Interleukin-2 (IL-2) amplifies immune stimuli and influences B cell differentiation. IL-2-deficient mice spontaneously develop intestinal inflammation if raised under specific pathogen-free (SPF) conditions. We quantitatively determined the aggressiveness and kinetics of gastrointestinal and hepatic inflammation in the presence or absence of viable bacteria in IL-2-deficient mice. Breeding colonies were maintained under SPF and germfree (GF) conditions. Intestinal tissues, serum, and mesenteric lymph nodes were obtained from mice at different ages for blind histological scoring, immunoglobulin measurements, mucosal T cell infiltration, and cytokine secretion. GF IL-2 −/− mice developed mild, focal, and nonlethal intestinal inflammation with delayed onset, whereas the more aggressive inflammation in SPF IL-2 −/− mice led to their death between 28 and 32 wk. Periportal hepatic inflammation was equal in the presence or absence of bacterial colonization. Intestinal immunoglobulin secretion decreased significantly by 13 wk of age in IL-2 −/− mice in both GF and SPF environments. In contrast to other genetically engineered rodents, IL-2 −/− mice develop mild focal gastrointestinal and active portal tract inflammation in the absence of viable bacteria.
Leukoreduction of blood products is a technique used to prevent leukocyte-induced transfusion reactions. Filters currently used for human blood products achieve at least a 99.9% reduction in leukocyte numbers per unit (450 mL) of blood. Goals of this study were to determine if a prestorage leukoreduction filter could effectively achieve leukoreduction of canine blood and to determine if viability of the leukoreduced red blood cell (RBC) product could be maintained after 35 days of storage. Blood collected from each dog was filtered through a leukoreduction filter at either room temperature or after cooling (4ЊC) for 4 hours. Filtration efficacy was determined by measurement of pre-and postfiltration leukocyte counts. In vitro viability of RBCs was determined by comparing RBC adenosine triphosphate concentration and percent hemolysis before and after the storage period. In vivo viability of stored cells was determined using a biotin-streptavidin-phycoerythrin labeling technique and flow cytometry. Blood filtered within 30 minutes of collection versus blood filtered after cooling had mean reductions in leukocyte numbers of 88.90 and 99.99%, respectively. The mean ATP and hemoglobin concentrations from the in vitro analysis were comparable to those obtained in previously for canine RBC adequately stored for 35 days. The mean in vivo 24-hour survival of the stored RBC was 84.7%. The leukoreduction filter used did not adversely affect in vitro or in vivo viability of canine RBCs. The filter effectively removed leukocytes from blood, with maximal efficiency of filtration achieved with use of cooled blood.
Background: Metronomic chemotherapy with alkylating agents has been shown to suppress tumor angiogenesis and prevent tumor recurrence in some settings. The use of adjuvant lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) administered in a metronomic fashion has not been evaluated in dogs.Hypothesis: Oral metronomic administration of lomustine will be well tolerated in dogs with spontaneously occurring malignant neoplasms.Animals: Eighty-one dogs with naturally occurring primary or metastatic tumors received metronomic administration of lomustine.Methods: Dogs were enrolled prospectively after cytological or histological diagnosis of a tumor that was unresectable, incompletely resected, refractory to chemotherapy, or metastatic. Dogs received once daily lomustine (2.84 mg/m 2 PO). End points of the trial were clinical, hematologic, or biochemical evidence of toxicosis, tumor progression, or death.Results: Starting dosage (median) was 2.84 mg/m 2 PO daily and treatment duration was 98 days (median, range, 1-770 days). The drug was discontinued in 22 dogs because of toxicoses. Toxicoses occurred in 13 dogs with gastrointestinal toxicosis, 4 dogs with thrombocytopenia, 3 dogs with increased alanine transaminase, 1 dog with neutropenia, and 1 dog with progressive azotemia. Eight dogs developed some degree of azotemia during treatment. Hepatotoxicosis was observed at a median of 265 days in 11 dogs. Thrombocytopenia was identified at a median of 432 days of administration.Conclusions and Clinical Importance: In dogs with metastatic or terminal neoplasms without renal compromise, metronomic administration of lomustine was well tolerated. This can provide a treatment strategy for dogs that do not have other standard-care treatment options, and warrants evaluation in primary therapy.
Systemic arterial dirofilariasis is an unusual manifestation of heartworm disease of dogs that results from aberrant migration of Dirofilaria immitis into the peripheral arterial circulation. To expand the clinical characterization of systemic arterial dirofilariasis, 5 dogs evaluated at the North Carolina State University's College of Veterinary Medicine were reviewed. Common clinical presentations included hindlimb lameness, paresthesia of hindlimbs, and interdigital ischemic necrosis resulting from thromboembolic disease. Visualization of heartworms with angiography or ultrasonography confirmed the diagnosis in all cases. All 5 eartwonn disease of dogs typically is manifested by H the presence of heartworms in the pulmonary artery and, to a lesser degree, the right ventricle. Adult heartworms also have been documented in the cranial and caudal vena cavae and right atrium in the case of caval syndrome.' Aberrant migration of adult worms into numerous tissues, including the brain, spinal cord, epidural space, anterior chamber, vitreous, peritoneal cavity, and subcutis, and the femoral arteries also has been reported."* Systemic arterial dirofilariasis is an unusual clinical entity that occurs as a result of an aberrant migration or development of adult L5 heartworms within the systemic arterial circulation. In one report, a dog with encephalitis and ischemic myositis had adult heartworms in its femoral arteries on postmortem examination.' Stuart et a]' also described a case of ischemic myopathy caused by the presence of adult heartworms and thromboses in the aorta and iliac arteries.To understand and define better the syndrome of systemic arterial dirofilariasis, we examined the clinical presentation and disease course in 5 dogs with documented systemic arterial dirofilariasis evaluated at North Carolina State University's College of Veterinary Medicine. Two dogs were seen between September and December 1994. Three dogs seen between 1986 and 1994 were identified in a search of the hospital medical records; case summaries were compiled from the medical records of these 3 cases. Case Studies Dog 1A 6-year-old, intxt male German Shepherd cross was examined for a 1-month history of a non-weight-bearing lameness of the right hindleg and paresthesia of both hind paws manifested as excessive licking and chewing of the digits. A cough of several months' duration had been noted by the owner. Abnormalities on physical examination included lethargy, exercise intolerance, and underweight body condition. Severe interdigital necrosis on the plantar surface of the right hindfoot resulted in exposure of the flexor tendons and metatarsal bones and concurrent sloughing of the metatarsal pads. Mild interdigital ulceration was present between the second and third digits on the left hindfoot. Peripheral perfusion in the right hindlimb was markedly decreased, as evidenced by a weak femoral pulse, cool extremities, and cyanotic nailbeds. Conscious proprioceptive deficits had been noted in the right hindleg by the referring veterinari...
Leukoreduction of blood products is a technique used to prevent leukocyte-induced transfusion reactions. Filters currently used for human blood products achieve at least a 99.9% reduction in leukocyte numbers per unit (450 mL) of blood. Goals of this study were to determine if a prestorage leukoreduction filter could effectively achieve leukoreduction of canine blood and to determine if viability of the leukoreduced red blood cell (RBC) product could be maintained after 35 days of storage. Blood collected from each dog was filtered through a leukoreduction filter at either room temperature or after cooling (4C) for 4 hours. Filtration efficacy was determined by measurement of pre-and postfiltration leukocyte counts. In vitro viability of RBCs was determined by comparing RBC adenosine triphosphate concentration and percent hemolysis before and after the storage period. In vivo viability of stored cells was determined using a biotin-streptavidin-phycoerythrin labeling technique and flow cytometry. Blood filtered within 30 minutes of collection versus blood filtered after cooling had mean reductions in leukocyte numbers of 88.90 and 99.99%, respectively. The mean ATP and hemoglobin concentrations from the in vitro analysis were comparable to those obtained in previously for canine RBC adequately stored for 35 days. The mean in vivo 24-hour survival of the stored RBC was 84.7%. The leukoreduction filter used did not adversely affect in vitro or in vivo viability of canine RBCs. The filter effectively removed leukocytes from blood, with maximal efficiency of filtration achieved with use of cooled blood.
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