Evaluation of Therapeutic Use of Antifibrinolytics in Cats.

Limited data are available regarding the use of the antifibrinolytic drugs tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) in cats. This study aimed to evaluate the indications for the use of TXA and EACA in cats and to describe dosing regimens used, occurrence of adverse events, and patient outcomes. This was a retrospective multicenter study. Medical databases were searched for feline patients billed for TXA or EACA between 2015 and 2021. Thirty-five cats met the inclusion criteria; 86% received TXA and 14% received EACA. The most common indication was nontraumatic hemorrhage (54%), followed by traumatic hemorrhage (17%) and elective surgery (11%). The median dose was 10 mg/kg for TXA and 50 mg/kg for EACA. Overall, 52% of cats survived to discharge. Potential adverse events were noted in 7/35 (20%) patients. Of these, 29% survived to discharge. No standardized dosing regimen was identified; rather, dose, dosing interval, and duration of administration varied markedly between patients. Administration was potentially associated with severe adverse events, although the retrospective design makes it difficult to establish a causal association with antifibrinolytic use. This study provides a base for future prospective studies by giving an insight into the use of antifibrinolytic drugs in cats.

Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease.

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) initiated by expression of the p210-BCR-ABL fusion protein. We demonstrate in a murine model of p210-BCR-ABL-induced MPD that gene targeting of Rac1 and Rac2 significantly delays or abrogates disease development. Attenuation of the disease phenotype is associated with severely diminished p210-BCR-ABL-induced downstream signaling in primary hematopoietic cells. We utilize NSC23766, a small molecule antagonist of Rac activation, to validate biochemically and functionally Rac as a molecular target in both a relevant animal model and in primary human CML cells in vitro and in a xenograft model in vivo, including in Imatinib-resistant p210-BCR-ABL disease. These data demonstrate that Rac is an additional therapeutic target in p210-BCR-ABL-mediated MPD.

Retrospective evaluation of systemic hypertension in dogs with nonassociative (primary) immune-mediated hemolytic anemia (December 2016 to April 2019): 26 cases.

OBJECTIVE: To report the prevalence of arterial hypertension in a population of dogs with nonassociative immune-mediated hemolytic anemia (IMHA) on presentation and during hospitalization. To determine the relationships of systolic blood pressure (SBP) with mortality and a prognostic indicator, the canine hemolytic anemia objective score. DESIGN: Retrospective observational study (December 2016 to April 2019). SETTING: University teaching hospital. ANIMALS: Twenty-six clinical dogs presenting to the ICU with nonassociative (primary) IMHA and a control group of 23 clinical dogs with idiopathic epilepsy hospitalized in the ICU for seizure treatment or monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hypertension was defined as SBP ≥ 160 mm Hg and severe hypertension as SBP ≥ 180 mm Hg. Mean SBP was significantly increased in IMHA dogs (161 mm Hg, SD = 21) compared to ICU control dogs (138 mm Hg, SD = 14; P < 0.005). Hypertension was present in 13 of 26 (50.0%) dogs across the period of hospitalization and was severe in three of 26 (11.5%). During at least 1 day of hospitalization, 18 of 26 (69.2%) dogs were hypertensive and eight of 26 (34.6%) were severely hypertensive. Hypertension was not associated with short-term mortality or canine hemolytic anemia objective score. CONCLUSIONS: In this retrospective study, hypertension was more prevalent in dogs with nonassociative IMHA than a control population of ICU-hospitalized dogs. An association between autoimmune conditions and hypertension has been previously reported in people but not within a canine population. Hypertension in dogs may have an inflammatory or autoimmune etiology. SBP should be monitored closely in canine IMHA, in case antihypertensive treatment is required.

Successful percutaneous drainage of a refractory caudal mediastinal paraesophageal abscess in a dog.

OBJECTIVE: To describe a novel technique for paraesophageal abscess drainage in a dog. CASE SUMMARY: A 6-year-old dog presented for pyrexia of unknown origin, subsequently confirmed to be due to a paraesophageal abscess. This was managed by the ultrasound-guided placement of a thoracostomy tube into the abscess, allowing drainage to be performed. This led to clinical resolution and, at an 8-month follow-up, the dog continued to do well. NEW OR UNIQUE INFORMATION PROVIDED: Paraesophageal abscessation is typically managed with surgical intervention, which carries inherent risks and complications. This report describes a novel technique that did not require general anesthesia or invasive surgical intervention, achieving clinical remission without any adverse effects. It also summarizes the current literature available on this condition.

Implementation of a postarrest debriefing tool in a veterinary university hospital.

OBJECTIVE: To describe the use of a postarrest debriefing tool (DBT) within a university teaching hospital and to evaluate user perceptions of the tool. DESIGN: Observational study over a 1-year period and associated hospital clinical personnel survey. SETTING: University teaching hospital. INTERVENTIONS: Qualitative data surrounding the use and utility of the DBT were analyzed, as well as survey results. MEASUREMENTS AND MAIN RESULTS: Forty-four arrests occurred during the study period. Debriefing was performed after 26 of 44 (59%) cardiopulmonary resuscitation (CPR) events, of which 22 of 26 (85%) were recorded using the DBT and four without the DBT. Return of spontaneous circulation did not significantly affect the use of the DBT (p = 0.753). Most events in which debriefing was not performed occurred outside of business hours (13/18; 72%). The most frequent positive debriefing comments related to cooperation/coordination within the team (22/167; 13%). The most frequent negative debriefing comments concerned equipment issues (36/167; 22%). Of the action points generated, 57% (34/60) were directed at equipment use/availability. Teams reported that emergency drugs were appropriately administered in 21 of 22 (95%) cases. In contrast, closed loop communication was reportedly only used during 6 of 22 (27%) events. The hospital survey response rate was 56 of 338 (17%) clinical staff, of whom 37 of 56 (66%) agreed or strongly agreed that debriefing had improved team performance during CPR. Overall, 33 of 56 (60%) staff felt that the DBT had improved the debriefing process at the hospital. However, 3 of 56 (5%) staff members felt that they were unable to state their opinions in a blame-free environment during debriefing. CONCLUSIONS: Implementation of a DBT enabled formal identification of strengths and training needs of resuscitation teams, and its implementation was viewed positively by the majority of hospital staff. However, further refinement of the tool and prospective studies evaluating its efficacy in improving outcome are warranted.

Comparison of effusion cell block and biopsy immunohistochemistry in mesothelial hyperplasia, mesothelioma, and carcinoma in dogs.

BACKGROUND: Determining the cause of effusions is challenging and might require a biopsy. Whether cell blocks from effusions are representative of biopsies requires investigation. A previously developed immunohistochemical panel aids in the differentiation of hyperplastic and neoplastic mesothelium in canine biopsies but has not been investigated in effusions. OBJECTIVES: The study aimed to assess cell blocks as an alternative to biopsies and determine whether immunohistochemistry helps distinguish hyperplastic mesothelium, mesothelioma, and carcinoma. METHODS: Effusions and biopsies were collected from five dogs with mesothelial hyperplasia (group MH), six with mesothelioma (group M), and five with carcinoma (group C). Immunohistochemistry (IHC) for cytokeratin, vimentin, Wilm's tumor protein 1 (WT1), desmin, glucose transporter 1 (GLUT1), and insulin-like growth factor II mRNA-binding protein 3 (IMP3) was performed. Sections were scored for staining intensity and the percentage of positively stained cells. RESULTS: In paired cell blocks and biopsies, vimentin and WT1 staining were positively correlated for intensity and the percentage of positive cells, although not all paired results were identical. The intensity of IMP3 staining in cell blocks was higher in group M than in group C (P = 0.012), and WT1 staining was higher in group MH than in group C (P = 0.020). For biopsies, the intensity of WT1 staining was higher in group MH than in group C (P = 0.031). In group C, WT1 was negative in all cell blocks and biopsies, and desmin was negative in four of five cases. CONCLUSIONS: IHC results for the cell blocks and biopsies were comparable for potentially useful markers, such as WT1, which helped discriminate between groups. IHC provided additional information, although results were not always definitive. Further studies on a larger population are required.

The effect of prazosin on outcome in feline urethral obstruction.

OBJECTIVE: To determine whether prazosin administration following urethral obstruction (UO) reduces the risk for recurrent urethral obstruction (rUO) or lower urinary tract signs, and to document adverse effects associated with prazosin use in cats. DESIGN: Double-blinded, prospective, interventional study. SETTING: University teaching hospital. ANIMALS: A population of 47 consecutive male cats with UO not associated with urinary tract calculi >2 mm in diameter. INTERVENTIONS: Cats were randomized to receive either prazosin (0.25 mg/cat PO q 12 h, n = 27) or placebo (n = 20) for 1 month following UO. MEASUREMENTS AND MAIN RESULTS: Cats were monitored for rUO, severity of lower urinary tract signs, and medication adverse effects during hospitalization and through weekly conversations with the owner during the 1- month study period and once more at 6 months following discharge. There was no difference in the rUO rate among cats that received prazosin or placebo prior to hospital discharge (2/26 (7%) versus 1/19 (5%), P = 1.00), during the 1- month medication period (4/26 (15%) versus 3/18 (17%), P = 0.776), or at 6 months following treatment for UO (7/19 (37%) versus 4/13 (31%), P = 0.811). There was no difference in the severity of lower urinary tract signs reported by the owners at the 1-, 2-, 3-, or 4-week follow-up periods among the cats in either group (P = 0.62, 0.68, 0.33, 1.00, respectively). Reported adverse effects from prazosin administration included lethargy, ptyalism, diarrhea, anorexia, and malodorous stool. CONCLUSIONS: Although our study results failed to find a difference in the incidence of rUO and severity of lower urinary tract signs among cats receiving prazosin and those receiving placebo, these study results should be interpreted cautiously as our study was underpowered to identify such differences. Larger placebo-controlled, prospective studies are needed to determine the clinical utility of prazosin in prevention of rUO.

Presumptive cocaine toxicosis in 19 dogs: 2004-2012.

OBJECTIVE: To characterize the incidence, signalment, presenting complaint, history, clinical signs, diagnostic test results, complications, treatment, length of hospitalization, and outcome of dogs presenting with presumptive cocaine toxicosis. DESIGN: Retrospective study from March 1, 2004 to March 1, 2012. SETTING: Twenty-four hour urban university veterinary teaching hospital. ANIMALS: Nineteen dogs presenting with clinical signs consistent with cocaine toxicosis and having a positive urine cocaine test. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All dogs had neurological abnormalities including bilateral mydriasis (11/19 [58%]), hyperexcitability/hyperesthesia (10/19 [53%]), ataxia (8/19 [42%]), focal or generalized muscle tremors (8/19 [42%]), reduced mental awareness (6/19 [32%]), and seizures (3/19 [16%]). Other signs included weakness (7/19 [37%]), vomiting (6/19 [32%]), and lethargy (3/19 [16%]). Tachycardia was apparent in 10/19 (53%) dogs, hypertension in 4/19 (21%), and hyperthermia in 5/19 (26%). Sinus tachycardia was the only reported cardiac arrhythmia. Bloodwork findings included hyperglycemia in 4/19 (21%) dogs, and increased plasma lactate concentration in 9/19 (47%). Most dogs (16/19 [84%]) were hospitalized for supportive care, which generally included isotonic crystalloid fluid administration, and treatment with sedative or anxiolytic drugs including diazepam, midazolam, acepromazine, and chlorpromazine. Two dogs required further anticonvulsant therapy (phenobarbital and propofol) and 1 dog was treated with a constant rate infusion of esmolol. All dogs survived to discharge, and the median length of hospitalization was 15 hours (10-30 h). CONCLUSIONS: Cocaine toxicosis was infrequently suspected. Neurological signs predominated, but cardiovascular alterations were also frequently reported. Hospitalization for monitoring and supportive care is recommended given the potential for life-threatening complications such as seizures, hypertensive crisis, and tachyarrhythmias. The prognosis for survival to hospital discharge can be good with the appropriate supportive care.

Pneumomediastinum in cats: 45 cases (2000-2010).

OBJECTIVE: To characterize the incidence, etiology, presenting complaint, clinical course, and outcome of cats with pneumomediastinum. DESIGN: Retrospective study from the period of January 1st, 2000 to December 31st, 2010. SETTING: University teaching hospital. ANIMALS: Forty-five cats with a radiographic diagnosis of pneumomediastinum. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical and radiographic records were reviewed to identify cats with a radiographic diagnosis of pneumomediastinum. Clinical data were retrieved, including signalment, history, presenting clinical signs, diagnostic test results, treatment, complications, and survival to discharge. In 31 of 45 (69%) cats the pneumomediastinum was secondary to an obvious inciting cause. General anesthesia with endotracheal intubation and positive pressure ventilation was the most common cause in 17 of 45 (38%) cases. This was followed by trauma in 12 of 45 (27%) cats, and tracheal foreign bodies in 2 of 45 (4%) cats. Spontaneous pneumomediastinum (unknown underlying cause) was diagnosed in 14 of 45 (31%) of cases. Onset of clinical signs and diagnosis of spontaneous pneumomediastinum was preceded by emesis in 6 of 14 cats. Common presenting signs were tachypnea seen in 27 of 45 (60%) cats, increased respiratory effort in 26 of 45 (58%) cats, and subcutaneous emphysema in 30 of 45 (66%) cats. Concurrent pneumothorax was identified in 21 of 45 (47%) cats, pleural effusion in 10 of 45 (22%), and pneumoretroperitoneum in 21 of 45 (47%). The mainstay of treatment was supportive care and treatment of the underlying disease process. The prognosis for recovery was good, with 87% survival until hospital discharge. CONCLUSIONS: Pneumomediastinum in cats is an infrequently diagnosed condition. It is often secondary to an event such as general anesthesia with endotracheal intubation and positive pressure ventilation but less frequently may occur spontaneously. The prognosis is good with appropriate supportive care.

Endo180 binds to the C-terminal region of type I collagen.

Type I collagen is a fibril-forming heterotrimer composed of two alpha1 and one alpha2 chains and plays a crucial role in cell-matrix adhesion and cell differentiation. Through a comprehensive differential display screening of oncogenic ras target genes, we have shown that the alpha1 chain of type I collagen (col1a1) is markedly down-regulated by the ras oncogene through the mitogen-activated protein kinase pathway. Although ras-transformed cells are no longer able to produce and secrete endogenous collagen, they can still adhere to exogenous collagen, suggesting that the cells express a collagen binding factor(s) on the cell surface. When the region of col1a1 encompassing the C-terminal glycine repeat and C-prodomain (amino acids 1000-1453) was affinity-labeled with human placental alkaline phosphatase, the secreted trimeric fusion protein could bind to the surface of Ras-transformed cells. Using biochemical purification followed by matrix-assisted laser desorption/ionization mass spectrometry analysis, we identified this collagen binding factor as Endo180 (uPARAP, CD280), a member of the mannose receptor family. Ectopic expression of Endo180 in CosE5 cells followed by in situ staining and quantitative binding assays confirmed that Endo180 indeed recognizes and binds to placental alkaline phosphatase. The interaction between Endo180 and the C-terminal region of type I collagen appears to play an important role in cell-matrix adhesion.

NDRG1 is necessary for p53-dependent apoptosis.

Although a number of target genes for the tumor suppressor p53 have been described, the mechanism of p53-dependent apoptosis is incompletely understood. Thus, it is essential to identify and characterize additional target genes that could mediate apoptosis. In the study reported here, we isolated a p53-regulated gene named NDRG1 (N-Myc down-regulated gene 1). Its expression is induced by DNA damage in a p53-dependent fashion. The promoter region of the NDRG1 gene contains a p53 binding site that confers p53-dependent transcriptional activation via a heterologous reporter. RNA interference and inducible gene expression approaches suggest that NDRG1 is necessary but not sufficient for p53-mediated caspase activation and apoptosis. This report further supports the notion that p53 controls a network of genes that are required for its apoptotic function.