Réflexion sur l’apport de l’ouvrage "Comment on écrit l’histoire" sur la formation à la recherche en droit

Les chercheurs spécialisés en droit ont souvent pris pour modèle la méthodologie de la recherche inspirée des différentes sciences humaines. Or, les réflexions élaborées par certains historiens sur leur propre méthodologie, plus particulièrement celles qui ont été livrées par Paul Veyne dans son ouvrage "Comment on écrit l’histoire", sont aussi très éclairantes pour toute personne qui s’interroge sur la méthodologie de la recherche en droit. Selon cet auteur, et paradoxalement, "l’histoire n’a pas de méthode" et les historiens "racontent des événements vrais qui ont l’homme pour acteur". Transposées au domaine du droit, ces affirmations libéreraient en quelque sorte le chercheur d’une quête d’une méthodologie "scientifique" tout en le soumettant à une exigence, celle de décrire des événements vrais. La transposition est-elle possible? L’épistémologie historique est-elle pertinente pour les juristes? Voilà les questions que l’auteur abordera dans l’article qui suit.

Conception d'une situation d'apprentissage qui permettra le passage de l'oral signé à l'écrit chez des apprenants sourds de niveau présecondaire, selon la syntaxe du français de la majorité

De nos jours, la communication écrite joue un rôle primordial pour tout individu qui désire se faire une place dans la société tant sur le plan personnel que socioprofessionnel. Chez les apprenants sourds, le passage à l’écrit du français de la majorité représente un grand défi et leurs phrases contiennent souvent des erreurs de syntaxe. Par exemple, les apprenants sourds auraient tendance à reproduire à l’écrit la syntaxe de la LSQ croyant que les règles de la grammaire de la phrase sont identiques. Dans cet essai, nous nous interrogeons sur les stratégies à adopter pour amener des adultes sourds gestuels à effectuer un transfert efficace de l’oral signé vers le français écrit. Pour ce faire, une situation d’apprentissage (S.A) destinée aux apprenants sourds de niveau présecondaire a été élaborée. Basée sur l’enseignement stratégique et la grammaire de la phrase de base, cette S.A exploite d’abord les bases du fonctionnement de la langue des signes québécoise (LSQ) pour ensuite introduire les notions de la phrase de base et de ses constituants selon la grammaire rénovée. Cette S.A a ensuite été soumise pour validation et rétroaction à la conseillère pédagogique du Centre d’éducation aux adultes où nous travaillons. Ses commentaires, conjugués aux observations notées lors de la mise à l’essai auprès de trois apprenants, ont permis de prendre conscience des forces de cette S.A et d’apporter des ajustements visant à optimiser l’efficacité des différentes activités d’apprentissage.

Étude du développement des habiletés en compréhension de discours informatifs oral et écrit d’élèves de 3ième et de 6ième année du primaire

Un vaste champ de disciplines tente présentement d'expliquer comment l'être humain acquiert la connaissance. De quelle façon, en effet, s'organise l'acte de compréhension lors du processus d'apprentissage? De façon plus spécifique, le domaine d'investigation de certains chercheurs se situe au niveau de l'étude des processus de compréhension impliqués durant la lecture ou l'audition d'un discours. La psychologie est l'une des disciplines qui tentent d'explorer le domaine de la compréhension du discours selon divers paradigmes. Parmi ceux-ci, la psychologie cognitive offre une approche qui met l'emphase à la fois sur le discours, l'individu et l'aspect contextuel. La psychologie cognitive se donne comme objectif de déterminer le niveau d'influence de chacune de ces facettes sur les processus cognitifs impliqués dans la compréhension. Elle élargit ainsi le champ habituel d'investigation afin de mieux expliquer comment s'actualisent les processus qui permettent à un individu de comprendre. À l'intérieur de ce paradigme explicatif, l'approche constructiviste raffine encore un peu plus la vision de l'acte de compréhension en plaçant le lecteur ou l'interlocuteur du discours dans une position active par rapport au discours. Durant l'acte de compréhension, le lecteur/interlocuteur "reconstruit" les idées ou éléments du discours afin de leur donner un sens. Ceci implique donc que chaque individu pourrait comprendre un même discours de façon différente, car le traitement de l'information ainsi réalisé est différent pour chacun. Dans la pratique, tous ces construits théoriques peuvent influer grandement sur la façon dont les intervenants du milieu considèrent l'enseignement de la lecture, ou encore le développement des habiletés en compréhension. Il est en effet primordial que les recherches, actuellement en cours dans le domaine de l'éducation, puissent éclairer un enseignement de la lecture qui se résume trop souvent au développement de connaissances grapho-phonétiques et grammaticales. La compréhension des processus qui régissent le traitement de l'information effectué lors de l'acte de lecture ou d'audition d'un discours ne peut que faciliter et rendre plus adéquate la démarche de l'enseignant. Les recherches en général portant sur la compréhension du discours, nous ont cependant habitué à considérer la compréhension comme étant une entité plus ou moins bien définie qui évolue au cours de l'enfance et de l'adolescence, et qui semblerait se stabiliser à l'âge adulte. On comprend "mieux" un discours à 12 ans qu'à 9 ans. C'est là une affirmation que l'on peut facilement vérifier empiriquement, et dont les écrits scientifiques sinon la totalité, du moins la majorité, viennent en confirmer la véracité. Malgré cela, nous en savons encore très peu sur les processus cognitifs qui chapeautent la compréhension ainsi que son développement. Est-ce que les processus de compréhension utilisés par un enfant de 9 ans sont les mêmes que ceux utilisés par un enfant de 12 ans? La littérature n'est pas bavarde à ce sujet, bien que récemment des efforts aient été faits en psychologie cognitive pour élucider cette question, plus particulièrement par l'approche constructiviste. L'aspect développemental des processus de compréhension est l'un des deux volets de cette recherche. Le second veut scruter les processus de compréhension selon deux modes de présentation; le mode oral et le mode écrit. […]

Conscience de l'écrit avant l'apprentissage formel : situation conceptuelle et recommandations pédagogiques en première année

Deux objectifs seront poursuivis par la présente recherche. Le premier sera de déterminer le niveau de conceptualisation du langage écrit des enfants de la maternelle. Sur la base de ces évaluations nous poursuivrons le second objectif, soit de déterminer si une intervention particulière peut influencer le développement des habiletés cognitives et métacognitives nécessaires à la compréhension de notre système d'écriture. Les résultats nous permettront de formuler des recommandations quant à l'attitude pédagogique à privilégier avant d'entreprendre l'enseignement formel pour faciliter d'emblée l'entrée dans l'écrit. Par le biais de cette recherche, nous tenterons de répondre à plusieurs interrogations. Lorsque l'enfant entre en première armée, quelles connaissances a-t-il du langage écrit et du fonctionnement de notre système d'écriture? Que peut faire l'enseignante ou l'enseignant de 1re année pour améliorer l'accès au code écrit de notre langue? Comment doit-elle, comment doit-il ajuster ses interventions sans nuire au travail intellectuel déjà entrepris par l'enfant? L'approche théorique d'Emilia Ferreiro ainsi que les travaux de Downing et Fijalkow serviront de fondement à notre étude. Grâce à l'épreuve d'écriture inventée qui a donné lieu à la psychogenèse de l'écriture élaborée par Ferreiro, nous pourrons analyser les productions écrites des enfants. Les protocoles ne seront pas mesurés en regard de la réussite ou de l'échec, mais selon le niveau atteint: «les réponses étant seulement la manifestation externe de mécanismes internes d'organisation» (Ferreiro, 1987, p. 16). L'épreuve du langage technique de la lecture-écriture issue de la théorie de la clarté cognitive élaborée par Downing et Fijalkow viendra compléter nos informations en permettant de situer le degré de clarté cognitive des enfants.

Écrire dans la classe de français à la FGA : processus créateur, motivation et culture de l'écrit

Dans notre recherche-intervention, nous nous sommes questionnée sur les façons d’instaurer motivation et culture de l’écrit dans la classe de français, chez les élèves du présecondaire à la cinquième secondaire, inscrits à la Formation Générale aux Adultes (FGA) au Centre Marchand de la Commission scolaire de la Rivière-du-Nord, à travers un processus créateur authentique et signifiant qui modifie les rapports parfois difficiles entre les élèves et l’écrit. Tout en tenant compte des caractéristiques des élèves concernés, nous avons abordé, entre autres, la créativité, le rapport entre soi, l’autre et le monde grâce à l’écriture libre, les interactions entre la lecture, l’écriture et l’oral, la motivation, le savoir-écrire en tant que compétence, le plaisir du texte et la démocratisation de l’écrit. Proposant une vision renouvelée de l’écriture, nous avons inclus dans nos classes des activités qui rompaient avec l’enseignement traditionnel du français (les ateliers d’écriture) et des outils qui favorisaient la continuité des tâches et l’autoévaluation (le portfolio de présentation, le recueil et la bande-annonce). Ces tâches nous ont permis d’instaurer une culture de l’écrit et d’agir sur la motivation des élèves. Nous en sommes arrivée à produire une analyse critique des modes d’intervention à privilégier pour que le processus créateur occupe la place qui lui revient dans la classe de français et pour que l’engagement des élèves, dans l’acte d’écrire, devienne plus signifiant et plus authentique, donc, conséquemment, plus motivant. Bref, conformément à l’esprit du renouveau pédagogique qui a fait son entrée au secondaire en 2005, nous souhaitons que notre recherche aide les enseignants de français à réévaluer l’importance du processus créateur, lequel fait partie intégrante de l’acte d’écrire, acte qui, lui-même, s’inscrit dans une continuité et une évolution encore peu mesurées.

Association Between Unilateral Tonsillar Enlargement And Lymphoma In Children: A Systematic Review And Meta-analysis.

Lymphoma is the most common head and neck malignancy in children, and palatine tonsils asymmetry is the most frequent clinical manifestation of tonsillar lymphoma. However, several studies with children with tonsillar asymmetry found no case of lymphoma, showing that the relationship of tonsillar asymmetry with lymphoma is unclear. In this review, we aimed to identify the association between tonsillar asymmetry and tonsillar lymphoma in children by conducting systematic reviews of the literature on children with palatine tonsil lymphoma and tonsillar asymmetry. Articles comprising the paediatric age group (up to 18 years) with information concerning clinical manifestations of tonsillar lymphoma or the diagnosis of the tonsillar asymmetry were included. The main cause of asymmetry of palatine tonsils was lymphoid hyperplasia, followed by lymphoma and nonspecific benign changes. The asymmetry of tonsils was present in 73.2% of cases of lymphoma. There was an association between asymmetric palatine tonsils and lymphoma, with a likelihood ratio of 43.5 for children with asymmetry of palatine tonsils and 8938.4 for children with asymmetry of tonsils and other signs of suspicion for malignancy. We also provide recommendations on the management of suspicious cases of palatine tonsil lymphoma.

Fibrodysplasia ossificans progressiva: case report

Fibrodysplasia ossificans progressiva is a rare genetic disease characterized by widespread soft tissue ossification and congenital stigmata of the extremities. We report on a male child followed for ten years since the age of 3 years and 9 months, when the diagnosis was made. He was born with bilateral hypoplasic hallux valgus and ventricular septal defect, corrected by transsternal approach when 32 months old. Restriction of neck mobility followed and foci of ectopic ossification appeared. Four crises of disease exacerbation were treated with oral prednisone and/or other antiinflammatory drugs. Sodium etidronate 5 to 10 mg/kg/day was prescribed intermittently during about six years but was discontinued due to osteopenia. The disease course has been relentless, with severe movement restriction including the chest wall. A review showed few similar case reports in the Brazilian literature. We revisit the criteria for diagnosis and the essentials of management and treatment.

BONA FIDE, STRONG-VARIABLE GALACTIC LUMINOUS BLUE VARIABLE STARS ARE FAST ROTATORS: DETECTION OF A HIGH ROTATIONAL VELOCITY IN HR CARINAE

We report optical observations of the luminous blue variable (LBV) HR Carinae which show that the star has reached a visual minimum phase in 2009. More importantly, we detected absorptions due to Si lambda lambda 4088-4116. To match their observed line profiles from 2009 May, a high rotational velocity of nu(rot) similar or equal to 150 +/- 20 km s(-1) is needed (assuming an inclination angle of 30 degrees), implying that HR Car rotates at similar or equal to 0.88 +/- 0.2 of its critical velocity for breakup (nu(crit)). Our results suggest that fast rotation is typical in all strong-variable, bona fide galactic LBVs, which present S-Dor-type variability. Strong-variable LBVs are located in a well-defined region of the HR diagram during visual minimum (the ""LBV minimum instability strip""). We suggest this region corresponds to where nu(crit) is reached. To the left of this strip, a forbidden zone with nu(rot)/nu(crit) > 1 is present, explaining why no LBVs are detected in this zone. Since dormant/ex LBVs like P Cygni and HD 168625 have low nu(rot), we propose that LBVs can be separated into two groups: fast-rotating, strong-variable stars showing S-Dor cycles (such as AG Car and HR Car) and slow-rotating stars with much less variability (such as P Cygni and HD 168625). We speculate that supernova (SN) progenitors which had S-Dor cycles before exploding (such as in SN 2001ig, SN 2003bg, and SN 2005gj) could have been fast rotators. We suggest that the potential difficulty of fast-rotating Galactic LBVs to lose angular momentum is additional evidence that such stars could explode during the LBV phase.

Discontinuation of continuous renal replacement therapy: A post hoc analysis of a prospective multicenter observational study

Objectives: To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes. However, there is lack of information on how and under what conditions continuous renal replacement therapy is discontinued. Design: Post hoc analysis of a prospective observational study. Setting. Fifty-four intensive care units in 23 countries. Patients: Five hundred twenty-nine patients (52.6%) who survived initial therapy among 1006 patients treated with continuous renal replacement therapy. Interventions: None. Measurements and Main Results., Three hundred thirteen patients were removed successfully from continuous renal replacement therapy and did not require any renal replacement therapy for at least 7 days and were classified as the ""success"" group and the rest (216 patients) were classified as the ""repeat-RRT"" (renal replacement therapy) group. Patients in the ""success"" group had lower hospital mortality (28.5% vs. 42.7%, p < .0001) compared with patients in the ""repeat-RRT"" group. They also had lower creatinine and urea concentrations and a higher urine output at the time of stopping continuous renal replacement therapy. Multivariate logistic regression analysis for successful discontinuation of continuous renal replacement therapy identified urine output (during the 24 hrs before stopping continuous renal replacement therapy: odds ratio, 1.078 per 100 mL/day increase) and creatinine (odds ratio, 0.996 per mu mol/L increase) as significant predictors of successful cessation. The area under the receiver operating characteristic curve to predict successful discontinuation of continuous renal replacement therapy was 0.808 for urine output and 0.635 for creatinine. The predictive ability of urine output was negatively affected by the use of diuretics (area under the receiver operating characteristic curve, 0.671 with diuretics and 0.845 without diuretics). Conclusions. We report on the current practice of discontinuing continuous renal replacement therapy in a multinational setting. Urine output at the time of initial cessation (if continuous renal replacement therapy was the most important predictor of successful discontinuation, especially if occurring without the administration of diuretics. (Crit Care Med 2009; 37:2576-2582)

Pulmonary lesion induced by low and high positive end-expiratory pressure levels during protective ventilation in experimental acute lung injury

Objective: To investigate the effects of low and high levels of positive end-expiratory pressure (PEEP), without recruitment maneuvers, during lung protective ventilation in an experimental model of acute lung injury (ALI). Design: Prospective, randomized, and controlled experimental study. Setting: University research laboratory. Subjects: Wistar rats were randomly assigned to control (C) [saline (0.1 ml), intraperitoneally] and ALI [paraquat (15 mg/kg), intra peritoneally] groups. Measurements and Main Results: After 24 hours, each group was further randomized into four groups (six rats each) at different PEEP levels = 1.5, 3, 4.5, or 6 cm H(2)O and ventilated with a constant tidal volume (6 mL/kg) and open thorax. Lung mechanics [static elastance (Est, L) and viscoelastic pressure (Delta P2, L)] and arterial blood gases were measured before (Pre) and at the end of 1-hour mechanical ventilation (Post). Pulmonary histology (light and electron microscopy) and type III procollagen (PCIII) messenger RNA (mRNA) expression were measured after 1 hour of mechanical ventilation. In ALI group, low and high PEEP levels induced a greater percentage of increase in Est, L (44% and 50%) and Delta P2, L (56% and 36%) in Post values related to Pre. Low PEEP yielded alveolar collapse whereas high PEEP caused overdistension and atelectasis, with both levels worsening oxygenation and increasing PCIII mRNA expression. Conclusions: In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and Delta P2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful. (Crit Care Med 2009; 37:1011-1017)

Impact of pressure profile and duration of recruitment maneuvers on morphofunctional and biochemical variables in experimental lung injury

Objective: To investigate the effects of the rate of airway pressure increase and duration of recruitment maneuvers on lung function and activation of inflammation, fibrogenesis, and apoptosis in experimental acute lung injury. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: Thirty-five Wistar rats submitted to acute lung injury induced by cecal ligation and puncture. Interventions: After 48 hrs, animals were randomly distributed into five groups (seven animals each): 1) nonrecruited (NR); 2) recruitment maneuvers (RMs) with continuous positive airway pressure (CPAP) for 15 secs (CPAP15); 3) RMs with CPAP for 30 secs (CPAP30); 4) RMs with stepwise increase in airway pressure (STEP) to targeted maximum within 15 secs (STEP15); and 5) RMs with STEP within 30 secs (STEP30). To perform STEP RMs, the ventilator was switched to a CPAP mode and positive end-expiratory pressure level was increased stepwise. At each step, airway pressure was held constant. RMs were targeted to 30 cm H(2)O. Animals were then ventilated for 1 hr with tidal volume of 6 mL/kg and positive end-expiratory pressure of 5 cm H(2)O. Measurements and Main Results: Blood gases, lung mechanics, histology (light and electronic microscopy), interleukin-6, caspase 3, and type 3 procollagen mRNA expressions in lung tissue. All RMs improved oxygenation and lung static elastance and reduced alveolar collapse compared to NR. STEP30 resulted in optimal performance, with: 1) improved lung static elastance vs. NR, CPAP15, and STEP15; 2) reduced alveolar-capillary membrane detachment and type 2 epithelial and endothelial cell injury scores vs. CPAP15 (p < .05); and 3) reduced gene expression of interleukin-6, type 3 procollagen, and caspase 3 in lung tissue vs. other RMs. Conclusions: Longer-duration RMs with slower airway pressure increase efficiently improved lung function, while minimizing the biological impact on lungs. (Crit Care Med 2011; 39:1074-1081)

Recruitment maneuver in experimental acute lung injury: The role of alveolar collapse and edema

Objective: In acute lung injury, recruitment maneuvers have been used to open collapsed lungs and set positive end-expiratory pressure, but their effectiveness may depend on the degree of lung injury. This study uses a single experimental model with different degrees of lung injury and tests the hypothesis that recruitment maneuvers may have beneficial or deleterious effects depending on the severity of acute lung injury. We speculated that recruitment maneuvers may worsen lung mechanical stress in the presence of alveolar edema. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: Thirty-six Wistar rats randomly divided into three groups (n = 12 per group). Interventions: In the control group, saline was intraperitoneally injected, whereas moderate and severe acute lung injury animals received paraquat intraperitoneally (20 mg/kg [moderate acute lung injury] and 25 mg/kg [severe acute lung injury]). After 24 hrs, animals were further randomized into subgroups (n = 6/each) to be recruited (recruitment maneuvers: 40 cm H(2)O continuous positive airway pressure for 40 secs) or not, followed by 1 hr of protective mechanical ventilation (tidal volume, 6 mL/kg; positive end-expiratory pressure, 5 cm H(2)O). Measurements and Main Results: Only severe acute lung injury caused alveolar edema. The amounts of alveolar collapse were similar in the acute lung injury groups. Static lung elastance, viscoelastic pressure, hyperinflation, lung, liver, and kidney cell apoptosis, and type 3 procollagen and interleukin-6 mRNA expressions in lung tissue were more elevated in severe acute lung injury than in moderate acute lung injury. After recruitment maneuvers, static lung elastance, viscoelastic pressure, and alveolar collapse were lower in moderate acute lung injury than in severe acute lung injury. Recruitment maneuvers reduced interleukin-6 expression with a minor detachment of the alveolar capillary membrane in moderate acute lung injury. In severe acute lung injury, recruitment maneuvers were associated with hyperinflation, increased apoptosis of lung and kidney, expression of type 3 procollagen, and worsened alveolar capillary injury. Conclusions: In the presence of alveolar edema, regional mechanical heterogeneities, and hyperinflation, recruitment maneuvers promoted a modest but consistent increase in inflammatory and fibrogenic response, which may have worsened lung function and potentiated alveolar and renal epithelial injury. (Crit Care Med 2010; 38: 2207-2214)

Benefit of antiretroviral therapy on survival of human immunodeficiency virus-infected patients admitted to an intensive care unit

Objective: To evaluate the impact of antiretroviral therapy (ART) and the prognostic factors for in-intensive care unit (ICU) and 6-month mortality in human immunodeficiency virus (HIV)-infected patients. Design: A retrospective cohort study was conducted in patients admitted to the ICU from 1996 through 2006. The follow-up period extended for 6 months after ICU admission. Setting: The ICU of a tertiary-care teaching hospital at the Universidade de Sao Paulo, Brazil. Participants: A total of 278 HIV-infected patients admitted to the ICU were selected. We excluded ICU readmissions (37), ICU admissions who stayed less than 24 hours (44), and patients with unavailable medical charts (36). Outcome Measure: In-ICU and 6-month mortality. Main Results: Multivariate logistic regression analysis and Cox proportional hazards models demonstrated that the variables associated with in-ICU and 6-month mortality were sepsis as the cause of admission (odds ratio [OR] = 3.16 [95% confidence interval [CI] 1.65-6.06]); hazards ratio [HR] = 1.37 [95% Cl 1.01-1.88)), an Acute Physiology and Chronic Health Evaluation 11 score >19 [OR = 2.81 (95% CI 1.57-5.04); HR = 2.18 (95% CI 1.62-2.94)], mechanical ventilation during the first 24 hours [OR = 3.92 (95% CI 2.20-6.96); HR = 2.25 (95% CI 1.65-3.07)], and year of ICU admission [OR = 0.90 (95% CI 0.81-0.99); HR = 0.92 [95% CI 0.87-0.97)]. CD4 T-cell count <50 cells/mm(3) Was only associated with ICU mortality [OR = 2.10 (95% Cl 1.17-3.76)]. The use of ART in the ICU was negatively predictive of 6-month mortality in the Cox model [HR = 0.50 (95% CI 0.35-0.71)], especially if this therapy was introduced during the first 4 days of admission to the ICU [HR = 0.58 (95% CI 0.41-0.83)]. Regarding HIV-infected patients admitted to ICU without using ART, those who have started this treatment during ICU, stay presented a better prognosis when time and potential confounding factors were adjusted for [HR 0.55 (95% CI 0.31-0.98)]. Conclusions: The ICU outcome of HIV-infected patients seems to be dependent not only on acute illness severity, but also on the administration of antiretroviral treatment. (Crit Care Med 2009; 37: 1605-1611)

Role of regulatory T cells in long-term immune dysfunction associated with severe sepsis

Objective: To investigate the role of regulatory T cells in the modulation of long-term immune dysfunction during experimental sepsis. It is well established that sepsis predisposes to development of a pronounced immunosuppression. Nevertheless, the mechanisms underlying the immune dysfunction after sepsis are still not well understood. Design: Prospective experimental study. Setting: University research laboratory. Interventions: Wild-type mice underwent cecal ligation and puncture and were treated with antibiotic during 3 days after surgery. On days 1, 7, or 15 after cecal ligation and puncture, the frequency of regulatory T cells, proliferation of CD4(+) T cells and bacterial counts were evaluated. Fifteen days after cecal ligation and puncture, surviving mice underwent secondary pulmonary infection by intranasal inoculation of nonlethal dose of Legionella pneumophila. Some mice received agonistic glucocorticoid-induced tumor necrosis factor receptor antibody (DTA-1) before induction of secondary infection. Measurements and Main Results: Mice surviving cecal ligation and puncture showed a markedly increased frequency of regulatory T cells in thymus and spleen, which was associated with reduced proliferation of CD4(+) T cells. Fifteen days after cecal ligation and puncture, all sepsis-surviving mice succumbed to nonlethal injection of L. pneumophila. Treatment of mice with DTA-1 antibody reduced frequency of regulatory T cells, restored CD4(+) T cell proliferation, reduced the levels of bacteria in spleen, and markedly improved survival of L. pneumophila infection. Conclusion: These findings suggest that regulatory T cells play an important role in the progression and establishment of immune dysfunction observed in experimental sepsis. (Crit Care Med 2010; 38: 1718-1725)

Metalloproteinase inhibition protects against cardiomyocyte injury during experimental acute pulmonary thromboembolism

Objectives: Up-regulated matrix metalloproteinases may be involved in the development of cardiomyocyte injury and the degradation of troponin associated with acute pulmonary thromboembolism. We examined whether pretreatment with doxycycline (a nonspecific matrix metalloproteinase inhibitor) protects against cardiomyocyte injury associated with acute pulmonary thromboembolism. Design: Controlled animal study. Setting: University research laboratory. Subjects: Mongrel dogs. Interventions: Anesthetized animals received doxycycline (10 mg/kg intravenously) or saline and acute pulmonary thromboembolism was induced with autologous blood clots injected into the right atrium. Control animals received doxycycline (or saline). Measurements and Main Results: Hemodynamic measurements were performed, and acute pulmonary thromboembolism increased baseline mean pulmonary arterial pressure and pulmonary vascular resistance by approximately 160% and 362%, respectively (both p<.05), 120 mins after acute pulmonary thromboembolism. Pretreatment with doxycycline attenuated these increases (to 125% and 232%, respectively; both p<.05). Although acute pulmonary thromboembolism tended to increase the right ventricle maximum rate of isovolumic pressure development and the maximum rate of isovolumic pressure decay, doxycycline produced no effects on these parameters. Gelatin zymograms of right ventricle showed that acute pulmonary thromboembolism marginally increased matrix metalloproteinase-9 (but not matrix metalloproteinase-2) levels in the right ventricle. A fluorometric assay to assess net matrix metalloproteinase activities showed that acute pulmonary thromboembolism increased matrix metalloproteinase activities in the right ventricle by >100% (p<.05), and this finding was confirmed by in situ zymography of the right ventricle. Doxycycline attenuated acute pulmonary thromboembolism-induced increases in right ventricle matrix metalloproteinase activities. Acute pulmonary thromboembolism induced neutrophil accumulation in the right ventricle, as estimated by myeloperoxidase activity, and doxycycline blunted this effect (p<.05). Serum cardiac troponin I concentrations, which reflect cardiomyocyte injury, increased after acute pulmonary thromboembolism, and this increase was attenuated by pretreatment with doxycycline (p<.05). Conclusions: We found evidence supporting the idea that acute pulmonary thromboembolism is associated with increased matrix metalloproteinase activities in the right ventricle, which may lead to degradation of sarcomeric proteins, including cardiac troponin I. Inhibition of matrix metalloproteinases may be an effective therapeutic intervention in the management of acute pulmonary thromboembolism. (Crit Care Med 2011; 39: 349-356)