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Biomedical subjects

D W Hayden

Publications and source records attributed to D W Hayden.

At least 19 recordsLinked to original sources

Comparison of histopathologic criteria and skeletal muscle fixation techniques for the diagnosis of polysaccharide storage myopathy in horses.

The purpose of the study reported here was to determine the effect of three methods of fixation of skeletal muscle biopsy specimens on the histopathologic appearance of muscle sections and to determine criteria that were most consistently associated with a diagnosis of polysaccharide storage myopathy (PSSM) in horses. Surgically excised semimembranosus muscle biopsy specimens were obtained from nine horses previously diagnosed with PSSM and from 15 control horses. Portions of each specimen were fixed in formalin, frozen immediately, and chilled for 24 hours prior to freezing. Sections stained with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and amylase-PAS were scored for histopathologic criteria by three investigators blinded to the sample origin. The presence of amylase-resistant, abnormal polysaccharide was found to be the most sensitive and specific diagnostic indicator for PSSM, and was readily detected regardless of the fixation technique or investigator. Other less-specific features associated with PSSM included atrophy and cytoplasmic and subsarcolemmal vacuoles; however, their histologic scores varied among fixation technique and investigators. Scores for subsarcolemmal and cytoplasmic amylase-sensitive glycogen in horses with PSSM were similar to those for control horses and varied among fixation techniques. In conclusion, PSSM is most accurately diagnosed in muscle biopsy specimens on the basis of appearance of amylase-resistant, abnormal polysaccharide, not amylase-sensitive glycogen, regardless of fixation technique. In general, frozen sections appeared to be better suited for studying myopathies because many histopathologic features of skeletal muscle were obscured by formalin fixation.

Animals↗

Natural infection of a horse with Fascioloides magna.

A 25-year-old Quarterhorse mare was euthanized for a variety of medical reasons. At necropsy, 7 liver flukes, identified as Fascioloides magna, were recovered from the liver. This is the first report of F. magna in a horse.

Animals↗

Putative metronidazole neurotoxicosis in a cat.

A presumptive case of metronidazole toxicity in a 3.4-kg adult cat is described. The cat had been treated for suspected inflammatory bowel disease with an anti-inflammatory dose of prednisone and metronidazole (73.5-147 mg/kg PO q24h) for approximately 40 days prior to presentation. Clinical signs were primarily related to the central nervous system, including acute tetraparesis, unresponsiveness, tremors, and vocalization. The patient was euthanatized after 12 days of supportive care. Necropsy revealed no significant macroscopic lesions. Histologic evaluation revealed multifocal, fairly well-demarcated foci of necrosis in the brainstem, extending from the diencephalon to the medulla oblongata. To our knowledge, this is the first report to document histologic lesions associated with metronidazole administration in a cat.

Animals↗

Hepatoblastoma with erythrocytosis in a young female horse.

A 2.5-year-old female Thoroughbred was examined because of lethargy, anorexia, and weight loss. Analysis of a CBC revealed erythrocytosis and an increase in PCV. Serum biochemical analysis revealed increases in activities of several hepatic enzymes. Ultrasonography revealed hepatomegaly and a heterogeneous appearance of the hepatic parenchyma. The horse did not improve despite supportive care, and it was euthanatized. Necropsy revealed numerous raised white to gray foci in the liver. Histologically, these foci consisted of neoplastic cells that resembled fetal hepatocytes, embryonal-type cells, and cells with features intermediate between those 2 cell types. Immunohistochemical staining revealed that hepatocytes stained strongly with anti-alpha-fetoprotein. On the basis of these results, hepatoblastoma was diagnosed. Diagnosis of hepatoblastoma is difficult, because it can appear histologically similar to other hepatic tumors, such as hepatocellular carcinomas. Definitive diagnosis requires histologic evaluation of tumor architecture and cell morphology. Immunohistochemical staining for alpha-fetoprotein in tumor cells may serve as a tumor marker but is not pathognomonic of hepatoblastoma. Paraneoplastic syndromes, such as erythrocytosis, can accompany hepatoblastoma. The prognosis for horses with hepatoblastoma is grave.

Animals↗

Randomized controlled trial of doxorubicin versus dactinomycin in a multiagent protocol for treatment of dogs with malignant lymphoma.

OBJECTIVE: To compare efficacy and toxicity of 2 multiagent chemotherapeutic protocols similar in all respects except that 1 incorporated dactinomycin and the other incorporated doxorubicin for treatment of dogs with malignant lymphoma. DESIGN: Randomized controlled trial. ANIMALS: 45 dogs with malignant lymphoma. PROCEDURE: Dogs were randomly assigned to a doxorubicin or dactinomycin treatment group. Time to first remission, duration of first remission, survival time, and prevalence of toxicoses, particularly number of episodes of dose-limiting neutropenia and gastrointestinal toxicoses, were compared between groups. RESULTS: 37 dogs received at least 1 dose of doxorubicin (21 dogs) or dactinomycin (16). Median time to first remission was not significantly different between groups, but median duration of first remission and median survival time were significantly longer for dogs in the doxorubicin treatment group than for dogs in the dactinomycin treatment group. Number of dogs that died, number of episodes of dose-limiting neutropenia, and number of episodes of gastrointestinal toxicoses were not significantly different between groups. CLINICAL IMPLICATIONS: A multiagent chemotherapeutic protocol incorporating doxorubicin was significantly more effective in dogs with malignant lymphoma than a similar protocol incorporating dactinomycin. Despite the lower cost and lack of cardiotoxicity, dactinomycin is not an equivalent substitute for doxorubicin in the initial treatment of dogs with malignant lymphoma.

Animals↗

Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer.

Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. The prevalence and immunophenotype of PIN in dogs with spontaneous prostate cancer has not been previously described. To investigate the association between PIN and prostate cancer, we evaluated the prostates of dogs with spontaneous prostate carcinoma. The prevalence of PIN was determined in formalin-fixed prostates from 29 dogs with spontaneous prostate cancer. Using immunoperoxidase techniques, we compared basal cell layer integrity (high molecular weight keratin 34 beta-E12), proliferative index (MIB-1), and microvessel density (Factor VIII-related antigen) in 14 prostates which contained benign epithelium, PIN, and carcinoma. PIN was present in 19 of 29 (66%) prostates from dogs with spontaneous prostate cancer. The basal cell layer was intact in benign epithelium, disrupted in 72% of acini with PIN, and absent in carcinoma. The mean proliferative index was 17%, 25%, and 40% for benign epithelium, PIN, and carcinoma, respectively, and these differences were significant. The mean microvessel density in foci of PIN and carcinoma (32 and 39 vessels per mm2, respectively) was greater than in benign epithelium (23 vessels per mm2). High-grade PIN is common in the prostates of dogs with spontaneous carcinoma. The basal cell layer is partially disrupted in PIN, whereas it is absent in prostate cancer. The proliferative index and microvessel density of PIN are intermediate between benign epithelium and cancer. These results are similar to those reported for human PIN and prostate cancer, and indicate that PIN is part of a morphologic continuum in the progression of prostate cancer. To our knowledge, this is the first description of high-grade PIN spontaneously occurring in animals. The canine prostate may serve as a useful model for examining factors that modulate PIN and prostate cancer progression.

Animals↗

Acquired B lymphocyte deficiency and chronic enterocolitis in a 3-year-old quarter horse.

This case report describes a 3-year-old American Quarter Horse with acquired immunodeficiency. Clinical signs included chronic diarrhea due to Salmonella typhimurium and bacterial pneumonia. Characterization of the immunodeficiency involved in vivo phytohemagglutinin (PHA) intradermal testing, in vitro lymphocyte proliferation in response to concanavalin A, immunofluorescence flow cytometry data on blood lymphocytes, serum protein electrophoresis and immunoglobulin (Ig) quantification. A diagnosis of B lymphocyte deficiency with resulting deficiencies in serum IgG, IgA and IgM and a concurrent decrease in T cell function was made based on these tests. Postmortem examination revealed no evidence of lymphosarcoma. This case represents a variation of young adult-onset B cell deficiency not previously described in the literature.

Animals↗

Apolipoprotein AI-derived pulmonary vascular amyloid in aged dogs.

Our studies confirm the common occurrence of a unique form of apolipoprotein AI (apoAI)-derived vascular amyloidosis in dogs that appears to be unrelated to other disease conditions, but is associated with aging. Vascular amyloid deposits were most frequently located within the intima and media of medium-sized pulmonary arteries, and were not confirmed in any other tissues. Pulmonary vascular amyloid immunoreactive with antiserum to purified N-terminal (1-71) canine apoAI amyloid protein was demonstrated retrospectively in 12.8% of necropsied dogs (N = 243) 10 years of age or older. In a subsequent expanded 1-year prospective study of necropsied dogs (N = 231) of all ages, apoAI-derived pulmonary vascular amyloid deposits were demonstrated in 0.7% of dogs < 10 years of age and in 22% of dogs 10 years of age or older. The incidence of this form of amyloid in dogs 10 years of age or older was significantly associated with advancing age (P < 0.00001). However, significant differences regarding gender, breed, or the frequency of selected common disease conditions were not observed when the dogs with apoAI-derived amyloid were compared with control dogs. The possibility that this new form of senile apoAI-derived amyloidosis is a manifestation of an age-associated aberration in apoAI metabolism or is related to a mutant form of apoAI is the subject of ongoing investigations.

Aging↗

The mechanism of force generation in myosin: a disorder-to-order transition, coupled to internal structural changes.

We propose a molecular mechanism of force generation in muscle, based primarily on site-specific spectroscopic probe studies of myosin heads in contracting muscle fibers and myofibrils. Electron paramagnetic resonance (EPR) and time-resolved phosphorescence anisotropy (TPA) of probes attached to SH1 (Cys 707, in the catalytic domain of the head) have consistently shown that most myosin heads in contracting muscle are dynamically disordered, undergoing large-amplitude rotations in the microsecond time range. Some of these disordered heads are bound to actin, especially in the early (weak-binding, preforce) phase of the ATPase cycle. The small ordered population (10-20%) is rigidly oriented precisely as in rigor, with no other distinct angle observed in contraction or in the presence of intermediate states trapped by nucleotide analogs. These results are not consistent with the classical model in which the entire head undergoes a 45 degree transition between two distinct orientations. Therefore, it has been proposed that the catalytic domain of the myosin head has only one stereospecific (rigor-like) actin-binding angle, and that the head's internal structure changes during force generation, causing the distal light-chain-binding domain to rotate. To test this model, we have performed EPR and TPA studies of probes attached to regulatory light chains (RLCs) in rabbit and scallop myofibrils and fibers. The RLC results confirm the predominance of dynamic (microsecond) rotational disorder in both relaxation and contraction, and show that the different mechanisms of calcium regulation in the two muscles produce different rotational dynamics. In rabbit myofibrils, RLC probes are more dynamically disordered than SH1 probes, especially in rigor and contraction,indicating that the light-chain-binding domain undergoes rotational motions relative to the catalytic domain when myosin heads interact with actin. An SH1-bound spin label, which is sensitive to myosin's internal dynamics, resolves three distinct conformations during contraction, and time-resolved EPR shows that these transitions are coupled to specific steps in the ATPase cycle. We propose that force is generated during contraction by a disorder-to-order transition, in which myosin heads first attach weakly to actin in a nonstereospecific mode characterized by large-scale dynamic disorder, then undergo at least two conformational transitions involving large-scale structural (rotational) changes within the head, culminating in a highly ordered strong-binding state that bears force.

Adenosine Triphosphate↗

Disseminated malignant histiocytosis in a golden retriever: clinicopathologic, ultrastructural, and immunohistochemical findings.

Diagnosis of malignant histiocytosis (MH), a disorder characterized by systemic proliferation of morphologically atypical histiocytes and their precursors, in an 8-year-old neutered female Golden Retriever was based on light and electron microscopic and immunohistochemical findings. Clinically, the dog presented with unilateral forelimb lameness. Eight days after surgical exploration of a swollen brachium, the dog developed sudden onset of posterior paresis, fecal and urinary incontinence, and a flaccid tail. Necropsy revealed infiltrative and nodular lesions in the right forelimb and regional lymph nodes, thoracic and abdominal cavities, and lumbar epidural space. Gross lesions were not found in the lungs or integument. Histopathologic examination showed infiltrates of atypical histiocytes in skeletal muscle, joint, and regional lymph nodes of the right forelimb; intercostal muscle; lung; liver; spleen; pancreas; kidneys; and spinal dura. Most tumor infiltrates were nodular and composed of loosely aggregated cells that were 10-30 microns in diameter with abundant eosinophilic to foamy cytoplasm, had central or eccentric nuclei, and were periodic acid-Schiff negative. Many binucleated cells, multinucleated giant cells, and mitotic figures were seen. Tumor cells contained phagocytosed erythrocytes, mononuclear cells, and some leukocytes. Ultrastructural features of tumor cells included cytoplasmic lipid droplets, lysosomes, and phagolysosomes. Immunohistochemical studies on paraffin-embedded sections showed positive reactivity to human T-cell Ag (clone UCHL-1) and for lysozyme, alpha-1-antitrypsin, and cathespin B. Polyclonal intracellular immunoglobulin reactivity and lectin binding (peanut, soybean, and wheat germ agglutinins and concanavalin A) were also demonstrated. Criteria for diagnosis of malignant histiocytic tumors and differential diagnosis are discussed.

Animals↗

Pulmonary vascular amyloidosis in aged dogs. A new form of spontaneously occurring amyloidosis derived from apolipoprotein AI.

The N-terminus of a mutant form of apolipoprotein AI [apoAI] has previously been shown to be the subunit protein of amyloid fibrils in a human kindred with a form of familial amyloid polyneuropathy (FAP, type III) and in a recently reported kindred with a form of non-neuropathic hereditary amyloidosis. In this study, we demonstrate by amino-acid sequence analysis, that a form of vascular amyloidosis occurring in the lungs of aged dogs is derived from a N-terminal fragment of apoAI and that no amino acid substitution is present in this confirmed sequence. This represents the first documentation of apoAI as a precursor for a form of amyloidosis in animals, and provides the first documentation of apoAI as a precursor for amyloid fibrils in a form of age-associated ("senile") amyloidosis. Secondary structure prediction analysis of the N-terminal regions of normal human and dog apoAI indicated a propensity for beta-pleated sheet conformation, and thus amyloidogenesis, in 40 and 45% of the respective sequences. These results suggest that apoAI (like transthyretin) may serve as an amyloid precursor protein for both familial and senile forms of amyloidosis. ApoAI should, therefore, be considered as a potential amyloid precursor when forms of human senile amyloidosis of unknown origin are evaluated.

Aging↗

Idiopathic, duodenogastric intussusception in an adult dog.

An adult Basset Hound was examined because of acute vomiting, signs of depression, dehydration, and signs of abdominal pain. Radiography revealed a soft tissue dense mass in the stomach. At exploratory laparotomy, 75% of the stomach was black, and the pylorus, proximal portion of the duodenum, and pancreas were found inverted into the stomach. The dog was euthanatized.

Animals↗

Clinical and pathologic features of prostatic adenocarcinoma in sexually intact and castrated dogs: 31 cases (1970-1987).

The medical records of 31 dogs diagnosed with prostatic carcinoma at the teaching hospital between January 1970 and October 1987 were reviewed to determine whether gender status had an effect on the clinical features or biologic behavior of the disease. The only significant difference between sexually intact and castrated dogs was increased prevalence of pulmonary metastasis in castrated dogs.

Adenocarcinoma↗