After consuming lunch, twenty-six male subjects ingested alcohol ad libitum over approximately one hour. At least 1.5 hours after drinking ceased, the subjects provided breath samples into a Breathalyzer® Model 900 or 900A. Immediately after providing the breath samples, blood was collected from the cubital vein using a sterile disposable plastic syringe. Part of the blood sample (3-10 mL) was placed into a blood tube containing 1 % sodium fluoride and 0.5 % sodium citrate and was analysed for alcohol by headspace gas chromatography. The remaining blood (3-10 mL) was placed in the subject's mouth for up to 30 seconds and then swallowed or expectorated. A second Breathalyzer test was conducted within ten minutes of the first. The blood alcohol concentrations of the subjects averaged 0.095 gldL and ranged between 0.044 to 0.168 gldL. The untruncated Breathalyzer results were significantly lower after introducing blood into the mouth (p=0.017). When these Breathalyzer results were truncated to two decimal places, however, these slight differences were eliminated. In addition, when the initial Breathalyzer results were compared to the blood alcohol concentrations the apparent blood breath ratios averaged 2319, with a range of 1947:1 to 2654:1. We conclude that blood in the mouth does not lead to an overestimation of the breath alcohol concentration of drinking subjects. RESUME Apres le repas du midi, on a demands it 26 sujets males de consommer de I'alcool ad libitum durant une perlode approximative d'une heure. Des echantillons d'haleine ont ete obtenus de ces sujets apres au moins une heure et demie suivant la fin de la perlode de consommation d'alcool et ont ete analyses it I'aide d'instruments de type Breathalyzer® modele 900 ou 900A. lmmedlatement apres I'obtention des ces echantillons d'haleine, du sang a ete preleve de ces sujets it I'aide d'une seringue de plastique sterile it usage unique. Une partie des echantillons de sang (3-10 mL) a ete tranferee it un tube qui contenait du fluorure de sodium it 1% et du citrate de sodium it 0.5%. La concentration d'alcool de ce sang a ete determinee par chromatographie en phase gazeuse it espace de tete. La quantlte reslduelle de sang (3-10 mL) a ete placee dans la bouche du sujet pour une duree de temps d'au moins 30 secondes et , par la suite, a ete avalee ou expectoree. Une deuxteme analyse d'alcool a ete faite it I'aide du Breathalyzer® durant les dix prochaines minutes apres la premiere analyse. La concentration moyenne d'alcool dans le sang etait de 0.095 g/dL avec un ecart de concentrations de 0.044 it 0.168 gldL. Les resultats non tronques obtenus avec le Breathalyzer® etaient significativement inferieurs apres I'introduction du sang dans la bouche (p=O.017). Cependant, apres que ces mernes resultats ont ete tronques jusqu'a la deuxlerne decimale, ces differences minimes ont ete eliminees. De plus, une comparaison des resunats initiaux provenant du Breathalyzer® avec les concentrations sanguines d'alcool a revele un rapport de la concentration d'alcool du sang i...
Introduction: Rett syndrome (RTT) is an X-linked disorder caused by mutations in the MECP2 gene resulting in various neurological, respiratory, and gastrointestinal symptoms. Up to 25% of deaths in RTT are sudden. Prolonged corrected QT (QTc) has also been reported and thought to be a cause of sudden death in RTT. Previous studies in mice with RTT showed that MECP2 mutations lead to persistent increased cardiac sodium current causing prolonged QTc and increasing risks of ventricular tachycardia. The aim of this study was to determine whether sodium channel blockers lidocaine (acutely) and mexiletine (chronically) shorten QTc in RTT patients. Hypothesis: Sodium channel blockers such as lidocaine (acutely) and mexiletine (chronically) significantly shorten QTc (≥ 30ms from baseline) in RTT patients with prolonged QTc. Methods: RTT patients with prolonged QTc were prospectively enrolled to receive a lidocaine attenuation test. The test consisted of a loading dose of 1 mg/kg intravenous lidocaine followed by a continuous infusion at 50 μg / (kg·min). Patients were deemed responders should their QTc shorten by 30 ms or more. These patients were then prescribed mexiletine for chronic therapy. Results: A total of 6 patients (all females) were given lidocaine and mexiletine. The median age of the cohort at the time of testing was 12 years (8-19 years), and the median QTc before therapy was 480.5 ms (476-506 ms). All 6 patients responded positively to lidocaine with median QTc shortening of 44.5 ms (33-54 ms, P = 0.018). The median daily dose of mexiletine was 8.75 mg/kg. The median duration of therapy was 5 months (4-12 months). Mexiletine shortened QTc by an average of 47 ms at latest follow-up ( P = 0.016). One patient developed whole-body tremors as a side effect of mexiletine, which was stopped. Conclusions: Sodium channel blockers that target late sodium channels were effective in shortening QTc thereby confirming the presence of late sodium current causing prolonged QTc in RTT. Therefore mexiletine could be used clinically in RTT patients with long QTc. Larger and longer studies are needed to confirm these drugs’ positive effects in shortening the QTc and reducing arrhythmic events in RTT patients.
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