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Biomedical subjects

N J Sharp

Publications and source records attributed to N J Sharp.

At least 19 recordsLinked to original sources
PubMed2001

Risk factors for development of status epilepticus in dogs with idiopathic epilepsy and effects of status epilepticus on outcome and survival time: 32 cases (1990-1996).

OBJECTIVE: To identify risk factors for episodes of status epilepticus (SE) in dogs with idiopathic epilepsy and determine how SE affects long-term outcome and survival time. DESIGN: Retrospective study. ANIMALS: 32 dogs with idiopathic epilepsy. PROCEDURE: Information on signalment, seizure onset, initiation of treatment, anticonvulsants administered, number of episodes of SE, overall seizure control, and long-term outcome was obtained from medical records and through telephone interviews. Differences between dogs that did and did not have episodes of SE were evaluated statistically. RESULTS: 19 (59%) dogs had 1 or more episodes of SE. Body weight was the only variable significantly different between dogs that did and did not have episodes of SE. Thirteen dogs (9 that did not have episodes of SE and 4 that did) were still alive at the time of the study and were > or = 10 years old. Six of the 19 (32%) dogs that had episodes of SE died of causes directly attributed to the seizure disorder. Mean life spans of dogs that did and did not have episodes of SE were 8.3 and 11.3 years, respectively. Survival time was significantly different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a substantial percentage of dogs with idiopathic epilepsy will have episodes of SE. Dogs with greater body weights were more likely to have episodes of SE, and early appropriate seizure treatment did not appear to decrease the risk that dogs would have episodes. Most dogs with idiopathic epilepsy had an expected life span, but survival time was shorter for dogs that had episodes of SE.

Animals↗
PubMed2001

Predictors of outcome after dorsal decompressive laminectomy for degenerative lumbosacral stenosis in dogs: 69 cases (1987-1997).

OBJECTIVE: To identify predictive factors of long-term outcome after dorsal decompressive laminectomy for the treatment of degenerative lumbosacral stenosis (DLSS) in dogs. DESIGN: Retrospective study. SAMPLE POPULATION: 69 client-owned dogs. PROCEDURE: Medical records of dogs that had undergone dorsal laminectomy at North Carolina State University and the University of Tennessee between 1987 and 1997 were reviewed. Dogs with diskospondylitis, traumatic lesions, or neoplasia of the lumbosacral region were excluded. All dogs had evidence of cauda equina compression on myelography, epidurography, computed tomography, or magnetic resonance imaging, along with subsequent confirmation of the lesion at surgery. Follow-up was performed by telephone inquiries to the referring veterinarian, the owner, or both, using a detailed questionnaire. RESULTS: The outcome was excellent or good in 54 of 69 (78%) dogs over a mean follow-up period of 38+/-22 months. Five of these 54 dogs had been incontinent for a median of 2 weeks prior to surgery. Six of the 15 dogs with a poor outcome had been incontinent for a median of 8 weeks before surgery. A significant correlation was detected between the presence of urinary and fecal incontinence prior to surgery and outcome. When duration of signs was considered, urinary incontinence was the only variable that significantly affected outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Decompressive laminectomy is an effective treatment for DLSS, although dogs with urinary or fecal incontinence have a worse prognosis than dogs that are continent before surgery. Chronic urinary incontinence is a predictor of poor outcome for dogs with DLSS.

Animals↗
PubMed2001

Evaluation of the dystrophin-glycoprotein complex, alpha-actinin, dysferlin and calpain 3 in an autosomal recessive muscular dystrophy in Labrador retrievers.

Labrador retrievers suffer from an autosomal recessive muscular dystrophy of unknown aetiology. Dogs affected with this disease develop generalized weakness associated with severe, generalized skeletal muscle atrophy and mild elevations in creatine kinase in the first few months of life. The severity of signs tends to progress over the first year of life but can vary from mild exercise intolerance to non-ambulatory tetraparesis. Beyond 1 year of age, the signs usually stabilize and although muscle mass does not increase, affected dogs' strength may improve slightly. The pathological changes present on muscle biopsy include marked variation in muscle fibre size with hypertrophied and round atrophied fibres present. There is an increased number of fibres with central nuclei and split fibres can be seen. It has been suggested that the disorder is a model for limb-girdle muscular dystrophy. In recent years, mutations in genes encoding the proteolytic enzyme, calpain 3, a novel protein named dysferlin, and components of the dystrophin-glycoprotein complex have been identified as causes of autosomal recessive limb-girdle muscular dystrophy. We have evaluated these proteins in normal dogs and in three Labrador retrievers with autosomal recessive muscular dystrophy using immunohistochemistry and Western blot analysis on frozen skeletal muscle. The results demonstrate that dystrophin, the sarcoglycans, alpha-actinin, dysferlin and calpain 3 are present in the normal and affected dogs. We conclude that this autosomal recessive muscular dystrophy is not due to a deficiency of alpha-actinin, or any of the known autosomal recessive limb-girdle muscular dystrophy proteins, although we cannot rule out a malfunction of any of these proteins.

Actinin↗
PubMed2001

Development of a functional scoring system in dogs with acute spinal cord injuries.

OBJECTIVES: To develop and compare the reliability of 2 methods of scoring pelvic limb gait in dogs recovering from thoracolumbar spinal cord injuries and to use this scoring system to determine the rate and level of functional recovery of dogs with acute thoracolumbar intervertebral disk herniations. ANIMALS: 46 dogs with spinal cord injuries resulting from intervertebral disk herniations. PROCEDURE: Dogs' gaits were videotaped at different time intervals after injury. In phase 1 of the study, the stages of recovery of pelvic limb function were identified, and a numeric scoring system was devised to reflect that recovery. In phase 2, pelvic limb gait was scored by different observers, using a numeric and a visual analog scale. Intra- and interobserver coefficients of variability of both methods were compared. In phase 3, pelvic limb function was scored, using the numeric scale at various intervals after acute thoracolumbar disk herniations. RESULTS: The numeric scale was significantly more reliable than the visual analog scale when both intra- and interobserver coefficients of variability were evaluated. Dogs that were paraplegic with no deep pain sensation recovered at different rates during the first 3 months, whereas dogs that were paraplegic with deep pain sensation typically recovered within 1 month of injury. CONCLUSIONS: Pelvic limb gait of dogs recovering from thoracolumbar spinal cord injuries can be reliably quantified, using a numeric scale. This scale will facilitate the performance of clinical trials aimed at improving the outcome of acute spinal cord injuries.

Animals↗
PubMed2000

Degenerative lumbosacral stenosis.

This article reviews the management of degenerative lumbosacral stenosis. Degenerative lumbosacral stenosis occurs when soft tissue and bony changes, possibly in conjunction with abnormal motion of the lumbosacral joint, impinge on the nerve roots or vasculature of the cauda equina. It occurs most frequently in middle-aged dogs of medium to large breed, especially the German Shepherd dog. Common signs are lumbosacral pain, lameness, pelvic limb weakness and ataxia, and urinary incontinence. Diagnosis is based on clinical features and imaging studies. Decompressive surgery is effective in most patients.

Animals↗
PubMed1999

Molecular analysis of a spontaneous dystrophin 'knockout' dog.

We have determined the molecular basis for skeletal myopathy and dilated cardiomyopathy in two male German short-haired pointer (GSHP) littermates. Analysis of skeletal muscle demonstrated a complete absence of dystrophin on Western blot analysis. PCR analysis of genomic DNA revealed a deletion encompassing the entire dystrophin gene. Molecular cytogenetic analysis of lymphocytes from the dam and both dystrophic pups confirmed a visible deletion in the p21 region of the affected canine X chromosome. Utrophin is up-regulated in the skeletal muscle, but does not appear to ameliorate the dystrophic canine phenotype. This new canine model should further our understanding of the physiological and biochemical processes in Duchenne muscular dystrophy.

Animals↗
PubMed1999

A description of cutaneous-subcutaneous pythiosis in fifteen dogs.

Information regarding signalment, duration of clinical signs, history of swimming, results of CBC and serum biochemical analyses, biopsy findings and mycological results, together with treatments and outcome, was retrieved from the medical records of 15 dogs with a diagnosis of pythiosis made between 1985 and 1995 at the Colleges of Veterinary Medicine, North Carolina State University and the University of Florida. Most of the dogs were young (median age 22 months) and represented larger breeds (> 20 kg). Lesions were characteristically chronic, ulcerated, and nodular with multiple draining tracts on the limbs, thoracic wall or perineal regions. The median duration of these lesions was 3 months with a range of 2 weeks-6 months. Seven dogs had a history of swimming. Peripheral eosinophilia was observed in 14 of the dogs. Cytological evaluation of discharge, aspirates, or impression smears made from biopsy specimens revealed hyphae in five of 11 dogs (45%). Histopathological evaluation using the Gomori Methenamine-Silver (GMS) stain was the most useful test for providing presumptive evidence of cutaneous pythiosis. Immunotherapy or antifungal therapy using either amphotericin B, liposomal nystatin, itraconazole, or ketoconazole were all unsuccessful. The only dog to survive underwent amputation of the affected limb; thus, the prognosis for cutaneous pythiosis in the dog is poor.

Animals↗
PubMed1999

Hydranencephaly and cerebellar hypoplasia in two kittens attributed to intrauterine parvovirus infection.

Six weeks after vaccination with modified live feline parvovirus vaccine, a cat gave birth to five kittens, three of which died soon afterwards. The remaining two kittens (A and B) survived, but at 8 weeks of age were unable to walk and showed abnormal behaviour, with lack of menace and oculovestibular responses, and severe dysmetria. These signs suggested multifocal disease associated with the cerebrum and cerebellum. Magnetic resonance imaging demonstrated severe bilateral (kitten A) or unilateral (kitten B) hydrocephalus or hydranencephaly, combined with cerebellar agenesis (kitten A) or severe hypoplasia (kitten B). Hydranencephaly was confirmed histopathologically in both kittens. Parvovirus was isolated from the kidney of one kitten. Parvoviral DNA was amplified by the polymerase chain reaction (PCR) from paraffin wax-embedded brain of both kittens. The severe malformations observed in these kittens presumably resulted from an in-utero parvovirus infection, possibly due to vaccination, that occurred late in the first, or early in the second, trimester of pregnancy.

Animals↗
PubMed1999

Chronic and acute compressive spinal cord lesions in dogs due to intervertebral disc herniation are associated with elevation in lumbar cerebrospinal fluid glutamate concentration.

Acute injury to the central nervous system initiates a series of biochemical events that cause secondary tissue damage. The accumulation of excessive concentrations of glutamate in the extracellular space causes excitotoxic damage, and is incriminated as a mediator of this secondary tissue damage. The aim of this study was to measure the concentration of glutamate in cerebrospinal fluid (CSF) obtained from the cerebellomedullary cistern and lumbar subarachnoid space in dogs with acute and chronic compressive injuries of the cervical and thoracolumbar spinal cord, and to correlate the glutamate concentration with injury severity. The results demonstrate that focal injuries of the spinal cord do not affect the glutamate concentration in CSF taken from the cerebellomedullary cistern. However, dogs with severe, acute thoracolumbar disc herniations have two- to 10-fold increases in glutamate concentration in their lumbar CSF at intervals of >12 h after injury. Moreover, the severity of their clinical signs is directly related to the glutamate concentration. Dogs with chronic compressive thoracolumbar lesions have a two-fold elevation of CSF glutamate concentration, suggesting that excitotoxicity may also be a component of chronic spinal cord compression.

Acute Disease↗
PubMed1998

A dominant negative mutant of the insulin-like growth factor-I receptor inhibits the adhesion, invasion, and metastasis of breast cancer.

The 5-year survival rate for women with metastatic breast cancer is only 25-30%; thus, the need to improve treatment is apparent. Overexpression of insulin-like growth factor-I receptor (IGF-IR) correlates with poor prognosis and local recurrence. In this study, we addressed whether functional impairment of IGF-IR affects adhesion, invasion, and metastasis of breast cancer. Impairment of IGF-IR function was achieved by transfecting a dominant negative form of the receptor, termed 486stop, into MDA-MB-435 metastatic breast cancer cells. The protein product of 486stop is secreted extracellularly, resulting in a bystander effect. Cellular adhesion to laminin and collagen was inhibited 94 and 88%, respectively. Furthermore, 486stop inhibited insulin-like growth factor-I-stimulated invasion through collagen IV by 75%. The dominant negative receptor was secreted, as evidenced by the observation that MDA-MB-435 and MDA-MB-231 cells were prevented from binding to laminin by 90% when treated with conditioned medium (CM) from 486stop-transfected cells. CM also inhibited the invasion of MDA-MB-231 cells across collagen IV by 80%. Finally, CM made MDA-MB-231 cells 30% more sensitive to Taxol-induced cell death. Growth in soft agar was suppressed by 486stop, but growth in monolayer was unaffected. When injected into the mammary fat pad, 486stop did not significantly suppress growth of the primary tumor, but metastasis to the lungs, livers, lymph nodes, and lymph vessels was significantly decreased compared to the vector control. In conclusion, inhibition of IGF-IR resulted in suppression of adhesion, invasion, and metastasis, providing a mechanistic rationale for targeting IGF-IR in the treatment of metastatic breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Alternative dystrophin gene transcripts in golden retriever muscular dystrophy.

Golden retriever muscular dystrophy (GRMD), the canine model of Duchenne muscular dystrophy (DMD), is caused by a splice site mutation in the dystrophin gene. This mutation predicts a premature termination codon in exon 8 and a peptide that is 5% the size of normal dystrophin. Western blot analysis of skeletal muscle from GRMD dogs reveals a slightly truncated 390-kD protein that is approximately 91% the size of normal dystrophin. This 390-kD dystrophin suggests that GRMD dogs, like some DMD patients, employ a mechanism to overcome their predicted frameshift. Reverse-transcriptase polymerase chain reaction on GRMD muscle has revealed two in-frame dystrophin transcripts which lack either exons 3-9 or exons 5-12. Both transcripts could be translated into a dystrophin protein of approximately 390 kD. An understanding of how truncated dystrophin is produced in GRMD may allow this mechanism to be manipulated toward a potential therapy for DMD.

Alternative Splicing↗
PubMed1994

Alpha-dystroglycan deficiency correlates with elevated serum creatine kinase and decreased muscle contraction tension in golden retriever muscular dystrophy.

The dystrophin-glycoprotein complex was examined in dystrophin-deficient dogs with golden retriever muscular dystrophy (GRMD) using immunoblot and immunofluorescence analysis. The dystrophin-associated proteins were substantially reduced in muscle from dogs with GRMD. Interestingly, regression analysis revealed a strong correlation between the amount of alpha-dystroglycan and serum creatine kinase levels and the contraction tension measured for a given peroneus longus muscle.

Animals↗
PubMed1994

Contraction tension and kinetics of the peroneus longus muscle in golden retriever muscular dystrophy.

Contraction tension and kinetics of the peroneus longus muscle were studied in dogs with the Duchenne homologue, golden retriever muscular dystrophy (GRMD), in advance of evaluating localized therapies such as myoblast transplantation. Absolute and both muscle- and body-weight-corrected twitch tension in GRMD dogs were low compared to normal litter mates at 3 months of age (p < 0.0005 for all). Tetanic tension was affected similarly. However, whereas absolute values were still reduced at 6 months (p < 0.0005 for twitch and 0.005 for tetany), twitch and tetanic tension corrected for either muscle or body weight was not statistically different, suggesting that the peroneus longus may be relatively spared in GRMD. Post-tetanic potentiation was more pronounced in GRMD versus normal dogs at both 3 (p < 0.0001) and 6 (p < 0.01) months. The degree of positive staircase at 3 months of age did not differ. Twitch contraction and relaxation times were dramatically prolonged, and there was concomitant sustained electrical activity, at, or before, 6 months of age in some severely affected dogs. Relatively few carriers were evaluated at these ages, but their values were similar to those of normal dogs. Apparent sparing of the peroneus longus muscle may limit application of this technique to evaluation of therapies administered early in life or in combination with toxins. Treatment to alter changes in contraction kinetics could also be assessed.

Aging↗
PubMed1994

Tarsal joint contracture in dogs with golden retriever muscular dystrophy.

Golden retriever muscular dystrophy (GRMD) is an X-linked myopathy homologous with Duchenne muscular dystrophy of human beings. Affected dogs have progressive clinical dysfunction due to muscle wasting and contractures. Deficits progress particularly rapidly between 3 and 6 months of age. To better characterize the role of contractures in this deterioration, the flexor surface, nonweight-bearing tarsal joint angle was measured in GRMD-affected dogs and clinically normal littermates at both ages. The mean +/- SD tarsal joint angle for clinically normal dogs decreased from 164.6 +/- 6.09 degrees to 145.6 +/- 8.80 degrees between 3 and 6 months (P < 0.0005). The value for GRMD-affected dogs decreased from 153.3 +/- 11.44 degrees to 117.6 +/- 24.55 degrees (P < 0.005). The angle for clinically normal dogs was greater than that for GRMD-affected dogs at both ages (P < 0.05 at 3 months and P < 0.01 at 6 months). The decrease in tarsal joint angle, at times to less than 90 degrees, correlated well with other phenotypic features of GRMD, such as loss of the ability to walk.

Animals↗
PubMed1993

Notexin-induced muscle injury in the dog.

Notexin, a myotoxic phospholipase, was used to induce focal necrosis in the sartorius muscles of normal mixed-breed adult dogs and in 12-week-old beagles. Notexin injury caused pathologic changes similar to those of Duchenne muscular dystrophy (DMD) and its canine homologue, golden retriever muscular dystrophy (GRMD). All three conditions are characterized by increased serum creatine kinase (CK) levels, sarcolemmal defects, delta lesions, hyaline degeneration of myofibers, calcium-positive myofibers, and minimal effects on neurovascular structures. Four and 24 h after exposure to notexin, serum CK levels were elevated, and many myofibers were necrotic. In addition, by 24 h the necrotic areas were heavily invaded by mononuclear cells, and calcium-positive myofibers were prominent. Capillaries appeared intact even in areas of marked myonecrosis. Massive cellular infiltrate and myotube formation was evident at 3 days post injury. By 7 days, most affected fascicles were occupied by small immature myofibers. Regeneration was largely complete at 21 days. Our results suggest that notexin-induced muscle injury in dogs will be useful in the evaluation of potential therapies for DMD such as myoblast transplantation.

Animals↗