Lyophilized platelets versus cryopreserved platelets for management of bleeding in thrombocytopenic dogs: A multicenter randomized clinical trial.

BACKGROUND: Thrombocytopenia in dogs is common in critical care medicine, but availability of fresh platelet concentrates in veterinary medicine can be limiting. Lyophilized platelets have long shelf-lives and can be easily transported, stored, and administered in various settings. OBJECTIVE: To evaluate the efficacy and safety of a novel trehalose-stabilized canine lyophilized platelet product in thrombocytopenic dogs with clinically-evident bleeding. ANIMALS: Eighty-eight dogs with platelet counts <50 × 103 /µL and a standardized bleeding assessment tool (DOGiBAT) score ≥2. METHODS: Multicenter, randomized, non-blinded, non-inferiority clinical trial comparing dimethyl sulfoxide (DMSO)-stabilized cryopreserved platelet concentrates (CPP) with trehalose-stabilized lyophilized platelets (LP) for control of bleeding in thrombocytopenic dogs. Dogs were randomized to receive 3 × 109 platelets/kg of LP or CPP. Primary outcome measures were change in DOGiBAT score, platelet count, need for additional red cell transfusion and all-cause mortality. RESULTS: Fifty dogs received LP and 38 received CPP. Baseline demographics and clinical characteristics of both groups were comparable. At 1-hour post-transfusion, LP were superior for change in DOGiBAT score, and non-inferior at 24-hours post-transfusion. The LP were non-inferior to CPP for change in platelet count, need for additional red blood cell units, and survival to discharge. The LP were superior for change in hematocrit at 1-hour post-transfusion, and non-inferior at 24-hours. No adverse effects were noted in either group. CONCLUSIONS AND CLINICAL IMPORTANCE: A novel trehalose-stabilized canine LP product appears to be logistically superior and is clinically non-inferior to DMSO-stabilized canine CPP for management of bleeding in thrombocytopenic dogs.

Delayed type III hypersensitivity reaction with acute kidney injury in two dogs following administration of concentrated human albumin during treatment for hypoalbuminemia secondary to septic peritonitis.

OBJECTIVE: To describe 2 dogs with acute kidney injury secondary to type III hypersensitivity reaction to 25% human serum albumin (HSA). CASE SERIES SUMMARY: Two dogs were presented with evidence of septic peritonitis. The dogs were hospitalized following definitive surgical correction of a jejunal laceration following routine ovariohysterectomy, and removal of a jejunal foreign body. In the postoperative period, both dogs developed hypoalbuminemia and received 25% HSA. At the time of initial discharge, both dogs were doing well clinically and had normal renal parameters. Eleven and 18 days after HSA infusion, respectively, both dogs were re-presented with clinical signs of inappetence, vomiting, and lameness that progressed to urticaria, peripheral and angioedema, and petechiae, consistent with a delayed type III hypersensitivity reaction. Treatment for the type III hypersensitivity reaction to HSA included administration of diphenhydramine and glucocorticoids. Despite partial resolution of edema and joint swelling, both dogs developed progressive azotemia together with hypoalbuminemia and proteinuria. One dog developed an anuric acute kidney injury (AKI). Both dogs were humanely euthanized. Histopathology of the kidneys of both dogs was consistent with immune complex deposition and vasculitis. NEW OR UNIQUE INFORMATION: Severe type III hypersensitivity reactions have been documented in healthy dogs and clinical patients following the administration of HSA. This report describes the first documented delayed type III hypersensitivity reaction in 2 dogs with septic peritonitis that resulted in AKI, glomerulonephritis, and oligo- to anuria in clinical patients following administration of 25% HSA.

Suspected Compartment Syndrome, Consumptive Thrombocytopenia, and Anemia Secondary to a Ruptured Arterial Aneurysm or Pseudoaneurysm Following Multiple Stifle Surgeries.

A 12 yr old male neutered beagle was presented on transfer to the intensive care unit with severe anemia, thrombocytopenia, and bruising detected 1 day after undergoing tibial plateau leveling osteotomy surgery. The patient had undergone extra-capsular stifle stabilization surgery 14 wk prior to treat ligament disease in the same knee. Laboratory testing and treatment for anemia, presumptive immune-mediated thrombocytopenia, and possible hemostatic disorder was initiated. A persistent anemia, progressive thrombocytopenia, and the development of a firm swelling and neurologic impairment in the limb raised concerns for compartment syndrome (CS). A musculoskeletal ultrasound revealed a large aneurysm in the caudal thigh surrounded by abnormal muscle tissue. The patient underwent amputation of the limb and recovered without further complication. Pathology findings were consistent with the development of femoral CS secondary to a ruptured peripheral arterial aneurysm or a pseudoaneurysm. A consumptive thrombocytopenia and regenerative anemia were attributed to periodic or progressive thrombosis of the vessel and regional hemorrhage. Postoperative CS can develop in combination with peripheral arterial aneurysm or pseudoaneurysm, and screening for vascular abnormalities as well as CS should be considered in complicated recovery from orthopedic surgery with compatible clinical signs including progressive soft tissue swelling, persistent anemia, and thrombocytopenia.

Disorders of micturition in small animal patients: clinical significance, etiologies, and management strategies.

OBJECTIVES: To review the physiology of micturition, the pathophysiology of micturition disorders, and current pharmacological agents used to treat these disorders. To discuss different urinary catheterization techniques, along with the risks of catheter-associated urinary tract infections attributed with these techniques. ETIOLOGY: Many critically ill veterinary patients are at risk of developing a number of neurological and non neurological micturition-related disorders. DIAGNOSIS: Micturition disorders can be diagnosed based on physical examination findings, urinary voiding contrast studies, urethral pressure profiles, and diagnostic testing such as urinalysis and urine cultures. THERAPY: Therapy can be either pharmacological, involvement of urinary catheterization, surgical, or a combination of all the above. The goal of the treatment is to correct the underlying causes resulting in the micturition-related disorder, and if possible, allow the patient to regain their normal physiological micturition behavior. PROGNOSIS: Depending on the underlying disease process and duration of the micturition disorder, the prognosis can be variable. In many instances, near-normal or normal function can return, but in severe cases, the patient may not regain its normal, appropriate micturition response.

Preliminary evaluation of the utility of comparing SpO2 /FiO2 and PaO2 /FiO2 ratios in dogs.

OBJECTIVE: To determine whether the ratio of pulse oximetry saturation/fraction of inspired oxygen (SpO2 /FiO2 , [SF]) correlates with the ratio of partial pressure of oxygen in arterial blood/FiO2 (PaO2 /FiO2 , [PF]) in dogs. DESIGN: Prospective, observational pilot study. SETTING: Urban tertiary veterinary referral center. ANIMALS: Thirty-eight client-owned dogs requiring assessment of oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas analysis with co-oximetry was performed on samples obtained from the dorsal pedal artery. Median SpO2 was 91.5% (range 80-97%) and median PaO2 was 70.1 mmHg (range 44.5-103.8 mmHg). Hypoventilation was uncommon and venous admixture was the predominant cause of hypoxemia in this population. Median SF was 435.7 (range 381.0-461.9) and median PF was 334.0 (range 211.9-494.3). Nine dogs (23.6%) had PF <300; no dogs had PF below 200. SF and PF were correlated (ρ = 0.618, P < 0.01). CONCLUSIONS: SF and PF in dogs spontaneously breathing room air have good correlation, suggesting that SF may be a useful, noninvasive surrogate for PF when assessing oxygenation in canine patients. Further studies are warranted to confirm and validate this relationship in spontaneously breathing and mechanically ventilated dogs on varying levels of FiO2 and to assess the ability of SF to predict outcome.

Stromal regulation of neoplastic development: age-dependent normalization of neoplastic mammary cells by mammary stroma.

There is mounting evidence that the stroma plays a crucial role in mammary gland carcinogenesis. Here, we report that mammary gland stroma from mature and multiparous rats prevents neoplastic development and encourages normal ductal growth of grafted epithelial cancer cells. Fifty thousand epithelial cancer cells were injected into the cleared fat pads of virgin hosts at 24, 52, 80, and 150 days of age and of hosts that had undergone two cycles of pregnancy, lactation, and involution. Six months after inoculation, tumor incidence was 75%, 100%, 50%, and 18.2% in 24-, 52-, 80-, and 150-day-old virgin rats, respectively, and 0% in the twice-parous animals. Most remarkably, these neoplastic cells appeared to form normal ducts in all hosts-Ha-ras-1 mutation served as a marker to identify the tumor origin of the outgrowths. The tumor development pattern suggests a parallel to the phenomenon of age- and reproductive state-dependent susceptibility and resistance to chemical carcinogens. As susceptibility to carcinogenesis decreases, the ability of the stroma to reprogram neoplastic epithelial cells increases. Thus, the neoplastic phenotype is context-dependent, and it therefore offers the intriguing possibility that the process of carcinogenesis is amenable to normalization or cure once the mechanisms of stroma-mediated normalization are elucidated and manipulated.

Androgenic and estrogenic activity in water bodies receiving cattle feedlot effluent in Eastern Nebraska, USA.

Studies reveal that surface waters worldwide are contaminated with hormonally active agents, many released from sewage treatment plants. Another potential source of aquatic hormonal contamination is livestock feedlot effluent. In this study, we assessed whether feedlot effluent contaminates watercourses by measuring a) total androgenic [methyltrienolone (R1881) equivalents] and estrogenic (17beta-estradiol equivalents) activity using the A-SCREEN and E-SCREEN bioassays and b) concentrations of anabolic agents via gas chromatography-mass spectroscopy and enzyme-based immunoassays. Water samples were collected over 3 years from up to six sites [all confluent with the Elkhorn River, Nebraska, USA: a feedlot retention pond (site 1), a site downstream from site 1 (site 2), a stream with intermediate livestock impact (site 3), and three sites with no observable livestock impact (sites 4-6)] and two sources of tap water. In 1999, samples from site 1 contained 9.6 pM R1881 equivalents and 1.7 pM 17beta-estradiol equivalents. Site 2 samples had estrogen levels similar to those in site 1 samples but lower androgen levels (3.8 pM R1881 equivalents). Androgen levels in site 3 samples were similar to those in site 2 samples, whereas estrogen levels decreased to 0.7 pM 17beta-estradiol equivalents. At site 6, androgen levels were approximately half those found at site 3, and estrogen levels were comparable with those at site 3. Sampling in later years was limited to fewer sites because of drought and lack of permission to access one site. Instrumental analysis revealed estrone but no significant levels of resorcylic acid lactones or trenbolone metabolites. Tap water was devoid of hormonal activity. We conclude that feedlot effluents contain sufficient levels of hormonally active agents to warrant further investigation of possible effects on aquatic ecosystem health.

The stroma as a crucial target in rat mammary gland carcinogenesis.

A complex network of interactions between the stroma, the extracellular matrix and the epithelium drives mammary gland development and function. Two main assumptions in chemical carcinogenesis of the mammary gland have been that carcinogens induce neoplasia by causing mutations in the DNA of the epithelial cells and that the alterations of tissue architecture observed in neoplasms are a consequence of this primary mutational event. Here, we use a rat mammary tissue recombination model and the chemical carcinogen N-nitrosomethylurea (NMU) to determine whether the primary target of the carcinogen is the epithelium, the stroma or both tissue compartments. Mammary epithelial cells were exposed in vitro either to the carcinogen or vehicle before being transplanted into the cleared fat pads of rats exposed to carcinogen or vehicle. We observed that neoplastic transformation of these mammary epithelial cells occurred only when the stroma was exposed in vivo to NMU, regardless of whether or not the epithelial cells were exposed to the carcinogen. Mammary epithelial cells exposed in vitro to the carcinogen formed phenotypically normal ducts when injected into a non-treated stroma. Mutation in the Ha-ras-1 gene did not correlate with initiation of neoplasia. Not only was it often found in both cleared mammary fat pads of vehicle-treated animals and intact mammary glands of untreated animals, but it was also absent in some tumors. Our results suggest that the stroma is a crucial target of the carcinogen and that mutation in the Ha-ras-1 gene is neither necessary nor sufficient for tumor initiation.