Phenotypic characterization of PIGN-associated paroxysmal dyskinesia in Soft-coated wheaten terriers and preliminary response to acetazolamide therapy.

A hereditary movement disorder in Soft coated wheaten terriers (SCWT) has been associated with a mutation in PIGN which encodes an enzyme involved in synthesis of glycosylphosphatidylinositol (GPI). The objective of this study was to describe and classify the clinical phenotype and assess therapeutic response. Twenty-five SCWT and related dogs homozygous for PIGN:c.398C>T with paroxysmal dyskinesia were available for inclusion. Medical records and video recordings of 17 dogs were evaluated in a retrospective case series. Affected dogs had episodes of involuntary, hyperkinetic movements and dystonia. Median age of onset was 2.5 years. A typical episode consisted of rapid, irregular hyperflexion and extension of the pelvic limbs with some degree of truncal dystonia. A mild episode consisted of spontaneous flexion of one pelvic limb while walking which could resemble a lameness. Episodes lasted several minutes to several hours and occurred up to 10 times/day or more. They were not associated with exercise or fasting but were sometimes triggered by excitement or stress. Acetazolamide therapy improved nine of 11 dogs, in seven cases abolishing episodes. Five of 17 dogs treated with other agents had mild improvement with clonazepam (n = 2), levetiracetam (n = 1), or phenobarbital (n = 2). Paroxysmal dyskinesias must be differentiated from seizure disorders since they often respond to different therapies. The SCWT phenotype consisted predominantly of hyperkinesia, and can respond dramatically to acetazolamide. GPI anchors proteins to the cell surface including carbonic anhydrase IV which modulates synaptic pH in the brain. Altered activity of this enzyme may be the target of acetazolamide therapy.

Diagnostic exercise. Cerebral mass in a puppy with respiratory distress and progressive neurologic signs.

A 5-month-old mongrel puppy with a history of respiratory disease presented with progressive neurologic dysfunction. Hematologic results included leukocytosis (neutrophilia with a left shift) and lymphopenia. A mass in the right forebrain, identified by magnetic resonance imaging, was biopsied during decompressive craniectomy. The histologic diagnosis was granulomatous meningoencephalitis with intralesional amoebae. The dog died within 24 hours of surgery. At necropsy, a well-demarcated granuloma was confined to the cerebrum, but granulomatous pneumonia was disseminated through all lobes of the lung. Concurrent infections included canine distemper, canine adenoviral bronchiolitis, and oral candidiasis. Canine distemper virus probably caused immunosuppression and increased susceptibility to secondary infections.

Characterization and mode of inheritance of a paroxysmal dyskinesia in Chinook dogs.

BACKGROUND: Paroxysmal dyskinesias are episodes of abnormal, involuntary movement or muscle tone, distinguished from seizures by the character of the episode and lack of seizure activity on ictal EEG. HYPOTHESIS: Paroxysmal dyskinesia is an inherited, autosomal recessive disorder in Chinook dogs. ANIMALS: Families of Chinook dogs with paroxysmal dyskinesia. METHODS: Pedigrees and medical histories were reviewed for 299 Chinook dogs. A family of 51 dogs was used for analysis. Episodes were classified as seizures, paroxysmal dyskinesia, or unknown, and segregation analysis was performed. RESULTS: Paroxysmal dyskinesia was identified in 16 of 51 dogs and characterized by an inability to stand or ambulate, head tremors, and involuntary flexion of 1 or multiple limbs, without autonomic signs or loss of consciousness. Episode duration varied from minutes to an hour. Inter-ictal EEGs recorded on 2 dogs with dyskinesia were normal. Three dogs with dyskinesia also had generalized tonic-clonic seizures. One of 51 dogs had episodes of undetermined type. Phenotype was unknown for 6 of 51 dogs, and 28 dogs were unaffected. Segregation was consistent with an autosomal recessive trait. CONCLUSIONS AND CLINICAL IMPORTANCE: This movement disorder is prevalent in the Chinook breed, and consistent with a partially penetrant autosomal recessive or polygenic trait. Insufficient evidence exists for definitive localization; episodes may be of basal nuclear origin, but atypical seizures and muscle membrane disorders remain possible etiologies. The generalized seizures may be a variant phenotype of the same mutation that results in dyskinesia, or the 2 syndromes may be independent.

Urinary 3-hydroxypropyl mercapturic acid (3-HPMA) concentrations in dogs with acute spinal cord injury due to intervertebral disc herniation.

The aim of this study was to investigate urinary 3-hydroxypropyl mercapturic acid (3-HPMA), a metabolite of acrolein, as a novel biomarker in acute spinal cord injury (ASCI) due to intervertebral disc herniation in dogs. Urine from 10 client-owned dogs with ASCI collected at presentation and 10 control dogs was analyzed for 3-HPMA. The median urinary 3-HPMA concentration in ASCI dogs was significantly higher than in control dogs, but was not correlated with the severity of ASCI. The median urinary 3-HPMA concentration in intact dogs was higher than in neutered dogs. Higher urinary 3-HPMA concentrations in dogs after ASCI support a role for acrolein, a cytotoxic by-product of lipid peroxidation, in canine ASCI. Urinary 3-HPMA could be used as a biomarker in future clinical trials to measure the effect of therapeutic intervention of reducing acrolein after ASCI.

Clinical Phenotype of Musladin-Lueke Syndrome in 2 Beagles.

Musladin-Lueke syndrome (MLS), previously termed Chinese Beagle syndrome, is an autosomal-recessive connective tissue disorder characterized by extensive fibrosis of the skin and joints that was first identified in Beagles in the 1970s. Recent research identified a founder mutation (c.660C>T; p.R221C) in the ADAMTSL2 gene in Beagles with MLS. Here, we report the detailed clinical phenotype and laboratory findings in 2 Beagles affected with MLS. We discuss these findings in relation to the human disorder geleophysic dysplasia (GD), which also arises from recessive ADAMTSL2 mutations, and recent findings in Adamtsl2-deficient mice.

The role of natural-enemy escape in a gallmaker host-plant shift.

The successful colonization of novel host-plant species by herbivorous insects may be facilitated by a reduction in natural-enemy attack on insect populations associated with the novel (derived) host plant. This is particularly true if natural enemies use host-plant or habitat cues in searching for their herbivore prey. In order to test whether the acquisition of enemy-free space could have influenced the host shift in the goldenrod ball gallmaker, Eurosta solidaginis, we estimated levels of natural-enemy attack in 25 host-race populations associated with Solidago altissima and S. gigantea (Compositae) spanning the zone of sympatry between S. altissima and S. gigantea host races in New England. Mortality due to attack by the parasitoid wasp Eurytoma obtusiventris was significantly higher for the ancestral than for the derived host race (30.5% versus 0.4%) across the transect, which is consistent with the enemy escape hypothesis. Contrary to this hypothesis, mordellid beetles caused significantly higher mortality on the derived than ancestral host race (17.1% versus 2.6%). Mortality by a second parasitoid wasp and birds showed no significant differences between the two host races. Overall, the derived host race had significantly higher survivorship across the transect (36.6% versus 20.8%). An analysis of survivorship and parasitoid mortality levels from sympatric sites in this study and previous studies showed a highly significant correlation between the levels of Eurytoma obtusiventris attack and the survivorship advantage of the derived host race. Observations of this parasitoid's searching behavior confirmed that it preferentially searches the ancestral host for fly larvae. Current patterns of host-race mortality and naturalenemy behavior and abundance are consistent with the facilitation of the host shift by escape from a specialist parasitoid.

Comparison of Pasteurella multocida serotyping systems.

Thirty-two type specific cultures used in four typing systems for serologically classifying Pasteurella multocida were compared as originally described for: (1) Little and Lyon's plate agglutination test; (2) Carter's indirect hemagglutination test, hyaluronidase decapsulation test, and acriflavine reaction; (3) Namioka's plate and tube agglutination tests; and (4) Heddleston's gel diffusion precipitin test. In addition, seven cultures from Robert's five passive protection groups were included. When reference cultures were examined by the typing system from which they were described, the results generally correlated with those results published. However, serotypes determined by one typing system generally did not correlate with serotypes determined by another system. Cultures of a single serotype in one system often represented more than one serotype in another system. Results indicated that cultures with one or two serotyping antigens in common may differ in other antigens. Because of the antigenic complexity of P multocida and the nature of the antigens involved in each test, a reliable correlation or equality between serotypes determined by different typing systems could not be made.

Virulence factors of Escherichia coli isolated from cows with acute mastitis.

A total of 184 Escherichia coli isolates recovered from cows with acute mastitis were examined for recognized pathogenic mechanisms and virulence factors commonly found in pathogenic groups of E coli. A modification of the Eng procedure (for detecting complement deficiencies in serum) was used to test for resistance to different animal sera. The Sereny test (for invasiveness), infant mouse test (for heat-stable enterotoxin), and Y-1 adrenal tumor cell assay (for heat-labile enterotoxin) were used. Hemagglutination tests, using rabbit, sheep, and guinea pig RBC, were done with and without added mannose. All of the 184 isolates were serum resistant in all tested sera. None of the isolates was invasive. Only 1 isolate was positive for heat-stable enterotoxin and 2 cultures were positive for heat-labile enterotoxin. Multiple patterns of hemagglutination were observed. The majority of the isolates exhibited both mannose-sensitive and mannose-resistant hemagglutinins with guinea pig and rabbit RBC. A few strains were positive only in mannose-sensitive or mannose-resistant hemagglutination tests. A few strains were negative in all hemagglutination tests. Based on our results, E. coli from cows with acute mastitis lack the virulence factors commonly observed in other E coli groups associated with disease. Serum resistance was the only characteristic that could be related to virulence.

Biochemical and serologic properties of Escherichia coli isolated from cows with acute mastitis.

Biochemical and serologic characteristics of 184 Escherichia coli isolates from cows with acute mastitis were determined. Trends or patterns unique to bovine isolates were not observed, except for the frequency of adonitol fermentation, which was positive in 84 (45.6%) of the cultures. Growth on Tergitol-7 agar had 3 types of colony morphologic characteristics; of these, the rough and intermediate textures predominated over those with smooth colony surfaces. A large variety of serovars was detected; the majority occurring as single isolates within a herd. Few K antigens were typeable. Only 2 isolates contained the K99 antigen. Seemingly, E coli organisms isolated from cows with acute mastitis cannot be distinguished as a specific pathogenic group on the basis of biochemical and serotest reactions.

Post-anesthetic cortical blindness in cats: twenty cases.

The medical records of 20 cats with post-anesthetic cortical blindness were reviewed. Information collected included signalment and health status, reason for anesthesia, anesthetic protocols and adverse events, post-anesthetic visual and neurological abnormalities, clinical outcome, and risk factors. The vascular anatomy of the cat brain was reviewed by cadaver dissections. Thirteen cats were anaesthetised for dentistry, four for endoscopy, two for neutering procedures and one for urethral obstruction. A mouth gag was used in 16/20 cats. Three cats had had cardiac arrest, whereas in the remaining 17 cases, no specific cause of blindness was identified. Seventeen cats (85%) had neurological deficits in addition to blindness. Fourteen of 20 cats (70%) had documented recovery of vision, whereas four (20%) remained blind. Two cats (10%) were lost to follow up while still blind. Ten of 17 cats (59%) with neurological deficits had full recovery from neurological disease, two (12%) had mild persistent deficits and one (6%) was euthanased as it failed to recover. Four cats (23%) without documented resolution of neurological signs were lost to follow up. Mouth gags were identified as a potential risk factor for cerebral ischemia and blindness in cats.

Serum D-lactate concentrations in cats with gastrointestinal disease.

BACKGROUND: Increased D-lactate concentrations cause neurological signs in humans with gastrointestinal disease. HYPOTHESIS/OBJECTIVES: To determine if serum D-lactate concentrations are increased in cats with gastrointestinal disease compared to healthy controls, and if concentrations correlate with specific neurological or gastrointestinal abnormalities. ANIMALS: Systematically selected serum samples submitted to the Gastrointestinal Laboratory at Texas A&M University from 100 cats with clinical signs of gastrointestinal disease and abnormal gastrointestinal function tests, and 30 healthy cats. METHODS: Case-control study in which serum D- and L-lactate concentrations and retrospective data on clinical signs were compared between 30 healthy cats and 100 cats with gastrointestinal disease. Association of D-lactate concentration with tests of GI dysfunction and neurological signs was evaluated by multivariate linear and logistic regression analyses, respectively. RESULTS: All 100 cats had a history of abnormal gastrointestinal signs and abnormal gastrointestinal function test results. Thirty-one cats had definitive or subjective neurological abnormalities. D-lactate concentrations of cats with gastrointestinal disease (median 0.36, range 0.04-8.33 mmol/L) were significantly higher than those in healthy controls (median 0.22, range 0.04-0.87 mmol/L; P = .022). L-lactate concentrations were not significantly different between the 2 groups of cats with gastrointestinal disease and healthy controls. D-lactate concentrations were not significantly associated with fPLI, fTLI, cobalamin, folate, or neurological abnormalities (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: D-lactate concentrations can be increased in cats with gastrointestinal disease. These findings warrant additional investigations into the role of intestinal microbiota derangements in cats with gastrointestinal disease, and the association of D-lactate and neurological abnormalities.