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Biomedical subjects

Joan R Coates

Publications and source records attributed to Joan R Coates.

16 recordsLinked to original sources

Effect of combined simvastatin and cyclosporine compared with simvastatin alone on cerebral vasospasm after subarachnoid hemorrhage in a canine model.

OBJECT: The object of this study was to determine whether the combination of cyclosporine and simvastatin could ameliorate cerebral vasospasm after subarachnoid hemorrhage (SAH) in a canine model to a greater extent than simvastatin alone. METHODS: Animals were assigned to one of three groups: control (five dogs), simvastatin alone (four), or simvastatin and cyclosporine (four). A double SAH model was used. Baseline basilar artery (BA) angiograms were obtained. These were repeated at Days 3, 7, and 10. Measurement of the BA diameter was performed. Decreased BA diameter was seen on Day 3 in the control and simvastatin/cyclosporine group. A return to baseline diameters was seen by Day 7. An increase from baseline diameter was seen in the simvastatin group at Day 10. CONCLUSIONS: Cyclosporine may interfere with the vasodilatory effects of simvastatin. Vasodilation greater than baseline is seen at Day 10 in the simvastatin group. The combination of simvastatin and cyclosporine does not ameliorate cerebral vasospasm in a canine model to a greater extent than simvastatin alone.

Analysis of Variance↗

A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis.

The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases characterized by progressive neuropathy and the accumulation of autofluorescent cytoplasmic granules. Clinical signs of a new canine NCL began in a 9-month-old male Dachshund with vomiting, mental dullness, and loss of previously learned commands and rapidly progressed to include disorientation, ataxia, visual deficits, generalized myoclonic seizures, and death at 12 months of age. Neurons throughout the CNS contained autofluorescent storage granules that stained with periodic acid-Schiff and Luxol fast blue stains. Electron microscopy revealed that the storage granule contents consisted of curvilinear-appearing material characteristic of human late infantile NCL caused by CLN2 mutations. Nucleotide sequence analysis of canine TPP1, the ortholog of human CLN2, revealed a single nucleotide deletion in exon 4 which predicted a frame shift with a premature stop codon. Brain tissue from the affected dog lacked detectable activity of the tripeptidyl-peptidase enzyme encoded by TPP1, whereas the specific activities of 15 other lysosomal enzymes were higher than those in the brains of three control dogs. The affected Dachshund was homozygous for the mutant c.325delC allele, his sire and dam were heterozygotes, and 181 unrelated dogs, including 77 Dachshunds, were all homozygous for the wild-type allele. A DNA assay that detects the mutant allele will help Dachshund breeders avoid producing affected puppies in future generations. Furthermore, this Dachshund NCL may prove to be a useful model for studying the pathogenesis of neurodegeneration in human late infantile NCL and for evaluating novel therapeutic interventions for this disease.

Aminopeptidases↗

Intracranial abscess caused by Rhodococcus equi infection in a foal.

CASE DESCRIPTION: A 4-month-old Missouri Fox Trotter colt was examined for a 5-week history of head tilt after treatment for suspected pulmonary Rhodococcus equi infection. CLINICAL FINDINGS: Computed tomography revealed osteolysis of the occipital, temporal, and caudal portion of the parietal bones of the left side of the cranium. A soft tissue mass compressing the occipital region of the cerebral cortex and cerebellum was associated with the osteolytic bone. TREATMENT AND OUTCOME: A rostrotentorial-suboccipital craniectomy approach was performed to remove fragmented occipital bone, debulk the intracranial mass, and obtain tissue samples for histologic examination and bacterial culture. All neurologic deficits improved substantially within 3 days after surgery. Bacterial culture of the resected soft tissue and bone fragments yielded R equi. CLINICAL RELEVANCE: Intracranial surgery in veterinary medicine has been limited to dogs and cats; however, in select cases, extrapolation of surgical techniques used in humans and small animals can assist with intracranial procedures in horses.

Actinomycetales Infections↗

Matrix metalloproteinase-9 activity in the cerebrospinal fluid and serum of dogs with acute spinal cord trauma from intervertebral disk disease.

OBJECTIVE: To detect matrix metalloproteinase (MMP)-9 in serum and CSF and determine relationships between MMP activity and severity of disease, duration of clinical signs, and duration of hospitalization in dogs with acute intervertebral disk disease (IVDD). ANIMALS: 35 dogs with acute IVDD and 8 clinically normal control dogs. PROCEDURE: CSF and serum were collected from affected and control dogs. Zymography was used to detect MMP-9. RESULTS: Activity of MMP-9 in CSF was detected in 6 of 35 dogs with IVDD; activity was significantly more common in dogs with duration of signs < 24 hours. Paraplegic dogs were more likely to have MMP-9 activity in the CSF than non-paraplegic dogs. No significant difference in hospitalization time was detected in dogs with IVDD between those with and without activity of MMP-9 in the CSF. Serum MMP-9 was detected more frequently in dogs with IVDD than in control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Data were consistent with results of experimental rodent spinal cord injury studies that indicate that MMP-9 is expressed early during secondary injury.

Animals↗

Genetic mapping of canine multiple system degeneration and ectodermal dysplasia loci.

We characterized a movement disorder of Chinese Crested dogs clinically and pathologically indistinguishable from canine multiple system degeneration (CMSD) previously recognized in Kerry Blue Terriers. This fatal disease segregated as an autosomal recessive in a 51-dog pedigree of both breeds and their crosses. The occurrence of affected dogs among first-generation crosses demonstrated that the mutations causing multiple system degeneration in these breeds are allelic. The CMSD locus maps to CFA1 (LOD > 18) and haplotype analysis narrowed the CFA1 target region to a 15-Mb segment that contains orthologs of genes on HSA6, including PARK2, the gene for the ubiquitin ligase parkin. Mutations in human PARK2 cause the most common form of familial Parkinson's disease, autosomal recessive juvenile parkinsonism, which has clinical and pathological similarities to canine multiple system degeneration. A second phenotype, canine ectodermal dysplasia (CED), segregated in the pedigree as an autosomal dominant with homozygous lethality. Dogs with ectodermal dysplasia have a sparse hair coat and abnormal dentition that is characteristic of the "hairless" variety of Chinese Cresteds. CED mapped to a region of CFA17 (LOD > 14) containing orthologs from HSA2. EDAR, the gene for the ectodysplasin A1 receptor, occurs on HSA2 but was excluded as the cause of canine ectodermal dysplasia.

Animals↗

Evaluation of a selective neurectomy model for low urethral pressure incontinence in female dogs.

OBJECTIVE: To develop a model of low urethral pressure incontinence and compare the relative contributions of the pudendal and hypogastric nerves with urethral function by performing selective neurectomy and ovariohysterectomy in dogs. ANIMALS: 19 healthy Foxhounds. PROCEDURE: Dogs were allocated into 2 groups. The first group (10 dogs) underwent bilateral hypogastric neurectomy and ovariohysterectomy and subsequent bilateral pudendal neurectomy. The second group (9 dogs) underwent bilateral pudendal neurectomy and subsequent hypogastric neurectomy and ovariohysterectomy. Urethral pressure profilometry and leak point pressure (LPP) tests were performed before and after each neurectomy. RESULTS: Before surgery, mean +/- SD LPP and maximal urethral closure pressure (MUCP) in all dogs were 169.3 +/- 24.9 cm H2O and 108.3 +/- 19.3 cm H2O, respectively; these values decreased to 92.3 +/- 27 cm H2O and 60.7 +/- 20.0 cm H2O, respectively, after both selective neurectomy surgeries. There was a progressive decline of LPP after each neurectomy; however, MUCP decreased only after pudendal neurectomy. Fifteen dogs had mild clinical signs of urinary incontinence. All dogs appeared to have normal bladder function as indicated by posturing to void and consciously voiding a full stream of urine. Urinary tract infection did not develop in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Hypogastric and pudendal neurectomy and ovariohysterectomy caused a maximum decrease in LPP whereas pudendal neurectomy caused a maximum decrease in MUCP. IMPACT ON HUMAN MEDICINE: This model may be useful for evaluation of treatments for improving urinary control in postmenopausal women.

Animals↗

A preliminary study of intravenous surfactants in paraplegic dogs: polymer therapy in canine clinical SCI.

Hydrophilic polymers, both surfactants and triblock polymers, are known to seal defects in cell membranes. In previous experiments using laboratory animals, we have exploited this capability using polyethylene glycol (PEG) to repair spinal axons after severe, standardized spinal cord injury (SCI) in guinea pigs. Similar studies were conducted using a related co-polymer Poloxamer 188 (P 188). Here we carried out initial investigations of an intravenous application of PEG or P 188 (3500 Daltons, 30% w/w in saline; 2 mL/kg I.V. and 2 mL/kg body weight or 300 mL P 188 per kg, respectively) to neurologically complete cases of paraplegia in dogs. Our aim was to first determine if this is a clinically safe procedure in cases of severe naturally occurring SCI in dogs. Secondarily, we wanted to obtain preliminary evidence if this therapy could be of clinical benefit when compared to a larger number of similar, but historical, control cases. Strict entry criteria permitted recruitment of only neurologically complete paraplegic dogs into this study. Animals were treated by a combination of conventional and experimental techniques within approximately 72 h of admission for spinal trauma secondary to acute, explosive disk herniation. Outcome measures consisted of measurements of voluntary ambulation, deep and superficial pain perception, conscious proprioception in hindlimbs, and evoked potentials (somatosensory evoked potentials [SSEP]). We determined that polymer injection is a safe adjunct to the conventional management of severe neurological injury in dogs. We did not observe any unacceptable clinical response to polymer injection; there were no deaths, nor any other problem arising from, or associated with, the procedures. Outcome measures over the 6-8-week trial were improved by polymer injection when compared to historical cases. This recovery was unexpectedly rapid compared to these comparator groups. The results of this pilot trial provides evidence consistent with the notion that the injection of inorganic polymers in acute neurotrauma may be a simple and useful intervention during the acute phase of the injury.

Animals↗

Neurologic complications after melarsomine dihydrochloride treatment for Dirofilaria immitis in three dogs.

Melarsomine dihydrochloride is highly effective against both sexes of adult and L5 Dirofilaria immitis. Common adverse reactions include injection site irritation and reluctance to move. Neurologic complications associated with i.m. injection of melarsomine dihydrochloride for treatment of heartworm disease in 3 dogs are described. Different degrees of neurologic complications have been identified; the pathophysiologic features are unknown. It is speculated that the compound migrates out of the injection site via fascial planes and causes an ascending inflammation along nerve roots. The resulting extradural cord compression secondary to extensive inflammation and necrosis of epidural fat could induce a variety of neurologic deficits. Alternatively, inappropriate injection technique may result in direct contact of melarsomine with neural tissue. A heightened awareness of proper injection technique might prevent the development of most neurologic complications.

Animals↗

Sublumbar abscess and diskospondylitis in a cat.

Diskospondylitis is uncommon in cats. We describe a cat with diskospondylitis of the L7-S1 intervertebral disk, and a concurrent sublumbar abscess. Radiographic, computed tomographic and ultrasonographic findings are presented. Aerobic and anaerobic cultures of blood and spinal fluid yielded no growth. Aerobic and anaerobic urine cultures resulted in growth of an Enterococcus sp. and Clostridium perfringens, respectively. The cat was successfully treated with enrofloxacin and amoxicillin/clavulanic acid. Clinical signs resolved completely, and based on follow-up ultrasonography there was no remaining evidence of the sublumbar abscess. Etiologic agents and outcome from other cats with diskospondylitis are reviewed.

Animals↗

Neonatal cerebellar ataxia in Coton de Tulear dogs.

A neonatal ataxia syndrome was observed in Coton de Tulear dogs. Seven affected pups (32%; 7/22) of both genders came from 5 different litters with phenotypically normal parents. Neurologic examination revealed normal mental status, head titubation, intention tremors, and severe gait, stance, and ocular ataxia beginning at 2 weeks of age. One of the pups was able to walk with assistance, but most of the affected pups were unable to stand and used propulsive movements ("swimming") for goal-oriented activities. They frequently would fall to lateral recumbency with subsequent decerebellate posturing and paddling. Ocular motor abnormalities included fine vertical tremors at rest and saccadic dysmetria. The condition was nonprogressive at least until 4 months of age. No specific abnormalities were identified in routine laboratory screening of blood and urine. Cerebrospinal fluid (CSF) analysis was normal in 1 dog, and a mild increase in protein concentration was observed in a second dog. CSF organic and amino acid concentrations were within normal limits. Magnetic resonance imaging and computed tomography of the brain, electromyography, motor nerve conduction studies, and brain stem auditory-evoked potentials were within normal limits. Postmortem examinations were performed on 5 affected dogs between 2 and 4 months of age. Routine light microscopic and immunocytochemical examination of brain, spinal cord, peripheral nerve, and muscle did not disclose any gross or histologic lesions. Compared with the cerebellum from an age-matched normal dog, the cerebellum from an affected dog showed synaptic abnormalities, including loss of presynaptic terminals and organelles associated with parallel fiber varicosities within the molecular layer and increased numbers of lamellar bodies in Purkinje cells. An autosomal recessive trait affecting development of the cerebellum is suspected.

Animals↗

Surgical removal of an intramedullary spinal cord foreign body granuloma in a dog.

A 2-year-old, spayed female, mixed-breed dog was presented for evaluation of a progressive asymmetric tetraparesis and cranial nerve deficits with a 3-week duration. Computed tomography showed a contrast-enhancing lesion along the left side of the junction of the medulla and the cervical spinal cord. An exploratory surgery determined the presence of an intramedullary lesion of the first cervical spinal cord segment. The mass was removed through a dorsal midline myelotomy. Microscopic examination identified a foreign body granuloma that contained a dense, anisotropic outer wall, supporting the conclusion that the foreign body was of plant origin. The dog recovered to a more improved ambulatory status than prior to surgery.

Animals↗

External hydrocephalus in two cats.

External hydrocephalus describes an accumulation of cerebrospinal fluid (CSF) between the cerebral hemispheres and the overlying arachnoid membrane, rather than within the lateral ventricles. Two young cats with encephalopathic signs were diagnosed with external hydrocephalus, one via magnetic resonance imaging and one via computed tomography. Both cats had abnormally large, broad heads, with no evidence of open fontanelles. A surgical shunt was placed in each cat to divert the accumulated CSF within the cranial cavity to the peritoneal space. Both cats improved dramatically soon after surgical shunting was performed, and they continue to do well clinically, approximately 42 months and 8 months postoperatively, respectively.

Animals↗

A retrospective comparison of cervical intervertebral disk disease in nonchondrodystrophic large dogs versus small dogs.

Medical records of 144 small-breed dogs (< or =15 kg) and 46 medium- to large-breed dogs (>15 kg) with surgically confirmed, Hansen type I, cervical intervertebral disk extrusions were reviewed. The most common clinical presentation was cervical hyperesthesia. The most common sites affected were the second (C(2)) to third (C(3)) cervical intervertebral disk space in small-breed dogs and the sixth (C(6)) to seventh (C(7)) cervical intervertebral disk space in the larger dogs. Following surgery, 99% of the dogs had resolution of cervical hyperesthesia and were able to ambulate unassisted. Seven (4%) dogs required a second surgery; four of these were large-breed dogs.

Animals↗

Myasthenia gravis and hypothyroidism in a dog with meningomyelitis.

A 12-year-old, spayed female miniature poodle was evaluated because of a 4-day history of paraparesis, dysuria, and tenesmus. Neurological assessment suggested peripheral nervous system dysfunction, predominantly pelvic limb weakness with a possible concurrent sixth lumbar (L(6)) to second sacral (S(2)) myelopathy. Further studies supported the diagnoses of myasthenia gravis, hypothyroidism, and meningomyelitis. To the authors' knowledge, this is the first reported case of concurrent myasthenia gravis and meningomyelitis in the dog. It was unclear whether the identified conditions evolved from a shared etiopathogenesis or were merely coincidental.

Animals↗

Vascular encephalopathy associated with bacterial endocarditis in four dogs.

Vascular encephalopathy is a commonly encountered clinical complication of infectious endocarditis in humans, but it has been infrequently reported in dogs. A series of four dogs with bacterial endocarditis that subsequently developed acute onset of neurological deficits is described. Clinical signs, diagnostic test results, and outcomes for each case are presented and compared with the human clinical syndrome.

Animals↗