Jan Rothuizen

Primary hepatitis in dogs: a retrospective review (2002-2006).

BACKGROUND Little is known about etiology, disease progression, treatment outcome, survival time, and factors affecting prognosis in dogs with primary hepatitis (PH). OBJECTIVES To review retrospectively different forms of hepatitis in a referral population, by the World Small Animal Veterinary Association Standardization criteria. ANIMALS One-hundred and one dogs examined for histologically confirmed PH between 2002 and 2006. Dogs with nonspecific reactive hepatitis were excluded. METHODS Retrospective study. Medical records were reviewed for prevalence, signalment, clinical and clinicopathologic manifestation, outcome, survival time, and prognostic factors for shortened survival. RESULTS PH occurred in 0.5% of dogs in this referral population. Acute (AH) and chronic hepatitis (CH) were diagnosed in 21 and 67 dogs, respectively. Progression from AH to CH occurred in 5/12 of the repeatedly sampled dogs. CH was idiopathic in 43 (64%) dogs, and was associated with copper accumulation in 24 (36%) dogs. Median survival time was longer in dogs with AH than in dogs with CH (either idiopathic or copper associated), and dogs with lobular dissecting hepatitis had the shortest survival time. Prognostic factors predicting shortened survival were associated with decompensated liver function and cirrhosis at initial examination. CONCLUSIONS AND CLINICAL IMPORTANCE The majority of PH in dogs is CH. Previous studies appear to have underestimated the etiologic role of copper in both AH and CH. Prognosis is reduced in dogs with hepatic cirrhosis or cirrhosis-related clinical findings. Further research into etiology and treatment effectiveness in all PH forms is needed.

Copper-Associated Chronic Hepatitis in Labrador Retrievers

This study summarizes the clinical and pathologic findings in 15 Labrador Retrievers with copper-associated chronic hepatitis (CACH). Our hypothesis was that this form of hepatitis is caused by a defect in hepatic copper metabolism, which most likely originates from a genetic defect. Affected Labradors consisted of 11 female and 4 male Labrador Retrievers. Eight family members of 2 of these patients were examined prospectively, as were 6 unrelated healthy Labrador Retrievers. All dogs were registered at the breed club. The average age at clinical presentation was 7 years (range, 2.5-10.5 years). All dogs were presented for anorexia, which was associated with vomiting in 8 patients. The diagnosis of CACH was based on histologic examination of liver biopsy specimens in all dogs, including semiquantitation of copper. A disproportionate increase in alanine aminotransferase (ALT) activity relative to alkaline phosphatase (ALP) activity, as well as the centrolobular localization of copper and the association of copper accumulation with hepatic lesions, suggested a primary copper storage disease rather than primary cholestatic liver disease causing copper accumulation. Mean hepatic copper concentration measured in related Labradors was 1,317 microg/g dry weight liver (range, 402-2,576 microg/g). Mean hepatic copper concentration of unrelated normal Labradors was 233 microg/g dry weight liver (range, 120-304 microg/g). Our findings support the hypothesis that a hereditary form of hepatitis occurs in Labrador retrievers and is caused by a defect in hepatic copper metabolism.

Age-related changes in the dog hypothalamic-pituitary-adrenocortical system: Neuroendocrine activity and corticosteroid receptors

Aging is associated with a progressive dysfunctioning of the hypothalamic-pituitary-adrenocortical (HPA) axis. We have studied the response of the HPA axis to stress and a hormonal (ovine corticotropin releasing factor (o-CRF) challenge in young (1.5-2 years) and aged (greater than 11 years) dogs. Compared to the young dogs, the aged animals displayed an increased basal concentration of both ACTH and cortisol. In addition, in response to an o-CRF challenge (1 microgram/kg i.v.) or an electric footshock (1 mA, alternatively on/off for 2 s) or immobilization (45 min) stress, the aged dogs showed significantly larger increments in ACTH and cortisol. Following the challenge test, the young and aged dogs reached their respective basal hormone levels at the same time, except for the o-CRF test. In the latter case, in contrast to the young controls, the aged dogs still showed an increased plasma cortisol level compared to the pre-challenge basal hormone concentration. Concerning the effect of aging on the brain and hypophyseal corticosteroid receptors, a selective decline (minus 50-75%) in mineralocorticoid receptor (MR) was observed in all measured brain regions (dorsal and ventral hippocampus, septum, hypothalamus) and anterior pituitary, whereas no change was found in brain glucocorticoid receptor (GR) number. The GR level in the anterior pituitary was even increased by 70%. In light of the role that MR and GR seem to play in the regulation of the HPA axis, it is concluded that the diminished MR number in the aged dog brain may underly the increased basal hormone levels and the elevated responsiveness of the HPA axis in these animals. The observation that the stress-induced elevations of cortisol and ACTH were not prolonged at senescence suggests that the GR-mediated negative feedback action of glucocorticoids is not altered, which is in line with the unchanged brain GR numbers in the aged dogs.

WSAVA Standards for Clinical and Histological Diagnosis of Canine and Feline Liver Diseases

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Gauged attenuation of congenital portosystemic shunts: results in 160 dogs and 15 cats.

Summary Portosystemic shunts were ligated over a gauged stainless steel rod in 160 dogs and 15 cats, using a midline celiotomy. The diameter of the rod varied with the size of the shunt and the diameter of the portal vein cranial to the shunt. Shunts were narrowed to the smallest diameter that did not cause signs of portal hypertension such as cyanosis of the stomach, pancreas, and small intestine. A slight discoloration was accepted only if the heart rate, end‐expiratory CO2%, or arterial blood pressure (if available) did not deviate more than 15% from the values that were recorded at the beginning of the surgical procedure. The perioperative mortality (0–30 days) was 29%. The most common cause of death was euthanasia because of hypoplasia of the portal vein cranial to the shunt. Animals with intrahepatic shunts had a significantly lower probability of survival than animals with extrahepatic portocaval or portoazygos shunts. In dogs, large breed and a high body weight were also significant risk factors for non‐survival. Age had a significant effect on risk of non‐survival, with an increased risk for older dogs, irrespective of the breed of the dog (large breed vs. small breed). The probability of survival without recurrence of hepatoencephalopathy (HE) after 1 and 4 years was 61.3% and 55.7%, respectively. The only variable that was significantly associated with non‐recurrence of HE was the breed of the dog, there being a lower probability for large breeds. Among the animals that survived surgery for more than 30 days, there was a significant higher probability of recurrence of HE in cats than in dogs.

Copper Metabolism and Oxidative Stress in Chronic Inflammatory and Cholestatic Liver Diseases in Dogs

Inherited defects of copper metabolism resulting in hepatic copper accumulation and oxidative-stress might cause breed-associated forms of hepatitis. Biliary excretion is the major elimination route of copper, therefore increased hepatic copper concentrations could also be caused by cholestasis. The aim of this study was to find criteria to determine whether copper-accumulation is primary or occurs secondary to hepatitis. Liver samples of Bedlington Terriers with copper toxicosis (CT), breeds with non-copper-associated chronic extrahepatic cholestasis (EC) or chronic hepatitis (CH), and healthy dogs were used. Copper metabolism was analyzed by means of histochemical staining (copper concentration) and quantitative reverse transcriptase polymerase chain reaction (Q-PCR) on copper excretion/storage (ATOX1, COX17, ATP7A, ATP7B, CP, MT1A, MURR1, XIAP). Oxidative stress was measured by determining GSH/GSSG ratios and gene-expression (SOD1, CAT, GSHS, GPX1, CCS, p27KIP, Bcl-2). Results revealed 5+ copper in CT, but no or 1-2+ copper in EC and CH. Most gene products for copper metabolism remained at concentrations similar to healthy dogs. Three clear exceptions were observed in CT: 3-fold mRNA increase of ATP7A and XIAP and complete absence of MURRI. The only quantitative differences between the diseased and the control groups were in oxidative stress, evidenced by reductions in all GSH/GSSG ratios. We conclude that 3+ or higher histochemical detection of copper indicates a primary copper storage disease. The expression profile of copper-associated genes can be used as a reference for future studies on copper-associated diseases. All 3 diseases have reduced protection against oxidative stress, opening a rationale to use antioxidants as possible therapy.

Central Action of Adrenal Steroids During Stress and Adaptation

Corticosteroids interact with receptors in the central nervous system. These receptors display heterogeneity and can be distinguished as corticosterone- and aldosterone-binding mineralocorticoid receptors and dexamethasone-binding glucocorticoid receptors. Ligand specificity of mineralocorticoid receptors for either corticosterone or aldosterone seems to be determined by co-localized transcortin and the enzyme, 11 beta-hydroxysteroid dehydrogenase. Aldosterone-selective mineralocorticoid receptors appear to be present in the circumventricular organs and the AV3V region of the hypothalamus and mediate behavior that is driven by salt appetite. Highest concentrations of mineralocorticoid receptors are found in neurons of the hippocampus. These limbic mineralocorticoid receptor sites mediate tonic influences of corticosterone on brain processes. Glucocorticoid receptors bind corticosterone with a tenfold lower affinity than do mineralocorticoid receptors, and are widely distributed in neuronal and glial cells of the brain. Glucocorticoid receptors are involved in the termination of the stress response (negative feedback). Studies involving measurement of glucocorticoid receptor mRNA and binding sites have revealed that glucocorticoid receptors are subject to autoregulation. After ADX, glucocorticoid receptor concentration increases, but is reduced after chronic stress, chronic administration of glucocorticoids, and at senescence. A diminished glucocorticoid receptor concentration may compromise the negative feedback action exerted by glucocorticoids after stress. After ADX, mineralocorticoid receptor binding is acutely up-regulated and reaches its maximum between 7 and 24 hours post-ADX. Mineralocorticoid receptor mRNA level shows a transient increase following ADX. Long-term ADX has no effect on the mineralocorticoid receptor concentration, but, interestingly, chronic dexamethasone treatment results in an up-regulation of mineralocorticoid receptors. Mineralocorticoid receptor level is decreased at senescence, but this age-related decrement can be reversed by chronic treatment with the ACTH4-9 analog, ORG 2766. Functionally, mineralocorticoid receptors and glucocorticoid receptors are involved in different aspects of the organization of the stress response, and in conjunction they control the stress responsiveness of the animal.

Morphological classification of circulatory disorders of the canine and feline liver

If you are searched for the book by WSAVA Liver Standardization Gr;Jan Rothuizen DVM PhD;Susan E. Bunch DVM PhD DipACVIM WSAVA Standards for Clinical and Histological Diagnosis of Canine and Feline Liver Diseases, 1e in pdf form, then you have come on to the correct website. We presented the complete variation of this book in doc, txt, DjVu, ePub, PDF forms. You can reading WSAVA Standards for Clinical and Histological Diagnosis of Canine and Feline Liver Diseases, 1e online by WSAVA Liver Standardization Gr;Jan Rothuizen DVM PhD;Susan E. Bunch DVM PhD DipACVIM or load. Further, on our site you can read the manuals and diverse art eBooks online, either download their. We wish draw on your consideration that our website does not store the book itself, but we provide url to website where you may downloading or reading online. So if need to downloading WSAVA Standards for Clinical and Histological Diagnosis of Canine and Feline Liver Diseases, 1e by WSAVA Liver Standardization Gr;Jan Rothuizen DVM PhD;Susan E. Bunch DVM PhD DipACVIM pdf, then you have come on to faithful site. We own WSAVA Standards for Clinical and Histological Diagnosis of Canine and Feline Liver Diseases, 1e ePub, doc, PDF, txt, DjVu forms. We will be glad if you will be back us afresh.

Coagulation disorders in dogs with hepatic disease.

Liver disease has been associated with abnormalities in haemostasis. In this study, coagulation times, platelet counts, platelet activity parameters, activities of individual coagulation factors, D-dimers, antithrombin (AT) and protein C activity were measured in 42 dogs with histologically confirmed liver disease. Outcome was correlated with histological diagnosis. One or more coagulation abnormalities were present in 57% of dogs with hepatic disease. Activated partial thromboplastin time was significantly prolonged in dogs with chronic hepatitis (CH), with or without cirrhosis. Mean platelet numbers, AT and factor IX activity were significantly lower in dogs with CH plus cirrhosis, compared to dogs with other hepatopathies. D-dimers were not significantly increased in any group. Only three dogs, all with different histological diagnoses, satisfied the criteria for disseminated intravascular coagulation (DIC). Haemostatic abnormalities were primarily seen in dogs with cirrhosis and this may be due to reduced synthesis rather than increased consumption of coagulation factors.

Cluster analysis of the genetic heterogeneity and disease distributions in purebred dog populations

Purebred dog populations have been subject to strong selection which has resulted in extreme differences between breeds and decreased heterogeneity within breeds. As a result, breed-specific inherited diseases have accumulated in many populations. The aim of this study was to analyse genetic heterogeneity in relation to the distribution of elbow dysplasia in labrador retrievers, portosystemic shunts in Irish wolfbounds, and hepatic copper toxicosis, in Bedlington terriers. Decreased heterogeneity was demonstrated in the multiple genetic interrelations in the three populations. In pedigrees containing seven generations of ancestors, the average number of common ancestors in all pair-wise combinations of dogs was five to six (range 0 to 18). These complex interrelationships were resolved by a cluster analysis on matrices of relatedness. This analysis gave clusters of highly related animals, the average relatedness of these clusters, and the average relatedness of the entire population, as expressions of its genetic variability. The mean relatedness was 0.032 for Irish wolihounds and Bedlington terriers, and 0-002 for labrador retrievers. The labrador retriever cohort was resolved into 31 clusters, and all cases of elbow dysplasia were concentrated in five highly related clusters with an overall incidence of 17 per cent. The Bedlington terrier cohort consisted of 12 clusters which all contained cases of copper toxicosis, with an overall incidence of 46 per cent. The Irish wolfhounds were divided into 14 clusters with a disease incidence of 4 per cent. Dogs with portosystemic shunts were found in four averagely related clusters. A genetic distribution became obvious only when relatedness due to common ancestors of the cases was used as a criterion, and the cases were then concentrated in five highly related clusters.