A micro-QuEChERS method coupled to GC-MS for the quantification of pesticides in specific maternal and fetal tissues.

The aim of this study was to establish a new QuEChERS (quick, easy, cheap, effective, rugged and safe) method coupled to gas chromatography-mass spectrometry (GC-MS) detection for the evaluation of the pesticide biodistribution in specific maternal and fetal tissues. This method was validated for the quantification of pesticides such as chlorotriazines (atrazine, simazine and propazine), their chlorinated metabolites (DIA, DEA and DACT). This new QuEChERS method was developed to facilitate extraction from small tissues such as fetal tissues (mean value: 200mg). The limits of detection, quantification, recovery, precision and accuracy were evaluated for different tissues (liver and brain) and blood. LOD and LOQ ranged between 0.34 and 3.27 ng/g and 1.04 to 9.91 ng/g, respectively. Recovery exceeded 80% for all pesticides, except DACT, with an associated RSD<15%. Precision and accuracy satisfied the criteria usually applied in the validation of bioanalytical methods. The results obtained indicate that this technique is suitable for use in studies of the biodistribution of pesticides in fetal tissues and can be used to evaluate the risk of exposure to pesticides during gestation.

Causes and consequences of anti-infective drug stock-outs.

Anti-infective drugs stock-outs are increasingly frequent, and this is unlikely to change. There are numerous causes for this, mostly related to parameters difficult to control: i) 60 to 80% of raw material or components are produced outside of Europe (compared to 20% 30 years ago), with subsequent loss of independence for their procurement; ii) the economic crisis drives the pharmaceutical companies to stop producing drugs of limited profitability (even among important drugs); iii) the enforcement of regulatory requirements and quality control procedures result in an increasing number of drugs being blocked during production. The therapeutic class most affected by drug stock-outs is that of anti-infective drugs, especially injectable ones, and many therapeutic dead ends have recently occurred. We provide an update on this issue, and suggest 2 major actions for improvement: i) to implement a group dedicated to anticipating drug stock-outs within the anti-infective committee in each health care center, with the objectives of organizing and coordinating the response whenever a drug stock-out is deemed at risk (i.e., contingency plans, substitution, communication to prescribers); ii) a national reflection lead by scientific societies, in collaboration with government agencies, upstream of the most problematic drug stock-outs, to elaborate and disseminate consensus guidelines for the management of these stock-outs.

In vitro evaluation of diffusion of lidocaine and alkalinized lidocaine through the polyurethane membrane of the endotracheal tube.

OBJECTIVES: Endotracheal tube (ETT) and its inflated cuff are likely to induce specific reactivity at the emergence time. In ICU, the tolerance of the ETT cuff could be a part of patient agitation and increased of sedation. MATERIALS AND METHODS: Using specific ICU ETT cuff (thin polyurethane cuff), we perform an in vitro evaluation of diffusion of lidocaine and alkalinized lidocaine (L-B) across the PU cuff for a long duration. We evaluate the safety of this procedure by a daily injection into the cuff. RESULTS: With lidocaine alone, we observed a low rate of diffusion through the cuff (<8% over 24h), whereas the L-B solution had a high diffusion (>90% over 24h). The released profiles were similar from day 0 to day 8, and no cuff rupture was reported over the 8-day study. CONCLUSION: The safety, controlled release, and lack of deleterious effects on cuff membrane were confirmed. In case of unexpected cuff rupture, an adequate determination of the mixture allows to obtain a safe solution with the achievement of a physiological pH (7.4) and the small dose of lidocaine (40 mg).

Mupirocin/chlorexidine to prevent methicillin-resistant Staphylococcus aureus infections: post hoc analysis of a placebo-controlled, randomized trial using mupirocin/chlorhexidine and polymyxin/tobramycin for the prevention of acquired infections in intubated patients.

PURPOSE: The reduction in acquired infections (AI) due to methicillin-resistant Staphylococcus aureus (MRSA) with the mupirocin/chlorhexidine (M/C) decontamination regimen has not been well studied in intubated patients. We performed post hoc analysis of a prior trial to assess the impact of M/C on MRSA AI and colonization. METHODS: We conducted a multicenter, placebo-controlled, randomized, double-blind study with the primary aim to reduce all-cause AI. The two regimens used [topical polymyxin and tobramycin (P/T), nasal mupirocin with chlorhexidine body wash (M/C), or corresponding placebos for each regimen] were administered according to a 2 × 2 factorial design. Participants were intubated patients in the intensive care units of three French university hospitals. The patients enrolled in the study (n = 515) received either active P/T (n = 130), active M/C (n = 130), both active regimens (n = 129), or placebos only (n = 126) for the period of intubation and an additional 24 h. The incidence and incidence rates (per 1,000 study days) of MRSA AI were assessed. Due to the absence of a statistically significant interaction between the two regimens, analysis was performed at the margins by comparing all patient receiving M/C (n = 259) to all patients not receiving M/C (n = 256), and all patients receiving P/T (n = 259) to all patients not receiving P/T (n = 256). RESULTS: Incidence [odds ratio (OR) 0.39, 95 % confidence interval (CI) (0.16-0.96), P = 0.04] and incidence rates [incidence rate ratio (IRR) 0.41, 95 % CI 0.17-0.97, P = 0.05] of MRSA AI were significantly lower with the use of M/C. We also observed an increase in the incidence (OR 2.50, 95 % CI 1.01-6.15, P = 0.05) and the incidence rate (IRR 2.90, 95 % CI 1.20-8.03, P = 0.03) of MRSA AI with the use of P/T. CONCLUSION: Among our study cohort of intubated patients, the use of M/C significantly reduced MRSA AI.

[Treatment of urinary tract infections in febrile infants: experience of outpatient intravenous antibiotic treatment]. / Manejo de la infección del tracto urinario en lactantes febriles: Experiencia de tratamiento antimicrobiano intravenoso ambulatorio.

OBJECTIVE: To describe the feasibility, effectiveness and safety of intravenous (iv) outpatient treatment in 2 to 24 month-old children with febrile urinary tract infection (UTI). METHOD: Children presenting to the ER, between April 2003-2005, with fever and no identifiable focus who had a diagnosis of UTI were randomized to receive iv antibiotic in the hospital or in an outpatient facility. Children were started on amikacin or ceftriaxona according to physician criteria followed by antimicrobial adjustment based on urine culture result and a later switch to an oral antimicrobial. Urine cultures were performed during and after completing the antimicrobial course. Adherence and effectiveness of antimicrobial treatment and treatment-associated complications were analyzed. RESULTS: The study included 112 patients, 58 inpatient children and 54 outpatient children, with an average age of 7.7 months. Duration of iv treatment did not differ among groups (2.8 days (SD 1.2) 2.7 +0.91 days in inpatients vs 2.9 + 1.9 days in outpatients (p = 0.22). In 100% of outpatient children and 100% of inpatient children (overall 101/101) urine cultures were negative on day 5. None of the children had a treatment-associated complication. Cost analysis yielded 73% of saving money (overall cost for inpatient treatment US 9,815 vs outpatient treatment US 2,650). CONCLUSIONS: Outpatient iv treatment in patients between 2 and 24 months with UTI and fever was effective, safe and of lower cost.

Manejo de la infección del tracto urinario en lactantes febriles: experiencia de tratamiento antimicrobiano intravenoso ambulatorio / Treatment of urinary tract infections in febrile infants: experience of outpatient intravenous antibiotic treatment

Objective: To describe the feasibility, effectiveness and safety of intravenous (iv) outpatient treatment in 2 to 24 month-old children with febrile urinary tract infection (UTI). Method: Children presenting to the ER, between April 2003-2005, with fever and no identifiable focus who had a diagnosis of UTI were randomized to receive iv antibiotic in the hospital or in an outpatient facility. Children were started on amikacin or ceftriaxona according to physician criteria followed by antimicrobial adjustment based on uriñe culture result and a later switch to an oral antimicrobial. Uriñe cultures were performed during and after completing the antimicrobial course. Adherence and effectiveness of antimicrobial treatment and treatment-associated complications were analyzed. Results: The study included 112 patients, 58 inpatient children and 54 outpatient children, with an average age of 7.7 months. Duration of iv treatment didnot differ among groups (2.8 days (SD 1.2) 2.7 +0.91 days ininpatients vs 2.9 + 1.9 days in outpatients (p = 0.22). In 100 percent of outpatient children and 100 percent of inpatient children (overall 101/101) uriñe cultures were negative on day 5. None of the children had a treatment-associated complication. Cost analysis yielded 73 percent of saving money (overall cost for inpatient treatment US 9,815 vs outpatient treatment US 2,650). Conclusions: Outpatient iv treatment in patients between 2 and 24 months with UTI and fever was effective, safe and of lower cost.

Objetivo: Describir la factibilidad, efectividad y seguridad del tratamiento intravenoso (iv) ambulatorio en niños de 2 meses a 2 años con infección del tracto urinario (ITU) y fiebre. Método: Entre abril 2003 y abril 2005 se realizó un estudio prospectivo en pacientes con fiebre sin foco derivados de Emergencia Infantil, finalmente diagnosticados como ITU, estableciéndose dos grupos con tratamiento iv: uno hospitalizado y otro ambulatorio. Se administró amikacina o ceftriaxona según criterio del médico de turno, hasta obtener resultado del urocultivo, y posteriormente se cambió a tratamiento oral. Se controló urocultivo intra y post tratamiento registrándose adherencia, efectividad y complicaciones. Resultados: Se incluyeron 112 pacientes (58 hospitalizados y 54 ambulatorios), con edad promedio de 7,8 meses. El promedio de días de tratamiento iv fue 2,8 días (SD 1,2) sin diferencias significativas entre ambos grupos 2,7 +0,91 días en los internados vs 2,9 + 1,9 días en los ambulatorios (p = 0,22). En 100 por ciento de ambos grupos de pacientes (en globo 101/101) el urocultivo obtenido al día 5 fue estéril. No hubo complicaciones del tratamiento o sobre la vía venosa. El análisis de costos concluyó que en globo, el manejo ambulatorio representó un 73 por ciento de ahorro económico (1.430.000 pesos chilenos vs 5.300.000 pesos en el sólo rubro de día-cama Conclusiones: El tratamiento iv ambulatorio en pacientes con ITU febril entre 2 y 24 meses fue efectivo, seguro y a un menor costo.

Influence of efflux transporters on liver, bile and brain disposition of amitriptyline in mice.

The aim of this work was to clarify the role of Abcb1 and the possible involvement of Abcc2 and Abcg2 in liver, bile and brain disposition of amitriptyline (AMI). AMI was administrated to Abcb1a deficient mice (n=36): CF1 (-/-) and CF1 (+/+) mice received via intraperitoneal route (i.p.) 5 mg/kg AMI and CF1 (+/+) mice received i.p. 5 mg/kg AMI+100 mg/kg quinidine (Abcb1 inhibitor). Then, Swiss mice (n=24) received i.p. 5 mg/kg AMI alone and in association with 200 mg/kg novobiocin (Abcg2 inhibitor), 20 mg/kg probenecid (Abcc2 inhibitor) and 100 mg/kg quinidine. Plasma concentrations of AMI were not influenced by novobiocin, probenecid and the lack of Abcb1, but were significantly increased by quinidine, resulting from the inhibition of hydroxylation mediated by CYP2D6. Brain distribution of AMI was not influenced by the lack of Abcb1 but was slightly significant with quinidine and not with novobiocin and probenecid. At the hepato-biliary interface, we showed the involvement of Abcb1, Abcc2 and Abcg2; indeed, AMI concentration was increased in liver and decreased in bile, where quinidine is the strongest inhibitor, followed by probenecid and novobiocin. These results show that in brain the effect of Abcb1, Abcc2 and Abcg2 should be negligible and that at the hepato-biliary level, Abcb1 plays a predominant role compared to Abcc2 and Abcg2.

Mucosal or systemic administration of rE2 glycoprotein antigen loaded PLGA microspheres.

We have evaluated the ability of recombinant E2 antigen, as a surfactant free formulation of poly (D,L-lactide-co-glycolide) (PLGA) microspheres, to elicit a systemic immune response after administration by mucosal routes (oral and nasal) in comparison to intramuscular route. The sequence encoding a truncated E2 glycoprotein of the classical swine fever virus (CSFV) was expressed in insect cells following infection with recombinant baculovirus, as a His-tagged recombinant antigen. The recombinant E2 glycoprotein (rE2) antigen was co-encapsulated with rabbit serum albumin (RSA) as a protein stabilizer. rE2/RSA loaded PLGA microspheres, with a mean diameter of 4 microm were obtained by a water in oil in water solvent extraction method (w/o/w). Rabbits were immunized with 10 microg of rE2 formulated in PLGA microspheres administrated by three different routes (oral, nasal and intramuscular). After 60 days, each rabbit in all three groups was challenge with 5 microg of rE2 glycoprotein solution by intradermal administration. Blood samples were collected weekly for 90 days and specific rE2 antigen antibodies measured. This work showed that rE2 antigen loaded microspheres was able to initiate an immune response. The intradermal challenge after nasal and oral administration had a clear boost effect on the systemic immune response. Moreover, the response after nasal administration was more intense and less variable than oral route. In conclusion, these data demonstrate a high potential of rE2 loaded PLGA microspheres for their use as a mucosal subunit vaccine.

Local anaesthetic use for the iliac crest-donor site: pharmacokinetic and pharmacodynamic evaluations.

During orthopaedic surgery of the limb, we performed a prospective, double blind controlled study on three parallel groups in 30 patients to evaluate the pharmacokinetic and pharmacodynamic effect of infiltration of the iliac crest bone graft harvest site with 20 ml of bupivacaine (100 mg), ropivacaine (150 mg) or saline as control group (n = 10 in each group). Then, in a sheep model of iliac crest infiltration, we compared the pharmacokinetics of single administration of plain bupivacaine (100 mg) and bupivacaine (500 mg)-loaded microspheres. In the clinical control group, pain from the iliac crest was worse than pain from the primary surgical site. Pain from the iliac crest was significantly reduced during the first 12 postoperative hours in local anaesthetic groups compared to the control group. However, during this period, pain from the primary surgical site was increased compared to the control group. Finally, there was no difference between the three groups in the average intake of PCA morphine. There was no significant pharmacokinetic and pharmacodynamic difference between plain bupivacaine and ropivacaine. The maximal plasma concentration (Cmax) of ropivacaine and bupivacaine were 964 (282) ng ml(-1) and 638 (366) ng ml(-1), respectively. In the sheep model, it was clearly shown that the release of bupivacaine from microspheres was controlled and prolonged despite the largest dose of bupivacaine used (500 mg; n = 4). Wound infiltration of iliac crest harvest site with local anaesthetic is an easy technique for postoperative analgesia. However, this effect lasts only 12 hours without reducing the morphine consumption due to an increase of pain from the primary surgical site. The local anaesthetic infiltration produced a significant peak of plasma level, which could be dangerous if another infiltration or regional anaesthetic technique was associated with it. Experimentally, as a drug delivery system, the use of local anaesthetic-loaded microspheres could be an interesting alternative.

[Disseminated and fatal adenovirus infection in an immunocompromised child]. / Infección diseminada por adenovirus de curso fatal en un niño inmunocomprometido.

Severe adenovirus (ADV) infections have become increasingly important in immunocompromised patients, mainly in pediatric stem cell transplant recipients. We report a case of disseminated ADV infection leading to death in a 12-year-old stem cell transplant recipient. The diagnosis was confirmed by viral isolation and viral genome detection in tissues and blood. Main issues associated with infection, diagnosis and therapeutic alternatives are reviewed. This case should alert clinicians to suspect and study this agent in high risk patients and highlights the importance of having antiviral drugs for ADV available in Chile.

Infección diseminada por adenovirus de curso fatal en un niño inmunocomprometido / Disseminated and fatal adenovirus infection in an immunocompromised child

Las infecciones graves por adenovirus (ADV) tienen una importancia creciente en pacientes inmuno-comprometidos, en especial en niños sometidos a trasplante de precursores hematopoyéticos (TPH). Se reporta un caso de infección por ADV inicialmente gastrointestinal y luego diseminada, de curso fatal, en un niño de 12 años, post LPH. El diagnóstico se confirmó mediante aislamiento viral y detección de genoma viral en tejidos y sangre. Se revisan los principales aspectos de la infección por ADV, su diagnóstico y las posibilidades terapéuticas. Este caso debe alertar a los médicos clínicos para sospechar y estudiar este agente viral en pacientes de alto riesgo y enfatiza la importancia de disponer en Chile de antivirales para su tratamiento.

Severe adenovirus (ADV) infections have become increasingly important in immunocompromised patients, mainly in pediatric stem cell transplant recipients. We report a case of disseminated ADV infection leading to death in a 12-year-old stem cell transplant recipient. The diagnosis was confirmed by viral isolation and viral genome detection in tissues and blood. Main issues associated with infection, diagnosis and therapeutic alternatives are reviewed. This case should alert clinicians to suspect and study this agent in high risk patients and highlights the importance of having antiviral drugs for ADV available in Chile.

Effect of epinephrine on epidural, intrathecal, and plasma pharmacokinetics of ropivacaine and bupivacaine in sheep.

BACKGROUND: Local vasoconstriction induced by epinephrine added to epidural local anaesthetics has been shown to improve their quality and duration of action in several clinical reports. There are several assumptions on the mechanisms. This study was designed to evaluate the influence of epinephrine on transmeningeal uptake of epidurally administered ropivacaine and bupivacaine by measuring local anaesthetic concentrations in the epidural and intrathecal spaces and in plasma. METHODS: Ropivacaine (50 mg) and bupivacaine (30 mg) were administered epidurally in sheep with and without epinephrine (75 microg). A microdialysis technique was used to simultaneously measure epidural and intrathecal drug concentrations. Resulting dialysate and plasma concentrations were used to calculate pharmacokinetic parameters for ropivacaine and bupivacaine. RESULTS: Co-administration of epinephrine decreased epidural clearance for ropivacaine [0.6 (sd 0.1) vs 0.4 (0.1) ml min(-1)] but not significantly for bupivacaine [1.2 (0.4) vs 0.8 (0.3) ml min(-1)]. The resultant increase in epidural area under the concentration-time curves (31% for ropivacaine and 52% for bupivacaine) was also observed in the intrathecal space (21% increase for ropivacaine and 37% for bupivacaine). There was no significant influence of epinephrine on ropivacaine plasma pharmacokinetics. Plasma Cmax for bupivacaine was decreased. CONCLUSIONS: These results show that epinephrine decreases the clearance and distribution processes involved in epidural disposition of ropivacaine and bupivacaine, leading to an increased uptake into the intrathecal space with an apparent more pronounced effect for bupivacaine.

[Human metapneumovirus as hospitalization cause in children under 3 years old with acute respiratory infections during 2004]. / Metapneumovirus humano como causa de hospitalización en niños bajo 3 años de edad, con infección respiratoria aguda, durante el año 2004.

Human metapneumovirus was detected in 15 of 123 children (12%) younger than 3 years of age hospitalized for treatment of acute respiratory infection between July and November 2004. The virus was detected by RT-PCR directly from nasopharyngeal swabs and/or from supernatants after cell culture. Children infected with hMPV were mostly younger than one year of age (67%), all presenting with fever and cough. The main cause for hospitalization was the need for oxygen therapy (73%). Four hMPV positive children had an identifiable co-morbid condition but had a similar clinical evolution when compared to previously healthy infants. Chest radiography showed an increase in interstitial infiltrates with focal consolidation in 6 children. Obstructive bronchial syndrome and bronchiolitis, with or without pneumonia, were the most frequent diagnosis associated with hMPV positivity. A rapid and sensitive diagnostic method is required to improve diagnosis and treatment of these patients.

Metapneumovirus humano como causa de hospitalización en niños bajo 3 años de edad, con infección respiratoria aguda, durante el año 2004 / Human metapneumovirus as hospitalization cause in children under 3 years old with acute respiratory infections during 2004

Metapneumovirus humano (MPVh) fue detectado entre julio y noviembre en 15 de 123 niños bajo 3 años de edad hospitalizados por infección respiratoria aguda (12 por ciento). Las muestras fueron estudiadas mediante técnicas de biología molecular (RPC-TR de muestra de hisopado nasofaríngeo y/o de sobrenadante de cultivo). El 67 por ciento de los niños hospitalizados con MPVh tenían menos de 1 año de edad, todos ellos presentaron tos y fiebre y el principal motivo de hospitalización fue el requerimiento de oxígeno en 73 por ciento de los casos. Si bien un tercio de los pacientes tenía patología previa, su evolución clínica no fue diferente respecto de los niños previamente sanos. El patrón radiológico mostró aumento de la trama intersticial, con focos de consolidación en 6 casos (40 por ciento). El diagnóstico más frecuente fue síndrome bronquial obstructivo o bronquiolitis, asociado o no a neumonía. Destaca la necesidad de un método de diagnóstico rápido para optimizar el diagnóstico diferencial, manejo y control de infecciones en estos pacientes.

Human metapneumovirus was detected in 15 of 123 children (12 percent) younger than 3 years of age hospitalized for treatment of acute respiratory infection between July and November 2004. The virus was detected by RT-PCR directly from nasopharyngeal swabs and/or from supernatants after cell culture. Children infected with hMPV were mostly younger than one year of age (67 percent), all presenting with fever and cough. The main cause for hospitalization was the need for oxygen therapy (73 percent). Four hMPV positive children had an identifiable co-morbid condition but had a similar clinical evolution when compared to previously healthy infants. Chest radiography showed an increase in interstitial infiltrates with focal consolidation in 6 children. Obstructive bronchial syndrome and bronchiolitis, with or without pneumonia, were the most frequent diagnosis associated with hMPV positivity. A rapid and sensitive diagnostic method is required to improve diagnosis and treatment of these patients.

Endocarditis por Streptococcus pneumoniae en niños: presentación de un caso clínico y revisión de la literatura / Endocarditis caused by Streptococcus pneumoniae in children: case report and review

La endocarditis causada por Streptococcus pneumoniae es una patología muy poco frecuente en niños, correspondiendo sólo a 3 - 7 por ciento de los casos. Sin embargo, su importancia radica en que se puede presentar de forma muy agresiva, con complicaciones como destrucción valvular y abscesos, y con una mortalidad reportada hasta 61 por ciento, de no mediar tratamiento antimicrobiano precoz y muchas veces cardiocirugía. En más del 50 por ciento se puede asociar a otros focos infecciosos, como meningitis, neumonía, sinusitis o mastoiditis. Se describe el caso de una lactante de 10 meses que presentó una meningitis asociada a endocarditis debidas a S. pneumoniae, con grave compromiso cardíaco, y que requirió reemplazo valvular. Se realizó una revisión de la literatura médica acerca de endocarditis por S. pneumoniae en niños.

Búsqueda de resistencia a amantadina en cepas de virus influenza A aisladas en Santiago de Chile, entre los años 2001 y 2002 / Search of amantadine-resistance in influenza A strains isolated in Santiago, Chile, 2001-2002

Amantadina es un fármaco eficaz para el tratamiento y prevención de influenza A. Su mecanismo de acción es inhibir la proteína M2. Su uso por períodos prolongados puede generar resistencia, la cual ocurre por mutaciones en el gen que codifica para la proteína M2. La mutación más frecuentemente encontrada se ubica en la posición 31. El uso de técnicas de biología molecular permite detectar estas mutaciones. Los objetivos fueron determinar la existencia de resistencia a amantadina en cepas de virus influenza A aisladas entre los años 2001 y 2002 en un laboratorio de virología en Santiago de Chile, y validar un nuevo método de biología molecular para reconocer cepas resistentes. Para ello se utilizó metodología de RPC y análisis de tamaño de fragmentos de restricción. En 31 cepas procesadas no se observó la presencia de cambios en la posición 31. Estos hallazgos sugieren que la resistencia a amantadina es muy baja o está ausente en nuestro medio. Esto podría explicarse por un limitado uso de este fármaco en esta población. El método descrito puede servir de base para un monitoreo prospectivo de resistencia, que pueda ser de utilidad al médico clínico.

Contralateral effect of amitriptyline and bupivacaine for sciatic nerve block in an animal model of inflammation.

BACKGROUND: Using a carrageenan inflammation rat model, we evaluated two experimental approaches to prolong sciatic nerve block on contralateral hyperalgesia. Method. We performed ipsilateral sciatic nerve block on the inflamed hind paw with bupivacaine-loaded microspheres suspended in dexamethasone (bupivacaine 12.5 mg) and with amitriptyline (6.25 and 12.5 mg) as ultralong-acting local anaesthetics. Bupivacaine (1.25 mg) was used as long-acting local anaesthetic and saline was used as a control. The sixth group received amitriptyline 6.25 mg intraperitoneally (n=10 for each group). RESULTS: The duration of ipsilateral nerve block was 2 h for bupivacaine, 7 h for amitriptyline 6.25 mg, 11 h for amitriptyline 12.5 mg and 21 h for bupivacaine-loaded microspheres in suspension with dexamethasone. Whereas contralateral hyperalgesia was not observed during block produced by bupivacaine-loaded microspheres, contralateral hyperalgesia was observed with sciatic nerve block using amitriptyline. CONCLUSIONS: Because of the differential effect observed on the contralateral side, the mechanism underlying the prolongation of ipsilateral block with amitriptyline may not result only from a prolonged Na(+) channel blockade but might be explained by a local toxic effect or lack of systemic actions.

Bupivacaine containing dry emulsion can prolong epidural anesthetic effects in rabbits.

To assess the prolongation of epidural bupivacaine by a novel lipid formulation, a physically stabilized bupivacaine containing dry emulsion was prepared by spray-drying. Bupivacaine release from the oil-in-water emulsion was studied using an in vitro two-phase stirred model, then the pharmacodynamic effects and the pharmacokinetics of bupivacaine from the spray-dried emulsion were evaluated and compared to a bupivacaine hydrochloride solution, following a two-period cross-over epidural administration in rabbits. The in vitro release characteristics suggested an extended release of bupivacaine from the emulsion compared to the solution. From the in vivo study, C(max) obtained with the emulsion (containing 5 mg bupivacaine) was not statistically different than from the solution (containing 2 mg bupivacaine) while T(max) was increased, suggesting a diminution of bupivacaine systemic absorption. The onset time of epidural anesthesia was similar for both formulations of bupivacaine used, while a significant blockade prolongation (360%) was observed with the emulsion compared to the solution, suggesting a controlled release of bupivacaine. Dry emulsions could be promising dosage forms to optimize the disposition of epidurally administered LAs.

Alkalinization of intra-cuff lidocaine and use of gel lubrication protect against tracheal tube-induced emergence phenomena.

BACKGROUND: We sought to determine the benefits of using alkalinized lidocaine 40 mg to fill the cuff of a tracheal tube (ETT) in combination with water-soluble gel lubrication to prevent post-intubation sore throat. METHODS: The work included an in vitro study of the diffusion of alkalinized lidocaine solution through the low-pressure, high-volume cuff of an ETT. We also performed a randomized controlled study (n=20 patients in each group) that included a group who received an alkalinized lidocaine-filled ETT cuff with lubrication of the tube using water-soluble gel (Group G), and two control groups who received an alkalinized lidocaine-filled cuff with ETT lubrication with water (Group W) or an air-filled cuff with ETT lubrication with water (Group C). RESULTS: Water-soluble gel lubrication (Group G) produced a lower incidence of sore throat during the 24-h post-extubation period than lubrication with water alone in the cuffs filled with alkalinized lidocaine (Group W), and compared with the air control group. The ability of lidocaine to pass through the cuff of an ETT when water-soluble gel and/or water alone was used as a lubricant was similar, as determined by lidocaine plasma concentrations (C(max) 45 ng x ml(-1)). Cough and restlessness before tracheal extubation were decreased in patients with the alkalinized lidocaine-filled cuffs compared with the air-filled cuffs. After extubation, nausea, vomiting, dysphonia and hoarseness were greater for patients with air-filled cuffs compared with the lidocaine-filled cuffs. No significant difference between the groups was recorded in arterial blood pressure and heart rate. In vitro data suggest that the lower the NaHCO(3) injection volume, the greater the release of lidocaine across a low-pressure, high-volume cuff. CONCLUSIONS: These data show benefits of using an alkalinized lidocaine-filled ETT cuff in combination with water-soluble gel lubrication in preventing post-intubation sore throat.

Effects of oil and bioremediation on mussel (Mytilus edulis L.) growth in mudflats.

Mussels (Mytilus edulis L.) were exposed to crude oil during a field experiment to evaluate two bioremediation strategies (nutrient addition and nutrient addition with tilling). The mussels were placed in 4 mesocosms: Control, Oil, Oil + Nutrients, and Oil + Nutrients + Tilled. Tilling appeared to be clearly detrimental to mussel growth. Additionally, this field experiment demonstrated that at temperatures below 5 degrees C, growth was reduced to rates undetectable by the laser diffraction method. The data on mussel shell length show that this technique does offer very sensitive and useful comparative measurements of physiological function. Measurement of shell growth has the advantage over other techniques in that it is non-invasive and non-destructive and thus may be used continuously without disturbing critical physiological and biochemical functions; however, bivalve physiology is strongly linked to environmental conditions, so it is important to include such measures (i.e. seawater temperature and turbidity) in the design of the biomonitoring program. Elevated polycyclic aromatic hydrocarbon (PAH) levels reflected bioaccumulation in mussels from all the oiled mesocosms. This correlated with reduction in growth rate. Maximum reduction in growth was observed in mussels from the tilled mesocosm which contained the lowest phenanthrene and dibenzothiophene concentrations. The tilling caused an increase in suspended solids which inhibited filter feeding activity, and resulted in suppressed growth and slower intake of PAH-laden sediment.