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Biomedical subjects

T J Divers

Publications and source records attributed to T J Divers.

At least 37 records · Page 2Linked to original sources

Equine motor neuron disease is not linked to Cu/Zn superoxide dismutase mutations: sequence analysis of the equine Cu/Zn superoxide dismutase cDNA.

The cDNA encoding the equine copper/zinc superoxide dismutase (SOD1) was cloned from leukocyte total RNA from healthy horses and its nucleotide (nt) sequence was determined. We further sequenced the SOD1 gene from 16 horses diagnosed with equine motor neuron disease (EMND) and eight unrelated, clinically normal horses to determine if this disease, similar to amyotrophic lateral sclerosis (ALS) in humans, is linked to SOD1 mutations. The 465-bp SOD1 coding region in the horse encodes 153 amino acid (aa) residues. Equine SOD1 exhibited 81.8 and 79.9% sequence identity to the human homolog at the nt and aa levels, respectively, with only five distinct aa in the two loops that constitute the active site of the enzyme. None of the human SOD1 mutations found in the familial form of ALS were detected in SOD1 of the 16 affected horses. Although DNA sequence analysis identified three potential polymorphisms in equine SOD1, these were silent and were found in both normal and EMND-afflicted horses. At this time, there is no conclusive evidence for EMND linkage to SOD1 mutations.

Amino Acid Sequence↗

Endothelial lipopigment as an indicator of alpha-tocopherol deficiency in two equine neurodegenerative diseases.

Two spontaneous neurodegenerative diseases of the horse, equine motor neuron disease (EMND) and equine degenerative myeloencephalopathy (EDM), have been associated with alpha-tocopherol deficiency, and both were characterized by prominent accumulations of endothelial lipopigment in the small vessels of the spinal cord. These endothelial pigment deposits appear to be reversible. In EMND horses pasture-supplemented for 9 months or more after the progression of weakness and wasting had arrested, there was very little endothelial lipopigment. The origin and the potential effects of these endothelial lipopigment accumulations are discussed.

Animals↗

Variations in urinary gamma glutamyl transferase/urinary creatinine ratio in horses with or without pleuropneumonia treated with gentamicin.

The urinary GGT/urinary creatinine (uGGT/uCR) ratio was measured on Days 1, 3 and 10 in 4 adult, healthy horses; in 6 adult, healthy horses treated with gentamicin at recommended dosages and 9 adult horses treated for pleuropneumonia with gentamicin at recommended dosages. Plasma creatinine and gentamicin trough concentrations were measured on the same days. The uGGT/uCr ratio was higher in the normal horses (mean +/- s.d. 22.85 +/- 13.69) than previously reported normal values (10.5 +/- 6.8) (Adams and McClure 1985). Analysis of variance for repeated measures was used to compare the ratio in the 3 groups while controlling for the effect of time. Sick horses had a significantly higher uGGT/uCr ratio than either of the 2 groups of normal horses. Both groups of horses that were treated with gentamicin had similar percentage increases in uGGT/uCr ratio over the treatment period with the most marked increases found between treatment Days 1 and 3. The increase in uGGT/Cr ratio was predominantly a result of an increase in uGGT activity rather than a decrease in uCr concentration. The increase in uGGT activity and uGGT/uCr ratio occurred without abnormalities in serum creatinine or gentamicin trough concentrations. These findings demonstrate that urine GGT activity and uGGT/uCr ratio should be expected to increase in response to gentamicin therapy at recommended dosages without measurable changes in serum creatinine. This suggests that an elevation of the uGGT/uCr ratio in horses being treated with gentamicin would not necessarily require changes in, or withdrawal of, the gentamicin treatment as long as increases in the plasma creatinine do not exceed 0.3 g/l and gentamicin trough concentrations are < 2 micrograms/l.

Animals↗

Incidence and risk factors of equine motor neuron disease: an ambidirectional study.

We have conducted an ambidirectional study to estimate the incidence of equine motor neuron disease (EMND) in the northeastern US. The clinical and pathological features of EMND are similar to those described in human motor neuron disease. We have also collected data on all EMND cases reported in the US and described the geographic distribution of the disease. To identify factors associated with the risk of EMND, the authors assembled 163 control horses from the population in which cases were identified. The significance of association between the hypothesized factors and the risk of EMND was evaluated using the logistic regression analysis and the risk was estimated using the odds ratio. Seventy-eight horses in North America were diagnosed with EMND between the period of January 1985 and November 1993. Most of the cases were identified in the Northeast of the US and the incidence of EMND appears to be increasing in this area. Factors found to be significantly associated with EMND were breed and the age of the horse. Quarter horses were the only breed with a significantly higher risk of EMND (odds ratio = 2.3). The risk of EMND increased with age, reached a peak around 16 years of age and then declined. The sex of the horse was not associated with the risk of the disease.

Age Distribution↗

Epidemiologic evidence for clustering of equine motor neuron disease in the United States.

OBJECTIVE: To examine the regional variations in the distribution of equine motor neuron disease (EMND) in the United States and the factors that might explain those variations. DESIGN: Cluster investigation and case-control study. SAMPLE POPULATION: The study population consisted of 97 horses with histopathologically confirmed EMND and 698 controls with diagnosis of other spinal cord disorders at 21 US veterinary teaching hospitals participating in the Veterinary Medical Data Base. PROCEDURE: The total horse population of the United States was divided into 21 regions, and the regional incidence rates of EMND from January 1985 through January 1995 were estimated. Moran's index of spatial autocorrelation was calculated to test for spatial clustering of the disease. The 21 regions were then joined in broader areas according to the similarity of their EMND rates by means of the cluster analysis statistical technique. Finally, the role of potential confounding factors (age at diagnosis, month of diagnosis, breed, and sex) in the present distribution of EMND was assessed, using logistic regression analysis. RESULTS: Differences in estimated rates across the 21 regions resulted in a strong pattern of spatial clustering of EMND in the United States. The geographic units were grouped into 5 risk regions, with the gradient of EMND incidence rates increasing from the western states (almost 0 cases/1,000,000 horse-years) toward New England (20.78 cases/1,000,000 horse-years). Reported risk factors of EMND (age, breed) and other extraneous factors (sex, month of diagnosis) could not explain the observed geographic variations of disease rates. Nevertheless, there is evidence of some confounding attributable to age and breed. CONCLUSIONS: Although the mechanism responsible for the clustering of EMND in northeastern states is still unexplained, it is not an epiphenomenon caused by regional differences in the distribution of the factors investigated.

Animals↗

Neurological manifestation of cholesterinic granulomas in three horses.

Cholesterinic granulomas have been previously reported as an incidental post mortem in horses. Three adult horses with diencephalic dysfunction due to cholesterinic granulomas are described. All the horses exhibited profound depression, somnolence and reluctance to move. One horse experienced generalised seizures. Cerebrosinal fluid was xanthochromic with an elevated total protein in two of the cases evaluated. The large cholesterinic granulomas caused expansion of the lateral ventricle and secondary hydrocephalus due to the build up of cerebrospinal fluid behind the mass. Cholesterinic granulomas are believed to result from choroid plexus congestion and haemorrhage.

Animals↗

Ataxia due to a vertebral haemangiosarcoma in a horse.

A haemangiosarcoma in a horse resulted in ataxia affecting all four legs, a low head carriage and a reluctance to flex the neck. Ancillary diagnostic procedures included the analysis of cerebrospinal fluid, standing lateral cervical radiographs and a myelogram. Post mortem a tumour was found which involved the body of the second cervical vertebra and the associated hypaxial muscles, with secondary intravertebral extradural infiltration and focal compressive myelopathy. A histological examination showed that the tumour was a haemangiosarcoma.

Animals↗

Evaluation of the thoraco-laryngeal reflex ('slap test') as an indicator of laryngeal adductor myopathy in the horse.

A study was conducted over a 12 month period to assess the accuracy of the 'slap test' in the diagnosis of laryngeal adductor myopathy. The thoraco-laryngeal reflexes of 15 horses with no clinical signs of idiopathic laryngeal hemiplegia (ILH) were recorded using a video-endoscope. These 'slap test' responses were examined independently by 3 assessors. The horses were subsequently subjected to euthanasia and samples taken from the cricoarytenoideus lateralis (CAL) muscles for histopathological examination and assessment of denervation atrophy. Despite normal adductory responses, moderate to severe atrophy of the left CAL muscles was seen in 5 horses. The remaining horses had varying degrees of adductor myopathy, invariably worse in the left side of the larynx. The 'slap test' as performed in this study was therefore unable to differentiate between horses with moderate to severe muscle changes and those without, making it useless as a diagnostic test for adductor myopathy. The reason for the preservation in adductor function despite advanced histological atrophy of the muscle may lie in the degree of reinnervation found in the muscles.

Animals↗

Evaluation of the thoraco-laryngeal reflex ('slap test') as an aid to the diagnosis of cervical spinal cord and brainstem disease in horses.

A study was conducted over a 12 month period to assess the specificity and sensitivity of the 'slap test', using endoscopic evaluation, in the detection of cervical spinal cord and caudal brainstem lesions in horses. Fifteen ataxic horses were subjected to the 'slap test' and subsequently examined post mortem. Twelve out of the 15 had histopathological lesions consistent with their clinical signs. Thirteen horses with no history of neurological dysfunction and no histopathological evidence of cervical spinal cord or brainstem disease were used as controls. The laryngeal adductory responses exhibited by all horses were filmed and later scored independently by 3 assessors. The proportion of animals diagnosed with cervical spinal cord and/or brainstem disease, defined by histopathological criteria, was found to be statistically similar to the proportion with abnormal 'slap test' responses, using the McNemar chi-Square test. Despite statistical significance between proportions, sensitivity of the 'slap test' was low, 50% for the left side on both days and 58% for the right side. Specificity was higher, 69% (Day 1) and 75% (Day 2) for the left side and 75% (Day 1) and 69% (Day 2) for the right side. In contrast to this, conventional neurological examination was found to be 100% sensitive and 81% specific in the detection of lesions of histopathological significance in the cervical spinal cord/caudal brainstem. Agreement between scores for the 'slap test' from the same assessor on different days was good, with values for kappa of 0.59 to 0.85. In contrast, agreement between assessors on the 'slap test' score was poor, with kappa 0.35.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Equine motor neuron disease: findings in 28 horses and proposal of a pathophysiological mechanism for the disease.

Over a three and one-half year period, 28 adult horses were diagnosed with equine motor neuron disease (EMND). The most commonly identified environmental risk factors for a horse having EMND were absence of grazing for more than a year and provision of poor quality hay. Quarter Horses were 5.4 times more at risk than other breeds but this was thought to be an epiphenomenon related to the frequency of Quarter Horses at boarding stables. Weight loss, excessive recumbency and/or trembling were the first signs noted. Other clinical diagnostic signs included: constant shifting of the weight in the rear limbs, abnormally low head carriage and muscle fasciculations. Excellent to ravenous appetites were present in all cases and marked coprophagia in some cases. Abnormally high serum concentration of muscle-derived enzymes was the only consistent serum chemistry abnormality found. Abnormal glucose absorption, increased cerebrospinal fluid total protein and intrathecal production of IgG were identified in a number of cases. Euthanasia was performed on 5 horses within 4 days of hospital admission, because of inability to stand or respiratory distress, and on 18 horses after the diagnosis had been completed. Five affected horses were maintained for observational purposes for periods of 9 months to over 2 years after the onset of clinical signs. They were given access to pasture and 2 were given supplemental vitamin E as the only therapy. Marked clinical improvement occurred in the 4 more acutely affected horses. Pathological findings, preference of type 1 muscle fibre atrophy and lipopigment accumulation within the capillary endothelium of the spinal cord of all cases, supported the hypothesis of EMND being an oxidative disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Diagnosis and epidemiological association of Listeria monocytogenes strains in two outbreaks of listerial encephalitis in small ruminants.

Two outbreaks of epizootic listerial encephalitis, one in sheep and one in goats, were investigated through pathology, microbiology, and DNA amplification-based techniques. Efforts were made to survey the diversity of Listeria monocytogenes strains in the silage consumed by affected animals and to verify the causal relationship between silage and disease outbreak. In both outbreaks, L. monocytogenes was isolated from silage and brain tissue samples. Random amplified polymorphic DNA patterns revealed two distinct L. monocytogenes strains, one of which was identical to the sheep brain isolate, in the silage associated with the outbreak in sheep. Three brain isolates and one silage isolate, all of which had different random amplified polymorphic DNA patterns, were found in the outbreak involving goats. All isolates from both outbreaks were indistinguishable in an in vitro assay for cell-to-cell spread and growth in macrophages. All brain isolates from the goat outbreak had identical intracellular ActA patterns, which were different from the pattern for the silage isolate. While the sheep brain isolate had an ActA pattern different from that of the corresponding silage isolate, the patterns for the brain isolates from the two outbreaks were not identical. This survey demonstrates the diversity of L. monocytogenes in silage and suggests the existence of one or more selective processes by which certain strains are more prone to give rise to disease.

Animals↗

Epidemiology of equine motor neuron disease.

Equine motor neuron disease (EMND) is a newly recognized neurodegenerative disorder of bulbospinal motor neurons in the horse. We conducted a case-control study to identify intrinsic factors associated with the risk of this disorder. Seventy-four cases and 160 controls were assembled. Controls included horses diagnosed with equine protozoal myelitis, equine degenerative myeloencephalopathy, and cervical stenotic myelopathy during the same time period as the cases. Logistic regression analysis was used to evaluate the association of each hypothesized factor while simultaneously controlling for the effect of other factors. Factors found to be significantly associated with the risk of the disease were breed and age of the horse. Quarterhorses are at a higher risk in comparison to other breeds of horse.

Age Factors↗

Eosinophilic cytoplasmic inclusions in sporadic equine motor neuron disease: an electron microscopic study.

Equine motor neuron disease (EMND) is a sporadic, progressive neurodegenerative disorder that has been identified recently in horses of different breeds in North America. The cause is unknown. Pathologic changes which occur in spinal and certain brain stem motor neurons include chromatolysis, swelling, neurofilamentous accumulation, and development of eosinophilic cytoplasmic inclusions. Punctate eosinophilic inclusions, the type usually encountered in degenerating neurons, resembled Bunina bodies at the light microscopic level, but differed in their ultrastructural composition. These and less common but larger juxtanuclear inclusions appeared to be aggregated vesicular residues of membranous organelle degradation. The third kind of eosinophilic inclusion was a marginated derivative of endoplasmic reticulum and consisted of large membrane-bound accumulations of finely granular material. It was concluded that, although the distribution and nature of the lesions in EMND appeared similar to those of human motor neuron disease, none of the equine eosinophilic inclusions duplicated the ultrastructure of Bunina bodies.

Animals↗

Risk factors associated with equine motor neuron disease: a possible model for human MND.

Equine motor neuron disease (EMND), a newly described neurodegenerative disease, bears a striking resemblance to progressive muscular atrophy (PMA) in humans. We present a comparison of the equine and human diseases and the results of a case-control study conducted to identify intrinsic factors associated with EMND. Cases included all horses with a confirmed diagnosis of EMND diagnosed in the United States since 1985 (32 cases). Controls included horses diagnosed with either cervical stenotic myelopathy, equine degenerative myeloencephalopathy, or protozoan myelitis at the Veterinary Teaching Hospital at the College of Veterinary Medicine, Cornell University (153 controls). Logistic regression analysis identified factors associated with the risk of EMND. Risk factors considered were age, sex, and breed of the horse. Most cases of EMND (30 of 32) have been sporadic. There was a breed association with the risk of EMND. Quarter horses were at a high risk for developing EMND (odds ratio [OR] = 12.7; 95% confidence interval, 3.3 to 49.6); thoroughbred horses were at increased risk (OR = 2.9, 0.8 to 10.4). There was also an age association with the risk of EMND. The risk increased with age, peaked at 16 years, and then declined, a pattern similar to that for amyotrophic lateral sclerosis in humans. There was no sex association with the disease. Despite the breed association, equine lymphocyte antigen studies have not revealed a systematic pattern, suggesting that genetic factors influencing susceptibility to EMND may be outside the major histocompatibility complex.

Animals↗

Persistent hyperbilirubinemia in a healthy thoroughbred horse.

Persistent hyperbilirubinemia and icterus are described in a healthy 4-year-old Thoroughbred horse. Hyperbilirubinemia was not related to food intake and was not associated with evidence of increased hemolysis or with acquired hepatic disease. The hyperbilirubinemia was thought to be a result of inappropriate conjugation of bilirubin rather than any abnormality in bilirubin uptake or excretion. The bilirubinemia in this horse appears most similar to a human syndrome, caused by a familial deficiency of bilirubin-uridine diphosphate glucuronyl transferase.

Animals↗