Plasmonic couplings in Ag-Au heterodimers.

The plasmonic coupling between silver (Ag) and gold (Au) nanoparticles (NPs) under four polarization modes was examined: a longitudinal mode (L-mode), where the electric field of a linearly polarized incident light parallels the dimer axis, and three transverse modes (T-modes), where the electric field of the light is perpendicular to the dimer axis. The coupling was studied using the discrete dipole approximation followed by an in-house postprocessing code that determines the extinction (Qext), absorption (Qabs), and near-field (Qnf) spectra from the individual NPs as well as the whole system. In agreement with the literature results, the extinction/absorption spectra of the whole dimer have two peaks, one near the Ag localized surface plasmon resonance (LSPR) region and the other at the Au LSPR region, with the peak at Ag LSPR being reduced in all modes and the peak at Au LSPR being red-shifted and increased in the L-mode but not in the T-modes. It is further shown that the scattering at the Ag LSPR region is reduced and becomes less than the isolated Ag NPs, but the absorption at the Ag LSPR is increased and becomes greater than the isolated Ag NPs for the 50 nm Ag-Au heterodimer. This suggests that the scattering from Ag NPs is being reabsorbed by the neighboring Au NPs due to the interband electronic transition in Au at that wavelength range. The Qext from the individual NP in the heterodimer shows the presence of the Fano profile on the Au NP but not on the Ag NP. This phenomenon was further investigated by using a dielectric particle (DP) placed near the Ag or Au NPs. The Fano profile appears in the absorbing DP spectra placed near either Ag or Au NPs. However, the Fano profile is masked upon further increases in the refractive index value of the DP particle. This explains the absence of a Fano profile on the Ag NPs in the Ag-Au heterodimer. The large near-field enhancement on both Ag and Au NPs at the Au plasmonic wavelength in the L-mode for large NPs was investigated through a DP-Au system. The large enhancement was shown to arise from a large imaginary component of the DP refractive index and a small real component. Through examination of both the near- and far-field properties of the individual NPs as well as the whole system and examinations of DP-Ag and DP-Au systems, our study provides a new understanding of the couplings between Ag and Au NPs.

An Investigation on the Use of Au@SiO2@Au Nanomatryoshkas as Gap-Enhanced Raman Tags.

Gap-enhanced Raman tags are a new type of optical probe that have wide applications in sensing and detection. A gap-enhanced Raman tag is prepared by embedding Raman molecules inside a gap between two plasmonic metals such as an Au core and Au shell. Even though placing Raman molecules beneath an Au shell seems counter-intuitive, it has been shown that such systems produce a stronger surface-enhanced Raman scattering response due to the strong electric field inside the gap. While the theoretical support of the stronger electric field inside the gap was provided in the literature, a comprehensive understanding of how the electric field inside the gap compares with that of the outer surface of the particle was not readily available. We investigated Au@SiO2@Au nanoparticles with diameters ranging from 35 nm to 70 nm with varying shell (2.5-10 nm) and gap (2.5-15 nm) thicknesses and obtained both far-field and near-field spectra. The extinction spectra from these particles always have two peaks. The low-energy peak redshifts with the decreasing shell thickness. However, when the gap thickness decreases, the low-energy peaks first blueshift and then redshift, producing a C-shape in the peak position. For every system we investigated, the near-field enhancement spectra were stronger inside the gap than on the outer surface of the nanoparticle. We find that a thin shell combined with a thin gap will produce the greatest near-field enhancement inside the gap. Our work fills the knowledge gap between the exciting potential applications of gap-enhanced Raman tags and the fundamental knowledge of enhancement provided by the gap.

Insight on the Coupling of Plasmonic Nanoparticles from Near-Field Spectra Determined via Discrete Dipole Approximations.

Coupling between plasmonic nanoparticles (NPs) in nanoparticle assemblies has been investigated extensively via far-field properties, such as absorption and scattering, but very rarely via near-field properties, and a quantitative investigation of near-field properties should provide great insight into the nature of the coupling. We report a numerical procedure to obtain reliable near-field spectra (Q NF) around spherical gold nanoparticles (Au NPs) using Discrete Dipole Approximation (DDA). The reliability of the method was tested by comparing Q NF from DDA calculations with exact results from the Mie theory. We then applied the method to examine Au NPs assembled in dimer, trimer, and up to pentamer in a linear arrangement. For the well-studied dimer system, we show that the Q NF enhancement, due to coupling in longitudinal mode, is much greater than the enhancement in Q ext. There is a linear correlation between the Q NF and Q ext peak positions, with the Q NF peak redshifted from the Q ext peak by an average of approximately 12 nm. In the case of the multimers, Q NF spectra from individual spheres were not always identical and become dependent on the sphere location. In the longitudinal model, the center sphere has the strongest Q NF spectra. For the transverse mode, we differentiate two different scenario, transverse-Y where both electric field (E) and light propagation vector (k) are perpendicular the chain axis, and transverse-X where k is parallel to the chain axis. In transverse-Y mode, coupling leads to reduced Q NF spectra and the center sphere has the lowest Q NF intensity. In transverse-X mode, there is retardation effect from the front sphere to the back sphere. The Q NF from the front sphere is stronger than from the back sphere. In addition, due to the phase lag in k-direction, the Q NF in transverse-X can differ quite significantly from transverse-Y for large particles. All these results could be understood when one considers how electric field from induced dipoles on neighboring NPs add on or subtract from the incident E-field. These results provide new insight into the coupling properties of Au NPs.

Effects of metronidazole on the fecal microbiome and metabolome in healthy dogs.

BACKGROUND: Metronidazole has a substantial impact on the gut microbiome. However, the recovery of the microbiome after discontinuation of administration, and the metabolic consequences of such alterations have not been investigated to date. OBJECTIVES: To describe the impact of 14-day metronidazole administration, alone or in combination with a hydrolyzed protein diet, on fecal microbiome, metabolome, bile acids (BAs), and lactate production, and on serum metabolome in healthy dogs. ANIMALS: Twenty-four healthy pet dogs. METHODS: Prospective, nonrandomized controlled study. Dogs fed various commercial diets were divided in 3 groups: control group (no intervention, G1); group receiving hydrolyzed protein diet, followed by metronidazole administration (G2); and group receiving metronidazole only (G3). Microbiome composition was evaluated with sequencing of 16S rRNA genes and quantitative polymerase chain reaction (qPCR)-based dysbiosis index. Untargeted metabolomics analysis of fecal and serum samples was performed, followed by targeted assays for fecal BAs and lactate. RESULTS: No changes were observed in G1, or G2 during diet change. Metronidazole significantly changed microbiome composition in G2 and G3, including decreases in richness (P < .001) and in key bacteria such as Fusobacteria (q < 0.001) that did not fully resolve 4 weeks after metronidazole discontinuation. Fecal dysbiosis index was significantly increased (P < .001). Those changes were accompanied by increased fecal total lactate (P < .001), and decreased secondary BAs deoxycholic acid and lithocholic acid (P < .001). CONCLUSION AND CLINICAL IMPORTANCE: Our results indicate a minimum 4-week effect of metronidazole on fecal microbiome and metabolome, supporting a cautious approach to prescription of metronidazole in dogs.

Prognostic indicators in cats with septic peritonitis (2002-2015): 83 cases.

OBJECTIVE: To identify physical exam findings, clinicopathological parameters, time to surgery, empirical antimicrobial use, and culture results that could be associated with outcome in cats with septic peritonitis (SP). DESIGN: Retrospective cohort study of cats from 2002 to 2015. SETTING: Four university teaching hospitals. ANIMALS: Eighty-three cats diagnosed with SP by cytology or culture. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Fifty-eight cats survived to discharge (69.9%); 1 cat was euthanized in surgery; 20 were euthanized postoperatively; 4 cats suffered cardiac arrest after surgery. The most common etiology of SP was secondary SP due to gastrointestinal perforation (49.4%), followed by primary SP (22.3%). Mean blood glucose concentration was significantly different between survivors and nonsurvivors (P = 0.006). Cats that received appropriate empirical antibiotic therapy were 4.4 times more likely to survive than cats that did not receive appropriate antibiotics (P = 0.018). CONCLUSIONS: As previously documented, SP secondary to gastrointestinal leakage was the most common etiology. In this population, cats with a higher blood glucose concentration on presentation had a worse prognosis. Cats that received appropriate empirical antimicrobial therapy were more likely to survive.

Prospective evaluation of S100A12 and S100A8/A9 (calprotectin) in dogs with sepsis or the systemic inflammatory response syndrome.

Pattern recognition receptors (e.g., S100A12 or S100A8/A9) hold promise as inflammatory biomarkers. We prospectively determined and compared serum S100A12 and S100A8/A9 concentrations in dogs with sepsis (n = 11) or systemic inflammatory response syndrome (SIRS; n = 8) over a 3-d period with each other, healthy controls (n = 50), and other clinical and clinicopathologic variables. Serum S100A12 and S100A8/A9 concentrations were significantly higher in dogs with sepsis or SIRS (all p < 0.05) at the time of hospital admission (day 1) compared to healthy controls, with no differences between patient groups. However, septic dogs had significantly lower serum S100A12 concentrations on day 2 and day 3 (both p < 0.05) compared to dogs with SIRS. Likewise, dogs with sepsis had significantly lower S100A8/A9 concentrations on day 2 (p < 0.05). Neither serum S100A12 nor S100A8/A9 concentrations were associated with survival to discharge. Our results suggest a differential expression of the S100/calgranulins between dogs with sepsis and those with SIRS. Serum S100A12 or S100A8/A9 concentration at the time of hospital admission did not differentiate dogs with sepsis from those with SIRS, but the trend of S100/calgranulin concentrations during the following 24-48 h may be a useful surrogate marker for differentiating sepsis from SIRS.

Serum alpha1 -proteinase inhibitor concentrations in dogs with systemic inflammatory response syndrome or sepsis.

OBJECTIVE: To determine whether the concentration of serum canine alpha1 -proteinase inhibitor (cα1 -PI) has diagnostic or prognostic utility in dogs with sepsis or noninfectious systemic inflammatory response syndrome (SIRS). DESIGN: Prospective, observational study from May to December 2010. SETTING: University teaching hospital ICU. ANIMALS: Sixty-nine client-owned dogs: 19 dogs with SIRS or sepsis and 50 healthy control dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum and plasma samples were collected from dogs with SIRS or sepsis on the day of hospital admission and once on the following 2 days, and on a single day in healthy controls. Patients were assessed using the 10-parameter Acute Patient Physiologic and Laboratory Evaluation (APPLEfull ) and 5-parameter (APPLEfast ) score. Serum cα1 -PI concentrations were measured, compared among groups of dogs, and evaluated for a correlation with the concentration of serum C-reactive protein, plasma interleukin-6, tumor necrosis factor-α, the APPLE scores, and survival to discharge. Serum cα1 -PI concentrations were significantly lower in dogs with SIRS/sepsis (P < 0.001) than in healthy controls. While day 1 serum cα1 -PI concentrations did not differ between dogs with SIRS and those with sepsis (P = 0.592), septic dogs had significantly lower serum cα1 -PI concentrations on days 2 (P = 0.017) and 3 (P = 0.036) than dogs with SIRS. Serum cα1 -PI concentrations did not differ between survivors and nonsurvivors (P = 1.000), but were inversely correlated with the APPLEfull score (ρ = -0.48; P = 0.040) and plasma interleukin-6 concentrations (ρ = -0.50; P = 0.037). CONCLUSIONS: These results suggest a role of cα1 -PI as a negative acute phase protein in dogs. The concentration of serum cα1 -PI at the time of hospital admission does not have utility to identify dogs with sepsis from those with noninfectious SIRS, but may be a useful surrogate marker for early stratification of illness severity.

Correlation between thromboelastography and traditional coagulation test parameters in hospitalized dogs.

A hospital-based, prospective cross-sectional study was used to compare kaolin-activated thromboelastography (TEG) parameters with traditional coagulation tests in 29 hospitalized dogs. Cases were included if the attending clinician requested coagulation testing. Blood was obtained from each dog and coagulation (prothrombin time, partial thromboplastin time, antithrombin activity, d-dimer concentration, and fibrinogen concentration) and TEG analyses were performed. Hematocrit (Hct) was also measured. Traditional coagulation results were evaluated for correlation with those from kaolin-activated TEG. Spearman's correlation was used to calculate correlation coefficients. Fibrinogen was positively correlated with maximum amplitude (Pearson r=0.72, P<0.001) and global clot strength (Pearson r=0.72, P<0.001). There was no correlation between any of the remaining coagulation variables, TEG parameters, or Hct. Results of kaolin-activated TEG and traditional coagulation tests are not interchangeable means of monitoring coagulation derangements in this intensive care unit patient population. Determination of a true outcome measure is necessary to establish TEG's clinical relevance to veterinary medicine.

Effects of oxymorphone hydrochloride or hydromorphone hydrochloride on minimal alveolar concentration of desflurane in sheep.

OBJECTIVE: To establish the minimum alveolar concentration (MAC) of desflurane and evaluate the effects of 2 opioids on MAC in sheep. ANIMALS: 8 adult nulliparous mixed-breed sheep. PROCEDURES: A randomized crossover design was used. Each sheep was evaluated individually on 2 occasions (to allow assessment of the effects of each of 2 opioids), separated by a minimum of 10 days. On each occasion, sheep were anesthetized with desflurane in 100% oxygen, MAC of desflurane was determined, oxymorphone (0.05 mg/kg) or hydromorphone (0.10 mg/kg) was administered IV, and MAC was redetermined. Physiologic variables and arterial blood gas and electrolyte concentrations were measured at baseline (before MAC determination, with end-tidal desflurane concentration maintained at 10%) and each time MAC was determined. Timing of various stages of anesthesia was recorded for both occasions. RESULTS: Mean ± SEM MAC of desflurane was 8.6 ± 0.2%. Oxymorphone or hydromorphone administration resulted in significantly lower MAC (7.6 ± 0.4% and 7.9 ± 0.2%, respectively). Cardiac output at MAC determination for desflurane alone and for desflurane with opioid administration was higher than that at baseline. No difference was identified among hematologic values at any point. Effects of oxymorphone and hydromorphone on durations of various stages of anesthesia did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE: MAC of desflurane in nulliparous adult sheep was established. Intravenous administration of oxymorphone or hydromorphone led to a decrease in MAC; however, the clinical importance of that decrease was minor relative to the effect in other species.

Characterization of microbial dysbiosis and metabolomic changes in dogs with acute diarrhea.

Limited information is available regarding the metabolic consequences of intestinal dysbiosis in dogs with acute onset of diarrhea. The aim of this study was to evaluate the fecal microbiome, fecal concentrations of short-chain fatty acids (SCFAs), as well as serum and urine metabolites in healthy dogs (n=13) and dogs with acute diarrhea (n=13). The fecal microbiome, SCFAs, and serum/urine metabolite profiles were characterized by 454-pyrosequencing of the 16S rRNA genes, GC/MS, and untargeted and targeted metabolomics approach using UPLC/MS and HPLC/MS, respectively. Significantly lower bacterial diversity was observed in dogs with acute diarrhea in regards to species richness, chao1, and Shannon index (p=0.0218, 0.0176, and 0.0033; respectively). Dogs with acute diarrhea had significantly different microbial communities compared to healthy dogs (unweighted Unifrac distances, ANOSIM p=0.0040). While Bacteroidetes, Faecalibacterium, and an unclassified genus within Ruminococcaceae were underrepresented, the genus Clostridium was overrepresented in dogs with acute diarrhea. Concentrations of fecal propionic acid were significantly decreased in acute diarrhea (p=0.0033), and were correlated to a decrease in Faecalibacterium (ρ=0.6725, p=0.0332). The predicted functional gene content of the microbiome (PICRUSt) revealed overrepresentations of genes for transposase enzymes as well as methyl accepting chemotaxis proteins in acute diarrhea. Serum concentrations of kynurenic acid and urine concentrations of 2-methyl-1H-indole and 5-Methoxy-1H-indole-3-carbaldehyde were significantly decreased in acute diarrhea (p=0.0048, 0.0185, and 0.0330, respectively). These results demonstrate that the fecal dysbiosis present in acute diarrhea is associated with altered systemic metabolic states.

Stability of hemostatic proteins in canine fresh-frozen plasma thawed with a modified commercial microwave warmer or warm water bath.

OBJECTIVE: To compare stability of hemostatic proteins in canine fresh-frozen plasma (FFP) thawed with a modified commercial microwave warmer (MCM) or warm water bath (37°C; WWB) or at room temperature (22°C). SAMPLE: Fresh-frozen plasma obtained from 8 canine donors of a commercial blood bank. PROCEDURES: A commercial microwave warmer was modified with a thermocouple to measure surface temperature of bags containing plasma. The MCM and a WWB were each used to concurrently thaw a 60-mL bag of plasma obtained from the same donor. Two 3-mL control aliquots of FFP from each donor were thawed to room temperature without use of a heating device. Concentrations of hemostatic proteins, albumin, and D-dimers; prothrombin time (PT); and activated partial thromboplastin time (aPTT) were determined for all samples. RESULTS: Significant decreases in concentrations of factors II, IX, X, XI, fibrinogen, von Willebrand factor, antithrombin, protein C, and albumin and significant increases in PT and aPTT were detected for plasma thawed with the MCM, compared with results for samples thawed with the WWB. Concentrations of factors VII, VIII, and XII were not significantly different between plasma thawed with the MCM and WWB. Concentrations of D-dimers were above the reference range for all thawed samples regardless of thawing method. No significant differences in factor concentrations were detected between control and WWB-thawed samples. CONCLUSIONS AND CLINICAL RELEVANCE: Significant differences in hemostatic protein concentrations and coagulation times were detected for plasma thawed with an MCM but not between control and WWB-thawed samples. Clinical importance of these changes should be investigated.

The impact of surgical timing and intervention on outcome in traumatized dogs and cats.

OBJECTIVE: To review the relevant human and veterinary literature regarding the timing of surgical intervention for trauma patients and the impact on outcome. DATA SOURCES: Original research, clinical studies, and review articles with no date restrictions from both human and veterinary literature. HUMAN DATA SYNTHESIS: Despite extensive research into the ideal timing of surgical intervention for human trauma victims, debate is ongoing and views are still evolving. Prior to the 1970s, the standard of care consisted of delayed surgical treatment, as these patients were considered too ill to undergo surgery. Beginning in the 1970s, and continuing for nearly 2 decades, early definitive surgical treatment was recommended. The most recent evolution of human trauma management incorporates the concept of damage control surgery, which acknowledges the importance of early skeletal stabilization or laparotomy for reducing morbidity while attempting to avoid complications such as acute respiratory distress syndrome or multiple organ dysfunction syndrome. VETERINARY DATA SYNTHESIS: Despite a relatively large amount of literature available regarding veterinary trauma, no evidence exists to provide the clinician guidance as to the ideal timing of surgery for trauma patients. With the exception of diaphragmatic hernia, no studies were identified that attempted to evaluate this variable. CONCLUSIONS: Veterinary-specific studies are needed to evaluate the impact of surgical timing on outcome following trauma. The information that can be obtained from studies in this area can improve veterinary trauma care and may be used as models for human trauma care through translational applications.

Evaluation of serum thyroid hormones in dogs with systemic inflammatory response syndrome or sepsis.

OBJECTIVE: To determine whether dogs with systemic inflammatory response syndrome (SIRS) or sepsis have derangements in serum thyroid hormone concentrations and to evaluate whether such derangements relate to illness severity or outcome. DESIGN: Prospective observational study. Dogs hospitalized with SIRS or sepsis between May and December 2010 were included. Serum thyroid hormone concentrations were measured in all dogs. Data obtained on admission were used to calculate the Acute Patient Physiologic and Laboratory Evaluation (APPLE) scores. SETTING: University teaching hospital. ANIMALS: Twenty-two consecutive client-owned dogs hospitalized with SIRS or sepsis were enrolled; 18 dogs completed the study and 4 dogs were excluded for incomplete data. Forty-nine healthy dogs owned by volunteers were used as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Decreased total thyroxine (TT4) concentrations were documented in all septic and 7/9 dogs with SIRS. Free T4 concentrations were decreased, but were within the reference interval in 12/18 dogs with SIRS or sepsis compared to control dogs (P < 0.001). Dogs with increased APPLE(fast) scores were less likely to survive (P = 0.017). CONCLUSIONS: Dogs with SIRS or sepsis have derangements in measured serum thyroid hormones. No relationships were identified between thyroid hormone concentrations and survival. The APPLE(fast) score was the only variable predictive of poor outcome.

Comparison of PCR and conventional blood culture to analyze blood from dogs with suspected sepsis.

Sepsis carries a poor prognosis in critically ill dogs. PCR-based diagnostics could be more sensitive for detecting bacteremia than conventional blood culture, allowing earlier initiation of appropriate therapy. Molecular techniques have been considered as ancillary tools for detecting bacteremia and identifying pathogens in humans and in dogs with bacterial endocarditis. This study compared PCR analysis and blood culture for detecting bacteremia in six dogs with suspected sepsis and six healthy control dogs. One blood culture from a dog with suspected sepsis was positive but none from the healthy controls. PCR was negative for extracts from all dogs. This pilot study does not support the hypothesis that culture-independent PCR-based techniques used directly on small samples of blood are useful for diagnosing bacteremia in dogs with suspected sepsis.

Multicenter evaluation of the administration of crotalid antivenom in cats: 115 cases (2000-2011).

OBJECTIVE: To evaluate use of crotalid antivenom, frequency of hypersensitivity reactions, and risk factors for hypersensitivity reactions and death in envenomed cats. DESIGN: Retrospective multicenter case series. ANIMALS: 115 envenomed cats treated with antivenom and 177 envenomed cats treated without antivenom. Procedures-Medical records from 5 institutions were searched by means of a multiple-choice survey with standardized answers for patient data including signalment, diagnosis, antivenom administration criteria, premedication, product, dose, administration rate, hypersensitivity reactions, and mortality rate. RESULTS: 95 of 115 (82.6%) cats received whole IgG antivenom, 11 (9.57%) received F(ab')2 antivenom, and 4 (3.48%) received Fab antivenom. The majority (101/115 [878%]) of cats received 1 vial of antivenom. In all cats, the median dilution of antivenom was 1:60 (range, 1:10 to 1:250) administered over a median period of 2.0 hours (range, 0.3 to 9.0 hours). There was no mortality rate difference between cats that did (6.67%) or did not (5.08%) receive antivenom. A type I hypersensitivity reaction was diagnosed in 26 of 115 (22.6%) cats. The use of premedications did not decrease type I hypersensitivity or improve mortality rate. Cats that had a type I hypersensitivity reaction were 10 times as likely to die as were those that did not have such a reaction. CONCLUSIONS AND CLINICAL RELEVANCE: The mortality rate of cats treated with antivenom was low. The administration of premedications did not improve mortality rate or prevent hypersensitivity reactions. The only variable associated with mortality rate was development of a type I hypersensitivity reaction. The rate of antivenom administration should be further evaluated as a possible risk factor for type I hypersensitivity reactions.

Serum calprotectin concentrations in dogs with idiopathic inflammatory bowel disease.

OBJECTIVE: To measure serum calprotectin concentration in dogs with inflammatory bowel disease (IBD) before and after initiation of treatment and evaluate its correlation with a clinical scoring system (canine IBD activity index), serum canine C-reactive protein concentration, and severity of histopathologic changes. ANIMALS: 34 dogs with idiopathic IBD and 139 healthy control dogs. PROCEDURES: From dogs with IBD, blood samples were collected immediately before (baseline) and 3 weeks after initiation of 1 of 2 treatments: prednisone (1 mg/kg, PO, q 12 h; n = 21) or a combination of prednisone and metronidazole (10 mg/kg, PO, q 12 h; 13). Blood samples were collected once from each of the control dogs. For all samples, serum calprotectin concentration was determined via radioimmunoassay. RESULTS: Mean serum calprotectin concentrations for dogs with IBD at baseline (431.1 µg/L) and 3 weeks after initiation of treatment (676.9 µg/L) were significantly higher, compared with that (219.4 µg/L) for control dogs, and were not significantly correlated with the canine IBD activity index, serum C-reactive protein concentration, or severity of histopathologic changes. The use of a serum calprotectin concentration of ≥ 296.0 µg/L as a cutoff had a sensitivity of 82.4% (95% confidence interval, 65.5% to 93.2%) and specificity of 68.4% (95% confidence interval, 59.9% to 76.0%) for distinguishing dogs with idiopathic IBD from healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Serum calprotectin concentration may be a useful biomarker for the detection of inflammation in dogs, but the use of certain drugs (eg, glucocorticoids) appears to limit its clinical usefulness.

Inherited disorders of hemostasis in dogs and cats.

Inherited disorders of hemostasis encompass abnormalities in primary hemostasis, coagulation, and fibrinolysis resulting from genetic mutations. There is significant variation in the phenotype expressed ranging from life limiting to the absence of overt clinical signs. Von Willebrand disease is the most common primary hemostatic disorder in dogs, and hemophilia A is the most common coagulation factor disorder. The diagnosis of inherited bleeding disorders is made by functional and/or quantitative evaluation. Genetic testing has added to the knowledge base, allowing prevention through targeted breeding. Avoidance of trauma and injury is paramount in the prevention of bleeding in animals diagnosed with inherited hemostatic disorders. Current therapeutic options include platelet transfusions, broad replacement of coagulation factors (e.g., plasma), targeted factor replacement (e.g., cryoprecipitate), antifibrinolytic agents and specific factor replacement, and treatment of the symptoms (i.e., bleeding) with blood transfusions.

Accidental and experimentally induced 5-fluorouracil toxicity in dogs.

OBJECTIVE: To summarize the literature involving 5-fluorouracil (5-FU) toxicosis in dogs. ETIOLOGY: 5-Fluorouracil's mechanism of action revolves around the metabolism of 5-FU into fluorouridine triphosphate which then interferes with RNA synthesis and function as well as the inhibition of thymidylate synthase which ultimately impairs DNA stability. Toxicity of 5-FU is the most pronounced on rapidly dividing cells. Toxicity manifests itself mainly in the neurologic, gastrointestinal, respiratory, or hematopoietic systems. DIAGNOSIS: History of accidental exposure to 5-FU-containing products. THERAPY: Therapy for 5-FU toxicosis involves typical decontamination procedures and symptomatic therapy for the subsequent toxicity. Seizure control and treatment of the severe gastrointestinal signs that follow are the primary goals in the acute setting. As the disease progresses, management of the sequelae to bone marrow suppression and pulmonary complications are essential. PROGNOSIS: The prognosis for dogs with ingestion of 5-FU is dependent on the amount consumed, with severe intoxication carrying a poor prognosis. Toxic doses can be as little as 5 mg/kg, and doses ≥40 mg/kg are reported to be uniformly fatal.

Cytologic diagnosis of disseminated histoplasmosis in the wall of the urinary bladder of a cat.

A 10 yr old domestic longhair presented with a 2.5 mo history of recurrent hematuria. Abdominal ultrasound examination demonstrated a thickened urinary bladder, abdominal lymphadenopathy, and a thickened and rounded spleen. Cytologic examination of fine-needle aspirate samples revealed Histoplasma capsulatum organisms in the urinary bladder wall and spleen. The cat was treated with itraconazole (10 mg/kg per os q 24 hr for 2.5 wk). The cat was euthanized after 19 days of treatment because of lack of improvement. To the authors' knowledge, this is the first documented case of feline disseminated histoplasmosis diagnosed in the urinary bladder wall.

Syntheses, structures, and photoisomerization of (E)- and (Z)-2-tert-butyl-9-(2,2,2-triphenylethylidene)fluorene.

"Sterically geared" 9-(2,2,2-triphenylethylidene)fluorene (1) is of potential interest as a photoactive moiety in molecular devices, and the 2-tert-butyl derivative (6) has been synthesized to investigate photoisomerization. E and Z stereoisomers of 6 were separated and identified by X-ray crystallography. The tert-butyl group does not introduce additional strain, and its close proximity to the trityl group in the Z isomer suggests an attractive van der Waals interaction. The UV spectra of (E)-6 and (Z)-6 are nearly identical, showing absorption bands that are similar to those of fluorene occurring at wavelengths longer than 240 nm. Photoisomerization of 6 was investigated at 266, 280 and 320 nm. Solutions initially containing only (E)-6 or (Z)-6 were irradiated with pulsed laser light, monitoring isomerization by 1H NMR spectroscopy. Negligible photodecomposition was observed when the solutions were agitated by N2 ebullition. Experimental data were fitted to theoretical curves to obtain photoisomerization quantum yields (phi(ZE) and phi(EZ)) ranging from 0.04 to 0.09. This first photoisomerization study of a dibenzofulvene reveals significant quantum yields, despite theoretical prediction of inefficient or negligible isomerization of the parent hydrocarbon, fulvene. Thermal isomerization of 6 at 270 degrees C (t(1/2) = 120 min) was also followed by 1H NMR spectroscopy, resulting in an estimated activation energy (deltaG(double dagger)) of 43 kcal/mol.