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1.
Objectives – To review the role of thrombin in physiology and clinical disease and to discuss the pharmacology of antithrombosis.
Data Sources – Original research articles, scientific reviews, textbooks.
Human Data Synthesis – Thrombin and thrombin receptors are involved in a variety of physiologic and pathologic processes resulting in a great deal of interest in thrombin-related pharmacologic intervention.
Veterinary Data Synthesis – Although there is little clinical research data available on thrombin specifically in veterinary patients, some of the original research on protease activated receptors was performed at veterinary institutions and many of the human molecular biology studies have been done on animals including dogs.
Conclusion – Thrombin plays a significant role in coagulation, anticoagulation, and fibrinolysis. Antithrombotic treatment is focused on preventing thrombosis while maintaining hemostasis. Pharmaceutical agents are selected for the specific component of the coagulation pathway associated with a specific disease process, for a proven prophylactic benefit with procedures that carry a risk of thromboembolism, for rapidity of onset and ease of reversibility, for limited monitoring requirements, and for oral formulation and bioavailablity. Recent insight into other aspects of thrombin physiology presents an opportunity for pharmacologic intervention in a variety of other processes such as inflammation and sepsis, peripheral blood cell activation and chemotaxis, vascular endothelial and smooth muscle activity, cellular development and tissue repair, mitogenesis, neoplasia, and the function of nervous tissue following injury.  相似文献   

2.
Objective – To provide a review of clinically relevant observations related to Bartonella species as emerging pathogens in veterinary and human medicine.
Data Sources – Literature as cited in PubMed and as generated by each of the authors who have contributed to various aspects of the clinical understanding of bartonellosis.
Human Data Synthesis – Important historical and recent publications illustrating the evolving role of animal reservoirs as a source of human infection.
Veterinary Data Synthesis – Comprehensive review of the veterinary literature.
Conclusions – In addition to inducing life-threatening illnesses, such as endocarditis, myocarditis, and meningoencephalitis and contributing to chronic debilitating disease, such as arthritis, osteomyelitis, and granulomatous inflammation in cats, dogs, and potentially other animal species; pets and wildlife species can serve as persistently infected reservoir hosts for the transmission of Bartonella spp. infection to veterinary professionals and others with direct animal contact.  相似文献   

3.
Objective: To review the current understanding of mechanisms involved in normal hemostasis and to describe the changes associated with pro‐inflammatory disease processes such as sepsis. Data sources: Original research articles and scientific reviews. Human data synthesis: Organ damage caused by sepsis is created in part by the interdependent relationship between hemostasis and inflammation. Markers of coagulation have been found to have prognostic value in human patients with sepsis and there are both experimental and clinical investigations of the therapeutic potential of modulating the hemostatic system in sepsis. Improvement of 28‐day all‐cause mortality in severe sepsis by treatment with recombinant human activated Protein C strongly supports the interdependence of hemostasis and inflammation in the pathophysiology of sepsis. Veterinary data synthesis: Publications reporting clinical evaluation of the hemostatic changes occurring in septic dogs or cats are minimal. Experimental animal models of sepsis reveal significant similarity between human and animal sepsis and may provide relevance to clinical veterinary medicine until prospective clinical evaluations are published. Conclusions: It is now apparent that inflammation and the coagulation system are intimately connected. Understanding this relationship provides some insight into the pathogenesis of the hemostatic changes associated with sepsis. This new updated view of hemostasis may lead to the development of novel therapeutic approaches to sepsis and disseminated intravascular coagulation in veterinary medicine.  相似文献   

4.
Objective – To review the hemostasis literature relevant to development of coagulopathy in the critically ill equine patient.
Data Source – Original scientific and review articles.
Human Data Synthesis – Inflammation plays a critical role in the activation and amplification of clot formation, as well as the impairment of physiologic anticoagulant mechanisms, and fibrinolysis. Earlier identification of coagulopathy in patients at risk and restoration of physiologic hemostasis may result in better outcome. Development of scoring systems based on information other than coagulation markers alone may better identify patients with subclinical coagulopathy.
Veterinary Data Synthesis – Critically ill equine patients commonly at risk for coagulopathy include those with severe gastrointestinal disease, septic foals, and adults subjected to severe systemic inflammatory response syndrome. Publications provide information regarding coagulation markers helpful for identification of hemostatic dysfunction in specific patient populations, as well as information regarding the influence of coagulopathy on outcome. Data regarding clinically relevant information on therapeutic intervention are lacking.
Conclusions – The relationship between inflammation and endotoxemia and development of coagulopathy is better understood in both human patients and the critically ill equine patient. Prospective clinical trials evaluating clinically relevant and financially feasible approaches to treatment are still needed.  相似文献   

5.
The potentially fatal hemostatic disorder of disseminated intravascular coagulation (DIC) is initiated in bacterial sepsis by lipopolysaccharide (LPS)-induced tissue factor (TF) expression on monocytes. Interleukin-10 (IL-10) is a potent inhibitory cytokine that downregulates monocyte inflammatory and procoagulant responses. We hypothesized that canine recombinant IL-10 (rIL-10) would inhibit LPS-induced TF upregulation on canine monocytes in a dose-dependent manner. Canine peripheral blood mononuclear cells (PBMC), obtained by double-density gradient centrifugation, and monocytes, purified from PBMC by immunomagnetic bead separation with an anti-canine CD14 antibody (Ab), were stimulated in suspension with LPS (0.1-1000ng/mL) for various times. Recombinant IL-10 (10-5000pg/mL) was added with LPS or up to 2h later. Tissue factor procoagulant activity was measured by cleavage of a chromogenic substrate by activated Factor X generated by the TF-factor VII complex. We found that rIL-10, when given concurrently or 1h after LPS, strongly inhibited LPS-induced TF procoagulant activity in canine PBMC and monocytes. This inhibition was dose-dependent and blocked by an anti-canine IL-10 Ab. Our results indicate that rIL-10 effectively inhibits LPS-induced TF upregulation in canine monocytes and could potentially be useful in limiting the development of DIC in dogs with endotoxemia.  相似文献   

6.
Objective – To review the human and veterinary literature on histamine physiology and pathophysiology and potential applications for clinical use in veterinary critical care. Data Sources – Human and veterinary clinical studies, reviews, texts, and recent research in histamine receptor and antagonist therapy. Human Data Synthesis – Recent progress in molecular biology has led to a more complete understanding of the enzymes involved in histamine metabolism and histamine receptor physiology. The past decade of research has confirmed the role of histamine in the classical functions (contraction of smooth muscle, increase in vascular permeability, and stimulation of gastric acid secretion) and has also elucidated newer ones that are now under investigation. Data on the roles of histamine in angiogenesis, circadian rhythm, bone marrow regeneration, bacterial eradication, and cancer are emerging in the literature. Newer histamine antagonists are currently in drug trials and are expected to advance the clinical field in treatment of allergic, gastrointestinal, and cognitive disorders. Veterinary Data Synthesis – Veterinary histamine research is directed at identifying the effects of certain pharmacological agents on blood histamine concentrations and establishing the relevance in clinical disease states. Research demonstrates important species differences in regards to histamine receptor physiology and tissue response. Studies in the area of trauma, sepsis, anaphylaxis, allergy, and gastrointestinal disorders have direct applications to clinical veterinary medicine. Conclusions – Histamine plays a key role in the morbidity and mortality associated with allergy, asthma, gastric ulcers, anaphylaxis, sepsis, hemorrhagic shock, anesthesia, surgery, cardiovascular disease, cancer, CNS disorders, and immune‐mediated disease. Histamine antagonism has been in common use to block its adverse effects. With recent advances in the understanding of histamine receptor physiology, pharmaceutical agents targeting these receptors have increased the therapeutic options.  相似文献   

7.
Objective – To review the clinical epidemiologic and pathophysiologic aspects of Hepatozoon americanum infection in dogs.
Data Sources – Data from veterinary literature were reviewed through Medline and CAB as well as manual search of references listed in articles pertaining to American canine hepatozoonosis.
Veterinary Data Synthesis – H. americanum is an emerging disease in endemic areas of the United States. It is vital that practitioners in these areas become familiar with the clinical syndrome of hepatozoonosis and the diagnostic modalities that can be utilized to document the presence of infection. Additionally, veterinarians must understand the epidemiology of the disease in order to better prevent infections in their veterinary patients. Recent data have been published that shed new light on transmission of H. americanum to dogs; however, much remains unknown regarding patterns of infection and the natural vertebrate host source.
Conclusions – While the prognosis for untreated H. americanum remains poor, for patients in which the disease is recognized and properly treated the outcome is favorable. Understanding the complex life cycle, numerous clinical symptoms, and treatment protocol will assist veterinarians who are treating patients with hepatozoonosis.  相似文献   

8.
Objective – To review zinc physiology and pathophysiology and the importance of zinc toxicity and deficiency in veterinary patients.
Data Sources – A review of human and veterinary medical literature.
Human Data Synthesis – There is a significant amount of original research in humans and animals on the role of zinc in multiple organ systems. There is also significant data available on human patients with zinc abnormalities.
Veterinary Data Synthesis – Zinc deficiency has been studied in dogs with genetic disease and dietary deficiency leading to dermatological disease and immune deficiency. Zinc toxicity has been described after ingestion of metallic foreign bodies containing zinc.
Conclusions – Historically, the role of zinc in health and disease has been studied through patients with toxicity or severe deficiency with obvious clinical signs. As the ubiquitous contribution of zinc to structure and function in biological systems was discovered, clinically significant but subtle deficiency states have been revealed. In human medicine, mild zinc deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiency, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accelerated aging, degenerative disease, and more. Determining the causal relationships between mild zinc deficiency and concurrent disease is complicated by the lack of sensitive or specific tests for zinc deficiency. The prevalence of zinc deficiency and its contribution to disease in veterinary patients is not well known. Continued research is warranted to develop more sensitive and specific tests to assess zinc status, to determine which patients are at risk for deficiency, and to optimize supplementation in health and disease.  相似文献   

9.
Pulmonary thromboembolism in dogs: 47 cases (1986-1987)   总被引:4,自引:0,他引:4  
Medical records of 47 dogs with pulmonary thromboembolism were reviewed. Middle-aged to older dogs predominated and dyspnea and arterial hypoxemia were consistent clinical findings. Thoracic radiographic findings were variable. Cardiac disease, neoplasia, hyperadrenocorticism, disseminated intravascular coagulation, and sepsis were identified most frequently. Multiple disease processes were identified in 64% of the dogs.  相似文献   

10.
A high mortality occurs in dogs with idiopathic immune-mediated haemolytic anaemia (IMHA) during the first 2 weeks after the diagnosis. The aim of this study was to investigate the inflammatory response and coagulation abnormalities in dogs with IMHA in relation to the prognosis and to establish the contribution of whole blood tissue factor (TF) and IL-8 gene expressions. Gene expressions in dogs with IMHA were compared to healthy dogs, dogs with DIC, dogs with sepsis, and in two groups of dogs that underwent intensive care treatment but had no evidence for either DIC or sepsis. The whole blood TF and IL-8 expressions were up regulated in all non-IMHA groups. Similarly, the TF expression in IMHA dogs was high, but the intravascular IL-8 expression was not increased. The dogs with IMHA had a pronounced inflammatory response that included a high WBC, left shift and monocytosis in comparison to the other disease groups. Coagulation factor activities in IMHA dogs were decreased fitting consumptive coagulopathy and the acute phase proteins FVIII and fibrinogen were increased. The platelet parameters suggested platelet activation and high platelet turnover in IMHA dogs. The model that best explained mortality contained monocytosis, increased activated partial thromboplastin time and elevated creatinine. Whole blood TF gene expression is up regulated and may contribute to consumptive coagulopathy in dogs with IMHA. Increased TF expression by activated platelets is an alternative explanation and should be investigated.  相似文献   

11.
Tissue factor (TF), a cell surface-associated cofactor and activator of coagulation factor VII, has been implicated in the local and systemic activation of coagulation associated with sepsis. This study describes the pattern of TF expression in experimental bovine pneumonic pasteurellosis and endotoxemia. Immunohistochemical techniques were used to localize TF antigen in tissue sections. Tissue factor expression was not observed in tissues from control animals. In response to Pasteurella haemolytica challenge, TF was expressed within alveolar walls, by mononuclear inflammatory cells within alveoli, and in walls of arteries, arterioles, bronchi, and bronchioles. Tissue factor was not detected in unaffected lung, liver, spleen, lymph node or kidney tissue. Administration of Escherichia coli endotoxin intravenously resulted in tissue factor expression in lung, spleen, and lymph node tissue. Results of this study indicate that TF is expressed locally at sites of inflammation and systemically in endotoxemia. Therefore, TF may be involved in coagulation events associated with pneumonic pasteurellosis.  相似文献   

12.
Objective – To review the human and veterinary literature on the biology of apoptosis in health and disease. Data Sources – Data were examined from the human and veterinary literature identified through Pubmed and references listed in appropriate articles pertaining to apoptosis. Human Data Synthesis – The role of apoptosis in health and disease is a rapidly growing area of research in human medicine. Apoptosis has been identified as a component of human autoimmune diseases, Alzheimer's disease, cancer, and sepsis. Veterinary Data Synthesis – Research data available from the veterinary literature pertaining to apoptosis and its role in diseases of small animal species is still in its infancy. The majority of veterinary studies focus on oncologic therapy. Most of the basic science and human clinical research studies use human blood and tissue samples and murine models. The results from these studies may be applicable to small animal species. Conclusions – Apoptosis is the complex physiologic process of programmed cell death. The pathophysiology of apoptosis and disease is only now being closely evaluated in human medicine. Knowledge of the physiologic mechanisms by which tissues regulate their size and composition is leading researchers to investigate the role of apoptosis in human diseases such as cancer, autoimmune disease and sepsis. Because it is a multifaceted process, apoptosis is difficult to target or manipulate therapeutically. Future studies may reveal methods to regulate or manipulate apoptosis and improve patient outcome.  相似文献   

13.
14.
Coagulation abnormalities are commonly encountered in critical illness. Traditionally, clinically relevant coagulation disorders have consisted mostly of bleeding associated with advanced stages of disseminated intravascular coagulation or toxin ingestion. However, advances in critical care have highlighted hypercoagulability as a clinically relevant state that must be recognized and treated to optimize the chances of a positive outcome. Retrospective studies of dogs with confirmed thrombosis in varying locations have identified populations most likely to experience hypercoagulable states. Diseases most frequently complicated by thrombosis include immune-mediated disease, neoplasia, systemic inflammation and sepsis, cardiac disease, protein-losing states, and infectious diseases. In this report, the existing retrospective studies will be discussed along with a review of specific disease processes that predispose to a hypercoagulable state. Studies targeting those populations most at risk for thrombotic complications are necessary for better understanding the need for prophylactic anticoagulant therapy.  相似文献   

15.
OBJECTIVE: To evaluate risk factors associated with death and development of perioperative complications in dogs undergoing surgery for treatment of gastric dilatation-volvulus (GDV). DESIGN: Retrospective case series. ANIMALS: 166 dogs. PROCEDURES: Records of dogs with confirmed GDV that underwent surgery were reviewed. Logistic regression was performed to identify factors associated with development of complications (ie, hypotension, arrhythmias, gastric necrosis necessitating gastrectomy, disseminated intravascular coagulation, peritonitis, sepsis, postoperative dilatation, postoperative vomiting, and incisional problems) and with short-term outcome (ie, died vs survived to the time of suture removal). RESULTS: Short-term mortality rate was 16.2% (27/166). Risk factors significantly associated with death prior to suture removal were clinical signs for > 6 hours prior to examination, combined splenectomy and partial gastrectomy, hypotension at any time during hospitalization, peritonitis, sepsis, and disseminated intravascular coagulation. Partial gastrectomy was not a significant risk factor for death but was for peritonitis, disseminated intravascular coagulation, sepsis, and arrhythmias. Age, gastrectomy, and disseminated intravascular coagulation were risk factors for development of hypotension. Use of a synthetic colloid or hypertonic saline solution was associated with a significantly decreased risk of hypotension. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the prognosis for dogs undergoing surgery because of GDV is good but that certain factors are associated with an increased risk that dogs will develop perioperative complications or die.  相似文献   

16.
Background – To review the physics of helium with regard to airway physiology, as well as known human and potential veterinary applications of administration of inhaled helium‐oxygen gas‐carrier mixture (heliox). Data Sources – Human and veterinary studies. Human Data Synthesis – Helium‐oxygen mixtures have been used in human medicine for over 70 years as an adjunct therapy in various upper and lower respiratory disorders. Helium's low density promotes laminar flow through partially obstructed airways, resulting in a decreased work of breathing. Veterinary Data Synthesis – Little to no evidence‐based medicine exists to support or oppose the use of heliox in veterinary species. However, domestic animal species and humans share several common pathophysiologic aspects of various obstructive airway disorders. Thus, veterinary patients may also ultimately and significantly benefit from this novel therapy. Conclusion – Prospective studies are needed in veterinary medicine to determine the utility of heliox in clinical scenarios.  相似文献   

17.
Objectives – To review the principles and available technology for pretransfusion testing in veterinary medicine and discuss the indications and importance of test performance before RBC transfusion.
Data Sources – Current human and veterinary medical literature: original research articles and scientific reviews.
Summary – Indications for RBC transfusion in veterinary medicine include severe anemia or tissue hypoxia resulting from blood loss, decreased erythrocyte production, and hemolyzing conditions such as immune-mediated anemia and neonatal isoerythrolysis. Proper blood sample collection, handling, and identification are imperative for high-quality pretransfusion testing. Point-of-care blood typing methods including both typing cards and rapid gel agglutination are readily available for some species. Following blood typing, crossmatching is performed on one or more donor units of appropriate blood type. As an alternative to technically demanding tube crossmatching methods, a point-of-care gel agglutination method has recently become available for use in dogs and cats. Crossmatching reduces the risk of hemolytic transfusion reactions but does not completely eliminate the risk of other types of transfusion reactions in veterinary patients, and for this reason, all transfusion reactions should be appropriately documented and investigated.
Conclusion – The administration of blood products is a resource-intensive function of veterinary medicine and optimizing patient safety in transfusion medicine is multifaceted. Adverse reactions can be life threatening. Appropriate donor screening and collection combined with pretransfusion testing decreases the occurrence of incompatible transfusion reactions.  相似文献   

18.
Plasma fibronectin concentrations were significantly (P less than 0.001) below the reference range in dogs with disseminated intravascular coagulation (DIC) secondary to nonlymphomatous neoplasia, acute necrotizing pancreatitis, sepsis, chronic active hepatitis, and heat stroke. There was no statistical evidence of a group effect. Decrease in fibronectin concentration was associated with severe DIC, although no attempt was made to correlate fibronectin concentration with prognosis. These findings parallel those reported for severely ill human beings with diseases associated with DIC. They exemplify the potential of spontaneous diseases in animals as models for the study of human disease.  相似文献   

19.
Objective – To describe a severe case of bacterial sepsis and disseminated candidiasis in a previously healthy dog.
Case Summary – Fungal sepsis was identified in a 2-year-old dog following intestinal dehiscence 4 days after abdominal surgery. Septic peritonitis was identified at admission and evidence of dehiscence at the previous enterotomy site was found during an exploratory laparotomy. Both gram-positive cocci and Candida albicans were cultured from the abdominal cavity. Candida sp. was also subsequently cultured from a central venous catheter. Euthanasia was performed due to failure to respond to therapy. Fungal organisms, morphologically consistent with Candida spp., were found in the lungs and kidney on postmortem histopathologic examination indicating disseminated candidiasis.
New or Unique Information Provided – Candida peritonitis is a well-recognized entity in humans and contributes to morbidity and mortality in critically ill patients. Abdominal surgery, intestinal perforation, presence of central venous catheters, and administration of broad-spectrum antibiotics are all considered to be suspected risk factors. This report describes the first known case of systemic candidiasis occurring secondary to Candida peritonitis and bacterial sepsis in a critically ill dog.  相似文献   

20.
Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression of the tumours was evaluated by immunohistochemistry using a polyclonal antibody against recombinant canine TF. In addition, thromboelastography, haemostatic and inflammatory parameters were evaluated in the patients. TF was recognized in 44% of benign and 58% of malignant tumours. TF localized to the cytoplasmic membrane of neoplastic luminal epithelial cells and/or diffusely in the cytoplasm. No association was found between TF expression and stage or grade of disease. A significant association between TF expression and antithrombin and plasminogen was found, and extensive TF expression was seen in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC).  相似文献   

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