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Biomedical subjects

A J Cooley

Publications and source records attributed to A J Cooley.

At least 19 recordsLinked to original sources

Leucocytoclastic vasculitis associated with Staphylococcus intermedius in the pastern of a horse.

A pregnant quarterhorse mare became acutely lame as a result of severe swelling of its right hind leg, thought to have been caused by a fracture or a muscle tear. Diagnostic procedures ruled out a traumatic musculoskeletal cause and a physical examination revealed chronic pastern dermatitis ('scratches'/'grease heel'). Histopathological evaluation of biopsy samples from the right hind leg was consistent with a leucocytoclastic vasculitis, and culture yielded Staphylococcus intermedius. The treatment and infectious causes of pastern dermatitis are discussed.

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Congenital hepatoblastoma in a neonatal alpaca cria.

A neonatal alpaca cria found to have minimal clinical abnormalities was diagnosed postmortem with an epithelial-type hepatoblastoma with combined embryonal and fetal patterns, based on previously reported morphological features. Camelid neoplasia and domestic animal hepatoblastomas are very rare, with only a single case of congenital hepatoblastoma in a domestic animal previously reported.

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The biologic response to laser thermal modification in an in vivo sheep model.

The purpose of this study was to evaluate the effect of nonablative laser energy on mechanical, histologic, ultrastructural, and biochemical properties of joint capsular tissue in an in vivo sheep model. Femoropatellar joint capsule was treated with the holmium:yttrium-aluminum-garnet laser via an arthroscope, and tissues were harvested immediately after surgery, or at 3, 7, 14, 30, 60, 90, and 180 days after surgery (n = 8/group). Laser treatment caused significant decreases in tissue stiffness from 0 to 7 days after surgery, then stiffness gradually increased after 14 days. Tissue strength was lowest 3 days after laser treatment. Histologic examination revealed immediate collagen hyalinization and cell necrosis, followed by active cellular response characterized by extensive fibroblast migration and capillary sprouting. Tissue appeared to be normal histologically 60 days after surgery; however, collagen fibrils remained uniformly small. This study showed an active tissue response secondary to thermal modification with concomitant recovery of mechanical properties by 30 days after surgery. Whether the shrinkage or joint stability was maintained with time remains to be evaluated. To clarify the advantages and disadvantages of this technique, a carefully controlled clinical trial with long term followup should be performed.

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Massive Dracunculus insignis infection in a dog.

An 11-year-old 13-kg (28.6-lb) spayed female Cocker Spaniel was examined because of subcutaneous nodules on the hind limbs and ventral aspects of the thorax and abdomen. Focal areas of erythema and pyoderma were associated with the nodules, and purulent exudate could be expressed from a fistula in the nodules. A nematode approximately 20.5 cm in length was isolated from a draining fistula in 1 nodule and identified as Dracunculus insignis. The dog was treated with ivermectin, fenbendazole, and metronidazole, but the owner was still able to recover worms from multiple nodules for the next year.

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Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong.

An H5N1 avian influenza A virus was transmitted to humans in Hong Kong in 1997. Although the virus causes systemic infection and is highly lethal in chickens because of the susceptibility of the hemagglutinin to furin and PC6 proteases, it is not known whether it also causes systemic infection in humans. The clinical outcomes of infection in Hong Kong residents ranged widely, from mild respiratory disease to multiple organ failure leading to death. Therefore, to understand the pathogenesis of influenza due to these H5N1 isolates, we investigated their virulence in mice. The results identified two distinct groups of viruses: group 1, for which the dose lethal for 50% of mice (MLD50) was between 0.3 and 11 PFU, and group 2, for which the MLD50 was more than 10(3) PFU. One day after intranasal inoculation of mice with 100 PFU of group 1 viruses, the virus titer in lungs was 10(7) PFU/g or 3 log units higher than that for group 2 viruses. Both types of viruses had replicated to high titers (>10(6) PFU/g) in the lungs by day 3 and maintained these titers through day 6. More importantly, only the group 1 viruses caused systemic infection, replicating in nonrespiratory organs, including the brain. Immunohistochemical analysis demonstrated the replication of a group 1 virus in brain neurons and glial cells and in cardiac myofibers. Phylogenetic analysis of all viral genes showed that both groups of Hong Kong H5N1 viruses had formed a lineage distinct from those of other viruses and that genetic reassortment between H5N1 and H1 or H3 human viruses had not occurred. Since mice and humans harbor both the furin and the PC6 proteases, we suggest that the virulence mechanism responsible for the lethality of influenza viruses in birds also operates in mammalian hosts. The failure of some H5N1 viruses to produce systemic infection in our model indicates that multiple, still-to-be-identified, factors contribute to the severity of H5N1 infection in mammals. In addition, the ability of these viruses to produce systemic infection in mice and the clear differences in pathogenicity among the isolates studied here indicate that this system provides a useful model for studying the pathogenesis of avian influenza virus infection in mammals.

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Orbital lymphosarcoma associated with reticuloendotheliosis virus in a peafowl.

Lymphosarcoma associated with infection by avian reticuloendotheliosis virus was diagnosed in an Indian peafowl with exophthalmia and exposure keratitis. Exenteration of the orbit was complicated by a profound oculocardiac reflex and extensive hemorrhage during surgery. Orbital bleeding was controlled by direct pressure, electrocautery, topical administration of bovine thrombin, and application of sterile gelatin sponges and oxidized regenerated cellulose. A blood transfusion was also performed. In addition to describing methods of handling intraoperative complications of orbital exenteration in birds, to the authors' knowledge, this is the first report to describe an association of reticuloendotheliosis virus, which more commonly affects poultry, with lymphosarcoma in an Indian peafowl.

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Efficacy of pyridoxine to ameliorate the cutaneous toxicity associated with doxorubicin containing pegylated (Stealth) liposomes: a randomized, double-blind clinical trial using a canine model.

A cutaneous reaction termed palmar-plantar erythrodysesthesia (PPES) or hand-foot syndrome can be dose limiting for Doxil, a doxorubicin containing pegylated (Stealth) liposome. The objective of this study was to determine the ability of concomitant pyridoxine therapy to prevent the development of PPES during Doxil therapy. Forty-one dogs with non-Hodgkin's lymphoma were randomized in a double-blind fashion to receive either oral pyridoxine or placebo daily during Doxil chemotherapy (1.0 mg/kg, i.v., every 3 weeks for a total of five treatments). Cutaneous toxicity was determined by clinical and histological scoring. No difference was observed in remission rates (71.4 versus 75%) achieved between groups. The likelihood of developing serious PPES and having to decrease or discontinue Doxil therapy was 4.2 times (relative risk) greater in placebo group dogs than in pyridoxine group dogs (P = 0.032). Pyridoxine did not completely abrogate PPES; however, it occurred later and less dramatically than in placebo-treated dogs and resulted in fewer treatment delays or discontinuations, allowing a higher cumulative dose of Doxil to be received. Compared to the 5.0 mg/kg cumulative target dose, pyridoxine-treated dogs received a median cumulative dose of 4.7 mg/kg (mean, 4.1 mg/kg), and the placebo-treated dogs received a median of 2.75 mg/kg (mean, 2.9 mg/kg; P < 0.028). A trend (P = 0.084) toward prolongation of remission length was observed in dogs receiving pyridoxine, which was likely attributable to their ability to receive more Doxil without delay or discontinuation. We conclude that pyridoxine is effective in delaying the onset and severity of PPES in this canine model.

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Effect of nonablative laser energy on the joint capsule: an in vivo rabbit study using a holmium:YAG laser.

BACKGROUND AND OBJECTIVE: The nonablative application of holmium:yttrium-aluminum-garnet (Ho:YAG) laser energy to the joint capsule of patients with glenohumeral instability has been found to shrink capsular tissue and to help stabilize the joint. The purpose of this study was to evaluate the effect of nonablative laser energy on the short-term histological properties of joint capsular tissue in an in vivo rabbit model. STUDY DESIGN/MATERIALS AND METHODS: Eighteen mature New Zealand white rabbits were used in this study. One randomly selected stifle was treated with laser energy, and the contralateral stifle was sham-operated. Animals were euthanized immediately after surgery (day 0), at 7 days postsurgery and 30 days postsurgery. Specimens were processed for histology and transmission electron microscopy. RESULTS: Laser-treated samples at day 0 showed diffuse hyalinization of collagen with nuclear karyorrhexis of fibroblasts. Laser-treated tissue at 7 days postsurgery revealed fibroblast proliferation around and into acellular hyalinized regions of collagen. At 30 days postlaser treatment, areas of fused collagen were greatly reduced as large reactive fibroblasts migrated and secreted matrix. CONCLUSION: This study illustrates the short-term in vivo tissue response to nonablative laser treatment, where acellular hyalinized regions of collagen are infiltrated by fibroblasts that have used the treated collagen as the framework for migration and secretion of new collagen matrix in order for tissue repair to proceed.

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Preclinical trial of doxorubicin entrapped in sterically stabilized liposomes in dogs with spontaneously arising malignant tumors.

PURPOSE: To prospectively evaluate the short-term toxicoses associated with pegylated-liposomal doxorubicin (Doxil) administered to dogs with measurable tumors of various histologic types and sites. Preliminary information regarding efficacy was also generated. METHODS: A group of 51 dogs with histologically confirmed malignancies received a total of 103 Doxil treatments given i.v. every 3 weeks at dosages ranging from 0.75 to 1.1 mg/kg in the context of a phase I dose-escalation trial. Acute and short-term toxicities as well as tumor response and duration of response were characterized. RESULTS: The maximally tolerated dose in tumor-bearing dogs was established as 1.0 mg/kg i.v. every 3 weeks. The dose-limiting toxicity was a cutaneous toxicity clinically resembling palmar-plantar erythrodysesthesia (PPES). An overall response rate of 25.5% was observed with five complete responders and eight partial responders. CONCLUSIONS: Doxil appeared to be well tolerated at dosages similar to those tolerated for free doxorubicin in tumor-bearing dogs. PPES was the dose-limiting toxicity encountered, rather than myelosuppresion as is the case with free doxorubicin in dogs. Doxil as a single agent may have a broad spectrum of activity and deserves further evaluation.

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Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria.

We determined the requirement for selected lymphocyte subsets and cytokines in the pathogenesis of experimental murine cerebral malaria (CM) by using gene-targeted knockout and mAb-suppressed mice. Plasmodium berghei ANKA infection induced CM in A 0/0 mice, which lack expression of surface MHC class II glycoproteins and consequently express a severe and chronic reduction in numbers of CD4+ T cells. However, when A 0/0 mice, which are on a C57BL/6 x 129 genetic background, or immune-intact C57BL/6 controls treated with anti-CD4 mAb were infected, none developed CM. The latter finding confirms an earlier report that CD4+ T cells are required for CM to occur and additionally indicates that the reduced numbers of CD4+ T cells present in A 0/0 mice are sufficient for CM development. Neither the recently described CD4+, NK1.1+ T cell subset shown to be present in A 0/0 mice nor traditional NK cells seem to be required for the induction of CM because A 0/0 and C57BL/6 mice severely depleted of both NK1.1+ populations with mAb developed CM as readily as did normal Ig-treated controls. Deficiency of Th1-associated cytokines (IFN-gamma or IL-2) in mice by gene-targeted disruptions completely inhibited CM development, whereas the lack of Th2-associated cytokines (IL-4 or IL-10) did not prevent this disease. Our observation that B cell-deficient JHD and microMT mice developed CM provides evidence that neither B cells, their products, nor B cell Ag presentation are a requisite for CM pathology. We further observed that neither beta 2m 0/0 knockout mice, which lack CD8+ alpha beta T cells, nor C57BL/6 mice depleted of CD8+ T cells with anti-CD8 mAb treatment developed CM, leading us to conclude that CD8+ T cells are also crucial for the development of CM.

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Laparoscopic methods for castration of equids.

OBJECTIVE: To evaluate 2 laparoscopic techniques for castration of horses. DESIGN: Prospective, randomized trial. ANIMALS: 6 sexually intact male ponies. PROCEDURE: Ponies were anesthetized and placed in dorsal recumbency. By means of restricted randomization, 1 testis in each pony was selected to undergo in situ destruction (i.e., vascular cauterization and ligation with the testis left in situ); the other testis was pulled back into the abdomen and removed. Baseline and stimulated testosterone concentrations were determined preoperatively and postoperatively. After euthanasia, the in situ testes were examined histologically. RESULTS: There were no surgical complications. In all ponies, postoperative baseline and stimulated testosterone concentrations were consistent with castration. The testicular parenchyma of the testes that had been left in situ underwent coagulative necrosis. CLINICAL IMPLICATIONS: In ponies and juvenile stallions, normally descended testes can be removed laparoscopically. Nonpalpable inguinal testes can be left in situ after laparoscopically ligating and transecting the testicular artery and vein. Additional experience with these approaches is necessary before their use can be recommended in mature stallions.

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Zygomatic osteoma with atypical heterogeneity in a dog.

An osteoma of the zygomatic bone in a young dog is described. It had large, centralized radiolucent regions consisting of fatty bone marrow and sparse trabeculae. A discrete, proliferative nodule within the osteoma consisted of closely-packed woven bone trabeculae and pleomorphic osteoblasts associated with haphazard osteoid deposits, resembling osteosarcoma-like change. These heterogeneous structural features were at variance with more classic reports of osteoma, which usually describe a uniform cancellous or cortical bone architecture.

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SK&F 86002, a dual cytokine and eicosanoid inhibitor, attenuates endotoxin-induced cardiopulmonary dysfunction in the pig.

Cytokines and eicosanoids are well documented important mediators of endotoxemia. Bicyclic imidazoles are a novel class of nonsteroidal anti-inflammatory compounds that display unique pharmacological profiles by reducing cytokine production and arachidonic acid metabolism. In this study, we evaluated the ability of the bicyclic imidazole, SK&F 86002, to attenuate endotoxin-induced cardiopulmonary dysfunction. Pigs were randomly assigned to one of four groups: LPS (n = 5), given .5 microgram/kg/h 055:B5 Escherichia coli lipopolysaccharide (LPS) intravenously (i.v.) for 6 h; saline (n = 5); SK&F 86002 (n = 3), given 50 mg/kg SK&F 86002 orally 30 min prior to anesthesia; and SK&F 86002 + LPS (n = 5). Administration of LPS resulted in cardiopulmonary dysfunction characterized by decreased stroke volume and arterial oxygen tension, and increased room air alveolar-arterial oxygen gradient, pulmonary arterial pressure, pulmonary vascular resistance, and peak intratracheal pressure. Additionally, LPS administration was associated with leukopenia and increased pulmonary myeloperoxidase activity. Pretreatment with SK&F 86002 attenuated LPS induced hypotension, hypoxemia and bronchoconstriction and blocked the pulmonary hypertension. SK&F 86002 blocked the LPS-induced increase in myeloperoxidase activity, indicating a reduction in pulmonary neutrophil infiltration, but had no effect on systemic leukopenia. Pretreatment with SK&F 86002 significantly attenuated LPS-induced increases in plasma thromboxane B2 and tumor necrosis factor-alpha. We hypothesize that ameliorating effects of SK&F 86002 in this endotoxin model of cardiopulmonary dysfunction are related to inhibition of cytokine and eicosanoid biosynthesis.

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