Patricia Murphy

Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet

The ketogenic diet (KD), a treatment for drug‐resistant epilepsy, elevates brain acetone. Acetone has been shown to suppress experimental seizures. Whether elevation of acetone is the basis of the anticonvulsant effects of the KD and whether acetone, like the KD, antagonizes many different types of seizures, however, is unknown. This study investigated the spectrum of the anticonvulsant effects of acetone in animal seizure models. Rats were injected with acetone intraperitoneally. Dose–response effects were measured in four different models: (1) the maximal electroshock test, which models human tonic‐clonic seizures; (2) the subcutaneous pentylenetetrazole test, which models human typical absence seizures; (3) the amygdala kindling test, which models human complex partial seizures with secondary generalization; and (4) the AY‐9944 test, which models chronic atypical absence seizures, a component of the Lennox–Gastaut syndrome. Acetone suppressed seizures in all of the models, with the following ED50s (expressed in mmol/kg): maximal electroshock, 6.6; pentylenetetrazole, 9.7; generalized kindled seizures, 13.1; focal kindled seizures, 26.5; AY‐9944, 4.0. Acetone appears to have a broad spectrum of anticonvulsant effects. These effects parallel the effects of the KD. Elevation of brain acetone therefore may account for the efficacy of the KD in intractable epilepsy. Ann Neurol 2003

Testing the raters: inter-rater reliability of standardized anaesthesia simulator performance

PurposeAssessment of physician performance has been a subjective process. An anaesthesia simulator could be used for a more structured and standardized evaluation but its reliability for this purpose is not known. We sought to determine if observers witnessing the same event in an anaesthesia simulator would agree on their rating of anaesthetist performance.MethodsThe study had the approval of the research ethics board. Two one-hour clinical scenarios were developed, each containing five anaesthetic problems. For each problem, a rating scale defined the appropriate score (no response to the situation: score=0; compensating intervention defined as physiological correction: score= 1; corrective treatment: defined as definitive therapy score=2). Video tape recordings, for assessment of inter-rater reliability, were generated through role-playing with recording of the two scenarios three times each resulting in a total of 30 events to be evaluated. Two clinical anaesthetists, uninvolved in the development of the study and the clinical scenarios, reviewed and scored each of the 30 problems independently. The scores produced by the two observers were compared using the kappa statistic of agreement.ResultsThe raters were in complete agreement on 29 of the 30 items. There was excellent inter-rater reliability (=0.96, P < 0.001).ConclusionThe use of videotapes allowed the scenarios to be scored by reproducing the same event for each observer. There was excellent inter-rater agreement within the confines of the study. Rating of video recordings of anaesthetist performance in a simulation setting can be used for scoring of performance. The validity of the scenarios and the scoring system for assessing clinician performance have yet to be determined.RésuméObjectifEn médecine, 1’évaluation de la performance demeure subjective. En anesthésie, un simulateur peut être utilisé pour foumir une évaluation mieux structure et standardisée mais on n’en connaît pas la fiabilité. Nous avons cherché à déterminer si, en anesthésie, les observateurs d’un phénomène simulé pouvaient s’entendre sur leur appréciation de la performance de I’anesthesiste.MethodesLe comité d’éthique avait approuvé cette étude. Deux scénarios cliniques d’une durée d’une heure comportant cinq problèmes anesthésiques ont été élaborés. Une échelle de cotation accordant un score à chacun (aucune réponse à ta situation =0, une intervention déftnie comme une correction physiologique = 1; une intervention thérapeutique considérée comme le traitement défmitif = 2). Des enregistrements sur vidéocassettes ont servi à évaluer la concordance entre les évaluateurs. Ces enregistrements témoignaient du rôle joué pendant les deux scénarios exécutés trois fois pour un total de 30 événements. Deux anesthésistes, ignorant le déroulement de l’étude et le contenu des scénanos, ont révisé et coté indépendamment les 30 problèmes. Les deux observateurs ont comparé les scores obtenus à l’aide de la méthode statistique d’accord kappa.RésultatsLes évaluateurs s’accordaient completement sur 29 des 30 sujets. La fiabilité entre évaluateurs était excellente (=0.96, P < 0,001).ConclusionL’utilisation des vidéocassettes a permis de coter les scénanos en reproduisant le même événement devant chacun des observateurs. Dans le cadre de l’étude, l’accord entre les évaluateurs était excellent. On peut utiliser 1’évaluation de (a performance d’un anesthésiste à l’aide d’enregistrements sur vidéocassette au cours d’une simulation. La validite des scénarios et du système de cotation reste à déterminer.

Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery.

PurposeTo evaluate the combination of rectal indomethacin with patient controlled intravenous morphine analgesia (PCA) on postoperative pain relief and opioid use after cardiac surgery.MethodsWith institutional ethics approval, 57 consenting adults undergoing elective aortocoronary bypass surgery were randomly assigned preoperatively in a double-blind fashion to receive either placebo (n = 26) or indomethadn 100 mg suppositories (n = 31), 2–3 hr postoperatively, and 12 hr later. Both groups utilized PCA morphine. Pain scores in the two treatment groups were assessed on a 10-cm visual analogue scale (VAS) (at rest and with cough) at 4, 6, 12, 18 and 24 hr after initial dosing, and were analyzed through a 2 × 5 repeated measures of variance. The 24 hr analgesic consumption, 12 and 24 hr chest tube blood loss, and time to tracheal extubation were also recorded, and compared for the two treatment arms through Student’s t test on independent samples.ResultsPostoperative morphine consumption in the first 24 hr was 38% less in the indomethadn group (22.40 ± 12.55 mg) than the placebo group (35.99 ± 25.84 mg), P= 0.019. Pain scores, measured with a VAS, were 26% to 66% lower in the indomethacinvs placebo group at rest (P=0.006), but not with cough, for all times assessed. There was no difference in blood loss (at 12 hr) or time to tracheal extubation for both groups.ConclusionThe combination of indomethacin with morphine after cardiac surgery results in reduced postoperative pain scores and opioid use without an increase in side effects.RésuméObjectifÉvaluer l’action combinée d’indométhacine rectale et d’analgésie contrôlée par le patient (ACP) avec de la morphine intraveineuse sur la douleur postopératoire et l’usage d’opioïde en cardiochirurgie.MéthodeAyant obtenu l’approbation du comité d’éthique de l’hôpital, 57 adultes consentants qui devaient subir un pontage aortocoronarien électif ont été répartis au hasard avant l’opération afin de recevoir en double insu, soit un placebo (n = 26), soit de l’indométhacine (n = 31) en suppositoires de 100 mg, 2–3 h après l’opération et 12 h plus tard. Tous ont utilisé de la morphine pour l’ACP. Les scores de douleur ont été évalués à l’aide d’une échelle visuelle analogue (EVA) de 10 cm (au repos et lors de la toux) à 4, 6, 12, 18 et 24 h après le dosage initial et analysés selon un plan 2 × 5 de mesures répétées de la variance. La consommation d’analgésique à 24 h, la perte sanguine au drain thoracique à 12 et 24 h et le moment de l’extubation endotrachéale ont été notés et comparés d’un groupe à l’autre par le test t de Student sur des échantillons indépendants.RésultatsLa demande postopératoire de morphine des 24 premières h a été de 38% moindre avec l’indométhacine (22,40 ± 12,55 mg) qu’avec le placebo (35,99 ± 25,84 mg),P = 0,019. Les scores de douleur de l’EVA ont été de 26% à 66% plus faibles pour l’indométhacine vs le placebo, au repos (P = 0,006), non lors de la toux, et ce, pour tous les temps de mesures. La perte sanguine a été semblable dans les deux groupes (à 12 h) ainsi que le temps total d’intubation.ConclusionAdministrée après une intervention cardiaque, la combinaison d’indométhacine et de morphine a réduit les douleurs et l’usage d’opioïdes sans augmenter les effets secondaires.

Cognitive functioning in adults with Attention-Deficit/ Hyperactivity Disorder

objectives: Children with Attention-Deficit/Hyperactivity Disorder (ADHD) appear to be deficient in executive control. The purpose of this study was to determine if adults with ADHD are also deficient in executive control. Method: The performance of 18 adults with ADHD and 18 control subjects was compared on two tests of executive control, and two control tasks. The executive control tasks used in the study were the Trail Making Test (B), and the Tower of Hanoi. The control tasks used were the Trail Making Test (A), and the Benton Facial Recognition Test. Results: The subjects with ADHD performed more poorly than did the normal controls on the executive control tasks. The subjects with ADHD, however, also performed more poorly on the Trail Making Test (A). Conclusions: The ADHD subjects showed a deficit in executive control, but this deficit was not confined to the executive control domain.

Effect of the ketogenic diet on the activity level of Wistar rats.

Children, adolescents, and adults with epilepsy often also show symptoms associated with attention-deficit/hyperactivity disorder (ADHD). The ketogenic diet, which is administered to children with epilepsy refractory to drug therapy, seems to improve behavior in individuals with symptoms of ADHD. The basis for this improvement is unknown, although it seems to be unrelated to seizure control. The present research was designed to investigate the effect of two ketogenic diets on the behavior of normal adult male rats. Two experiments were conducted. In experiment 1, 36 subjects were placed on one of three diets: a control diet, a 6.3:1 ketogenic diet, and a 4:1 ketogenic diet. In experiment 2, 20 subjects were placed either on a control diet or on a 4:1 ketogenic diet. The activity level of each subject was measured using an open field test. Time spent immobile, grooming, and in exploratory behavior was measured for 600 s. Subjects were tested once before initiation of the diets and once while on the diets. No significant group differences were found in activity level before initiation of the diets. After initiation of the diets, subjects in both ketogenic groups showed a significantly lower activity level than the rats on the control diet. The ketogenic diet decreases activity level in an animal model. This behavioral change may relate to the improved behavior seen when children with symptoms of ADHD are placed on the diet.

The ketogenic diet causes a reversible decrease in activity level in Long–Evans rats

Individuals with epilepsy also often exhibit symptoms of attention deficit hyperactivity disorder (ADHD). The ketogenic diet, which is a high fat, low protein, and low carbohydrate diet used in the treatment of intractable epilepsy, also appears to improve symptoms of ADHD in individuals with both disorders. Previous research suggests that the diet decreases the activity level of rats. The purpose of the present research was to further investigate the effects of the ketogenic diet on activity level, using an animal model. Two experiments were conducted. The first experiment examined the time frame and reversibility of the effect of the diet on activity level. The second experiment examined the relationship between activity level and anxiety level. In both experiments, adult male Long-Evans rats were placed on either a ketogenic diet or a control diet. The results of the first experiment show that the ketogenic diet can cause a decrease in activity level within 24 h and that the results are reversible. The results of Experiment 2 show that the decrease in activity level is not linked to a change in anxiety level. The ketogenic diet may be of use in the treatment of ADHD.

Transfusion of ABO-nonidentical platelets is not associated with adverse clinical outcomes in cardiovascular surgery patients

BACKGROUND: Current blood transfusion standards in Canada and the United States permit transfusion of ABO‐nonidentical platelets when ABO‐identical platelets are not available. This practice increases the availability of platelets, a component in chronic shortage in Ontario, Canada because of the 5‐day shelf‐life. The impact of transfusing ABO‐nonidentical platelets on patient outcomes is unknown.

Use of the ketogenic diet as a treatment for epilepsy refractory to drug treatment

The ketogenic diet is a high-fat, low-carbohydrate and low-protein diet used in the treatment of epilepsy that does not respond to antiepileptic drugs. The diet has been found to be very effective in treating intractable epilepsy in children. There is also some evidence that the diet is useful in treating drug-resistant epilepsy in infants, adolescents and adults. This paper traces the history and development of the ketogenic diet and reviews the clinical and animal research investigating its effects.

Use of a structured panel process to define antimicrobial prescribing appropriateness in critical care

Background Antimicrobial prescribing is frequently reported as appropriate or inappropriate, particularly in the ICU. However, the definitions used are non-standardized and lack validity and reliability. Objectives To develop standardized definitions of appropriateness for antimicrobial prescribing in the critical care setting. Methods We used consensus-based modified Delphi and RAND appropriateness methodology to develop criteria to define appropriateness of antimicrobial prescribing. A multiphased approach with an online questionnaire followed by a facilitated in-person meeting was utilized and included clinicians from a variety of practice areas (e.g. surgeons, infectious diseases specialists, intensivists, transplant specialists and pharmacists). Results There were a total of 23 criteria agreed upon to define the following categories of antimicrobial prescribing: appropriate; effective but unnecessary; inappropriate; and under-treatment. Conclusions These standardized criteria for appropriateness may be generalizable to other patient populations and utilized with other tools to adjudicate prescribing practices.