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Biomedical subjects

P A March

Publications and source records attributed to P A March.

13 recordsLinked to original sources
PubMed1999

Evaluation of hypothermia-induced analgesia and influence of opioid antagonists in leopard frogs (Rana pipiens).

Hypothermia results in diminished voluntary muscle activity, and is frequently used as a means of providing deep anesthesia to ectotherms and some mammals. In ectotherms, however, it is unclear if hypothermia produces true pain insensation. A needle-probe thermometer was used to demonstrate in frogs (Rana pipiens) that local hypothermia (9 degrees C) could be induced by placement of a tourniqueted leg into ice water (6 degrees C) for 10 min in contrast to the contralateral nontourniqueted leg (21.8 degrees C) kept out of ice water. Analgesia was tested by placement of dilutions of acetic acid on the rear leg. Further tests using groups of 10 frogs demonstrated that frogs with local hypothermia tolerated greater concentrations of acetic acid (mean acetic acid test score = 11) than morphine (10 mg/kg)-treated (9.6) or nontreated (5.8) frogs. Additional studies showed that morphine analgesia was blocked with naloxone doses as low as 0.01 mg/kg and hypothermia-induced analgesia at 10 mg/kg. Naltrexone blocked morphine analgesia at dosages as low as 0.01 mg/kg and hypothermia-induced analgesia at 0.10 mg/kg. In summary, this study demonstrates that hypothermia induces significant analgesia in an amphibian, and that this analgesia is partially blocked by naloxone and naltrexone, suggesting that the effect is mediated at least partially by opioid receptors.

Analgesia↗
PubMed1998

Seizures: classification, etiologies, and pathophysiology.

Epilepsy is a disorder of recurrent seizures that are neural in origin. Partial seizures are usually due to a structural cerebrocortical lesion and may be simple or complex. Brain injuries may alter inherent neuronal properties and neuronal circuits and lead to recurrent excitatory activity. Potentiation of excitatory synapses and depression of inhibitory synapses are probable critical events in epileptogenesis. The pathogenic factors underlying primary or idiopathic generalized seizures are not as well understood. A more diffuse or multifocal state of neuronal excitability may be the result of early congenital events that are magnified over time. The progression of subclinical neuronal excitatory activity to a clinical seizure may relate directly to the phenomenon of cortical plasticity.

Animals↗
PubMed1997

GABAergic neuroaxonal dystrophy and other cytopathological alterations in feline Niemann-Pick disease type C.

Feline Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal storage disease which shares many of the clinical, biochemical and pathological features of the corresponding human disorder. Cytopathological alterations in distinct neuronal cell populations were investigated in this animal model to gain a better understanding of the pathogenesis of brain dysfunction. Golgi and immunocytochemical methods were employed to characterize the cell architectural changes occurring in neuronal somata, dendrites and axons at different stages of disease progression. Cortical pyramidal neurons in laminae II, III, and V exhibited various degrees of meganeurite and/or swollen axon hillock formation with or without ectopic dendritogenesis. Enlarged axon hillock regions with neuritic processes and spines were recognized early in the progression of feline NPC but were less prevalent in mid to late stages of the disease. Glutamic acid decarboxylase (GAD) immunocytochemistry demonstrated immunoreactive spheroids in numerous GABAergic axons in neocortex, subcortical areas, and cerebellum. Parvalbumin-immunoreactive axonal spheroid distribution in brain closely mirrored results from the GAD studies, whereas calbindin D-28k-immunoreactive spheroids were conspicuously absent in most cortical and subcortical areas examined. Purkinje cell axonal spheroid formation progressed in a distal to proximal direction, with eventual involvement of recurrent axon collaterals. Purkinje cell death and a concomitant decrease in the numbers of spheroids in the cerebellum were observed late in the disease course. Clinical neurological signs in feline NPC occur in parallel with neuronal structural alterations and suggest that GABAergic neuroaxonal dystrophy is a contributor to brain dysfunction in this disease.

Age Factors↗
PubMed1996

Degenerative brain disease.

Inherited degenerative diseases of the brain are chronically progressive and often lead to severe debilitation. The cerebellum is particularly susceptible to degenerative processes. For lysosomal storage disorders, the metabolic defect is often known and diagnostic tests are available. For other abiotrophies, the inborn error of metabolism is not known and diagnosis is made on postmortem. Pathogenesis of brain dysfunction is not well understood in a majority of the neurodegenerative diseases.

Animals↗
PubMed1995

Pathogenesis of brain dysfunction in Batten disease.

Animal models of Batten disease and other neuronal storage disorders offer important opportunities to study the pathogenesis of brain dysfunction in this family of diseases. Although all of these conditions exhibit progressive intraneuronal storage, we have found that other aspects of the cellular pathology of Batten disease differ markedly from those of storage disorders caused by lysosomal hydrolase deficiencies. Likewise, lysosomal of cerebral cortex and other select brain regions, a prominent characteristic of Batten disease, does not occur in most other storage disorders. Our studies indicate that Batten disease has findings in common with human neurodegenerative diseases and that neuron death may be caused by excitotoxicity occurring secondary to the combined effects of suboptimal mitochondrial function and GABAergic (inhibitory) cell loss.

Animals↗
PubMed1995

Morphological alterations in neocortical and cerebellar GABAergic neurons in a canine model of juvenile Batten disease.

The pathogenesis of brain dysfunction in a canine model of juvenile Batten disease was studied with techniques designed to determine sequential changes in mitochondrial morphology and cytochrome oxidase (CO) activity, and in neurons and synapses using gamma-aminobutyric acid (GABA) as a neurotransmitter. Histochemical and immunocytochemical methods were employed. Mitochondrial alterations were found in a select population of nonpyramidal neurons in neocortex and claustrum, and in cerebellar basket cells. Proportions of affected neurons at any one time remained constant over the disease course, with morphologically-abnormal mitochondria first being recognized at age 6 months. Enlarged mitochondria were readily identifiable at the light microscope (LM) level as large CO-positive or mitochondrial antibody-positive granular structures. Colabelling with antibodies to GABA or to parvalbumin (PV) indicated that most of these cells were GABAergic. Ultrastructurally, atypical mitochondria were characterized by globular enlargement, intramitochondrial membranous inclusions, and disorganized internal structure. CO activity in all other cell somata and in neuropil was diminished compared with normal, age-matched tissue. Glutamic acid decarboxylase (GAD), PV, and GABA studies demonstrated loss of GABAergic neurons and synapses in cortex and cerebellum of affected dogs. These results indicate that abnormal mitochondria are present in neurons in Batten disease, and suggest that suboptimal mitochondrial function may play a role in the pathogenic mechanisms of brain dysfunction in this disorder.

Animals↗
PubMed1994

Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease.

Neuronal storage disorders are fatal neurodegenerative diseases of humans and animals that are caused by inherited deficiencies of lysosomal hydrolase activity. Affected individuals often appear normal at birth but eventually develop progressive neurologic symptoms including sensory and motor deficits, mental retardation, and seizures. We have examined efficacy of bone marrow transplantation as a means of enzyme replacement, using cats with the lysosomal storage disease alpha-mannosidosis. Treated animals showed little or no progression of neurologic signs 1-2 years after transplant, whereas untreated cats became severely impaired and reached endstage disease by 6 months of age. Increased lysosomal alpha-mannosidase activity was found in brain tissue of the treated animals, and electron microscopy revealed no evidence of lysosomal storage within most neurons. Histochemical localization of acidic alpha-D-mannoside mannohydrolase (EC 3.2. 1.24), using 5-bromo-4-chloro-3-indolyl alpha-D-mannopyranoside, showed that functional enzyme was present in neurons, glial cells, and cells associated with blood vessels. This study provides direct evidence that bone marrow transplantation as treatment for a neuronal storage disease can lead to significant levels of a missing lysosomal hydrolase within neurons of the central nervous system and to compensation for the genetic metabolic defect.

Animals↗
PubMed1992

Neural regulation of respiration. Physiology and pathophysiology.

The central nervous system links the body's metabolic demands with the neuromuscular act of breathing. Automatic and voluntary control systems function together to adjust ventilation in response to chemical and somatic signals. Excitatory or inhibitory outputs from higher brain centers descend the spinal cord and influence the motoneurons to the respiratory muscles. Lesions at any level can disrupt the normal respiratory pattern and may or may not produce alveolar hypoventilation. Several neurologic diseases of importance in veterinary practice may affect the respiratory system. Ventilatory insufficiency tends to occur late in the progression of these disease. Prompt localization of the lesion and correction of the underlying dysfunction is often critical to patient survival.

Animals↗
PubMedDate not supplied

Terminal restlessness.

Explore the source record for details and available documents.

Anti-Anxiety Agents↗
PubMedDate not supplied

Diagnosis, treatment, and temporary remission of disseminated paecilomycosis in a vizsla.

A case of disseminated paecilomycosis in a three-year-old vizsla is described. Clinical signs of lethargy, weight loss, lymphadenopathy, diarrhea, and vestibulocochlear deficits were exhibited. Dense colonization of bone marrow by the fungus was found early in the disease course. Serial culture of bone-marrow aspirates and in vitro sensitivity testing helped monitor disease progression and guide antifungal therapy. Clinical and laboratory parameters demonstrated marked improvement for a period of 12 weeks. Multisystemic disease with central nervous system involvement was found at necropsy.

Animals↗
PubMedDate not supplied

Acute bilateral trigeminal neuropathy associated with nervous system lymphosarcoma in a dog.

A nine-year-old dog presented with clinical signs consistent with bilateral trigeminal neuropathy. Multicentric lymphoma was diagnosed, and neoplastic lymphocytes were identified in the cerebrospinal fluid. Electromyography revealed spontaneous activity in temporal and masseter muscles. Histopathological examination demonstrated neoplastic cell invasion of temporal and masseter myofibers and of multiple peripheral nerves, including the trigeminal nerve. Central nervous system pathology consisted primarily of spinal root and leptomeningeal lymphoid cell infiltration with relative sparing of spinal cord and brain parenchyma.

Animals↗