Familial reflex myoclonus in Labrador Retrievers

Three 6-week-old male purebred yellow Labrador Retrievers were presented with intermittent stimulus-sensitive contractions of the appendicular and axial muscles. Five littermates were normal, although the grandsire of the affected litter had sired 2 previous litters containing similarly affected pup. Although alert and responsive, the affected dogs appeared decerebrate with extensor rigidity and opisthotonus during handling. During severe episodes, respiratory distress was observed. Generalized contractions were initiated by voluntary movements, but at rest the muscles relaxed. Neurologic deficits were not detected, although efforts to elicit segmental reflexes, assess muscle tone, or assist walking resulted in generalized stiffness. Electromyograms from the semitendinous muscles (musculi semitendinosus) had increased motor unit amplitude (up to 5,000 microV) with polyphasic action potentials. There were no myotonic discharges. A reduced interference pattern was seen. A single tactile stimuli of the distal limb resulted in 3 responses, each lasting less than or equal to 10 ms at latencies of 0 to 12 ms, 20 to 30 ms, and 35 to 40 ms, characteristic for reflex myoclonus. The motor nerve conduction velocities were normal for age (32 to 35 ms). Age-matched control dogs had motor unit action potentials of 100 to 200 microV and single compound motor unit discharges to single tactile stimuli. Therapeutic trials with diazepam and clonazepam produced minimal effects on the muscle contractions. Values of urinalyses, complete blood cell counts, and serum chemistries were within normal limits. Frozen muscle section biopsy findings, including enzyme histochemical assessment of muscle fiber types, were normal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anury in two Cairn terriers

Congenital anury (taillessness) was observed in 2 Cairn Terriers. Fecal staining of the hind limbs was evident in both dogs. A mating of the affected dogs produced a litter of 2 apparently normal pups. The small litter size may have been attributable to lethal gene combinations similar to those described in mice. The radiographic appearance of the caudal and sacral vertebrae was atypical in both tailless dogs. Results of myelography and electrodiagnostic testing of anal sphincter function were normal in one of the dogs. One of the tailless dogs was euthanatized and was found to lack specific muscles and muscle parts responsible for normal defecation, which resulted in fecal staining of the hind limbs. Pedigree analysis revealed the tailless dogs to be closely related and slightly inbred, suggesting a hereditary etiologic factor for anury.     

Babesiosis in a litter of pups

Babesia canis infection was diagnosed in a litter of seven 3-week-old Mastiff pups kept in a north Florida kennel. The pups were evaluated because of poor weight gain; the smallest pup also was markedly lethargic. Six of the pups were anemic and thrombocytopenic. A positive linear correlation between PCV and absolute reticulocyte count suggested that the variation in PCV may have been related more to the ability of a pup to increase erythrocyte production than to a difference in magnitude of erythrocyte destruction. All pups recovered from clinical signs and hematologic abnormalities attributable to babesiosis within 2.5 weeks after treatment with diminazene aceturate. Transient neurologic signs observed in 1 pup 3 days after treatment were believed to represent an adverse drug reaction. The dam of the litter had a serum titer of 1:640 for B canis, but appeared healthy, as did approximately 30 other adult dog in the kennel. The strain of B canis infecting dogs in the kennel caused severe illness and death in some pups, but clinically inapparent disease in adult dogs.     

Neosporosis in Beagle dogs: clinical signs, diagnosis, treatment, isolation and genetic characterization of Neospora caninum

Clinical neosporosis was diagnosed in a litter of five pups born to a Beagle bitch from Virginia, USA. Four of the pups developed limb weakness starting at 4 weeks of age. The dogs were suspected to have neosporosis based on clinical signs and empirically treated with Clindamycin (75 mg, oral, twice daily, total 150 mg) starting at 9 weeks of age and the dosage was doubled at 13 weeks of age. Antibodies to Neospora caninum were detected in sera of the dam and pups when first tested serologically at the age of 4 months. The owner donated the pup with the worst clinical signs and the dam for research; both dogs were euthanized. Viable N. caninum was isolated in gamma interferon gene knock out (KO) mice and in cell culture from the pup killed at 137 days of age. Tissue cysts, but no tachyzoites, were found in histological sections of brain and muscles. The isolate was also identified as N. caninum by PCR and sequence analysis and designated NC-9. N. caninum was neither isolated by bioassay in KO mice nor found in histological sections of tissues of the bitch. Clinical signs in the remaining three pups improved considerably after a 6-month treatment with Clindamycin; N. caninum antibody titers were still persistent in these pups at 23 months of age. Results indicate that medication with Clindamycin can improve clinical condition but not eliminate N. caninum infection.     

Metabolic and structural abnormalities in dogs with early left ventricular dysfunction induced by incessant tachycardia

OBJECTIVE: To assess morphologic and metabolic abnormalities in dogs with early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP). ANIMALS: 7 Beagles. PROCEDURE: Plasma carnitine concentrations were measured before and after development of ELVD induced by RRVP. At the same times, transvenous endomyocardial biopsy was performed, and specimens were submitted for determination of myocardial carnitine concentrations and histologic, morphometric, and ultrastructural examination. RESULTS: In 4 dogs in which baseline plasma total carnitine concentration was normal, RRVP induced a decrease in myocardial total and free carnitine concentrations and an increase in myocardial esterified carnitine concentration. In 3 dogs in which baseline plasma total carnitine concentration was low, plasma and myocardial carnitine concentrations were unchanged after pacing. Structural changes associated with pacing included perinuclear vacuolization in 3 dogs. Morphometric analyses indicated there was a decrease in myofiber cross-sectional diameter and area following pacing. Electron microscopy revealed changes in myofibrils and mitochondria following pacing. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that moderate to severe alterations in myocyte cytoarchitecture are present in dogs with ELVD induced by RRVP and that in dogs with normal plasma carnitine concentrations, myocardial carnitine deficiency may be a biochemical marker of ELVD. Results also indicated that transvenous endomyocardial biopsy can be used to evaluate biochemical and structural myocardial changes in dogs with cardiac disease.     

Familial canine dermatomyositis: clinicopathologic, immunologic, and serologic studies

Laboratory studies were performed on 3 Collies with familial canine dermatomyositis, 6 progeny from a breeding of 2 of the Collies (incross litter), and 4 progeny from the breeding of an affected Collie male and a normal Labrador Retriever (outcross litter). Hematologic abnormalities were leukogram changes consistent with inflammation, and, in 2 severely affected incross dogs, anemia of inflammatory disease. Serum muscle enzyme activities were not markedly increased. High concentrations of immune complexes and proportionally increased total immunoglobulin G were present in the sera of moderately and severely affected incross dogs. The same dogs had weakly positive direct Coombs' tests, and 1 affected outcross dog had a strongly positive direct Coombs' test. Rheumatoid factor was present in a severely affected incross dog. A few dogs had polyclonal globulin increases that were attributed to inflammation. Low antibody titers to canine calicivirus were present in 3 dogs and a low titer to canine coronavirus was present in 1 dog.     

Familial canine dermatomyositis: clinical, electrodiagnostic, and genetic studies

Three Collies with a skin disorder, 6 progeny from a breeding of 2 of the Collies (incross litter), and the 4 progeny from the breeding of an affected Collie male and a normal Labrador Retriever female (outcross litter) were examined. By 7 to 11 weeks of age, all 6 dogs in the incross litter developed a qualitatively similar, but variably severe, dermatitis of the ears, face, lips, tip of the tail, and over bony prominences of limbs. Later, myopathic signs characterized by bilaterally symmetrical skeletal muscle atrophy of the head, neck, trunk, and extremities; facial palsy; decreased jaw tone; stiff gait; and hyperreflexia were observed in the dogs more severely affected by the dermatitis. Of the 4 dogs in the outcross litter, 3 had similar, but milder, clinical manifestations of the dermatitis and myopathy. Cutaneous lesions consisted of intraepidermal and subepidermal vesicles or pustules with intradermal infiltration by leukocytes. Muscle lesions included myositis; myofiber degeneration, regeneration, and atrophy; and fibrosis. A generalized myopathy in the severely affected dogs was indicated by abnormal readings on needle electromyograms and normal motor nerve conduction velocities. Spontaneous needle electromyogram abnormalities were fibrillation potentials, positive sharp waves, and bizarre high-frequency discharges. Retrospective and prospective genetic analyses disclosed a definite familial tendency and indicated the condition has an autosomal dominant component.     

Cystic bone lesions in related Old English Sheepdogs

At 6 months of age, an Old English Sheepdog with swollen and painful distal radial/ulnar metaphyses was found to have multiple cystic lesions in left and right radius and ulna. Cystic bone lesions were also detected radio-graphically in two clinically normal littermates and in the sire and dam of the litter. Radiographic changes of nutritional secondary hyperparathyroidism were found in the three affected pups and in two other individuals from the litter of eight.
The cystic lesions in one pup were drained surgically and the cyst wall curetted, while the other two pups were not treated. The lesions in all three pups gradually resolved and had almost completely disappeared by 10 months of age.     

Congenital peripheral vestibular disease attributed to lymphocytic labyrinthitis in two related litters of Doberman pinscher pups

Five Doberman Pinscher pups from a litter of 10 (litter A) and 3 of 9 pups from a subsequent mating of the same bitch (litter B) had clinical signs consistent with unilateral or bilateral peripheral vestibular disease. Results of CBC, serum biochemical analysis, urinalysis, ophthalmologic examination, deep otoscopic examination, and CSF analysis were normal in all affected pups. Bacteriologic culture results from CSF were negative and affected pups did not have canine distemper antibody titers in CSF. The most severely affected littermates were euthanatized and necropsied at the owner's request. Gross lesions were not found at necropsy, but marked lymphocytic labyrinthitis was discovered microscopically in decalcified sections of the labyrinthine system. The case history and histologic findings were suggestive of an infectious, most likely viral, cause, but organisms were not isolated from specimens of CNS tissue. The involvement of the same bitch in the 2 litters suggests heritable factors. One mildly affected pup apparently recovered or compensated for its vestibular dysfunction.     

Neospora caninurn Infection in English Springer Spaniel Littermates

Progressive paraparesis developed in four male English Springer Spaniel pups from a litter of five during the first 10 weeks of life. Two of the pups, which had the earliest onset of neurologic signs, were euthanatized without further workup. However, a detailed investigation was completed on the remaining two littermates at 12 weeks of age. Both pups had progressive paraparesis for 3 to 4 weeks before presentation, with one dog developing subsequent asymmetric pelvic limb extensor rigidity. Based on results from neurologic examination, cerebrospinal fluid (CSF) analysis, electrophysiology, and muscle/nerve biopsy, a presumptive diagnosis of protozoal polyradiculitis and polymyositis was made. Necropsy of the most severely affected pup confirmed the clinical diagnosis of inflammatory nerve root and muscle disease but no organisms were found. To increase the potential yield of organisms, the second pup was placed on immunosuppressive doses of corticosteroids and euthanatized 2 weeks later. Numerous organisms were found in lesions in muscle and the central nervous system. Organisms grew in tissue culture and were isolated from the peritoneal fluid of gerbils inoculated with infected tissue. Organisms were not isolated from inoculated mice, guinea pigs, rabbits, and hamsters. No parasites were seen in feces or tissues of three cats fed infected dog tissues. Serologic testing demonstrated a strong positive titer to Neospora caninum in both pups, and electron microscopy showed the characteristic morphology of this parasite.     

Reproductive evaluation of male beagles and the safety of ivermectin

Ivermectin had no adverse effects on spermatogenesis, fertility, or reproductive performance of Beagle dogs when administered orally at 600 micrograms/kg (0.6 mg/kg) of body weight monthly for 8 treatments. Semen was collected every 3 days from 28 days before treatment began until 83 days thereafter from 6 ivermectin-treated Beagles and 6 similar water-treated controls (38 collections/dog). All dogs were then bred to 2 nontreated bitches each; litter size, birth weights, and pup abnormalities and mortalities were evaluated. After all pups were whelped, each dog was euthanatized and necropsied, and the testis and epididymis were examined microscopically.     

Infections with Encephalitozoon cuniculi and Leptospira interrogans, serovars grippotyphosa and ballum, in a kennel of foxhounds

Leptospira interrogans serovars grippotyphosa and ballum were isolated from kidney and urine of an American Foxhound pup. The pup was from a litter of 12, all of which were unthrifty. Titers for serovar grippotyphosa in pups from the litter ranged from 200 to 6,400 and 23 of 36 adult dogs in the kennel had titers to that serovar. None of the sera was tested for antibodies to serovar ballum. Leptospires were not isolated from or observed in 2 littermates and 1 penmate, but gram-positive organisms morphologically compatible with Encephalitozoon cuniculi were detected in their brains and kidneys.     

Autosomal recessive severe combined immunodeficiency of Jack Russell terriers.

Because of unexplained mortality among 33 sibling offspring of a single pair of dogs, a family of Jack Russell Terriers was investigated. Twelve pups, 5 male and 7 female, died between 8 and 14 weeks of age. Six of those animals died in the field within 50 hours following vaccination with modified live vaccines. Subsequent histopathologic examination revealed the absence of splenic white pulp in 4 dogs and hepatic inclusions diagnostic for adenoviral infection in 2 dogs. Two additional litters yielded 2 pups with the same splenic and hepatic lesions. These observations led to a detailed study of 7 siblings whelped specifically for this investigation. Four of these 7 siblings had a profound lymphopenia and a decrease in serum immunoglobulins. Six of these dogs were necropsied at 7 weeks of age, and 4 of them had marked hypoplasia of all lymphoid tissue. The affected pups had an 86% decrease in mean thymic weight, with poor corticomedullary differentiation, and very few CD3-positive (T cell) thymocytes were detected immunohistochemically. However, the affected thymic tissue stained intensely with a immunochemical stain for cytokeratin. The other affected lymphoid tissues were identified histologically only by stromal architectural characteristics. Lymph nodes lacked both CD3 and CD79a (B cell) positive cells. The analyzed breeding data were consistent with an autosomal recessive mode of inheritance. This canine severe combined immunodeficiency has immunologic and pathologic features similar to those observed in immunodeficient C.B-17 mice and Arabian horses.     

Histochemical differentiation of fiber types in neonatal canine skeletal muscle

Differentiation of fiber types in developing canine skeletal muscle was studied, using morphologic, morphometric, and histochemical techniques. Sample collections were made from 6 muscles from the pectoral and pelvic limbs of 16 healthy pups between 1 day and 12 weeks of age. In newborn pups, 90% to 95% of the fibers in the 6 muscles were classified as undifferentiated or type IIC; the remaining fibers were classified either normal or large-size type I. Large-size type I fibers usually accounted for 2% to 4% of the total population and were considered analogous with the B fiber of Wohlfart. These fibers were larger than all other fiber types and disappeared after pups reached 4 to 5 weeks of age. After 2 to 4 weeks, the number of undifferentiated fibers decreased with the appearance of, and the concomitant numerical increases of, normal size type I and type IIA fibers. The percentages of type I and IIA fibers approached proportions of the adult dog by 12 weeks, at which time a type IIA fiber predominance was present in biceps femoris, lateral head of the gastrocnemius, cranial tibial, and long head of the triceps. Type I fibers predominated in medial head of the triceps and superficial digital flexor after 4 to 5 weeks. The mean fiber diameters of type I and IIA fibers were similar to any given muscle throughout the postnatal development. All fiber types stained uniformly with the oxidative stain nicotinamide adeninedinucleotide-tetrazolium reductase during the first 12 weeks of life, whereas a distinction between type I and II fibers was evident after 3 to 4 weeks with the periodic acid-Schiff stain reaction.     

Transmission and attempted isolation of the etiologic agent associated with lymphofollicular hyperplasia of the canine species.

From 18 donor dogs of different breeds and ages, follicular lesions of the third eyelid (plica senilunaris conjunctiva) and genitalia were surgically removed, trypsinized, and inoculated on monolayers of HeLa, rabbit kidney, and canine kidney cell cultures. Blind passages of the lesion material were made every 96 hours for 10 to 15 cell culture passages. Cellular suspensions prepared from the lesions were grown in test tubes and passaged 3 times at 10-day intervals between passages. All cultures were observed each day for cytopathic effect. Transmission studies were made by (1) inoculating normal pups with cellular suspensions of the lesions from an infected dog and an infected pup, (2) placing normal pups in contact with infected ones for contact transmission, and (3) inoculating normal animals with cell suspensions prepared from inoculated monolayers. Cytopathic changes were not seen in any of the cell culture monolayers. All transmission attempts were successful, in that characteristic lesions comparable in appearance to those seen in natural infections were produced in susceptible pups. The lesion material from an infected pup was found to be infective for a normal pup after 6 passages in tissue culture (primary rabbit kidney cells) despite absence of cytopathic effect.     

Pup mortality in laboratory mice – infanticide or not?

Background

Despite being the most commonly used mammal in biomedical research, problems with perinatal mortality in mice have received little attention and the causes of pup death are still poorly known. Females are often housed alone with their litters and since the lost pups are generally eaten, it is commonly assumed that the mother has killed them. However, more detailed observations than have been reported previously in the literature are required to establish if the cause of death is infanticide. Litter loss can only be prevented efficiently after underlying causes have been carefully investigated and interpreted. The aim of this study was to investigate if females actively kill their pups by observing the behaviour of females and pups in litters that later were lost. We used video recordings of females that lost their entire litter to observe females in detail from parturition until the pups died. In total, 10 C57BL/6 females (wildtype and the knockouts Hfe^−/− and β2m^−/−) were studied, housed in Makrolon II cages with or without access to a small amount of nesting material.

Results

Three of the females had pups that were never seen moving, and another three females had one or two pups that never moved, indicating that some pups were most likely still-born. In five females with live-born pups, detailed observations from the time when a pup was last seen moving until it died were possible to carry out. We observed females eating dead offspring and interacting with both moving and dead pups. However, we never observed a pup stop moving when manipulated by the female, nor were any wounds seen in the pups. Hence, we found no evidence of infanticide when studying females that had lost their entire litter.

Conclusion

These results suggest that other causes than infanticide plays a major role in mouse pup death, and stress the need for more systematic and careful investigations of the causality of litter loss.     

Shetland Sheepdog leukodystrophy

Three litters of Shetland Sheepdog pups born to the same bitch and 2 different sires were studied because of uncontrollable seizures or progressive neurologic dysfunction. Four pups from the 1st litter, 1 from the 2nd litter, and 4 from the 3rd litter had severe diffuse spongy degeneration of the white matter of the brain and spinal cord. An inherited basis for this syndrome was suspected. The purpose of this study was to evaluate the pups with currently available screening tests for the metabolic, biochemical, infectious, and toxicologic causes of leukodystrophy seen in humans and animals. Computed tomography scans revealed diffuse hypomyelination in the affected pup. Complete postmortem examination, including histopathology and electron microscopy, delineated a leukodystrophy resembling human Canavan's disease, but amino acid and organic acid metabolism abnormalities were not detected. No etiology for Shetland Sheepdog leukodystrophy has been found, but this condition represents another familial disease in the purebred dog population.     

Primary hyperparathyroidism in German shepherd dogs: a disorder of probable genetic origin

Primary hyperparathyroidism was diagnosed in two German shepherd pups from a litter of four females. Clinical signs were apparent by two weeks of age and included stunted growth, muscular weakness, and polydipsia/polyuria. Radiography revealed diffuse reduction in bone density. Both pups had marked hypercalcemia, hypophosphatemia, increased plasma immunoreactive parathyroid hormone concentrations and increased fractional clearance of inorganic phosphate in the urine. Intravenous infusion of one affected pup with calcium gluconate failed to suppress the plasma concentration of immunoreactive parathyroid hormone, suggesting autonomous secretion of parathyroid hormone. Necropsy of the other pup at eight weeks of age revealed diffuse hyperplasia of parathyroid chief cells, nodular hyperplasia of thyroid C-cells, skeletal alterations consistent with fibrous osteodystrophy, hypercalcemic nephropathy, and extensive mineralization of the lungs and gastric mucosa. The dam and sire were half sibs. One male pup from a previous litter of six had developed similar clinical signs and radiographic lesions, suggesting autosomal recessive inheritance. This is the first report of hereditary primary hyperparathyroidism in domestic animals, a disease which may be analogous to hereditary neonatal primary hyperparathyroidism in children.     

Hormonal response to dobutamine cardiac stress testing in a conscious canine model of early left ventricular dysfunction induced by chronic rate overload

The aims of this study were to investigate (1) hormonal activation before and during dobutamine cardiac stress testing (DST) in a canine model of early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP) and (2) the relationship between this hormonal profile and carnitine concentrations.Before the pacing period, the 6 dogs were assigned to 2 groups according their baseline total plasma carnitine concentration. A DST was performed on each dog before activation of the pacemaker and every 3 to 4 days during development of 3 progressive stages of ELVD (stages 1, 2 and 3). Plasma atrial natriuretic factor (ANF), angiotensin II (ANG II) and endothelin-1 (ET-1) levels were measured at the start and at the end of each DST. Effects of ELVD, DST and plasma carnitine concentration on these measurements were tested.The RRVP induced a significant increase of ANF and ANG II and a non significant trend toward increase of ET-1 in all dogs.Before the pacing period, ANF remained constant during the DST in dogs with normal total plasma carnitine concentration, while it significantly decreased in dogs with low total plasma carnitine concentration. Dobutamine stress testing induced a significant decrease in ANF in all dogs in ELVD. Dobutamine infusion induced a significant increase in ANG II in all dogs before as well as during the pacing period while ET-1 was unchanged.These results suggest that investigation of the hormonal profile before and after a dobutamine challenge might provide important diagnostic information in dogs with asymptomatic or mildly symptomatic cardiac dysfunction of different origins.     

Effects of racing and training on serum thyroid hormone concentrations in racing Greyhounds.

OBJECTIVES: To determine the effects of racing and training on serum thyroxine (T4), triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations in Greyhounds. ANIMALS: 9 adult racing Greyhounds. PROCEDURE: Serum thyroid hormone concentrations were measured before and 5 minutes after a race in dogs trained to race 500 m twice weekly for 6 months. Resting concentrations were measured again when these dogs had been neutered and had not raced for 3 months. Postrace concentrations were adjusted relative to albumin concentration to allow for effects of hemoconcentration. Thyroid hormone concentrations were then compared with those of clinically normal dogs of non-Greyhound breeds. RESULTS: When adjusted for hemoconcentration, total T4 concentrations increased significantly after racing and TSH concentrations decreased; however, there was no evidence of a change in free T4 or total or free T3 concentrations. Resting total T4 concentrations increased significantly when dogs had been neutered and were not in training. There was no evidence that training and neutering affected resting TSH, total or free T3, or free T4 concentrations. Resting concentrations of T3, TSH, and autoantibodies against T4, T3, and thyroglobulin were similar to those found in other breeds; however, resting free and total T4 concentrations were lower than those found in other breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Except for total T4, thyroid hormone concentrations in Greyhounds are affected little by sprint racing and training. Greyhounds with low resting total and free T4 concentrations may not be hypothyroid.