George Voorhout

The Dog as an Animal Model for Intervertebral Disc Degeneration

Study Design. Prospective observational and analytic study. Objective. To investigate whether spontaneous intervertebral disc degeneration (IVDD) occurring in both chondrodystrophic (CD) and nonchondrodystrophic dogs (NCD) can be used as a valid translational model for human IVDD research. Summary of Background Data. Different animal models are used in IVDD research, but in most of these models IVDD is induced manually or chemically rather than occurring spontaneously. Methods. A total of 184 intervertebral discs (IVDs) from 19 dogs of different breeds were used. The extent of IVDD was evaluated by macroscopic grading, histopathology, glycosaminoglycan content, and matrix metalloproteinase 2 activity. Canine data were compared with human IVD data acquired in this study or from the literature. Results. Gross pathology of IVDD in both dog types (CD and NCD) and humans showed many similarities, but the cartilaginous endplates were significantly thicker and the subchondral cortices significantly thinner in humans than in dogs. Notochordal cells were still present in the IVDs of adult NCD but were not seen in the CD breeds or in humans. Signs of degeneration were seen in young dogs of CD breeds (<1 year of age), whereas this was only seen in older dogs of NCD breeds (5–7 years of age). The relative glycosaminoglycan content and metalloproteinase 2 activity in canine IVDD were similar to those in humans: metalloproteinase 2 activity increased and glycosaminoglycan content decreased with increasing severity of IVDD. Conclusion. IVDD is similar in humans and dogs. Both CD and NCD breeds may therefore serve as models of spontaneous IVDD for human research. However, as with all animal models, it is important to recognize interspecies differences and, indeed, the intraspecies differences between CD and NCD breeds (early vs. late onset of IVDD, respectively) to develop an optimal canine model of human IVDD.

Cross-sectional study of the prevalence and clinical features of osteoarthritis in 100 cats

To assess clinical signs and relevance of osteoarthritis (OA) in cats, the radiographic prevalence of OA in the appendicular skeleton of 100 client-owned cats (≥ 6 years old) was assessed. Possible associations between radiographic OA, clinical locomotor system examination, and owner-perceived behavioural changes were evaluated. OA was most prevalent in the shoulders, elbows, hips and tarsal joints with 61% of cats having OA in at least one joint and 48% in more than one joint. Overall, clinical examination of the larger peripheral joints had the highest sensitivity and specificity for radiographic OA. Regression analysis showed age to be related to OA (P = 0.002), as were decreased mobility and grooming (P = 0.008), although there was a correlation with age. Finally, increased inappropriate elimination was associated with OA (P = 0.046). It was concluded that the prevalence of OA in cats is strikingly high and increases with age. OA in cats seems to be associated with behavioural changes.

Termination of mid-gestation pregnancy in bitches with aglepristone, a progesterone receptor antagonist

Six pregnancies were terminated in mid-gestation with aglépristone, a progesterone receptor antagonist, in 5 beagle bitches in order to determine the effects of aglépristone on plasma concentrations of prolactin and progesterone, the duration of the luteal phase, and the interestrous interval. In addition, the effects of aglépristone on the condition of the uterus and fetuses were examined by ultrasonography. After confirmation of pregnancy by ultrasonography, the dogs received 10 mg, s.c. aglépristone per kg body weight on 2 consecutive days at about 30 d post ovulation. Before, during and after treatment with aglépristone, plasma samples were collected for determination of the concentrations of prolactin and progesterone. The condition of the uterus and fetuses was assessed by ultrasonography the day before and at least 3 times a week for at least 2 wk after aglépristone administration. Termination of pregnancy occurred within 4 to 7 d after the start of aglépristone treatment, which was well tolerated, with no side-effects except slight vaginal discharge. The results of ultrasonographic examination indicated that aglépristone leads to abortion but not to fetal resorption. Elevated plasma concentrations of prolactin were observed during aglépristone treatment, while plasma progesterone levels remained unchanged. Pregnancy termination with aglépristone resulted in premature cessation of luteal function. In addition, the interestrous interval was shortened. The latter effects may be the consequence of actions of the progesterone receptor antagonist at the hypothalamus-pituitary level. In conclusion, aglépristone proved to be a safe and effective abortifacient in mid-gestation in the bitch. The results of the present study also indicated that aglépristone directly or indirectly influences pituitary function.

Progress in transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in dogs and cats

Cushings disease or pituitary-dependent hyperadrenocorticism (PDH) is common in dogs and rare in cats. PDH is caused by a pituitary tumor producing adrenocorticotropin (ACTH). Pituitary imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is required to assess the size and location of the pituitary adenoma in relation to the surgical landmarks. In a specialized veterinary institution, microsurgical transsphenoidal hypophysectomy has proven to be a safe and effective treatment for dogs (n=84) and cats (n=7) with Cushings disease. Pituitary surgery requires a team approach and the neurosurgeon performing hypophysectomies must master a learning curve. The surgical results compared favorably with those for dogs with PDH treated medically with mitotane at the same institution. The recurrence rate after initially successful surgery increases with longer follow up-times. Pituitary function testing in 39 dogs with PDH treated with hypophysectomy revealed that, much more so than the other adenohypophyseal cell types, residual corticotropes present in the sella turcica after surgery are functional. Such normal ACTH secreting cells may maintain normocorticism whereas residual adenoma cells may lead to mild recurrence after relatively long periods of remission. Microsurgical transsphenoidal hypophysectomy is an effective treatment for canine and feline Cushings disease.

Calcium metabolism in great dane dogs fed diets with various calcium and phosphorus levels

The influence of dietary calcium on calcium metabolism was investigated in growing dogs that reach an adult body weight similar to that of humans. Seven groups of dogs (n greater than or equal to 5) were raised on a diet with a composition meeting the National Research Council (NRC) requirements (1974), but differing in calcium content, with or without a constant ratio to phosphorus. Control dogs fed 1.1% calcium and 0.9% phosphorus (all on a dry matter basis) were fed ad libitum (n = 10) or in restricted amounts (n = 6); dogs fed high calcium (3.3%) diets received either 0.9% phosphorus (n = 6) or 3.0% phosphorus (n = 6); dogs fed low calcium (0.55%) diets received either 0.9% phosphorus (n = 5 + 6) or 0.5% phosphorus (n = 8). Food intake, circulating total calcium and inorganic phosphorus concentrations and calcium metabolism, with 45Ca kinetics, were studied at 8, 14, 20 and 26 wk of age. Except for the difference in food intake in two groups at 14 wk (i.e., 0.55% calcium-0.9% phosphorus higher and 3.3% calcium-0.9% phosphorus lower, respectively, than the controls) no differences were noticed during the rest of the study. The mean plasma calcium concentrations did not differ between groups during the studies, whereas that of inorganic phosphorus revealed temporal aberrations in two groups. An absorption coefficient alpha of 45-66% was found for the control group. High and low calcium diets gave rise to values of 23-43% and 70-97%, respectively, for alpha irrespective of the phosphorus content of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism

OBJECT The aim of this study was to determine prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism (PDH). METHODS One veterinary neurosurgeon performed transsphenoidal hypophysectomies in 181 dogs with PDH over a 12-year period. Survival analysis was performed with the Kaplan-Meier method. Prognostic factors were analyzed with the univariate Cox proportional hazard analysis followed by stepwise multivariate analysis. The log-rank test was used to assess disease-free fractions in three groups categorized according to early postoperative urinary corticoid/creatinine (C/C) ratios. RESULTS Multivariate analysis revealed that old age, large pituitary size, and high preoperative concentrations of plasma adrenocorticotropic hormone were associated with an increased risk of PDH-related death. In addition, large pituitary size, thick sphenoid bone, high C/C ratio, and high concentration of plasma alpha-melanocyte-stimulating hormone (alpha-MSH) before surgery were associated with an increased risk of disease recurrence in the dogs that went into remission after hypophysectomy. Disease-free fractions were significantly higher in dogs with postoperative urinary C/C ratios in the lower normal range (< 5 x 10(-6)) than in dogs with postoperative C/C ratios in the upper normal range (5-10 x 10(-6)). CONCLUSIONS The results of this study indicate that pituitary size, sphenoid bone thickness, plasma alpha-MSH concentration, and preoperative level of urinary cortisol excretion are predictors of long-term remission after transsphenoidal hypophysectomy for PDH in dogs. Urinary C/C ratios measured 6 to 10 weeks after surgery can be used as a guide for predicting the risk of tumor recurrence.

Imaging of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism.

Detailed imaging of the pituitary gland is a prerequisite for a successful outcome of transsphenoidal hypophysectomy in dogs because it allows for accurate preoperative localization and assessment of the size of the pituitary gland. Cisternography allows assessment of even small increases in the height of the pituitary gland, but the magnitude of suprasellar expansion of pituitary tumors cannot be assessed with this technique. Large pituitary tumors with suprasellar expansion can readily be detected with conventional contrast-enhanced computed tomography (CT), while pituitary microadenomas can be localized with dynamic contrast-enhanced CT. Dynamic examination of the entire pituitary may be possible with spiral dynamic CT. Magnetic resonance imaging (MRI) of the canine pituitary gland provides a clear differentiation between the pituitary gland and the surrounding structures, but it remains to be investigated whether in dogs MRI can replace dynamic CT for the detection of microadenomas and whether it allows accurate localization of the pituitary gland relative to the surgical landmarks.

Results of adrenalectomy in 36 dogs with hyperadrenocorticism caused by adrenocortical tumour

A total of 38 adrenocortical tumours were removed from 36 dogs with hyperadrenocorticism. The surgical approach was by way of a unilateral flank laparotomy (32 dogs; 14 left and 18 right), a bilateral flank laparotomy (3 dogs) or a midline celiotomy (1 dog). Two dogs were euthanized during surgery because their tumours could not be resected. Eight dogs died from post-operative complications. Pancreatic necrosis with peritonitis was the most common cause of death. Eight of the 26 dogs that survived had signs of recurrence of hyperadrenocorticism. Unsuppressible hyperadrenocorticism was found in four dogs; one dog had probably pre-existent pituitary-dependent hyperadrenocorticism, and adrenocortical function could not be re-examined in the remaining three dogs. Among the 37 tumours examined microscopically expansion of neoplastic tissue into blood vessels was found in 22 of them. Four adrenal glands with adrenocortical tumours also contained phaeochromocytomas. Necropsy was performed in eight dogs. Metastases were found in the lungs of two dogs and in the lungs and liver in one dog. In combination with the data of previous reports, it is suggested that histological findings in surgery specimens are not good predictors for the clinical outcome.

Effect of diets with different calcium and phosphorus contents on the skeletal development and blood chemistry of growing great danes

The skeletal development of three groups of great dane dogs, fed a diet composed according to the published nutritional requirements for dogs (controls) or with increased calcium or calcium and phosphorus content, was examined radiographically, histologically and biochemically. The diets were fed from the time the dogs first began eating food in addition to their dams milk, until they were 17 weeks old. Thereafter, the calcium and phosphorus intakes of the dogs in the high calcium groups were normalised for a further 10 weeks. The dogs fed the high calcium diet without a proportionally high phosphorus intake became hypercalcaemic and hypophosphataemic, and had severe disturbances in skeletal development, growth, and mineralisation which were typical for rickets. After their calcium intake was normalised the lesions of rickets resolved but osteochondrotic lesions became apparent. The dogs fed the high calcium and phosphorus diet became slightly hypophosphataemic, their growth was retarded, and they had disturbances in skeletal development resembling osteochondrosis, which had only partly resolved after 10 weeks on the normal calcium and phosphorus diet.

Urinary excretion of glucocorticoids in the diagnosis of hyperadrenocorticism in cats

In dogs and humans, the measurement of urinary corticoid excretion has become a standard screening test for the diagnosis of hyperadrenocorticism. Mainly because the urinary excretion of cortisol was considered to be very low in cats, its measurement was not used in the diagnosis of hyperadrenocorticism in this species. We therefore studied the urinary excretion of [3H]cortisol and measured the corticoid/creatinine (C/C) ratio in healthy cats and in cats with hyperadrenocorticism in order to evaluate the applicability of this measurement in the diagnosis of feline hyperadrenocorticism. The median urinary excretion of intravenously administered [3H]cortisol was 1.85% (measured as excreted 3H; range, 1.56 to 1.99; n = 4). High-performance liquid chromatography analysis showed a small peak of cortisol and a large peak consisting primarily of conjugates of cortisol and/or its metabolites. The 2.5 and 97.5 percentiles of the urinary C/C ratio in healthy cats were 2 x 10(-6) to 36 x 10(-6) (n = 42). The C/C ratio was significantly higher in six cats with pituitary-dependent hyperadrenocorticism (median, 122 x 10(-6); range 51 x 10(-6) to 272 x 10(-6)). The administration of a high dose of dexamethasone (0.1 mg/kg thrice daily per os) led to marked suppression of the C/C ratio in healthy cats (median suppression of the average of the C/C ratio of the first two consecutive days was 92%; range, 74 to 96%; n = 12), as well as in five cats with pituitary-dependent hyperadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)