The early systemic and gastrointestinal oxygenation effects of hemorrhagic shock resuscitation with hypertonic saline and hypertonic saline 6% dextran-70: A comparative study in dogs

The smaller volemic state from hypertonic (7.5%) saline (HS) solution administration in hemorrhagic shock can determine lesser systemic oxygen delivery and tissue oxygenation than conventional plasma expanders. In a model of hemorrhagic shock in dogs, we studied the systemic and gastrointestinal oxygenation effects of HS and hyperoncotic (6%) dextran-70 in combination with HS (HSD) solutions in comparison with lactated Ringer's (LR) and (6%) hydroxyethyl starch (HES) solutions. Forty-eight mongrel dogs were anesthetized, mechanically ventilated, and subjected to splenectomy. A gastric air tonometer was placed. in the stomach for intramucosal gastric CO2 (Pgco(2)) determination and for the calculation of intramucosal. pH (pHi):[pHi = pHa - log(Pgco(2)/Paco(2))].The dogs were hemorrhaged (42% of blood volume) to hold mean arterial blood pressure at 40-50 mm Hg over 30 min and were then resuscitated with LR (n = 12) in a 3:1 relation to removed blood volume; HS (n = 12), 6 mL / kg; HSD (n = 12), 6 mL / kg; and HES (mean molecular weight, 200 kDa; degree of substitution, 0.5) (n = 12) in a 1:1 relation to the removed blood volume. Hemodynamic, systemic, and gastric oxygenation variables were measured at baseline, after 30 min of hemorrhage, and 5, 60, and 120 min after intravascular fluid resuscitation. After fluid resuscitation, HS showed significantly lower arterial pH and mixed venous Po-2 and higher systemic oxygen uptake index and systemic oxygenation extraction than LR and HES (P < 0.05), whereas HSD showed significantly lower arterial pH than LR and HES (P < 0.05). Only HS and HSD did not return arterial pH and pHi to control levels (P < 0.05). In conclusion, all solutions improved systemic and gastrointestinal oxygenation after hemorrhagic shock in dogs. However, the HS solution showed the worst response in comparison to LR and HES solutions in relation to systemic oxygenation, whereas HSD showed intermediate values. HS and HSD solutions did not return regional oxygenation to control values.

Anthropometric midarm measurements can detect systemic fat-free mass depletion in patients with chronic obstructive pulmonary disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Three-year follow-up study of respiratory and systemic manifestations of chronic obstructive pulmonary disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Systemic response induced by Scorpaena plumieri fish venom initiates acute lung injury in mice

Scorpaena plumieri venomous fish inflicted severe injuries in humans characterized by systemic effects and cardiovascular abnormalities. Although cardiotoxic and hypotensive effects induced in rats by this venom have been studied, little is known about their effect on bronchial epithelial permeability and airway inflammation in mice. The primary goal of this study was to determine whether the intraplantar or intraperitoneal injection of S. plumieri venom results in systemic response, and whether this event initiates acute lung injure. We found that BALB/c mice developed neutrophilic infiltrates, areas of lung hemorrhage and alveolar macrophage activation within 24 h after injection with S. plumieri venom. These histopathological changes were associated with an early increase in BAL fluid protein and early induction of cytokines, chemokines and matrix metaloproteinases, followed by a later increase in BAL fluid neutrophils. These findings provide clear evidence that the injection of S. plumieri venom in footpad or peritoneal cavity of mice results in venom deposition in the airway and initiates a sustained inflammatory response in the lungs. (C) 2007 Elsevier Ltd. All rights reserved.

Analysis of systemic inflammatory response in the carcinogenic process of uterine cervical neoplasia

The inflammatory response is an active process in cervical cancer and may act in the progression and/or regression of the lesion. At the site of inflammation, macrophages and neutrophils are present as well as cytokines such as TNF-alpha and IFN-gamma. This study aims to evaluate the inflammatory response levels in women with cervical intraepithelial lesions (CIN) and with squamous cell carcinoma (SCC) of the cervix. Serum samples obtained from women without evidence of disease (n = 30), with CIN (n = 30) and with SCC of the cervix (n = 30) were analyzed for the activities of N-acetylglucosaminidase (NAG) and myeloperoxidase (MPO) by enzymatic assay and the serum levels of TNF-alpha and IFN-gamma by ELISA assay. The activities of NAG and MPO and the level of TNF-alpha were higher in women with CIN compared to the women with SCC. The levels of IFN-gamma were lower in the group of women with CIN compared to the group with SCC. There was not a significant association between the degree of the CIN and the staging of the SCC of the cervix and the degree of inflammation as assessed by the levels of inflammatory markers. The inflammatory response was inversely correlated with the progression of the carcinogenic process. In the three groups, the control group, women with CIN and women with invasive SCC, there was no association between the degree of preinvasive lesions and staging of the SCC of the cervix. (C) 2011 Elsevier Masson SAS. All rights reserved.

Diuron exposure induces systemic and organ-specific toxicity following acute and sub-chronic exposure in male Wistar rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Systemic congenital lymphangiomatosis

A linfoangiomatose é uma doença rara, caracterizada pela exarcebação da proliferação dos canais linfáticos, ocorrendo em crianças e adultos jovens. Nós descrevemos um caso extremamente raro de linfoangiomatose sistêmica congênita, em um recém-nascido que apresentava ascite e insuficiência respiratória, desenvolvidos imediatamente após o nascimento. O óbito ocorreu nas primeiras horas de vida. Achados de autópsia demonstraram numerosos cistos em tecido mole da região cervical, mediastino, diafragma, e em diversos outros órgãos incluindo: fígado, baço, tireóide e rins. O grave e difuso acometimento de cistos nos pulmões pela linfoangiomatose foi associado ao mau prognóstico e morte no caso relatado.

Preliminary Criteria for Global Flares in Childhood-Onset Systemic Lupus Erythematosus

Objective. To develop widely acceptable preliminary criteria of global flare for childhood-onset systemic lupus erythematosus (cSLE).Methods. Pediatric rheumatologists (n = 138) rated a total of 358 unique patient profiles with information about the cSLE flare descriptors from 2 consecutive visits: patient global assessment of well-being, physician global assessment of disease activity (MD-global), health-related quality of life, anti-double-stranded DNA antibodies, disease activity index scores, protein: creatinine (P:C) ratio, complement levels, and erythrocyte sedimentation rate (ESR). Based on 2,996 rater responses about the course of cSLE (baseline versus followup), the accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve) of candidate flare criteria was assessed. An international consensus conference was held to rank these candidate flare criteria as per the American College of Rheumatology recommendations for the development and validation of criteria sets.Results. The highest-ranked candidate criteria considered absolute changes (Delta) of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) or British Isles Lupus Assessment Group (BILAG), MD-global, P:C ratio, and ESR; flare scores can be calculated (0.5 x Delta SLEDAI + 0.45 x Delta P:C ratio + 0.5 x Delta MD-global + 0.02 x Delta ESR), where values of >= 1.04 are reflective of a flare. Similarly, BILAG-based flare scores (0.4 x Delta BILAG + Delta 0.65 x Delta P:C ratio + 0.5 + Delta MD-global + 0.02 x Delta ESR) of >= 1.15 were diagnostic of a flare. Flare scores increased with flare severity.Conclusion. Consensus has been reached on preliminary criteria for global flares in cSLE. Further validation studies are needed to confirm the usefulness of the cSLE flare criteria in research and for clinical care.

Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Macrophage Activation Syndrome in Juvenile Systemic Lupus Erythematosus A Multinational Multicenter Study of Thirty-Eight Patients

Objective. To describe the clinical and laboratory features of macrophage activation syndrome as a complication of juvenile systemic lupus erythematosus (SLE).Methods. Cases of juvenile SLE-associated macrophage activation syndrome were provided by investigators belonging to 3 pediatric rheumatology networks or were found in the literature. Patients who had evidence of macrophage hemophagocytosis on bone marrow aspiration were considered to have definite macrophage activation syndrome, and those who did not have such evidence were considered to have probable macrophage activation syndrome. Clinical and laboratory findings in patients with macrophage activation syndrome were contrasted with those of 2 control groups composed of patients with active juvenile SLE without macrophage activation syndrome. The ability of each feature to discriminate macrophage activation syndrome from active disease was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic curve.Results. The study included 38 patients (20 with definite macrophage activation syndrome and 18 with probable macrophage activation syndrome). Patients with definite and probable macrophage activation syndrome were comparable with regard to all clinical and laboratory features of the syndrome, except for a greater frequency of lymphadenopathy, leukopenia, and thrombocytopenia in patients with definite macrophage activation syndrome. Overall, clinical features had better specificity than sensitivity, except for fever, which was highly sensitive but had low specificity. Among laboratory features, the best sensitivity and specificity was achieved using hyperferritinemia, followed by increased levels of lactate dehydrogenase, hypertriglyceridemia, and hypofibrinogenemia. Based on the results of statistical analysis, preliminary diagnostic guidelines for macrophage activation syndrome in juvenile SLE were developed.Conclusion. Our findings indicate that the occurrence of unexplained fever and cytopenia, when associated with hyperferritinemia, in a patient with juvenile SLE should raise the suspicion of macrophage activation syndrome. We propose preliminary guidelines for this syndrome in juvenile SLE to facilitate timely diagnosis and correct classification of patients.

Tragedy on grade crossing: driver failure or systemic fragility?

In 2010, an accident occurred in Americana-SP, Brazil, involving two trains and one bus on a Grade Crossing, when 10 people died and 17 were injured including workers. This paper aims to analyze the accident using the Model of Analysis and Prevention of Work Accidents (MAPA). The method provides observation of work, interviews and analysis of documents to understand precedents of the event in the following stages: to understand the usual work from the involved people, the changes occurred in the system, the operation of barriers, managerial and organizational aspects. By the end, measures are suggested to avoid new occurrences. The accident took place at night in a site with insufficient lighting. The working conditions of bus drivers, train operators and watchmen are inadequate. There were only symbolic barriers (visual and acoustic signals) triggered manually by watchman upon train operator radio communication. The fragility of the barrier system associated to poor lighting and short time to trigger the signaling seem to play a critical role in the event. Contrary to the official report which resulted in guilt of the bus driver, the conclusion of the paper emphasizes the fragility of the safety system and the need of level crossing reproject.

Systemic evaluation on ischemia and reperfusion injury of splanchnic organs in rats

OBJETIVO: Avaliar as alterações hemodinâmicas e sistêmicas decorrentes de isquemia e reperfusão (I/R) esplâncnica em ratos. MÉTODOS: Vinte ratos foram divididos em dois grupos: grupo controle: os animais foram submetidos à cirurgia, mas não a I/R e foram tratados com solução fisiológica (5 ml/kg/h) por 150 minutos; grupo I/R: os animais foram submetidos à administração contínua de solução fisiológica e à oclusão do tronco celíaco, artéria mesentérica superior e artéria mesentérica inferior por 30 minutos, seguidos por 120 minutos de reperfusão. Avaliou-se a pressão arterial média, pressão venosa, fluxo sangüíneo na aorta e na artéria mesentérica superior, freqüência cardíaca, temperatura esofágica e hematócrito. RESULTADOS: Durante a reperfusão, no grupo I/R, houve uma diminuição progressiva da pressão arterial média, fluxo sangüíneo na aorta e artéria mesentérica superior, freqüência cardíaca e temperatura esofágica; pressão venosa e hematócrito não sofreram alteração. CONCLUSÃO: O modelo de isquemia provocado por oclusão da artéria mesentérica superior, artéria mesentérica inferior e tronco celíaco por 30 minutos seguidos por 120 minutos de reperfusão provoca alterações sistêmicas evidenciadas por hipotensão, diminuição do fluxo sangüíneo mesentérico, da freqüência cardíaca e da temperatura esofágica.

Protective effects of carvedilol on systemic vascular damage induced by angiotensin II: Organ-specific effects independent of antihypertensive effects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)