Prevalence of Gastroesophageal Reflux in Cats During Anesthesia and Effect of Omeprazole on Gastric pH.

BackgroundGastroesophageal reflux (GER) is poorly characterized in anesthetized cats, but can cause aspiration pneumonia, esophagitis, and esophageal stricture formation.ObjectiveTo determine whether pre-anesthetic orally administered omeprazole increases gastric and esophageal pH and increases serum gastrin concentrations in anesthetized cats, and to determine the prevalence of GER using combined multichannel impedance and pH monitoring.AnimalsTwenty-seven healthy cats undergoing elective dental procedures.MethodsProspective, double-masked, placebo-controlled, randomized clinical trial. Cats were randomized to receive 2 PO doses of omeprazole (1.45-2.20 mg/kg) or an empty gelatin capsule placebo 18-24 hours and 4 hours before anesthetic induction. Blood for measurement of serum gastrin concentration was collected during anesthetic induction. An esophageal pH/impedance catheter was utilized to continuously measure esophageal pH and detect GER throughout anesthesia.ResultsMean gastric pH in the cats that received omeprazole was 7.2 ± 0.4 (range, 6.6-7.8) and was significantly higher than the pH in cats that received the placebo 2.8 ± 1.0 (range, 1.3-4.1; P < .001). Omeprazole administration was not associated with a significant increase in serum gastrin concentration (P = .616). Nine of 27 cats (33.3%) had ≥1 episode of GER during anesthesia.Conclusions and clinical relevancePre-anesthetic administration of 2 PO doses of omeprazole at a dosage of 1.45-2.20 mg/kg in cats was associated with a significant increase in gastric and esophageal pH within 24 hours, but was not associated with a significant increase in serum gastrin concentration. Prevalence of reflux events in cats during anesthesia was similar to that of dogs during anesthesia

Ultrasonic Transducer And Method For Using Same

An improved ultrasonic transducer fabricated on a silicon base has a piezoelectric layer of polyvinylidene fluoride-trfluroethylene copolymer. The piezoelectric layer is sandwiched between two conductive electrodes, all of which are supported on a dielectric layer on top of the silicon base. At least one of the electrodes forms a Fresnel zone plate to focus the ultrasonic signals from the transducers. To improve the performance of the transducer, the silicon base behind the active area is removed, leaving the dielectric layer as a membrane to support the electrodes and the piezoelectric layer. The resulting void in the silicon base is filled with an acoustically matched backing, such as an epoxy, to enhance the wideband performance of the transducer. The transducer is especially suited for characterizing anatomical structures or features requiring very high resolution.Georgia Tech Research Corp.Medical College Of Georgia Research Institut

Reliability of a high-intensity endurance cycling test.

This study assessed the reproducibility of performance and selected metabolic variables during a variable high-intensity endurance cycling test. 8 trained male cyclists (age: 35.9 ± 7.7 years, maximal oxygen uptake: 54.3 ± 3.9 mL·kg - 1·min - 1) completed 4 high-intensity cycling tests, performed in consecutive weeks. The protocol comprised: 20 min of progressive incremental exercise, where the power output was increased by 5% maximal workload (Wmax) every 5 min from 70% Wmax to 85% Wmax; ten 90 s bouts at 90% Wmax, separated by 180 s at 55% Wmax; 90% Wmax until volitional exhaustion. Blood samples were drawn and heart rate was monitored throughout the protocol. There was no significant order effect between trials for time to exhaustion (mean: 4 113.0 ± 60.8 s) or total distance covered (mean: 4 6126.2 ± 1 968.7 m). Total time to exhaustion and total distance covered showed very high reliability with a mean coefficient of variation (CV) of 1.6% (95% Confidence Intervals (CI) 0.0 ± 124.3 s) and CV of 2.2% (95% CI 0.0 ± 1904.9 m), respectively. Variability in plasma glucose concentrations across the time points was very small (CV 0.46-4.3%, mean 95% CI 0.0 ± 0.33 to 0.0 ± 0.94 mmol·L - 1). Plasma lactate concentrations showed no test order effect. The reliability of performance and metabolic variables makes this protocol a valid test to evaluate nutritional interventions in endurance cycling

Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs

Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability

Pharmacokinetic/Pharmacodynamic Correlation of Cefquinome Against Experimental Catheter-Associated Biofilm Infection Due to Staphylococcus aureus.

Biofilm formations play an important role in Staphylococcus aureus pathogenesis and contribute to antibiotic treatment failures in biofilm-associated infections. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of cefquinome against an experimental catheter-related biofilm model due to S. aureus, including three clinical isolates and one non-clinical isolate. The minimal inhibitory concentration (MIC), minimal biofilm inhibitory concentration (MBIC), biofilm bactericidal concentration (BBC), minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) and in vitro time-kill curves of cefquinome were studied in both planktonic and biofilm cells of study S. aureus strains. The in vivo post-antibiotic effects (PAEs), PK profiles and efficacy of cefquinome were performed in the catheter-related biofilm infection model in murine. A sigmoid E max model was utilized to determine the PK/PD index that best described the dose-response profiles in the model. The MICs and MBICs of cefquinome for the four S. aureus strains were 0.5 and 16 μg/mL, respectively. The BBCs (32-64 μg/mL) and MBECs (64-256 μg/mL) of these study strains were much higher than their corresponding BPC values (1-2 μg/mL). Cefquinome showed time-dependent killing both on planktonic and biofilm cells, but produced much shorter PAEs in biofilm infections. The best-correlated PK/PD parameters of cefquinome for planktonic and biofilm cells were the duration of time that the free drug level exceeded the MIC (fT > MIC, R (2) = 96.2%) and the MBIC (fT > MBIC, R (2) = 94.7%), respectively. In addition, the AUC24h/MBIC of cefquinome also significantly correlated with the anti-biofilm outcome in this model (R (2) = 93.1%). The values of AUC24h/MBIC for biofilm-static and 1-log10-unit biofilm-cidal activity were 22.8 and 35.6 h; respectively. These results indicate that the PK/PD profiles of cefquinome could be used as valuable guidance for effective dosing regimens treating S. aureus biofilm-related infections

Splanchnic Removal of Atrial Natriuretic Factor (ANF) in Man

In order to assess the effect of food ingestion on splanchnic disposal of human alpha-atrial natriuretic peptide (ANF), hepatic-intestinal removal of ANF was determined before and after a test meal. Hepatic venous and arterial plasma samples were obtained from six subjects, most of whom had only disorders of minor degree. Hepatic blood flow (HBF) increased significantly after meal ingestion (1.10 ± 0.17 [SEM] to 1.51 ± 0.26 L/min, P < .01). Baseline arterial ANF (10.9 ± 3.1 pmol/L) did not change significantly. In contrast, hepatic venous ANF increased after meal intake (5.7 ± 2.0 to 8.4 ± 1.9 pmol/L, P < .05), and accordingly the splanchnic fractional extraction decreased (0.53 ± 0.09 to 0.35 ± 0.08), although this was not statistically significant. Splanchnic clearance of ANF increased from 347 ± 90 mL/min to a maximal value of 615 ± 158 mL/min (P < .05). Splanchnic removal of ANF was 3.0 ± 0.5 pmol/min before and increased to a maximum value (7.1 ± 2.2 pmol/min, P < .05) 35 minutes after ingestion of the meal. Our results showed enhanced splanchnic removal of ANF after food intake. This is due to increased hepatic-intestinal clearance of the peptide consequent on increased splanchnic blood flow, rather than altered fractional extraction of ANF

Ultradian, circadian and seasonal rhythms in cortisol secretion and adrenal responsiveness to ACTH and yarding in unrestrained red deer (Cervus elaphus) stags

Seasonal changes in the activity and responsiveness of the adrenal gland in red deer (Cervus elaphus) stags were quantified by measuring 24 h endogenous cortisol secretory profiles and plasma cortisol responses to either administration of exogenous ACTH or a standardised stressor during November (period of velvet growth), February (pre-rut), April (mid-rut) and July (post-rut) (southern hemisphere) using a remote blood sampling device (DracPac). Ultradian rhythms in the concentration of plasma cortisol were observed resulting from the episodic secretion of cortisol from the adrenal cortex at a mean rate of 0.8 pulses/h. Circadian rhythms in plasma cortisol concentrations were also found in 11 out of the 20 complete 24 h profiles (mean amplitude, 3.8+/-1.4 ng/ml). Seasonal rhythms in mean 24 h plasma cortisol concentrations and cortisol pulse parameters were also observed. Mean 24 h plasma cortisol concentrations were higher in November (12.5+/-1.0 ng/ml) than in February (6.3+/-1.0 ng/ml), April (4.0+/-1.0 ng/ml) or July (4.2+/-1. 0 ng/ml). Cortisol pulse height, nadir and amplitude were all significantly higher in November than at other times of the year (P<0.01). Peak cortisol concentrations following infusion of ACTH(1-24) (0.04 IU kg(-1)) were higher (P<0.05) in November (55.8+/-2.7 ng/ml) and lower (P<0.001) in April (33.7+/-1.8 ng/ml) than those in February and July (48.7+/-2.0 ng/ml and 45.4+/-2.0 ng/ml respectively). The area under the cortisol response curve was significantly smaller (P<0.05) in April (266.6+/-15.3 ng/ml/190 min) than at other times of the year (February, 366.1+/-15.3 ng/ml/190 min; July, 340.7+/-15.3 ng/ml/190 min and November, 387.8+/-21.2 ng/ml/190 min). These data demonstrate that the adrenal gland of the red deer stag exhibits ultradian, circadian and seasonal rhythms in activity, and that its responsiveness to ACTH varies with season. November, a period of reproductive quiescence in the southern hemisphere, with new antler growth and rapid weight gain, is associated with higher mean plasma cortisol concentrations and a greater responsiveness to exogenous ACTH. In contrast, the breeding season is associated with lower adrenal activity and responsiveness

Sustained high-level expression of human factor IX (hFIX) after liver-targeted delivery of recombinant adeno-associated virus encoding the hFIX gene in rhesus macaques

The feasibility, safety, and efficacy of liver-directed gene transfer was evaluated in 5 male macaques (aged 2.5 to 6.5 years) by using a recombinant adeno-associated viral (rAAV) vector (rAAV-2 CAGG-hFIX) that had previously mediated persistent therapeutic expression of human factor IX (hFIX; 6%-10% of physiologic levels) in murine models. A dose of 4 × 1012 vector genomes (vgs)/kg of body weight was administered through the hepatic artery or portal vein. Persistence of the rAAV vgs as circular monomers and dimers and high-molecular-weight concatamers was documented in liver tissue by Southern blot analysis for periods of up to 1 year. Vector particles were present in plasma, urine, or saliva for several days after infusion (as shown by polymerase chain reaction analysis), and the vgs were detected in spleen tissue at low copy numbers. An enzyme-linked immunosorption assay capable of detecting between 1% and 25% of normal levels of hFIX in rhesus plasma was developed by using hyperimmune serum from a rhesus monkey that had received an adenoviral vector encoding hFIX. Two macaques having 3 and 40 rAAV genome equivalents/cell, respectively, in liver tissue had 4% and 8% of normal physiologic plasma levels of hFIX, respectively. A level of hFIX that was 3% of normal levels was transiently detected in one other macaque, which had a genome copy number of 25 before abrogation by a neutralizing antibody (inhibitor) to hFIX. This nonhuman-primate model will be useful in further evaluation and development of rAAV vectors for gene therapy of hemophilia B. © 2002 by The American Society of Hematology

Triglyceride-rich lipoproteins prevent septic death in rats.

Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P &lt; or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P &lt; or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P &lt; or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P &lt; or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P &lt; or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis

Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research

Adequate animal models are required to study the preclinical pharmacokinetics (PK), pharmacodynamics (PD) and safety of drugs in the pediatric subpopulation. Over the years, pigs were presented as a potential animal model, since they display a high degree of anatomical and physiological similarities with humans. To assess the suitability of piglets as a preclinical animal model for children, the ontogeny and maturation processes of several organ systems have to be unraveled and compared between both species. The kidneys play a pivotal role in the PK and PD of various drugs, therefore, the glomerular filtration rate (GFR) measured as clearance of endogenous creatinine (Jaffe and enzymatic assay) and exo-iohexol was determined in conventional piglets aging 8 days (n = 16), 4 weeks (n = 8) and 7 weeks (n = 16). The GFR data were normalized to bodyweight (BW), body surface area (BSA) and kidney weight (KW). Normalization to BSA and KW showed an increase in GFR from 46.57 to 100.92 mL/min/m2 and 0.49 to 1.51 mL/min/g KW from 8 days to 7 weeks of age, respectively. Normalization to BW showed a less pronounced increase from 3.55 to 4.31 mL/min/kg. The postnatal development of the GFR was comparable with humans, rendering the piglet a convenient juvenile animal model for studying the PK, PD and safety of drugs in the pediatric subpopulation. Moreover, to facilitate the assessment of the GFR in growing piglets in subsequent studies, a formula was elaborated to estimate the GFR based on plasma creatinine and BW, namely eGFR =1.879 × BW^1.092/Pcr^0.600