Clinical trials in spontaneous disease in dogs: a new paradigm for investigations of sepsis

Objective: To provide evidence that naturally occurring sepsis in dogs provides a unique opportunity to test new therapies in clinically relevant settings. Data sources: Human and veterinary literature. Human data synthesis: Sepsis is a devastating condition responsible for most intensive care unit deaths. Most clinical trials targeting inflammatory mediators of sepsis have failed to improve outcome in clinical patients despite promising results in laboratory animal models. Animal models of sepsis fail to reproduce the clinical syndrome and therefore lead to conclusions that may not be relevant to clinical care. Veterinary data synthesis: Sepsis is recognized but not well‐characterized in companion animal species. Despite some species variability, the cardiopulmonary response to sepsis in dogs is similar to humans. Additionally, inflammatory and coagulation changes that accompany canine sepsis are consistent with those documented in humans. Sepsis secondary to canine parvoviral infection offers the advantages of relative population homogeneity, predictable course, and easy early diagnosis. The disadvantages of canine parvovirus are that it affects a predominantly young and healthy population and results in low mortality with aggressive supportive care. Septic peritonitis and pneumonia have high mortality but can be challenging to diagnose, have a variable course, and affect a heterogeneous population, which can be an advantage or a disadvantage. Conclusions: Similar to trials currently being performed in canine cancer patients, veterinary clinical trials of new sepsis therapeutics may provide a unique opportunity to advance the treatment of sepsis in dogs, humans, and other species. Spontaneous sepsis from canine parvovirus, peritonitis, and pneumonia are common clinical conditions in which therapeutics can be tested.     

非线性传染率的流行病模型的周期解与Hopf分支的存在性

本文讨论一类具有非线性传染率的流行病模型的动力形态,并给出该系统出现同宿分支与周期轨道分支的条件.     

Plasma interleukin-6 response is predictive for severity and mortality in canine systemic inflammatory response syndrome and sepsis

BACKGROUND: Sepsis is still a major cause of death in both human and veterinary medicine. Early diagnosis is essential for appropriate treatment. Identification of patients at risk for developing sepsis is already possible in human medicine through the measurement of plasma interleukin-6 (IL-6) levels. In veterinary medicine, however, this has been investigated only in canine experimental models. OBJECTIVES: The purpose of this study was to measure IL-6 plasma levels in dogs with naturally occurring systemic inflammatory response syndrome (SIRS) and sepsis and to analyze the value of IL-6 as a predictive parameter for severity and mortality. METHODS: Included in the study were 79 dogs that had been admitted to the small animal clinics of Munich and Berlin from July 2004 to July 2005 and that satisfied the diagnostic criteria for SIRS and sepsis as defined using established parameters. Measurement of plasma IL-6 levels on days 0, 1, and 2 was performed by the use of a colorimetric bioassay based on IL-6-dependent cell growth. RESULTS: Septic foci were identified in 43 patients (septic group), and 36 patients were enrolled in the SIRS group. The frequency of positive blood cultures was 11%. The overall mortality rate was 48%. Higher plasma IL-6 levels on the day of admission were significantly correlated with a more severe degree of disease, increased mortality rate, and earlier fatality. CONCLUSIONS: Plasma IL-6 concentration is predictive of outcome in canine SIRS and sepsis and may be a valuable laboratory parameter for assessing critically ill dogs.     

Neutrophilic myeloperoxidase index and mean light absorbance in neonatal septic and nonseptic foals

Background: Two neutrophilic indices reported by the ADVIA 120 Hematology Analyzer, neutrophilic myeloperoxidase index (MPXI), and mean light absorbance (neutrophil X mean [NXM]) have been proposed as indicators of systemic inflammatory disease in horses and of neutrophil activation in coronary ischemic syndromes in people. Objective: The aim of this study was to evaluate NXM and MPXI in healthy, sick nonseptic, and sick septic foals to determine whether conditions likely associated with neutrophil activation result in decreases in these variables. Methods: In this retrospective study, CBC data from 61 neonatal foals presented to the Equine Teaching Hospital of Barcelona were evaluated for correlations between MPXI, NXM, percentage of large unstained cells, neutrophil count, and percentage of band neutrophils. Results obtained in septic (n=32), sick nonseptic (n=22), and healthy foals (n=7) were compared. In addition, results recorded in septic/neutropenic (n=12), septic/non‐neutropenic (n=20), nonseptic/neutropenic (n=8), nonseptic/non‐neutropenic (n=14), and healthy foals (n=7) were also compared. Results: A weak negative correlation was found between MPXI and neutrophil count and between NXM and percentage of band neutrophils. Septic/neutropenic foals had significantly higher MPXI values (median 17.9, minimum–maximum 4.7–42.5) than did septic/non‐neutropenic (1.5, ?24.4 to 22.3), nonseptic/neutropenic (6.6, 0.6–17.9), and nonseptic/non‐neutropenic foals (8.8, ?10.1 to 16.8) but did not differ significantly from controls (12.8, ?8.5 to 20.4). Conclusions: Significant differences in NXM or MPXI were not found when disease groups were compared with controls; however, septic/neutropenic foals had significantly higher median MPXI than other groups of sick foals. Further prospective studies are needed to clarify if this finding is related to decreased neutrophil function or activation in septic/neutropenic foals.