The neurotoxic effects of amitriptyline are mediated by apoptosis and are effectively blocked by inhibition of caspase activity

Oral tricyclic antidepressants, widely used as adjuncts in the treatment of chronic pain, block sodium channels in vitro and nerve conduction in vivo. However, toxicity of amitriptyline has been observed after neural application. We therefore investigated the mechanism and possible prevention of amitriptyline neurotoxicity. To assess dose-dependent neurotoxicity of amitriptyline, we incubated neuron cultures from adult rat dorsal root ganglia with amitriptyline and quantified neuronal survival. Additionally, we investigated accepted markers of apoptosis (mitochondrial membrane potential, cytosolic cytochrome c, and activated caspase-3) and co-incubated amitriptyline with an inhibitor of caspase activity, z-vad-fmk, to assess the effect on cell survival. We found a dose-dependent neurotoxic effect of amitriptyline. Neurons incubated with amitriptyline exhibited loss of mitochondrial membrane potential, release of cytochrome c into the cytoplasm, and activation of caspase-3. Co-incubation with z-vad-fmk substantially improved neuronal survival in culture. In conclusion, amitriptyline-induced neurotoxicity is mediated by apoptosis and is attenuated by inhibition of caspase activity, suggesting that inhibition of apoptotic pathways may be efficient at alleviating local anesthetic-induced neurotoxicity. In vivo studies will have to corroborate whether the co-injection of anti-apoptotic drugs with local anesthetics decreases neurotoxic side effect

An anatomic landmark to simplify subclavian vein cannulation: the "deltoid tuberosity"

The subclavian vein is frequently used to obtain central venous access. Several landmarks exist to determine the puncture site and angle, but they may require patient manipulation and anatomic measurements. We studied the feasibility of using the deltoid tuberosity, located on the lateral aspect of the clavicle, as an anatomic landmark. This would not necessitate these maneuvers and could therefore facilitate subclavian vein access. To systematically investigate this landmark, we conducted a study in four phases: 1) Two blindfolded examiners determined the distance between the tuberosity's medial border and the clavicle's lateral end in 100 dried clavicles and then 2) performed subclavian vein cannulation in 20 fresh human cadavers using the tuberosity and the suprasternal notch as landmarks. 3) Three-dimensional reconstructions of the subclavian artery and vein and surrounding structures were derived from computed tomography datasets of 10 patients. The length of the path of a virtual subclavian vein cannulation with the deltoid tuberosity landmark was measured bilaterally. 4) In a prospective, randomized trial, subclavian vein cannulation was performed in 60 patients with a standard approach or with the deltoid tuberosity as landmark. Interobserver difference between measurements in phase 1 was 3 +/- 1 mm (mean +/- sd); subclavian vein cannulation was achieved in 19 of 20 cases, whereas the subclavian artery was cannulated in one case (phase 2). In phase 3, there was no significant difference in skin-vein distance between the left (4.9 +/- 0.5 cm) and right (4.7 +/- 0.6 cm) sides. In phase 4, subclavian vein cannulation could be performed in all patients; moreover, subclavian vein cannulation was significantly (P <0.01) faster in the deltoid tuberosity group versus the standard approach group (23 +/- 16 versus 34 +/- 14 s). We conclude that the clavicle's tuberosity may reflect an alternative anatomic landmark to simplify subclavian vein cannulation by minimizing patient manipulation and anatomic measurement

Pilot study: volatile organic compounds as a diagnostic marker for head and neck tumors

In the last decade, the analysis of volatile organic compounds (VOC) has undergone a rapid development. In this pilot study, patients with HNSCC were tested with a proton transfer reaction-mass spectrometry in order to establish a minimal invasive screening method. Overall in a period of 2 years, 22 carcinoma patients were recruited for the study. All patients had a newly diagnosed histologically secured squamous cell carcinoma of the upper aerodigestive tract. These results were statistically compared with 3 control groups: healthy controls, high-risk, and posttherapy patients. Two hundred nine different masses were measured; 188 of these were evaluated. The statistical workup of the 4 study groups produced 42 different masses, which showed a statistically significant difference from the carcinoma group compared with the control groups. A screening method for HNSCC using VOC seems to be possible, but further investigation is necessar