Anti-arrhythmic effects of lidocaine metabolites

Patients on lidocaine infusions for the control of arrhythmias accumulate significant concentrations of lidocaine metabolites. The potency of lidocaine in suppressing digitalis-induced arrhythmias in guinea pig atria was compared to that of two of the metabolites of lidocaine monoethyglycinexylidide (MEGX), and glycinexylidide (GX). The potency of MEGX relative to lidocaine was 0.833. GX was only $\text{1}\text{10}$ as potent. Thus, it would seem that MEGX may contribute to the total anti-arrhythmic effect of a lidocaine infusion.     

Mitochondrial DNA mutations in oral squamous cell carcinoma

It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations within the ND2 gene of histologically normal parotid salivary gland tissue of smokers may be molecular biomarkers for smoking-induced mtDNA damage. Oral squamous cell carcinoma (SCC) is strongly related to cigarette smoking; therefore, we used PCR and direct sequencing to establish whether mtDNA mutations were also present in oral SCC which could be used as additional biomarkers for smoking-associated DNA damage. In addition to searching for mutations in the ND2 gene, the mitochondrial D-Loop was also analysed. Three mutation hotspots were observed in the D-Loop at nt 146, 152 and 186, two of which (nt 146 and 152) have also been implicated in oesophageal SCC, another smoking-related cancer. The mutation hotspot observed at nt 186 has not previously been reported in other tumours. Furthermore, we show that the mutations previously reported within the ND2 gene in normal parotid tissue of smokers were not evident in these samples, but that a mutation hotspot occurs at nucleotide 4917 in oral SCC. We also show that D-Loop mutations occur predominantly in male smokers and female non-smokers and that this association with gender is statistically significant (P = 0.003). We conclude that the mtDNA mutation hotspots found in this study, in particular nt 186, are potential biomarkers for oral SCC. However, owing to gender-specific differences in occurrence in smokers and non-smokers, and a lack of environmental smoking history, in general, it is difficult to associate these mutations with mtDNA damage induced by smoking. If the mutations observed in the subset of male patients are smoking induced, given our previous findings, mutation hotspots in the ND2 gene may be tissue specific suggesting the causative mutagens for mtDNA damage within these tissues are likely to be different.     

Percutaneous versus surgical tracheostomy: A randomized controlled study with long-term follow-up

OBJECTIVE: To compare the safety, availability, and long-term sequelae of percutaneous vs. surgical tracheostomy. DESIGN: Prospective, randomized, controlled study. SETTING: Combined medical/surgical intensive care unit in a tertiary referral hospital. PATIENTS: Two hundred critically ill mechanically ventilated patients who required tracheostomy. INTERVENTIONS: Tracheostomy by either percutaneous tracheostomy or surgical tracheostomy performed in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the aggregate incidence of predefined moderate or severe complications. The secondary outcome measures were the incidence of each of the components of the primary outcome. Long-term follow-up included clinical assessment, flow volume loops, and bronchoscopy. Both groups were well matched for age, gender, admission Acute Physiology and Chronic Health Evaluation II score, period of endotracheal intubation, reason for intubation, and admission diagnosis. There was no statistical difference between groups for the primary outcome. Bleeding requiring surgical intervention occurred in three percutaneous tracheostomy patients and in no surgical tracheostomy patient (p = .2). Postoperative infection (p = .044) and cosmetic sequelae (p = .08) were more common in surgical tracheostomy patients. There was a shorter delay from randomization to percutaneous tracheostomy vs. surgical tracheostomy (p = .006). Long-term follow-up revealed no complications in either group. CONCLUSIONS: Both percutaneous tracheostomies and surgical tracheostomies can be safely performed at the bedside by experienced, skilled practitioners.