bluuebunny/crossref_metadata_2025 huggingface dataset:
Constitutive activity of cannabinoid‐2 (CB2) receptors plays an essential role in the protean agonism of (+)AM1241 and L768242
Authors: Mancini I , Brusa R , Quadrato G , Foglia C , Scandroglio P , Silverman LS , Tulshian D , Reggiani A , Beltramo M
Published: June 2009

Background and purpose: Cannabinoid‐2 (CB2) receptor‐selective agonists have shown anti‐nociceptive activity in models of neuropathic and inflammatory pain, and the two agonists most widely used, (+/−)AM1241 [(2‐iodo‐5‐nitrophenyl)‐[1‐(1‐methylpiperidin‐2‐ylmethyl)‐1H‐indol‐3‐yl‐methanone] and L768242 [(2,3‐dichloro‐phenyl)‐[5‐methoxy‐2‐methyl‐3‐(2‐morpholin‐4‐yl‐ethyl)‐indol‐1‐yl]‐methanone] (GW405833), have been suggested to be protean agonists. Here we investigated the role of the constitutive activity of CB2receptors in (+)AM1241 and L768242 protean agonism.

Experimental approach: Pharmacological profiles of CB2receptor ligands were evaluated in Chinese hamster ovary cells expressing recombinant human (hCB2) or rat (rCB2) receptors, by measuring modulation of cAMP. To assess the influence of constitutive activity on pharmacological profile, constitutive activity was abolished by pretreatment with AM630 [(6‐iodo‐2‐methyl‐1‐[2‐(4‐morpholinyl)ethyl]‐1H‐indol‐3‐yl](4‐methoxyphenyl) methanone)], followed by extensive washing.

Key results: In cell lines expressing either hCB2or rCB2receptors, (+)AM1241 did not reverse forskolin stimulation of cAMP levels. Conversely, L768242 was an inverse agonist at both hCB2and rCB2receptors. Abolition of constitutive activity disclosed (+)AM1241 and L768242 agonist activity, while activity of CP55940 [5‐(1,1‐dimethylheptyl)‐2‐[(1R,2R,5R)‐5‐hydroxy‐2‐(3‐hydroxy‐propyl)‐cyclohexyl]‐phenol] was unaffected and AM630 became a neutral antagonist. In presence of constitutively active CB2receptors, (+)AM1241 antagonized CP55940, but when constitutive activity was abolished, it acted as a partial agonist with additive or antagonistic behaviour, depending on concentration.

Conclusions and implications: These results show that (+)AM1241 and L768242 are protean agonists at both hCB2and rCB2receptors. Abolition of constitutive activity reveals the agonist activity of these compounds. Thus, differences betweenin vivoandin vitroprofiles of CB2receptor agonists could be due to different levels of constitutive activity in recombinant versus native CB2receptors.
Bovine glycomacropeptide induces cytokine production in human monocytes through the stimulation of the MAPK and the NF‐κB signal transduction pathways
Authors: Requena Pilar , Daddaoua Abdelali , Guadix Emilia , Zarzuelo Antonio , Suárez María Dolores , De Medina Fermín Sánchez , Martínez‐Augustin Olga
Published: June 2009

Background and purpose:  Bovine glycomacropeptide (BGMP) is a natural milk peptide that is produced naturally in the gastrointestinal tract during digestion. Glycomacropepide has intestinal anti‐inflammatory activity, but the mechanism of action is unknown. Here we have characterized the effects of BGMP on monocytes.

Experimental approach:  We have used human THP‐1 cells as an in vitro monocyte model. The effect of BGMP on the secretion of tumour necrosis factor (TNF), interleukin (IL)‐1β and IL‐8 was assessed, as well as the involvement of the NF‐κB and MAP kinase signalling pathways. The stimulatory effect of BGMP was also tested in human peripheral blood monocytes.

Key results:  BGMP up‐regulated the secretion of TNF, IL‐1β and IL‐8 in a concentration‐dependent fashion. The biological activity was exerted by the intact peptide, because cytokine secretion was not affected by protease inhibitors. The secretion of IL‐8 and specially TNF and IL‐1β was blocked by PD98059, SP600125, SB203580 and Bay11‐7082, suggesting the involvement of the MAP kinases p38, c‐Jun N‐terminal kinase and ERK and particularly the NF‐κB pathway, although IL‐8 secretion was independent of p38. BGMP was shown to elicit the phosphorylation of IκB‐α and the nuclear translocation of the NF‐κB subunits p50 and p65. The effect of BGMP on cytokine secretion was validated in human primary blood monocytes.

Conclusions and implications:  BGMP stimulates human monocytes, operating via MAP kinase and NF‐κB pathways. BGMP may exert an indirect intestinal anti‐inflammatory effect by potentiating host defences against invading microorganisms.
Mammalian P2X7 receptor pharmacology: comparison of recombinant mouse, rat and human P2X7 receptors
Authors: Donnelly‐Roberts Diana L , Namovic Marian T , Han Ping , Jarvis Michael F
Published: June 2009

Background and purpose: Acute activation of P2X7 receptors rapidly opens a non‐selective cation channel. Sustained P2X7 receptor activation leads to the formation of cytolytic pores, mediated by downstream recruitment of hemichannels to the cell surface. Species‐ and single‐nucleotide polymorphism‐mediated differences in P2X7 receptor activation have been reported that complicate understanding of the physiological role of P2X7 receptors. Studies were conducted to determine pharmacological differences between human, rat and mouse P2X7 receptors.

Experimental approach: Receptor‐mediated changes in calcium influx and Yo‐Pro uptake were compared between recombinant mouse, rat and human P2X7 receptors. For mouse P2X7 receptors, wild‐type (BALB/c) and a reported loss of function (C57BL/6) P2X7 receptor were also compared.

Key results: BzATP [2,3‐O‐(4‐benzoylbenzoyl)‐ATP] was more potent than ATP in stimulating calcium influx and Yo‐Pro uptake at rat, human, BALB/c and C57BL/6 mouse P2X7 receptors. Two selective P2X7 receptor antagonists, A‐740003 and A‐438079, potently blocked P2X7 receptor activation across mammalian species. Several reported P2X1 receptor antagonists [e.g. MRS 2159 (4‐[(4‐formyl‐5‐hydroxy‐6‐methyl‐3‐[(phosphonooxy)methyl}‐2‐pyridinyl)azo]‐benzoic acid), PPNDS and NF279] blocked P2X7 receptors. NF279 fully blocked human P2X7 receptors, but only partially blocked BALB/c P2X7 receptors and was inactive at C57BL/6 P2X7 receptors.

Conclusions and implications: These data provide new insights into P2X7 receptor antagonist pharmacology across mammalian species. P2X7 receptor pharmacology in a widely used knockout background mouse strain (C57BL/6) was similar to wild‐type mouse P2X7 receptors. Several structurally novel, selective and competitive P2X7 receptor antagonists show less species differences compared with earlier non‐selective antagonists.
Agonist‐specific patterns of β2‐adrenoceptor responses in human airway cells during prolonged exposure
Authors: Düringer Caroline , Grundström Gunilla , Gürcan Eylem , Dainty Ian A , Lawson Mandy , Korn Solange H , Jerre Anders , Håkansson Hanna Falk , Wieslander Elisabet , Fredriksson Karin , Sköld Carl Magnus , Löfdahl Magnus , Löfdahl Claes‐Göran , Nicholls David J , Silberstein David S
Published: June 2009

Background and purpose:  β2‐Adrenoceptor agonists (β2‐agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, β2‐adrenergic agonist stimulation induces desensitization of the β2‐adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of β2‐agonists in cellular and in vitro tissue models.

Experimental approach:  β2‐Adrenoceptor‐induced responses and subsequent loss of receptor responsiveness were studied in primary human airway smooth muscle cells and bronchial epithelial cells by measuring cAMP production. Receptor responsiveness was compared at equi‐effective concentrations, either after continuous incubation for 24 h or after a 1 h pulse exposure followed by a 23 h washout. Key findings were confirmed in guinea pig tracheal preparations in vitro.

Key results:  There were differences in the reduction of receptor responsiveness in human airway cells and in vitro guinea pig trachea by a panel of β2‐agonists. When restimulation occurred immediately after continuous incubation, loss of responsiveness correlated with initial effect for all agonists. After the 1 h pulse exposure, differences between agonists emerged, for example isoprenaline and formoterol induced the least reduction of responsiveness. High lipophilicity was, to some extent, predictive of loss of responsiveness, but other factors appeared to be involved in determining the relationships between effect and subsequent loss of responsiveness for individual agonists.

Conclusions and implications:  There were clear differences in the ability of different β2 agonists to induce loss of receptor responsiveness at equi‐effective concentrations.
Functional evidence for the expression of P2X1, P2X4 and P2X7 receptors in human lung mast cells
Authors: Wareham K , Vial C , Wykes RCE , Bradding P , Seward EP
Published: June 2009

Background and purpose: P2X receptors are widely expressed in cells of the immune system with varying functions. This study sought to characterize P2X receptor expression in the LAD2 human mast cell line and human lung mast cells (HLMCs).

Experimental approach: Reverse transcriptase polymerase chain reaction (RT‐PCR) and patch clamp studies were used to characterize P2X expression in mast cells using a range of pharmacological tools.

Key results: RT‐PCR revealed P2X1, P2X4 and P2X7 transcripts in both cell types; mRNA for P2X6 was also detected in LAD2 cells. Under whole‐cell patch clamp conditions, rapid application of ATP (1–1000 µM) to cells clamped at −60 mV consistently evoked inward currents in both types of cells. Brief application of ATP (1 s) evoked a rapidly desensitizing P2X1‐like current in both cell types. This current was also elicited by αβmethylene ATP (10 µM, 94% cells,n= 31) and was antagonized in LAD2 cells by NF 449 (1 µM) and pyridoxal phosphate‐6‐azo(benzene‐2,4‐disulphonic acid) (1–10 µM). A P2X7‐like non‐desensitizing current in response to high concentrations of ATP (1–5 mM) was also seen in both cell types (96% LAD2,n= 24; 54% HLMCs,n= 24) which was antagonized by AZ11645373 (1 µM). P2X7‐like responses were also evoked in LAD2 cells by 2′(3′)‐0‐(4‐benzoylbenzoyl)ATP (300 µM). A P2X4‐like current was evoked by 100 µM ATP (80% LAD2,n= 10; 21% HLMCs,n= 29), the amplitude and duration of which was potentiated by ivermectin (3 µM).

Conclusion and implications: Our data confirmed the presence of functional P2X1, P2X4 and P2X7 receptors in LAD2 cells and HLMCs.
Silibinin prevents amyloid β peptide‐induced memory impairment and oxidative stress in mice
Authors: Lu P , Mamiya T , Lu LL , Mouri A , Zou LB , Nagai T , Hiramatsu M , Ikejima T , Nabeshima T
Published: June 2009

Background and purpose:  Accumulated evidence suggests that oxidative stress is involved in amyloid β (Aβ)‐induced cognitive dysfunction. Silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), has been shown to have antioxidative properties; however, it remains unclear whether silibinin improves Aβ‐induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by Aβ25–35 in mice.

Experimental approach:  Aggregated Aβ25–35 (3 nmol) was intracerebroventricularly administered to mice. Treatment with silibinin (2, 20 and 200 mg·kg−1, once a day, p.o.) was started immediately after the injection of Aβ25–35. Locomotor activity was evaluated 6 days after the Aβ25–35 treatment, and cognitive function was evaluated in a Y‐maze and novel object recognition tests 6–11 days after the Aβ25–35 treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the Aβ25–35 injection.

Key results:  Silibinin prevented the memory impairment induced by Aβ25–35 in the Y‐maze and novel object recognition tests. Repeated treatment with silibinin attenuated the Aβ25–35‐induced accumulation of malondialdehyde and depletion of glutathione in the hippocampus.

Conclusions and implications:  Silibinin prevents memory impairment and oxidative damage induced by Aβ25–35 and may be a potential therapeutic agent for Alzheimer's disease.
Actions of veratridine on tetrodotoxin‐sensitive voltage‐gated Na+currents, NaV1.6, in murine vas deferens myocytes
Authors: Zhu Hai‐Lei , Wassall Richard D. , Takai Maki , Morinaga Hidetaka , Nomura Masatoshi , Cunnane Thomas C. , Teramoto Noriyoshi
Published: June 2009

Background and purpose: The effects of veratridine, an alkaloid found inLiliaceaeplants, on tetrodotoxin (TTX)‐sensitive voltage‐gated Na+channels were investigated in mouse vas deferens.

Experimental approach: Effects of veratridine on TTX‐sensitive Na+currents (INa) in vas deferens myocytes dispersed from BALB/c mice, homozygous mice with a null allele of NaV1.6 (NaV1.6−/−) and wild‐type mice (NaV1.6+/+) were studied using patch‐clamp techniques. Tension measurements were also performed to compare the effects of veratridine on phasic contractions in intact tissues.

Key results: In whole‐cell configuration, veratridine had a concentration‐dependent dual action on the peak amplitude of INa: INawas enhanced by veratridine (1–10 µM), while higher concentrations (≥30 µM) inhibited INa. Additionally, two membrane current components were evoked by veratridine, namely a sustained inward current during the duration of the depolarizing rectangular pulse and a tail current at the repolarization. Although veratridine caused little shift of the voltage dependence of the steady‐state inactivation curve and the activation curve for INa, veratridine enhanced a non‐inactivating component of INa. Veratridine caused no detectable contractions in vas deferens from NaV1.6−/−mice, although in tissues from NaV1.6+/+mice, veratridine (≥3 µM) induced TTX‐sensitive contractions. Similarly, no detectable inward currents were evoked by veratridine in NaV1.6−/−vas deferens myocytes, while veratridine elicited both the sustained and tail currents in cells taken from NaV1.6+/+mice.

Conclusions and implications: These results suggest that veratridine possesses a dual action on INaand that the veratridine‐induced activation of contraction is induced by the activation of NaV1.6 channels.
Integrative Medicine: Incorporating Medicine and Health into the Canon of Medieval European History
Authors: Green Monica H.
Published: June 2009

Hitherto peripheral (if not outright ignored) in general medieval historiography, medieval medical history is now a vibrant subdiscipline, one that is rightly attracting more and more attention from ‘mainstream’ historians and other students of cultural history. It does, however, have its particular characteristics, and understanding its source materials, methods, and analytical limitations may help those not trained in the field better navigate, explore and potentially contribute to its possibilities for illuminating the intersections of medicine and health with other aspects of medieval culture. Although this article focuses primarily on western Europe, many of its observations are also relevant to the Islamic world and Byzantium precisely because all three cultures shared many of the same intellectual traditions and social structures. The attached bibliography serves as a general introduction to the current state of the field.
Onshore record of Hudson River drainage to the continental shelf from the late Miocene through the late Wisconsinan deglaciation, USA: synthesis and revision
Authors: STANFORD SCOTT D.
Published: June 2009

Stanford, S. D. 2009: Onshore record of Hudson River drainage to the continental shelf from the late Miocene through the late Wisconsinan deglaciation, USA: synthesis and revision. Boreas, 10.1111/j.1502‐3885.2009.00106.x. ISSN 0300‐9483.

Fluvial and glacial deposits in New Jersey, Long Island, and the Hudson valley provide a record of Hudson River drainage since the late Miocene. Late Miocene fluvial deposits record southerly flow across the emerged inner New Jersey shelf. In the late Miocene–early Pliocene this drainage incised, shifted southwesterly, and discharged to the shelf south of New Jersey. During late Pliocene or Early Pleistocene glaciation, discharge to the shelf in the New York City area was established. This drainage incised and stabilized in the Early and Middle Pleistocene and remained open during pre‐Wisconsinan (Oxygen Isotope Stage 6? (OIS‐6?)) and late Wisconsinan (OIS‐2) glacial advances. During late Wisconsinan retreat, moraine deposits dammed the valley at the Narrows to form Lake Albany. From 19 to 15.5 kyr BP (all dates in 14C yr), Hudson drainage was directed eastward into the Long Island Sound lowland. Drainage of Lake Wallkill into Lake Albany at 15.5 kyr BP breached the Narrows dam and initiated the unstable phase of Lake Albany, which was controlled by eroding spillways, first on the moraine dam, then on emerged lake‐bottom in the mid‐Hudson valley. Marine incursion between 12 and 11 kyr BP limited fluvial incision of the lake bottom, stabilizing the Quaker Springs, Coveville, and upper Fort Ann spillways. Lowering sea level between 11 and 10 kyr BP allowed incision from the upper to lower Fort Ann threshold. Sediment eroded by lake outflows between 15 and 10.5 kyr BP was trapped in the glacially deepened lower valley. Little inland sediment reached the shelf after 20 kyr BP.
Schmidt hammer exposure‐age dating: developing linear age‐calibration curves using Holocene bedrock surfaces from the Jotunheimen–Jostedalsbreen regions of southern Norway
Authors: MATTHEWS JOHN A. , OWEN GERAINT
Published: June 2009

Matthews, J. A. & Owen, G. 2009: Schmidt hammer exposure‐age dating: developing linear age‐calibration curves using Holocene bedrock surfaces from the Jotunheimen–Jostedalsbreen regions of southern Norway. Boreas, 10.1111/j.1502‐3885.2009.00107.x. ISSN 0300‐9483.

The approach to calibrated‐age dating of rock surfaces using Schmidt hammer R‐values is developed, potential errors in dating Holocene rock surfaces are estimated and limitations are assessed. Multiple sites from glacially abraded bedrock outcrops of two ages (glacier forelands deglaciated for c. 100 years and adjacent late‐Preboreal terrain deglaciated for c. 9700 years) are used to analyse the variability of mean R‐values and to construct linear age‐calibration curves for three sub‐regions in the Jotunheimen–Jostedalsbreen regions of southern Norway. Conservative potential dating errors of 246–632 years are estimated using 95% confidence intervals associated with two control points, the width of the error limits being significantly greater for the Preboreal surfaces than for the younger Little Ice Age surfaces. Substantial improvements over previous age calibrations are largely attributable to the use of multiple sites as part of a research design that has effectively controlled for geological differences between the three sub‐regions. In the context of the Holocene time scale, the technique is seen as complementary to cosmogenic‐nuclide dating (which currently has lower precision) and lichenometric dating (which has a lower temporal range).
Overestimation of Fire Risk in the Northern Spotted Owl Recovery Plan
Authors: HANSON CHAD T. , ODION DENNIS C. , DELLASALA DOMINICK A. , BAKER WILLIAM L.
Published: June 2009

Abstract:  The U.S. Fish and Wildlife Service's recent recovery plan for one of the most carefully watched threatened species worldwide, the Northern Spotted Owl (Strix occidentalis caurina), recommended a major departure in conservation strategies in the northwestern United States. Due to concern about fire, the plan would switch from a reserve to a no‐reserve strategy in up to 52% of the owl's range. Fuel treatments (e.g., thinning) at regular intervals also would occur on up to 65–70% of dry forests in this area. Estimations of fire risk, however, were based on less than a decade of data and an anecdotal assessment of a single, large fire. We found that decadal data are inherently too short, given infrequent large fires, to accurately predict fire risk and trends. Rates of high‐severity fire, based on remote‐sensing data, are far lower than reported in the plan and in comparison with the rate of old‐forest recruitment. In addition, over a 22‐year period, there has been no increase in the proportion of high‐severity fire. Our findings refute the key conclusions of the plan that are the basis for major changes in conservation strategies for the Spotted Owl. The best available science is needed to address these strategies in an adaptive‐management framework. From the standpoint of fire risk, there appears to be ample time for research on fire and proposed treatment effects on Spotted Owls before designing extensive management actions or eliminating reserves.
Parameter Estimation and Actuator Characteristics of Hybrid Magnetic Bearings for Axial Flow Blood Pump Applications
Authors: Lim Tau Meng , Cheng Shanbao , Chua Leok Poh
Published: June 2009

Axial flow blood pumps are generally smaller as compared to centrifugal pumps. This is very beneficial because they can provide better anatomical fit in the chest cavity, as well as lower the risk of infection. This article discusses the design, levitated responses, and parameter estimation of the dynamic characteristics of a compact hybrid magnetic bearing (HMB) system for axial flow blood pump applications. The rotor/impeller of the pump is driven by a three‐phase permanent magnet brushless and sensorless motor. It is levitated by two HMBs at both ends in five degree of freedom with proportional–integral–derivative controllers, among which four radial directions are actively controlled and one axial direction is passively controlled. The frequency domain parameter estimation technique with statistical analysis is adopted to validate the stiffness and damping coefficients of the HMB system. A specially designed test rig facilitated the estimation of the bearing's coefficients in air—in both the radial and axial directions. Experimental estimation showed that the dynamic characteristics of the HMB system are dominated by the frequency‐dependent stiffness coefficients. By injecting a multifrequency excitation force signal onto the rotor through the HMBs, it is noticed in the experimental results the maximum displacement linear operating range is 20% of the static eccentricity with respect to the rotor and stator gap clearance. The actuator gain was also successfully calibrated and may potentially extend the parameter estimation technique developed in the study of identification and monitoring of the pump's dynamic properties under normal operating conditions with fluid.
Biocompatibility Assessment of Peritoneal Dialysis Solutions With a New In Vitro Model of Preconditioned Human HL60 Cells
Authors: Koball Sebastian , Korten Gero , Stange Jan , Schmidt Reinhard , Mitzner Steffen
Published: June 2009

The purposes of this study were to test the human promyelocytic cell line HL60 for its usability as a new cell model for the immune barrier of the peritoneum, and to investigate the impact of different peritoneal dialysis (PD) solutions in the model. HL60 cells were stimulated by retinoic acid and recombinant human granulocyte and macrophage colony‐stimulating factor to differentiate into neutrophilic granulocytes. Cells were incubated in different commercially available PD solutions. After a 4‐h incubation, functional (chemiluminescence phagocytosis) and viability tests (Live‐Dead, XTT) were performed. High glucose concentrations (>1.36%) and low pH values (<7.0) appeared to be detrimental for neutrophil functions and for neutrophil viability. There is a quantitative correlation between glucose concentration and the cytotoxicity of standard PD solutions (PD 1.36% glucose shows 42.6% higher chemiluminescence than PD 3.86% glucose [P < 0.05]). PD solution containing icodextrin shows 74.3% higher chemiluminescence than PD 3.86% glucose, and PD solution with amino acids shows 52.4% higher chemiluminescence than PD 3.86% glucose which is a sign for better biocompatibility in these tests (P < 0.05). The test system is useful for biocompatibility investigations of PD solutions and their effect on immune cells, for example, neutrophil granulocytes. It does not depend on donor variability and availability in comparison to models based on primary isolated leukocytes.
Lobar Torsion After Lung Transplantation—A Case Report and Review of the Literature
Authors: Shakoor Hasan , Murthy Sudish , Mason David , Johnston Douglas , Shah Sonia S. , Carrillo Maria C. , Mehta Atul C.
Published: June 2009

Lobar torsion is a rare complication following lung transplantation. Early detection and immediate therapeutic intervention can lead to a favorable outcome. We report an unusual case of left lingular torsion following single lung transplantation performed for idiopathic pulmonary fibrosis. The patient experienced severe ventilatory compromise immediately after leaving the operating room, and a chest X‐ray revealed a well‐demarcated area of consolidation involving the left mid‐ and lower lung zones. Lingular torsion was promptly diagnosed and corrected surgically. The possibility of acute lobar torsion should be considered in lung transplant recipients who experience acute respiratory compromise in the early postoperative period. Early diagnosis and correction can avoid pulmonary infarction and the need for lobar resection.
Human Clinical Fitting Study of the DexAide Right Ventricular Assist Device
Authors: Ootaki Yoshio , Ootaki Chiyo , Massiello Alex , Horvath David , Chen Ji‐Feng , Mihaljevic Tomislav , Navia Jose L. , Smedira Nicholas G. , Golding Leonard A.R. , Fukamachi Kiyotaka
Published: June 2009

The DexAide right ventricular assist device (RVAD) has been developed as an implantable RVAD. The purpose of this study was to determine the final design and optimal anatomical placement of the DexAide RVAD when implanted simultaneously with either of two commercially available left ventricular assist devices (LVADs) in patients. A mock‐up DexAide RVAD was used to assess configuration with each of two types of commercially available LVADs at the time of LVAD implantation in three human clinical cases. The pump body of the DexAide RVAD was placed either in the preperitoneal space or in the right thoracic cavity. The DexAide RVAD placed into the right thoracic cavity is suitable for use with the Novacor or HeartMate II LVADs. The results of this study will guide the finalization of the inflow cannula and optimal placement of the DexAide RVAD for human clinical trials.
An In Vivo Autotransplant Model of Renal Preservation: Cold Storage Versus Machine Perfusion in the Prevention of Ischemia/Reperfusion Injury
Authors: La Manna Gaetano , Conte Diletta , Cappuccilli Maria Laura , Nardo Bruno , D'Addio Francesca , Puviani Lorenza , Comai Giorgia , Bianchi Francesca , Bertelli Riccardo , Lanci Nicole , Donati Gabriele , Scolari Maria Piera , Faenza Alessandro , Stefoni Sergio
Published: June 2009

There is increasing proof that organ preservation by machine perfusion is able to limit ischemia/reperfusion injury in kidney transplantation. This study was designed to compare the efficiency in hypothermic organ preservation by machine perfusion or cold storage in an animal model of kidney autotransplantation.

Twelve pigs underwent left nephrectomy after warm ischemic time; the organs were preserved in machine perfusion (n = 6) or cold storage (n = 6) and then autotransplanted with immediate contralateral nephrectomy. The following parameters were compared between the two groups of animals: hematological and urine indexes of renal function, blood/gas analysis values, histological features, tissue adenosine‐5′‐triphosphate (ATP) content, perforin gene expression in kidney biopsies, and organ weight changes were compared before and after preservation.

The amount of cellular ATP was significantly higher in organs preserved by machine perfusion; moreover, the study of apoptosis induction revealed an enhanced perforin expression in the kidneys, which underwent simple hypothermic preservation compared to the machine‐preserved ones. Organ weight was significantly decreased after cold storage, but it remained quite stable for machine‐perfused kidneys.

The present model seems to suggest that organ preservation by hypothermic machine perfusion is able to better control cellular impairment in comparison with cold storage.
Migrainous Vertigo Responsive to Intravenous Methylprednisolone: Case Reports
Authors: Prakash Sanjay , Shah Nilima D.
Published: June 2009

Migrainous vertigo (MV) is a newer evolving concept in which vertigo is causally related to migraine. We report 4 patients with MV. Episodes of severe MV of more than 1‐day duration were successfully terminated by intravenous methylprednisolone (IV MPS) in 2 patients. Two other patients who had attacks of MV almost daily also showed complete response to IV MPS.
Recurrent Coital Headache Associated With an Unruptured Carotid Saccular Aneurysm
Authors: Uterga Juan M. , De Garay Miguel A. Gonzalez , De Luna Itziar Ortiz , Uribarri Juan B.
Published: June 2009

We report the case of a 48‐year‐old woman whose recurrent coital headache ceased following intracranial internal carotid artery aneurysm embolization.
Seizure frequency and sex steroids in women with partial epilepsy on antiepileptic therapy
Authors: Murialdo Giovanni , Magri Flavia , Tamagno Gianluca , Ameri Pietro , Camera Antonella , Colnaghi Silvia , Perucca Piero , Ravera Giambattista , Galimberti Carlo Andrea
Published: June 2009

Purpose:  Neuroactive sex steroids influence neuron excitability, which is enhanced by estradiol (E2) and decreased by progesterone (Pg). In epilepsy, the production, metabolism, biologic availability, and activity of sex hormones may be affected by seizures themselves or by antiepileptic drugs (AEDs). This cross‐sectional observational study was aimed at evaluating the relationships between sex steroids, seizure frequency, and other clinical parameters in women with partial epilepsy (PE) on AED treatments.

Methods:  Serum E2, Pg, sex hormone binding globulin (SHBG) levels, free E2 (fE2), and E2/Pg ratios were determined during the follicular and luteal phases in 72 adult women with PE, and in 30 healthy controls. Hormonal data were correlated with seizure frequency, age, body weight, body mass index (BMI), disease onset and duration, and AED therapies.

Results:  In patients, E2, fE2, and Pg levels were lower in both ovarian phases, whereas those of SHBG were higher than in controls. No significant changes in hormone levels and in prevalence of anovulatory cycles were observed between patients grouped according to their seizure frequency. However, when compared with those in healthy controls, luteal fE2 and Pg levels were chiefly impaired in women with more frequent seizures, mostly undergoing AED polytherapies, but not in those with absent or rarer seizures.

Conclusions:  The actual changes in sex steroid levels and E2/Pg ratios did not explain an increased seizure frequency in adult women with AED‐treated PE, but patients with more severe disease showed more relevant changes in their sex hormone profile and impaired Pg levels during the luteal phase.
Stiripentol open study in Japanese patients with Dravet syndrome
Authors: Inoue Yushi , Ohtsuka Yoko , Oguni Hirokazu , Tohyama Jun , Baba Hiroshi , Fukushima Katsuyuki , Ohtani Hideyuki , Takahashi Yukitoshi , Ikeda Shunya
Published: June 2009

Purpose:  To survey the treatment situation of Dravet syndrome in Japan and to compare this result with effectiveness of stiripentol (STP) add‐on therapy in an open‐label multicenter study.

Methods:  Medical records of patients with Dravet syndrome who visited the study institutions during 2006 were surveyed to examine the effect of antiepileptic drugs (AEDs) on clonic or tonic–clonic seizures (GTCS). Patients older than 1 year of age treated with at least one conventional AED and more than four GTCS per month were invited to participate in the STP study. Seizure status and adverse effects during the first 4 weeks of STP (50 or 1,000 mg/day) add‐on therapy (early period) and during long‐term treatment were compared with baseline.

Results:  Only 15% of the treatment trials with 15 conventional AEDs in 112 patients succeeded in reducing seizures by more than 50%. With STP, GTCS were reduced more than 50% in 14 of 23 patients (61%), including 2 who became seizure‐free, in the early period. Moreover, duration of seizures was shortened in 10 patients and status epilepticus decreased in 6. These effects continued in the long‐term although to a lesser degree. Adverse effects (loss of appetite, sleep disturbance, ataxia, hyperactivity/irritability) disappeared after dose modification in most cases. STP was effective at a lower than initial dose in five patients. Some patients benefited from STP added on clobazam despite mutation in CYP2C19.

Conclusion:  Our data suggest that an early introduction of STP into Japan will result in substantial patient benefit.
Structures involved at the time of temporal lobe spikes revealed by interindividual group analysis of EEG/fMRI data
Authors: Kobayashi Eliane , Grova Christophe , Tyvaert Louise , Dubeau François , Gotman Jean
Published: June 2009

Purpose:  We measured metabolic changes associated with temporal lobe (TL) spikes using combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). We selected 18 patients with temporal lobe epilepsy (TLE) who underwent a 2‐h simultaneous EEG–fMRI and had unilateral or bilateral independent TL spikes for interindividual group analysis, in order to identify consistent blood oxygenation level dependent (BOLD) responses to TL spikes.

Methods:  EEG was postprocessed and spikes were visually identified. fMRI data were preprocessed with motion correction, spatial smoothing, and removal of low frequency drifts. Spike timings were used as events for fMRI statistical analysis. Four hemodynamic response functions were used to account for variability in the BOLD response.

Results:  Group analysis revealed common areas of BOLD activations and deactivations. The hemodynamic response function (HRF) peaking 3 s after the spike showed activation involving ipsilaterally the mesial temporal structures (presumably the hippocampus), putamen/globus pallidus, inferior insula, and superior temporal gyrus. The HRF peaking at 5 s showed activations involving ipsi‐ and contralaterally the superior temporal gyrus and inferior insula. Both HRFs showed bilateral posterior cingulate deactivations.

Discussion:  We disclosed involvement of a network of activated areas during unilateral TL spikes, including ipsilateral mesial temporal structures, basal ganglia, and bilateral neocortical temporal regions. Despite the low temporal resolution of fMRI we demonstrated that contralateral temporal involvement occurred later than ipsilateral activation. This contralateral change took place in the absence of visible EEG changes. The posterior cingulate deactivation may reflect the interconnections between this region and other limbic structures. It may also partially correspond to a suspension of the default mode network, as previously described for TL spikes.
Drug resistant ADLTE and recurrent partial status epilepticus with dysphasic features in a family with a novel LGI1mutation: electroclinical, genetic, and EEG/fMRI findings
Authors: Bonaventura Carlo Di , Carni Marco , Diani Erica , Fattouch Jinane , Vaudano Elisabetta A. , Egeo Gabriella , Pantano Patrizia , Maraviglia Bruno , Bozzao Luigi , Manfredi Mario , Prencipe Massimiliano , Giallonardo Teresa A. , Nobile Carlo
Published: June 2009

Purpose:  We characterized a family with autosomal dominant lateral temporal epilepsy (ADLTE) whose proband presented uncommon electroclinical findings such as drug‐resistant seizures and recurrent episodes of status epilepticus with dysphasic features.

Methods:  The electroclinical characteristics and LGI1 genotype were defined in the family. In the proband, the ictal pattern was documented during video‐EEG monitoring and epileptic activity was mapped by EEG/fMRI.

Results:  The affected members who were studied had drug‐resistant seizures. In the proband, seizures with predominant dysphasic features often occurred as partial status epilepticus. The video‐EEG‐documented ictal activity and fMRI activation clearly indicated the elective involvement of the left posterior lateral temporal cortex. Sequencing of LGI1 exons revealed a heterozygous c.367G>A mutation in exon 4, resulting in a Glu123Lys substitution in the protein sequence.

Conclusions:  The uncommon clinical pattern (high seizure frequency, drug‐resistance) highlights the variability of the ADLTE phenotype and extends our knowledge of the clinical spectrum associated with LGI1 mutations.
The Emergency of Climate Change: Why Are We Failing to Take Action?
Authors: Frantz Cynthia M. , Mayer F. Stephan
Published: June 2009

Latane and Darley developed a five‐stage model to understand why people do and do not help other people in emergency situations. We extend their five‐stage model to explore why people do and do not take action against climate change. We identify the factors that make climate change difficult to notice and ambiguous as an emergency; we explore barriers to taking responsibility for action; and we discuss the issues of efficacy and costs versus benefits that make action unlikely. The resulting analysis is useful on two levels. For educators and policy makers, the model suggests the most efficacious approaches to galvanizing action among U.S. citizens. For social scientists, the model provides a valuable framework for integrating research from diverse areas of psychology and suggests fruitful avenues for future empirical research.
Thirteen Dimensions of Health in Elderly Sri Lankans: Results from a National Sri Lanka Aging Survey
Authors: Østbye Truls , Malhotra Rahul , Chan Angelique
Published: June 2009

OBJECTIVES: To explore age and sex differences in distribution of 13 health dimensions with a focus on self‐rated health (SRH) and the association between SRH and other health dimensions in elderly Sri Lankans.

DESIGN: Sri Lanka Aging Survey, a nationally representative cross‐sectional survey.

SETTING: Community based.

PARTICIPANTS: Inhabitants of 13 districts in Sri Lanka aged 60 and older (N=2,413).

MEASUREMENTS: Self‐reported SRH, hearing, activities of daily living (ADLs), instrumental activities of daily living (IADLs), mobility, physical disability, chronic diseases, stress and worry, mood, cognition, social participation, social support, and financial health.

RESULTS: The prevalence of being “healthy” in most health dimensions, including SRH, declined with age. Men were more likely to report better SRH; independence in ADLs, IADLs, and mobility; absence of physical disability and chronic diseases; and good mental health. Absence of chronic diseases, independence in ADLs and IADLs, freedom from stress and worry, and absence of depression were associated with positive (excellent/very good/good) SRH. The male SRH advantage was not significant in adjusted analyses, and sex did not modify the association between SRH and other health dimensions.

CONCLUSION: Several of the dimensions associated with positive SRH are to a certain extent modifiable and therefore provide a potential for improvement in SRH of elderly Sri Lankans. Differences between this study and studies from elsewhere in the associations between different health dimensions and SRH, and in how sex modifies these associations, suggest that some of the associations may depend on cultural context.
Computerized Decision Support to Reduce Potentially Inappropriate Prescribing to Older Emergency Department Patients: A Randomized, Controlled Trial
Authors: Terrell Kevin M. , Perkins Anthony J. , Dexter Paul R. , Hui Siu L. , Callahan Christopher M. , Miller Douglas K.
Published: June 2009

OBJECTIVES: To evaluate the effectiveness of computer‐assisted decision support in reducing potentially inappropriate prescribing to older adults.

DESIGN: Randomized, controlled trial.

SETTING: An academic emergency department (ED) in Indianapolis, Indiana, where computerized physican order entry was used to write all medication prescriptions.

PARTICIPANTS: Sixty‐three emergency physicians were randomized to the intervention (32 physicians) or control (31 physicians) group.

INTERVENTION: Decision support that advised against use of nine potentially inappropriate medications and recommended safer substitute therapies.

MEASUREMENTS: The primary outcome was the proportion of ED visits by seniors that resulted in one or more prescriptions for an inappropriate medication. The main secondary outcomes were the proportions of medications prescribed that were inappropriate and intervention physicians' reasons for rejecting the decision support.

RESULTS: The average age of the patients was 74, two‐thirds were female, and just over half were African American. Decision support was provided 114 times to intervention physicians, who accepted 49 (43%) of the recommendations. Intervention physicians prescribed one or more inappropriate medications during 2.6% of ED visits by seniors, compared with 3.9% of visits managed by control physicians (P=.02; odds ratio=0.55, 95% confidence interval=0.34–0.89). The proportion of all prescribed medications that were inappropriate significantly decreased from 5.4% to 3.4%. The most common reason for rejecting decision support was that the patient had no prior problems with the medication.

CONCLUSION: Computerized physican order entry with decision support significantly reduced prescribing of potentially inappropriate medications for seniors. This approach might be used in other efforts to improve ED care.Trial Registration: Clinical trials.gov Identifier: NCT00297869.
Prospective Study of Serum 25‐Hydroxyvitamin D Level, Cardiovascular Disease Mortality, and All‐Cause Mortality in Older U.S. Adults
Authors: Ginde Adit A. , Scragg Robert , Schwartz Robert S. , Camargo Carlos A.
Published: June 2009

OBJECTIVES: To evaluate the association between serum 25‐hydroxyvitamin D (25(OH)D) levels and mortality in a representative U.S. sample of older adults.

DESIGN: Prospective cohort from the Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality files.

SETTING: Noninstitutionalized U.S. civilian population.

PARTICIPANTS: Three thousand four hundred eight NHANES III participants aged 65 and older enrolled from 1988 to 1994 and followed for mortality through 2000.

MEASUREMENTS: Primary exposure was serum 25(OH)D level at enrollment. Primary and secondary outcomes were all‐cause and cardiovascular disease (CVD) mortality, respectively.

RESULTS: During the median 7.3 years of follow‐up, there were 1,493 (44%) deaths, including 767 CVD‐related deaths. Median 25(OH)D level was 66 nmol/L. Adjusting for demographics, season, and cardiovascular risk factors, baseline 25(OH)D levels were inversely associated with all‐cause mortality risk (adjusted hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92–0.98, per 10 nmol/L 25[OH]D). Compared with subjects with 25(OH)D levels of 100 nmol/L or higher, the adjusted HR for subjects with levels less than 25.0 nmol/L was 1.83 (95% CI=1.14–2.94) and for levels of 25.0 to 49.9 nmol/L was 1.47 (95% CI=1.09–1.97). The association appeared stronger for CVD mortality (adjusted HR=2.36, 95% CI=1.17–4.75, for subjects with 25[OH]D levels<25.0 nmol/L vs those ≥100.0 nmol/L) than for non‐CVD mortality (adjusted HR=1.42, 95% CI=0.73–2.79, for subjects with 25[OH]D levels<25.0 nmol/L vs those ≥100.0 nmol/L).

CONCLUSION: In noninstitutionalized older adults, a group at high risk for all‐cause mortality, serum 25(OH)D levels had an independent, inverse association with CVD and all‐cause mortality. Randomized controlled trials of vitamin D supplementation in older adults are warranted to determine whether this association is causal and reversible.
Effect of Fish Oil Supplementation on Quality of Life in a General Population of Older Dutch Subjects: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Van De Rest Ondine , Geleijnse Johanna M. , Kok Frans J. , Van Staveren Wija A. , OldeRikkert Marcel G.M. , Beekman Aartjan T.F. , De Groot Lisette C.P.G.M.
Published: June 2009

OBJECTIVES: To investigate the effect of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation on quality of life (QOL).

DESIGN: Randomized, double‐blind, placebo‐controlled trial.

SETTING: Independently living individuals from the general older Dutch population.

PARTICIPANTS: Three hundred two individuals aged 65 and older without depression or dementia.

INTERVENTION: 1,800 mg/d EPA‐DHA (n=96), 400 mg/d EPA‐DHA (n=100), or placebo capsules (n=106) for 26 weeks.

MEASUREMENTS: QOL was assessed using the short version of the World Health Organization QOL questionnaire (WHOQOL‐BREF). The WHOQOL‐BREF covers four domains: physical health, psychological health, social relationships, and satisfaction with environment. The total score range is 26 to 130, with higher scores indicating a more favorable condition.

RESULTS: Mean age of the participants was 70, and 55% were male. Plasma concentrations of EPA‐DHA increased 238% in the high‐dose and 51% in the low‐dose EPA‐DHA group, reflecting excellent adherence. Median baseline total WHOQOL scores ranged from 107 to 110 in the three groups and were not significantly different from each other. After 26 weeks, the mean difference from placebo was −1.42 (95% confidence interval (CI)=−3.40–0.57) for the high‐dose and 0.02 (95% CI=−1.95–1.99) for the low‐dose fish oil group. Treatment with 1,800 mg or 400 mg EPA‐DHA did not affect total QOL or any of the separate domains after 13 or 26 weeks of intervention.

CONCLUSION: Supplementation with high or low doses of fish oil for 26 weeks did not influence the QOL of healthy older individuals.
Identifying Star Performers: The Relationship Between Ambitious Targets and Nursing Home Quality Improvement
Authors: Baier Rosa , Butterfield Kristen , Patry Gail , Harris Yael , Gravenstein Stefan
Published: June 2009

Setting Targets—Achieving Results (STAR) is a Web‐based tool that helps nursing home leadership select annual performance goals, or targets, for a subset of publicly reported quality measures. Previous results demonstrate that nursing homes whose staff implement STAR targets demonstrate greater improvement on the related outcomes. In this analysis, the authors hypothesized that nursing homes whose staff select the most ambitious targets (reflecting large improvement over their current performance) may be more successful in their related quality improvement efforts than homes with less‐ambitious targets (reflecting lesser improvement). The authors analyzed data from 7,091 Medicare‐ or Medicaid‐certified nursing homes that set STAR targets in 2005 or 2006 for two quality measures: the proportion of residents who were physically restrained daily and the proportion of high‐risk residents with pressure ulcers. Targets were classified as ambitious or less ambitious based on the 75th and 50th rank‐ordered percentiles, respectively. Improvement was calculated using four‐quarter averages for baseline (the year ending when the target was set) and remeasurement (the subsequent year). The results indicate that nursing homes with ambitious targets demonstrate greater improvement than their peers selecting less‐ambitious targets. With limited federal and local resources to assist providers with quality improvement, target values may be a used as a “flag” to help agencies allocate scarce resources to nursing homes committed to quality improvement efforts and with the organizational capacity to improve.