Can the neutrophil count from hepatic fine-needle aspirate cytology be used to diagnose hepatitis in dogs? A pilot study.

BACKGROUND: The cytologic diagnosis of inflammation on canine hepatic aspirates can be confounded by neutrophilic infiltrates in the liver of dogs with nodular regeneration, by extramedullary hematopoiesis, and by marked blood contamination. OBJECTIVES: We aimed to assess the association between neutrophil counts on hepatic cytology and the histopathologic diagnosis in dogs with hepatitis and non-inflammatory hepatopathy. We also sought to determine a cut-off value for the cytologic diagnosis of hepatitis. METHODS: In a retrospective blinded pilot study, three observers independently reviewed hepatic aspirates that had corresponding histopathologic examinations performed within 2 days. The number of neutrophils per 200 hepatocytes was determined and averaged among observers. Only neutrophils within or directly in contact with a cluster of ≥5 hepatocytes were counted, and only intact hepatocytes within an approximate monolayer were included. Data are presented as the median (range), and the Mann-Whitney U test is used to make comparisons between groups. RESULTS: Eighteen cases were included (13 hepatitis and five vacuolar hepatopathy). Aspirates with a histopathologic diagnosis of hepatitis had increased numbers of neutrophils compared with those of vacuolar hepatopathy (7.7 [0.3-18.3] vs 3.0 [1.0-5.3]; P = .038). Receiver operating characteristic curve analysis indicated that ≥6 neutrophils were 61.5% (CI 31.6%-86.1%) sensitive and 100% (CI 47.8%-100%) specific for identifying hepatitis. CONCLUSIONS: Liver aspirates from hepatitis cases have a higher number of neutrophils on cytology compared with those from vacuolar hepatopathy; however, larger studies, including those with dogs with other liver pathologies, are required. Identification of six or more neutrophils per 200 hepatocytes is highly suggestive of hepatitis.

Contemporary Outcomes After Partial Resection of Infected Aortic Grafts.

INTRODUCTION: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection. METHODS: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed. RESULTS: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (P = 0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; P = 0.01) as well as aortoenteric fistula (HR 1.9, P = 0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, P = 0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, P = 0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, P = 0.01) and less likely to have patent repairs during follow up (59% vs. 32%, P = 0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01) CONCLUSION: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material.

Retrospective evaluation of clinical outcome after chemotherapy for lymphoma in 15 equids (1991-2017).

BACKGROUND: Prognosis associated with lymphoma in horses is poorly characterized, and treatment is often palliative. Long-term outcome after chemotherapy for horses with lymphoma is not well documented. OBJECTIVE: To report long-term outcome of horses with lymphoma treated with chemotherapy. ANIMALS: Fifteen equids. METHODS: Retrospective case series. Medical record search and call for cases on the ACVIM listserv for horses treated with chemotherapy for lymphoma. RESULTS: Fifteen cases with adequate data were identified. Complete remission was achieved in 5 horses (33.3%), partial response was achieved in 9 equids (60%), and stable disease was achieved in 1 horse. Overall response rate was 93.3% (14/15). Overall median survival time was 8 months (range, 1-46 months). Nine horses experienced a total of 14 adverse effects attributable to chemotherapy. Adverse effects were graded according to the Veterinary Cooperative Oncology Group common terminology criteria for adverse events grading system (grade 1 alopecia, n = 2; grade 1 neutropenia, n = 2; grade 1 lymphopenia, n = 3; grade 1 lethargy, n = 1; grade 2 neurotoxicity, n = 1; grade 2 colic, n = 1; grade 1 hypersensitivity, n = 1; grade 2 hypersensitivity, n = 2; grade 5 hypersensitivity, n = 1). Higher grade adverse effects most commonly were associated with doxorubicin administration (n = 4), including 1 horse that died 18 hours post-administration. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemotherapy can be used successfully for treatment of horses with lymphoma. Adverse effects, most commonly mild, occurred in approximately two-thirds of treated horses.

The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis.

In normal cells, aberrant oncogene expression leads to the accumulation of cytotoxic metabolites, including reactive oxygen species (ROS), which can cause oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c-myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53 is a downstream target of c-Myc and hematological malignancies, such as adult T-cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc overexpression. We therefore hypothesized that p53-regulated pro-survival signals may thwart the cell's metabolic anticancer defenses to support oncogene-activation in lymphoid cancers. Here we show that the Tp53-induced glycolysis and apoptosis regulator (TIGAR) promotes c-myc oncogene-activation by the human T-cell leukemia virus type-1 (HTLV-1) latency-maintenance factor p30II, associated with c-Myc deregulation in ATL clinical isolates. TIGAR prevents the intracellular accumulation of c-Myc-induced ROS and inhibits oncogene-induced cellular senescence in ATL, acute lymphoblastic leukemia, and multiple myeloma cells with elevated c-Myc expression. Our results allude to a pivotal role for p53-regulated antioxidant signals as mediators of c-Myc oncogenic functions in viral and non-viral lymphoid tumors.

Mouse aldo-keto reductase AKR7A5 protects V79 cells against 4-hydroxynonenal-induced apoptosis.

We have developed transgenic Chinese hamster V79 cell lines in order to examine the potential for a mouse aldo-keto reductase, AKR7A5, to protect against the toxicity of 4-hydroxynonenal (4-HNE) and related toxic aldehydes. Stable expression of mouse AKR7A5 in V79 cells conferred four-fold increased resistance to 4-HNE cytotoxicity using the MTT assay compared to empty vector-transfected V79 cells. Cells expressing AKR7A5 showed a decrease in mutation rate compared to control cells in the presence of 4-HNE as measured by HGPRT mutagenicity assay. Furthermore, the cells expressing AKR7A5 showed decreased 4-HNE-induced caspase-3 activity in both a time and dose-dependent manner compared to control cells. These results show that in V79 cells 4-HNE mediates apoptosis via caspase-3 activation and that the AKR7A5 enzyme is able to metabolize 4-HNE in cells, thereby attenuating 4-HNE-induced apoptosis. AKR7A isozymes may therefore be important in protecting against toxic aldehydes derived from lipid peroxidation in vivo.

Serum gamma glutamyl transferase activity in horses with right or left dorsal displacements of the large colon.

The purpose of this study was to test the hypothesis that horses with right dorsal displacement of the large colon (RDDLC) have elevations in serum gamma glutamyl transferase (GGT) activity when compared with horses with left dorsal displacement of the large colon (LDDLC). Medical records from 37 horses with RDDLC and 48 horses with LDDLC were reviewed. Horses were included for study if the RDDLC or LDDLC was confirmed by exploratory laparotomy or postmortem examination and if a serum GGT measurement was obtained within 24 hours before surgery. The proportion of horses with GGT activity within or above the reference range was determined. Of 37 horses, 18 (49%; exact binomial 95% confidence interval, 32-66%) with RDDLC and, of 48 horses, 1 (2%; 95% CI, 0-11%) with LDDLC had GGT above the reference range. Horses with RDDLC had higher serum GGT than did horses with LDDLC. Of 37 horses, 36 (97%) with RDDLC were discharged with a good prognosis and none returned as a result of hepatic disease. Evaluation of surgical and postmortem examinations revealed that positioning of the colon in horses with RDDLC results in compression of the bile duct, which can cause extrahepatic bile duct obstruction and a subsequent elevation in serum GGT activity.

Detoxication of the environmental pollutant acrolein by a rat liver aldo-keto reductase.

Acrolein is a highly reactive hazardous air pollutant of human health concern, particularly as it is a component of cigarette smoke. It can be metabolized by enzymes including the aldo-keto reductase (AKR) family of enzymes. AKR7A1 is a member of the AKR7 sub-family and can catalyse the reduction of toxic aldehydes, including alpha-unsaturated carbonyl compounds, to alcohols [Biochem. J. 312 (1995) 535]. In this study, the role of AKR7A1 in protecting against acrolein toxicity has been assessed by stably-expressing a cDNA encoding AKR7A1 in Chinese hamster V79 cells. Cells expressing AKR7A1 showed over 2-fold increased resistance to acrolein compared to V79 cells alone, as measured by 3-[4,4-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays. IC50 increased from 45 microM in control V79-pCI-neo cells to 125microM for V79-AKR7A1 cells. Cells expressing AKR7A1 were also found to be less susceptible to DNA damage, showing a decrease in mutation rate in the presence of acrolein as measured by hypoxanthine guanine phosphoribosyl transferase (HGPRT) mutagenicity assays. The mutation rate for acrolein-exposed control cells was 20-fold higher than for acrolein-exposed AKR7A1-expressing cells. These results indicate that AKR7A1 has the potential to protect against acrolein-induced damage in vivo.