Design and validation of a multiplex specific primer-directed polymerase chain reaction assay for killer-cell immunoglobulin-like receptor genetic profiling.

Current methodologies for the analysis of the killer-cell immunoglobulin-like receptor (KIR) locus utilize specific primer-directed polymerase chain reaction (SSP-PCR), which require a wide range of DNA input, multiple reaction conditions, and up to 16 individual reactions. We have developed and validated a multiplex SSP-PCR method for the genetic analysis of the KIR locus. Design and optimization of four multiplex groups targeting 14 genes and their alleles on the KIR locus has been completed. Each multiplex group contains PCR products that differ in size by a minimum of 15 bp to allow sufficient fragment length resolution for size discrimination by gel electrophoresis. This assay allows for efficient genotyping of the KIR locus while requiring a minimum amount of DNA input, utilizing the simplicity of SSP-PCR.

[Diagnosis of caseous lymphadenitis in sheep from Patagonia]. / Diagnóstico de pseudotuberculosis en ovinos patagónicos.

Caseous lymphadenitis (CLA) is a chronic bacterial, infectious and contagious disease caused by Corynebacterium pseudotuberculosis. It affects sheep and results in abscesses of the lymph nodes in subcutaneous tissue, as well as in internal organs such as lungs, liver and kidneys. Differential diagnosis of the disease is based on the isolation and biochemical identification of the etiological agent. The purpose of this study was to characterize the bacteria isolated from typical CLA lesions in sheep from Patagonia, Argentina, at metabolic and genetic levels. Macroscopic observations show a fibrous membrane containing caseous necrotic tissue. Histopathological analysis shows an eosinophilic necrotic area surrounded by epitheloid cells and polymorphonuclear infiltration. Other analyses performed such as microscopic observations, in vitro culture, biochemical tests and 16s rDNA sequencing confirmed diagnosis of caseous lymphadenitis due to C. pseudotuberculosis.

Toxic effects of dissolved heavy metals on Desulfovibrio vulgaris and Desulfovibrio sp. strains.

Biological treatment of metal-containing wastewaters with sulphate-reducing bacteria (SRB) is an attractive technique for the bioremediation of this kind of medium. In order to design a suitable engineering process to address this environmental problem, it is crucial to understand the inhibitory effect of dissolved heavy metals on these bacteria. Batch studies were carried out to evaluate the toxic effects of several heavy metal ions [Cr(III), Cu(II), Mn(II), Ni(II) and Zn(II)] on two cultures of SRB (Desulfovibrio vulgaris and Desulfovibrio sp.). The experimental data indicate that SRB show different responses to each metal. At the highest metal concentration tolerated for each metal, the precipitation levels for D. vulgaris were as follows: 24.7%-15 ppm Cr(III), 45%-4 ppm Cu(II), 60%-10 ppm Mn(II), 96%-8.5 ppm Ni(II) and 9%-20 ppm Zn(II). The corresponding values for Desulfovibrio sp. were: 25.5%-15 ppm Cr(III), 71%-4 ppm Cu(II), 66.2%-10 ppm Mn(II), 96.1%-8.5 ppm Ni(II) and 93%-20 ppm Zn(II). Results obtained in batch studies will be taken into account for the subsequent design of a sulphate-reducing bioreactor to reduce levels of heavy metals present in different types of contaminated media.

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4-5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.

Abnormal coagulation profile in brain tumor patients during surgery.

Neurosurgical patients are at high risk for the development of thrombosis and thromboembolism. We compared the perioperative clotting factor and coagulation parameters of 20 patients undergoing elective craniotomy for brain tumors to those of 20 patients undergoing elective abdominal surgery. We also measured the levels of plasma arginine vasopressin to determine if changes in this hormone might be associated with changes in clotting factors, activated partial thromboplastin times, or bleeding times. The results demonstrated a significant reduction in partial thromboplastin times and bleeding times in the neurosurgery group, which began at the initiation of surgery and lasted to the end of the study (12 h postoperatively). Elevations in factor assays and plasma arginine vasopressin occurred in both groups during surgery, but there were no differences between the neurosurgical and abdominal surgical patients, except with Factor IX levels, which were elevated only in the neurosurgical patients. Serum osmolality and hemoglobin levels were significantly higher in the neurosurgical cohort. These results suggest that there are hemostatic differences between neurosurgical patients with brain tumors and abdominal surgery patients that cannot be explained solely by elevations in plasma arginine vasopressin or the clotting factors measured; these differences may be the consequence of perioperative variables such as dehydration and hyperosmolality.

Myocardial ischemia during the weaning period.

OBJECTIVES: To estimate the incidence of silent myocardial ischemia, its pattern over time and its relationship to the time and mode of weaning high-risk cardiac patients after noncardiac surgery. DESIGN: Prospective study with random assignment to one of three weaning modes. SETTING: A surgical intensive care unit in a university hospital and a Veterans Administration hospital. PATIENTS: Sixty-two patients meeting standard criteria for extubation were randomized to one of three modes of weaning: synchronized intermittent mandatory ventilation (n = 19), T-Bar (n = 21) or continuous positive airway pressure (n = 22). METHODS: Ischemia was monitored with a continuous two-lead (V5, III) ST segment analyzer. Tracings were reviewed by a cardiologist. Ischemia was defined as greater than 1 mm ST segment depression 60 milliseconds after the J point. The monitoring period included a prewean (mean 654.0 minutes), wean (mean 46.5 minutes) and postwean (mean 1223.4 minutes) period. RESULTS: Of 62 patients, 12 (19.3%) experienced ischemia at some time during the monitoring period, most often during the weaning period. Ischemia during weaning was detected in 3 of 21 (14.3%) T-Bar patients and 2 of 22 (9.1%) continuous positive airway pressure patients but in no synchronized intermittent mandatory ventilation patients. CONCLUSION: This study demonstrates that silent myocardial ischemia occurs frequently in high-risk postoperative patients, with the highest incidence during weaning.

A comparison: the efficacy of sevoflurane-nitrous oxide or propofol-nitrous oxide for the induction and maintenance of general anesthesia.

STUDY OBJECTIVE: To compare sevoflurane-nitrous oxide with propofol-nitrous oxide for the induction and maintenance of anesthesia, and to determine the rates of recovery following each anesthetic. DESIGN: Randomized, controlled study. SETTING: Teaching hospital. PATIENTS: 50 ASA physical status I and II patients, ranging in age from 18 to 70 years. INTERVENTIONS: General anesthesia was induced with either sevoflurane or propofol and maintained with 60% to 70% nitrous oxide and either sevoflurane or a propofol infusion and supplemental fentanyl. At the conclusion of surgery, the oxygen flow was increased to 6 L/min and all anesthetics were discontinued simultaneously. Patients were monitored for the nature and speed of induction and emergency from anesthesia. MEASUREMENTS AND MAIN RESULTS: Induction of anesthesia was significantly slower in the sevoflurane group than in the propofol group (2.0 +/- 1.1 vs. 0.8 +/- 0.5 min, respectively). The ease of induction and the time required for emergence from anesthesia were the same in both study groups (eye opening: 9.0 +/- 4.4 min vs. 8.0 +/- 5.0 min; following commands: 11.2 +/- 5.0 min vs. 9.8 +/- 6.9 min; extubation: 9.1 +/- 4.5 min vs. 8.6 vs. 5.1 min in the sevoflurane and propofol groups, respectively). Patients in the sevoflurane group experienced nausea and vomiting more frequently than patients in the propofol group (13 and 5 patients vs. 3 and 0 patients in the sevoflurane and propofol groups, respectively), which were not related to the administration of neostigmine or intraoperative opioids. CONCLUSION: Sevoflurane allows for rapid inhalation induction of, and emergence from, general anesthesia.

Combined strategy for the precipitation of heavy metals and biodegradation of petroleum in industrial wastewaters.

The precipitation of chromium(III), copper(II), manganese(II) and zinc(II) by biogenic hydrogen sulfide generated by sulfate-reducing bacteria, Desulfovibrio sp., and the degradation of total petroleum hydrocarbons (TPH) in the presence of heavy metal by Pseudomonas aeruginosa AT18 have been carried out. An anaerobic stirred tank reactor was used to generate hydrogen sulfide with Desulfovibrio sp. culture and the precipitation of more than 95% of each metal was achieved in 24 h (metal solutions contained: 60, 49, 50 and 80 mg L(-1) of chromium, copper, manganese and zinc sulfates). A stirred tank reactor with P. aeruginosa AT18, in the presence of the heavy metal solution and 2% (v/v) of petroleum, led to the degradation of 60% of the total petroleum hydrocarbons and the removal of Cr(III) 99%, Cu(II) 93%, Zn(II) 46% and Mn(II) 88% in the medium through biosorption phenomena. These results enabled the development of an integrated system in which the two processes were combined. The overall aim of the study was achieved, with 84% of TPH degraded and all of the metals completely removed. Work is currently underway aimed at improving this system (decrease in operation time, culture of P. aeruginosa in anaerobic conditions) in an effort to apply this process in the bioremediation of natural media contaminated with heavy metals and petroleum.

Valoración de impacto ambiental en el Puerto Moa-Holguín / Environmental impact assessment in Moa-Holguín Port

Las operaciones de descarga de los buques-tanques, la recepción y distribución de productos derivados del crudo de petróleo en el área de almacenamiento, el movimiento de insumos como el carbón antracita, amoniaco y azufre, la carga de lotes de minerales así como el mantenimiento de los tanques, conducen al vertimiento directo de hidrocarburos que afectan los diferentes ecosistemas en los cuales se encuentra situada la fuente contaminante. Se presenta la caracterización de los ecosistemas afectados por esta contaminación, atendiendo a los impactos ambientales identificados y la previa caracterización del área, utilizando herramientas de evaluación de criterios de expertos mediante la metodología Delphi. El estudio de impacto ambiental se realizó de forma cualitativa a través de las matrices causa-efecto, valoración e importancia del impacto. Los factores del medio más afectado fueron las aguas superficiales y subterráneas y la salud e higiene; las acciones más agresivas fueron la emisión de contaminantes (vertimiento al medio suelo de hidrocarburos/ liberación al medio aire de gases, ruidos y materiales particulados/ vertimiento y contaminación del acuatorio por arrastres de sedimentos, hidrocarburos y sustancias químicas) y la acumulación de residuos (creación de vertederos industriales).

The operations of unloading ships the reception and distribution of products derivate of oil crude in the storage area, the movement of raw materials like coal anthracite, ammonia and sulphur, the load of lots of minerals as well as the maintenance of ships, direct leads to the appearance of hydrocarbons that affects the different ecosystems which he meets in once the contaminating source in the municipal Moa. It is present the characterization of ecosystems affected with oil's hydrocarbons, attending to environmental impacts identified by the expert group and the prior characterization of the area using assessment tools expert judgment using Delphi methodology. The environmental impact study was realized of qualitative form through matrix of cause-effect, valuation and importance of impact. The environmental factors of resulting surface/groundwater and health and hygiene the most attacked while impacts were more aggressive emissions (throwing to the ground hydrocarbons/ liberation to the midway air of gases, noises and materials in particles, throwing and contamination of the source for dragging of sediments, hydrocarbons and chemical substances) and accumulation waste (creation of drains industrials).

Characterization of Staphylococcus aureus mutants expressing reduced susceptibility to common house-cleaners.

AIMS: To characterize mutants of Staphylococcus aureus expressing reduced susceptibility to house cleaners (HC), assess the impact of the alternative sigma factor SigB on HC susceptibility, and determine the MIC of clinical methicillin-resistant S. aureus (MRSA) to a HC. METHODS AND RESULTS: Susceptibility to HC, HC components, H2O2, vancomycin and oxacillin and physiological parameters were determined for HC-reduced susceptibility (HCRS) mutants, parent strain COL and COLsigB::kan. HCRS mutants selected with three HC expressed reduced susceptibility to multiple HC, HC components, H2O2 and vancomycin. Two unique HCRS mutants also lost the methicillin resistance determinant. In addition, all HCRS mutants exhibited better growth at two temperatures, and one HCRS mutant expressed reduced carotenoid production. COLsigB::kan demonstrated increased susceptibility to all HC and many HC components. sigB operon mutations were not detected in one HCRS mutant background. Of 76 clinical MRSA, 20 exhibited reduced susceptibility to a HC. CONCLUSIONS: HCRS mutants demonstrate altered susceptibility to multiple antimicrobials. While sigB is required for full HC resistance, one HCRS mechanism does not involve sigB operon mutations. Clinical MRSA expressing reduced susceptibility to a common HC were detected. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that HCRS mutants are not protected against, nor selected by, practical HC concentrations.

Chemical structure, surface properties and biological activities of the biosurfactant produced by Pseudomonas aeruginosa LBI from soapstock.

Pseudomonas aeruginosa LBI isolated from petroleum-contaminated soil produced rhamnolipids (RL(LBI)) when cultivated on soapstock as the sole carbon source. HPLC-MS analysis of the purified culture supernatant identified 6 RL homologues (%): R(2) C(10) C(10) 28.9; R(2) C(10) C(12:1) 23.0; R(1) C(10) C(10) 23.4; R(2) C(10) C(12) 11.3; R(2) C(10) C(12) 7.9; R(2) C(10) C(12) 5.5. To assess the potential antimicrobial activity of the new rhamnolipid product, RL(LBI), its physicochemical properties were studied. RL(LBI) had a surface tension of 24 mN m(-1) and an interfacial tension of 1.31 mN m(-1); the cmc was 120 mg l(-1). RL(LBI) produced stable emulsions with hydrocarbons and vegetable oils. This product showed good antimicrobial behaviour against bacteria: MIC for Bacillus subtilis, Staphylococcus aureus and Proteus vulgaris was 8 mg l(-1), for Streptococcus faecalis 4 mg l(-1), and for Pseudomonas aeruginosa 32 mg l(-1). RL(LBI) was active against phytopathogenic fungal species, MIC values of 32 mg l(-1) being found against Penicillium, Alternaria, Gliocadium virens and Chaetonium globosum. Due to its physicochemical properties and antimicrobial behaviour, RL(LBI) could be used in bioremediation treatment and in the food, cosmetic and pharmaceutical industries.

Enhanced biodegradation of Casablanca crude oil by a microbial consortium in presence of a rhamnolipid produced by Pseudomonas aeruginosa AT10.

The biodegradation of oil products in the environment is often limited by their low water solubility and dissolution rate. Rhamnolipids produced by Pseudomonas aeruginosa AT10 were investigated for their potential to enhance bioavailability and hence the biodegradation of crude oil by a microbial consortium in liquid medium. The characterization of the rhamnolipids produced by strain AT10 showed the effectiveness of emulsification of complex mixtures. The addition of rhamnolipids accelerates the biodegradation of total petroleum hydrocarbons from 32% to 61% at 10 days of incubation. Nevertheless, the enhancement of biosurfactant addition was more noticeable in the case of the group of isoprenoids from the aliphatic fraction and the alkylated polycyclic aromatic hydrocarbons (PHAS) from the aromatic fraction. The biodegradation of some targeted isoprenoids increased from 16% to 70% and for some alkylated PAHs from 9% to 44%.

The nature of spontaneous recovery from mivacurium-induced neuromuscular block.

UNLABELLED: The hypothesis of this study was that, in a given patient, recovery from a tracheal intubating dose of mivacurium would indicate the time course of spontaneous recovery after discontinuation of an infusion of mivacurium. Thirty-eight male patients consented to participate in the study. After induction of anesthesia and endotracheal intubation, the ulnar nerve was stimulated with train-of-four (TOF) stimuli at 12-s intervals. Patients received 0.3 mg/kg mivacurium in two evenly divided doses of 0.15 mg/kg each, separated by 30 s. Complete ablation of TOF responses occurred in most patients. Once the first twitch in the TOF (T ) had recovered to 25% of its baseline height, a mivacurium infusion was begun to maintain 95% suppression of T1. As surgery was nearing completion, the infusion was discontinued, and neuromuscular function was allowed to recover spontaneously. Data were analyzed for recovery intervals after the administration of the initial doses of mivacurium and after discontinuation of the infusion. Analysis of variance was used to determine the strength of correlation between the time from administration of the initial 0.3 mg/kg dose to 5% recovery of T1 and the times to recovery of TOF ratios of 70% and 90%. The 25%-75% recovery interval after discontinuation of the infusion ranged from 2.8 to 11.3 min. The time interval after administration of mivacurium 0.3 mg/kg to 5% recovery of T1 correlated with both the time to recovery of a TOF ratio of 70% and 90%. Recovery to a TOF of 90% after discontinuation of the infusion required approximately the same amount of time as recovery to 5% T1 after the administration of 0.3 mg/kg mivacurium. Each patient's recovery of neuromuscular function after discontinuation of a mivacurium infusion was related to his recovery after the administration of 0.3 mg/kg mivacurium. Therefore, the need for pharmacologic antagonism of block can be anticipated well before the end of an anesthetic. IMPLICATIONS: Mivacurium (0.3 mg/kg) was administered to 38 patients. As they began to recover muscle strength, a mivacurium infusion was begun and later discontinued as surgery was nearing completion. Each patient's early recovery (administration to 5% recovery of T1) after the initial dose of mivacurium correlated well with more complete recovery of muscle strength after discontinuation of an infusion. This relationship enables early prediction of recovery speed after a mivacurium infusion.

Pharmacodynamics and the plasma concentration of mivacurium during spontaneous recovery and neostigmine-facilitated recovery.

BACKGROUND: The authors examined the plasma concentrations of the isomers of mivacurium and its pharmacodynamics during spontaeous and neostigmine-facilitated recovery after a mivacurium infusion. METHODS: Sixteen patients receiving nitrous oxide-opioid anesthesia received 0.25 mg/kg mivacurium. Patient response to neuromuscular stimulation was determined using a mechanomyograph Once T1 had recovered to 25% of its baseline height, a mivacurium infusion was begun and adjusted to maintain 95-99% neuromuscular block. The infusion was discontinued after 90 min and muscle strength allowed to recover either spontaneously or after neostigmine/glycopyrrolate (0.05/0.01 mg/kg). Plasma concentrations of the isomers of mivacurium after discontinuation of the infusion were determined using an HPLC assay. Differences between the groups were determined using a one-way analysis of variance with a Bonferroni-corrected t test or Student t test as appropriate. P < or = 0.05 was considered significant. RESULTS: Differences in the times for recovery to a train-of-four ratio of 70% did not achieve statistical significance (mean+/-SD, 13.3+/-6.0 vs. 16.3+/-2.5 min for the neostigmine and spontaneous groups, respectively). Plasma cholinesterase activity decreased significantly from baseline values after administration of neostigmine (5.88+/-0.21 vs. 0.43+/-0.04 U/ml plasma). Plasma concentrations of the trans-trans isomer were significantly greater in the neostigmine group than in the spontaneous recovery group 5, 6, 8, and 10 min after discontinuation of the infusion. Differences in the plasma concentration of the cis-trans isomer did not achieve statistical significance. CONCLUSIONS: Although administration of neostigmine decreased plasma cholinesterase activity and caused the trans-trans isomer to remain in the plasma at higher concentration, it did not delay recovery from mivacurium-induced block.

Pharmacokinetics of cisatracurium in patients receiving nitrous oxide/opioid/barbiturate anesthesia.

BACKGROUND: Cisatracurium, one of the ten isomers in atracurium, is a nondepolarizing muscle relaxant with an intermediate duration of action. It is more potent and less likely to release histamine than atracurium. As one of the isomers composing atracurium, it presumably undergoes Hofmann elimination. This study was conducted to describe the pharmacokinetics of cisatracurium and its metabolites and to determine the dose proportionality of cisatracurium after administration of 2 or 4 times the ED(95). METHODS: Twenty ASA physical status 1 or 2 patients undergoing elective surgery under nitrous oxide/opioid/barbiturate anesthesia were studied. Patients received a single rapid intravenous bolus does of 0.1 or 0.2 mg x kg-1 (2 or 4 times the ED(95), respectively) cisatracurium. All patients were allowed to recover spontaneously to a train-of-four ratio > or = 0.70 after cisatracurium-induced neuromuscular block. Plasma was extracted, acidified, and stored frozen before analysis for cisatracurium, laudanosine, the monoquaternary acid, and the monoquaternary alcohol metabolite. RESULTS: The clearances (5.28 +/- 1.23 vs. 4.66 +/- 0.67 ml x min(-1) x kg(-1) and terminal elimination half-lives (22.4 +/- 2.7 vs. 25.5 +/- 4.1 min) were not statistically different between patients receiving 0.1 mg x kg(-1) and 0.2 mg x kg(-1), respectively. Maximum concentration values for laudanosine averaged 38 +/- 21 and 103 +/- 34 ng x ml(-1) for patients receiving the 0.1 and 0.2 mg x kg(-1) doses, respectively. Maximum concentration values for monoquaternary alcohol averaged 101 +/- 27 and 253 +/- 51 ng x ml(-1), respectively. Monoquaternary acid was not quantified in any plasma sample. CONCLUSIONS: Cisatracurium undergoes Hofmann elimination to form laudanosine. The pharmacokinetics of cisatracurium are independent of dose after single intravenous doses of 0.1 and 0.2 mg x kg(-1).

The cardiovascular effects and histamine-releasing properties of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia.

BACKGROUND: Atracurium consists of a mixture of ten stereoisomers. One of these isomers, 51W89, is a potent intermediate-acting nondepolarizing neuromuscular blocking agent. Its ED95 is 0.05 mg.kg-1 in patients receiving nitrous oxide/opioid anesthesia. In preclinical trials, 51W89 did not show evidence of histamine release in cats at doses up to 80 times the human ED95. This study was undertaken to determine the cardiovascular effects and histamine-releasing properties of 51W89 in patients undergoing elective surgical procedures. METHODS: Sixty patients, ASA physical status 1 or 2, anesthetized with nitrous oxide/fentanyl/thiopental were studied. Patients received either 2 times the ED95 of atracurium or 51W89 or 4 or 8 times the ED95 of 51W89 as a rapid intravenous bolus under stable anesthesia, before surgical stimulation. Blood pressure and heart rate were measured by oscillometry and the electrocardiogram in patients receiving 2 times the ED95 of 51W89 or atracurium and by an intraarterial catheter and a tachograph triggered by the arterial pulse waveform in patients receiving 4 or 8 times the ED95 of 51W89. Maximal blood pressure and heart rate changes during the 5 min after administration of the muscle relaxant were recorded. Venous blood samples were obtained before the administration of relaxant and at 2 and 5 min after the administration of relaxant for determination of plasma histamine concentrations by radioenzymatic assay. RESULTS: Maximal blood pressure and heart rate changes in all groups of patients receiving 51W89 were small and similar to those observed in patients receiving 2 times the ED95 of atracurium. The mean maximum percent changes (+/- SE) in heart rate and mean arterial pressure were -0.6 +/- 1.5 and 0.4 +/- 2.5, respectively, in the group receiving 2 times the ED95 atracurium; -1.3 +/- 3.3 and 2.3 +/- 4.4, respectively, in the group receiving 2 times the ED95 51W89; -2.6 +/- 1.0 and 2.6 +/- 1.5, respectively, in the group receiving 4 times the ED95 51W89; and -2.4 +/- 1.5 and -1.0 +/- 1.3, respectively, in the group receiving 8 times the ED95 51W89. No patient developed a decrease in blood pressure > or = 20% or an increase in heart rate > or = 20% that was attributable to muscle relaxant administration. There was no dose-related change in plasma histamine concentration associated with the administration of 51W89. One patient in the study developed transient facial flushing after the administration of atracurium. CONCLUSIONS: 51W89 is a benzylisoquinolinium-type, nondepolarizing muscle relaxant that does not affect plasma histamine concentrations. No cutaneous flushing or clinically important cardiovascular effects were noted after rapid injection of doses up to and including 8 times its ED95 (0.4 mg.kg-1) in healthy patients undergoing elective surgical procedures.

The clinical neuromuscular pharmacology of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia.

BACKGROUND: Atracurium is a mixture of ten stereoisomers. 51W89, one of these isomers, is a potent nondepolarizing intermediate-duration neuromuscular blocking agent. Preclinical studies have shown 51W89 to be significantly more potent than atracurium but with a similar neuromuscular blocking profile. This study was undertaken to establish the neuromuscular blocking potency and pharmacodynamics of 51W89 in patients undergoing elective surgical procedures. METHODS: Ninety-nine ASA physical status 1 or 2 patients undergoing elective surgical procedures under nitrous oxide/opioid/barbiturate anesthesia were studied. The neuromuscular blocking effect of 51W89 was assessed after administration of bolus doses from 0.015 to 0.4 mg/kg, as well as during and after continuous infusions from 11 to 249 min in length. RESULTS: The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.048 mg/kg. At 0.10 mg/kg, maximum block developed within 5.2 +/- 0.3 min, and recovery to 95% twitch height occurred 64.4 +/- 3.9 min after injection. At 0.4 mg/kg, onset was 1.9 +/- 0.1 min, and 95% recovery developed within 121.0 +/- 5.9 min. Comparative recovery indexes from 5% to 95% or from 25% to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.4 mg/kg (means ranged from 29.6 to 32.3 min and from 12.6 to 14.3 min, respectively). The average infusion rate necessary to maintain approximately 95% twitch suppression was 1.35 micrograms/kg/min. Recovery indexes from infusions were 5-95% 33.2 +/- 1.8 min and 25-75% 15.0 +/- 0.6 min, not differing significantly from recovery indexes from single bolus doses. Twenty-five patients received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at twitch height recovery of between 6% and 21%. Antagonism to 95% control twitch height developed within 6.8 +/- 0.3 min, and the neostigmine-accelerated 25-75% recovery index was 2.8 +/- 0.2 min. CONCLUSIONS: 51W89 is a potent nondepolarizing neuromuscular blocking agent that shows noncumulative intermediate-duration neuromuscular blocking pharmacodynamics.

Effects of acid-base correction on hemodynamics, oxygen dynamics, and resuscitability in severe canine hemorrhagic shock.

OBJECTIVE: To compare the effects of hypertonic saline, sodium bicarbonate, and Carbicarb resuscitation on acid-base balance, hemodynamics, and oxygen dynamics in a reperfused, canine hemorrhagic shock model. DESIGN: Prospective, randomized trial. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-five anesthetized, mongrel dogs. INTERVENTIONS: After the administration of anesthesia, the dogs were intubated and mechanically ventilated. Vascular catheters were inserted into each femoral artery, for continuous blood pressure monitoring, intermittent blood sampling, and for establishing controlled hemorrhage. A pulmonary artery catheter was inserted via the right jugular vein. Inhaled and exhaled gases were continuously analyzed using a metabolic gas monitor. The animals were subjected to 90 mins of controlled hemorrhagic shock. They were then randomly given a 2.5-mL/kg equimolar injection of 8.4% sodium bicarbonate, Carbicarb, or 5.84% hypertonic saline. The sodium load per kilogram of body weight was identical in all three groups. Thirty minutes later, the animals were retransfused with the shed blood over 15 mins and further observed for 120 mins. MEASUREMENTS AND MAIN RESULTS: Carbicarb and sodium bicarbonate both significantly increased bicarbonate concentrations compared with saline. Arterial and venous blood pH increased more with Carbicarb than with bicarbonate but this increase was not statistically significant. After shock but before retransfusion, all three treatments moderately increased blood pressure, cardiac index, oxygen delivery index, and oxygen consumption index to a similar extent. After retransfusion, blood pressure, cardiac index, and oxygen dynamics temporarily improved in all groups, without significant improvement in the bicarbonate and Carbicarb-treated animals, despite their excellent acid-base status. CONCLUSIONS: In severe canine hemorrhagic shock, Carbicarb, bicarbonate, and hypertonic saline appear to possess similar hemodynamic properties despite the buffering properties of bicarbonate and Carbicarb. The similar responses may be due to their identical sodium content. Arterial pH correction does not appear to further improve the responses to blood retransfusion.

Diagnóstico de pseudotuberculosis en ovinos patagónicos / Diagnosis of caseous lymphadenitis in sheep from Patagonia

La linfadenitis caseosa (LAC) es una enfermedad bacteriana supurativa crónica que afecta a ovinos. El agente etiológico es Corynebacterium pseudotuberculosis. El diagnóstico diferencial con otras afecciones que presentan manifestaciones clínicas similares sólo puede hacerse sobre la base del aislamiento y la identificación del agente etiológico. El objetivo de este trabajo fue caracterizar metabólica y genéticamente al agente causal de abscesos granulomatosos observados en ovinos en la región patagónica. En las muestras, se observó un contenido caseoso rodeado de una membrana fibrosa, y en el examen histopatológico, un centro de necrosis caseosa rodeado por células epitelioides, linfocitos y polinucleares. Mediante estudios microscópicos, bacteriológicos y moleculares fue confirmada la infección causada por C. pseudotuberculosis biovar ovis.

Caseous lymphadenitis (CLA) is a chronic bacterial, infectious and contagious disease caused by Corynebacterium pseudotuberculosis. It affects sheep and results in abscesses of the lymph nodes in subcutaneous tissue, as well as in internal organs such as lungs, liver and kidneys. Differential diagnosis of the disease is based on the isolation and biochemical identification of the etiological agent. The purpose of this study was to characterize the bacteria isolated from typical CLA lesions in sheep from Patagonia, Argentina, at metabolic and genetic levels. Macroscopic observations show a fibrous membrane containing caseous necrotic tissue. Histopathological analysis shows an eosinophilic necrotic area surrounded by epitheloid cells and polymorphonuclear infiltration. Other analyses performed such as microscopic observations, in vitro culture, biochemical tests and 16s rDNA sequencing confirmed diagnosis of caseous lymphadenitis due to C. pseudotuberculosis.