Urinary acetonitrile concentrations correlate with recent smoking behaviour

OBJECTIVES: To assess the concentration of acetonitrile (a saturated aliphatic nitrile) in the urine of habitual cigarette smokers and non-smokers, as exposure to smoke can be measured by monitoring ambient air or by in vivo tests, but acetonitrile measured in exhaled breath is reportedly a quantitative marker of recent smoking behaviour. SUBJECTS AND METHODS: The study included 101 volunteers (57 men and 44 women, mean age 49 years). An absence of urinary tract infection on urine analysis or clinical history was mandatory. The subjects were classified into five groups, i.e. a control group of non-smokers and four groups according to the number of cigarettes smoked daily. Urine samples were stored at 8 degrees C until acetonitrile was measured, within 24 h of collection, using proton-transfer reaction mass spectrometry (PTR-MS). Each measurement was repeated at least 10 times, and the mean used for statistical analysis. RESULTS: The mean (sd) acetonitrile level in the urine of 46 non-smokers was 3.74 (1.78) parts per billion volatile (ppbv). The concentration of acetonitrile increased with the number of cigarettes smoked daily, the highest concentration being in the subgroup of 13 very heavy smokers (>30 cigarettes/day) with means up to 28.04 (5.38) ppbv. CONCLUSION: PTR-MS is a quick, noninvasive online method for determining urinary acetonitrile levels, a marker for recent active and passive smoking behaviour, and thus for checking compliance. As smoking has been shown to affect the genesis of bladder cancer, further studies are required to determine the association of acetonitrile with bladder cancer.     

Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin

Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid l-arginine. iNOS-derived NO plays an important role in numerous physiological (e.g. blood pressure regulation, wound repair and host defence mechanisms) and pathophysiological (inflammation, infection, neoplastic diseases, liver cirrhosis, diabetes) conditions. iNOS is the synthase isoform most commonly associated with malignant disease. Nevertheless, the role of iNOS during tumor development is highly complex, and incompletely understood. Both promoting and deterring actions have been described, presumably depending upon the local concentration of iNOS within the tumor microenvironment. In particular, pivotal effects such as malingnant transformation, angiogenesis, and metastasis are modulated by iNOS. On the other hand, NO derived from macrophages has a potentially cytotoxic/cytostatic effect upon tumor cells. Hence, therapeutical interference with iNOS activity is of considerable interest, especially in tumors where metastatic activity, host defence mechanisms and the level of differentiation seem to be correlated to iNOS expression. This review will aim to summarize the dual actions of iNOS as simultaneous tumor promoter and suppressor.     

The incidence of lumbar ligamentum flavum midline gaps

Lumbar epidural anesthesia and analgesia has gained increasing importance in perioperative pain therapy for abdominal and lower limb surgery. The loss-of-resistance technique, used to identify the epidural space, is thought to rely on the penetration of the ligamentum flavum. However, the exact morphology of the ligamentum flavum at different vertebral levels remains controversial. Therefore, in this study, we directly investigated the incidence of lumbar ligamentum flavum midline gaps in embalmed cadavers. Vertebral column specimens were obtained from 45 human cadavers. On each dissected level, ligamentum flavum midline gaps were recorded. The incidence of midline gaps per number of viable specimens at the following levels was: L1-2 = 10 of 45 (22.2%), L2-3 = 5 of 44 (11.4%), L3-4 = 5 of 45 (11.1%), L4-5 = 4 of 43 (9.3%), L5/S1 = 0 of 33 (0%). In conclusion, the present study determined the frequency of lumbar ligamentum flavum midline gaps. Gaps in the lumbar ligamentum flavum are most frequent between L1 and L2 but are more rare below this level. When using the midline approach, the ligamentum flavum may not impede entering the epidural space in all patients. IMPLICATIONS: The ligamentum flavum is a crucial anatomical landmark for the safe performance of epidural anesthesia. However, the present study demonstrates some failure of the lumbar ligamentum flavum as a landmark. This may mean that, using a midline approach, one cannot always rely on the ligamentum flavum as a perceptible barrier to epidural needle advancement.     

Mitigation of direct neurotoxic effects of lidocaine and amitriptyline by inhibition of p38 mitogen-activated protein kinase in vitro and in vivo

BACKGROUND: Local anesthetic-induced direct neurotoxicity (paresthesia, failure to regain normal sensory and motor function) is a potentially devastating complication of regional anesthesia. Local anesthetics activate the p38 mitogen-activated protein kinase (MAPK) system, which is involved in apoptotic cell death. The authors therefore investigated in vitro (cultured primary sensory neurons) and in vivo (sciatic nerve block model) the potential neuroprotective effect of the p38 MAPK inhibitor SB203580 administered together with a clinical (lidocaine) or investigational (amitriptyline) local anesthetic. METHODS: Cell survival and mitochondrial depolarization as marker of apoptotic cell death was assessed in rat dorsal root ganglia incubated with lidocaine or amitriptyline either with or without the addition of SB203580. Similarly, in a sciatic nerve block model, the authors assessed wallerian degeneration by light microscopy to detect a potential mitigating effect of MAPK inhibition. RESULTS: Lidocaine at 40 mm/approximately 1% and amitriptyline at 100 microm reduce neuron count, but coincubation with the p38 MAPK inhibitor SB203580 at 10 mum significantly reduces cytotoxicity and the number of neurons exhibiting mitochondrial depolarization. Also, wallerian degeneration and demyelination induced by lidocaine (600 mm/approximately 15%) and amitriptyline (10 mm/approximately 0.3%) seem to be mitigated by SB203580. CONCLUSIONS: The cytotoxic effect of lidocaine and amitriptyline in cultured dorsal root ganglia cells and the nerve degeneration in the rat sciatic nerve model seem, at least in part, to be mediated by apoptosis but seem efficiently blocked by an inhibitor of p38 MAPK, making it conceivable that coinjection might be useful in preventing local anesthetic-induced neurotoxicity.     

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 measurements.     

Craniotomy during ECMO in a severely traumatized patient

Summary Extracorporeal membrane oxygenation (ECMO) can be a last resort treatment in acute respiratory distress syndrome after thoracic trauma. However, co-existent brain trauma is considered to be a contra-indication for ECMO. This is the first report on successful craniotomy under ECMO treatment in a multiply traumatized patient with severe thoracic and brain injuries. This successful treatment with beneficial neurological outcome suggests that ECMO therapy should not be withheld from severely injured patients with combined brain and thoracic trauma presenting with life-threatening hypoxemia. Moreover, even craniotomy may be performed during ECMO therapy without major bleeding and adverse effects on neurological function.     

Online monitoring of air quality at the postanesthetic care unit by proton-transfer-reaction mass spectrometry

The subthreshold exposure to trace anesthetic gases is not associated with considerable risk of adverse health effects. Online control of ambient air exchange at the postoperative workplace may help in supervising air quality and lead to cost reduction. A proton-transfer-reaction mass spectrometer system was used for online monitoring of volatile organic compounds, especially anesthetic gases. The mean exposure to sevoflurane and isoflurane at the urological postanesthesia care unit (PACU) was 15.9 and 9.5 parts per billion, respectively. Sevoflurane and isoflurane concentrations at the urological PACU showed a patient turnover-dependent burden during our investigation period. Because modern PACUs have a high ventilation capacity, the 24-h occupational burden by anesthetic gases at the PACU is relatively low. Monitoring and controlling of ambient air by automatic built-in alarm systems would be useful for quality control of the postoperative workplace. Moreover, energy costs of ventilation systems could be reduced by coupling ventilation capacity to the effective exposure.     

The analgesic efficacy of intravenous versus oral tramadol for preventing postoperative pain after third molar surgery.

PURPOSE: The aim of this study was to compare the analgesic efficacy of single-dose preoperative intravenous versus oral tramadol for preventing pain after third molar surgery. PATIENTS AND METHODS: Seventy-two patients undergoing elective third molar surgery were randomized to receive either intravenous (n = 36) or oral (n = 36) tramadol 50 mg. The intravenous group received an oral placebo capsule followed by intravenous tramadol 50 mg preoperatively. The oral tramadol group received a 50-mg oral tramadol capsule followed by intravenous placebo saline preoperatively. In both groups, a standard intravenous sedation technique was administered and the impacted third molars were removed under local anesthesia. The difference in postoperative pain was assessed by 4 primary end points: hourly pain intensity as measured by a 100-mm visual analog scale for 8 hours, time to rescue analgesic, postoperative acetaminophen consumption, and a 5-point global assessment scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent). RESULTS: Throughout the 8-hour investigation period, patients reported significantly lower pain intensity scores in the intravenous versus oral group (15.9 +/- 9.6 mm versus 36.9 +/- 17.2 mm, P = .03). Patients also reported significantly longer time to rescue analgesic (7.0 hours versus 3.5 hours, P = .00001), lesser postoperative acetaminophen consumption (1,823 +/- 1,266 mg versus 3,558 +/- 1,418 mg, P = .000006), and better global assessment (2.6 +/- 0.9 versus 1.1 +/- 0.8, P = .01) for the intravenous versus oral group. CONCLUSIONS: We conclude that preoperative intravenous tramadol is superior to oral tramadol for preventing postoperative pain following third molar surgery. However, it should be noted that there is a difference in the bioavailability between the 2 formulations of up to 30%, which may explain the findings.