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Acute hepatic necrosis was diagnosed in a dog. Gram staining and fluorescence in situ hybridization identified Salmonella enterica in the liver, subsequently confirmed as S. enterica serotype I 4,5,12:-:1,2. This is the first report of acute hepatic necrosis with liver failure caused by Salmonella in a dog.
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Enfermedades de los Perros/diagnóstico , Perros/microbiología , Necrosis Hepática Masiva/diagnóstico , Salmonelosis Animal/diagnóstico , Salmonelosis Animal/patología , Salmonella typhi/clasificación , Animales , Enfermedades de los Perros/microbiología , Enfermedades de los Perros/mortalidad , Femenino , Hibridación Fluorescente in Situ , Hígado/enzimología , Hígado/microbiología , Hígado/patología , Necrosis Hepática Masiva/microbiología , Necrosis Hepática Masiva/mortalidad , Salmonelosis Animal/microbiología , Salmonella typhi/aislamiento & purificación , Salmonella typhi/patogenicidad , SerotipificaciónRESUMEN
OBJECTIVE: The aim of this study was to develop an SLE disease model that simulates long-term outcomes of SLE to estimate the long-term effectiveness and cost-effectiveness of SLE treatments. METHODS: Longitudinal data from 1354 patients from the Hopkins Lupus Cohort were included in the analysis. Statistical models were created to estimate disease activity [Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) SLEDAI scale] and prednisone dose over time using linear regression. Survival models for organ damage and mortality were created. The models were combined in a predictive simulation of SLE organ damage and mortality. Predictions were assessed against the Hopkins Lupus Cohort data. RESULTS: The analyses found that change in the annual average SLEDAI score was associated with the previous annual average SLEDAI score, renal involvement, age, male gender, African American ethnicity, anaemia, haematological involvement, increased DNA binding and low complement. The annual average prednisone dose increased for every unit increase in annual average SLEDAI. Organ damage and mortality modelling demonstrated that adjusted mean SLEDAI and binary SLEDAI organ involvement indicators predicted mortality, cardiovascular, renal, neuropsychiatric, pulmonary, gastrointestinal, ocular and skin damage. The cumulative average prednisone dose was associated with risk of cardiovascular, ocular, musculoskeletal, neuropsychiatric and gastrointestinal damage, gonadal failure and diabetes mellitus. The simulation reproduced mean SLEDAI and organ damage scores from the Hopkins Lupus Cohort. CONCLUSION: Longitudinal modelling of an SLE cohort confirmed relationships between risk factors and long-term outcomes in SLE. The models serve to estimate the probability of SLE outcomes over time and can be used to estimate the effectiveness and cost-effectiveness of new treatments.
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Anemia/terapia , Costos de la Atención en Salud , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/terapia , Prednisona/uso terapéutico , Adulto , Negro o Afroamericano , Anemia/etiología , Estudios de Cohortes , Análisis Costo-Beneficio , Femenino , Humanos , Inmunosupresores/economía , Modelos Lineales , Estudios Longitudinales , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/mortalidad , Nefritis Lúpica/etiología , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Evaluación de Resultado en la Atención de Salud , Prednisona/economía , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores Sexuales , Análisis de Supervivencia , Población BlancaRESUMEN
BACKGROUND: Chronic pancreatitis (CP) is common in English cocker spaniels (ECS). It is histologically similar to IgG4-related disease (IgG4-RD) in humans and is characterized by duct destruction, interlobular fibrosis, and dense periductular and perivenous lymphocytic aggregates. However, the clinical manifestations of CP in ECS have not been previously described. OBJECTIVES: Characterize the clinical manifestations of CP in a group of ECS, including similarities and differences to IgG4-RD in humans. ANIMALS: One-hundred four ECS with CP and 44 client owned control ECS without CP (both healthy and diseased controls). METHODS: Affected dogs were divided into 2 groups according to the methods used to diagnose CP. Case records were searched for signalment, clinical, and clinicopathological findings, and evidence of keratoconjunctivitis sicca (KCS), proteinuria, other immune-mediated diseases, and anal sacculitis. RESULTS: Involvement of other organs was common. Affected ECS presented with a high frequency of KCS (n = 49), proteinuria (n = 47), anal gland disease (n = 36), atopy (n = 21), and other immune-mediated diseases (n = 16). Those with parti-color hair coats, particularly blue roan, had a strong association with CP, suggesting a link between coat color and autoimmune conditions in this breed. CONCLUSIONS AND CLINICAL IMPORTANCE: English cocker spaniels with CP show clinical similarities to humans with IgG4-RD and common involvement of other organs. Clinicians should evaluate affected Cocker Spaniels for proteinuria, keratoconjunctivitis sicca, and other potential immune-mediated diseases.
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Enfermedades de los Perros , Pancreatitis Crónica , Animales , Enfermedades de los Perros/patología , Perros , Pancreatitis Crónica/veterinaria , Pancreatitis Crónica/patología , Masculino , Femenino , Estudios de Casos y Controles , Queratoconjuntivitis Seca/veterinaria , Queratoconjuntivitis Seca/patologíaRESUMEN
BACKGROUND: Copper-associated chronic hepatitis (CuCH) is poorly characterised in Cavalier King Charles spaniels (CKCS). METHODS: Hepatic copper accumulation was qualitatively and quantitatively assessed, and blood samples were used for genetic testing to screen for known CuCH-associated genetic variants. RESULTS: The study included 13 CKCS with CuCH and eight unaffected controls. Increased transaminase activities, elevated biliary enzyme concentrations and portal hypertension were documented in 100%, 73% and 38% of dogs with CuCH, respectively. Five dogs had three or more abnormalities in measures of liver function. All 11 dogs with CuCh that underwent genetic testing were homozygous negative for the COMMD1 deletion and ATP7A variant but homozygous positive (n = 7) or heterozygous (n = 4) for the ATP7B variant. Liver histology often demonstrated marked architectural distortion by severe, bridging fibrosis and regenerative nodules with lymphoplasmacytic inflammation. Centrilobular copper accumulation characterised early cases with minimal fibrosis. When fibrosis was significant, copper was often differentially concentrated within regenerative nodules. Chelation therapy resolved laboratory derangements and portal hypertension in five of seven dogs. Of the 7 non-surviving dogs with CuCH, 6 had not received chelation therapy. LIMITATIONS: Limitations include a small cohort size and the lack of pedigree analyses to corroborate heritability. CONCLUSIONS: CuCH should be considered in CKCS with suspected liver disease. Long-term prognosis seems favourable in dogs receiving chelation therapy, notwithstanding the presence of previously reported negative prognostic markers.
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Enfermedades de los Perros , Hipertensión Portal , Humanos , Perros , Animales , Cobre , Fibrosis , Hepatitis Crónica/genética , Hepatitis Crónica/veterinaria , Hipertensión Portal/genética , Hipertensión Portal/veterinaria , Enfermedades de los Perros/genéticaRESUMEN
BACKGROUND: Bedlington terrier copper toxicosis (CT) is due to a homozygous exon deletion in COMMD1. CT also occurs in Bedlingtons lacking this deletion. An association with two ABCA12 single nuceotide polymorphism (SNP) splice variants was reported. Labrador retriever CT is associated with a missense mutation in ATP7B, and with a protective mutation in ATP7A. METHODS: Liver and DNA samples from 24 affected and 10 unaffected Bedlingtons were assessed for copper and genetic variants. Allelic frequencies were compared. The ATP7B mutation frequency was investigated in 144 dogs of other breeds. RESULTS: The ABCA12 SNPs showed no differences between groups. The COMMD1 deletion was less frequent in unaffected than in affected dogs and in affected dogs post-2001 than pre-2001. The ATP7B mutation was more frequent in affected than unaffected Bedlingtons. Thirty-five of 144 dogs of other breeds were homo- or heterozygous for the ATP7B mutation. The ATP7A mutation was absent from Bedlingtons. LIMITATIONS: Clinical information and qualitative copper measurements were unavailable for most dogs. CONCLUSION: The COMMD1 deletion remains present in Bedlington terriers but is no longer the primary cause of CT. ABCA12 SNPs were not associated with CT. The ATP7B:c.4358G>A mutation was significantly associated with Bedlington CT and was more common in dogs of this breed than in the 144 dogs of other breeds.
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Cobre , Enfermedades de los Perros , Perros , Animales , Cobre/toxicidad , Mutación , Hígado , Polimorfismo de Nucleótido Simple , Enfermedades de los Perros/genéticaRESUMEN
A suite of models was used to examine the links between climate, fuels and fire behaviour in dry eucalypt forests in south-eastern Australia. Predictions from a downscaled climate model were used to drive models of fuel amount, the moisture content of fuels and two models of forest fire behaviour at a location in western Sydney in New South Wales, Australia. We found that a warming and drying climate produced lower fine fuel amounts, but greater availability of this fuel to burn due to lower moisture contents. Changing fuel load had only a small effect on fuel moisture. A warmer, drier climate increased rate of spread, an important measure of fire behaviour. Reduced fuel loads ameliorated climate-induced changes in fire behaviour for one model. Sensitivity analysis of the other fire model showed that changes in fuel amount induced changes in fire behaviour of a similar magnitude to that caused directly by sensitivity to climate. Projection of changes in fire risk requires modelling of changes in vegetation as well as changes in climate. Better understanding of climate change effects on vegetation structure is required.
RESUMEN
BACKGROUND: Biliary sludge (BS) frequently is identified on ultrasonographic examination and is described as incidental. It is hypothesized that biliary stasis and hypersecretion play a role in both BS and gallbladder mucocele (GBM) formation. Recent studies have documented similarities in composition of BS and GBM, and there are several examples of progression from BS to GBM in the veterinary literature. OBJECTIVES: To assess the relationship between the presence of BS and later development of GBM in dogs, over time periods >12 months. ANIMALS: A total of 154 dogs with BS and ultrasonographic follow-up >12 months. METHODS: Medical records were retrospectively collected from 9 UK-based referral centers for all available time points. A semiobjective scoring system was used to track volume of BS within the gall bladder (GB) over time. RESULTS: Twenty dogs developed GBM during the study period. Shetland Sheepdogs (odds ratio [OR], 40.99; 95% confidence interval [CI], 3.61-465.95; P = .003) and Border Terriers (OR, 11.66; 95% CI, 3.28-46.63; P < .001) were independent risk factors for the development of GBM. Non-gravity-dependent BS (NDBS) was noted to form before GBM development in 9/20 dogs, and breeds at-risk for GBM were more likely to have NDBS. Odds for the development of GBM increased with BS score. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with NDBS may be at risk for the development of GBM and a stratified BS scoring system could allow for semiobjective monitoring over time, particularly in at-risk breeds.
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Enfermedades de los Conductos Biliares , Enfermedades de los Perros , Enfermedades de la Vesícula Biliar , Mucocele , Animales , Bilis/diagnóstico por imagen , Enfermedades de los Conductos Biliares/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Perros , Enfermedades de la Vesícula Biliar/veterinaria , Mucocele/veterinaria , Estudios Retrospectivos , Ultrasonografía/veterinariaRESUMEN
BACKGROUND: Ursodeoxycholic acid is used in human medicine for litholytic management of choleliths, but the efficacy of medical management in dogs with cholelithiasis is unknown. OBJECTIVES: To describe the clinical features and outcomes of dogs with cholelithiasis, focusing on cases that received medical treatment, and to identify patient factors that influenced decision-making for surgical or medical management. ANIMALS: Thirty-eight dogs with cholelithiasis identified on abdominal ultrasonography (AUS). METHODS: Medical records of dogs with cholelithiasis on AUS between 2010 and 2019 were retrospectively reviewed. Cases were classified as symptomatic (n = 18) or incidental (n = 20) and divided into medically treated (n = 13), surgically treated (n = 10), and no treatment (n = 15) groups. Biochemical variables and cholelith location were compared between symptomatic and incidental groups using Mann-Whitney U and chi-squared tests, respectively. Survival times were compared using Kaplan-Meier survival analysis. RESULTS: Symptomatic cases had higher alkaline phosphatase (P = .03), gamma-glutamyl transferase (P = .03), and alanine transferase (P = .02) activities than did incidental cases. A higher proportion of symptomatic cases (44.4%) had choledocholithiasis than did incidental cases (0%; P = .003). Seventy percent of surgically managed dogs, 7.7% of medically managed dogs, and 0% of nontreated dogs had choledocholiths at presentation. Seventeen dogs had follow-up AUS: cholelithiasis completely resolved in 4/8 medically treated, 5/7 of surgically treated, and 1/2 nontreated dogs. Median survival time was 457.4 days, with no significant difference between incidental and symptomatic dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Medical treatment can be effective for management of cholelithiasis in dogs, with clinical presentation and cholelith location playing important roles in treatment decision-making.
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Colelitiasis , Enfermedades de los Perros , Abdomen , Animales , Colelitiasis/cirugía , Colelitiasis/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/cirugía , Perros , Humanos , Estudios Retrospectivos , Ultrasonografía/veterinariaRESUMEN
The clinical presentations of both liver disease and pancreatitis are nonspecific and overlapping, which may cause difficulty in diagnosis. In our retrospective pilot study, we assessed whether dogs with evidence of portal hypertension and absence of pancreatitis on pancreatic histology have increases in canine pancreatic lipase immunoreactivity (cPLI) and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase. We included dogs that had been presented between 2008 and 2019 if they had normal pancreatic histology, histologically confirmed hepatopathy, and if canine pancreas-specific lipase (Spec cPL; Idexx) or DGGR lipase had been measured. Only dogs with portal hypertension were included. Six dogs fulfilled the inclusion criteria. Four of 6 and 2 of 6 dogs had Spec cPL and DGGR lipase exceeding the upper reference limit, respectively. From the 4 dogs with increased Spec cPL, 2 had concentrations of 200-400 µg/L and 2 had concentrations ≥ 400 µg/L. Our results suggest that canine portal hypertension might lead to increased Spec cPL and DGGR lipase values in the absence of pancreatitis on histology. Until more evidence in a larger number of dogs with portal hypertension is available, both tests should be interpreted cautiously in the presence of portal hypertension.
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Enfermedades de los Perros/diagnóstico , Hipertensión Portal/veterinaria , Páncreas/enzimología , Pancreatitis/veterinaria , Animales , Perros , Lipasa , Páncreas/fisiopatología , Pancreatitis/diagnóstico , Proyectos Piloto , Estudios RetrospectivosRESUMEN
Cellular senescence is a molecular hallmark of ageing that is associated with multiple pathologies, and DNA damage marker γH2AX, together with cell cycle inhibitor p21, have been used as senescence markers in multiple species including dogs. Idiopathic canine chronic hepatitis has recognised breed-related differences in predisposition and prognosis, but reasons behind this are poorly understood. This retrospective study using archived post mortem tissue aimed to provide insight into liver ageing in 51 microscopically normal canine livers across seven breed categories, including those with and without increased risk of chronic hepatitis. Immunohistochemistry was conducted for γH2AX, p21, and cell proliferation marker Ki67, and the mean number of positive hepatocytes per high power field was determined. All three markers were strongly correlated to each other, but no age-dependent expression was seen in the combined study population. Overall expression levels were low in most dogs, with median values representing less than 1.5% of hepatocytes, but this increased to 20-30% in individual dogs at the upper end of the range. Individual breed differences were noted in two breeds that have increased risk of chronic hepatitis, with English Springer Spaniels having lower expression of Ki67 than other dogs, and Labradors having higher expression of Ki67 and γH2AX than other dogs. These results warrant further investigation in these breeds and highlight a need to validate reliable markers of cellular senescence in dogs.
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Envejecimiento/fisiología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Perros/metabolismo , Histonas/metabolismo , Antígeno Ki-67/metabolismo , Hígado/metabolismo , Envejecimiento/genética , Animales , Senescencia Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Perros/clasificación , Perros/genética , Regulación de la Expresión Génica/fisiología , Histonas/genética , Antígeno Ki-67/genética , Estudios RetrospectivosRESUMEN
OBJECTIVE: To compare survival of dogs with a congenital portosystemic shunt (CPSS) that received medical or surgical treatment. DESIGN: Prospective cohort study. ANIMALS: 126 client-owned dogs with a single CPSS. PROCEDURES: Dogs were examined at 1 of 3 referral clinics, and a single CPSS was diagnosed in each. Dogs received medical or surgical treatment without regard to signalment, clinical signs, or results of hematologic or biochemical analysis. Survival data were analyzed via a Cox regression model. RESULTS: During a median follow-up period of 579 days, 18 of 126 dogs died as a result of CPSS. Dogs treated via surgical intervention survived significantly longer than did those treated medically. Hazard ratio for medical versus surgical treatment of CPSS (for the treatment-only model) was 2.9 (95% confidence interval, 1.1 to 7.2). Age at CPSS diagnosis did not affect survival. CONCLUSIONS AND CLINICAL RELEVANCE: Both medical and surgical treatment can be used to achieve long-term survival of dogs with CPSS, although results of statistical analysis supported the widely held belief that surgery is preferable to medical treatment. However, the study population consisted of dogs at referral clinics, which suggested that efficacy of medical treatment may have been underestimated. Although surgical intervention was associated with a better chance of long-term survival, medical management provided an acceptable first-line option. Age at examination did not affect survival, which implied that early surgical intervention was not essential. Dogs with CPSS that do not achieve acceptable resolution with medical treatment can subsequently be treated surgically.
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Antibacterianos/uso terapéutico , Disacáridos/uso terapéutico , Enfermedades de los Perros/terapia , Hepatopatías/veterinaria , Sistema Porta/anomalías , Animales , Dieta/veterinaria , Enfermedades de los Perros/congénito , Enfermedades de los Perros/mortalidad , Perros , Femenino , Hepatopatías/congénito , Hepatopatías/mortalidad , Hepatopatías/terapia , Masculino , Sistema Porta/cirugíaRESUMEN
In recent years, increased awareness of feline pancreatitis by the veterinary profession and improved diagnostic modalities have led to an increased frequency of diagnosis of pancreatitis in this species. Consequently, pancreatic diseases, especially chronic pancreatitis, are considered highly prevalent, even in populations of apparently healthy individuals. This prevalence has led to the suspicion that the condition may be overdiagnosed. This article summarizes the difficulties of diagnosis of acute and chronic pancreatitis, assesses the reasons why this is a challenging disease to recognize, and considers whether these difficulties could result in either overdiagnosis or underdiagnosis.
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Enfermedades de los Gatos/diagnóstico , Pancreatitis/veterinaria , Animales , Gatos , Uso Excesivo de los Servicios de Salud , Pancreatitis/diagnósticoRESUMEN
BACKGROUND: English springer spaniels (ESS) show an increased risk of chronic hepatitis (CH). In a previous study of 68 ESS with CH, in which only one dog received corticosteroids, a median survival time of 189 days was noted. Some ESS with CH appear to improve with prednisolone treatment; therefore, we aimed to investigate the response to prednisolone in this breed. PARTICIPANTS: ESS with histologically confirmed idiopathic CH were treated with prednisolone 1-2 mg/kg/day. Nine female and three male ESS were enrolled (median age at diagnosis of five years). Patients were monitored clinically and had biochemistry samples taken to assess markers of hepatocellular damage and function. RESULTS: The mean starting dose of prednisolone was 1.1 mg/kg/day. All symptomatic patients showed an initial clinical improvement. Two cases were euthanased while receiving prednisolone. The median time since diagnosis is 1715 days (range: 672-2105 days) and the remaining patients are clinically well, with seven patients still receiving a mean dose of 0.4 mg/kg prednisolone every other day. Statistical analysis demonstrated significant (P<0.05) reductions in serum alkaline phosphatase, alanine aminotransferase and bilirubin following 2-4 weeks of prednisolone treatment. CONCLUSION: This study demonstrates improved clinical and biochemical parameters when some ESS with CH are managed with prednisolone and standard supportive treatments.
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Enfermedades de los Perros/tratamiento farmacológico , Hepatitis Crónica/veterinaria , Prednisolona/uso terapéutico , Animales , Perros , Femenino , Hepatitis Crónica/tratamiento farmacológico , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Canine idiopathic eosinophilic lung disease (ELD) is sparsely documented in the literature. METHODS: Clinical presentation and outcome of dogs diagnosed with ELD (eosinophilic bronchitis or eosinophilic bronchopneumonia) were reviewed. Subgroups were made based on chronicity of clinical signs and findings of thoracic imaging: NCI (no changes in thoracic imaging), BRON (bronchial/peribronchial pattern), INT (bronchointerstitial/interstitial/alveolar). RESULTS: Seventy cases were included. There were more young to adult, crossbreed and female dogs. Compared with the other two groups NCI dogs showed lower bronchoalveolar lavage fluid eosinophilic pleocytosis and absence of circulating eosinophilia, bronchiectasis or death due to respiratory disease. All dogs responded clinically to corticosteroids. Median treatment duration was four months. Remission (no clinical signs after treatment discontinuation for >one month) and long-term remission (>six months) was achieved in 60 per cent, and 51 per cent of patients, respectively. Relapse occurred in 26 per cent of cases after remission but was rare (3 per cent) after long-term remission. The one-year, two-year and four-year survival to death due to respiratory disease was 98 per cent, 97 per cent and 91 per cent, respectively. CONCLUSION: Prognosis and initial clinical response for ELD was generally good although achievement of long-term remission was only seen in 51 per cent of dogs. Different outcomes based on chronicity of signs, corticosteroid dose, thoracic imaging abnormalities and other clinical variables were not appreciated.
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Corticoesteroides/uso terapéutico , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/tratamiento farmacológico , Eosinofilia Pulmonar/veterinaria , Animales , Perros , Femenino , Estudios de Seguimiento , Masculino , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/tratamiento farmacológico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Overweight and obesity have been adversely associated with longevity in dogs but there is scarce knowledge on the relation between body composition and lifespan. We aimed to investigate the effects of body composition, and within-dog changes over time, on survival in adult Labradors using a prospective cohort study design. The dogs had a median age of 6.5 years at study start and were kept in similar housing and management conditions throughout. The effects of the various predictors, including the effect of individual monthly-recorded change in body weight as a time varying covariate, were evaluated using survival analysis. RESULTS: All dogs were followed to end-of-life; median age at end-of-life was 14.0 years. Body composition was measured annually with dual-energy x-ray absorptiometer (DEXA) scans between 6.2 and 17.0 years. All 39 dogs had DEXA recorded at 8, 9 and 10 years of age. During the study the mean (± SD) percent of fat (PF) and lean mass (PL) was 32.8 (± 5.6) and 64.2 (± 5.5) %, respectively, with a mean lean:fat ratio (LFR) of 2.1 (± 0.6); body weight (BW) varied from 17.5 to 44.0 kg with a mean BW change of 9.9 kg (± 3.0). There was increased hazard of dying for every kg increase in BW at 10 years of age; for each additional kg of BW at 10 years, dogs had a 19% higher hazard (HR = 1.19, P = 0.004). For the change in both lean mass (LM) and LFR variables, it was protective to have a higher lean and/or lower fat mass (FM) at 10 years of age compared to 8 years of age, although the HR for change in LM was very close to 1.0. For age at study start, older dogs had an increased hazard. There was no observed effect for the potential confounders sex, coat colour and height at shoulders, or of the time-varying covariate. CONCLUSIONS: These results suggest that even rather late-life control efforts on body weight and the relationship between lean and fat mass may influence survival in dogs. Such "windows of opportunity" can be used to develop healthcare strategies that would help promote an increased healthspan in dogs.
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Composición Corporal/fisiología , Peso Corporal/fisiología , Perros/fisiología , Longevidad/fisiología , Tejido Adiposo , Animales , Estudios Longitudinales , Análisis de SupervivenciaRESUMEN
BACKGROUND: Reports of chronic hepatitis in dogs caused by Leptospira spp. are confined to small case series. Fluorescence in situ hybridization (FISH) allows the identification of spirochetes in liver samples. Consequently, this technique may help elucidate the role of Leptospira spp. in cases of chronic hepatitis. OBJECTIVES: To describe cases of hepatic leptospirosis in dogs diagnosed by FISH and subsequent polymerase chain reaction (PCR) speciation, with the absence of clinically relevant renal involvement. ANIMALS: Ten client-owned dogs. METHODS: Retrospective case series from the University of Cambridge presented between 2013 and 2016 or cases consulted by telephone advice during this time period. Cases were selected based on histopathologically confirmed granulomatous hepatitis and leptospiral organisms identified by FISH and PCR speciation (Leptospira interrogans/kirschneri). RESULTS: All cases had increased liver enzyme activities, and FISH in combination with PCR speciation-confirmed infection with L. interrogans/kirschneri. Four dogs underwent repeat liver biopsy, FISH and PCR speciation 4-15 months after initial presentation and doxycycline treatment with 1 dog undergoing repeat sampling at necropsy. Three dogs that underwent repeat biopsy remained positive for L. interrogans/kirschneri infection. Six dogs were alive at the time of manuscript preparation and 4 dogs were euthanized as a result of progressive liver disease. CONCLUSIONS AND CLINICAL IMPORTANCE: The presence of hepatic leptospiral organisms may be associated with chronic granulomatous hepatitis without clinical evidence of renal involvement. Further studies are necessary to elucidate the etiological role of these organisms in the disease.
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Enfermedades de los Perros/microbiología , Leptospira , Leptospirosis/veterinaria , Hepatopatías/veterinaria , Animales , Enfermedades de los Perros/patología , Perros , Femenino , Hibridación Fluorescente in Situ/veterinaria , Leptospirosis/microbiología , Leptospirosis/patología , Hígado/microbiología , Hígado/patología , Hepatopatías/microbiología , Hepatopatías/patología , Masculino , Reacción en Cadena de la Polimerasa/veterinaria , Estudios RetrospectivosRESUMEN
This consensus statement on chronic hepatitis (CH) in dogs is based on the expert opinion of 7 specialists with extensive experience in diagnosing, treating, and conducting clinical research in hepatology in dogs. It was generated from expert opinion and information gathered from searching of PubMed for manuscripts on CH, the Veterinary Information Network for abstracts and conference proceeding from annual meetings of the American College of Veterinary Medicine and the European College of Veterinary Medicine, and selected manuscripts from the human literature on CH. The panel recognizes that the diagnosis and treatment of CH in the dog is a complex process that requires integration of clinical presentation with clinical pathology, diagnostic imaging, and hepatic biopsy. Essential to this process is an index of suspicion for CH, knowledge of how to best collect tissue samples, access to a pathologist with experience in assessing hepatic histopathology, knowledge of reasonable medical interventions, and a strategy for monitoring treatment response and complications.
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Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/terapia , Hepatitis Crónica/veterinaria , Animales , Enfermedades de los Perros/patología , Perros , Hepatitis Crónica/diagnóstico , Hepatitis Crónica/patología , Hepatitis Crónica/terapia , Hígado/patologíaRESUMEN
BACKGROUND: Chronic hepatitis (CH) occurs commonly in dogs but is associated with a variable and largely unpredictable prognosis. p21, a cell-cycle inhibitor and marker of cellular senescence, is upregulated in human liver disease and is a better prognostic marker than histological or clinical scoring systems. OBJECTIVE: To quantify hepatocyte p21 immunopositivity in histopathology samples from dogs with CH and determine its association with outcome. ANIMALS: Twenty-six client-owned dogs with histologically confirmed CH, and 15 dogs with normal liver histology. METHODS: Medical records and liver histopathology samples were retrospectively reviewed to identify cases of CH. Immunohistochemistry for p21 was performed on all samples and hepatocyte immunopositivity was visually quantified. Relationships between p21 and dog age and dog survival time were statistically evaluated. RESULTS: Hepatocyte p21 immunopositivity in dogs with CH was high (median percentage of positive hepatocytes: 90%, range: 20%-98%) and exceeded 70% in 23/26 cases with no association with age. In control dogs, p21 immunopositivity was low (≤15% positive hepatocytes in 12/15 cases) and was positively correlated with age (rs = 0.63; P = .011). Dogs with p21 immunopositivity exceeding 91.8% (upper tercile) had significantly shorter survival compared to dogs with less than 88.9% immunopositivity (lowest tercile; 218 versus 874 days, P = .006). Increasing hepatocyte p21 immunopositivity was significantly negatively associated with survival time (HR 4.12; 95% CI 1.34-12.63; P = .013). CONCLUSIONS AND CLINICAL IMPORTANCE: Marked p21 immunopositivity in dogs with CH might be indicative of widespread hepatocellular senescence. A significant association with survival time also suggests a potential value for p21 quantification in determining prognosis.
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Enfermedades de los Perros/metabolismo , Hepatitis Animal/metabolismo , Hepatocitos/metabolismo , Animales , Biomarcadores , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Enfermedades de los Perros/patología , Perros , Femenino , Regulación de la Expresión Génica , Hepatitis Animal/patología , Hígado/patología , Masculino , Estudios RetrospectivosRESUMEN
The objectives of this study were fourfold: technical validation of a commercial canine 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase assay, to calculate a reference interval for DGGR lipase by the indirect a posteriori method, to establish biological validity of the assay, and to assess agreement between DGGR lipase and specific canine pancreatic lipase (Spec cPL) assays. Dogs with histologically confirmed acute pancreatitis (n=3), chronic pancreatitis (n=8) and normal pancreatic tissue (n=7) with stored (-80°C) serum samples were identified. Relevant controls were selected. Precision, reproducibility and linearity of DGGR lipase, and the effect of sample haemolysis and freezing, were assessed. Sensitivity and specificity of DGGR lipase and Spec cPL were determined. Agreement between these two parameters was calculated using Cohen's kappa coefficient (κ). The DGGR lipase assay demonstrated excellent precision, reproducibility and linearity. Sample haemolysis and storage at -80°C for 12 months did not influence the assay. DGGR lipase (>245IU/l) and Spec cPL (>400µg/l) both showed poor sensitivity but excellent specificity for acute pancreatitis, and poor to moderate sensitivity but excellent specificity for chronic pancreatitis. Substantial agreement (κ=0.679) was found between DGGR lipase and Spec cPL. The validated DGGR lipase assay had similar sensitivity and specificity for the diagnosis of acute and chronic pancreatitis to Spec cPL. DGGR lipase is a reliable alternative to Spec cPL for the diagnosis of pancreatitis.