Of logos and men: semantic memory impairment for unique entities in a case of semantic variant of primary progressive aphasia.

In this study, an individual (NG) with the semantic varient of primary progressive aphasis (svPPA) was assessed with tasks designed to investigate the recognition and activation of semantic knowledge about unique entities. NG had significant difficulties in the recognition of brand names and famous names but was largely unimpaired in the recognition of logos and famous faces. However, she was impaired in tasks requiring the activation of semantic representations of logos, brand names, famous faces, and famous names. These results suggest that the recognition of unique entities results from the interaction of perceptual and conceptual processes and, that the ability to activate semantic information about these entities can be affected in svPPA.

Texture analysis on MR images helps predicting non-response to NAC in breast cancer.

BACKGROUND: To assess the performance of a predictive model of non-response to neoadjuvant chemotherapy (NAC) in patients with breast cancer based on texture, kinetic, and BI-RADS parameters measured from dynamic MRI. METHODS: Sixty-nine patients with invasive ductal carcinoma of the breast who underwent pre-treatment MRI were studied. Morphological parameters and biological markers were measured. Pathological complete response was defined as the absence of invasive and in situ cancer in breast and nodes. Pathological non-responders, partial and complete responders were identified. Dynamic imaging was performed at 1.5 T with a 3D axial T1W GRE fat-suppressed sequence. Visual texture, kinetic and BI-RADS parameters were measured in each lesion. ROC analysis and leave-one-out cross-validation were used to assess the performance of individual parameters, then the performance of multi-parametric models in predicting non-response to NAC. RESULTS: A model based on four pre-NAC parameters (inverse difference moment, GLN, LRHGE, wash-in) and k-means clustering as statistical classifier identified non-responders with 84 % sensitivity. BI-RADS mass/non-mass enhancement, biological markers and histological grade did not contribute significantly to the prediction. CONCLUSION: Pre-NAC texture and kinetic parameters help predicting non-benefit to NAC. Further testing including larger groups of patients with different tumor subtypes is needed to improve the generalization properties and validate the performance of the predictive model.

Intravenous nitroglycerin for prevention of pancreatitis after therapeutic endoscopic retrograde cholangiography: a randomized, double-blind, placebo-controlled multicenter trial.

BACKGROUND AND STUDY AIMS: Several studies have suggested that nitroglycerin promotes pancreatic drainage and thereby helps to prevent pancreatitis occurring after endoscopic retrograde cholangiography (ERC). We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of intravenous nitroglycerin for preventing acute pancreatitis in moderate- to high-risk patients undergoing ERC. PATIENTS AND METHODS: The patients underwent therapeutic ERC for gallstone removal, bile duct stenosis, or sphincter of Oddi dysfunction (SOD). They were randomly allocated to receive an intravenous nitroglycerin bolus of 0.1 mg, then 35 microg/kg per minute intravenously (maximum dose 9 mg) for 6 h, or an identical placebo regimen. Serum amylase and lipase levels were determined before and 24 h after ERC. RESULTS: The study was terminated after the interim analysis. The intention-to-treat population consisted of 208 patients enrolled in 20 centers, of whom 105 received nitroglycerin and 103 placebo therapy. Post-ERC pancreatitis (mild/moderate/severe) occurred in 25 patients, comprising 10 (3/5/2) in the nitroglycerin arm and 15 (5/6/4) in the placebo arm (OR 0.62, 95 % CI 0.26 - 1.45; P = 0.26). Pancreatitis-related hospital stays were similar in the two groups (median 4 days, range 2 - 13 days in the nitroglycerin group; median 5 days, range 2 - 20 days in the placebo group). The incidence of pancreatitis in patients with SOD did not differ between the groups (4/11 in the nitroglycerin arm, and 4/15 in the placebo arm). Adverse events were more frequent in the nitroglycerin group and led to cessation of drug infusion in 10 patients in the nitroglycerin arm and in 2 patients in the placebo arm ( P = 0.019). CONCLUSION: In this study, nitroglycerin offered a limited and clinically nonsignificant benefit for the prevention of post-ERC pancreatitis. Its use did not improve the technical success rate of ERC.

New types of streptomycin-resistant mutants of Escherichia coli.

Mutagenesis of Escherichia coli K12 cells with ethyl methanesulfonate and selection of streptomycin-resistant mutants after a long delay for phenotypic expression allowed us to isolate new types of streptomycin-resistant ribosomes. Misreading patterns of the ribosomes in the presence of streptomycin revealed that most of the streptomycin-resistant mutants isolated under these conditions differed from the four classical types of streptomycin-resistant mutants studied and characterized by Strigini, P. and Gorini, L. (1970) J. Mol. Biol. 47, 517-530.

Methylene blue inhibits the antithrombotic effect of nitroglycerin.

OBJECTIVES: The aim of this study was to examine whether cyclic guanosine monophosphate (GMP) may be involved in the antithrombotic action of nitroglycerin. BACKGROUND: Nitroglycerin has been shown to inhibit platelet function in vitro by stimulating prostacyclin or inhibiting thromboxane A2 production, or both. Nitroglycerin has also been shown to possess potent antithrombotic properties in vivo. However, the mechanism of this antithrombotic effect is unclear. METHODS: Nitroglycerin was infused to produce a 10% decrease in mean arterial pressure in 27 normal pigs by exposing their circulating arterial blood to porcine aortic media in an ex vivo perfusion chamber. Eight pigs received an infusion of nitroglycerin alone; eight received an infusion of methylene blue, a guanylate cyclase inhibitor, followed by nitroglycerin infusion and five pigs received an infusion of nitroglycerin followed by methylene blue and subsequent infusion of cyclic GMP. RESULTS: With nitroglycerin alone, quantitative autologous indium-111-labeled platelet deposition (x10(6) on the aortic media was decreased to 63.9 +/- 10.4% (p = 0.01) of the baseline control platelet deposition. Methylene blue given before nitroglycerin tended to increase platelet deposition relative to baseline and platelet deposition after nitroglycerin was 142 +/- 35% (p = NS) of baseline value. In pigs that received all three agents, nitroglycerin reduced platelet deposition to 42.3 +/- 12.2% of baseline value; this decrease was then attenuated by subsequent methylene blue infusion but was enhanced by cyclic GMP infusion to 16.4 +/- 3.8% of baseline value (p = 0.006 vs. baseline control and p = 0.02 versus methylene blue infusion). CONCLUSIONS: Guanylate cyclase inhibition with methylene blue abolishes the antithrombotic effect of nitroglycerin, which can be enhanced by cyclic GMP.

Renoprotective effects of trimetazidine against ischemia-reperfusion injury and cold storage preservation: a preliminary study.

BACKGROUND: Initial ischemia-reperfusion injury is associated with organ retrieval, storage, and transplantation adversely affects early graft function and influences the development of chronic graft dysfunction. We have recently shown that the protective agent trimetazidine (TMZ) added to preservation solutions: Euro-collins (EC) and University of Wisconsin (UW) was efficient to protect kidneys from ischemia-reperfusion injury in an isolated perfused kidney model. We extended these observations to investigate the role of this drug in the development and progression of organ dysfunction in the autotransplant pig kidney model. METHODS: Five experimental groups were studied. After 48-hr cold preservation, autotransplantation and immediate controlateral nephrectomy was then performed in group EC (EC+placebo (n=8), EC+TMZ (n=8), UW+placebo (n=7), and (UW+TMZ) (n=7) and compared with control group (uninephrectomized, n=4) during 14 days. Blood and urine samples were collected for the measurement of creatinine and blood urea nitrogen on postoperative days 1, 3, 5, 7, 11, and 14. Histological analysis was performed after reperfusion and at day 14. RESULTS: Survivals were 100% in group B and D versus 42% in group A and 57% in group C. Urine production occurred earlier after autotransplantation from TMZ preserved kidneys than in placebo preserved groups. Peak creat and blood urea nitrogen was significantly greater in groups B and D than in groups A and C. TMZ was also efficient both to reduce ischemia-reperfusion injury and to decrease cellular infiltration. CONCLUSION: These results support the beneficial effect of TMZ against ischemia-reperfusion injury and its early effects on grafts in the form of delayed graft function and decreased graft survival. In addition, TMZ reduces inflammatory cellular infiltration in the renal parenchyma.

Acute and delayed antithrombotic effects of alcohol in humans.

Alcohol intake, especially in the form of red wine, has been shown to inhibit platelet function. However, whether alcohol in spirits may inhibit platelet-dependent thrombosis in humans up to 6 hours after ingestion is unknown and was assessed in this study. Platelet thrombus that is formed on exposure of an aortic media (simulating deep arterial injury or plaque rupture) to flowing blood was assessed in an ex vivo Badimon's superfusion chamber at shear rates of 754 or 2,546 seconds(-1) (simulating flow in normal or stenosed arteries). Twelve healthy subjects were studied before and at 20 minutes and 6 hours after consumption of 2 ounces of 40% alcohol. Blood alcohol level was 1.1+/-0. 1, 8.2+/-0.7, and 1.3+/-0.2 mmol/L at baseline, 20 minutes and 6 hours, respectively, after alcohol consumption (analysis of variance [ANOVA] p = 0.0001). Compared with baseline, platelet thrombus formation at the low shear rate flow was significantly decreased by 57% and 61% at 20 minutes and 6 hours, respectively, after alcohol intake (ANOVA p = 0.0001). Platelet thrombus deposition at the high shear rate was similarly inhibited to 68% and 64% of baseline values at 20 minutes and 6 hours, respectively (ANOVA p = 0.003). Men and women showed equal benefit. Thus, moderate alcohol intake in humans significantly inhibited platelet thrombus deposition under low and high shear rates of arterial flow conditions. This antithrombotic effect of a single alcohol drink, persisting for 6 hours and even after blood alcohol level has returned to baseline, may be clinically relevant to the cardioprotective effects of alcohol in men and women.

Antithrombotic properties of transdermal nitroglycerin in stable angina pectoris.

Nitroglycerin provides an external source of nitric oxide which stimulates guanylate cyclase and produces vasodilatation and inhibition of platelet function. The antithrombotic effects of intravenous nitroglycerin were recently documented in various experimental models and in patients with unstable angina. This protocol was designed to evaluate whether these effects could also be detected with transdermal nitroglycerin in patients with stable angina. In a randomized, double-blind, controlled parallel trial, 22 patients received transdermal nitroglycerin, 0.6 mg/hour (11 patients), or placebo (11 patients). Platelet aggregation to adenosine diphosphate (ADP) and to thrombin was measured in whole blood. Thrombus formation was assessed on porcine aortic media exposed to the patient's venous blood for 3 minutes at shear rates of 2,546 and 754 s-1. Platelet aggregation to ADP decreased from 7.7 +/- 0.8 to 5.3 +/- 0.8 ohms (p < 0.05) with nitroglycerin, and to thrombin from 15.6 +/- 1.2 to 12 +/- 1.2 ohms (p < 0.05). Thrombus size at the high-shear rate decreased from 2.8 +/- 0.7 to 1.0 +/- 0.3 microns 2 (p < 0.05), and at the low-shear rate from 2.5 +/- 0.5 to 1.0 +/- 0.2 microns 2 (p < 0.05). Placebo had no significant effect on platelet aggregation and platelet thrombus deposition. These parameters were all reduced by > or = 20% in 8 patients taking nitroglycerin but only in 3 patients taking placebo (p < 0.05). Transdermal nitroglycerin significantly inhibits platelet aggregation and mural thrombus formation in patients with angina pectoris.

Effects of nitroglycerin at therapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction.

The platelet aggregation response to adenosine diphosphate (ADP) and to thrombin was quantified in 10 patients, 5 with unstable angina pectoris and 5 with acute myocardial infarction, before, during and after a 45-minute infusion of nitroglycerin. An impedance aggregometer allowing rapid bedside studies in whole blood was used. The reproducibility of the methods was documented to be within 10%. Doses of nitroglycerin were titrated for a 10 mm Hg decrease in mean arterial blood pressure with mean doses being 1.2 +/- 0.2 (standard error of the mean) micrograms/kg/min. Nitroglycerin decreased the area under the aggregation curve induced by ADP from 43 +/- 3.6 to 30 +/- 6.3 cm2 (p = 0.007) and by thrombin from 8.9 +/- 1.7 to 4.1 +/- 0.9 cm2 (p = 0.003). Peak responses to ADP were decreased from 13.3 +/- 1 to 9.1 +/- 1.7 ohms (p = 0.005) and to thrombin from 9.3 +/- 2 to 5.0 +/- 1.2 ohms (p = 0.003). All patients had greater than or equal to 50% inhibition with 1 agent or the other and the inhibition was greater than 50% with each of the 2 aggregating agents in 6 patients. Analyses performed on blood withdrawn 15 minutes after the discontinuation of nitroglycerin showed a return to baseline before nitroglycerin results. When analyses were delayed and performed on blood preserved at room temperature for 30 minutes, no effect of nitroglycerin could be detected. Thus, bedside platelet aggregation studies document a significant and reversible effect of nitroglycerin at therapeutic doses on platelet function.

Automated reticulocyte counting and immature reticulocyte fraction measurement. Comparison of ABX PENTRA 120 Retic, Sysmex R-2000, flow cytometry, and manual counts.

We evaluated reticulocyte counting and measurement of immature reticulocyte fraction (IRF) with the ABX PENTRA 120 Retic blood analyzer on 300 blood samples. Reticulocyte counts were compared with those obtained by visual counting of 2,000 RBCs, by the TOA (Kobe, Japan) Sysmex R-2000 and a flow cytometry method. The parameters analyzed were the percentages of reticulocytes on all analyzers and the IRF with different modalities. The Retic Count kit (Becton Dickinson, San Jose, CA) was used with the Coulter (Hialech, FL) XL, and a mean channel of fluorescence (MCF) was calculated to fit the reticulocyte maturation. Reticulocyte counting with the ABX (Montpellier, France) PENTRA 120 Retic showed excellent precision and linearity with no significant carryover. Reticulocyte counts were stable after blood storage for 72 hours at 4 degrees C but not at room temperature (RT). IRF parameters values were stable for only 8 hours at 4 degrees C and 6 hours at RT. Comparisons of the methods showed good intraclass correlation (RI) for reticulocyte percentages between ABX PENTRA 120 Retic and Sysmex R-2000, ABX PENTRA 120 Retic and flow cytometry, Sysmex R-2000 and flow cytometry, and ABX PENTRA 120 Retic and manual counting. IRF values were correlated between fluorescence rates and RNA content, but in each case, low RI values were found, showing that Sysmex and ABX IRF values were not concordant. We obtained a significant correlation between mean fluorescence index and the MCF measured by flow cytometry, but the 2 methods were not concordant using the RI. The ABX PENTRA 120 Retic is a good instrument for analyzing reticulocyte count and percentage and allows a good analysis of IRF with several modalities.

High metabolization of catecholestrogens by type 1 estrogen sulfotransferase (hEST1).

Recently, two types of estrogen sulfotransferase, chronologically named types 1 and 2 estrogen sulfotransferase (hEST1 and hEST2), have been described. Since hEST2 selectively catalyzes the sulfonation of ethinyl estradiol as well as that of estrone (E1) and estradiol (E2), but poorly the sulfonation of catecholestrogens, we wanted to assess the ability of hEST1 to metabolize these compounds. We overexpressed hEST1 in Escherichia coli in fusion with GST, then purified the enzyme using a glutathione affinity column, and obtained GST-free enzyme by digestion with thrombin. Using [35S]-phosphosadenosine phosphosulfate (PAPS) as cofactor, we showed that hEST1 efficiently metabolizes the transformation of 2-OH-E2 and 2-OH-E1. However, the transformation of 4-OH-E1 and 4-OH-E2 is much less efficient. Our results also show that hEST1 metabolizes more efficiently E2 than E1. Since hEST1 mRNA is produced from the same gene as MPST using different alternative promoters and since it is expressed in most breast cancer cells (MCF-7, ZR-75-1, T47-D, MDA-231, and MDA-418), studies of the expression and activity of hEST1 will be most important to have a better knowledge about its involvement in the control of the genotoxicity of estrogens and catecholestrogens.

Comparative biosynthetic pathway of androstenol and androgens.

It has been shown recently that androstenol and androstanol could modulate gene expression through the nuclear orphan receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor). Although, in the pig, androstenol is produced in high amounts and is active as a pheromone, its role in the human is ill defined. Androstenol possesses a structure similar to that of androgens, with the exception that it does not possess an oxygen at position 17 that is crucial for androgenic and estrogenic activity. It has been shown that human and boar testis homogenates could produce androstenol, but details of the biosynthetic pathway had not yet been elucidated. It has also been shown recently that androstenol could modulate the activity of CAR and PXR and the expression of some cytochrome P450 drug-metabolizing enzymes. We wanted to determine the precise biosynthetic pathway of androstenol and other closely related steroids. Using transformed human embryonic kidney (HEK-293) cells that stably express 3 beta-hydroxysteroid dehydrogenase, 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase, we have shown that these enzymes are able to efficiently transform the precursor 5,16-androstadien-3 beta-ol into androstenol. We thus provided evidence that androstenol, the ligand for CAR and PXR, is produced by the biosynthetic pathway of sex steroids.

Non-linear kinetics of glutamyl-tRNA synthesis catalyzed by high molecular weight complexes from rat brain neuronal cells but not from glial cells.

High molecular weight complexes of aminoacyl-tRNA synthetases isolated from rat brain catalyze the formation of glutamyl-tRNA with an initial lag time of the order of 1 min, as previously reported for the formation of glutamyl-tRNA and glutaminyl-tRNA catalyzed by similar complexes from bovine brain (Vadeboncoeur and Lapointe, Eur. J. Biochem., 109 (1980) 581-587). To determine the type(s) of brain cell(s) where this phenomenon occurs, we have studied the kinetics of glutamyl-tRNA formation catalyzed by high molecular weight complexes of aminoacyl-tRNA synthetases isolated from neuronal and from glial cells, either transformed (Neuro-2A and C6), or from primary cultures, or isolated from rat brain. The delay in the formation of glutamyl-tRNA was observed only in the case of neuronal cells isolated from rat brain, whereas a delay in the formation of glutaminyl-tRNA was also seen in these cells, as well as in neuronal cells in primary culture and in synaptosomes. The kinetics of formation of aspartyl-tRNA and valyl-tRNA catalyzed by high molecular weight complexes from all these cells was linear.

A comparison of direct, indirect, and fiberoptic laryngoscopy to evaluate vocal cord paralysis after thyroid surgery.

After thyroidectomy, the anesthesiologist usually performs a laryngoscopy to detect laryngeal edema and nerve palsies. The goal of this study was to compare three different methods of laryngeal examination after tracheal extubation of the patients. For that purpose, between 1990 and 1995, a prospective series of 1608 patients operated for thyroidectomy has been studied. The series was divided into 4 groups. In group I (n = 200), four anesthesiologists have evaluated the efficiency of the immediate postextubation direct laryngoscopy. In group II (n = 100), one anesthesiologist has compared the direct, indirect, and flexible laryngoscopies in every patient in a fixed and timed fashion. In group III (n = 100), the four examiners have evaluated the flexible laryngoscopy at a different timing so as to eliminate the possible temporal relationship of the ease of visualization in group II. In group IV (n = 1208), the four examiners have evaluated flexible laryngoscopy, on a large scale, at any time during the 1-h stay in the recovery room. Special attention was directed to the patients with known cardiovascular diseases. Direct and indirect laryngoscopies were only effective in 76 and 73%, respectively, of the patients, whereas flexible laryngoscopy was effective in 99.6% of them. Flexible laryngoscopy was easy to perform in 96.5% of the patients versus 65 and 55% with direct and indirect laryngoscopies. Finally, variations in monitored cardiovascular parameters were significantly lower with flexible and indirect laryngoscopies than with direct laryngoscopy. These mild variations induced by flexible laryngoscopy were well tolerated by patients with known cardiovascular diseases. Flexible laryngoscopy is the best method for an immediate laryngoscopic examination after thyroidectomy.

Creatine supplementation does not improve sprint performance in competitive swimmers.

This study was conducted to examine the effects of creatine (Cr) supplementation on sprint swimming performance and energy metabolism. Twenty highly trained swimmers (9 female, 11 male) were tested for blood ammonia and for blood lactate after the 25-, 50-, and 100-m performance in their best stroke on two occasions 7 d apart. After the first trial, subjects were evenly and randomly assigned to either a creatine (5 g creatine monohydrate 4 times per day for 5 d) or a placebo group (same dosage of a lactose placebo) in a double-blind research design. No significant differences in performance times were observed between trials. Post-exercise blood ammonia concentration decreased in the 50- and 100-m trials in the creatine group and in the 50-m trial in the placebo group. The supplementation period had no effect on post-exercise blood lactate. Therefore, creatine supplementation cannot be considered as an ergogenic aid for sprint performance in highly trained swimmers although adenine nucleotide degradation may be reduced during sprint exercise after 5 d of creatine ingestion.

Modeled responses to training and taper in competitive swimmers.

This study investigated the effect of training on performance and assessed the response to taper in elite swimmers (N = 18), using a mathematical model that links training with performance and estimates the negative and positive influences of training, NI and PI. Variations in training, performance, NI, and PI were studied during 3-, 4-, and 6-wk tapers. The fit between modeled and actual performance was significant for 17 subjects; r2 ranged from 0.45 to 0.85, P < 0.05. Training was progressively reduced during tapers. Performance improved during the first two tapers: 2.90 +/- 1.50% (P < 0.01) and 3.20 +/- 1.70% (P < 0.01). Performance improvement in the third taper was not significant (1.81 +/- 1.73%). NI was reduced during the first two tapers (P < 0.01 and P < 0.05, respectively), but not during the third. PI did not change significantly during tapers. Thus, the present results show that the model used is a valuable method to describe the effects of training on performance. Performance improvement during taper was attributed to a reduction in NI. PI did not improve with taper, but it was not compromised by the reduced training periods.

Airway complications in thyroid surgery.

Perioperative and postoperative morbidity and mortality were studied in a series of 3,008 thyroidectomies. Compressive symptoms, frequent in substernal and cancerous goiters, were present in 11.0% of the patients, although a low rate of dyspnea (2.7%) was observed. In large goiters, some orotracheal intubations were difficult. In such cases, the transtracheal approach can also be difficult, so failure should be anticipated. Postoperative causes of respiratory obstruction included local hemorrhages, bilateral recurrent nerve palsies, and laryngeal edema. A tracheal collapse was not observed. These respiratory obstructions led to repeat surgery in 11 patients, tracheostomy in 3, and temporary reintubation with steroid therapy in 1. The recurrent laryngeal nerve, which may have been affected preoperatively, was found to be damaged postoperatively in 0.5% of the patients with benign goiters, compared to 10.6% of the patients with thyroid cancer. In this last group a bilateral palsy was observed in 3 cases with prolonged or extensive surgery. After these short-term orotracheal intubations (114 minutes on average), injuries of the airway caused by the endotracheal tube were found in 4.6% of the patients.

Intranasal midazolam in piglets: pharmacodynamics (0.2 vs 0.4 mg/kg) and pharmacokinetics (0.4 mg/kg) with bioavailability determination.

Intranasal midazolam was studied in two series of piglets: series 1, n = 20 (18 +/- 3 kg), a randomized double blind pharmacodynamic study to compare doses of 0.2 mg/kg and 0.4 mg/kg; series 2, n = 9 (42 +/- 8 kg), a pharmacokinetic study with a 0.4 mg/kg dose administered either intravenously (i.v.) or intranasally (i.n.) in a cross-over protocol with a one-week wash-out period between each. In series 1, midazolam caused significant anxiolysis and sedation within 3 to 4 min, without a significant difference between 0.2 and 0.4 mg/kg doses for any of the studied parameters. In series 2, after intranasal midazolam administration of 0.4 mg/kg, plasma concentrations attained a maximum (Cmax) of 0.13 +/- 0.04 mg/l at 5 min (median Tmax) and remained higher than 0.04 mg/l until 60 min. The bioavailability factor (F) in this study was F = 0.64 +/- 0.17 by the intranasal route. The terminal half-life (T1/2 lambda z) = 145 +/- 138 min was comparable with the i.v. administration half-life (158 +/- 127 min). In conclusion, optimal intranasal midazolam dose in piglets was 0.2 mg/kg, which procures rapid and reliable sedation, adapted to laboratory piglets.

Pharmacokinetics of lidocaine with epinephrine in piglets following epidural anaesthesia.

The time course of arterial plasma lidocaine concentration, following an epidural anaesthesia via the sacrococcygeal or the S4-S5 trans-sacral approach, was studied in nine healthy piglets (7.8 +/- 1.3 weeks). Plasma lidocaine concentrations were measured for up to six hours after administration (5 mg/kg). Peak plasma concentration was 1.83 +/- 0.17 mg/l. Pharmacokinetic parameters determined from an independent compartment model were not different from those observed after an epidural administration of lidocaine via the sacrococcygeal space in children, except for a wide variability in the time taken to reach the maximum concentration (27.3 +/- 7.4 min) and a shorter half-life of elimination (82.8 +/- 7.0 min). The total body clearance of lidocaine was similar in piglets (17.3 +/- 1.6 ml/min/kg) to that in children. The shorter half-life of elimination was therefore attributed to a smaller volume of distribution in piglets (2.0 +/- 0.2 l/kg).

Postthyroidectomy analgesia: morphine, buprenorphine, or bupivacaine?

STUDY OBJECTIVE: To compare three analgesic regimens for pain relief after thyroidectomy. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Inpatient anesthesia in a university department of endocrine surgery. PATIENTS: 342 patients scheduled for elective thyroidectomy with nitrous oxide-oxygen-isoflurane anesthesia in addition to fentanyl. INTERVENTIONS: Group 1 received preoperative oral controlled release morphine 10 mg, and Group 2 received postoperative sublingual buprenorphine 0.2 mg. Group 3 received 0.25% bupivacaine (10 ml) wound infiltration before skin closure. Eight hours after tracheal extubation, patients received a second dose of the same drug in each group except in Group 3, where medication was changed to sublingual buprenorphine 0.2 mg. MEASUREMENTS AND MAIN RESULTS: Patients in Group 2 required fewer additional analgesics: 0.54 +/- 0.68 vs. 0.96 +/- 0.84 in Group 1 and 0.79 +/- 0.78 in Group 3. Patients in Group 2 demonstrated a better pain score and this group showed a higher percentage of satisfied patients: 96% vs. 85% in Group 1 and 91% in Group 3. Group 2 also included more patients requiring no analgesics: 56% vs. 32% in Group 1 and 42% in Group 3. The side effects in all three groups did not differ. CONCLUSION: The administration of sublingual buprenorphine after thyroidectomy provides better analgesia than small doses of oral controlled-release morphine or than 0.25% bupivacaine wound infiltration at the end of surgery.