Strategy-proofness and essentially single-valued cores revisited

We consider general allocation problems with indivisibilities where agents' preferences possibly exhibit externalities. In such contexts many different core notions were proposed. One is the gamma-core whereby blocking is only allowed via allocations where the non-blocking agents receive their endowment. We show that if there exists an allocation rule satisfying ‘individual rationality’, ‘efficiency’, and ‘strategy-proofness’, then for any problem for which the gamma-core is non-empty, the allocation rule must choose a gamma-core allocation and all agents are indifferent between all allocations in the gamma-core. We apply our result to housing markets, coalition formation and networks.

Possible role for K+ in endothelium-derived hyperpolarizing factor–linked dilatation in rat middle cerebral artery

Background and Purpose— Endothelium-derived hyperpolarizing factor (EDHF) and K+ are vasodilators in the cerebral circulation. Recently, K+ has been suggested to contribute to EDHF-mediated responses in peripheral vessels. The EDHF response to the protease-activated receptor 2 ligand SLIGRL was characterized in cerebral arteries and used to assess whether K+ contributes as an EDHF. Methods— Rat middle cerebral arteries were mounted in either a wire or pressure myograph. Concentration-response curves to SLIGRL and K+ were constructed in the presence and absence of a variety of blocking agents. In some experiments, changes in tension and smooth muscle cell membrane potential were recorded simultaneously. Results— SLIGRL (0.02 to 20 μmol/L) stimulated concentration and endothelium-dependent relaxation. In the presence of NG-nitro-L-arginine methyl ester, relaxation to SLIGRL was associated with hyperpolarization and sensitivity to a specific inhibitor of IKCa, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (1μmol/L), reflecting activation of EDHF. Combined inhibition of KIR with Ba2+ (30μmol/L) and Na+/K+-ATPase with ouabain (1 μmol/L) markedly attenuated the relaxation to EDHF. Raising extracellular [K+] to 15 mmol/L also stimulated smooth muscle relaxation and hyperpolarization, which was also attenuated by combined application of Ba2+ and ouabain. Conclusions— SLIGRL evokes EDHF-mediated relaxation in the rat middle cerebral artery, underpinned by hyperpolarization of the smooth muscle. The profile of blockade of EDHF-mediated hyperpolarization and relaxation supports a pivotal role for IKCa channels. Furthermore, similar inhibition of responses to EDHF and exogenous K+ with Ba2+ and ouabain suggests that K+ may contribute as an EDHF in the middle cerebral artery.

Intraocular pressure evaluation of equines anesthetized with romifidine, tiletamine/zolazepam, halothane and vecuronium

O objetivo deste estudo foi o de avaliar uma associação anestésica com e sem a utilização de relaxante muscular não-despolarizante e seu efeito sobre a pressão intra-ocular de eqüinos. Também objetivou-se uma técnica anestésica sem efeitos adversos que possa ser utilizada em procedimentos e cirurgias oftálmicas nesta espécie animal. Para tanto, dezesseis eqüinos foram divididos aleatoriamente em dois grupos de oito animais cada. Os animais do grupo I foram pré-medicados com romifidina, induzidos com tiletamina/zolazepam e a anestesia foi mantida com halotano e vecurônio. Os animais do grupo II receberam a mesma associação anestésica, com exceção do vecurônio. No decorrer do experimento, a pressão intra-ocular, a pressão arterial e a freqüência cardíaca foram avaliadas em diferentes momentos. A associação anestésica composta pela romifidina, tiletamina/ zolazepam e halotano com e sem vecurônio não promoveu alterações estatisticamente significativas na pressão intra-ocular de eqüinos e o seu uso é exeqüível em procedimentos oftálmicos nesta espécie animal.

Efeito do propofol associado à efedrina no tempo de latência do cisatracúrio

OBJETIVOS: Este estudo teve por objetivo avaliar a eficácia da efedrina na prevenção dos efeitos hemodinâmicos induzidos pela associação do propofol e do remifentanil, assim como os efeitos sobre o tempo de latência do cisatracúrio. MÉTODOS: Sessenta pacientes com idade entre 18 e 52 anos, estado físico ASA I ou II, foram divididos em três grupos, aleatoriamente: G I - propofol 1%; G II - propofol 1% + efedrina 0,5 mg.ml-1 e G III - propofol 1% + efedrina 1,0 mg.ml-1 (velocidade de infusão igual a 180 ml.h-1), até a perda da consciência. Administrou-se remifentanil (0,5 mg.kg-1.min-1) e cisatracúrio na dose de 0,15 mg.kg-1. Foram registrados os dados demográficos, os sinais vitais (PAS, PAM, PAD, FC e SpO2) e o tempo de latência do cisatracúrio. RESULTADOS: Os grupos foram homogêneos com relação aos dados demográficos. Houve diminuição estatisticamente significativa dos valores de PAS, PAM, PAD e FC, um e três minutos após a administração do propofol, porém sem significado clínico importante e sem diferença entre os grupos. As medianas para os tempos de latência do cisatracúrio foram: 178 s (G2 e G3) e 183 s (G1), mas sem diferença significante entre os grupos. CONCLUSÃO: Não houve diminuição clinicamente importante dos parâmetros hemodinâmicos avaliados nos grupos que receberam ou não a efedrina e o tempo de latência do cisatracúrio foi o mesmo para os diferentes grupos.

Lack of chemoprevention of dietary Agaricus blazei against rat colonic aberrant crypt foci

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Tempo de latencia do rocuronio e da succinilcolina e condicoes de intubacao traqueal

Background and Objectives - Pulmonary aspiration of gastric content during induction of anesthesia for emergency surgical procedures is a serious complication; fast endotracheal intubation under these circumstances is of vital importance to secure the airways. Despite its numerous side effects, succinylcholine is used for this purpose. Rocuronium is the most recently introduced aminoesteroid neuromuscular blocking drug with short onset. The objective of this study was to compare the onset time and intubating conditions of rocuronium and succinylcholine. Methods - After informed consent, forty-five patients were randomly allocated into three groups of 15: Group I (GI) = succinylcholine 1 mg.kg-1; Group II (GII) = rocuronium 0.6 mg.kg-1; Group III (GIII) = rocuronium 0.9 mg.kg-1. Every patient was premedicated with midazolam 15 mg per os and induction of anesthesia was made with fentanyl 10 μg.kg-1 and etomidate 0.3 mg.kg-1. The neuromuscular block was monitored with the TOP-Guard neuromuscular transmission monitor. The TOP-Guard neuromuscular monitor uses an accelerometer to measure the response to nerve stimulation. The stimulating electrodes were placed close to the course of the ulnar nerve at the wrist. The onset time was considered as the time between the end of neuromuscular drug injection and the twitch height (T1) decrease to 10%. Heart rate and arterial blood pressure were registered at 6 moments before and after induction of anesthesia. Results - The onset time results were: Group I, 71 s; Group II, 120 s and Group III, 70 s or GI = GIII < GII (F = 8.862; p < 0.01). There were 43 patients exhibiting excellent intubating conditions and 2 with good intubating conditions. Heart rate and arterial blood pressure showed alterations due to induction of anesthesia and intubation. Conclusions - Rocuronium 0.9 mg.kg-1 can be used in rapid sequence induction because it has a short onset time which is similar to that of succnylcholine. It is likely that rocuronium would be a good indication in patients with high intracranial pressure, burns and neuromuscular diseases.

Tempo de latencia e duracao do efeito do brometo de rocuronio no paciente submetido ao transplante renal

Background and Objectives - Successful cadaver kidney transplantation relies on a fast procedure. Patients with chronic renal failure may present with a delayed gastric emptying making it critical a fast tracheal intubation and airway maintenance. Rocuronium a recently introduced nondepolarizing neuromuscular blocker with a fast onset. The aim of this study was to evaluate onset time and duration of rocuronium effects in patients undergoing renal transplantation. Methods - Sixty patients were allocated into two groups of 30: Group R (GR) = patients undergoing renal transplantation and Group N (GN) = patients with normal renal function. All patients were premedicated with oral midazolam (15 mg) and anesthesia was induced with 30 μg.kg-1 alfentanil, 0.3 mg.kg-1 etomidate and 0.6 mg.kg-1 rocuronium injected through a central venous catheter. neuromuscular block was monitored by acceleromyography in the ulnar nerve pathway. The following parameters were evaluated: time between administration of rocuronium and first twitch reduction to 5% after supra-maximal stimulation (T1) (onset time = OT); time for first twitch to return to 25% (clinical duration = R25); time elapsed between 25% and 75% recovery of first twitch (relaxation recovery time = R25-75). Heart rate (HR) and mean blood pressure (MBP) were recorded in 6 moments. Results - Median OT was 31 sec. in GR and 47 sec. in GN. Median R25 was 51.5 min in GR and 33.5 min in GN. Median R25-75 was 28 min in GR and 20 min in GN. MBP and HR were higher in GR. Tracheal intubation conditions were excellent for most patients in both groups. Conclusions - These results open the possibility of 0.6 mg.kg-1 rocuronium being injected through a central venous catheter when a faster onset is needed. Due to wide differences in individual responses, monitoring of neuromuscular block is recommended.

Bupivacaína, Ropivacaína e Levobupivacaína em Analgesia e Anestesia de Parto. Repercussões Materno-Fetais

Background and Objectives - Bupivacaine has been a very useful local anesthetic in Obstetrics in spite of its potential cardiotoxicity. In obstetric analgesia, ropivacaine is preferred to bupivacaine, and levobupivacaine is less cardiotoxic than the racemic mixture. The aim of this study was to compare the maternal-fetal effects of bupivacaine, ropivacaine and levobupivacaine in obstetric analgesia and anesthesia. Methods - Participated in this study 33 term pregnant women, physical status ASA I and II submitted to epidural anesthesia who received 18.75 mg (in 15 ml completed with 9% saline) of: GI - bupivacaine, GII - ropivacaine, and GIII - levobupivacaine. Pain intensity, sensory block level, onset time, quality of analgesia, motor block intensity, analgesia duration and time for labor resolution were evaluated. For vaginal delivery, 40 mg (in 8 ml of saline) of the same local anesthetic were used; for cesarean delivery, the dose has been mg in 20 ml solution. Newborns of these mothers were evaluated through the Apgar score in minutes 1, 5 and 10, and through the Amiel-Tison method (neurologic and adaptative capacity score - NACS) at 30 min, 2 h, and 24 h. Results - There were no significant statistical differences among groups as to sensory block level, onset time, quality of analgesia, labor analgesia duration, time for labor resolution, and Apgar scores at minute 1. Ast to motor block, GIII > GII and GI was intermediary. In relation to pain intensity, there was a trend for GI > GIII. For Apgar scores in minute 5, GII > (GI = GIII), and in minute 10 (GI = GII) < GIII. NACS at 2 h showed, GII > GI > GIII, and at 24 h, GII > GIII > GI. Conclusions - Ropivacaine has relieved maternal pain with less motor block. Newborns of GII mothers (ropivacaine) showed the best Apgar and NACS scores.

Effects of magnesium sulphate on the pharmacodynamics of rocuronium in patients aged 60 years and older: A randomised trial

BACKGROUND There is little information on the interaction between magnesium sulphate (MgSO4) and rocuronium in elderly patients. With a growing number of older patients who need surgical procedures, it is increasingly important to study this age group. OBJECTIVE To evaluate the effects of MgSO4 administration on the pharmacodynamics of rocuronium in patients aged 60 years or older. DESIGN A randomised controlled trial. SETTING A tertiary care hospital. PATIENTS Sixty-four patients, aged 60 years or older, American Society of Anesthesiologists (ASA) physical status classes I to III, scheduled for elective oncological head and neck surgery. Exclusion criteria were severe renal insufficiency (calculated creatinine clearance <30 ml min-1), preoperatorive serum magnesium concentration of more than 1.25 mmol l1 and patients receiving drugs known to affect neuromuscular function. INTERVENTIONS Patients were randomly allocated to one of two groups: in the magnesium group, patients received MgSO4 30mgkg1 intravenously, for 10 min, and then a continuous intravenous infusion at a rate of 1 g h-1. The control group received the same volume of physiological saline. Neuromuscular function was evaluated continuously in both groups. MAIN OUTCOME MEASURES Total recovery time was the primary outcome. Onset time, clinical duration, recovery index and recovery time were considered as secondary endpoints. Values are given as mean [SD]. RESULTS Total recovery time from neuromuscular block (NMB) was 113 [36] min in the magnesium group and 101 [39] min in the control group. Clinical duration was 69 [23] min in the magnesium group and 59 [28] min in the control group. Recovery index was 19 [36] min in the magnesium group and 17 [6] min in the control group. Recovery timewas 44 [22] min in the magnesium group and 42 [18] min in the control group. There were no statistically significant differences between the groups in any of the recovery indices. In the magnesium group, the mean onset time was 144 [58] s, significantly shorter than the onset time in the group that received physiological saline, which was 187 [90] s (P-0.03). Group variances were compared using an F test: onset time varied significantly less in the magnesium group (P-0.02). CONCLUSION In oncology patients of 60 or more years of age, preadministration of MgSO4, with the doses used in this study, significantly reduced the onset time of NMB induced by rocuronium. © 2013 European Society of Anaesthesiology.

Efeitos determinados pela amitriptilina, administrada pela via subaracnóidea, sobre a medula e as meninges: estudo experimental em cães

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Analysis of rocuronium in human plasma by liquid chromatography-tandem mass spectrometry with application in clinical pharmacokinetics

Rocuronium (ROC) is a neuromuscular blocking agent used in surgical procedures which is eliminated primarily by biliary excretion. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for analysis of ROC in human plasma. Separation of ROC and IS (verapamil) was performed using an endcapped C-18 column and a mixture of water:acetonitrile:trifluoracetic acid (50:50:0.1, v/v) as mobile phase. Aliquots of 100 mu L of human plasma were extracted at pH 3, using dichloromethane. The lower limit of quantification of 5 ng/mL shows the high sensitivity of this method. Intra- and inter-assay precision (as relative standard deviation) was all <= 14.2% and accuracy (as relative standard error) did not exceed 10.1%. The validated method was successfully applied to quantify ROC concentrations in patients under surgical procedures up to 6 h after the administration of the 0.4-0.9 mg/kg ROC. The pharmacokinetic parameter estimations of ROC showed AUC/dose of 563 mu g min/mL, total clearance of 2.5 mL/min/kg, volume of distribution at steady state of 190 mL/kg and mean residence time of 83 min. (C) 2013 Elsevier B.V. All rights reserved.

Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease

OBJECTIVES: To assess the safety and cardiopulmonary adaptation to high altitude exposure among patients with coronary artery disease. METHODS: 22 patients (20 men and 2 women), mean age 57 (SD 7) years, underwent a maximal, symptom limited exercise stress test in Bern, Switzerland (540 m) and after a rapid ascent to the Jungfraujoch (3454 m). The study population comprised 15 patients after ST elevation myocardial infarction and 7 after a non-ST elevation myocardial infarction 12 (SD 4) months after the acute event. All patients were revascularised either by percutaneous coronary angioplasty (n = 15) or by coronary artery bypass surgery (n = 7). Ejection fraction was 60 (SD 8)%. beta blocking agents were withheld for five days before exercise testing. RESULTS: At 3454 m, peak oxygen uptake decreased by 19% (p < 0.001), maximum work capacity by 15% (p < 0.001) and exercise time by 16% (p < 0.001); heart rate, ventilation and lactate were significantly higher at every level of exercise, except at maximum exertion. No ECG signs of myocardial ischaemia or significant arrhythmias were noted. CONCLUSIONS: Although oxygen demand and lactate concentrations are higher during exercise at high altitude, a rapid ascent and submaximal exercise can be considered safe at an altitude of 3454 m for low risk patients six months after revascularisation for an acute coronary event and a normal exercise stress test at low altitude.

Unimpaired autoreactive T-cell traffic within the central nervous system during tumor necrosis factor receptor-mediated inhibition of experimental autoimmune encephalomyelitis.

The critical role of tumor necrosis factor (TNF) as a mediator in autoimmune inflammatory processes is evident from in vivo studies with TNF-blocking agents. However, the mechanisms by which TNF, and possibly also its homologue lymphotoxin alpha, contributes to development of pathology in rheumatoid arthritis and Crohn disease and in animal models like experimental autoimmune encephalomyelitis is unclear. Possibilities include regulation of vascular adhesion molecules enabling leukocyte movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage. Here we show that administration of a TNF receptor (55 kDa)-IgG fusion protein prevented clinical signs of actively induced experimental autoimmune encephalomyelitis. Significantly, the total number of CD4+ T lymphocytes isolated from the central nervous system of clinically healthy treated versus diseased control animals was comparable. By using a CD45 congenic model of passively transferred experimental autoimmune encephalomyelitis to enable tracking of myelin basic protein-specific effector T lymphocytes, prevention of clinical signs of disease was again demonstrated in treated animals but without quantitative or qualitative impediment to the movement of autoreactive T lymphocytes to and within the central nervous system. Thus, despite the uninterrupted movement of specific T lymphocytes into the target tissue, subsequent disease development was blocked. This provides compelling evidence for a direct effector role of TNF/lymphotoxin alpha in autoimmune tissue damage.

Effects of Commonly Used Solubilizing Agents on a Model Nerve-Muscle Synapse

Solubility represents a limiting factor when testing new compounds in animal experiments, since solubilizing agents generally have pharmacological effects that can interfere with the studied substance. Vehicles are commonly used for solubilizing certain substances including apolar and polar extracts obtained from medicinal plants. In this study, fifteen vehicles were investigated on mice neuromuscular preparations. A known in vitro neuroblocker myotoxin from Bothrops jararacussu venom, bothropstoxin-I, was used as a pharmacological tool for testing the medicinal potential of apolar and polar extracts (hexane, dichloromethane, ethyl acetate and methanol) obtained from Casearia sylvestris Sw. leaves, which in turn were used for testing their solubility and concomitantly to produce no change on basal response of indirectly stimulated mouse phrenic nerve-diaphragm preparations. Taken together in vitro biological system and extracts solubility, our results showed that dimethyl sulphoxide and polyethylene glycol 400 were the better vehicles, and methanol extract solubilized on PEG 400 was the only one able to act against the paralysis induced by the myotoxin. Thus, this study points out to the relevant role that vehicles exhibit for extracting the potential pharmacological activity of plants in a given test system.

Detection of West Nile Virus Infection in birds in the United States by blocking ELISA and immunohistochemistry

A blocking ELISA targeting an immunodominant West Nile epitope on the West Nile Virus NS1 protein was assessed for the detection of West Nile-specific antibodies in blood samples collected from 584 sentinel chickens and 238 wild birds collected in-New Jersey from May-December 2000. Ten mallard ducks (Anas platyrhynchos) experimentally infected with West Nile virus and six uninfected controls were also tested. The ELISA proved specific in detecting WNV antibodies in 9/10 chickens and 4/4 wild birds previously confirmed as positive by Plaque Reduction Neutralization test (PRNT) at the Center for Disease Control, Division of Vector Borne Diseases, Fort Collins, CO, USA (CDC). Nine out of the ten experimentally infected mallard ducks also tested positive for WN antibodies in the blocking ELISA, while 6/6 uninfected controls did not. Additionally, 1705 wild birds, collected in New Jersey from December 2000-November 2001 and Long Island, New York between November 1999 and August 2001 were also tested for WN antibodies by the blocking ELISA. These tests identified 30 positive specimens, 12 of which had formalin-fixed tissues available to allow detection of WN specific viral antigen in various tissues by WNV-specific immunohistochemistry. Our results indicate that rapid and specific detection of antibodies to WN virus in sera from a range of avian species by blocking ELISA is an effective strategy for WN Virus surveillance in avian hosts. In combination with detection of WN-specific antigens in tissues by immunohistochemistry (IHC) the blocking ELISA will also be useful for confirming WN infection in diseased birds.