Feasibility and safety of ultra-low tidal volume ventilation without extracorporeal circulation in moderately severe and severe ARDS patients.

PURPOSE: Mechanical ventilation with ultra-low tidal volume (VT) during ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury, with the main drawback of worsening respiratory acidosis. We hypothesized that VT could be reduced down to 4 ml/kg, with clinically significant decrease in driving pressure, without the need for extracorporeal CO2 removal, while maintaining pH > 7.20. METHODS: We conducted a non-experimental before-and-after multicenter study on 35 ARDS patients with PaO2/FiO2 ≤ 150 mmHg, within 24 h of ARDS diagnosis. After inclusion, VT was reduced to 4 ml/kg and further adjusted to maintain pH ≥ 7.20, respiratory rate was increased up to 40 min-1 and PEEP was set using a PEEP-FiO2 table. The primary judgment criterion was driving pressure on day 2 of the study, as compared to inclusion. RESULTS: From inclusion to day 2, driving pressure decreased significantly from 12 [9-15]  to 8 [6-11] cmH2O, while VT decreased from 6.0 [5.9-6.1] to 4.1 [4.0-4.7] ml/kg. On day 2, VT was below 4.2 ml/kg in 65% [CI95% 48%-79%], and below 5.25 ml/kg in 88% [CI95% 74%-95%] of the patients. 2 patients (6%) developed acute cor pulmonale after inclusion. Eleven patients (32%) developed transient severe acidosis with pH < 7.15. Fourteen patients (41%) died before day 90. CONCLUSION: Ultra-low tidal volume ventilation may be applied in approximately 2/3 of moderately severe-to-severe ARDS patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients.

Effect of preoxygenation using non-invasive ventilation before intubation on subsequent organ failures in hypoxaemic patients: a randomised clinical trial.

BACKGROUND: Previous data showed that non-invasive ventilation (NIV) applied for 3 min before tracheal intubation ensured better oxygenation compared with using a non-rebreather bag-valve-mask. We aimed to determine whether preoxygenation using NIV is effective in reducing the incidence of organ dysfunction in hypoxaemic, critically ill patients in intensive care. METHODS: A multicentre, randomised, open-label trial evaluating 100% FiO2 administered with NIV (99 patients) vs with face mask (102 patients) for 3 min before tracheal intubation. The primary endpoint was the maximal value of Sequential Organ Failure Assessment score within 7 days after intubation. RESULTS: The median (inter-quartile range) values of the maximal value of the Sequential Organ Failure Assessment score within 7 days post-intubation were not significantly different between the two randomised groups: nine (6-12) in the NIV group vs 10 (6-12) in the face mask group (P=0.65). In patients treated by NIV prior to the randomisation, there was a significant increase in the occurrence in adverse events in patients randomised to face mask [odds ratio=5.23 (1.61;16.99), P=0.0059]. CONCLUSIONS: This study failed to demonstrate any benefits of using NIV as a preoxygenation method to reduce organ dysfunction compared with usual preoxygenation in hypoxaemic, critically ill patients requiring tracheal intubation for invasive ventilation. NIV should not be discontinued for preoxygenation in the cases of patients treated by NIV before the decision to intubate. CLINICAL TRIAL REGISTRATION: NCT00472160.

Hidatidosis pulmonar bilateral: Reporte de caso / 0 BILATERAL PULMONARY HYDATID DISEASE: CASE REPORT AND REVISION

La hidatidosis es una zoonosis de distribución mundial producida por cestodos del género Echinococcus. Afecta principalmente regiones agrícolas y ganaderas. Es una enfermedad endémica en nuestro país, las mayores incidencias reportadas en Sudamérica corresponden Argentina, Chile, Uruguay y Brasil. El hígado es el principal órgano en el humano, le sigue en frecuencia el pulmón. La clínica suele ser inespecífica. Los síntomas más frecuentes son la tos y el dolor torácico, siendo un hallazgo en estudios imagenológicos. El diagnóstico de sospecha es a través de imágenes, apoyado en antecedentes epidemiológicos y serológicos. La radiografía de tórax asociada a la clínica permite el diagnóstico certero en hasta el 95% de los casos, sin embargo, los avances en la TC y su capacidad de caracterización la han hecho parte habitual del estudio preoperatorio. El tratamiento de la hidatidosis pulmonar es quirúrgico y consiste en la erradicación de los quistes, la corrección de los efectos de la presencia del quiste en el órgano (periquística y cavidad residual) y tratar las complicaciones que el quiste ha provocado en su evolución (fístulas bronquiales y siembra pleural). El tratamiento médico está reservado para quistes múltiples, únicos univesiculares menores de 5cm, pacientes de alto riesgo quirúrgico o inoperables y como quimioprofilaxis pre y postoperatoria. Existe consenso en que la cirugía con preservación de parénquima pulmonar es la elección, reservándose las resecciones pulmonares para aquellos casos en los que el tejido adyacente se encuentra seriamente dañado o infectado o cuando las aéreas de atelectasias son presumiblemente irrecuperables

Hydatidosis is a worldwide distribution zoonosis caused by Cestodes of the genus echinococcus. Mainly affects agricultural and livestock regions. Is an endemic disease in our country, the highest reports in South America correspond to Argentina, Chile, Uruguay and Brazil. The liver is the main target of the parasite, followed in frequency by the lungs. The clinical signs are usually non-specific. Most common symptons are cough and pain chest, being a finding in imaging studies. The presumptive diagnosis is made trough images, support by epidemiological and serological records. The chest x-Ray associated with the clinical symptons allows 95% of accuracy, however advances in CT allows to visualize the difference between the cyst and the normal tissue, this has turned it into a usual step in preoperative studies. The treatment of pulmonary hydatidosis is surgical and consists of the elimination of the cysts, the correction of the effects made by the presence of them in the organ (pericysts and residual cavity) and heal the complications the cysts may have done during the evolution (bronchial fistulas and pleural seeding). The medical treatment (non surgical) is only indicated in multiple cysts or unique uni vesiculares cysts under 5 cm, high risk surgical or inoperable patients and as pre and postoperative chemoprophylaxis. There is general agreement that lung parenchymal preservation surgery is the choice, reserving the pulmonary resections in cases that adjacent tissue is severely damaged of infected or when areas of atelectasis are presumably lost

How I do it? Cranial setup for cranial settling.

BACKGROUND: Expanded endonasal endoscopic techniques allow us to treat several pathologies related to the odontoid process and craniocervical junction. Cases such as giant basilar invagination represent a surgical challenge. METHODS: The authors provide technical nuances and describe how to complete an endoscopic endonasal odontoidectomy and release the craniocervical junction with the aim of restoring a correct sagittal balance in cases with giant basilar invagination. The study of cadaveric specimens adds clarifying dissections. CONCLUSIONS: Endonasal endoscopic odontoidectomy and craniocervical junction joint release allow the treatment of irreducible basilar invagination and restoration of better sagittal balance before posterior cervical occipitocervical fusion.

Association study of 37 genes related to serotonin and dopamine neurotransmission and neurotrophic factors in cocaine dependence.

Cocaine dependence is a neuropsychiatric disorder in which both environmental and genetic factors are involved. Several processes, that include reward and neuroadaptations, mediate the transition from use to dependence. In this regard, dopamine and serotonin neurotransmission systems are clearly involved in reward and other cocaine-related effects, whereas neurotrophic factors may be responsible for neuroadaptations associated with cocaine dependence. We examined the contribution to cocaine dependence of 37 genes related to the dopaminergic and serotoninergic systems, neurotrophic factors and their receptors through a case-control association study with 319 single nucleotide polymorphisms selected according to genetic coverage criteria in 432 cocaine-dependent patients and 482 sex-matched unrelated controls. Single marker analyses provided evidence for association of the serotonin receptor HTR2A with cocaine dependence [rs6561333; nominal P-value adjusted for age = 1.9e-04, odds ratio = 1.72 (1.29-2.30)]. When patients were subdivided according to the presence or absence of psychotic symptoms, we confirmed the association between cocaine dependence and HTR2A in both subgroups of patients. Our data show additional evidence for the involvement of the serotoninergic system in the genetic susceptibility to cocaine dependence.

Outbreak of extended spectrum beta-lactamase-producing Klebsiella pneumoniae in an intensive care unit (Brest).

INTRODUCTION: We had for aim to describe control and investigation of an outbreak caused by a strain of Extended spectrum beta-lactamase producing Klebsiella pneumoniae in intensive care units of the Brest teaching hospital. PATIENTS AND METHOD: The case definition was a patient infected by or carrying the epidemic strain. Control measures and investigations are presented. A case-control study was conducted in the surgical intensive care unit. Each case was matched with two controls based on admission times in the unit. The study focused on diagnostic and therapeutic procedures, and potential contacts with healthcare workers, in this context of cross transmission. RESULTS: Between February and May 2011, nine cases were reported in the surgical ICU and two in the medical ICU. Eighteen controls were matched with the nine surgical ICU cases. Several factors were found to be statistically associated with infection or colonization by the epidemic strain: the surgical block in which patients had been operated and the ward of first hospitalization; the number of trans-esophageal and trans-thoracic echocardiographies, of central venous catheter insertions, and of surgical operations; intubation. The total number of invasive procedures was also found to be statistically higher among cases. CONCLUSION: This study identified factors associated with colonization or infection by the epidemic strain. These factors might have been involved in the transmission tree, and be vulnerable elements for the prevention of nosocomial infections and colonisations, and their epidemic spread.

Investigation and management of an imipenem-resistant oxa-23 Acinetobacter baumannii outbreak in an intensive care unit.

OBJECTIVES: The study objectives were to describe the investigation and management of an imipenem-resistant Acinetobacter baumannii outbreak that occurred in the 15-bed ICU of a tertiary care teaching hospital (Brest, France), during the summer 2008. PATIENTS AND METHODS: Patients harboring an imipenem-resistant A. baumannii strain were defined as case patients. We described case occurrence and steps taken to control the outbreak: contact isolation, reinforcement of hygiene procedures, unit shutdown decision, unit disinfection, and reopening. We also made a case control study and a cost analysis of the outbreak management. RESULTS: During a 10-day period, five patients were positive for a single clone of imipenem-resistant oxa-23 A. baumannii. Four patients presented with ventilation-acquired pneumonia and one was asymptomatic. The first two patients died one day after the first swab which led to the identification of A. baumannii. No additional case was noted in the ICU or in other hospital units after deciding to close the ICU. The cost of outbreak management was estimated at 264,553 euros. The case control study identified several factors associated with infection or colonization: length of stay in the ICU, chronic respiratory disease, number of previous antibiotic classes used, duration of ventilation, prone position, echocardiography, and presence of a nasogastric tube. CONCLUSION: This outbreak occurred during the summer period requiring the shutdown of the ICU and inducing a considerable cost. Rapid reactions of the ICU staff during the outbreak enabled to limit the epidemic.

Evaluation of angiogenesis with the expression of VEGF and CD34 in human non-small cell lung cancer.

Angiogenesis is an essential process in the progression of malignant tumors and the most potent angiogenic factor is the vascular endothelial growth factor (VEGF). On the other hand, the CD34 is an endothelial antigen that has been used to highlight the microvasculature vessel density (MVD) as a direct marker of the degree of neoangiogenesis. In the present study we report the VEGF expression and its relationship with MVD, measured by CD34, in two lineages of non-small cell lung cancer (NSCL): low differentiated adenocarcinomas and epidermoid carcinomas, in order to consider the possibility of using the correlation between both antibodies as a prognostic factor. Tumor sections were stained by immunohistochemistry for CD34 and VEGF. The results showed that the mean value of VEGF for adenocarcinoma was significantly higher than the one for epidermoid carcinoma (p < 0.001). However, the mean of MVD did not show significant differences between both types of tumors. The conventional factors taken into consideration (age over 60, sex, and presence of lymph nodes) was not significantly related to the angiogenic factors examined. In conclusion, we could affirm that CD34 is a better prognostic marker of neoangiogenesis in NSCLC, because both types of tumors have the same clinical prognosis, and so we expected the same behaviour from both markers.

Reliability of the Spanish version of the Composite Scale of Morningness.

AIM: The aim of this study was to examine the reliability of the Spanish version of Composite Scale of Morningness (CSM) and its ability to measure the circadian typology. SUBJECTS AND METHODS: Voluntary and unpaid psychology students (N= 391; 132 men and 259 women), aged between 17 and 33, completed the questionnaire between the months of September and December. RESULTS: The total score was independent of age and gender, with a close to normal distribution and a non-significant negative skewness. The internal consistency was high (Cronbach's alpha= 0.87) and factor analysis extracted three factors labeled Time of Retiring (items 2 and 7), Activity Planning (items 8, 9, and 13) and Morning Affect (items 3-6, and 10-12). With the 10th and 90th percentiles as cut-off scores, scorers below 22 (N= 40; 10.2%) are classified as evening-types and scorers above 39 as morning-types (N= 28; 7.2%). CONCLUSION: The Spanish questionnaire shares most of the good psychometric properties of other versions of the CSM, and thus can be used for Spanish-speaking student samples. Nevertheless, further studies of normative data in workers and aged subjects are needed in order to validate CSM.

Immediate and delayed voluntary ethanol effects on motor performance, learning and inhibition in rats.

The effects of prolonged voluntary ethanol consumption on psychomotor performance, operant conditioning and inhibition were examined in adult male Wistar rats. Animals were food deprived and alcohol or control solution was available 1 h/day during 15 days, with free water for the rest of the day. Then, rats were tested in a two-bottle paradigm (solution and water available) for 1 h/day during 19 days, and subjects were tested daily for psychomotor performance and operant conditioning immediately or 6 h after (delayed) the solution access. Psychomotor performance was tested in an 80 degrees -inclined screen. Successive conditioning phases were: free shaping (FS), continuous reinforcement (CRF), operant extinction (EXT), successive discrimination (DIS) and two-stimuli test (TST). Alcohol consumption deteriorated psychomotor performance and improved the animal's ability to learn simple associations between stimuli and responses (free shaping and extinction), in immediate and delayed groups. Finally, alcohol deteriorated behavioral inhibition (DIS and TST) tested immediately after drinking. Taken together, results suggest that prolonged voluntary ethanol intake could induce permanent psychomotor impairment and associative learning facilitation, and also an impairment of the inhibition related to the intoxication state.

Methylxanthines reverse the adipsic and aphagic syndrome induced by bilateral 6-hydroxydopamine lesions of the nigrostriatal pathway in rats.

This study investigated whether methylxanthines (caffeine and theophylline) would restore food and water intake in rats made aphagic and adipsic by bilateral 6-hydroxydopamine lesions of the nigrostriatal bundle, and these results were compared with the effects of d-amphetamine, the dopamine D(1) agonist SKF 38393, and the D(2/3) agonist quinpirole. In a separate experiment, we investigated whether the selective D(1) antagonist, SCH 23390, or the selective D(2) antagonist, sulpiride, would prevent the caffeine-induced restoration of food and water intake in bilaterally 6-hydroxydopamine denervated rats. The results showed that caffeine, theophylline, and quinpirole significantly reversed the aphagia and adipsia observed in lesioned animals. SKF 38393 had no significant effects on water intake, while it significantly restored food intake at the highest dose used. In contrast, d-amphetamine had no significant effects on food or water intake. Results from the second experiment showed that sulpiride attenuated the caffeine-induced restoration of food and water intake in lesioned rats to a greater extent than did SCH 23390. These data suggest that methylxanthines may mediate their effects on food and water intake in bilateral 6-hydroxydopamine-lesioned rats through an action at the dopaminergic system.

Effects of sub-chronic combined treatment with pergolide and caffeine on contralateral rotational behavior in unilateral 6-hydroxydopamine-denervated rats.

We studied the synergistic effects of pergolide and bromocriptine with caffeine on turning behavior in 6-OHDA denervated rats. Both pergolide and bromocriptine were synergistic with caffeine, and prevented tolerance to caffeine-induced turning. When caffeine was removed, tolerance to bromocriptine effects was observed for 1 day only, while no tolerance was observed to pergolide. These results suggest that caffeine could be useful in the treatment of Parkinson's disease, preferentially as an adjuvant of mixed dopaminergic agonists like pergolide.

Lack of synergism between caffeine and SKF 38393 on rotational behavior in 6-hydroxydopamine-denervated rats.

We have recently shown a synergistic effect between caffeine and the dopamine D(2) receptor agonist, bromocriptine, on contralateral rotational behavior in unilaterally 6-hydroxydopamine-denervated rats. In addition, we found that bromocriptine prevented caffeine-induced tolerance to this behavior following repeated treatment. In the present study, we investigated whether or not the dopamine D(1) receptor agonist, (+/-)-phenyl-2,3,4, 5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393), presented similar characteristics. Different groups of rats received simultaneous injections of either vehicle plus vehicle, caffeine (40 mg/kg) plus vehicle, SKF 38393 (0.5, 1, 2, and 4 mg/kg) plus vehicle, or caffeine plus SKF 38393 (0.5, 1, 2, and 4 mg/kg) for 5 consecutive days, and both ipsilateral and contralateral rotational behavior was measured. Results showed that, on the first day of treatment, caffeine produced significantly more rotational behavior than did a low dose of SKF 38393 (0.5 mg/kg), and significantly less turning than at higher doses (2 and 4 mg/kg). Combined treatment with caffeine and a high dose of SKF 38393 (4 mg/kg) produced significantly more rotational behavior than did caffeine plus vehicle. With repeated administration, caffeine produced sustained tolerance to its effects on rotational behavior, whereas SKF 38393 did not. In the groups treated with low doses of SKF 38393 (0.5, and 1 mg/kg) plus caffeine, tolerance was observed while in the groups that received high doses of SKF 38393 (2 and 4 mg/kg) plus caffeine, no tolerance was observed to rotational behavior. These results suggest that maximal stimulation of dopamine D(1) receptors may be needed to prevent the tolerance effects of caffeine in this animal model. This finding may have clinical relevance to the therapeutic treatment of Parkinson's disease.

Striatal dopaminergic D(2) receptor density measured by [(123)I]iodobenzamide SPECT in the prediction of treatment outcome of alcohol-dependent patients.

OBJECTIVE: The authors' goal was to study striatal dopaminergic dopamine 2 (D(2)) receptors as a biological marker of early relapse in detoxified alcoholic patients by using [(123)I]iodobenzamide ([123I]IBZM) single photon emission computed tomography (SPECT). METHOD: The authors performed [(123)I]IBZM SPECT on 21 alcohol-dependent inpatients during detoxification and on nine healthy volunteers, using the ratios of basal ganglia to occipital lobes for SPECT quantification. Depending on treatment outcome 3 months after hospital discharge, patients were determined to be relapsers or nonrelapsers. RESULTS: Alcohol-dependent subjects with early relapse (within 3 months after hospital discharge) showed a higher uptake of [(123)I]IBZM in the basal ganglia during detoxification (mean ratio=1.83, SD=0.9) than patients who did not have early relapse (mean ratio=1.69, SD=0.11). CONCLUSIONS: These results suggest that low levels of dopamine, or an increased density of free striatal dopaminergic D(2) receptors, could be related to early relapse in alcohol-dependent patients. Therefore, [(123)I]IBZM SPECT could become a biological marker of vulnerability to relapse for alcoholic patients in recovery.

The novel type B MAO inhibitor PF9601N enhances the duration of L-DOPA-induced contralateral turning in 6-hydroxydopamine lesioned rats.

The present study examined the effect of the highly potent and selective MAO B inhibitor PF9601N on L-DOPA-induced rotational behavior in unilateral nigrostriatal 6-hydroxydopamine lesioned rats. Three doses of PF9601N (20, 40 and 60mg/kg) were administered 30 min before an injection of L-DOPA (25mg/kg), and both contralateral and ipsilateral rotational behavior was measured. In addition, we also studied the effect produced by another MAO B inhibitor, deprenyl (20mg/kg), the MAO A inhibitor, clorgyline (20mg/kg), and the dopamine reuptake inhibitor, GBR2909 (7.5 mg/kg) on L-DOPA-induced rotational behavior. The results showed that PF9601N plus L-DOPA significantly enhanced the duration of contralateral rotational behavior with respect to L-DOPA plus vehicle in a dose-related manner. At the dose of 40 and 60mg/kg, PF9601N produced significantly more overall contralateral turning than L-DOPA plus vehicle, and at the dose of 60mg/kg, PF9601N produced significantly more turning behavior than L-DOPA plus deprenyl. These results suggest that PF9601N may be used as a novel tool in the treatment of Parkinson's disease.

Scopolamine prevents tolerance to the effects of caffeine on rotational behavior in 6-hydroxydopamine-denervated rats.

Continuous administration of caffeine has been shown to induce tolerance to its psychostimulant effects. In this study, using unilateral 6-hydroxydopamine nigrostriatal denervated rats, we tested the hypothesis that the muscarinic receptor antagonist, scopolamine, would prevent the tolerance to caffeine-induced contralateral rotational behavior. For that purpose we administered either caffeine (40 mg/kg) plus saline or scopolamine (5, 10 and 20 mg/kg) plus saline, as well as caffeine in combination with the various doses of scopolamine for 7 consecutive days, and measured ipsilateral and contralateral rotational behavior. The results showed that acute injections of scopolamine plus saline produced similar levels of both ipsilateral and contralateral turning, while caffeine produced more contralateral than ipsilateral turning. Tolerance to caffeine-induced contralateral turning was observed as of the second administration, while scopolamine plus saline injections did not produce significant changes in rotational behavior with repeated treatment. Scopolamine co-administered with caffeine significantly attenuated the increased contralateral turning produced by acute injections of caffeine plus saline, but significantly prevented the tolerance effects with repeated administration. These findings strongly suggest that muscarinic cholinergic processes may be involved in tolerance to caffeine-induced contralateral turning. The results are interpreted in terms of the possible interactions between dopamine, adenosine and acetylcholine neurotransmitter systems within the basal ganglia circuitry involved in motor behavior.