bluuebunny/crossref_metadata_2025 huggingface dataset:
Low dose of propranolol down‐modulates bone resorption by inhibiting inflammation and osteoclast differentiation
Authors: Rodrigues WF , Madeira MFM , da Silva TA , Clemente‐Napimoga JT , Miguel CB , Dias‐da‐Silva VJ , Barbosa‐Neto O , Lopes AH , Napimoga MH
Published: September 2011

BACKGROUND AND PURPOSE Bones are widely innervated, suggesting an important role for the sympathetic regulation of bone metabolism, although there are controversial studies. We investigated the effects of propranolol in a model of experimental periodontal disease.

EXPERIMENTAL APPROACH Rats were assigned as follows: animals without ligature; ligated animals receiving vehicle and ligated animals receiving 0.1, 5 or 20 mg·kg−1 propranolol. After 30 days, haemodynamic parameters were measured by cardiac catheterization. Gingival tissues were removed and assessed for IL‐1β, TNF‐α and cross‐linked carboxyterminal telopeptides of type I collagen (CTX) by elisa, or intercellular adhesion molecule 1 (ICAM‐1), receptor activator of NF‐κ B ligand (RANKL) and osteoprotegerin (OPG) by Western blot analysis. Sections from the mandibles were evaluated for bone resorption. Also, we analysed the ability of propranolol to inhibit osteoclastogenesis in vitro.

RESULTS Propranolol at 0.1 and 5 mg·kg−1 reduced the bone resorption as well as ICAM‐1 and RANKL expression. However, only 0.1 mg·kg−1 reduced IL‐1β, TNF‐α and CTX levels as well as increased the expression of OPG, but did not alter any of the haemodynamic parameters. Propranolol also suppressed in vitro osteoclast differentiation and resorptive activity by inhibiting the nuclear factor of activated T cells (NFATc)1 pathway and the expression of tartrate‐resistant acid phosphatase (TRAP), cathepsin K and MMP‐9.

CONCLUSIONS AND IMPLICATIONS Low doses of propranolol suppress bone resorption by inhibiting RANKL‐mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters.
Characteristics of concatemeric GABAA receptors containing α4/δ subunits expressed in Xenopus oocytes
Authors: Shu Hong‐Jin , Bracamontes John , Taylor Amanda , Wu Kyle , Eaton Megan M , Akk Gustav , Manion Brad , Evers Alex S , Krishnan Kathiresan , Covey Douglas F , Zorumski Charles F , Steinbach Joe Henry , Mennerick Steven
Published: September 2011

BACKGROUND AND PURPOSE GABAA receptors mediate both synaptic and extrasynaptic actions of GABA. In several neuronal populations, α4 and δ subunits are key components of extrasynaptic GABAA receptors that strongly influence neuronal excitability and could mediate the effects of neuroactive agents including neurosteroids and ethanol. However, these receptors can be difficult to study in native cells and recombinant δ subunits can be difficult to express in heterologous systems.

EXPERIMENTAL APPROACH We engineered concatemeric (fused) subunits to ensure δ and α4 subunit expression. We tested the pharmacology of the concatemeric receptors, compared with a common synaptic‐like receptor subunit combination (α1 +β2 +γ2L), and with free‐subunit α4/δ receptors, expressed in Xenopus oocytes.

KEY RESULTS δ‐β2 −α4 +β2‐α4 cRNA co‐injected into Xenopus oocytes resulted in GABA‐gated currents with the expected pharmacological properties of α4/δ‐containing receptors. Criteria included sensitivity to agonists of different efficacy, sensitivity to the allosteric activator pentobarbital, and modulation of agonist responses by DS2 (4‐chloro‐N‐[2‐(2‐thienyl)imidazo[1,2‐a]pyridine‐3‐yl benzamide; a δ‐selective positive modulator), furosemide, and Zn2+. We used the concatemers to examine neurosteroid sensitivity of extrasynaptic‐like, δ‐containing receptors. We found no qualitative differences between extrasynaptic‐like receptors and synaptic‐like receptors in the actions of either negative or positive neurosteroid modulators of receptor function. Quantitative differences were explained by the partial agonist effects of the natural agonist GABA and by a mildly increased sensitivity to low steroid concentrations.

CONCLUSIONS AND IMPLICATIONS The neurosteroid structure‐activity profile for α4/δ‐containing extrasynaptic receptors is unlikely to differ from that of synaptic‐like receptors such as α1/β2/γ2‐containing receptors.
Orexin A in rat rostral ventrolateral medulla is pressor, sympatho‐excitatory, increases barosensitivity and attenuates the somato‐sympathetic reflex
Authors: Shahid Israt Z , Rahman Ahmed A , Pilowsky Paul M
Published: September 2011

BACKGROUND AND PURPOSE The rostral ventrolateral medulla (RVLM) maintains sympathetic nerve activity (SNA), and integrates adaptive reflexes. Orexin A‐immunoreactive neurones in the lateral hypothalamus project to the RVLM. Microinjection of orexin A into RVLM increases blood pressure and heart rate. However, the expression of orexin receptors, and effects of orexin A in the RVLM on splanchnic SNA (sSNA), respiration and adaptive reflexes are unknown.

EXPERIMENTAL APPROACH The effect of orexin A on baseline cardio‐respiratory variables as well as the somato‐sympathetic, baroreceptor and chemoreceptor reflexes in RVLM were investigated in urethane‐anaesthetized, vagotomized and artificially ventilated male Sprague‐Dawley rats (n= 50). orexin A and its receptors were detected with fluorescence immunohistochemistry.

KEY RESULTS Tyrosine hydroxylase‐immunoreactive neurones in the RVLM were frequently co‐localized with orexin 1 (OX1) and orexin 2 (OX2) receptors and closely apposed to orexin A‐immunoreactive terminals. Orexin A injected into the RVLM was pressor and sympatho‐excitatory. Peak effects were observed at 50 pmol with increased mean arterial pressure (42 mmHg) and SNA (45%). Responses to orexin A (50 pmol) were attenuated by the OX1 receptor antagonist, SB334867, and reproduced by the OX2 receptor agonist, [Ala11, D‐Leu15]orexin B. Orexin A attenuated the somato‐sympathetic reflex but increased baroreflex sensitivity. Orexin A increased or reduced sympatho‐excitation following hypoxia or hypercapnia respectively.

CONCLUSIONS AND IMPLICATIONS Although central cardio‐respiratory control mechanisms at rest do not rely on orexin, responses to adaptive stimuli are dramatically affected by the functional state of orexin receptors.
Role of endothelin‐1 in the hyper‐responsiveness to nitrovasodilators following acute NOS inhibition
Authors: Bourque Stephane L , Whittingham Heather A , Brien Susan E , Davidge Sandra T , Adams Michael A
Published: September 2011

BACKGROUND AND PURPOSE Acute NOS inhibition in humans and animals is associated with hypersensitivity to NO donors. The mechanisms underlying this phenomenon have not been fully elucidated. The purpose of the present study was to assess whether hypersensitivity to NOS‐blockade is linked to endothelin‐1 (ET‐1) signalling.

EXPERIMENTAL APPROACH Sprague Dawley rats were instrumented with indwelling arterial and venous catheters for continuous assessments of haemodynamic parameters and drug delivery, respectively. Mesenteric arteries were isolated and tested for reactivity by wire myography.

KEY RESULTS NOS blockade with L‐NG‐nitroarginine methyl ester (L‐NAME) caused a pronounced increase in arterial blood pressure (BP) (∼40 mmHg). In L‐NAME‐treated animals, the dose of sodium nitroprusside (SNP) required to cause a significant reduction in arterial BP was lower than in vehicle‐treated rats (P < 0.001), and the magnitude of the reduction in BP was greater. Similar results were obtained with other NO mimetics, but not isoprenaline; moreover, decreasing the BP back to baseline levels with prazosin after L‐NAME treatment did not attenuate the hyper‐responsiveness to NO donors. The increased responsiveness to NO donors was abolished by pretreatment with the ETA/B receptor antagonist, PD145065, or the ETA receptor‐specific antagonist ABT627. Ex vivo, L‐NAME treatment potentiated the constriction induced by big endothelin‐1 (bET‐1), the precursor to active ET‐1, but had no effect on the ET‐1‐mediated constriction.

CONCLUSIONS AND IMPLICATIONS These data suggest that the increased sensitivity to NO donors is mediated, at least in part, by ET‐1 in vivo, and the mechanism may involve the conversion of bET‐1 to ET‐1.
Restoration of ion channel function in deafness‐causing KCNQ4 mutants by synthetic channel openers
Authors: Leitner Michael G , Feuer Anja , Ebers Olga , Schreiber Daniela N , Halaszovich Christian R , Oliver Dominik
Published: September 2011

BACKGROUND AND PURPOSE DFNA2 is a frequent hereditary hearing disorder caused by loss‐of‐function mutations in the voltage‐gated potassium channel KCNQ4 (Kv7.4). KCNQ4 mediates the predominant K+ conductance, IK,n, of auditory outer hair cells (OHCs), and loss of KCNQ4 function leads to degeneration of OHCs resulting in progressive hearing loss. Here we explore the possible recovery of channel activity of mutant KCNQ4 induced by synthetic KCNQ channel openers.

EXPERIMENTAL APPROACH Whole cell patch clamp recordings were performed on CHO cells transiently expressing KCNQ4 wild‐type (wt) and DFNA2‐relevant mutants, and from acutely isolated OHCs.

KEY RESULTS Various known KCNQ channel openers robustly enhanced KCNQ4 currents. The strongest potentiation was observed with a combination of zinc pyrithione plus retigabine. A similar albeit less pronounced current enhancement was observed with native IK,n currents in rat OHCs. DFNA2 mutations located in the channel's pore region abolished channel function and these mutant channels were completely unresponsive to channel openers. However, the function of a DFNA2 mutation located in the proximal C‐terminus was restored by the combined application of both openers. Co‐expression of wt and KCNQ4 pore mutants suppressed currents to barely detectable levels. In this dominant‐negative situation, channel openers essentially restored currents back to wt levels, most probably through strong activation of only the small fraction of homomeric wt channels.

CONCLUSIONS AND IMPLICATIONS Our data suggest that by stabilizing the KCNQ4‐mediated conductance in OHCs, chemical channel openers can protect against OHC degeneration and progression of hearing loss in DFNA2.
Cyclosporin A and cardioprotection: from investigative tool to therapeutic agent
Authors: Hausenloy DJ , Boston‐Griffiths EA , Yellon DM
Published: September 2011

Ischaemic heart disease (IHD) is the leading cause of death and disability worldwide. The pathophysiological effects of IHD on the heart most often result from the detrimental effects of acute ischaemia–reperfusion injury (IRI) on the myocardium. Therefore, novel therapeutic targets for protecting the myocardium against acute IRI are required to reduce injury to the heart, preserve cardiac function and improve clinical outcomes in patients with IHD. In this regard, the mitochondrial permeability transition pore (mPTP) has emerged as a critical target for cardioprotection which is readily amenable to intervention at the time of myocardial reperfusion. The formation and opening of the mPTP at the onset of myocardial reperfusion is a major determinant of mitochondrial dysfunction and cardiomyocyte death in the setting of acute IRI. The seminal discovery in the late 1980s that mPTP opening could be pharmacologically inhibited by the immunosuppressive agent, cyclosporin A (CsA), has been fundamental in the elucidation of the critical role of the mPTP as a mediator of acute IRI and, therefore, a viable target for cardioprotection. Its initial role as an investigative tool was used to identify mitochondrial cyclophilin D to be a regulatory component of the mPTP. The mPTP as a viable target for cardioprotection has recently been translated into the clinical setting with CsA reducing myocardial infarct size in patients. In this article, we review the intriguing role of CsA as a tool for investigating the mPTP as a target for cardioprotection and its potential role as a therapeutic agent for patients with IHD.
Single nucleotide polymorphisms associated with metastatic tumour antigen 1 overexpression in patients with hepatocellular carcinoma
Authors: Lee Sae Hwan , Chung Young‐Hwa , Kim Jeong A. , Lee Danbi , Jin Young‐Joo , Shim Ju Hyun , Jang Myoung‐Kuk , Cho Eun‐Young , Shin Eun‐Soon , Lee Jong‐Eun , Park Neung Hwa , Yu Eunsil , Lee Young Joo
Published: September 2011

Backgrounds/Aims

Metastatic tumour antigen 1 (MTA1) promotes angiogenesis by stabilizing hypoxia‐inducible factor‐1α (HIF‐1α), which is closely associated with frequent postoperative recurrence and poor survival in patients with HCC. In this study, we determined single nucleotide polymorphisms (SNPs) in angiogenesis‐related genes that are associated with MTA1 overexpression in HCC tissues.

Methods

A total of 376 patients with HCC who had received curative surgical resection or liver transplantation were enrolled (312/21/43; HBV/HCV/NBNC). MTA1 expression was determined via immunohistochemistry. Thirty‐three common SNPs sites (frequency ≥5%) in the angiogenic protein gene that are closely connected to one another were selected, including MTA1, VEGF, HIF‐1α, FGF‐2, and IGF‐II.

Results

Expression of MTA1 was detected in 120 HCC tissues (31%). An A allele at position IVS4‐81G/A of the MTA1 gene (P = 0.016) and the TT genotype at position +12916C of the VEGF gene (P = 0.023) were significantly associated with MTA1 overexpression. However, the TT genotype at position −13021C (P = 0.011) and the haplotypes CT‐CT (−11228C; −13021C) of the IGF‐II gene (Pcor = 0.033) were more common in patients with MTA1‐negative HCC. Using multivariate analysis, the A allele at IVS4‐81G/A in MTA1 gene (P = 0.015) and a T allele (TT+CT genotype) at −13021C in IGF‐II (P = 0.002) were independent risk factors in HCC recurrence after curative surgical resection.

Conclusions

The genetic polymorphisms IVS4‐81G/A in MTA1 and +12916C in VEGF genes were correlated with MTA1 overexpression. The SNPs in MTA1 and IGF‐II genes may be important risk factors for the recurrence of HCC.
Early Holocene in Gästrikland, east central Sweden: shore displacement and isostatic recovery
Authors: Berglund Mikael
Published: September 2011

In Gästrikland in central Sweden, deglaciation took place c. 11 000 cal. a BP. In the present study the shore displacement during the earliest ice‐free period is investigated by the 14C dating of sediment from isolated lake basins. The shore displacement in Gästrikland includes an initial phase (∼500 years) of rapid regression, followed by a slowing of the relative sea level (RSL) fall to a rate similar to that of the remaining Holocene c. 9250 cal. a BP. The Ancylus Lake stage of the Baltic Sea belongs to the analysed interval. The RSL curve and glacial unloading history are used to separate and quantify elements of isostatic uplift. The postglacial uplift is ∼260 m, of which ∼45 m forms a rapid initial rise, which can be treated as qualitatively separate from the later, slower rise. There is considerable glacial unloading just prior to the deglaciation, but calculations suggest that only a small part of this relates directly to the rapid early Holocene rebound: most unloading is transferred either to uplift immediately prior to the deglaciation or to subsequent Holocene or future uplift. The isostatic rise in Gästrikland occurring between the end of the Younger Dryas stadial and the deglaciation, c. 11 500–11 000 cal. a BP, is estimated to be 100–110 m. Observations and estimations are incompatible with a Weichselian maximum ice thickness much smaller that 3000 m. The lack of glacial unloading during the Younger Dryas has a measurable impact on the Holocene isostatic rebound in Gästrikland, reducing it by an estimated 20–25 m.
The Development of Two Different Malignancies in a Patient with Large Congenital Melanocytic Nevus
Authors: AMBROS TADEU , FURIAN ROQUE , RICCARDI FELICE
Published: September 2011

Abstract:  Patients with large congenital melanocytic nevus (LCMN) have a high risk of developing malignant melanoma (MM) and other malignancies. We report a case of a mesenchymal malignancy that best fit the diagnosis of a malignant peripheral nerve sheath tumor and subsequent development of a MM developing from a LCMN. There are no previous reports of a second primary malignant neoplasm arising from a LCMN.
Failure to Thrive in Infants with Complicated Facial Hemangiomas
Authors: Thomas Meghan W. , Burkhart Craig N. , Vaghani Sapna P. , Morrell Dean S. , Wagner Annette M.
Published: September 2011

Abstract:  We have observed that some children with facial hemangiomas of infancy have feeding difficulties coincident with periods of failure to thrive. We evaluated the early oral sensory and feeding experiences of four children with facial hemangiomas through medical record review and parental surveys to investigate their contribution to the patients’ failure to thrive. All children with feeding irregularities experienced some degree of oral sensory impairment and required early oral sensory intervention, but there were varying reports of difficulty or delay in the development of oral feeding. The nature of these difficulties is discussed. Infants with complicated facial hemangiomas with perioral and airway involvement may be at higher risk for feeding and oral sensory problems. We recommend close monitoring for failure to thrive and early evaluation by speech or occupational therapists.
Multiple Nuchal Fibromas in a 2‐Year‐Old Without Gardner Syndrome
Authors: LeBlanc Keith G. , Wenner Morgan , Davis Loretta S.
Published: September 2011

Abstract:  Nuchal fibromas, uncommon benign soft tissue tumors typically arising along the posterior neck, are often associated with Gardner syndrome (GS). These tumors have rarely been reported in association with scleroderma or as secondary to trauma and diabetes. Nuchal fibromas not associated with GS have been described predominantly in men aged 30 to 50. We report a 2‐year‐old African American girl with multiple nuchal fibromas along the posterior aspect of her neck and upper back. Retinal examination showed no signs of congenital hypertrophy of the retinal pigment epithelium, and genetic testing for the adenomatous polyposis coli gene mutation seen in GS was negative.
A Hemoglobin‐Based Multifunctional Therapeutic: Polynitroxylated Pegylated Hemoglobin
Authors: Hsia Carleton Jen Chang , Ma Li
Published: September 2011

Polynitroxylated pegylated hemoglobin (PNPH) as a multifunctional therapeutic takes advantage of the ability of hemoglobin (Hb) to transport oxygen, the antioxidative stress activities from the redox coupling of nitroxide and heme iron, and the hypercolloid properties of pegylation. The published preclinical data demonstrating that PNPH acts as a neurovascular protective multifunctional therapeutic in an animal model simulating prehospital resuscitation of traumatic brain injury (TBI) with hemorrhagic shock (HS) are reviewed. Preliminary results on the potential utility of PNPH for neurovascular protection in thrombolytic stroke therapy and for correction of vascular dysfunction through transfusion in sickle‐cell disease (SCD) are also discussed. We hypothesize that with PNPH, Hb has more than been tamed—it has become a therapeutic and not just a nontoxic extracellular oxygen carrier—and that successful PNPH development as a multifunctional therapeutic that protects the neurovasculature and reduces oxidative stress may represent a paradigm shift in transfusion and critical care medicine, which may meet a number of unmet medical needs resulting from oxidative stress and inadequate blood flow, such as HS, TBI, SCD, and stroke.
An Anti‐Suction Control for an Intra‐Aorta Pump Using Blood Assistant Index: A Numerical Simulation
Authors: Gao Bin , Gu Kaiyun , Zeng Yi , Chang Yu
Published: September 2011

With the extensive use of the left ventricular assist device (LVAD) as a treatment of heart failure, suction detection has become a key issue that directly affects the treatment. To detect the phenomenon of suction, a blood assistant index (BAI) is defined, which reflects the unloading level of the pump. The BAI is a ratio of the external work of LVAD and the input power of cardiovascular system. Using the theory of model‐free adaptive control algorithm, an anti‐suction controller, which chooses the heart rate and BAI as control variables, is designed. As a key feature, the proposed control algorithm adjusts the pump speed according to not only the blood demand of circulatory system but also the function of the native heart. Subsequently, the performance and robustness of the controller are evaluated using a numerical simulation of the assisted circulation and an in vitro experiment. The simulation and experimental results demonstrate that the BAI detects the suction occur accurately, and the controller can maintain the heart rate and BAI tracking the reference values with a response time of less than 6 s.
The Effectiveness of Continuing Group Psychotherapy for Outpatients with Alcohol Dependence: 77‐Month Outcomes
Authors: Kim Jee Wook , Choi Yong Sung , Shin Kyung Chul , Kim Ok Hwa , Lee Dong Young , Jung Myung Hun , Lee Boung Chul , Kang Tae‐Cheon , Choi Ihn‐Geun
Published: September 2011

Background:  Group psychotherapy (PT) is one of the most common interventions used to treat alcohol dependence (AD), and it is assumed to be effective. Despite its common clinical use, long‐term trials that have been conducted to examine the efficacy of group PT in the treatment of outpatients with AD are limited and often lack appropriate comparisons. On that basis, a long‐term comparative trial was performed with the main objective of evaluating the effectiveness of continuing group PT for outpatients with AD.

Methods:  Quasi‐experimental trial was conducted from January 2004 to May 2010 in 177 AD subjects who had completed an inpatient 10‐week alcohol treatment program. Abstinence rates of the combined group (experimental group: outpatient individual PT plus group PT, N = 94) and the standard outpatient individual PT‐only group (comparison group, N = 83) were statistically compared using Kaplan–Meier survival analysis. Predictive factors of abstinence rate for alcohol were assessed using Cox regression analysis.

Results:  Abstinence rates of the combined PT group were significantly high relative to those of the outpatient individual PT‐only group. Significant predictive factors for the alcohol abstinence rate were outpatient group PT and age. Even after controlling for confounding factors, outpatient group PT was a significant predictive factor for the alcohol abstinence rate.

Conclusions:  Our findings indicate that for AD patients who had completed an inpatient 10‐week alcohol treatment, outpatient group PT appears to be an effective form of continuing care or aftercare within the context of an outpatient service delivery system.
Severity of Acute Illness is Associated with Baseline Readiness to Change in Medical Intensive Care Unit Patients with Unhealthy Alcohol Use
Authors: Clark Brendan J. , Smart Alexandra , House Robert , Douglas Ivor , Burnham Ellen L. , Moss Marc
Published: September 2011

Background:  Unhealthy alcohol use predisposes to multiple conditions that frequently result in critical illness and is present in up to one‐third of patients admitted to a medical intensive care unit (ICU). We sought to determine the baseline readiness to change in medical ICU patients with unhealthy alcohol use and hypothesized that the severity of acute illness would be independently associated with higher scores on readiness to change scales. We further sought to determine whether this effect is modified by the severity of unhealthy alcohol use.

Methods:  We performed a cross‐sectional observational study of current regular drinkers in 3 medical ICUs. The Alcohol Use Disorders Identification Test was used to differentiate low‐risk and unhealthy alcohol use and further categorize patients into risky alcohol use or an alcohol use disorder. The severity of a patient’s acute illness was assessed by calculating the Acute Physiologic and Chronic Health Evaluation II (APACHE II) score at the time of admission to the medical ICU. Readiness to change was assessed using standardized questionnaires.

Results:  Of 101 medical ICU patients who were enrolled, 65 met the criteria for unhealthy alcohol use. The association between the severity of acute illness and readiness to change depended on the instrument used. A higher severity of illness measured by APACHE II score was an independent predictor of readiness to change as assessed by the Stages of Change Readiness and Treatment Eagerness Scale (Taking Action scale; p < 0.01). When a visual analog scale was used to assess readiness to change, there was a significant association with severity of acute illness (p < 0.01) that was modified by the severity of unhealthy alcohol use (p = 0.04 for interaction term).

Conclusions:  Medical ICU patients represent a population where brief interventions require further study. Studies of brief intervention should account for the severity of acute illness and the severity of unhealthy alcohol use as potential effect modifiers.
Thoracic Kyphosis Associated with Hemivertebra
Authors: Moissonnier Pierre , Gossot Pauline , Scotti Stefano
Published: September 2011

Objective

To radiographically assess the influence of thoracic hemivertebra on kyphosis and neurologic status in 45 dogs.

Study Design

Case series.

Animals

French Bulldogs without neurologic signs (n = 41) and 4 dogs with compressive spinal cord disease associated with hemivertebra.

Methods

Thoracic spinal radiographs were divided into 3 groups: 1 = dogs with no hemivertebra, 2 = dogs with hemivertebra but no associated neurologic signs, and 3 = dogs with hemivertebra associated with clinical signs. Vertebral canal height, vertebral column angle, and the step between 2 adjacent vertebrae were measured in each group.

Results

Vertebral canal height was not significantly different in the 3 groups; however, mean vertebral column angle was significantly (P < .001) different between groups 1 (178°) and 2 (169°), and group 3 (133°). Median cranial step was significantly different between groups (P < .001): 0 mm (group 1), 0.3 mm (group 2), 3 mm (group 3).

Conclusions

Vertebral canal height does not differ between normal dogs and dogs with thoracic hemivertebra. There is an important association between neurologic signs and kyphosis and subluxation.

Clinical Relevance

Vertebral realignment without vertebral canal opening could lead to spinal cord decompression in dogs affected by thoracic hemivertebra.
Use of the PleuralPort Device for Management of Pleural Effusion in Six Dogs and Four Cats
Authors: Brooks Aimee C. , Hardie Robert J.
Published: September 2011

Objective

To describe the placement technique, complications, and outcomes associated with use of the PleuralPort device for management of pleural effusion in dogs and cats.

Study Design

Case Series.

Animals

Six dogs and 4 cats.

Methods

Medical records of all animals with pleural effusion managed with the PleuralPort device were reviewed. Data regarding signalment, fluid analysis, placement technique, duration of function, duration of implantation, complications, and outcome were collected. Owners and referring veterinarians were contacted for follow‐up information.

Results

Nine animals had chylous effusion and 1 dog had pleural carcinomatosis. Eleven ports were placed with 1 cat receiving bilateral ports. Four animals developed complications. One cat developed pneumothorax immediately after implantation and was euthanatized. In 2 dogs and 1 cat, the ports obstructed. The 6 remaining animals had functioning ports at time of death or resolution of effusion and no longer required use of the port. No significant port migration, irritation, or infection of the device was reported. Excluding the cat with pneumothorax, median duration of port function was 20 days (range 1–391), and median duration of port implantation was 391 days (range 6–723).

Conclusions

The PleuralPort device is a feasible option for the management of pleural effusion in dogs and cats.
The Development and Psychometric Validation of the Central Sensitization Inventory
Authors: Mayer Tom G. , Neblett Randy , Cohen Howard , Howard Krista J. , Choi Yun H. , Williams Mark J. , Perez Yoheli , Gatchel Robert J.
Published: September 2011

Central sensitization (CS) has been proposed as a common pathophysiological mechanism to explain related syndromes for which no specific organic cause can be found. The term “central sensitivity syndrome (CSS)” has been proposed to describe these poorly understood disorders related to CS. The goal of this investigation was to develop the Central Sensitization Inventory (CSI), which identifies key symptoms associated with CSSs and quantifies the degree of these symptoms. The utility of the CSI, to differentiate among different types of chronic pain patients who presumably have different levels of CS impairment, was then evaluated. Study 1 demonstrated strong psychometric properties (test–retest reliability = 0.817; Cronbach’s alpha = 0.879) of the CSI in a cohort of normative subjects. A factor analysis (including both normative and chronic pain subjects) yielded 4 major factors (all related to somatic and emotional symptoms), accounting for 53.4% of the variance in the dataset. In Study 2, the CSI was administered to 4 groups: fibromyalgia (FM); chronic widespread pain without FM; work‐related regional chronic low back pain (CLBP); and normative control group. Analyses revealed that the patients with FM reported the highest CSI scores and the normative population the lowest (P < 0.05). Analyses also demonstrated that the prevalence of previously diagnosed CSSs and related disorders was highest in the FM group and lowest in the normative group (P < 0.001). Taken together, these 2 studies demonstrate the psychometric strength, clinical utility, and the initial construct validity of the CSI in evaluating CS‐related clinical symptoms in chronic pain populations. ▪
Comparative Effectiveness in Pain‐Related Outcomes and Health Care Utilizations between Veterans with Major Depressive Disorder Treated with Duloxetine and Other Antidepressants: A Retrospective Propensity Score‐Matched Comparison
Authors: Shi Lizheng , Liu Jinan , Zhao Yang
Published: September 2011

Objectives:  This study aimed to compare pain‐related outcomes and health care utilization among patients with major depressive disorder (MDD) treated with duloxetine versus other antidepressants in the Veterans Health Administration (VHA).

Methods:  Patients initiating duloxetine or other antidepressants between October 1, 2005, and October 1, 2008 were extracted from the Veterans Integrated Service Network (VISN) 16 data warehouse. All patients included had at least 1 MDD diagnosis (ICD‐9‐CM: 296.2 or 296.3) and continuous eligibility in the 12 months prior to the initiation. Patients with prior diabetes (ICD‐9‐CM: 250.xx), schizophrenia (295.xx), or bipolar disorder (ICD‐9‐CM: 296.4x–296.8x) diagnosis were excluded. Duloxetine and nonduloxetine patients were matched via propensity scoring (1:1 ratio). Opioid use patterns, diagnosed substance abuse, self‐reported pain score, and health care utilization over the 12‐month postindex period were compared between cohorts.

Results:  Compared with duloxetine‐treated patients (N = 439), nonduloxetine‐treated patients (N = 439) during the postindex period had more opioid scripts (4.8 vs. 3.6, P = 0.002), longer use of opioid (133 vs. 100 days, P = 0.004), and a higher prevalence of substance abuse (41.00% vs. 23.69%, P < 0.001). Nonduloxetine‐treated group had 12.0 more outpatient visits (41.8 vs. 29.8, P < 0.0001), 0.16 more hospital admissions (0.32 vs. 0.16, P = 0.001), and 2.36 more hospital days (3.37 vs. 1.01, P = 0.005). Additionally, nonduloxetine‐treated patients were more likely to be hospitalized (17.8% vs. 10.9%, P = 0.004) over the postindex period.

Conclusion:  Controlling for cross‐cohort differences, veterans with MDD treated with duloxetine were associated with lower risks of opioid use and substance abuse and lower health care utilization than those treated with other antidepressants. ▪
Demographics of successful, unsuccessful and deferral visits at six blood centers over a 4‐year period
Authors: Custer Brian , Schlumpf Karen , Simon Toby L. , Spencer Bryan R. , Wright David J. , Wilkinson Susan L. ,   for the NHLBI Retrovirus Epidemiology Donor Study‐II (REDS‐II)
Published: September 2011

BACKGROUND: Descriptions of donor demographics are of value in formulating recruitment and retention strategies. The demographics of successful (SV), unsuccessful (UV; meaning a nonuseable unit), and deferred (DV) donor visits over a 4‐year period were investigated using Retrovirus Epidemiology Donor Study (REDS)‐II databases.

STUDY DESIGN AND METHODS: Fourteen deferral categories were created that included low hematocrit (Hct) or hemoglobin (Hb), feeling unwell, malaria travel, malaria other, couldn't wait, blood pressure or pulse, medical diagnosis, medication, test results, higher‐risk behavior, variant Creutzfeldt‐Jakob disease (CJD), CJD, needle exposure or tattoo, and other. Rates per 10,000 donor presentations were determined for each category globally and for six subcategorizations (first‐time or repeat donor status, sex, race/ethnicity, age, education, and fixed or mobile donation location). Deferral rates were also calculated on simultaneous stratifications of donor status, sex, and race/ethnicity.

RESULTS: Of 5,607,922 donor presentations there were 4,553,145 SVs (81.2%), 302,828 UVs (5.4%), and 751,381 DVs (13.4%). Overall rates of deferral ranged from 0.6 per 10,000 presentations for CJD, human growth hormone, or dura mater exposure to 777 per 10,000 presentations for low Hct or Hb. Deferral rates were remarkably different by first‐time or repeat donor status, sex, race/ethnicity, and other demographics. The highest overall deferral rate was 3953 per 10,000 presentations, or nearly 40% in first‐time, female, Asian donors, and the lowest rate was 5.6% in repeat, male, white donors.

CONCLUSION: Successful donation visits according to demographic characteristics need to be placed within the context of all donor visits. Deferral rates indicate that the burden of donor deferral is high. Efforts to expand the diversity of the donor base through recruitment of minority donors may bring additional challenges because certain deferral reasons were proportionally much higher in these groups.
Evolving Macroeconomic Dynamics in a Small Open Economy: An Estimated Markov Switching DSGE Model for the UK
Authors: LIU PHILIP , MUMTAZ HAROON
Published: September 2011

This paper investigates the possibility of shifts in the UK economy using a Markov switching open economy dynamic stochastic general equilibrium (DSGE) model. We find overwhelming evidence to reject the hypothesis that the deep structural parameters of the underlying structural model had stayed constant throughout the sample period and there is significant changes to the volatility of the structural shocks. Counterfactual experiments based on the model with the best empirical fit indicate that the change in the policy rule as well as changes to the volatility of the structural shocks over the sample period are crucial features in explaining UK’s macroeconomic performance.
Inflation Targeting as Constrained Discretion
Authors: KIM JUNHAN
Published: September 2011

This paper suggests a simple framework for modeling inflation targeting as constrained discretion. Although it is widely claimed that inflation targeting has been successful in maintaining low and stable inflation, an announcement of an inflation target does not by itself mean that central bankers are precommiting to how they conduct monetary policy. In comparison to the assumption of many theoretical studies, central banks conduct monetary policy in a discretionary fashion and rarely precommit to a rule in reality. Therefore, the central bank in this paper is modeled as discretionary, yet faced with a constraint, that an average of future inflation over a certain horizon should be kept on or near the preannounced target level. It is natural to add this constraint to the central banker’s optimization problem, since inflation targeting involves one way or another an evaluation of the performance over a certain horizon. So it is argued that the better outcome of inflation targeting does not come from a commitment but from “constrained discretion.” This paper also sheds some light on optimal targeting horizon.
Ventricular Activation Sequence during Left Ventricular Pacing Promotes QRS Complex Oversensing in the Atrial Channel
Authors: JASTRZEBSKI MAREK
Published: September 2011

Background:
 Left ventricular (LV)‐only pacing has a significant effect on delay in depolarization of parts of the ventricles that are likely oversensed in the right atrial channel. The study aimed to assess the impact of ventricular activation sequence on QRS oversensing and far‐field endless‐loop pacemaker tachycardia (ELT) in patients who received cardiac resynchronization therapy (CRT) devices.

Methods:
 The study examined 102 patients with CRT devices. Oversensing artifacts in the atrial channel were inspected on intracardiac electrograms, and their timing with respect to the beginning of QRS was determined during DDD‐right ventricular (RV), DDD‐LV, DDD‐biventricular (BiV), and AAI pacing modes. The occurrence of ELT during DDD‐LV pacing with a postventricular atrial refractory period (PVARP) of 250 ms was also assessed.

Results:
 The timing of oversensing artifacts (in relation to the beginning of surface QRS) was dependent on ventricular activation sequence, occurring promptly following intrinsic activation via the right bundle branch (47.1 ± 26.4 ms), later during RV pacing (108.7 ± 22.5 ms) or BiV pacing (109.4 ± 23.1 ms), and significantly later, corresponding to the final part of the QRS, during LV pacing (209.6 ± 40.0 ms, range: 140–340 ms, P < 0.001). Oversensing was significantly more frequent during LV than during RV pacing (35.3% vs 22.5%, P < 0.001). Far‐field ELT was observed in six patients.

Conclusions:
 Oversensing artifacts in the atrial channel are likely caused by depolarization of the basal part of the right ventricle. The novel mechanism of QRS oversensing outside PVARP, caused by a reversed ventricular activation sequence during LV‐only pacing, may be important in some CRT patients. (PACE 2011; 34:1682–1686)
Implantable Cardioverter‐Defibrillator Recipient Attitudes towards Device Deactivation: How Much do Patients Want to Know?
Authors: RAPHAEL CLAIRE E. , KOA‐WING MICHAEL , STAIN NOLAN , WRIGHT IAN , FRANCIS DARREL P. , KANAGARATNAM PRAPA
Published: September 2011

Background:
 Patients receiving implantable cardioverter‐defibrillators (ICDs) often have severely impaired left ventricular function and a poor prognosis. Having an ICD in situ effectively denies them the possibility of a quick, arrhythmic death. It is still unclear if and when the end of life and device deactivation should be discussed with patients and how much patients want to know prior to ICD implantation.

Methods:
 Patients with an active ICD for chronic heart failure were interviewed regarding their attitude toward the ICD, their recollection of the consent procedure, and how they felt the end of life should be discussed with ICD patients (n = 54). Patients who had received ICD therapies (n = 25) were reviewed as a subgroup with extended questions regarding attitudes toward device deactivation.

Results:
 Fifty‐four patients were recruited. Most patients were not aware that the ICD could be deactivated. The vast majority of patients (84%) wanted to be involved in the deactivation decision; 40% felt this discussion should be prior to ICD implantation but others felt the discussion should only occur if the patient was terminally ill (16%) or in the last few days of life (5%).

Conclusion:
 Patients with ICDs are routinely counseled about the benefits of ICDs, but options for device deactivation are not well understood by patients. Most patients would like to be involved in deactivation decisions and we feel this should be discussed well in advance. (PACE 2011; 34:1628–1633)
The Use of Dabigatran Immediately After Atrial Fibrillation Ablation
Authors: WINKLE ROGER A. , MEAD R. HARDWIN , ENGEL GREGORY , KONG MELISSA H. , PATRAWALA ROB A.
Published: September 2011

Dabigatran After AF Ablation. Introduction: Atrial fibrillation (AF) ablation requires postprocedural anticoagulation to prevent thromboembolic events because of the ablation procedure itself or due to recurrent AF postprocedure. Dabigatran is a new anticoagulant and may be useful after AF ablation to prevent thromboembolic events.

Methods and Results: We evaluated 123 consecutive patients who were started on dabigatran after AF ablation. Patients were given enoxaparin 0.5 mg/kg at the end of the procedure, which was repeated 12 hours later and then discontinued. Dabigatran was started 22 hours postablation with drug dose based on renal function. Primary outcomes were thromboembolic events, bleeding complications, and side effects over a 30‐day follow‐up period.

The preablation anticoagulant was warfarin in 56 (45.5%) patients, dabigatran in 34 (27.6%), and aspirin in 26 (21.1%). Seven (5.7%) patients were on no anticoagulant before ablation. The patients on dabigatran before ablation with normal renal function had the drug stopped 36 hours preablation. There were no preprocedural or intraprocedural thromboembolic episodes or bleeding. Three patients received dabigatran 75 mg bid and the rest 150 mg bid. There were no postablation strokes, transient ischemic attacks, or systemic thromboemboli in any patient. Three patients discontinued dabigatran and were changed to warfarin, 2 because of gastrointestinal side effects and 1 because of a diffuse rash.

Conclusions: Dabigatran is safe and well tolerated after AF ablation. It did not cause bleeding complications and there were no thromboembolic events. Dabigatran appears to be an alternative to warfarin after AF ablation. (J Cardiovasc Electrophysiol, Vol. 23 p. 264‐268, March 2012.)
Left Atrial Deformation Imaging with Ultrasound Based Two‐Dimensional Speckle‐Tracking Predicts the Rate of Recurrence of Paroxysmal and Persistent Atrial Fibrillation After Successful Ablation Procedures
Authors: HAMMERSTINGL CHRISTOPH , SCHWEKENDIEK MARIEKE , MOMCILOVIC DIANA , SCHUELER ROBERT , SINNING JAN‐MALTE , SCHRICKEL JAN W. , MITTMANN‐BRAUN ERICA , NICKENIG GEORG , LICKFETT LARS
Published: September 2011

Predict AF. Objective: Since predictors of recurrence of atrial fibrillation (AF) after ablation procedures are poorly defined, this prospective study was conducted to assess the value of left atrial (LA) deformation imaging with two‐dimensional speckle‐tracking (2D‐ST) to predict AF recurrences after successful ablation procedures.

Methods and results:
One hundred and three consecutive patients (age 58.1 ± 16.6 years, 72.8% male) with AF (76 paroxysmal, 27 persistent) and 30 matched controls underwent transthoracic echocardiography and 2D‐ST‐LA‐deformation analysis with assessment of LA‐radial and LA‐longitudinal strain (Sr, Sl), and velocities derived from the apical 4‐ and 2‐chamber views (4CV, 2CV). AF recurrence was assessed during 6 months of follow‐up. For determination of AF‐related LA changes, AF patients were compared to controls and patients with AF recurrences after ablation procedures (n = 30, 29.1%) were compared with patients who maintained sinus rhythm (n = 73, 70.9%). Atrial deformation capabilities were significantly reduced (P  <  0.0005) in patients with AF (4CVSl 17.8 ± 13.5%; 4CVSr 22.3 ± 14.9%; 4CV‐velocities 2.53 ± 0.97 seconds) when compared with controls (4CVSl 31.3 ± 12.4%; 4CVSr 30.3 ± 9.1%; 4CV‐velocities 3.48 ± 1.01 cm/s). Independent predictors for AF recurrence after ablation procedures were 2CV‐LA‐global‐strain (Sr, P = 0.03; Sl, P = 0.003), 4CV‐LA‐gobal‐strain (Sr, P = 0.03; Sl, P = 0.02), and regional LA‐septal wall‐Sl (P = 0.008). LA‐global‐strain parameters were superior to regional LA function analysis for the prediction of AF recurrences, with cutoff values (cov), hazard ratios (HR), positive and negative predictive values (PPV, NPV) were: 4CVSl cov, 10.79% (HR 27.8, P  <  0.0005; PPV 78.8%, NPV 93.9%), 4CVSr cov, −16.65% (HR 24.8, P < 0.0005; PPV 69.4%, NPV 96.6%), 2CVSl cov, 12.31% (HR 22.7, P  <  0.0005; PPV 75.8%, NPV 95.3%), and 2CVSr cov, −14.9% (HR 12.9, P < 0.0005; PPV 64.3%, NPV 93.2%).

Conclusion:
Compared with controls, AF itself seems to decrease LA deformation capabilities. The assessment of global LA strain with 2D‐ST identifies patients with high risk for AF recurrence after ablation procedures. This imaging technique may help to improve therapeutic guiding for patients with AF. (J Cardiovasc Electrophysiol, Vol. 23 p. 247‐255, March 2012.)
Dofetilide Reduces the Frequency of Ventricular Arrhythmias and Implantable Cardioverter Defibrillator Therapies
Authors: BAQUERO GISELLE A. , BANCHS JAVIER E. , DEPALMA SONDRA , YOUNG SALLIE K. , PENNY‐PETERSON ERICA D. , SAMII SORAYA M. , WOLBRETTE DEBORAH L. , NACCARELLI GERALD V. , GONZALEZ MARIO D.
Published: September 2011

Dofetilide Reduces VT/VF and ICD Therapies. Background: Patients with an implanted cardioverter defibrillator (ICD) and ventricular arrhythmias leading to ICD therapies have poor clinical outcomes and quality of life. Antiarrhythmic agents and catheter ablation are needed to control these arrhythmias. Dofetilide has only been approved for the treatment of atrial fibrillation. The role of dofetilide in the control of ventricular arrhythmias in patients with an ICD has not been established.

Objective: Evaluate the safety and efficacy of dofetilide in a consecutive group of patients with an ICD and recurrent ventricular tachycardia (VT) and/ or ventricular fibrillation (VF) after other antiarrhythmic drugs have failed to suppress these arrhythmias.

Methods: We studied 30 patients (age 59  ±  11; 5 women) with symptomatic VT or VF and ICDs for secondary prevention of sudden cardiac death. These patients had an average of 1.8  ±  4.5 episodes of VT/VF per month despite antiarrhymic therapy. Twenty‐one patients (70%) had recurrent appropriate ICD therapies prior to initiation of dofetilide, and 9 (30%) VTs below the programmed detection rate of the ICD. Twenty‐three patients (77%) had coronary artery disease. Mean ejection fraction was 30 ± 14% and 26/30 (87%) had congestive heart failure. All patients had previously failed 2 ± 1 antiarrhythmic drugs including amiodarone (n = 19) and sotalol (n = 10).

Results: During the first month of treatment, 25 patients (83%) had complete suppression of VT/VF and of the 21 patients with ICD therapies 16 (76%) had no therapies during the first month of treatment. During a follow‐up period of 32  ±  32 months, dofetilide reduced the monthly episodes of VT/VF from 1.8  ±  4.5 to 1.0  ±  3.5 (P = 0.006). Monthly ICD therapies decreased from 0.9 ± 1.4 to 0.4 ± 1.7 (P = 0.037). In 9 patients that presented with slow VTs under the ICD detection zone, dofetilide reduced monthly VT/VF episodes from 0.7  ±  0.6 to 0.1  ± 0.1 (P = 0.01) and 6 (67%) had no further ICD therapies. Dofetilide was discontinued in 13 patients (43%) after 24  ±  30 months due to failure to control VT/VF (n = 7), placement of a left ventricular assist device (n = 3), catheter ablation (n = 1), heart transplantation (n = 1), and left ventricular restoration surgery (n = 1). There were 7 documented deaths (2 patients died suddenly; 3 patients of progressive heart failure; and 2 of non‐cardiac causes).

Conclusions: In patients with an ICD and ventricular arrhythmias, dofetilide decreases the frequency of VT/VF and ICD therapies even when other antiarrhythmic agents, including amiodarone, have previously been ineffective. Recurrences still occur in some patients requiring catheter ablation, mechanical support, or heart transplantation. (J Cardiovasc Electrophysiol, Vol. 23 p. 296‐301, March 2012.)