Publications (44)202.91 Total impact
-
Article: Bioenergetics, Mitochondrial Dysfunction and Oxidative Stress in the Pathophysiology of Septic Encephalopathy.
[show abstract] [hide abstract]
ABSTRACT: Sepsis is a major cause of mortality and morbidity in intensive care units (ICU). Acute and longterm brain dysfunctions have been demonstrated both in experimental models and septic patients. Sepsis-associated encephalopathy (SAE) is an early and frequent manifestation, but is under diagnosed, due to the absence of specific biomarkers and to confounding factors such as sedatives used in the ICU. SAE may have acute and long-term consequences including development of autonomic dysfunction, delirium and cognitive impairment. The mechanisms of SAE involve mitochondrial and vascular dysfunctions, oxidative stress, neurotransmission disturbances, inflammation and cell death. Here we review specific evidence that links bioenergetics, mitochondrial dysfunction and oxidative stress in the setting of brain dysfunctions associated to sepsis.Shock (Augusta, Ga.) 03/2013; · 2.87 Impact Factor -
Article: Bacterial Clearance in Septic Mice Is Modulated by MCP-1/CCL2 and Nitric Oxide.
[show abstract] [hide abstract]
ABSTRACT: Bacterial clearance is one of the most important beneficial consequences of the innate immune response. Chemokines are important mediators controlling leukocyte trafficking and activation, whereas reactive oxygen and nitrogen species are effectors in bacterial killing. In the present work, we used in vivo and in vitro models of infections to study the role of monocyte chemoattractant protein 1 (MCP-1)/CCL2 and nitric oxide (NO) in the bacterial clearance in sepsis. Our results show that MCP-1/CCL2 and NO levels are increased in the peritoneal cavity of mice 6 h after sepsis induced by cecal ligation and puncture. Pretreatment with anti-MCP-1/CCL2 monoclonal antibodies increased the number of colony-forming units (CFUs) recovered in the peritoneal lavage fluid. Moreover, CFU counts were increased in the peritoneal fluid of CCR2 mice subjected to cecal ligation and puncture. In vitro stimulation of peritoneal macrophages with recombinant MCP-1/CCL2 reduced CFU counts in the supernatant after challenge with Escherichia coli. Conversely, treatment with anti-MCP-1/CCL2 increased CFU counts under the same experimental condition. Stimulation of cultured macrophages with MCP-1/CCL2 and interferon had a synergistic effect on NO production. Macrophages from CCL2 mice showed a consistent decrease in NO production when compared with wild-type controls after stimulation with LPS + interferon. Finally, we showed incubation of macrophages with E. coli, and the ERK inhibitor U0126 increased CFU numbers and decreased intracellular levels of NO. In conclusion, we demonstrated for the first time that MCP-1/CCL2 has a crucial role in the clearance of bacteria by mechanisms involving increased expression of inducible NO synthase and production of NO by ERK signaling pathways.Shock (Augusta, Ga.) 01/2013; 39(1):63-9. · 2.87 Impact Factor -
Article: Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria.
[show abstract] [hide abstract]
ABSTRACT: Cerebral malaria (CM) is the most severe manifestation of Plasmodium falciparum infection in children and non-immune adults. Previous work has documented a persistent cognitive impairment in children who survive an episode of CM that is mimicked in animal models of the disease. Potential therapeutic interventions for this complication have not been investigated, and are urgently needed. HMG-CoA reductase inhibitors (statins) are widely prescribed for cardiovascular diseases. In addition to their effects on the inhibition of cholesterol synthesis, statins have pleiotropic immunomodulatory activities. Here we tested if statins would prevent cognitive impairment in a murine model of cerebral malaria. Six days after infection with Plasmodium berghei ANKA (PbA) mice displayed clear signs of CM and were treated with chloroquine, or chloroquine and lovastatin. Intravital examination of pial vessels of infected animals demonstrated a decrease in functional capillary density and an increase in rolling and adhesion of leukocytes to inflamed endothelium that were reversed by treatment with lovastatin. In addition, oedema, ICAM-1, and CD11b mRNA levels were reduced in lovastatin-treated PbA-infected mice brains. Moreover, HMOX-1 mRNA levels are enhanced in lovastatin-treated healthy and infected brains. Oxidative stress and key inflammatory chemokines and cytokines were reduced to non-infected control levels in animals treated with lovastatin. Fifteen days post-infection cognitive dysfunction was detected by a battery of cognition tests in animals rescued from CM by chloroquine treatment. In contrast, it was absent in animals treated with lovastatin and chloroquine. The outcome was similar in experimental bacterial sepsis, suggesting that statins have neuroprotective effects in severe infectious syndromes in addition to CM. Statin treatment prevents neuroinflammation and blood brain barrier dysfunction in experimental CM and related conditions that are associated with cognitive sequelae, and may be a valuable adjuvant therapeutic agent for prevention of cognitive impairment in patients surviving an episode of CM.PLoS Pathogens 12/2012; 8(12):e1003099. · 9.13 Impact Factor -
Article: The many facets of procalcitonin in the critically ill population*.
Critical care medicine 10/2012; 40(10):2903-5. · 6.37 Impact Factor -
Article: Chest computed tomography findings in severe influenza pneumonia occurring in neutropenic cancer patients.
[show abstract] [hide abstract]
ABSTRACT: To describe the chest computed tomography findings for severe influenza H1N1 infection in a series of hospitalized neutropenic cancer patients. We performed a retrospective systematic analysis of chest computed tomography scans for eight hospitalized patients with fever, neutropenia, and confirmed diagnoses of influenza H1N1. The clinical data had been prospectively collected. Six of eight patients (75%) developed respiratory failure and required intensive care. Prolonged H1N1 shedding was observed in the three mechanically ventilated patients, and overall hospital mortality in our series was 25%. The most frequent computed tomography findings were ground-glass opacity (all patients), consolidation (7/8 cases), and airspace nodules (6/8 cases) that were frequently moderate or severe. Other parenchymal findings were not common. Five patients had features of pneumonia, two had computed tomography findings compatible with bronchitis and/or bronchiolitis, and one had tomographic signs of chronicity. In this series of neutropenic patients with severe influenza H1N1 infection, chest computed tomography demonstrated mainly moderate or severe parenchymatous disease, but bronchiolitis was not a common feature. These findings associated with febrile neutropenia should elicit a diagnosis of severe viral infection.Clinics (São Paulo, Brazil) 01/2012; 67(4):313-8. · 1.59 Impact Factor -
Article: The impact of coagulation parameters on the outcomes of patients with severe community-acquired pneumonia requiring intensive care unit admission.
[show abstract] [hide abstract]
ABSTRACT: Coagulation abnormalities are frequent in patients with severe infections. However, the predictive value of d-dimer and of the presence of associated coagulation derangements in severe community-acquired pneumonia (CAP) remains to be thoroughly evaluated. The aim of this study was to investigate the predictive value of coagulation parameters in patients with severe CAP admitted to the intensive care unit. d-Dimer, antithrombin, International Society of Thrombosis and Hemostasis score, clinical variables, Sequential Organ Failure Assessment (SOFA), The Acute Physiology and Chronic Health Evaluation II (APACHE II) and the CURB-65 score were measured in the first 24 hours. Results are shown as median (25%-75% interquartile range). The main outcome measure was hospital mortality. Ninety patients with severe CAP admitted to the intensive care unit were evaluated. Overall hospital mortality was 15.5%. d-Dimer levels in nonsurvivors were higher than those in survivors. In the univariate analysis, d-dimer, SOFA, and APACHE II scores were predictors of death. The discriminative ability of d-dimer (area under receiver operating curve = 0.75 [95% confidence interval, 0.64-0.83]; best cutoff for d-dimer was 1798 ng/mL) for in-hospital mortality was comparable with APACHE II and SOFA and better than C-reactive protein. Moreover, the addition of d-dimer to APACHE II or SOFA score increased the discriminative ability of both scores (area under the receiver operating curve = 0.82 [0.72-0.89] and 0.84 [0.75-0.91], respectively). d-Dimer levels are good predictors of outcome in severe CAP and may augment the predictive ability of scoring systems as APACHE II and SOFA.Journal of critical care 03/2011; 26(5):496-501. · 2.13 Impact Factor -
Article: Bioenergetic failure of human peripheral blood monocytes in patients with septic shock is mediated by reduced F1Fo adenosine-5'-triphosphate synthase activity.
[show abstract] [hide abstract]
ABSTRACT: Increasing evidence points to the role of mitochondrial dysfunction in the pathogenesis of sepsis. Previous data indicate that mitochondrial function is affected in monocytes from septic patients, but the underlying mechanisms and the impact of these changes on the patients' outcome are unknown. We aimed to determine the mechanisms involved in mitochondrial dysfunction in peripheral blood mononuclear cells from patients with septic shock. A cohort of patients with septic shock to study peripheral blood mononuclear cell mitochondrial respiration by high-resolution respirometry analyses and to compare with cells from control subjects. Three intensive care units and an academic research laboratory. Twenty patients with septic shock and a control group composed of 18 postoperative patients without sepsis or shock. Ex vivo measurements of mitochondrial oxygen consumption were carried out in digitonin-permeabilized peripheral blood mononuclear cells from 20 patients with septic shock taken during the first 48 hrs after intensive care unit admission as well as in peripheral blood mononuclear cells from control subjects. Clinical parameters such as hospital outcome and sepsis severity were also analyzed and the relationship between these parameters and the oxygen consumption pattern was investigated. We observed a significant reduction in the respiration specifically associated with adenosine-5'-triphosphate synthesis (state 3) compared with the control group (5.60 vs. 9.89 nmol O2/min/10(7) cells, respectively, p < .01). Reduction of state 3 respiration in patients with septic shock was seen with increased prevalence of organ failure (r = -0.46, p = .005). Nonsurviving patients with septic shock presented significantly lower adenosine diphosphate-stimulated respiration when compared with the control group (4.56 vs. 10.27 nmol O2/min/10(7) cells, respectively; p = .004). Finally, the presence of the functional F1Fo adenosine-5'-triphosphate synthase complex (0.51 vs. 1.00 ng oligo/mL/10(6) cells, p = .02), but not the adenine nucleotide translocator, was significantly lower in patients with septic shock compared with control cells. Mitochondrial dysfunction is present in immune cells from patients with septic shock and is characterized as a reduced respiration associated to adenosine-5'-triphosphate synthesis. The molecular basis of this phenotype involve a reduction of F1Fo adenosine-5'-triphosphate synthase activity, which may contribute to the energetic failure found in sepsis.Critical care medicine 02/2011; 39(5):1056-63. · 6.37 Impact Factor -
Article: Impact of systemic corticosteroids on the clinical course and outcomes of patients with severe community-acquired pneumonia: a cohort study.
[show abstract] [hide abstract]
ABSTRACT: Our aim was to evaluate the impact of corticosteroids on clinical course and outcomes of patients with severe community-acquired pneumonia (CAP) requiring invasive mechanical ventilation. This was a cohort study of patients with severe CAP from 2 intensive care units in tertiary hospitals in Brazil and Portugal. A total of 111 patients were included (median age, 69 years; 56% men; 34% hospital mortality). Corticosteroids were prescribed in 61 (55%) patients. Main indications for their use were bronchospasm (52.5%) and septic shock (36%). Mortality rate of patients treated with and without corticosteroids was comparable (29.5% vs 32%, P = .837). No significant differences were observed on clinical course from day 1 to day 7 as assessed by the Sequential Organ Failure Assessment score (P = .95). Furthermore, C-reactive protein declined similarly in both groups (P = .147). In a multivariate analysis, mortality was associated with older age and higher Acute Physiology and Chronic Health Evaluation II score. In patients with severe CAP requiring invasive mechanical ventilation, adjunctive therapy with corticosteroids did not influence intensive care unit and hospital mortality. In addition, no changes were observed on weaning from vasopressors, on recovery from organ failure/dysfunction as assessed by the Sequential Organ Failure Assessment score, as well as on C-reactive protein course.Journal of critical care 10/2010; 26(2):193-200. · 2.13 Impact Factor -
Article: Early fluid resuscitation in sepsis: evidence and perspectives.
[show abstract] [hide abstract]
ABSTRACT: Hemodynamic instability plays a major role in the pathogenesis of systemic inflammation, tissue hypoxia, and multiple organ dysfunction in sepsis. Aggressive fluid replacement is one of the key interventions for the hemodynamic support in severe sepsis. In this scenario, the ability to restore the imbalance between tissue oxygen demand and supply, the heterogeneity in microcirculation, and endothelial dysfunction in the early stages of sepsis are associated with reduced mortality. In 2001, a single-center randomized controlled trial showed impressive reductions in hospital mortality when patients presenting to the emergency department with severe sepsis were treated with an aggressive protocol of fluids, blood transfusion, and inotropes aiming to improve tissue perfusion. However, external validation of this trial remains to be carried out. To date, there is no unequivocal evidence that such strategy is both universally feasible and effective. In the present article, we review the current evidence and comment on the future perspectives on early fluid resuscitation in severe sepsis.Shock (Augusta, Ga.) 09/2010; 34 Suppl 1:40-3. · 2.87 Impact Factor -
Article: Cortisol levels and adrenal response in severe community-acquired pneumonia: a systematic review of the literature.
[show abstract] [hide abstract]
ABSTRACT: Our aim was to review the literature on the prevalence and impact of critical-illness related corticosteroid insufficiency (CIRCI) on the outcomes of patients with severe community-acquired pneumonia (CAP). We reviewed Cochrane, Medline, and CINAHL databases (through July 2008) to identify studies evaluating the adrenal function in severe CAP. Main data collected were prevalence of CIRCI and its mortality. We screened 152 articles and identified 7 valid studies. Evaluation of adrenal function varied, and most studies used baseline total cortisol levels. The prevalence of CIRCI in severe CAP ranged from 0% to 48%. Among 533 patients, 56 (10.7%) had cortisol levels of 10 μg/dL or less and 121 patients (21.2%) had cortisol levels of 15 μg/dL or less. In a raw analysis, there was no significant difference in mortality when patients with cortisol levels less than 10 μg/dL (8.6 vs 15.5%; P = .55) or less than 15 μg/dL (12.4 vs 16%; P = .38) were compared with those with cortisol above these levels. In the meta-analysis, relative risk for mortality were 0.81 (confidence interval, 0.39-1.7; P = .59; χ(2) = 1.04) for cortisol levels less than 10 μg/dL and relative risk was 0.67 (confidence interval, 0.4-1.14; P = .84; χ(2) = 1.4) for cortisol levels less than 15 μg/dL. A significant proportion of patients with severe CAP fulfilled criteria for CIRCI. However, CIRCI does not seem to affect the outcomes. Noteworthy, the presence of elevated cortisol levels is associated with increased mortality and may be useful as a prognostic marker in patients with severe CAP.Journal of critical care 09/2010; 25(3):541.e1-8. · 2.13 Impact Factor -
Article: A central role for free heme in the pathogenesis of severe sepsis.
[show abstract] [hide abstract]
ABSTRACT: Low-grade polymicrobial infection induced by cecal ligation and puncture is lethal in heme oxygenase-1-deficient mice (Hmox1(-/-)), but not in wild-type (Hmox1(+/+)) mice. Here we demonstrate that the protective effect of this heme-catabolizing enzyme relies on its ability to prevent tissue damage caused by the circulating free heme released from hemoglobin during infection. Heme administration after low-grade infection in mice promoted tissue damage and severe sepsis. Free heme contributed to the pathogenesis of severe sepsis irrespective of pathogen load, revealing that it compromised host tolerance to infection. Development of lethal forms of severe sepsis after high-grade infection was associated with reduced serum concentrations of the heme sequestering protein hemopexin (HPX), whereas HPX administration after high-grade infection prevented tissue damage and lethality. Finally, the lethal outcome of septic shock in patients was also associated with reduced HPX serum concentrations. We propose that targeting free heme by HPX might be used therapeutically to treat severe sepsis.Science translational medicine 09/2010; 2(51):51ra71. · 7.80 Impact Factor -
Article: An urban perspective on sepsis in developing countries.
The Lancet Infectious Diseases 05/2010; 10(5):290-1. · 17.39 Impact Factor -
Article: Bioimaging of copper alterations in the aging mouse brain by autoradiography, laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry.
[show abstract] [hide abstract]
ABSTRACT: Copper may play an important role in the brain in aging and neurodegenerative diseases. We compare the active Cu uptake, Cu-containing enzyme levels, and total Cu distribution in the brains of young and aging mice. (67)Cu was administered intravenously to 2, 7-9, and 14 month old mice. Active uptake of (67)Cu in the brain was measured at 24 h by digital phosphor autoradiography. Cerebral superoxide dismutase-1 (SOD-1) and cytochrome-C oxidase subunit-1 (CCO-1) levels were analyzed by immunohistochemistry. The total Cu distribution in brain section was determined by imaging laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In aging mice, active (67)Cu uptake and SOD-1 levels were significantly decreased in the brain, whereas blood (67)Cu and CCO-1 levels were similar for all mice, irrespective of age. Paradoxically, global Cu cerebral content was increased in aged mice, suggesting that regulation of active Cu uptake by the brain may be linked to total Cu levels in an attempt to maintain Cu homeostasis. However, focal areas of both decreased Cu uptake and Cu content were noted in the striatum and ventral cortex in aging mice. These focal areas of Cu deficit correspond to the regions of greatest reduction in SOD-1 in the aged mice. In aging, dysregulated Cu homeostasis may result in decreased SOD-1 levels, which may contribute to oxidative vulnerability of the aging brain. This study illustrates the importance of a multi-modality approach in studying the biodistribution and homeostasis of Cu in the brain.Metallomics 05/2010; 2(5):348-53. · 3.90 Impact Factor -
Article: Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza.
[show abstract] [hide abstract]
ABSTRACT: The innate immune system provides a first line of defense against invading pathogens by releasing multiple inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor-alpha, which directly combat the infectious agent and recruit additional immune responses. This exuberant cytokine release paradoxically injures the host by triggering leakage from capillaries, tissue edema, organ failure, and shock. Current medical therapies target individual pathogens with antimicrobial agents or directly either blunt or boost the host's immune system. We explored a third approach: activating with the soluble ligand Slit an endothelium-specific, Robo4-dependent signaling pathway that strengthens the vascular barrier, diminishing deleterious aspects of the host's response to the pathogen-induced cytokine storm. This approach reduced vascular permeability in the lung and other organs and increased survival in animal models of bacterial endotoxin exposure, polymicrobial sepsis, and H5N1 influenza. Thus, enhancing the resilience of the host vascular system to the host's innate immune response may provide a therapeutic strategy for treating multiple infectious agents.Science translational medicine 03/2010; 2(23):23ra19. · 7.80 Impact Factor -
Article: Characteristics and outcomes of patients with cancer requiring admission to intensive care units: A prospective multicenter study
[show abstract] [hide abstract]
ABSTRACT: OBJECTIVE: To evaluate the characteristics and outcomes of patients with cancer admitted to several intensive care units. Knowledge on patients with cancer requiring intensive care is mostly restricted to single-center studies. DESIGN: Prospective, multicenter, cohort study. SETTING: Intensive care units from 28 hospitals in Brazil. PATIENTS: A total of 717 consecutive patients included over a 2-mo period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 667 (93%) patients with solid tumors and 50 (7%) patients had hematologic malignancies. The main reasons for intensive care unit admission were postoperative care (57%), sepsis (15%), and respiratory failure (10%). Overall hospital mortality rate was 30% and was higher in patients admitted because of medical complications (58%) than in emergency (37%) and scheduled (11%) surgical patients (p < .001). Adjusting for covariates other than the type of admission, the number of hospital days before intensive care unit admission (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01-1.37), higher Sequential Organ Failure Assessment scores (OR, 1.25; 95% CI, 1.17-1.34), poor performance status (OR, 3.40; 95% CI, 2.19 -5.26), the need for mechanical ventilation (OR, 2.42; 95% CI, 1.51-3.87), and active underlying malignancy in recurrence or progression (OR, 2.42; 95% CI, 1.51-3.87) were associated with increased hospital mortality in multivariate analysis. CONCLUSIONS: This large multicenter study reports encouraging survival rates for patients with cancer requiring intensive care. In these patients, mortality was mostly dependent on the severity of organ failures, performance status, and need for mechanical ventilation rather than cancer-related characteristics, such as the type of malignancy or the presence of neutropenia.Critical Care Medicine 01/2010; 38(1):9-15. · 6.33 Impact Factor -
Article: Sepsis is a major determinant of outcome in critically ill HIV/AIDS patients.
[show abstract] [hide abstract]
ABSTRACT: New challenges have arisen for the management of critically ill HIV/AIDS patients. Severe sepsis has emerged as a common cause of intensive care unit (ICU) admission for those living with HIV/AIDS. Contrastingly, HIV/AIDS patients have been systematically excluded from sepsis studies, limiting the understanding of the impact of sepsis in this population. We prospectively followed up critically ill HIV/AIDS patients to evaluate the main risk factors for hospital mortality and the impact of severe sepsis on the short- and long-term survival. All consecutive HIV-infected patients admitted to the ICU of an infectious diseases research center, from June 2006 to May 2008, were included. Severity of illness, time since AIDS diagnosis, CD4 cell count, antiretroviral treatment, incidence of severe sepsis, and organ dysfunctions were registered. The 28-day, hospital, and 6-month outcomes were obtained for all patients. Cox proportional hazards regression analysis measured the effect of potential factors on 28-day and 6-month mortality. During the 2-year study period, 88 HIV/AIDS critically ill patients were admitted to the ICU. Seventy percent of patients had opportunist infections, median CD4 count was 75 cells/mm3, and 45% were receiving antiretroviral therapy. Location on a ward before ICU admission, cardiovascular and respiratory dysfunctions on the first day after admission, and the presence of severe sepsis/septic shock were associated with reduced 28-day and 6-month survival on a univariate analysis. After a multivariate analysis, severe sepsis determined the highest hazard ratio (HR) for 28-day (adjusted HR, 3.13; 95% CI, 1.21-8.07) and 6-month (adjusted HR, 3.35; 95% CI, 1.42-7.86) mortality. Severe sepsis occurred in 44 (50%) patients, mainly because of lower respiratory tract infections. The survival of septic and nonseptic patients was significantly different at 28-day and 6-month follow-up times (log-rank and Peto test, P < 0.001). Severe sepsis has emerged as a major cause of admission and mortality for hospitalized HIV/AIDS patients, significantly affecting short- and longer-term survival of critically ill HIV/AIDS patients.Critical care (London, England) 01/2010; 14(4):R152. · 4.61 Impact Factor -
Article: (18)-F-fluorodeoxyglucose positron emission tomography/computed tomography study in acute lung injury/acute respiratory distress syndrome.
Critical care medicine 01/2010; 38(1):347-8; author reply 348. · 6.37 Impact Factor -
Article: H1N1pdm influenza infection in hospitalized cancer patients: clinical evolution and viral analysis.
[show abstract] [hide abstract]
ABSTRACT: The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir. A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3-69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range=11-63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples. Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation.PLoS ONE 01/2010; 5(11):e14158. · 4.09 Impact Factor -
Article: Cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy.
[show abstract] [hide abstract]
ABSTRACT: Neurological impairments are frequently detected in children surviving cerebral malaria (CM), the most severe neurological complication of infection with Plasmodium falciparum. The pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. In the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatment. Infection of C57BL/6 and Swiss (SW) mice with Plasmodium berghei ANKA (PbA) or a lethal strain of Plasmodium yoelii XL (PyXL), respectively, resulted in documented CM and sustained persistent cognitive damage detected by a battery of behavioral tests after cure of the acute parasitic disease with chloroquine therapy. Strikingly, cognitive impairment was still present 30 days after the initial infection. In contrast, BALB/c mice infected with PbA, C57BL6 infected with Plasmodium chabaudi chabaudi and SW infected with non lethal Plasmodium yoelii NXL (PyNXL) did not develop signs of CM, were cured of the acute parasitic infection by chloroquine, and showed no persistent cognitive impairment. Reactive oxygen species have been reported to mediate neurological injury in CM. Increased production of malondialdehyde (MDA) and conjugated dienes was detected in the brains of PbA-infected C57BL/6 mice with CM, indicating high oxidative stress. Treatment of PbA-infected C57BL/6 mice with additive antioxidants together with chloroquine at the first signs of CM prevented the development of persistent cognitive damage. These studies provide new insights into the natural history of cognitive dysfunction after rescue therapy for CM that may have clinical relevance, and may also be relevant to cerebral sequelae of sepsis and other disorders.PLoS Pathogens 01/2010; 6(6):e1000963. · 9.13 Impact Factor -
Article: Characteristics and outcomes of patients with cancer requiring admission to intensive care units: A prospective multicenter study *
[show abstract] [hide abstract]
ABSTRACT: Objective: To evaluate the characteristics and outcomes of patients with cancer admitted to several intensive care units. Knowledge on patients with cancer requiring intensive care is mostly restricted to single-center studies. Design: Prospective, multicenter, cohort study. Setting: Intensive care units from 28 hospitals in Brazil. Patients: A total of 717 consecutive patients included over a 2-mo period. Interventions: None. Measurements and Main Results: There were 667 (93%) patients with solid tumors and 50 (7%) patients had hematologic malignancies. The main reasons for intensive care unit admission were postoperative care (57%), sepsis (15%), and respiratory failure (10%). Overall hospital mortality rate was 30% and was higher in patients admitted because of medical complications (58%) than in emergency (37%) and scheduled (11%) surgical patients (p < .001). Adjusting for covariates other than the type of admission, the number of hospital days before intensive care unit admission (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01–1.37), higher Sequential Organ Failure Assessment scores (OR, 1.25; 95% CI, 1.17–1.34), poor performance status (OR, 3.40; 95% CI, 2.19 –5.26), the need for mechanical ventilation (OR, 2.42; 95% CI, 1.51–3.87), and active underlying malignancy in recurrence or progression (OR, 2.42; 95% CI, 1.51–3.87) were associated with increased hospital mortality in multivariate analysis. Conclusions: This large multicenter study reports encouraging survival rates for patients with cancer requiring intensive care. In these patients, mortality was mostly dependent on the severity of organ failures, performance status, and need for mechanical ventilation rather than cancer-related characteristics, such as the type of malignancy or the presence of neutropenia.Critical Care Medicine 12/2009; 38(1):9-15. · 6.33 Impact Factor
Top co-authors
Top Journals
Institutions
-
2008–2012
-
Universidade Federal do Rio de Janeiro
- Programa Biologia Molecular e Biotecnologia
Rio de Janeiro, Rio de Janeiro, Brazil -
University of Utah
- Department of Human Molecular Biology and Genetics
Salt Lake City, UT, USA
-
-
2003–2012
-
Fundação Oswaldo Cruz
- • Instituto de Pesquisa Clínica Evandro Chagas (IPEC)
- • Departamento de Fisiologia e Farmacodinâmica
Rio de Janeiro, Rio de Janeiro, Brazil
-
-
2008–2011
-
Brazilian National Cancer Institute
Rio de Janeiro, Rio de Janeiro, Brazil
-
-
2007–2010
-
Instituto Evandro Chagas
Belém, Estado do Para, Brazil
-
-
2004–2005
-
Hospital Universitário Clementino Fraga Filho
Rio de Janeiro, Rio de Janeiro, Brazil
-
