No description available.

Systemic inflammation is a leading cause of mortality and morbidity in both human and equine intensive care patients. This systemic inflammatory response may be due to insult from bacterial, viral, fungal or parasitic invasion or from trauma or hypoxemia. Local and systemic release of a wide variety of endogenous pro-inflammatory mediators results in activation of the innate immune system in order to resolve the insult. In sepsis this initial appropriate host response becomes amplified and deregulated leading to refractory hypotension and multiple organ dysfunction. The exact incidence of sepsis (SIRS due to bacterial infection) has not been reported in the equine literature (Roy 2004). Since early recognition and treatment of sepsis are associated with improved outcome the search for markers to accurately predict presence of sepsis and likelihood of survival continues. The serum concentration of both procalcitonin and its related molecule CGRP have been documented to increase in humans with SIRS, yet no literature exists as to the production or role of CGRP in equine patients with SIRS. This study showed that equine CGRP was produced in detectable quantities by healthy adult horses and neonatal foals less than two weeks of age using a rat á-CGRP ELISA. The low percentage recovery of CGRP from samples and the high lower limit of detection for the assay prevented establishment of a normal concentration range of CGRP in healthy horses. In both adult horses and foals with documented SIRS, CGRP concentrations were significantly increased at time of presentation to the hospital (p<0.0002, p<0.003 respectively). A trend towards increased serum CGRP concentration was present in anaesethized horses exposed to endotoxin, but this was not statistically significant (p< 0.067). / Master of Science

narmq2@hotmail.com / Objetivo: La inflamación sistémica empeora los trastornos circulatorios en el paciente cirrótico y recientemente el síndrome de respuesta inflamatoria sistémica (SRIS) podría ser un indicador pronóstico en ellos. El objetivo del estudio fue determinar si la presencia de SRIS al ingreso en pacientes cirróticos hospitalizados está asociada a complicaciones o mortalidad. Materiales y métodos: Estudio de cohortes retrospectiva, realizado en el Hospital Nacional Daniel Alcides Carrión. Se admitieron pacientes cirróticos hospitalizados desde julio 2008 hasta diciembre 2010 sin comorbilidades importantes, neoplasia maligna, infección VIH, o estancia fue menor a 72 horas. Se evaluó presencia de SRIS al ingreso y la aparición de complicaciones o muerte después de 72 horas del ingreso. Resultados: Fueron 150 pacientes cirróticos admitidos, se excluyeron 6, tres por supervivencia menor a las 72 horas, uno por neoplasia, uno por insuficiencia cardiaca severa y dos por insuficiencia renal crónica. En total 144 pacientes ingresaron al estudio, 95 (66%) pacientes presentaron SRIS al ingreso. No hubo diferencia significativa en cuanto a edad, sexo, etiología, en ambos grupos. SRIS estuvo asociado a mayores puntajes de MELD y Child-Pugh Turcotte. De los pacientes con SRIS, 41 (43%) se complicaron y 16 (16,8%) fallecieron, mientras que del grupo sin SRIS 5 (10,2%) se complicaron y 2 (4%) fallecieron , ( p <0,0001y p =0,028 respectivamente). Las complicaciones más frecuentes fueron las infecciones y encefalopatía hepática. En el análisis multivariado SRIS estuvo asociado a complicaciones ( p <0,006) mas no a mortalidad ( p <0,276). Conclusiones: SRIS es frecuente en pacientes cirróticos hospitalizados y está asociado a complicaciones intrahospitalarias. / Objective: The systemic inflammation worsens circulatory disorders in cirrhotic patients and recently the systemic inflammatory response syndrome (SIRS) may be a prognostic indicator therein. The aim of the study was to determine whether the presence of SIRS at admission in hospitalized cirrhotic patients is associated with complications or mortality. Materials and methods: A retrospective cohorts study was conducted at the Daniel Alcides Carrion National Hospital. Hospitalized cirrhotic patients admitted from July 2008 to December 2010 without significant comorbidities, malignancy, HIV infection, or stay less than 72 hours were included. Presence of SIRS at admission and the occurrence of complications or death after 72 hours of admission were evaluated. Results: 150 cirrhotic patients were admitted, six were excluded; three for lower survival at 72 hours, one for neoplasia, one for severe heart failure and two for chronic renal failure. One hundred forty four patients were included, 95 (66%) patients had SIRS at admission. There was no significant difference in age, sex, etiology, in both groups. SIRS was associated with higher scores of MELD and Child-Turcotte Pugh. Of the group of patients with SIRS, 41 (43%) had complications and 16 (16.8%) died, while the group without SIRS 5 (10.2%) had complications and two (4%) died ( p <0.0001 and p =0.028 respectively). The most common complications were infections and hepatic encephalopathy. In multivariate analysis SIRS was associated with complications ( p <0.006) but not with mortality ( p <0.276). Conclusions: SIRS is common in hospitalized cirrhotic patients and is associated with in-hospital complications.

Objetivo: La inflamación sistémica empeora los trastornos circulatorios en el paciente cirrótico y recientemente el síndrome de respuesta inflamatoria sistémica (SRIS) podría ser un indicador pronóstico en ellos. El objetivo del estudio fue determinar si la presencia de SRIS al ingreso en pacientes cirróticos hospitalizados está asociada a complicaciones o mortalidad. Materiales y métodos: Estudio de cohortes retrospectiva, realizado en el Hospital Nacional Daniel Alcides Carrión. Se admitieron pacientes cirróticos hospitalizados desde julio 2008 hasta diciembre 2010 sin comorbilidades importantes, neoplasia maligna, infección VIH, o estancia fue menor a 72 horas. Se evaluó presencia de SRIS al ingreso y la aparición de complicaciones o muerte después de 72 horas del ingreso. Resultados: Fueron 150 pacientes cirróticos admitidos, se excluyeron 6, tres por supervivencia menor a las 72 horas, uno por neoplasia, uno por insuficiencia cardiaca severa y dos por insuficiencia renal crónica. En total 144 pacientes ingresaron al estudio, 95 (66%) pacientes presentaron SRIS al ingreso. No hubo diferencia significativa en cuanto a edad, sexo, etiología, en ambos grupos. SRIS estuvo asociado a mayores puntajes de MELD y Child-Pugh Turcotte. De los pacientes con SRIS, 41 (43%) se complicaron y 16 (16,8%) fallecieron, mientras que del grupo sin SRIS 5 (10,2%) se complicaron y 2 (4%) fallecieron, (p<0,0001y p=0,028 respectivamente). Las complicaciones más frecuentes fueron las infecciones y encefalopatía hepática. En el análisis multivariado SRIS estuvo asociado a complicaciones (p<0,006) mas no a mortalidad (p<0,276). Conclusiones: SRIS es frecuente en pacientes cirróticos hospitalizados y está asociado a complicaciones intrahospitalarias. / Objective: The systemic inflammation worsens circulatory disorders in cirrhotic patients and recently the systemic inflammatory response syndrome (SIRS) may be a prognostic indicator therein. The aim of the study was to determine whether the presence of SIRS at admission in hospitalized cirrhotic patients is associated with complications or mortality. Materials and methods: A retrospective cohorts study was conducted at the Daniel Alcides Carrion National Hospital. Hospitalized cirrhotic patients admitted from July 2008 to December 2010 without significant comorbidities, malignancy, HIV infection, or stay less than 72 hours were included. Presence of SIRS at admission and the occurrence of complications or death after 72 hours of admission were evaluated. Results: 150 cirrhotic patients were admitted, six were excluded; three for lower survival at 72 hours, one for neoplasia, one for severe heart failure and two for chronic renal failure. One hundred forty four patients were included, 95 (66%) patients had SIRS at admission. There was no significant difference in age, sex, etiology, in both groups. SIRS was associated with higher scores of MELD and Child-Turcotte Pugh. Of the group of patients with SIRS, 41 (43%) had complications and 16 (16.8%) died, while the group without SIRS 5 (10.2%) had complications and two (4%) died (p<0.0001 and p=0.028 respectively). The most common complications were infections and hepatic encephalopathy. In multivariate analysis SIRS was associated with complications (p<0.006) but not with mortality (p<0.276). Conclusions: SIRS is common in hospitalized cirrhotic patients and is associated with in-hospital complications. Key words: Liver cirrhosis; Systemic inflammatory response syndrome; Complications (source: MeSH NLM).

Early detection of infection, identification of microorganism, and correct choice of antibiotics are critical in the management of sepsis. Quantitative real-time polymerase chain reaction (RT-PCR) has the potential to improve the timeliness, sensitivity, and accuracy of detecting pathogens. In this study we utilize this method to detect the enteric bacterial counts in the blood from patients with systemic inflammatory response syndrome (SIRS) in the emergency department (ED). The universal primers utilized in RT-PCR are specific for 23S ribosomal DNA (rDNA) and wec F gene. The results show that in SIRS patients with positive culture results from specimen collected within 10 days after presenting to ED, and patients surviving for less than 28 days, the serum bacterial DNA load of enteric Gram negative bacilli is higher. In SIRS patients with shock, patients fulfilling both white blood cell counts and respiratory criteria of SIRS, and patients fulfilling both white blood cell counts and respiratory criteria of SIRS with Acute Physiology and Chronic Health Evaluation II score more than 20, the serum bacterial DNA load of enteric Gram negative bacilli and 28-day mortality are both higher. These results suggest that bacterial translocation may happen in patients with SIRS and may be related to higher mortality in patients with SIRS.

No description available.

Abstract Cardiac surgery with cardiopulmonary bypass induces the activation of systemic inflammatory response syndrome (SIRS) and results in at least some degree of global myocardial ischemia. Although these responses are usually short-lived, they may lead to serious complications and organ system failures. The present study evaluated the effects of high-dose glucose-insulin (1IU/kg/h) treatment (GIK) administered with the hyperinsulinemic normoglycemic clamp technique and a leukocyte-depleting filter on markers of systemic inflammatory response and myocardial ischemia-reperfusion injury in certain cardiac surgical risk groups. The study involved four prospective randomized controlled clinical trials and 119 patients. Cardioprotective effects were measured as myocardial enzyme release, recovery of contractile function and incidence of arrhythmias in all studies. The hemodynamic and metabolic effects of high-dose glucose-insulin treatment were evaluated in patients admitted for combined aortic valve (AS) and coronary surgery (40) and for urgent coronary surgery (39), and the latter study also involved proinflammatory cytokine and C-reactive protein analyses. The impacts of leukocyte filter on the expression of neutrophil adhesion molecules along with proinflammatory cytokines were evaluated in patients admitted for combined aortic valve (AS) and coronary surgery (20) and for solitary coronary surgery (20). The high-dose glucose-insulin treatment was associated with better preserved myocardial contractile function and less need for inotropic support after combined aortic valve and coronary surgery (I) and attenuation of postoperative CRP release after urgent coronary surgery (II). No effects on postoperative myocardial enzyme release (I, II) or on proinflammatory cytokine responses (II) were detected. The number of hypoglycemic events was low. The use of a leukocyte filter throughout the cardiopulmonary bypass period increased the neutrophil adhesion molecule CD11b expression in patients with both normal and prolonged CPB times and was associated with an enhanced proinflammatory cytokine response (III, IV). In conclusion, high-dose glucose-insulin treatment is safe, but requires strict control of blood glucose level. It reduces the need for inotropic support in patients with compromised cardiac status. The use of leukocyte filter leads to increased leukocyte activation and proinflammatory reaction.

There were three objectives of this study. The first was to determine if commercially available fluorochromes could be used to determine the glucocorticoid receptor (GR) density and binding affinity (BA) in equine peripheral blood mononuclear cells. The second was to determine if there was a correlation between elevated plasma cortisol and GR density or binding affinity in healthy adult horses. The third objective was to evaluate the HPA axis in adult horses presenting with systemic inflammatory response syndrome (SIRS), and to determine where any alterations in HPA axis function occur in these patients compared to healthy adults. For the first part of the study, peripheral venous blood was collected from 3 healthy research horses on 3 days. Peripheral blood mononuclear cells were isolated using Ficoll gradient centrifugation. Phycoerythrin (PE)-CD44 was then used to extracellularly label leukocytes, and then an intracellular GR antibody was used to determine a baseline measurement of GR density and fluorescein isothiocyanate (FITC)-dexamethasone was used to determine binding affinity via flow cytometric analysis. Comparison of control samples to those for CD44, GR density, and GR binding affinity showed a statistically significant difference for all samples (P<0.0001, P<0.0001, and P<0.0001 respectively). This showed that the CD44, GR antibody, and FITC-dexamethasone could successfully be used to analyze equine peripheral blood mononuclear cells for GR activity. For the second part of the study, an ACTH stimulation test was performed on 8 healthy horses in order to induce an increase in endogenous cortisol production. Plasma cortisol levels, GR density, and GR binding affinity were measured at baseline, 4, 8, and 24 hours after treatment. Median basal cortisol concentration was 4.9, range 3.2-6.1 μg/dl. This initially increased following ACTH stimulation to 5.6, range 4.8-7.4 μg/dl, then showed a significant decrease by 8 hours post ACTH administration to 1.4, range 1.1-2.7 μg/dl (P=0.0221). No correlation was observed between plasma cortisol concentration in healthy horses and GR density or binding affinity (r=-0.145, P=0.428 and r=0.046, P=0.802, respectively). For the third phase of the study, horses (N=10) with systemic inflammatory response syndrome (SIRS) were compared to healthy, age and sex matched controls (N=10) presenting for lameness evaluation or ophthalmologic examination. Blood was collected from SIRS cases and controls on presentation to the Equine Medical Center. A CBC, serum biochemistry, and serum ACTH and cortisol measurements were performed. GR density and binding affinity were also determined. Nonsurvivors had a significantly decreased GR binding affinity (P=0.008) and demonstrated a trend towards an increase in the ACTH:cortisol ratio. ROC analysis was performed for serum ACTH and cortisol concentrations, the ACTH:cortisol ratio, GR density and GR binding affinity, and triglycerides to determine cut-off values associated with nonsurvival. These were then used to analyze this population using Fischer's exact test to determine the odds ratio (OR) associated with nonsurvival for each variable. This revealed that a serum triglyceride concentration greater than 28.5 mg/dl was associated with nonsurvival (OR=117, 95% CI, 1.94-7060). The other variables were not found to be significantly associated with nonsurvival, although a Delta BA% of less than 35.79% was found to be closely associated with nonsurvival (OR=30.33, 95% CI, 0.96-960.5). Additionally, a significant negative correlation was detected between the plasma ACTH concentration and Delta BA% (r=-0.685, P=0.029) and the ACTH:cortisol ratio and the Delta BA% (r=-0.697, P=0.025). This study showed that nonsurviving horses with SIRS had a significantly decreased GR binding affinity compared to survivors, and a tendency toward an increase in their ACTH:cortisol ratios. This confirms that HPA axis dysfunction occurs in adult horses with SIRS as tissue resistance to glucocorticoids, and potentially relative adrenal insufficiency as well. These results suggest that there are horses with SIRS that might benefit from "physiologic" doses of synthetic glucocorticoids to complement their relative adrenal insufficiency in addition to their poor tissue sensitivity. Further research should focus on methods to more rapidly determine which horses might benefit from treatment with glucocorticoids on presentation, as well as to more accurately determine prognosis for survival. / Master of Science

A Coagulação Intravascular Disseminada (CID) é uma síndrome caracterizada pela ativação sistêmica da coagulação sanguínea, levando à trombose microvascular difusa e podendo comprometer a função de múltiplos órgãos. O acelerado consumo de plaquetas e fatores de coagulação pode, no entanto, dar origem a um estado de hipocoagulabilidade, o que confere à CID uma característica paradoxal na qual o excesso de coagulação pode causar uma diátese hemorrágica. Doenças que levam à Síndrome de Resposta Inflamatória Sistêmica (SIRS) estão entre os principais gatilhos da CID. A pancreatite é uma dessas doenças. O maior desafio para o médico veterinário é diagnosticar a CID na fase precoce, silenciosa e de hipercoagulabilidade, visto que os testes laboratoriais de rotina, como contagem de plaquetas, tempo de protrombina (TP) e tempo de tromboplastina parcial ativada (TTPA), detectam apenas o estado de hipocoaguabilidade, que se estabelece na fase mais avançada da síndrome. Nesse contexto ganham importância os analisadores tromboelastográficos, equipamentos que avaliam a coagulação em sangue total e que, ao menos em tese, podem informar a velocidade de formação do coágulo, a força máxima que ele atinge e os padrões de sua dissolução. Este estudo é o primeiro realizado em cães com o aparelho ReoRox G2 (MediRox), uma da marcas disponíveis no mercado. Limites de referência para as variáveis do aparelho foram definidos a partir da análise do sangue de 49 animais clinicamente saudáveis para três tipos de reação: acelerada com fator tecidual (TF), acelerada com TF e um antagonista de agregação plaquetária (abciximab) e apenas com sangue recalcificado. Em seguida, foram comparados a esse intervalo de referência os valores obtidos pela análise tromboelastográfica do sangue de seis pacientes com pancreatite recém-diagnosticada. Nos três tipos de reação pelo menos 50% dos pacientes do Grupo Pancreatite apresentaram alterações sugestivas de hipercoagulabilidade. A variável MAXELAST (força máxima do coágulo) foi a que esteve alterada com mais frequência entre os animais doentes. Não houve alteração nos marcadores de velocidade de fibrinólise. Estudos prospectivos que associem outras variáveis de trombose, protocolos de tratamento e prognóstico de pacientes com doenças subjacentes que predisponham à CID são necessários para que se possa afirmar que o traçado obtido pela tromboelastografia realmente representa um estado de hipercoagulabilidade in vivo em pacientes com pancreatite. / Disseminated Intravascular Coagulation (DIC) is a syndrome characterized by systemic activation of blood clotting, leading to diffuse microvascular thrombosis and may compromise multiple organ function. The accelerated consumption of platelets and coagulation factors may, however, originate a state of hypocoagulability, which gives the DIC a paradoxical characteristic in which excess coagulation can lead to a hemorrhagic diathesis. Diseases which cause Systemic Inflammatory Response Syndrome (SIRS) are among the major triggers of DIC, including pancreatitis. The greatest challenge for veterinarians is to diagnose DIC in the early, silent and hypercoagulable phase, since routine laboratory tests, such as platelet count, prothrombin time (PT) and activated partial thromboplastin time (APTT), detect only the state of hypocoagulability, which occurs in the most advanced stage of the syndrome. In this context, thromboelastography analyzers stand out. They are equipment which evaluate coagulation in whole blood and, at least in theory, inform the speed of clot formation, its maximum force and how it dissolves. This is the first study performed in dogs with the ReoRox G2 (MediRox), one of the brands available in the market. Limits of reference were defined from blood analysis of 49 healthy animals for three reaction types: accelerated with tissue factor (TF), accelerated with TF and a platelet aggregation antagonist (abciximab) and with only recalcified blood. Next, values obtained by blood thromboelastographic analysis of six patients with newly diagnosed pancreatitis were compared to this reference range. In all three types of reactions, at least 50% of patients in the Pancreatitis Group presented alterations suggestive of hypercoagulability. The variable MAXELAST (maximum clot strength) was the one that was most frequently altered among ill animals. There was no change in fibrinolysis rate markers. Prospective studies associating other thrombosis variables, treatment protocols, and prognosis of patients with underlying diseases predisposing to DIC are necessary to confirm that the pathway obtained by thromboelastography actually represents a state of hypercoaguability in vivo in patients with pancreatitis.

A Coagulação Intravascular Disseminada (CID) é uma síndrome caracterizada pela ativação sistêmica da coagulação sanguínea, levando à trombose microvascular difusa e podendo comprometer a função de múltiplos órgãos. O acelerado consumo de plaquetas e fatores de coagulação pode, no entanto, dar origem a um estado de hipocoagulabilidade, o que confere à CID uma característica paradoxal na qual o excesso de coagulação pode causar uma diátese hemorrágica. Doenças que levam à Síndrome de Resposta Inflamatória Sistêmica (SIRS) estão entre os principais gatilhos da CID. A pancreatite é uma dessas doenças. O maior desafio para o médico veterinário é diagnosticar a CID na fase precoce, silenciosa e de hipercoagulabilidade, visto que os testes laboratoriais de rotina, como contagem de plaquetas, tempo de protrombina (TP) e tempo de tromboplastina parcial ativada (TTPA), detectam apenas o estado de hipocoaguabilidade, que se estabelece na fase mais avançada da síndrome. Nesse contexto ganham importância os analisadores tromboelastográficos, equipamentos que avaliam a coagulação em sangue total e que, ao menos em tese, podem informar a velocidade de formação do coágulo, a força máxima que ele atinge e os padrões de sua dissolução. Este estudo é o primeiro realizado em cães com o aparelho ReoRox G2 (MediRox), uma da marcas disponíveis no mercado. Limites de referência para as variáveis do aparelho foram definidos a partir da análise do sangue de 49 animais clinicamente saudáveis para três tipos de reação: acelerada com fator tecidual (TF), acelerada com TF e um antagonista de agregação plaquetária (abciximab) e apenas com sangue recalcificado. Em seguida, foram comparados a esse intervalo de referência os valores obtidos pela análise tromboelastográfica do sangue de seis pacientes com pancreatite recém-diagnosticada. Nos três tipos de reação pelo menos 50% dos pacientes do Grupo Pancreatite apresentaram alterações sugestivas de hipercoagulabilidade. A variável MAXELAST (força máxima do coágulo) foi a que esteve alterada com mais frequência entre os animais doentes. Não houve alteração nos marcadores de velocidade de fibrinólise. Estudos prospectivos que associem outras variáveis de trombose, protocolos de tratamento e prognóstico de pacientes com doenças subjacentes que predisponham à CID são necessários para que se possa afirmar que o traçado obtido pela tromboelastografia realmente representa um estado de hipercoagulabilidade in vivo em pacientes com pancreatite. / Disseminated Intravascular Coagulation (DIC) is a syndrome characterized by systemic activation of blood clotting, leading to diffuse microvascular thrombosis and may compromise multiple organ function. The accelerated consumption of platelets and coagulation factors may, however, originate a state of hypocoagulability, which gives the DIC a paradoxical characteristic in which excess coagulation can lead to a hemorrhagic diathesis. Diseases which cause Systemic Inflammatory Response Syndrome (SIRS) are among the major triggers of DIC, including pancreatitis. The greatest challenge for veterinarians is to diagnose DIC in the early, silent and hypercoagulable phase, since routine laboratory tests, such as platelet count, prothrombin time (PT) and activated partial thromboplastin time (APTT), detect only the state of hypocoagulability, which occurs in the most advanced stage of the syndrome. In this context, thromboelastography analyzers stand out. They are equipment which evaluate coagulation in whole blood and, at least in theory, inform the speed of clot formation, its maximum force and how it dissolves. This is the first study performed in dogs with the ReoRox G2 (MediRox), one of the brands available in the market. Limits of reference were defined from blood analysis of 49 healthy animals for three reaction types: accelerated with tissue factor (TF), accelerated with TF and a platelet aggregation antagonist (abciximab) and with only recalcified blood. Next, values obtained by blood thromboelastographic analysis of six patients with newly diagnosed pancreatitis were compared to this reference range. In all three types of reactions, at least 50% of patients in the Pancreatitis Group presented alterations suggestive of hypercoagulability. The variable MAXELAST (maximum clot strength) was the one that was most frequently altered among ill animals. There was no change in fibrinolysis rate markers. Prospective studies associating other thrombosis variables, treatment protocols, and prognosis of patients with underlying diseases predisposing to DIC are necessary to confirm that the pathway obtained by thromboelastography actually represents a state of hypercoaguability in vivo in patients with pancreatitis.