Retrospective cohort study of changes in hip joint phenotype of dogs in the United States.

OBJECTIVE: To determine whether there had been a significant improvement in hip joint phenotype of dogs in the United States by comparing results of evaluations done by the Orthopedic Foundation for Animals of dogs born between 1972 and 1980 with those of dogs born between 1989 and 1992 and determining whether there had been an increase in the percentage of dogs classified as having excellent hip joint phenotype. DESIGN: Retrospective cohort study. SAMPLE POPULATION: 270,978 evaluations. PROCEDURE: Numbers and percentages of dogs classified as having excellent hip joint phenotype during each period and change between periods in percentages of dogs classified as having excellent hip joint phenotype were calculated. RESULTS: Percentage of dogs born between 1989 and 1992 that were classified as having excellent hip joint phenotype (15,289/143,668; 10.64%) was significantly higher than percentage of dogs born between 1972 and 1980 that were classified as having excellent hip joint phenotype (9,960/127,310; 7.82%). The increase in percentage of dogs classified as having excellent hip joint phenotype was significantly higher for male (51%) than for female (27%) dogs. CLINICAL IMPLICATIONS: Results suggest that there has been an improvement in the hip joint phenotype of dogs in the United States between the 1970s and early 1990s and that the improvement has been greater among male than among female dogs.

The inheritance of osteochondritis dissecans and fragmented coronoid process of the elbow joint in labrador retrievers.

Five matings between dogs bilaterally affected with osteochondritis dissecans and fragmented coronoid processes resulted in a distribution of lesions in the elbows of the offspring that indicated the diseases were inherited independently as polygenic traits.

Inheritance of histiocytosis in Bernese mountain dogs.

One hundred and twenty-seven cases of histiocytosis in Bernese mountain dogs (BMD) were evaluated to determine if the tumour is inherited. Family data ruled out autosomal recessive, autosomal dominant and sex-linked modes of inheritance. The trait was determined to be inherited with a polygenic mode of inheritance. The salient points permitting this conclusion are: pedigrees developed from independently selected propositi link up allowing the tracing of all cases through several generations; multiple cases occur in the same litter; multiple cases have been produced by given dams and sires; there is a higher frequency of the disease among offspring of affected parents when compared to offspring of normal parents that produced histiocytosis and all offspring in the general population of BMDs; the fact that histiocytosis is common in BMDs and rare in eight other breeds and accounts for 25.4 per cent of the 500 tumours studied in this breed. The heritability of this trait was calculated to be 0.298.

Studies of adenine nucleotide biochemistry in the Chediak-Higashi syndrome.

The Chediak-Higashi syndrome (CHS) is an inherited disorder of humans and of several animal species, characterized by partial albinism, pseudohemophilia, increased susceptibility to disease, and large inclusions in all granule-forming cells. In this study, various parameters of adenine nucleotide biochemistry were examined in beige mouse kidney tissue and in peripheral blood leukocytes from CHS mink. There were no differences in the total protein content, total ATPase activity or the magnesium (Mg2+) ATPase or the sodium-potassium (Na(+)-K+) ATPase activities, the concentrations of ATP, ADP, and AMP, or the adenylate energy charge (AEC) in kidney extracts from beige and normal mice. In studies of leukocytes, there were no differences in the concentrations of ATP, ADP, AMP, and cAMP or the AECs in total leukocyte preparations and in extracts from granulocytes or nongranulocytes. These results can be explained by any one of several hypotheses: no storage pool of adenine nucleotides exists in the tissues examined; or the alleged storage pool is not affected by CHS; or the quantity of nucleotides in the alleged storage pool is too minute to be evaluated by current techniques; or the CHS defect might cause a shift from the storage pool to the metabolic pool.

Platelet aggregation and dense granule secretion in a colony of dogs with spontaneous hypertension.

AIM: Since canine hereditary essential hypertension has been previously reported in a colony of Siberian husky dogs, we tested the suitability of this model for use in studies on the platelet defect identified in humans with essential hypertension. METHODS: Platelet aggregation and dense granule ATP secretion were measured in dogs with essential hypertension and normotensive control dogs. RESULTS: The platelets from the hypertensive group showed significantly increased aggregation and secretion in response to stimulation with ADP. There was no significant increase in aggregation or secretion when platelets from hypertensive dogs were stimulated by platelet-activating factor, thrombin, calcium ionophore A23187 or phorbol myristate acetate. CONCLUSION: The increased aggregation and secretion responses in platelets from the hypertensive dogs suggest that a defect similar to that reported in humans with essential hypertension exists and that further investigation is warranted.

Cellular basis of decreased rate of longitudinal growth of bone in pseudoachondroplastic dogs.

Regulation of growth of long bones occurs in cartilage growth plates, where proliferation of chondrocytes, matrix synthesis, and an increase in vertical height in the direction of growth all contribute to the final length of a bone. In this study, we tested the hypothesis that an increase in chondrocytic vertical height is a major variable that accounts for the decreased rate of growth of long bones in Scottish deerhound dogs that had pseudoachondroplasia. The diagnosis of pseudoachondroplasia is based, primarily, on the demonstration of alternating electron-dense and electron-lucent lamellae with a periodicity of 100 to 150 nanometers in dilated rough endoplasmic reticulum. These ultrastructural changes are similar to those seen in humans who have pseudoachondroplasia. In Scottish deerhounds that have the disease, growth of bone is approximately 65 per cent of that in normal animals. There were striking differences in the diameters of proliferating and hypertrophic chondrocytes in pseudoachondroplastic animals compared with normal animals. Specifically, the horizontal diameter of proliferating chondrocytes was 22.7 micrometers in normal animals and 11.3 micrometers in pseudoachondroplastic animals. The vertical diameter of proliferating chondrocytes was 4.8 and 7.6 micrometers in normal and pseudoachondroplastic animals. In the distal 100 micrometers of the hypertrophic zone, the mean horizontal diameter of hypertrophic chondrocytes was 29.6 and 19.1 micrometers and the mean vertical diameter was 22.8 and 18.6 micrometers in normal and pseudoachondroplastic animals. All these differences were statistically significant. The changes in vertical height resulted in a significant difference in the incremental difference in vertical height between chondrocytes from the proliferative and hypertrophic zones in normal animals (18.0 micrometers per chondrocyte) and pseudoachondroplastic animals (11.0 micrometers per chondrocyte). Each chondrocyte in the abnormal plates achieved only 61 per cent of the incremental difference of chondrocytes in normal plates. The mean cellular volume of chondrocytes in the hypertrophic zone was 13,050 cubic micrometers in the normal animals and 10,740 cubic micrometers in the pseudoachondroplastic animals. This difference was not statistically significant. These results are discussed in relation to current theories of the role of the shape and change in volume of chondrocytes in the regulation of longitudinal growth of bone.(ABSTRACT TRUNCATED AT 400 WORDS)

Mink as a predictive model in toxicology.

This paper reviewed the biomedical and toxicological database concerning the use of mink as a predictive model of human responses. It is concluded that substantial information exists on the mink genetics, physiology, metabolism, nutritional requirements, and susceptibility to infectious disease; and provides a foundation upon which interspecies extrapolation may be considered. In addition, information on the response of mink to several dozen toxic substances revealed that mink respond in a qualitatively and quantitatively similar manner to other more commonly employed species as well as humans. Our conclusion does not infer that mink should be used routinely in toxicological testing for estimation of human responses. However, it indicates that toxicological data from this species may be a useful complement in risk assessment processes based upon data obtained from traditionally employed models such as rats and dogs.

Clinical, radiographic, pathologic, and genetic features of osteochondrodysplasia in Scottish deerhounds.

Clinical, radiographic, pathologic, and genetic features of a form of osteochondrodysplasia in 5 related Scottish Deerhound pups from 2 litters were evaluated. All pups appeared to be phenotypically normal at birth. At approximately 4 or 5 weeks, exercise intolerance and retarded growth were observed. Kyphosis, limb deformities, and joint laxity gradually developed. Radiography of the affected pups revealed skeletal changes characterized by abnormalities in long bones and vertebrae, with involvement of epiphyses, growth plates, and metaphyses. Short long bones and vertebrae and irregular and delayed epiphyseal ossification were most noticeable in younger pups; in older pups, bony deformities became more prominent. In skeletally mature dogs, osteopenia and severe deformities were seen. The histologic changes of the growth plate were compatible with a diagnosis of chondrodysplasia. Growth plate chondrocytes contained periodic acid Schiff-positive, diastase-resistant cytoplasmic inclusions. A single autosomal recessive mode of inheritance was suspected.

Lesions in Brangus cattle with Chediak-Higashi syndrome.

Hair, peripheral blood leukocytes, and other tissues from two related Brangus calves with phenotypic characteristics of Chediak-Higashi syndrome were examined by light and electron microscopy. Enlarged, pleomorphic, cytoplasmic granules, morphologically compatible with lysosomes, were seen in several neutrophils, many eosinophils, renal tubular epithelial cells, and Kupffer cells. Hair shafts of the calves showed irregular distribution and clumping of melanin granules. Severe infection and a possible hemorrhagic tendency were recognized. These Brangus calves represent the third breed of cattle affected with this genetic disease.

Primary hypertension in a colony of dogs.

A 5-year-old female Siberian husky that was diagnosed as an essential hypertensive was bred several times over a 5-year period, producing a colony of 39 offspring. Thirty of the 39 animals were subjected to biweekly systemic arterial blood pressure determinations with femoral arterial puncture and were placed into two hypertensive and two normotensive groups based on mean blood pressure: Group 1 (mean blood pressure, 128 +/- 12 mm Hg), Group 2 (mean blood pressure, 121 +/- 3 mm Hg), Group 3 (mean blood pressure, 114 +/- 8 mm Hg), and Group 4 (mean blood pressure, 101 +/- 9 mm Hg). Groups 1, 2, and 3 had mean blood pressures significantly higher than that of Group 4 (p less than 0.05). Ten dogs (representatives from Groups 1, 2, and 3) were subjected to more detailed clinical testing including angiography, echocardiography, ophthalmic examination, plasma catecholamine and renin activity measurements, plasma lead and cadmium determinations, cerebrospinal fluid examination, renal profile, and serum chemistry and hematological analysis. Five unrelated normotensive Siberian huskies were compared with colony dogs by using echocardiography. Groups 1 and 2 showed a clear but statistically insignificant upward trend in left ventricular wall thickness indexed against body weights when compared with that in Group 3 and in the unrelated five normal Siberian dogs. Thus, the only specific difference from group to group in the colony at the termination of this study was the difference in mean blood pressure. Based on these data, it is possible and likely that aging will reveal changes secondary to chronic primary hypertension. The pathogenesis of this hereditary disorder remains unknown.

Canine essential hypertension: probable mode of inheritance.

Essential hypertension (EH) in dogs is a relatively recently reported phenomenon. In this colony the canine disorder follows family lines and has a probable polygenic mode of inheritance, although the specific mode of inheritance has not been defined since an autosomal dominant trait has not clearly been ruled out. Direct intra-arterial femoral punctures are used to monitor blood pressure elevations, which tend to increase with advancing age. As in man, there are dogs with blood pressures intermediate between affected and normal dogs.

The mode of inheritance of craniomandibular osteopathy in West Highland White terrier dogs.

Craniomandibular osteopathy is a disease of several breeds of dogs, principally West Highland White and Scottish terriers. It is characterized by a non-neoplastic proliferation of bone on the ramus of the mandible and/or the tympanic bulla. The disease in various respects resembles Paget's disease and infantile cortical hyperostosis of humans. A retrospective pedigree analysis of a kindred of West Highland White terriers was performed to determine if the trait was inherited and to determine mode of inheritance. This study indicated that in West Highland White terriers, the condition is an autosomal recessive trait.

Transplantation of pancreatic islets in dogs.

Dispersed pancreatic islet tissue, prepared by collagenase digestion without separation of exocrine and endocrine components, was transplanted into the splenic pulp of 12 dogs made diabetic by total pancreatectomy. Four dogs (group 1) were given autotransplants, and all became euglycemic 4.5 +/- 1.5 days (mean +/- SE) after the transplantation was done. Three of these dogs remained euglycemic until splenectomized 60 days after transplantation was done. Four dogs (group 2) given allogeneic transplants from histocompatible littermates within the same group were administered cyclosporine (40 mg/kg of body weight/day; starting 2 days before transplantation was done until dogs were splenectomized), and 3 of these dogs became euglycemic 8.0 +/- 2.0 days after the transplant was done. Two of the 3 dogs that became euglycemic remained so until splenectomized 60 days after transplantation was done, and the 3rd was euglycemic until 31 days after transplantation. Four dogs (group 3) given allogeneic islet transplants from nonrelated histocompatible donors within the same group were given cyclosporine (40 mg/kg/day; as described for group 2), and none became euglycemic.

Genetic disorders affecting reproduction and periparturient care.

There are numerous genetic diseases influencing reproduction and periparturient care in dogs including such disorders as anasarca, cleft palate, swimmers, congenital heart disease, and the various conditions that cause excessive bleeding. It is probable that all breeds of dogs are at risk for these or other traits that influence whelping and neonatal care. Therefore, genetic counseling should be considered as an important aspect of prenatal and pediatric veterinary medicine.

The familial occurrence of lymphocytic thyroiditis in borzoi dogs.

A group of related borzoi dogs were studied over a 6-year period to ascertain the cause of primary hypothyroidism. Four generations of dogs were analyzed. Two littermates with lymphocytic thyroiditis were mated and the 10 offspring were all diagnosed, on the basis of thyroid biopsy evaluation, as having lymphocytic thyroiditis by age 2.5 years. A wide range of thyroid gland lesions was demonstrated in this litter of dogs. This report documents the occurrence of lymphocytic thyroiditis in three successive generations of an inbred group of borzoi dogs. An autosomal recessive mode of inheritance for the trait in this group of dogs is proposed.

Clinical and histological features of primary progressive, familial thyroiditis in a colony of borzoi dogs.

A six-year study of clinical data and the morphologic changes involved in lymphocytic thyroiditis in a colony of related borzoi dogs was conducted. Lesions observed included initial degenerative thyroidal parenchymal changes which progressed to subacute inflammation with subsequent fibrosis and end stage thyroid gland disease. This study encompasses three successive generations of this borzoi colony and documents the progression of the histologic changes from the initial thyroid gland degenerative lesions to the end stage parenchymal atrophy. Spontaneous, familial thyroiditis has not been reported previously in the borzoi breed.

Angiostrongylosis in a greyhound.

Angiostrongylus vasorum infection was diagnosed at necropsy of a Greyhound imported from Ireland. Granulomatous masses and pulmonary arterial thrombosis were associated with adult and larval stages of metastrongyle nematodes. Hemorrhages, widespread in subcutaneous tissue and muscle masses and at serosal surfaces, were suggestive of the onset of the bleeding disorder that has been seen in angiostrongylosis in Europe. The mollusks that can serve as intermediate hosts are known to be common in the United States, and therefore establishment of this parasite from imported racing or breeding stock is possible.

Abnormal release of storage pool adenine nucleotides from platelets of dogs affected with basset hound hereditary thrombopathy.

Platelets from dogs affected with Basset Hound Hereditary Thrombopathy (BHT), have a thrombasthenia-like aggregation defect but release storage pool ATP in quantities not significantly different from normal controls or BHT heterozygotes when stimulated with 1 X 10(-5)M ADP and 0.22 U/ml thrombin. However, the release occurs so rapidly in the BHT platelets stimulated with ADP that it is complete in approximately one-sixth of the time required for release from normal control and heterozygote platelets. Sequential electron micrographs reveal early release of BHT dense body constituents 30 seconds after stimulation with 1 X 10(-5)M ADP while resting BHT morphology is indistinguishable from normal control animals.

Comparative pathology of connective tissue diseases.

Selected examples of animal models for human connective tissue diseases are reviewed, with emphasis on those which can be verified by genetic, immunologic, and biochemical studies. Desnick et al. have stated that the study of animal models in inborn errors of metabolism will "have a dramatic impact on the future development and evaluation of effective therapies for a variety of human enzyme diseases." It is hoped that these discussions, including comments on the importance of animal models for specific human diseases of the connective tissue, will yield significant benefits in human health.