite the absence of expression of polyglutamine-expanded ataxin-7 in Purkinje cells, we documented severe Purkinje cell degeneration in 92Q SCA7 transgenic mice. We also detected an N-terminal truncation fragment of ataxin-7 in transgenic mice and in SCA7 patient material with both anti-ataxin-7 and anti-polyglutamine specific antibodies. The appearance of truncated ataxin-7 in nuclear aggregates correlates with the onset of a disease phenotype in the SCA7 mice, suggesting that nuclear localization and proteolytic cleavage may be important features of SCA7 pathogenesis. The non-cell-autonomous nature of the Purkinje cell degeneration in our SCA7 mouse model indicates that polyglutamine-induced dysfunction in adjacent or connecting cell types contributes to the neurodegeneration.

In studies on affective priming of pronunciation responses, two words are presented on each trial and participants are asked to read the second word out loud. Whereas some studies revealed shorter reaction times when the two words had the same valence than when they had a different valence, other studies either found no effect of affective congruence or revealed a reversed effect. In the present experiments, a significant effect of affective congruence only emerged when filler trials were presented in which the prime and target were identical and participants were instructed to attend to the primes (Experiment 2). No effects were found when participants were merely instructed to attend to or ignore the primes (Experiment 1), or when affectively incongruent filler trials were presented and participants were instructed to ignore the primes (Experiment 2).

We studied 12 patients with brain tumors in the vicinity of the sensorimotor region to provide a preoperative three-dimensional visualization of the functional anatomy of the rolandic cortex. We also evaluated the role of cortex-muscle coherence analysis and anatomical landmarks in identifying the sensorimotor cortex. The functional landmarks were based on neuromagnetic recordings with a whole-scalp magnetometer, coregistred with magnetic resonance images. Evoked fields to median and tibial nerve and lip stimuli were recorded to identify hand, foot and face representations in the somatosensory cortex. Oscillatory cortical activity, coherent with surface electromyogram during isometric muscle contraction, was analyzed to reveal the hand and foot representations in the precentral motor cortex. The central sulcus was identified also by available anatomical landmarks. The source locations, calculated from the neuromagnetic data, were displayed on 3-D surface reconstructions of the individual brains, including the veins. The preoperative data were verified during awake craniotomy by cortical stimulation in 7 patients and by cortical somatosensory evoked potentials in 5 patients. Sources of somatosensory evoked fields identified correctly the postcentral gyrus in all patients. Useful corroborative information was obtained from anatomical landmarks in 11 patients and from cortex-muscle correlograms in 8 patients. The preoperative visualization of the functional anatomy of the sensorimotor strip assisted in designing the operational strategy, facilitated orientation of the neurosurgeon during the operation, and speeded up the selection of sites for intraoperative stimulation or mapping, thereby helping to prevent damage of eloquent brain areas during surgery.

Background: Moderate to severe pain occurs after craniotomy in 60% of patients. We evaluated the feasibility and safety of patient-controlled analgesia (PCA) with oxycodone in neurosurgical patients, and compared the efficacy of paracetamol with ketoprofen., Methods: In the study there were 45 patients, who received either paracetamol 1000 mg or ketoprofen 100 mg three times a day. Oxycodone-boluses 0.03 mg/kg were given by PCA-device maximally three times an hour, lock-out time 10 min. The amount of oxycodone used, pain scores and side-effects were recorded., Results: The ketoprofen group required less oxycodone than the paracetamol group (medians 37.1 mg vs 19.6 mg, P < 0.05). The VAS scores were comparable between the groups at the beginning of the study, during the first postoperative evening and the next morning, but the paracetamol group had a higher score at the conclusion of the study (P < 0.05). The patients in both groups were equally satisfied with the pain relief. There were no differences in side-effects between the groups., Conclusions: PCA with oxycodone is a suitable method for pain control after craniotomy. No progressive hypoventilation, desaturation or excessive sedation were encountered. Ketoprofen appeared to be more effective than paracetamol.

We have compared impingement of the tracheal tube against the larynx using a standard preformed tube, warmed preformed tube or two flexible spiral-wound tracheal tubes with different tip designs, in 100 adult patients undergoing orotracheal fibreoptic intubation under general anaesthesia, in a prospective, randomized study. The rates of impingement were 20 of 30 with the standard tube, 12 of 30 with the warmed standard tube (P = 0.07) and eight of 20 with both spiral tubes. However, impingement with the spiral tubes took longer to overcome if a sharp tipped rather than an obtuse tipped tube was used. Manipulations after impaction led to oesophageal intubation in one patient, and in one patient fibreoptic intubation failed. We conclude that resistance to the tracheal tube occurred frequently when the spiral-wound tubes were used.

Resistance to the passage of the tracheal tube has been reported to occur in up to 36% of patients subjected to orotracheal fibreoptic intubation. In this prospective study we assessed five radiological measurements of the upper airway in an attempt to find anatomical causes of obstruction to passage of the tube. Forty-nine patients undergoing fibreoptic orotracheal intubation under general anaesthesia were studied. Pre-operatively, the Mallampati grade and the thyromental distance were assessed. The plain films, CT scans or MR images of the cervical spine were used for measurement of the position of the vocal cords, the length of the epiglottis and the size of the tongue. The resistance to the passage of the tube was graded as none, mild, moderate or severe. The length of the epiglottis and the size of the tongue, but not the position of the vocal cords, had positive correlations with the severity of impingement. The pre-operative bedside tests did not correlate with difficulties in fibreoptic intubation.

The best view obtained by levering the tip of the McCoy laryngoscope blade with or without modified cricoid pressure was studied in 100 patients presenting for general surgery. The airway was assessed pre-operatively (Mallampati score, thyromental distance, mouth opening, protrusion of the jaw and weight) in an attempt to identify the patients who might benefit from the use of the McCoy laryngoscope. The vocal cords were visible at laryngoscopy with the blade in the neutral position in 32 cases. In the 68 remaining patients the vocal cords were partly visible in 48. The epiglottis only was seen in 18 patients and in two not even the epiglottis could be visualised. Elevation of the blade or modified cricoid pressure improved the view in 38/68 cases and 57/68 cases, respectively (p < 0.001, Wilcoxon signed rank). Using our method of pre-operative assessment we were unable to identify those patients who might benefit from either manipulation.

Acromegaly is recognized as a cause of difficulty in airway management and tracheal intubation. We evaluated prospectively the conditions for laryngoscopy and fibreoptic intubation in 15 acromegalic patients. Each patient served as his or her own control. Ventilation of the lungs with a face mask was successful in all patients. In five of 15 patients the vocal cords could not be seen using the Macintosh laryngoscope with a size 5 blade. Difficult laryngoscopy was associated significantly with the number of attempts required to see the vocal cords with the fibrescope (P < 0.01, Spearman rank correlation). The larynx could not be seen with both techniques in one patient, and the trachea was intubated blindly with the help of an introducer. Our results showed that fibreoptic intubation may prove difficult or fail in acromegalic patients. Difficulties in seeing the vocal cords with a fibrescope were present most often in patients who also had probable intubation difficulties with a rigid laryngoscope.

Background: Fibreoptic intubation has been suggested to be the best method to manage a compromised airway. This retrospective study was designed to compare endotracheal intubation with the help of a rigid laryngoscope or a fibrescope in patients with rheumatoid arthritis., Methods: Intubation difficulties with the laryngoscope and the fibrescope in patients with rheumatoid arthritis were investigated during a period of five and a half years. The anaesthesia records were used for analysis. The patients were divided into two groups (group I with 41 patients and group II with 37 patients) reflecting the change in the routine airway management in patients with rheumatoid arthritis in our hospital from the beginning of 1993. Before that time the patients were usually intubated orotracheally under general anaesthesia, but since 1993 rheumatoid patients with anticipated difficulties in endotracheal intubation have been preferably intubated fibreoptically awake under sedation and topical anaesthesia with a fibrescope., Results: Major difficulties in endotracheal intubations were encountered in 13% of patients in group I and in 8% in group II. On two occasions in group I tracheostomy was needed. In one of these patients, emergency tracheostomy was performed. In the latter group, the main reason for prolonged fibreoptic intubations was lack of experience., Conclusion: The introduction of fibreoptic intubation technique has had a favourable influence on the safety in the airway management of surgical patients with rheumatoid arthritis.

The most common indication for employing the fibreoptic technique for intubation is when a difficult intubation is anticipated. It may also be used when intubation unexpectedly proves difficult with a rigid laryngoscope in anaesthetized patients. However, failures with orotracheal fibreoptic intubation have been reported in up to 9.5% of cases, although only two possible equipment related causes of intubation difficulties have been identified. The Berman intubating airway and the Ovassapian intubation airway in fibreoptic orotracheal intubation have been compared in 65 patients. The study was randomized and for fibreoptic endoscopy each patient served as his or her own control. The results indicate that both airways can be used for orotracheal fibreoptic intubation in anaesthetized patients. The Berman airway offers easier visualization of the vocal cords than the Ovassapian airway, provided that the Berman airway is of an adequate size and positioned in the midline. Upon impingement of the intubation tube, completing the tracheal intubation is more difficult with the Berman airway than the Ovassapian airway.

Background: Side-stream spirometry offers a non-invasive method to monitor continuously respiratory mechanics in intubated patients. We studied the effects of different positions on dynamic lung compliance during anaesthesia., Methods: The study consisted of 56 patients, operated in supine, prone, kneeling or lateral park-bench position. Dynamic lung compliance and inspiratory peak pressure were recorded after induction of anaesthesia, 15 min and 1 h after posturing the patient., Results: The first measured compliances were comparable in all groups. The compliance in the lateral and the prone positions was significantly lower than in the supine position at 15 min (P < 0.01) and 1 h (P < 0.001) after the posture change. The peak inspiratory pressure was significantly lower in the kneeling position than in the other groups (P < 0.01 at the first measurement, P < 0.001 at the later measurements). No correlation was found between body mass index and compliance., Conclusion: We found that dynamic lung compliance decreased significantly upon change of posture from supine to lateral or prone position, whereas in the kneeling position no change in compliance was observed. We suggest that the kneeling position might be preferable to the prone position.

Orotracheal fibreoptic intubation under general anaesthesia in children was studied in eleven consecutive patients of three months to eight-years-of-age without anticipated intubation difficulties. One case report is also included. Three fibrescopes with a different diameter were used in the study. The fibrescope used was chosen so that it fitted snugly in the tracheal tube. The fibreoscopy was prolonged in one patient due to mucus and two tries were needed. Resistance to the tracheal tube upon intubation was encountered in five patients, only one of these patients was older than two years. Fibreoptic intubation succeeded in nine patients. Two patients were intubated with the Macintosh laryngoscope. The problems encountered in children during orotracheal fibreoptic intubation under general anaesthesia are the same as with adults: easy fibreoscopy is not always followed by easy tracheal intubation, there may be prolonged fibreoscopy and failed intubations. Manipulation of the tracheal tube can lead to successful tracheal intubation and resistance to the tube is more common in smaller children.

In this randomized, experimental study in 18 pigs, we have investigated the effects of inspiratory air in oxygen, 100% oxygen and 50% nitrous oxide in oxygen on the detection and consequences of venous air embolism. Each animal was tested with injections of 1.0 ml kg-1 and 2.0 ml kg-1 of air. All animals, except one in the nitrous oxide group, survived the air emboli. Systolic and diastolic arterial pressures decreased significantly in all groups after both injections of air. Pulmonary diastolic pressures increased most in the nitrous oxide group. End-tidal concentration of carbon dioxide decreased significantly in all groups after air injections. The difference in concentration of oxygen in the inspiratory and expiratory gas (O2 (I-E)) was lowest in the air group after both injections of air. On the basis of our studies we suggest that nitrous oxide should not be used during surgery associated with an increased risk of venous air embolism.

The incidence of a difficult laryngoscopy or intubation varies from 1.5% to 13%, and failed intubation has been identified as one of the anaesthesia-related causes of death or permanent brain damage. Problems in the airway management can be predicted based on previous anaesthesia records, the medical history of the patient and a physical examination. Several radiological measurements have been reported to be associated with a difficult intubation. The sensitivities of the commonly used bedside tests i.e. the Mallampati classification and the thyromental distance have been reported to be from 42% to 81%, and from 62% to 91%, respectively. The figures for the specificity have varied from 66% to 84% and from 25% to 82%, respectively. The other subjective assessments and objective measurements employed for the prediction of a difficult intubation reach comparable sensitivities and specificities. Evidently, the positive predictive value is improved, if combinations of tests are used.

I-125 seeds were permanently implanted into 25 parasellar-clival meningiomas (median age of patients, 56 y) and 19 globoid meningiomas in the elderly (median age of patients, 77 y) using stereotactic technique and 3-D dose planning. Total dose at the tumour margin was increased during the series from 100 Gy to 150 Gy. The procedure caused no mortality and no serious bleeding, but injury to the III cranial nerve due to puncture occurred in one (4%) of the 25 parasellar-clival meningiomas. In two (4.5%) of the 44 cases the postoperative CT scan showed a misplaced seed, located at the tumour surface. Nonenhancing hypodense rings developed around the seeds ('hot spots') with a median diameter of 10.5 mm at 12 months corresponding to a median initial activity of 8.7 mCi. In general, meningiomas responded by slow reduction in volume. The parasellar-clival meningiomas were followed-up for a median of 19 months (6-32), and so far 4 tumours have shrunk moderately, 13 slightly, and 5 not at all. Pre-operative III, V or VI cranial nerve signs were present in 17 patients and subsided in 8 of them. On the other hand, facial numbness developed or increased in 9 of the 25 patients, indicating that the V nerve is rather sensitive to this type of irradiation. In the 19 meningiomas of the elderly, the median follow-up time was 14 months (5-26). The median relative tumour volume was 46% at 12 months. Accounting for tumour-related deaths only, the actuarial survival rate was 78% at 12 months and 62% at 24 months. In general, brain oedema persisted despite reduction in tumour volume. Stereotactic implantation of I-125 seeds into intracranial meningiomas is relatively safe. Interstitial radiotherapy represents a potential tool in the control of medium-sized intracranial meningiomas with minimal brain oedema, but its long-term impact and untoward effects remain to be followed-up.

The effects of dextran on the antithrombin (AT) III activity and blood coagulation, evaluated with thromboelastography, were investigated in 26 patients (anaesthesia risk class I or II) scheduled for minor surgery under general anaesthesia. In the Dextran group the patients were infused first with dextran 7 ml/kg, then with Ringer's acetate. In the Ringer group, the patients received only Ringer's acetate. In the recovery room fluid therapy was continued with 5% dextrose in water until the first postoperative day. Blood loss and fluid replacement were comparable in the groups. Haematocrit (Hcr) decreased significantly in the Dextran group, and the platelet count decreased in both groups during surgery. The median baseline AT III values were similar in the study groups. In the recovery room, the median AT III value was lower in the Dextran than in the Ringer group, 78% and 92%, respectively (P < 0.05). By the following day, the AT III values had returned near the initial level. After surgery, the maximal amplitude of thromboelastogram was 48 mm in the Dextran group, and 58 mm in the Ringer group (P < 0.05). In conclusion, fluid replacement with dextran resulted in modest and short-lived alterations in blood coagulation.

Venous air embolism (VAE) is a recognized complication of surgery performed with the patient in the sitting position, but it occurs also during other operations. We report two cases of VAE, associated with a notable decrease in dynamic lung compliance, detected by side-stream spirometry. Based on these cases, an experiment with 10 pigs was designed to evaluate the usefulness of side-stream spirometry in the diagnosis of VAE. Three doses of air (0.5, 1.0 and 2.0 ml kg-1) were injected via the proximal part of a 5- French gauge pulmonary artery catheter. Only the largest dose was followed by haemodynamic deterioration. Significant increases in end-tidal oxygen content and decreases in dynamic lung compliance were detected with all doses of air together with conventional signs of VAE, that is increases in pulmonary artery pressures and arterial carbon dioxide tensions, and decreases in end-tidal concentration of carbon dioxide. We conclude that continuous monitoring of end-tidal oxygen concentration and side-stream spirometry offers valuable supplements to other monitoring techniques in the detection of VAE.

Two fibreoptic bronchoscopes with insertion cords of different diameters (3.7 and 5.0 mm) were compared during fibreoptic intubation in 84 adult patients (ASA 1-2) undergoing orotracheal intubation under general anaesthesia. The fibrescope used was randomly selected. The incidence of resistance to passage of the tracheal tube through the vocal cords was higher using the thinner fibrescope, 14/40 (35%) as compared with the thicker fibrescope, 5/44 (11%) (p < 0.05). Intubation failed with the thinner fibrescope in 8/40 (20%) of patients, whereas all intubations with the thicker fibrescope were successful in six patients after manipulation of the tracheal tube (p < 0.01). With the thinner fibrescope manipulation of the tracheal tube after impingement led to intubation of the trachea in 6/14 (43%) patients. The duration of intubation was significantly shorter with the thicker fibrescope (p < 0.05). There were two instances of oesophageal intubation with the thinner fibrescope. A fibrescope with a thicker insertion cord is more suitable for orotracheal fibreoptic intubation in adult patients.

Methylparaben, the preservative of various local anaesthetic solutions, is a potential allergen. In a double-blind study, 0.5% prilocaine with (Citanest, n = 100) or without (n = 100) methylparaben were compared for the occurrence of skin reactions after intravenous regional anaesthesia of the arm in surgical patients. Skin reactions were registered after the deflation of the tourniquet cuff, and intradermal tests were performed with 0.5% prilocaine, 0.1% methylparaben and saline in all patients. Seventeen patients in the Citanest group and four patients in the methylparaben-free prilocaine group developed erythematous skin reactions in the exposed arm after deflation of the tourniquet cuff (P < 0.05, between the groups). The skin symptoms disappeared within an hour and were always restricted to the region which had been anaesthetised. None of the affected patients had positive intradermal tests. The observed skin reactions are probably non-IgE-mediated anaphylactoid reactions in which the presence of methylparaben in the local anaesthetic solution plays a major role.

Objectives: This three-part study examined the feasibility of reducing operator radiation exposure during coronary angioplasty., Background: As case loads and complexity increase, some cardiologists are receiving increasing radiation scatter doses. Techniques to reduce this are therefore becoming more important., Methods: First, the determinants of the operator dose were assessed by measuring the differences in scatter dose with different camera views. The relative contribution of fluoroscopy as opposed to cine was then quantified. Finally, operators were provided with these data, and subsequent changes in technique were evaluated., Results: Left anterior oblique views resulted in 2.6 to 6.1 times the operator dose of equivalently angled right anterior oblique views. Increasing steepness of the left anterior oblique view also resulted in a progressive increase in operator dose, with left anterior oblique 90 degrees causing eight times the dose of left anterior oblique 30 degrees and three times that of left anterior oblique 60 degrees. In the 45 coronary angioplasty cases prospectively analyzed, fluoroscopy was found to be a greater source of total radiation than cine by a 6.3:1 ratio (range 1.1 to 15.8). Once operators were made aware of the importance of left anterior oblique fluoroscopy, there was a marked reduction in its use. When this was not feasible, there was a reduction in the steepness of the angulation. Left anterior oblique fluoroscopy during angioplasty of the left anterior descending and circumflex coronary arteries was reduced from 40% of total screening time to approximately 5%, and left anterior oblique angulation for fluoroscopy during angioplasty of the right coronary artery decreased from 43.6 degrees (+/- 9.1 degrees) to 29.4 degrees (+/- 2.2 degrees). Success rates (90% vs. 89%) and screening times (19.5 vs. 20.7 min) remained unchanged in 200 coronary angioplasties performed after the study. Average operator radiation dose (measured by radiation badges worn under lead at waist level) was reduced from 32.6 to 14.3 microSv/operator per week despite a slight increase in case load., Conclusions: Fluoroscopy is the major source of total radiation exposure during coronary angioplasty, with left anterior oblique views providing the highest dose. Modification of views is feasible and will result in significant reduction of operator radiation dose.

Epidurally administered fentanyl is commonly used in postoperative pain management. The onset of action is rapid, but the duration of analgesia is short. In this study we examined the hypothesis that a poorly soluble salt of fentanyl (fentanyl pamoate) would create a depot of the drug in the epidural space and thus provide prolonged analgesia. The dose-response relationship and duration of analgesic action of epidural fentanyl citrate (FC) and fentanyl pamoate (FP) were studied in white male Sprague-Dawley rats. Somatic and visceral nociceptive stimulation (tail flick and colorectal distension, respectively) were used to test the analgesic effects of the drugs. The calculated dose producing 100% of the maximum possible effect (100% MPE) for FP was 31 micrograms toward somatic and 33 micrograms toward visceral noxious stimulation, and for FC it was 3 micrograms toward both stimulations. The antinociceptive effects were similar, with 31 micrograms of FP and 3 micrograms of FC. The areas under the time-response curves (AUC) were significantly higher with FP than with FC when high doses (5 micrograms of FC or 50 micrograms of FP) were used, but with doses expected to produce 100% MPE, differences between the study drugs were not observed in the duration of analgesia. We conclude that the duration of antinociceptive effect of fentanyl can be prolonged when administered as a poorly soluble salt.

Background: Ventilation of the lungs with isoflurane in nitrous oxide and oxygen has been shown to increase the plasma concentration of norepinephrine. Whether this increase is related to the tachycardia and increased arterial blood pressures, seen following a sudden increase in the concentration of isoflurane, was tested in humans., Methods: Twenty-two healthy patients in whom the trachea was intubated were given 15 min of stable isoflurane-O2-air anesthesia [end-tidal concentration of isoflurane (ETIso) of 1.3%] (baseline). Patients were then randomly allocated to one of two groups. For 13 "IsoHigh" patients, the inspired concentration of isoflurane was increased abruptly. In those patients, the ETIso was kept at 2.6% for 10 min, i.e., until the end of the study, after which the depth of anesthesia was reduced. For nine "IsoLow" control patients, the ETIso level of 1.3% was continued until the end of the study. Heart rate, arterial pressures, catecholamine levels, and end-tidal concentration of CO2 were recorded at baseline and at 1, 1.5, 2, 4, 6, and 10 min after increase in isoflurane., Results: IsoHigh patients showed significant increases in heart rate (40% from 84.6 to 118.1 beats/min), systolic arterial pressure (SAP, 23%, from 96.4 to 118.3 mmHg), and diastolic arterial pressure (DAP, 30%, from 53.9 to 70.0 mmHg); all three variables peaked at 2 min. Significant increases occurred also in norepinephrine levels (80%, from 0.342 to 0.615 ng/ml) and in end-tidal concentration of CO2 (from 4.22% to 4.43%), both of which peaked at 4 min. Epinephrine levels did not increase significantly, although significant differences were seen between IsoHigh and IsoLow patients during the trial. IsoLow patients had no changes in these variables., Conclusions: A sudden increase in isoflurane concentration is associated with a transient but clinically significant increase in heart rate, arterial pressures, and norepinephrine concentration.

Cardiovascular collapse following intravascular bupivacaine may be resistant to treatment. The effect of amrinone on recovery from bupivacaine-induced severe cardiovascular depression was evaluated in 20 pigs (13-26 kg) in a placebo-controlled randomized double-blind study. Under 0.7% isoflurane anesthesia at FIO2 0.21, 0.5% bupivacaine 2 mg.kg-1.min-1 was infused until mean arterial pressure was 40% of the baseline. Cardiac output and heart rate decreased 75% and 50% from the baseline, respectively. The total dose of bupivacaine was 17 +/- 6 (SD) mg.kg-1 in the control and 19 +/- 5 mg.kg-1 in the amrinone group, resulting in mean plasma concentrations of 42 +/- 6 and 53 +/- 19 micrograms.ml-1, respectively. A bolus of amrinone 4 mg.kg-1 (n = 10) was given immediately after cardiovascular depression, followed by an infusion of 0.6 mg.kg-1.min-1. The control animals received corresponding volumes of physiologic saline (n = 10). After cardiovascular depression, the lungs were ventilated with FIO2 1.0 without anaesthetics or sympathomimetic support. Electric activity of the heart ceased in all control animals in 3.9 +/- 2 min after cardiovascular depression despite atropine and external cardiac compression. All animals in the control group and 5 of 10 animals in the amrinone group were given atropine (P less than 0.01). The animals receiving amrinone survived without cardiac compression (P less than 0.0001). During bupivacaine infusion, all animals developed burst suppression in the electroencephalogram. At the time of cardiovascular depression, in 8 of 10 control and in 6 of 10 amrinone animals, the electroencephalogram was isoelectric.(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective study of problems of postoperative airway maintenance after surgery for mandibular cancers was conducted. Twenty-seven patients treated in an intensive care unit after mandibular resection and primary reconstruction were included. The mean duration of nasotracheal intubation in 22 patients was 33.7 hours. Reintubation because of breathing difficulties was required in four cases. In one of these cases, failed intubation led to an emergency cricothyroidostomy. Failure to perform reintubation resulted in the death of one patient. One patient was tracheostomized after 5 days of nasotracheal intubation. Prolonged nasotracheal intubation after major surgery for oral malignant neoplasms may be an alternative to tracheostomy, provided that adequate monitoring is available after extubation. The safe duration of endotracheal intubation is difficult to determine. Primary reconstruction does not eliminate the need for an artificial airway after tumor surgery.

The effect of prophylactic minitracheostomy on the incidence of postoperative atelectasis and pulmonary gas exchange was evaluated in a prospective, random control study of 29 patients undergoing thoracotomy. Fourteen were randomly allocated to have a minitracheostomy, which was done in the recovery room immediately after operation, and the remainder acted as controls. Increased radiodensity and atelectasis were seen more often on the chest radiographs of the control patients on the first (p less than 0.05) and on the seventh postoperative days (p less than 0.01), irrespective of the extent of the pulmonary operation. Bronchial lavage under general anaesthesia or sedation was required by 6 of the 15 control patients, but by none of those who had had a minitracheostomy (p less than 0.05). These results support the hypothesis that minitracheostomy is a useful adjunct to postoperative care after thoracotomy.

Thirty-six children (mean age 2.4 years) premedicated with oral chloral hydrate 70 mg kg-1 and atropine 0.03 mg kg-1 were anaesthetized with either 3.75% isoflurane or 2.5% halothane in 70% nitrous oxide in oxygen. The eyelash reflex disappeared in 39 +/- 7 s (mean +/- SD) with isoflurane and in 56 +/- 16 s with halothane (P less than 0.001). Tachypnoea was seen with both anaesthetics. Coughing, breath holding, stridorous breathing and respiratory depression were seen during isoflurane but not during halothane induction (P less than 0.01). In nine of 20 children anaesthetized with isoflurane, the ventilation had to be assisted before intubation. Endotracheal intubation was possible in 224 +/- 35 s with isoflurane and in 281 +/- 64 s with halothane (P less than 0.01). Intubating conditions were satisfactory in 80% of the children anaesthetized with either volatile agent. Cardiovascular responses to endotracheal intubation were minimal with both anaesthetics. No cardiac dysrhythmias were noted. Heart rate was higher during isoflurane than during halothane induction. Diastolic arterial pressure was lower during isoflurane than during halothane induction immediately and 5 min after intubation.