bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic hypothermia for neonatal encephalopathy: a UK survey of opinion, practice and neuro‐investigation at the end of 2007
Authors: Kapetanakis Andrew , Azzopardi Denis , Wyatt John , Robertson Nicola J
Published: December 2008

Background: The 2007 Cochrane review of therapeutic hypothermia for neonatal encephalopathy (NE) indicates a significant reduction in adverse outcome. UK National Institute for Clinical Excellence guidelines are awaited.

Objective: To benchmark current opinion and practice to inform future strategies for optimal knowledge transfer for therapeutic hypothermia.

Methods: A web based questionnaire (30 sections related to opinion and practice of management of NE) sent to the clinical leads of Level I, II and III neonatal units throughout the UK in November/December 2007.

Results: One hundred and twenty‐five (out of 195) UK neonatal units responded (response rate 66%). Ten percent, 37.5% and 51.5% responses were from level I, II and III units respectively. Twenty eight percent of all units provided therapeutic hypothermia locally (52% of level III units), however 80% of responders would offer therapeutic hypothermia if there was the facility. Overall, 57% of responders considered therapeutic hypothermia effective or very effective – similar for all unit levels; 43% considered more data are required. Regional availability of therapeutic hypothermia exists in 55% of units and 41% of units offer transfer to a regional centre for therapeutic hypothermia.

Conclusion: In the UK in 2007, access to therapeutic hypothermia was widespread although not universal. More than half of responders considered therapeutic hypothermia effective. Fifty‐five percent of perinatal networks have the facility to offer therapeutic hypothermia. The involvement of national bodies may be necessary to ensure the adoption of therapeutic hypothermia according to defined protocols and standards; registration is important and will help ensure universal neurodevelopmental follow up.
Australian Society for Geriatric Medicine Position Statement on Physical Restraint Use in the Elderly
Authors: Flicker Dr Leon
Published: December 2008

Generally, physical restraints are used on patients who have significant cognitive impairment. For those patients who are competent, informed consent should be obtained before their use. If the patient is unable to give informed consent and a legal guardian is available, then informed consent should be obtained from the guardian. If there is no guardian, the next of kin should be informed of the need to use restraints.
Impact of cyclic hypoxia on HIF‐1α regulation in endothelial cells – new insights for anti‐tumor treatments
Authors: Martinive Philippe , Defresne Florence , Quaghebeur Elise , Daneau Géraldine , Crokart Nathalie , Grégoire Vincent , Gallez Bernard , Dessy Chantal , Feron Olivier
Published: December 2008

Heterogeneities in tumor blood flow are associated with cyclic changes in pO2 or cyclic hypoxia. A major difference from O2 diffusion‐limited or chronic hypoxia is that the tumor vasculature itself may be directly influenced by the fluctuating hypoxic environment, and the reoxygenation phases complicate the usual hypoxia‐induced phenotypic pattern. Here, we determined the cyclic hypoxia‐driven pathways that modulate hypoxia inducible factor (HIF)‐1α abundance in endothelial cells to identify possible therapeutic targets. We found that exposure of endothelial cells to cycles of hypoxia/reoxygenation led to accumulation of HIF‐1α during the hypoxic periods and the phosphorylation of protein kinase B (Akt), extracellular regulated kinase (ERK) and endothelial nitric oxide synthase (eNOS) during the reoxygenation phases. We identified stimulation of mitochondrial respiration and activation of the phosphoinositide‐3 kinase (PI3K)/Akt pathway during intervening reoxygenation periods as major triggers of the stabilization of HIF‐1α. We also found that the NOS inhibitor nitro‐l‐arginine methyl ester further stimulated the cyclic hypoxia‐driven HIF‐1α accumulation and the associated gain in endothelial cell survival, thereby mirroring the effects of a PI3K/Akt inhibitor. However, combination of both drugs resulted in a net reduction in HIF‐1α and a dramatic in decrease in endothelial cell survival. In conclusion, this study identified cyclic hypoxia, as reported in many tumor types, as a unique biological challenge for endothelial cells that promotes their survival in a HIF‐1α‐dependent manner through phenotypic alterations occurring during the reoxygenation periods. These observations also indicate the potential of combining Akt‐targeting drugs with anti‐angiogenic drugs, in particular those interfering with the NO pathway.
Cholangiocarcinoma in USA‐ versus Asian‐born Asians: Is viral hepatitis a factor?
Authors: HAMMILL Chet , WONG Linda L , CONCEPCION Jennifer , TSAI Naoky
Published: December 2008

Aim:  Though liver and biliary tract cancers are more common in Asian countries they are increasing in incidence in the USA. This study attempted to clarify the risk factor profile for immigrant Asians compared with the USA population.

Methods:  A retrospective review was made of 128 cholangiocarcinoma cases presenting to a tertiary referral center from 1996–2007. Data were collected on patient characteristics, risk factors, tumor characteristics, treatment and survival. We then compared Asian immigrants (n = 40) to USA‐born Asians (n = 46).

Results:  In our cohort, the mean age was 66.7 years, of whom 54% were men, 51% had cholelithiasis, 51% were smokers, 41% used alcohol, 10% had hepatitis C and 27% had hepatitis B. In four patients, one each had sclerosing cholangitis, liver flukes, choledochal cyst and previous biliary tract surgery. The distribution of tumors was as follows: 43 intrahepatic (ICC) and 85 extrahepatic cholangiocarcinoma (ECC) including 43 proximal, nine middle and 33 distal tumors. Immigrants were more likely to be younger (mean age 63 vs 70 years old) and to have ICC than ECC (50% vs 26%) and hepatitis B (46% vs 14%). There was no significant difference between groups in hepatitis C, smoking, alcohol, cholelithasis, resectability or survival.

Conclusion:  Traditionally described risk factors for cholangiocarcinoma are not as evident in this largely Asian cohort. Asian immigrants were more likely to have ICC and have hepatitis B though whether hepatitis B is directly carcinogenic to the biliary tract is not clear. Immigrant status did not seem to have an effect on outcome from cholangiocarcinoma.
Simultaneous comparison of multiple molecules using tissue array analysis in the thyroid neoplasm
Authors: YAMADA Hiroko , HASEGAWA Yasuhisa , KOSHIKAWA Takashi , NAKASHIMA Tsutomu , YATABE Yasushi
Published: December 2008

Aim:  Differential diagnosis, including the respective distinctions between benign and malignant tumors, follicular and papillary neoplasms, and follicular adenoma and follicular carcinoma, are always required in clinical practice, because therapeutic strategy largely depends on the diagnosis made.

Methods:  The present study describes a novel approach to obtaining clinically useful markers by means of the simultaneous comparison of multiple molecules using tissue array analysis. The markers examined in this study include galectin‐3, CD44v6, p53, HBME‐1, maspin and S100A4, which were reportedly useful for making these distinctions in association with metastasis and invasion. A total of 45 cases of thyroid tumors (seven adenomatous goiters, 16 follicular adenomas, 12 follicular carcinomas and 10 papillary carcinomas) were analyzed.

Results:  The results demonstrated the following suggestive phenotypes: galectin‐3‐, HBME‐1‐ and maspin+ as benign lesions, galection‐3‐, HBME‐1+ and maspin‐ as follicular carcinoma, and galectin‐3+, HBME‐1+ and maspin+ as papillary carcinoma.

Conclusions:  The expression of the molecules was assessed in each case and the expression profiles were compared. Useful multiple molecules were selected for each distinction and were correlated with each other. To understand the complex relationship, a logistic regression model was constructed. These results suggested that combined analysis of multiple molecules enhanced the differential diagnostic accuracy.
Predicting the response to targeted therapy in metastatic colorectal cancer
Authors: AZAD Arun , TEBBUTT Niall C
Published: December 2008

Colorectal cancer is the second most common cause of cancer‐related deaths in Australia. The median survival of metastatic colorectal cancer remains poor, but novel targeted therapies offer promise in improving patient outcomes. However, it is vital to identify which patients with metastatic colorectal cancer will benefit from targeted therapy. Predictive biomarkers offer significant benefit by refining the treatment population to a subgroup that has a greater prospect of benefit from therapy. This provides efficacy benefits, but also minimizes the overall toxicity and cost of treatment. In this review we examine current knowledge regarding predictive biomarkers for targeted agents in metastatic colorectal cancer, with a particular focus on emerging biomarkers such as oncogenic mutations. We also highlight issues that require further exploration in the quest for personalized therapy in metastatic colorectal cancer.
Consensus approaches to best practice management of gastrointestinal stromal tumors
Authors: ZALCBERG John R , DESAI Jayesh , MANN Bruce , FOX Stephen , GOLDSTEIN David , MCARTHUR Grant , CLARK Matthew , YIP Desmond
Published: December 2008

Gastrointestinal stromal tumors are rare mesenchymal tumors of the gastrointestinal tract. Progress in diagnosis has led to increased recognition of this disease, and the availability of effective, molecularly targeted therapy has revolutionised its management. Treatment of metastatic gastrointestinal stromal tumors with imatinib has led to unprecedented improvements in progression free and overall survival and there are ongoing investigations into the optimal pre‐operative and adjuvant use of imatinib. Second‐line sunitinib is now available for patients who develop resistance to imatinib, and third‐ and fourth‐line therapies are being investigated in clinical trials. In this ever‐changing environment, evidence from controlled clinical trials and the authors' experience were used to comprehensively outline current best practice management of patients with gastrointestinal stromal tumors.
Probability in Semantics
Authors: Cohen Ariel
Published: December 2008

In truth‐conditional theories of the semantics of natural language, the main tool used is logic. There are, however, cases where a probabilistic account is attractive. The role of probability can vary from complementing a truth‐conditional account to replacing it. In this article, I discuss three test cases of the use of probability in semantics: generics and frequency adverbs, vagueness, and conditionals. For each case, I examine the motivation for using probability and the role it plays in the theory.
Obese Cities: How Our Environment Shapes Overweight
Authors: Smith Dianna M. , Cummins Steven
Published: December 2008

The rapid rise in obesity rates over the last 30 years has profound implications for the health of populations. That this rise has occurred over a relatively short biological time scale suggests that changes in the environments to which we are exposed may be to blame, rather than individual genetic endowment. Focusing on developed world nations, this article briefly reviews this emerging ‘ecological’ perspective in the search for the causes of obesity. This article explores how aspects of our environment might disrupt ‘energy balance’ through influencing food consumption and physical activity. It focuses on three hypothesised pathways for environmental risk: the organisation of built physical space, the social environment and the political environment. The article demonstrates that a consideration of scale and context are also important in the search for the environmental drivers of weight gain.
Institutions for Interstate Water Resources Management1
Authors: Mandarano Lynn A. , Featherstone Jeffrey P. , Paulsen Kurt
Published: December 2008

Abstract:  This paper evaluates alternative approaches to management of interstate water resources in the United States (U.S.), including interstate compacts, interstate associations, federal‐state partnerships, and federal‐interstate compacts. These governance structures provide alternatives to traditional federalism or U.S. Supreme Court litigation for addressing problems that transcend political boundaries and functional responsibilities. Interstate compacts can provide a forum for ongoing collaboration and are popular mechanisms for allocating water rights among the states. Federal‐interstate compacts, such as the Delaware River Basin Compact and federal‐state partnerships, such as the National Estuary Program, are also effective and complementary approaches to managing water resources. However, all of these approaches can only make modest improvements in managing water resources given the complicated and fragmented nature of our federalist system of government.
Uncertainty Reduction of the Flood Stage Forecasting Using Neural Networks Model1
Authors: Kim Sungwon , Kim Hung Soo
Published: December 2008

Abstract:The Elman Discrete Recurrent Neural Networks Model (EDRNNM), which is one of the special types of neural networks model, is developed and applied for the flood stage forecasting at the Musung station (No. 1) of the Wi‐stream catchment, which is one of the International Hydrological Program representative basins, Korea. A total of 135 different training patterns, which involve hidden nodes, standardization process, data length, and lead‐time, are selected for the minimization of the architectural uncertainty. The model parameters, such as optimal connection weights and biases, are estimated during the training performance of the EDRNNM, and we apply them to evaluate the validation performance of the EDRNNM. Sensitivity analysis is used to reduce the uncertainty of input data information of the EDRNNM. As the results of sensitivity analysis, the Improved EDRNNM consists of four input nodes resulting from the exclusion of Dongkok station (No.5) in initial five input nodes group of the EDRNNM. The accuracy of flood stage forecasting during the training and validation performances of the Improved EDRNNM remains the same as that of the EDRNNM. The Improved EDRNNM, therefore, gives highly reliable flood stage forecasting. The best optimal EDRNNM, so called the Improved EDRNNM, is determined by elimination of the uncertainties of architectural and input data information in this study. Consequently, we can avoid unnecessary data collection and operate the flood stage forecasting system economically.
Economic benefits of standing forests in highland areas of Borneo: quantification and policy impacts
Authors: Naidoo Robin , Malcolm Trent , Tomasek Adam
Published: December 2008

There exist thousands of valuation studies for environmental goods and services, but the degree to which these have influenced policy is uncertain, especially in developing countries. Here, we demonstrate that a rapid assessment of the benefits of standing forests in the highlands of Borneo is feasible and can provide useful and timely information for conservation policy decisions. We used existing biophysical and economic information to characterize values associated with forests in areas proposed for oil palm plantation development. We focused on three classes of benefits: avoided damages associated with increased greenhouse gas emissions (carbon storage), avoided damages associated with increased fires, and the economic benefits of forest–agriculture mosaics. Carbon storage values dominated the overall value of standing forests and were of similar magnitude to benefits from oil palm plantations. Other values were smaller but nevertheless important to different stakeholder groups. We document how the results were used to influence the Indonesian government's policy on oil palm plantations in the highlands of Borneo. While we cannot quantify the precise policy impact of the valuation work, it appears to have played a role in the decision to shelve the oil palm project.
Hitting the target and missing the point: target‐based conservation planning in context
Authors: Carwardine Josie , Klein Carissa J. , Wilson Kerrie A. , Pressey Robert L. , Possingham Hugh P.
Published: December 2008

Conservation planning is often informed by quantitative targets: these are minimum amounts of the distribution of a species, vegetation type, or other biodiversity feature intended for protection. Targets are set for the global reserve system, and are also used at national and local levels to plan for both on‐ and off‐reserve conservation. Understandably, the conservation community holds a range of opinions about target‐based approaches to conservation planning. One school of thought is that the approach is inadequate, inflexible, and even counterproductive in many socioecological systems. We investigate the perceived limitations of target‐based conservation planning, and find that most have resulted from poor communication and misuse of targets, leading to misconceptions and misunderstandings. Here we put target‐based conservation planning in context by: (1) summarizing reported limitations of the approach and differentiating between those that are real and those that are misconceived; (2) identifying ways that some of the real limitations have, and can, be overcome, and (3) comparing target‐based conservation planning to alternative conservation prioritization approaches. We hope to stimulate further discussion that will guide and improve target‐based conservation planning.
Assisted colonization in a changing climate: a test‐study using two U.K. butterflies
Authors: Willis Stephen G. , Hill Jane K. , Thomas Chris D. , Roy David B. , Fox Richard , Blakeley David S. , Huntley Brian
Published: December 2008

Recent climatic change in temperate regions has been rapid and there is mounting speculation that species are failing to keep track of suitable climate, perhaps necessitating assisted colonization for some species. An inability to spread into new areas may result in large reductions in species’ ranges in the future, and threaten the survival of some species. Here we use “species‐climate” models to predict suitable sites for introductions beyond current range margins, using two U.K. butterfly species. We introducedMelanargia galathea(marbled white) andThymelicus sylvestris(small skipper) into two sites in northern England, ∼65 and ∼35 km beyond their then‐range margins, respectively, to sites that were predicted to be climatically suitable and that appeared to contain suitable habitat for the species. Both introduced populations grew and expanded their range over 6 years (2001–2006; still thriving in 2008), suggesting the existence of a colonization lag and providing evidence that well‐planned assisted colonization can be successful. We suggest that assisted colonization may be a feasible and cost‐effective means of enabling certain species to track climatic change.
New species of Bulbophyllum from eastern Malesia (Orchidaceae)
Authors: Vermeulen J. J.
Published: December 2008

Thirty‐eight new species of Bulbophyllum are described; thirty‐seven of these are from New Guinea, the remaining species is assumed to have originated from Ceram; notes on additional miscellaneous species from New Guinea are provided.
Agouticarpa spinosa sp. nov. – a thorny member of the Alibertia group (Rubiaceae–Gardenieae) from northern Peru
Authors: Persson Claes , Delprete Piero G.
Published: December 2008

Agouticarpa spinosa C. Persson & Delprete, a new species of the Alibertia group (Rubiaceae–Gardenieae) endemic to northern Peru, is described and illustrated. It is primarily distinguished from other Agouticarpa species by having thorns and single‐flowered male inflorescences.
Continuous Glucose Monitoring in Dogs and Cats
Authors: Wiedmeyer C.E. , DeClue A.E.
Published: December 2008

Use of continuous glucose monitoring in veterinary medicine is gaining popularity. Through use of a commercially available continuous glucose monitor system, insights into daily glucose changes in dogs and cats are achievable. The continuous glucose monitoring system measures glucose concentrations in the interstitial fluid of the subcutaneous space by use of a small, flexible probe. When placed in the subcutaneous tissue, the probe is connected to a recording device that is attached to the animal and records the interstitial fluid glucose concentration every 5 minutes (288 readings per 24 hours). Once attached and properly calibrated, the instrument can remain in place for several days, hospitalization of the patient is not necessary, and the normal daily routine of the animal can be maintained. The data from the recording device are then downloaded and a very detailed picture of the interstitial fluid glucose concentration over that time period can be obtained. Subcutaneous interstitial fluid glucose concentrations have a good correlation to blood glucose concentrations within a defined range. The continuous glucose monitoring system has distinct advantages over traditional blood glucose curves and is a valuable tool for managing diabetic dogs and cats. In addition, other clinical uses for continuous glucose monitoring are being developed. This review is designed to outline the technology behind the continuous glucose monitoring system, describe the clinical use of the instrument, provide clinical examples in which it may be useful, and discuss future directions for continuous glucose monitoring in dogs and cats.
Evaluation of Plasma C‐Terminal Atrial Natriuretic Peptide in Healthy Cats and Cats with Heart Disease
Authors: Hori Y. , Yamano S. , Iwanaga K. , Kano T. , Tanabe M. , Uechi M. , Kanai K. , Nakao R. , Hoshi F. , Higuchi S.
Published: December 2008

Background: The clinical implications of evaluating C‐terminal atrial natriuretic peptide (ANP) concentration in cats are still controversial.

Hypothesis: The objective of this study was to investigate the relationship between plasma C‐terminal ANP concentration and left atrial pressure (LAP) in healthy cats with volume overload (study 1), and to compare plasma C‐terminal ANP in normal cats and cats with cardiomyopathy (study 2).

Animals: Five healthy adult cats were used in study 1, and clinically healthy cats (n=8) and cats with cardiomyopathy (n=14) were used in study 2.

Methods: In study 1, cats were anesthetized and given acetated Ringer's solution (100 mL/kg/h for 60 minute) via the cephalic vein. Hemodynamic measurements and blood samples, collected from the jugular vein, were performed at 10‐min intervals. In study 2, blood samples from normal cats and cats with cardiomyopathy were collected from the cephalic vein. The plasma C‐terminal ANP concentration was determined by radioimmunoassay for human α‐ANP.

Results: In study 1, volume overload significantly increased the C‐terminal ANP concentration and LAP from baseline. The C‐terminal ANP concentration was strongly correlated with the mean LAP. In study 2, age, E wave velocity, and the ratios of the left atrium to aorta were significantly higher in the cats with cardiomyopathy compared with the normal cats. The C‐terminal ANP concentration was significantly higher in the cats with cardiomyopathy compared with the normal cats.

Conclusions and Clinical Importance: Our results suggest that the measurement of plasma C‐terminal ANP in cats may provide additional information for the diagnosis of heart disease.
Endocrine and Immunologic Effects of Inhaled Fluticasone Propionate in Healthy Dogs
Authors: Cohn L.A. , DeClue A.E. , Reinero C.R.
Published: December 2008

Background:Inhaled glucocorticoids reduce airway inflammation while minimizing systemic effects in several species.

Hypothesis:Inhaled fluticasone suppresses the hypothalamic–pituitary–adrenal axis (HPAA), modifies immune function, and induces clinical signs to a lesser extent than PO‐administered prednisone in dogs.

Animals:Seven healthy adult pet dogs.

Methods:Dogs were randomized to 1 of 3 treatment groups in a crossover design: fluticasone propionate (220 μg actuation of a metered dose inhaler delivered via a spacer and mask, q12h), placebo (spacer and mask alone, q12h), or prednisone (1 mg/kg PO q24h). Each treatment was administered for 3 weeks followed by a 4‐week washout. Appetite, attitude, and water consumption were recorded during the last week of each treatment period. Urine cortisol : creatinine ratios, ACTH stimulation tests, white blood cell counts, lymphocyte phenotype, and serum IgM and IgA concentrations were recorded at each baseline and after the last day of each treatment. Clinical observations were expressed descriptively. Friedman's test was applied to all data comparisons. Pairwise comparisons were made with a mixed model analysis when data were normally distributed, whereas signed rank tests were used otherwise (significanceP‐value <.01).

Results:Appetite and water consumption increased during prednisone treatment. Peak serum cortisol concentrations post‐ACTH were significantly decreased in prednisone‐ and fluticasone‐treated dogs compared with placebo (prednisone > fluticasone). Serum IgM concentrations were significantly decreased in dogs treated with prednisone.

Conclusions and Clinical Importance:As used, fluticasone suppresses the HPAA to a lesser extent than prednisone and may avert systemic signs associated with PO‐administered glucocorticoids in dogs.
Chronicity of Atrial Fibrillation Affects Duration of Sinus Rhythm after Transthoracic Cardioversion of Dogs with Naturally Occurring Atrial Fibrillation
Authors: Bright J.M. , ZumBrunnen J.
Published: December 2008

Background: Atrial fibrillation (AF) in dogs can be managed by electrical cardioversion to sinus rhythm, but early recurrence of AF occurs in some dogs. In humans, the commonly evaluated clinical variables for prediction of early relapse of AF are left atrial size and duration of AF. It is unclear whether the duration of AF affects maintenance of sinus rhythm after cardioversion in dogs with spontaneous AF.

Hypothesis: That duration of sinus rhythm after cardioversion is related to the chronicity of AF.

Animals: Forty‐one consecutive dogs that had undergone successful transthoracic cardioversion for spontaneous AF were evaluated.

Methods: The relationship between the duration of documented AF and the duration of sinus rhythm after cardioversion was statistically evaluated using data obtained retrospectively. The effects of structural heart disease and pretreatment with amiodarone were also evaluated.

Results: The presence of structural heart disease and the duration of documented AF had significant effects on maintenance of sinus rhythm after cardioversion (P <.001 and P=.022, respectively). The duration of documented AF was inversely related to the duration of sinus rhythm (P=.022) in dogs with and without structural heart disease.

Conclusions and Clinical Importance: Estimates of duration of sinus rhythm based on the duration of documented AF are provided for dogs with and without heart disease allowing prediction of risk for early AF relapse.
Safety and Efficacy of Oral Low‐Volume Sodium Phosphate Bowel Preparation for Colonoscopy in Dogs
Authors: Daugherty M.A. , Leib M.S. , Rossmeisl J.H. , Almy F.S. , Ward D.L.
Published: December 2008

Background: Sodium phosphate (NaP) is a low‐volume, hyperosmolar laxative that is an effective bowel‐cleansing agent in humans.

Hypothesis: NaP will be as safe and efficacious as polyethylene glycol (PEG) bowel preparation for colonoscopy in dogs.

Animals: Eight purpose‐bred healthy dogs.

Methods: In phase I, standard (NaP and enemas; NaP1) and control preparations (PEG and enemas) were compared in a crossover design to determine the safety and efficacy of NaP. Serial clinical and serum analytical evaluations were used to determine the safety of NaP. In phase II, the efficacy of the standard NaP preparation was compared with 3 other NaP variations, which excluded enema or included bisacodyl, with or without enemas in a crossover design. An observer blinded to the bowel preparation assigned a score of 1–4 (1=clean colon; 4=unacceptable colon cleansing preventing adequate endoscopic evaluation) to each of 5 regions of the colon.

Results: The mean total colon cleansing score (TCS), defined as the sum of scores from each region, of the control (9.4) was less than NaP1 (13.6) (P < 0.05). There were no significant differences in regional or TCS for the remaining 4 NaP protocols. NaP1 resulted in moderate, but clinically occult, hyperphosphatemia and hypocalcemia, which resolved within 24 hours.

Conclusions and Clinical Importance: Despite the safety and ease of administration of the NaP preparations, the NaP bowel‐cleansing preparations used in this study cannot be recommended for use because of the inadequate quality of bowel preparation compared with the protocol using PEG‐containing fluids.
Cardiopulmonary Resuscitation in Small Animal Medicine: An Update
Authors: Plunkett S.J. , McMichael M.
Published: December 2008

In December 2005, the American Heart Association published new guidelines for cardiopulmonary cerebral resuscitation (CPCR) in humans for the 1st time in 5 years. Many of the recommendations are based on research conducted in animal species and may be applicable to small animal veterinary patients. One important change that may impact how CPCR is performed in veterinary medicine is the recommendation to avoid administration of excessive ventilatory rates because this maneuver severely decreases myocardial and cerebral perfusion, decreasing the chance of survival. The new guidelines also emphasize the importance of providing well‐executed, continuous, uninterrupted chest compressions. Interruption of chest compressions should be avoided and, if necessary, should be minimized to <10 seconds. During defibrillation, immediate resumption of chest compressions for 2 minutes after a single shock, before reassessment of the rhythm by ECG, is recommended. This recommendation replaces previous recommendations for the delivery of 3 defibrillatory shocks in rapid succession. Allowing permissive hypothermia postresuscitation has been found to be beneficial and may increase success rate. Medications utilized in cardiopulmonary resuscitation, including amiodarone, atropine, epinephrine, lidocaine, and vasopressin, along with the indications, effects, routes of administration, and dosages, are discussed. The application of the new guidelines to veterinary medicine as well as a review of cardiopulmonary resuscitation in small animals is provided.
Noninvasive Assessment of Systolic Left Ventricular Torsion by 2‐Dimensional Speckle Tracking Imaging in the Awake Dog: Repeatability, Reproducibility, and Comparison with Tissue Doppler Imaging Variables
Authors: Chetboul V. , Serres F. , Gouni V. , Tissier R. , Pouchelon J.L.
Published: December 2008

Background: Left ventricular (LV) torsional deformation plays an important role in myocardial function. However, it has never been assessed in the awake dog, because magnetic resonance imaging and sonomicrometry have been the only methods available so far.

Hypothesis: Two dimensional speckle tracking echocardiography (STE), a new ultrasound imaging technique, provides a repeatable and reproducible noninvasive assessment of systolic LV wringing motion in the awake dog.

Animals: Six healthy dogs were used to determine the repeatability and reproducibility of STE variables (study 1). These variables also were prospectively assessed in a population of 35 healthy dogs (study 2).

Methods: Peak LV basal and apical systolic rotations were measured by STE from right parasternal short‐axis views using automatic frame‐to‐frame tracking of gray‐scale speckle patterns. Systolic LV torsion (LVtor, °) was defined as apical rotation relative to the base.

Results: All within‐day and between‐day coefficients of variation were <20% (6.8–18.0%). Amplitude of apical systolic rotation was significantly higher (P < .001) than the basal value (5.4 ± 3.2° and −3.1 ± 1.3°, respectively). Global LVtor was significantly correlated with systolic longitudinal LV myocardial velocity gradient assessed by tissue Doppler (P < .05), but not with either systolic radial LV myocardial velocity gradient or the ratio of early mitral inflow velocity to early mitral annular velocity (Em/Ea).

Conclusions and clinical importance: Speckle tracking echocardiography is a repeatable and reproducible method for assessing systolic LV torsional deformation. The combination of these new STE indices with tissue Doppler variables could provide a new approach for quantifying canine LV systolic function.
Evaluation of Human Recombinant Tissue Factor‐Activated Thromboelastography in 49 Dogs with Neoplasia
Authors: Kristensen A.T. , Wiinberg B. , Jessen L.R. , Andreasen E. , Jensen A.L.
Published: December 2008

Background: Abnormal routine coagulation assay results have been reported to be common in veterinary patients with neoplasia, but the overall hemostatic functional state, including hypercoagulability, has not been described.

Hypothesis: The overall hemostatic functional state, including hypercoagulability, can be assessed in dogs with neoplasia by tissue factor (TF)‐activated thromboelastography (TEG).

Animals: Thirty‐six dogs with malignant neoplasia and 13 dogs with benign neoplasia presented to the Small Animal Veterinary Teaching Hospital, The University of Copenhagen, Frederiksberg, Denmark.

Methods: Prospective study evaluating the overall hemostatic functional state in dogs with neoplasia by a newly validated TF‐activated TEG assay and routine coagulation parameters activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet count, and D‐dimer concentration.

Results: Hemostatic dysfunction was observed in 28/49 (57%) dogs with neoplasia. Twenty‐four were dogs with malignant neoplasia, the majority of which 18/36 (50%) were hypercoagulable, whereas 6/36 (17%) were hypocoagulable. All hypocoagulable dogs had metastatic disease. The proportion of dogs with altered hemostasis was significantly different between dogs with malignant and benign neoplasia.

Conclusions and Clinical Importance: TF‐activated TEG detected hypercoagulable and hypocoagulable states in this population of dogs with neoplasia. The most common hemostatic abnormality in dogs with malignant neoplasia was hypercoagulability. These findings suggest that this novel hemostatic function test may be of value as a cage side method for the assessment of overall hemostatic function in dogs with cancer, including the detection of both hyper‐ and hypocoagulable states as well as mixed disorders.
Idiopathic Immune‐Mediated Hemolytic Anemia: Treatment Outcome and Prognostic Factors in 149 Dogs
Authors: Piek C.J. , Junius G. , Dekker A. , Schrauwen E. , Slappendel R.J. , Teske E.
Published: December 2008

Background: Canine idiopathic immune‐mediated hemolytic anemia (IMHA) is associated with a high mortality, especially in the 1st 2 weeks after diagnosis despite treatment.

Objectives: To determine treatment outcome and identify prognostic variables in order to define areas of future research.

Animals: One hundred forty‐nine dogs with hematocrit <30% and either a positive Coombs' test or spherocytosis and with no evidence of disease that can trigger IMHA were included.

Methods: Retrospective cohort study. All dogs were treated with prednisolone and azathioprine according to a standard protocol. Survival analysis was performed by the Kaplan‐Meier method. Variables recorded at the time of diagnosis were tested as possible prognostic variables in a univariate and multivariate Cox proportional hazard model.

Results: The main predictors for mortality in dogs with idiopathic IMHA are the presence of increased plasma urea concentration, bands, thrombocytopenia, and petechiae at the time of diagnosis. The estimated Kaplan‐Meier half‐year survival was 72.6% (95% confidence interval [CI]: 64.9–81.3%). Mortality occurred mostly within the 1st 2 weeks. Cox proportional hazards analysis indicated that increased plasma urea concentration, icterus, and petechiae were the major independent predictors of mortality in the 1st 2 weeks. In most dogs that survived IMHA, a 3‐month protocol of azathioprine with prednisolone maintained clinical remission. The estimated half‐year survival for dogs that survived the 1st 2 weeks was 92.5% (95% CI: 86–99.3%).

Conclusions and Clinical Importance: If the dogs survived IMHA, a 3‐month protocol of prednisolone and azathioprine was effective with regard to survival and clinical outcome. Future research should be directed at identifying whether thrombotic tendency in dogs with IMHA is the main contributor to the development of increased plasma urea concentration, icterus, thrombocytopenia, and petechiae.
Thrombotic Endocarditis in 10 Alpacas
Authors: Firshman A.M. , Wünschmann A. , Cebra C.K. , Bildfell R. , McClanahan S.L. , Valentine B.A. , McKenzie E. , Waitt L. , Margiocco M. , Sisson D.D.
Published: December 2008

Background:A description of the clinical signs and necropsy findings in 10 alpacas with thrombotic endocarditis.

Animals:Clinical cases admitted to 2 veterinary referral hospitals between May 1998 and December 2006.

Methods:A retrospective study was performed by searching hospital records to identify alpacas diagnosed with endocarditis.

Results:Common clinical findings included sternal recumbency, tachycardia, tachypnea, and abdominal distension. Heart sounds were recorded as normal in 7 of 10 alpacas. Pleural and pericardial effusion and ascites were often present. Complete blood cell counts often suggested inflammation, and liver enzyme activity was often increased. When echocardiography was performed, a soft tissue density was imaged within the right ventricle. All alpacas died or were euthanized. Necropsy revealed mural endocarditis with right ventricular or biventricular fibrinous thrombi obliterating the ventricular lumina with no valvular involvement in 6 of 10 affected animals. Bacteria were not consistently identified as a cause for the endocarditic lesions. Eight of the 10 alpacas had evidence of hepatic fluke infestation.

Conclusions and Clinical Importance:Valvular and mural thrombotic endocarditis should be included in the list of differential diagnoses for hepatomegaly, abdominal distension, and other signs of right‐sided congestive heart failure in alpacas. The prognosis of this disease is grave.
Prognostic Usefulness of Blood Leukocyte Changes in Canine Parvoviral Enteritis
Authors: Goddard A. , Leisewitz A.L. , Christopher M.M. , Duncan N.M. , Becker P.J.
Published: December 2008

Background: Despite treatment, many dogs still die of complications related to canine parvoviral (CPV) enteritis. Effective prognostication would be beneficial in managing this disease.

Hypothesis: We hypothesize that the occurrence of leukocytopenias at admission and at 24 and 48 hours after admission, and changes in absolute leukocyte counts over time, could be used to predict outcome.

Animals: Sixty‐two puppies with confirmed CPV.

Methods: A prospective study was performed. CBC was performed daily until discharge or death (in which case a postmortem examination was performed).

Results: Of the nonsurvivors (10/62; 16%), 9 died because of complications of the disease and 1 was euthanized because of a poor prognosis. There was a statistical significant difference in the occurrence of leukocytopenias between groups at 24 and 48 hours postadmission. The survivors showed a significant increase over time in certain leukocyte types (specifically lymphocytes) compared with values at admission. The positive predictive value for survivors was high. Nonsurvivors had marked thymic and lymphoid atrophy and marked bone marrow hypocellularity.

Conclusion: An accurate prognosis could be obtained at 24 hours after admission by evaluating the change in total leukocyte, band neutrophil, lymphocyte, monocyte, and eosinophil counts.
Cytokine Dysregulation in Aged Horses and Horses with Pituitary Pars Intermedia Dysfunction
Authors: McFarlane D. , Holbrook T.C.
Published: December 2008

Background: Equine pituitary pars intermedia dysfunction (PPID) is the result of a loss of dopaminergic inhibition of the pars intermedia secondary to neurodegeneration of periventricular hypothalamic neurons. The pathologic events contributing to development of neurodegeneration or clinical signs in equids with PPID are unknown. Chronic inflammation may contribute to initiation or progression of PPID.

Hypothesis: Horses with PPID have a distinct systemic cytokine profile compared with that of normal adult or aged horses. The cytokine profile of healthy aged horses differs from that of adult horses.

Animals: Aged horses with PPID, healthy aged‐matched controls, and adult controls (n = 14 per group).

Methods: Total leukocyte cytokine expression was determined by quantitative polymerase chain reaction (PCR), and tumor necrosis factor (TNF)‐α plasma concentration was determined by enzyme‐linked immunosorbent assay (ELISA). Peripheral blood mononuclear cell (PBMC) TNF‐α response after endotoxin (lipopolysaccharide [LPS]) treatment was assessed by ELISA.

Results: Aged healthy horses had increased expression of interleukin (IL)‐6, IL‐8, and interferon‐γ as well as PBMC TNF‐α release after LPS stimulation compared with healthy adult horses. In contrast, aged horses with PPID had increased IL‐8 expression, but expression of other cytokines was similar to that of healthy adult horses, not age‐matched controls.

Conclusions and Clinical Importance: Aged horses show evidence of a proinflammatory state that may contribute to development of age‐associated diseases. Horses with PPID have increased expression of IL‐8, which may influence the ability of horses with PPID to respond to bacterial pathogens. The general decrease in proinflammatory cytokine expression observed in horses with PPID may be the outcome of high plasma concentrations of anti‐inflammatory hormones.
Postoperative Bleeding in Retired Racing Greyhounds
Authors: Lara‐García A. , Couto C.G. , Iazbik M.C. , Brooks M.B.
Published: December 2008

Background:Some retired racing Greyhounds (RRG) that undergo surgery bleed excessively.

Hypothesis:Greyhounds that bleed excessively will have one or more preoperative hemostatic abnormalities that can be used to predict the risk and severity of postoperative bleeding.

Animals:Eighty‐eight RRG undergoing ovariohysterectomy or castration.

Methods:All dogs were evaluated preoperatively with a physical exam, CBC, platelet count, OSPT, APTT, platelet function with PFA‐100a; fibrinogen,d‐dimer, plasminogen (Plmg), antiplasmin (AP), antithrombin (AT), and vWF concentration (vWF:Ag); vWF collagen binding assay (vWF:CBA), and Factor XIII assay. Assays were repeated in the dogs that bled, and in an age‐ and sex‐matched control group of RRG.

Results:Twenty‐six percent of the dogs had bleeding 36–48 hours after surgery. AP (P<.0001) and AT concentration (P= .007) were significantly lower, and vWF:CBA (P= .0284) was higher preoperatively in the dogs with excessive hemorrhage. A lower platelet count (P= .001) and hematocrit (P= .002), shorter OSPT (P= .0002) and higher plasma fibrinogen (P<.0001), and AP (P= .001) concentration were detected at the time of bleeding compared with preoperative values in the dogs that bleed excessively. The same findings were observed postoperatively for the control group, except for the decrease in hematocrit.

Conclusions and Clinical Importance:The results indicate that this excessive postoperative bleeding is not attributable to a primary or secondary hemostatic defect, but could result from altered fibrinolysis.
Investigating CXCR4 Expression in Canine Appendicular Osteosarcoma
Authors: Fan T.M. , Barger A.M. , Fredrickson R.L. , Fitzsimmons D. , Garrett L.D.
Published: December 2008

Background: Chemokine receptors (CXCRs) are transmembrane proteins classically studied for their participation in leukocyte homing. By their binding of cognate ligands, CXCRs orchestrate key cellular processes, including directional migration. Several different CXCRs are expressed on cancer cells and dictate tissue‐specific metastases. In pediatric osteosarcoma (OSA), CXCR4 expression by tumor cells may participate in metastasis to tissues containing CXCL12, the partnering ligand for CXCR4. Canine and pediatric OSA share many biological similarities, including preferential metastasis to lung, bone, and lymph node.

Hypothesis: In canine immortalized cell lines and naturally occurring tumor samples, OSA cells will express CXCR4. In canine OSA cell lines, CXCR4 will participate in directional cell migration.

Methods: In vitro, CXCR4 expression in canine OSA cell lines was assessed by reverse‐transcriptase polymerase chain reaction, Western blot analysis, flow cytometry, and immunocytochemistry. In vitro, involvement of CXCR4‐mediated signaling for directional migration was investigated with a commercial assay. In vivo, CXCR4 expressions were evaluated in primary tumors and pulmonary metastases with immunocytochemistry and immunohistochemistry, respectively.

Results: In vitro, canine OSA cells express CXCR4 mRNA and protein. Ligation of CXCR4 with exogenous CXCL12 results in directional migration of canine OSA cell lines. In vivo, majority (8/11) of the canine OSA primary tumors, but minority (2/8) of the pulmonary metastases express CXCR4 protein.

Conclusions and Clinical Importance: Canine OSA cells express CXCR4, and its signaling participates in directional migration. Most dogs with spontaneously arising OSA express CXCR4 within their primary tumors.
The Effect of Age on Serum Antibody Titers after Rabies and Influenza Vaccination in Healthy Horses
Authors: Muirhead T.L. , McClure J.T. , Wichtel J.J. , Stryhn H. , Frederick Markham R.J. , McFarlane D. , Lunn D.P.
Published: December 2008

Background:The proportion of geriatric horses within the equine population has increased in the past decade, but there is limited information on the immune function of these animals.

Hypothesis:Aged horses will have a lesser increase in serum antibody response to vaccination.

Animals:Thirty‐four aged healthy horses (≥ 20 years) and 29 younger adult horses (4–12 years) of various breeds.

Methods:All horses were vaccinated with vaccines of killed rabies and influenza virus. Horses in each age group were allocated to receive either rabies or influenza booster vaccine 4 weeks after the initial vaccination. Serum samples were taken at 0, 4, 8, and 24 weeks. Rabies serum neutralization titers and equine influenza virus specific antibody sub‐isotypes (IgGa, IgGb, IgG(T), and IgA) as well as single radial hemolysis (SRH) titers were determined.

Results:Rabies antibody titers were similar in the 2 age groups at all sampling times. Aged horses had higher IgGa and IgGb influenza antibody titers before vaccination than younger horses but similar titers after vaccination (P= .004 andP= .0027, respectively). Younger horses had significantly greater increases in titer than aged horses at all sampling times for IgGa (P= .001) and at 8 and 24 weeks for IgGb (P= .041 and .01, respectively). There was no detectable serum IgG(T) at any time point. A significant booster vaccine effect was seen for both antirabies and anti‐influenza titers. Anti‐influenza titer before vaccination also had a significant effect on subsequent antibody response.

Conclusions and Clinical Importance:Healthy aged horses generated a primary immune response to a killed rabies vaccine similar to that of younger adult horses. Aged horses had a significantly reduced anamnestic response to influenza vaccine.