Bacterial culture and immunohistochemical detection of bacteria and endotoxin in cats with suppurative cholangitis-cholangiohepatitis syndrome.

OBJECTIVE: To characterize the frequency and type of bacterial infection by culture- and immunohistochemical (IHC)-based methods and determine the impact of infection on clinical features and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS). ANIMALS: 168 client-owned cats with S-CCHS (cases). PROCEDURES: Clinical features, bacterial culture results, culture-inoculate sources, and survival details were recorded. Cases were subcategorized by comorbidity (extrahepatic bile duct obstruction, cholelithiasis, cholecystitis, ductal plate malformation, biopsy-confirmed inflammatory bowel disease, and biopsy-confirmed pancreatitis) or treatment by cholecystectomy or cholecystoenterostomy. Culture results, bacterial isolates, Gram-stain characteristics, and IHC staining were compared among comorbidities. Lipoteichoic acid IHC staining detected gram-positive bacterial cell wall components, and toll-like receptor expression IHC reflected pathologic endotoxin (gram-negative bacteria) exposure. RESULTS: Clinical features were similar among cases except for more frequent abdominal pain and lethargy in cats with positive culture results and pyrexia, abdominal pain, and hepatomegaly for cats with polymicrobial infections. Bacteria were cultured in 93 of 135 (69%) cats, with common isolates including Enterococcus spp and Escherichia coli. IHC staining was positive in 142 of 151 (94%) cats (lipoteichoic acid, 107/142 [75%]; toll-like receptor 4, 99/142 [70%]). With in-parallel interpretation of culture and IHC-based bacterial detection, 154 of 166 (93%) cats had bacterial infections (gram-positive, 118/154 [77%]; gram-negative, 111/154 [72%]; polymicrobial, 79/154 [51%]). Greater frequency of bacterial isolation occurred with combined tissue, bile, and crushed cholelith inoculates. Infection and gram-positive bacterial isolates were associated with significantly shorter long-term survival times. CLINICAL RELEVANCE: S-CCHS was associated with bacterial infection, pathologic endotoxin exposure, and frequent polymicrobial infection in cats. Combined tissue inoculates improved culture detection of associated bacteria.

Clinical features, concurrent disorders, and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome.

OBJECTIVE: To characterize clinical features, comorbidities, frequency of bacterial isolation, and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS). ANIMALS: 168 client-owned cats with S-CCHS. PROCEDURES: Data were prospectively (1980 to 2019) collected regarding clinical features, comorbidities, bacterial infection, illness duration, and treatments. Variables were evaluated for associations with survival time. RESULTS: Median age of cats was 10.0 years, with no breed or sex predilection observed. Common clinical features included hyporexia (82%), hyperbilirubinemia (80%), lethargy (80%), vomiting (80%), jaundice (67%), weight loss (54%), and hypoalbuminemia (50%). Comorbidities included extrahepatic bile duct obstruction (53%), cholelithiasis (42%), cholecystitis (40%), and ductal plate malformation (44%) as well as biopsy-confirmed inflammatory bowel disease (60/68 [88%]) and pancreatitis (41/44 [93%]). Bacterial cultures were commonly positive (69%) despite prebiopsy antimicrobial administration in most cats. Of surgically confirmed choleliths, diagnostic imaging identified only 58%. Among 55 cats with "idiopathic pancreatitis," 28 (51%) were documented to have transiting choleliths, and 20 had pancreatic biopsies confirming pancreatitis. Cholelithiasis (with or without bile duct obstruction) and cholecystectomy were associated with survival advantages. Survival disadvantages were found for leukocytosis, ≥ 2-fold increased alkaline phosphatase, and hyperbilirubinemia. Cholecystoenterostomy had no survival impact. Cats with ductal plate malformations were significantly younger at diagnosis and death than other cats. Chronic treatments with antimicrobials, S-adenosylmethionine, and ursodeoxycholic acid were common postbiopsy. CLINICAL RELEVANCE: S-CCHS in cats was associated with bacterial infection and various comorbidities and may be confused with pancreatitis. Surgically correctable morbidities (ie, cholecystitis, cholecystocholelithiasis) and cholecystectomy provided a significant survival advantage.

Disparities in hepatic copper concentrations determined by atomic absorption spectroscopy, inductively coupled plasma mass spectrometry, and digital image analysis of rhodanine-stained sections in dogs.

OBJECTIVE: To investigate disparities in hepatic copper concentrations determined by atomic absorption spectroscopy (AAS), inductively coupled plasma mass spectrometry (ICP-MS), and digital image analysis of rhodanine-stained sections. ANIMALS: 516 dogs. PROCEDURES: Medical records of dogs for which hepatic biopsy specimens had been submitted between January 1999 and December 2019 for evaluation of copper content were reviewed. Paired hepatic copper concentrations obtained with digital image analysis and AAS or ICP-MS were compared, and Spearman rank correlation coefficients were calculated to test for correlations between qualitative copper accumulation scores and hepatic copper concentrations. For dogs for which ≥ 4 rhodanine-stained hepatic sections were available, intraindividual variation in copper distribution across hepatic sections was evaluated. RESULTS: Median hepatic copper concentrations obtained with digital image analysis exceeded concentrations obtained with AAS or ICP-MS. Concentrations were also higher in older dogs (≥ 9 years vs < 9 years), dogs of breeds with a typical body weight ≥ 20 kg (44 lb), and dogs with necroinflammatory changes or uneven copper distribution. Qualitative copper accumulation scores were significantly associated with hepatic copper concentrations; however, the correlation between qualitative score and concentration obtained with digital image analysis (rs = 0.94) was higher than the correlation between qualitative score and concentration obtained with AAS (rs = 0.75) or ICP-MS (rs = 0.57). The coefficient of variation for hepatic copper concentrations obtained with digital image analysis was significantly higher for dogs with higher hepatic copper concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that spectroscopic-spectrometric analysis of hepatic biopsy specimens commonly underestimated the concentration obtained by digital image analysis of rhodanine-stained sections.

Reference limits for hepatic bile duct-to-arteriole and bile duct-to-portal tract ratios in healthy cats.

OBJECTIVE To establish reference limits for hepatic bile duct-to-arteriole ratio (BD:A) and bile duct-to-portal tract ratio (BD:PT) in healthy cats and assess whether these parameters could be used to support a diagnosis of biliary ductopenia in cats. SAMPLE Hepatic biopsy samples from healthy cats (n = 20) and cats with ductopenia (2). PROCEDURES Hepatic biopsy samples from healthy cats were used to count the number of bile ducts and hepatic arterioles in 20 portal tracts for each cat. Mean BD:A and mean BD:PT for each cat were calculated, and these values were used to determine reference limits for mean BD:A and mean BD:PT. Results of histologic evaluation, including immunohistochemical staining in some instances, were compared for healthy cats versus cats with ductopenia. RESULTS Of the 400 portal tracts from healthy cats, 382 (95.5%) and 396 (99.0%) had BD:A and BD:PT, respectively, ≥ 1.0, with less variability in BD:A. Mean BD:A and BD:PT were markedly lower in both cats with ductopenia, compared with values for healthy cats. However, only mean BD:A for cats with ductopenia was below the reference limit of 0.59. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that systematic evaluation of BD:A, with a lower reference limit of 0.59 to define biliary ductopenia in cats, may be a discrete and easily applied morphometric tool to enhance detection of ductopenia in cats. However, application of this ratio required evaluation of ≥ 20 portal tracts with cross-sectioned portal elements to determine a mean BD:A value.

Clinical features of progressive vacuolar hepatopathy in Scottish Terriers with and without hepatocellular carcinoma: 114 cases (1980-2013).

OBJECTIVE: To characterize signalment, clinical features, clinicopathologic variables, hepatic ultrasonographic characteristics, endocrinologic profiles, treatment response, and age at death of Scottish Terriers with progressive vacuolar hepatopathy (VH) with or without hepatocellular carcinoma (HCC). DESIGN: Retrospective case series. ANIMALS: 114 Scottish Terriers with progressive VH. PROCEDURES: Electronic databases from 1980 to 2013 were searched for adult (age > 1 year) Scottish Terriers with histopathologic diagnoses of diffuse glycogen-like VH. Available sections of liver specimens were histologically reevaluated to confirm diffuse VH with or without HCC; 8 dogs with HCC only had neoplastic tissue available. Physical examination, clinicopathologic, treatment, and survival data were obtained. RESULTS: 39 of 114 (34%) dogs with VH had HCC detected at surgery or necropsy or by abdominal ultrasonography. Histologic findings indicated that HCC was seemingly preceded by dysplastic hepatocellular foci. No significant differences were found in clinicopathologic variables or age at death between VH-affected dogs with or without HCC. Fifteen of 26 (58%) dogs with high hepatic copper concentrations had histologic features consistent with copper-associated hepatopathy. Although signs consistent with hyperadrenocorticism were observed in 40% (46/114) of dogs, definitive diagnosis was inconsistently confirmed. Assessment of adrenal sex hormone concentrations before and after ACTH administration identified high progesterone and androstenedione concentrations in 88% (22/25) and 80% (20/25) of tested dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that VH in Scottish Terriers may be linked to adrenal steroidogenesis and a predisposition to HCC. In dogs with VH, frequent serum biochemical analysis and ultrasonographic surveillance for early tumor detection are recommended.

Describing and predicting frequent callers to an ambulance service: analysis of 1 year call data.

AIMS: Ambulance services in England receive around 8 million calls a year, and no known studies have explored characteristics of frequent callers. This study aimed to identify the characteristics of the most frequent callers to Yorkshire Ambulance Service (YAS) between April 2010 and March 2011. METHODS: Top 100 frequent callers to YAS were analysed using population comparison, case control and multiple regression methods. 7808 calls were made by the frequent callers, and data were analysed to predict total number of calls made, and explore characteristics of frequent callers. RESULTS: Six call codes were associated with a higher number of calls. Frequent callers were assigned slower response levels, or often no call code. Calls increased during the times of 4:00-9:00, 16:00-20:00 and 22:00-2:00, and in the months of December, January and February. Men and patients with all but the very highest conveyance rates had a higher number of different reasons for calling. Patients with a medical diagnosis were more likely to be conveyed, while patients with a psychiatric classification had a higher number of different reasons for calling, were older and were more likely to call for 'assault/sexual assault' or 'haemorrhage/laceration'. CONCLUSIONS: Frequent callers to YAS were a heterogeneous group that differed from the overall population served, resulting in numerous implications for the delivery of services for this group of patients. Further research is required to determine if and how frequent callers differ from frequent attenders at emergency departments.

Frequent callers to and users of emergency medical systems: a systematic review.

BACKGROUND: There appears to be a paucity of studies examining the characteristics and impact of frequent users upon emergency medical services (EMS). OBJECTIVE: To review current primary research on frequent users of EMS and to identify possible gaps in the literature. METHODS: Ovid, PubMed and CINAHL/Medline were systematically searched for articles that were published in English and either referred to frequent callers to or users of an EMS, or referred to frequent users of other services where admissions were via ambulance. Studies were included regardless of quality. FINDINGS: Eighteen studies were included. Ten were emergency department based, seven in EMS and one in a psychiatric emergency service. In emergency department studies, frequent users were more likely to arrive via ambulance than infrequent users. In EMS studies, between 0.2% and 23% of patients using EMS were frequent users accounting for 1.4% to 40% of all ambulance use. No two EMS studies used the same definition of a frequent user. No studies focused on characteristics of callers to EMS. Two studies explored interventions for frequent callers to EMS, with mixed results in reducing ambulance use. DISCUSSION: It is unknown to what extent frequent callers impact upon EMS resources. Research should identify predictors and characteristics of frequent users of EMS, and a consistent definition of a frequent caller to or user of EMS would provide greater comparability. The lack of studies identified in this review suggests that further research is needed in order to inform policy and practice.

Presumed primary and secondary hepatic copper accumulation in cats.

OBJECTIVE: To determine signalments, clinical features, clinicopathologic variables, imaging findings, treatments, and survival time of cats with presumed primary copper-associated hepatopathy (PCH) and to determine quantitative measures and histologic characteristics of the accumulation and distribution of copper in liver samples of cats with presumed PCH, extrahepatic bile duct obstruction, chronic nonsuppurative cholangitis-cholangiohepatitis, and miscellaneous other hepatobiliary disorders and liver samples of cats without hepatobiliary disease. DESIGN: Retrospective cross-sectional study. ANIMALS: 100 cats with hepatobiliary disease (PCH [n = 11], extrahepatic bile duct obstruction [14], cholangitis-cholangiohepatitis [37], and miscellaneous hepatobiliary disorders [38]) and 14 cats without hepatobiliary disease. PROCEDURES: From 1980 to 2013, cats with and without hepatobiliary disease confirmed by liver biopsy and measurement of hepatic copper concentrations were identified. Clinical, clinicopathologic, and imaging data were compared between cats with and without PCH. RESULTS: Cats with PCH were typically young (median age, 2.0 years); clinicopathologic and imaging characteristics were similar to those of cats with other liver disorders. Copper-specific staining patterns and quantification of copper in liver samples confirmed PCH (on the basis of detection of > 700 µg/g of liver sample dry weight). Six cats with PCH underwent successful treatment with chelation (penicillamine; n = 5), antioxidants (5), low doses of elemental zinc (2), and feeding of hepatic support or high-protein, low-carbohydrate diets, and other hepatic support treatments. One cat that received penicillamine developed hemolytic anemia, which resolved after discontinuation of administration. Three cats with high hepatic copper concentrations developed hepatocellular neoplasia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that copper accumulates in livers of cats as primary and secondary processes. Long-term management of cats with PCH was possible.

Influence of body condition on plasma prednisolone and prednisone concentrations in clinically healthy cats after single oral dose administration.

Influence of body condition (over-conditioned vs. normal-conditioned) on plasma glucocorticoid concentrations after single dose oral prednisolone or prednisone in 11 cats (5 normal-conditioned and 6-over-conditioned) was investigated using a two-drug crossover trial (3-week washout interval). Body condition was determined using criterion-referenced bioelectrical impedance together with plasma drug concentrations (prednisolone [active drug] and prednisone [pro-drug]) measured by HPLC. Although interconversion of each drug to the other was confirmed, a single 2mg/kg body weight oral dose of prednisolone produced significantly higher plasma prednisolone concentration (∼4-fold higher AUC) compared to prednisone. Significantly higher plasma drug concentrations in over-conditioned cats (∼2-fold) compared to normal-conditioned cats might explain their perceived increased risk for glucocorticoid associated side effects (hepatic lipidosis, diabetes mellitus). Findings suggest low comparative bioavailability of oral prednisone compared to prednisolone in cats and consideration of lean body mass or ideal body weight for dosing practices.

Hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis: 72 cases (1980-2010).

OBJECTIVE: To evaluate differences in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis. DESIGN: etrospective case-control study. SAMPLE: Liver tissue specimens from 36 Labrador Retrievers with chronic hepatitis and 36 age- and sex-matched Labrador Retrievers without chronic hepatitis (control dogs). PROCEDURES: Liver tissue specimens were obtained during 2 study periods (1980 to 1997 and 1998 to 2010). For each tissue specimen, a histologic score was assigned independently by each of 2 interpreters, and the hepatic copper concentration was qualitatively determined via rhodanine staining and quantitatively determined via atomic absorption spectroscopy. RESULTS: Mean hepatic copper concentration was significantly higher in dogs with chronic hepatitis (614 µg/g of dry weight [range, 104 to 4,234 µg/g of dry weight]), compared with that in control dogs (299 µg/g of dry weight [range, 93 to 3,810 µg/g of dry weight]), and increased significantly over time. A higher proportion of liver tissue specimens collected during the 1998-2010 study period had hepatic copper concentrations > 400 µg/g of dry weight (the upper limit of the reference range), compared with the proportion of liver tissue specimens collected during the 1980-1997 study period. The qualitative copper score did not accurately predict quantitative hepatic copper concentration in 33% of study dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the increase in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis over time may be the result of increased exposure of dogs to environmental copper, most likely via the diet.

Influence of dietary supplementation with (L)-carnitine on metabolic rate, fatty acid oxidation, body condition, and weight loss in overweight cats.

OBJECTIVE: To investigate the influence of dietary supplementation with l-carnitine on metabolic rate, fatty acid oxidation, weight loss, and lean body mass (LBM) in overweight cats undergoing rapid weight reduction. ANIMALS: 32 healthy adult neutered colony-housed cats. PROCEDURES: Cats fattened through unrestricted ingestion of an energy-dense diet for 6 months were randomly assigned to 4 groups and fed a weight reduction diet supplemented with 0 (control), 50, 100, or 150 µg of carnitine/g of diet (unrestricted for 1 month, then restricted). Measurements included resting energy expenditure, respiratory quotient, daily energy expenditure, LBM, and fatty acid oxidation. Following weight loss, cats were allowed unrestricted feeding of the energy-dense diet to investigate weight gain after test diet cessation. RESULTS: Median weekly weight loss in all groups was ≥ 1.3%, with no difference among groups in overall or cumulative percentage weight loss. During restricted feeding, the resting energy expenditure-to-LBM ratio was significantly higher in cats that received l-carnitine than in those that received the control diet. Respiratory quotient was significantly lower in each cat that received l-carnitine on day 42, compared with the value before the diet began, and in all cats that received l-carnitine, compared with the control group throughout restricted feeding. A significant increase in palmitate flux rate in cats fed the diet with 150 µg of carnitine/g relative to the flux rate in the control group on day 42 corresponded to significantly increased stoichiometric fat oxidation in the l-carnitine diet group (> 62% vs 14% for the control group). Weight gain (as high as 28%) was evident within 35 days after unrestricted feeding was reintroduced. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary l-carnitine supplementation appeared to have a metabolic effect in overweight cats undergoing rapid weight loss that facilitated fatty acid oxidation.

Influence of treatment with ultralow-dose aspirin on platelet aggregation as measured by whole blood impedance aggregometry and platelet P-selectin expression in clinically normal dogs.

OBJECTIVE: To evaluate the influence of treatment with ultralow-dose aspirin (ULDAsp) on platelet aggregation, P-selectin (CD62P) expression, and formation of platelet-leukocyte aggregates in clinically normal dogs. ANIMALS: 18 clinically normal dogs. PROCEDURES: Studies were conducted before and 24 hours after ULDAsp administration (0.5 mg/kg, PO, q 24 h, for 2 days). Whole blood impedance aggregometry for the assessment of platelet function was performed with sodium citrate-anticoagulated blood and aggregation agonists (ADP at 20, 10, and 5 µmol/L; collagen at 10, 5, and 2 µg/mL). Onset, maximum response, and rate of platelet aggregation were recorded. Flow cytometric assays were configured to detect thrombin-induced CD62P expression and platelet-leukocyte aggregates in EDTA-anticoagulated whole blood. Externalized platelet CD62P and constitutive CD61 (GPIIIa) were labeled with antibodies conjugated to phycoerythrin (PE) and fluorescein isothiocyanate (FITC), respectively. Red blood cell-lysed paraformaldehyde-fixed EDTA-anticoagulated whole blood was dual labeled with CD61-FITC and a panleukocyte antibody (CD18-PE) to characterize platelet-leukocyte aggregates. RESULTS: ULDAsp significantly delayed platelet aggregation onset with ADP at 20 µmol/L by 54% to 104%, attenuated maximum aggregation with various concentrations of ADP and collagen by ≥ 41%, and slowed aggregation rate with the highest ADP and collagen concentrations by ≥ 39%. Depending on the parameter tested, up to 30% of dogs failed to have an ULDAsp effect. Thrombin stimulation significantly increased CD62P expression in platelets and platelet-leukocyte aggregates, but ULDAsp did not alter basal or thrombin-stimulated CD62P expression. CONCLUSIONS AND CLINICAL RELEVANCE: ULDAsp treatment of clinically normal dogs impaired platelet aggregation in most dogs, but did not influence CD62P platelet membrane expression.

Influence of biopsy specimen size, tissue fixation, and assay variation on copper, iron, and zinc concentrations in canine livers.

OBJECTIVE-To determine whether metal concentrations in canine liver specimens were influenced by specimen size, assay variability, tissue processing (formalin fixation and deparaffinization), or storage in paraffin blocks. SAMPLE POPULATION-Liver specimens (fresh frozen and deparaffinized) from 2 dogs with chronic hepatitis (high copper but unremarkable iron concentration [liver 1] and unremarkable copper but high iron concentration [liver 2]) as well as fresh and deparaffinized-archived liver specimens from 20 dogs with various hepatopathies. PROCEDURES-Fresh frozen liver specimens (obtained via simulated needle-core and wedge biopsy), fresh hepatic tissue, and deparaffinized-archived specimens (0.5 to 14 years old) were analyzed for concentrations of copper, iron, and zinc by atomic absorption flame spectrometry. Clinical severity scores were assigned on the basis of tissue metal concentrations. RESULTS-Interassay variation of metal standards was < 4%. Measurements of liver tissues on 8 consecutive days yielded high coefficients of variation (3.6% to 50%) reflecting heterogenous histologic metal distribution; variation was highest in liver 1 and deparaffinized-archived tissues. Heterogenous metal distribution was confirmed by histologic evaluation. The largest range of metal concentrations was detected in wedge biopsy specimens. In tissues with high metal concentrations, copper and iron concentrations were significantly lower in needle-core versus wedge biopsy specimens. A higher zinc concentration in deparaffinized-archived specimens masked a low zinc concentration in fresh liver tissue of 10 of 20 (50%) dogs. CONCLUSIONS AND CLINICAL RELEVANCE-Retrospective measurement of copper and iron concentrations but not zinc concentrations in deparaffinized-archived liver specimens provided relevant information. The value of needle-core biopsy specimens for measurement of metal concentrations is questionable.

Evaluation of platelet function screening tests to detect platelet procoagulant deficiency in dogs with Scott syndrome.

BACKGROUND: Clinical diagnosis of platelet dysfunction is complex and technically challenging. The wide repertoire of platelet responses requires a test panel to assess different parameters of platelet reactivity. While "global" hemostasis analyzers and whole blood assays have potential for testing platelet function, their ability to evaluate platelet procoagulant activity is ill-defined. OBJECTIVES: The aim of this study was to determine whether platelet procoagulant deficiency, the pathophysiologic defect of Scott syndrome, could be detected in point-of-care and whole blood assays. METHODS: Study subjects were 4 Scott syndrome-affected German Shepherds and 8 control dogs. We evaluated 2 point-of-care instruments: the platelet function analyzer (PFA-100) and thromboelastograph (TEG). TEG analysis was performed on recalcified citrated whole blood with and without tissue-factor activation. A whole blood flow cytometric assay was configured to detect thrombin-induced platelet P-selectin expression and platelet-derived microparticle release. Cytometric samples were analyzed after 1 hour and 1 day of storage. RESULTS: We found no significant differences between Scott and control dogs in PFA-100 COL/ADP closure times or in any TEG parameter in tissue-factor-activated samples. In nonactivated samples, mean clotting time (K) and time to maximal rate of thrombus generation were significantly prolonged in Scott dogs; however, values overlapped with those of control dogs. Cytometric analysis of samples from Scott dogs showed significantly diminished platelet-derived microparticle release. Samples from all dogs reanalyzed after 1 day of storage had nonspecific increases in basal P-selectin expression and vesiculation. CONCLUSION: A whole blood cytometric assay to detect stimulated platelet microparticle release can be used to screen for Scott syndrome. However, platelet activation artifacts preclude overnight storage for next-day analysis.

Changes in gallbladder volume in healthy dogs after food was withheld for 12 hours followed by ingestion of a meal or a meal containing erythromycin.

OBJECTIVE: To assess the influence of meal ingestion and orally administered erythromycin on gallbladder volume in dogs. ANIMALS: 22 healthy dogs. PROCEDURES: Ultrasonographically determined gallbladder dimensions in unsedated dogs were used to calculate volume. Measurements were recorded after food was withheld for 12 hours (time 0) and 15, 30, 45, 60, 90, and 120 minutes after a 100-g meal without (n = 22) or with erythromycin (1.0 mg/kg [7], 2.5 mg/kg [7], and both dosages [8]). Gallbladder ejection fraction represented the percentage of volume change from time 0. Intraday and interday coefficients of variation determined operator repeatability and physiologic variation. RESULTS: We did not detect significant differences in gallbladder volume per unit of body weight between treatments at time 0 or in ejection fraction percentage within or between treatments. Median time 0 gallbladder volume was 0.6 mL/kg (range, 0.4 to 1.9) but was > 1.0 mL/kg in 3 of 22 (14%) dogs and or= 25% with at least 1 treatment, but 2 dogs with a gallbladder volume or= 25% were typical. No treatment consistently induced greater gallbladder contraction. Dogs with a gallbladder volume > 1.0 mL/kg and ejection fraction < 25% may require a combined meal and erythromycin protocol.

The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells.

T0901317 is a potent non-steroidal synthetic liver X receptor (LXR) agonist. T0901317 blocked androgenic stimulation of the proliferation of androgen-dependent LNCaP 104-S cells and androgenic suppression of the proliferation of androgen-independent LNCaP 104-R2 cells, inhibited the transcriptional activation of an androgen-dependent reporter gene by androgen, and suppressed gene and protein expression of prostate specific antigen (PSA), a target gene of androgen receptor (AR) without affecting gene and protein expression of AR. T0901317 also inhibited binding of a radiolabeled androgen to AR, but inhibition was much weaker compared to the effect of the antiandrogens, bicalutamide and hydroxyflutamide. The LXR agonist T0901317, therefore, acts as an antiandrogen in human prostate cancer cells.

Evaluation of plasma protein C activity for detection of hepatobiliary disease and portosystemic shunting in dogs.

OBJECTIVE: To determine the diagnostic value of protein C (PC) for detecting hepatobiliary disease and portosystemic shunting (PSS) in dogs. DESIGN: Prospective study. ANIMALS: 238 clinically ill dogs with (n = 207) and without (31) hepatobiliary disease, including 105 with and 102 without PSS. PROCEDURES: Enrollment required routine hematologic, serum biochemical, and urine tests; measurement of PC activity; and a definitive diagnosis. Total serum bile acids (TSBA) concentration and coagulation status, including antithrombin activity, were determined in most dogs. Dogs were grouped into hepatobiliary and PSS categories. Specificity and sensitivity were calculated by use of a PC cutoff value of 70% activity. RESULTS: Specificity for PC activity and TSBA concentrations was similar (76% and 78%, respectively). Best overall sensitivity was detected with TSBA, but PC activity had high sensitivity for detecting PSS and hepatic failure. Protein C activity in microvascular dysplasia (MVD; PC > or = 70% in 95% of dogs) helped differentiate MVD from portosystemic vascular anomalies (PSVA; PC < 70% in 88% of dogs). A receiver operating characteristic curve (PSVA vs MVD) validated a useful cutoff value of < 70% activity for PC. CONCLUSIONS AND CLINICAL RELEVANCE: Combining PC with routine tests improved recognition of PSS, hepatic failure, and severe hepatobiliary disease and signified a grave prognosis when coupled with hyperbilirubinemia and low antithrombin activity in hepatic failure. Protein C activity can help prioritize tests used to distinguish PSVA from MVD and sensitively reflects improved hepatic-portal perfusion after PSVA ligation.

Vacuolar hepatopathy in dogs: 336 cases (1993-2005).

OBJECTIVE: To determine disorders associated with vacuolar hepatopathy (VH), morphologic hepatic and clinicopathologic abnormalities, and affiliation with steroidogenic hormone excess in dogs. DESIGN: Retrospective case series. Animals-336 dogs with histologically confirmed moderate or severe VH. PROCEDURES: Information on signalment, results of diagnostic testing, definitive diagnoses, and exposure to glucocorticoids (ie, exogenous glucocorticoid administration or high endogenous concentrations of steroidogenic hormones) was obtained from medical records. Dogs were grouped by underlying disorder, glucocorticoid exposure, acinar zonal distribution of lesions, and histologic severity. RESULTS: 12 disease groups (neoplastic, acquired hepatobiliary, neurologic, immune-mediated, gastrointestinal tract, renal, infectious, cardiac disease, diabetes mellitus, portosystemic vascular anomaly, adrenal gland dysfunction, and miscellaneous disorders) were identified. There were 186 (55%) dogs with and 150 (45%) dogs without evidence of glucocorticoid exposure. Acinar zonal distribution of hepatic vacuolation and clinicopathologic values did not differ between dogs with and without evidence of glucocorticoid exposure. However, a 3-fold increased likelihood of severe VH was associated with steroidogenic hormone exposure. Of 226 dogs with high serum alkaline phosphatase activity, 102 (45%) had no evidence of glucocorticoid exposure. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that neoplasia and congenital or acquired hepatobiliary disease are common in dogs with VH and provide support for the suggestion that VH, high alkaline phosphatase activity, and illness-invoked physiologic stress may be associated. Histologic confirmation of VH should initiate a diagnostic search for a primary disease if glucocorticoid treatment and hyperadrenocorticism are ruled out.

Aminobacter ciceronei sp. nov. and Aminobacter lissarensis sp. nov., isolated from various terrestrial environments.

The bacterial strains IMB-1(T) and CC495(T), which are capable of growth on methyl chloride (CH(3)Cl, chloromethane) and methyl bromide (CH(3)Br, bromomethane), were isolated from agricultural soil in California fumigated with CH(3)Br, and woodland soil in Northern Ireland, respectively. Two pesticide-/herbicide-degrading bacteria, strains ER2 and C147, were isolated from agricultural soil in Canada. Strain ER2 degrades N-methyl carbamate insecticides, and strain C147 degrades triazine herbicides widely used in agriculture. On the basis of their morphological, physiological and genotypic characteristics, these four strains are considered to represent two novel species of the genus Aminobacter, for which the names Aminobacter ciceronei sp. nov. (type strain IMB-1(T)=ATCC 202197(T)=CIP 108660(T)=CCUG 50580(T); strains ER2 and C147) and Aminobacter lissarensis sp. nov. (type strain CC495(T)=NCIMB 13798(T)=CIP 108661(T)=CCUG 50579(T)) are proposed.

Analysis of genes involved in methyl halide degradation in Aminobacter lissarensis CC495.

Aminobacter lissarensis CC495 is an aerobic facultative methylotroph capable of growth on glucose, glycerol, pyruvate and methylamine as well as the methyl halides methyl chloride and methyl bromide. Previously, cells grown on methyl chloride have been shown to express two polypeptides with apparent molecular masses of 67 and 29 kDa. The 67 kDa protein was purified and identified as a halomethane:bisulfide/halide ion methyltransferase. This study describes a single gene cluster in A. lissarensis CC495 containing the methyl halide utilisation genes cmuB, cmuA, cmuC, orf 188, paaE and hutI. The genes correspond to the same order and have a high similarity to a gene cluster found in Aminobacter ciceronei IMB-1 and Hyphomicrobium chloromethanicum strain CM2 indicating that genes encoding methyl halide degradation are highly conserved in these strains.