Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite after oral and intravenous administration of pentoxifylline to healthy adult horses

OBJECTIVE: To determine serum pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite in horses after administration of a single IV dose and after single and multiple oral doses. ANIMALS: 8 healthy adult horses. PROCEDURES: A crossover study design was used with a washout period of 6 days between treatments. Treatments were IV administration of a single dose of pentoxifylline (8.5 mg/kg) and oral administration of generic sustained-release pentoxifylline (10 mg/kg, q 12 h, for 8 days). Blood samples were collected 0, 1, 3, 6, 12, 20, 30, and 45 minutes and 1, 2, 4, 6, 8, and 12 hours after IV administration. For oral administration, blood samples were collected 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, and 12 hours after the first dose and 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, and 24 hours after the last dose. RESULTS: Elimination of pentoxifylline was rapid after IV administration. After oral administration, pentoxifylline was rapidly absorbed and variably eliminated. Higher serum concentrations of pentoxifylline and apparent bioavailability were observed after oral administration of the first dose, compared with values after administration of the last dose on day 8 of treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, oral administration of 10 mg of pentoxifylline/kg results in serum concentrations equivalent to those observed for therapeutic doses of pentoxifylline in humans. Twice daily administration appears to be appropriate. However, serum concentrations of pentoxifylline appear to decrease with repeated dosing; thus, practitioners may consider increasing the dosage if clinical response diminishes with repeated administration.     

Evaluation of biomarkers of kidney injury following 4% succinylated gelatin and 6% hydroxyethyl starch 130/0.4 administration in a canine hemorrhagic shock model

Objective : To investigate the association between synthetic colloids and biomarkers of acute kidney injury (AKI) in dogs with hemorrhagic shock. Design : Experimental interventional study. Setting : University. Animals : Twenty‐four healthy ex‐racing Greyhounds. Interventions : Anesthetized Greyhounds subjected to hemorrhage for 60 min were resuscitated with 20 mL/kg of fresh whole blood (FWB), 6% hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL/kg of isotonic crystalloid (CRYST) over 20 min (n = 6 per treatment). Concentrations of biomarkers of AKI were measured at baseline, end of hemorrhage, and at 40 (T60), 100 (T120), and 160 (T180) min after fluid bolus. Biomarkers included neutrophil gelatinase‐associated lipocalin in urine and serum (uNGAL; sNGAL), and urine cystatin C (uCYSC), kidney injury molecule‐1 (uKIM), clusterin (uCLUST), osteopontin, gamma‐glutamyl transferase, monocyte chemoattractant protein‐1 (uMCP), interleukin‐6, interleukin‐8, protein (uPROT), hyaluronan, and F₂‐isoprostanes. Renal histology was scored for tubular injury and microvesiculation. Biomarker fold‐change from baseline was compared between groups using mixed effects models (Bonferroni–Holm corrected P<0.05). Frequencies of histology scores were compared by Fisher's exact test. Measurements and main results : In dogs treated with GELO, uNGAL fold‐change was markedly greater compared with all other groups at T60, T120, and T180 (all P<0.001), and uCYSC was greater at T60 compared with CRYST (P<0.001), and at T120 and T180 compared with all other groups (all P<0.001). Smaller, albeit significant, between‐group differences in uKIM, uCLUST, uMCP, and urine protein concentration were observed across the FWB, GELO, and HES groups, compared with CRYST. The GELO group more frequently had marked tubular microvesiculation than the other groups (P = 0.015) although tubular injury scores were comparable. Conclusion : In dogs with hemorrhagic shock, GELO was associated with greater magnitude increases in urine biomarkers of AKI and more frequent marked tubular microvesiculation, compared with FWB, CRYST, and HES.     

Characteristics and outcomes in surgical management of severe acute pancreatitis: 37 dogs (2001–2007)

Objective – Describe clinical characteristics and outcomes associated with canine patients undergoing surgical intervention for treatment of acute pancreatitis.
Design – Retrospective outcome study from 2001 to 2007.
Animals – Thirty-seven dogs.
Interventions – None.
Measurements and Main Results – The following data were collected for dogs who underwent surgical intervention in the course of treatment for severe acute pancreatitis: preoperative clinicopathologic and physical data, ultrasonographic findings, surgical procedure detail, histopathologic findings, and transfusion requirements. The survival rate was 80.8% in dogs with extrahepatic biliary obstruction, 64.3% in dogs undergoing necrosectomy, and 40.6% with pancreatic abscess. Overall survival was 63.6%. Surgical complications included intraoperative and postoperative hemorrhage in 12 dogs, postoperative development of diabetes mellitus in 3 dogs, exocrine pancreatic insufficiency in 1 dog, and bacterial peritonitis in 2 dogs.
Conclusion – Surgical intervention and aggressive postoperative care may be pursued in select dogs with severe acute pancreatitis. In dogs with extrahepatic biliary obstruction secondary to acute pancreatitis, surgical intervention may be associated with a good prognosis whereas dogs with pancreatic abscess formation may have a more guarded prognosis.     

Extrapituitary and Pituitary Pathological Findings in Horses with Pituitary Pars Intermedia Dysfunction: A Retrospective Study

The objective of this study was to describe the histopathologic changes observed in extrapituitary organs as well as the pituitary glands of horses with pituitary pars intermedia dysfunction (PPID). Adrenal gland, thyroid gland, liver, lung, kidney, heart, and pituitary gland from 32 horses with clinical and histologic evidence of PPID and 20 control horses were reviewed histologically. Ten of the control horses were aged animals (≥15 years), allowing those changes attributed to age to be identified. In addition to previously reported changes in adrenal gland and liver, an association was established between PPID and several extrapituitary histopathologic changes, namely bronchiolitis, proliferative glomerulopathy, and myocardial lipofuscinosis and fibrosis. The potential biologic significance of these changes is discussed and, although the retrospective design of the current study precludes establishment of causal relationships between the observed extrapituitary changes and PPID, these findings suggest that further investigations are warranted.     

Coccidioidomycosis in dogs and cats: a review

The dimorphic fungi Coccidioides immitis and Coccidioides posadasii are the causative agents of coccidioidomycosis. Dogs and cats residing in and visiting endemic areas are at risk of exposure to infectious arthrospores. The primary infection is pulmonary and frequently results in chronic cough. Disseminated disease is common and causes cutaneous, osseous, cardiac, ocular, nervous system, or other organ disease. Radiographic changes include a variable degree of interstitial pulmonary infiltration, hilar lymphadenopathy, and osseous lesions. Serological titers support the diagnosis, but definitive diagnosis relies on identification of Coccidioides in cytological or tissue samples. Coccidioidomycosis should be considered in any dog or cat that has been potentially exposed during the previous 3 years and is presented with chronic illness, respiratory signs, lameness, lymphadenopathy, nonhealing cutaneous lesions, or neurological, ocular, or cardiac abnormalities.     

A mechanical comparison of 4.5 mm narrow and 3.5 mm broad plating systems for stabilization of gapped fracture models

OBJECTIVE: To evaluate and compare the mechanical properties of 4.5 narrow and 3.5 broad plating systems using their respective cortical and cancellous screws in unstable, central, and eccentric gap fracture models. STUDY DESIGN: Mechanical evaluation and comparison of 2 dynamic compression plate (DCP) systems. SAMPLE POPULATION: Eighteen cortical and 30 cancellous gapped fracture models. METHODS: DCP (4.5 mm narrow, 3.5 mm broad) with their respective cortical screws were applied to cortical bone density polyurethane foam blocks to construct center gap cortical fracture models that were tested in gap closing monotonic 4-point bending. DCP (4.5 mm narrow, 3.5 mm broad) with their respective cancellous screws were applied to cancellous bone density polyurethane foam blocks to construct eccentric gap cancellous fracture models. The cancellous constructs were tested in monotonic gap opening and gap closing cantilever bending and in cyclic axial loading. Univariate and multivariate repeated measures ANOVA were used to compare the maximum loads at failure of the 4.5 mm constructs and 3.5 mm constructs. RESULTS: The 4.5 mm narrow plating system withstood significantly higher loads at failure than the 3.5 mm broad plating system in 4-point bending (P<.0001) and gap opening cantilever bending (P<.0001). The 4.5 mm system failed in gap closing cantilever bending by plastic deformation of the plate, whereas the 3.5 mm system failed by screw pullout. There was no difference between the 2 systems in cyclic axial loading. CONCLUSION: Results indicate that the 4.5 mm narrow plating system has a mechanical advantage over the 3.5 mm broad plating system for stabilization of gapped fracture models. CLINICAL RELEVANCE: The 4.5 mm narrow plating system may be mechanically advantageous compared with the 3.5 mm broad plating system for stabilizing unreconstructed comminuted long bone fractures in large dogs.     

Characterization of a wild-type strain of Francisella tularensis isolated from a cat.

Francisella tularensis type A is the primary cause of tularemia in animals and humans in North America. The majority of research on F. tularensis has been done with the attenuated live vaccine strain (LVS), which is a type B, but very few wild-type F. tularensis strains have been characterized. A gram-negative coccobacillus that was isolated in pure culture from the lungs of a cat that died after being lost for 5 days was received for identification at the Virginia-Maryland Regional College of Veterinary Medicine Teaching hospital. The isolate (strain TI0902) was not identified (or was misidentified) by commercial identification systems; however, it was identified as F. tularensis subspecies tularensis (type A) by sequencing a portion of the 16S ribosomal RNA gene. Furthermore, repetitive extragenic palindromic sequences-polymerase chain reaction amplified a 4-kb DNA fragment from TI0902 that was characteristic of F. tularensis type A but not type B. The electrophoretic profile of the lipopolysaccharide of strain TI0902 was identical to that of the LVS by Western blotting with antiserum to LVS. The protein-enriched outer membrane of strain TI0902 contained 6-8 proteins, which were similar in molecular size to those from the LVS. Electron microscopy of negatively stained and alcian blue-stained LVS and TI0902 cells showed that both strains were coccobacillary in shape and may be encapsulated. However, after mouse challenge, the TI0902 strain was clearly more virulent than the LVS strain. Results of this study indicate that the genotype and phenotype of wild-type F. tularensis type A strain TI0902 is similar, but not identical, to that of the LVS strain. Further studies will help determine whether pathogenesis and host-pathogen interactions are also similar between the 2 strains.     

Packed red blood cell transfusions in dogs with gastrointestinal hemorrhage: 55 cases (1999-2001)

Fifty-five dogs received packed red blood cell (PRBC) transfusions for gastrointestinal (GI) hemorrhage during a 26-month period (1999 to 2001), accounting for 11.7% of the PRBC transfusions in that time. Thirty-nine (61%) dogs had an intestinal pathology (primary or secondary) as the cause of GI hemorrhage, including intestinal masses, gastroenteritis, hepatic disease, and renal disease. Nonsteroidal and steroidal anti-inflammatory drug use was found frequently in dogs with GI hemorrhage. Sixteen (39%) dogs were identified as having immune-mediated thrombocytopenia (IMT) and associated GI hemorrhage. Dogs with IMT received more transfusions of PRBC than nonIMT dogs (P<0.03) and received a significantly larger total volume of PRBC (P<0.01) during hospitalization.     

Real-time polymerase chain reaction testing for the detection of Mycobacterium genavense and Mycobacterium avium complex species in avian samples

Diagnosis of avian mycobacteriosis, caused by Mycobacterium genavense or species belonging to the Mycobacterium avium complex (MAC), is problematic. Polymerase chain reaction (PCR) offers rapid and sensitive detection of minute quantities of DNA, and conventional protocols have been used for evaluating avian specimens. The recent development of real-time PCR offers several advantages over conventional PCR. In attempts to improve diagnosing avian mycobacteriosis, a real-time TaqMan PCR assay was developed targeting the 65-kD heat shock protein gene of M. genavense and MAC spp. Nineteen reference isolates, 16 clinical isolates, and 32 avian tissue samples were used to evaluate the assay. When sufficient amplicons were produced, the species of mycobacteria was determined by standard sequencing of TaqMan PCR products and compared with results from commercial mycobacteriology laboratories and/or standard sequencing of conventional PCR products. The TaqMan PCR detected DNA from reference isolates of M. genavense, MAC spp., and Mycobacterium tuberculosis complex spp. Of the clinical isolates, the TaqMan PCR detected DNA from 10 of 12 Mycobacterium avium avium isolates and two of three Mycobacterium avium intracellulare isolates. For the tissue samples, the TaqMan PCR amplified DNA in six of nine samples that were identified by sequencing of conventional PCR products and/or by commercial mycobacteriology laboratories as being MAC spp. positive and three of four samples that were positive for M. genavense. There was some disagreement between speciation results from the TaqMan PCR and those from commercial mycobacteriology laboratories or conventional PCR or both. This disagreement was suspected to be because of relatively small numbers of base pairs in the TaqMan PCR products. The TaqMan PCR may provide a useful tool for evaluating clinical samples for DNA from mycobacteria species that most commonly infect birds; however, further refinement is needed in order to improve sensitivity and provide more accurate speciation.