bluuebunny/crossref_metadata_2025_split huggingface dataset:
The melanocortin MC1 receptor agonist BMS‐470539 inhibits leucocyte trafficking in the inflamed vasculature
Authors: Leoni G , Voisin M‐B , Carlson K , Getting SJ , Nourshargh S , Perretti M 
Published: March 2010

Background and purpose:  Over three decades of research evaluating the biology of melanocortin (MC) hormones and synthetic peptides, activation of the MC type 1 (MC1) receptor has been identified as a viable target for the development of novel anti‐inflammatory therapeutic agents. Here, we have tested a recently described selective agonist of MC1 receptors, BMS‐470539, on leucocyte/post‐capillary venule interactions in murine microvascular beds.Experimental approach:  Intravital microscopy of two murine microcirculations were utilized, applying two distinct modes of promoting inflammation. The specificity of the effects of BMS‐470539 was assessed using mice bearing mutant inactive MC1 receptors (the recessive yellow e/e colony).Key results:  BMS‐470539, given before an ischaemia–reperfusion protocol, inhibited cell adhesion and emigration with no effect on cell rolling, as assessed 90 min into the reperfusion phase. These properties were paralleled by inhibition of tissue expression of both CXCL1 and CCL2. Confocal investigations of inflamed post‐capillary venules revealed immunostaining for MC1 receptors on adherent and emigrated leucocytes. Congruently, the anti‐inflammatory properties of BMS‐470539 were lost in mesenteries of mice bearing the inactive mutant MC1 receptors. Therapeutic administration of BMS‐470539 stopped cell emigration, but did not affect cell adhesion in the cremasteric microcirculation inflamed by superfusion with platelet‐activating factor.Conclusions and implications:  Activation of MC1 receptors inhibited leucocyte adhesion and emigration. Development of new chemical entities directed at MC1 receptors could be a viable approach in the development of novel anti‐inflammatory therapeutic agents with potential application to post‐ischaemic conditions.
AE9C90CB: a novel, bladder‐selective muscarinic receptor antagonist for the treatment of overactive bladder
Authors: Sinha S , Gupta S , Malhotra S , Krishna NS , Meru AV , Babu V , Bansal V , Garg M , Kumar N , Chugh A , Ray A 
Published: March 2010

Background and purpose: AE9C90CB (N‐ [(1R, 5S, 6R)‐3‐azabicyclo [3.1.0] hex‐6‐ylmethyl]‐2‐hydroxy‐N‐methyl‐2, 2‐diphenylacetamide), a novel muscarinic receptor antagonist, was synthesized for the treatment of overactive bladder. Here we describe thein vitroandin vivoprofiles of AE9C90CB for action in bladder over salivary gland and compare it with four agents already in clinical use (tolterodine, oxybutynin, solifenacin and darifenacin).Experimental approach: Radioligand binding assay and isolated tissue‐based functional assay were used to evaluate affinity, potency, and receptor subtype selectivity of compounds. Inhibition of carbachol‐induced increase in intravesicular pressure and salivary secretion were measured in anaesthetized rabbits to assess the functional selectivity.Key results: In vitroradioligand binding study using human recombinant muscarinic receptors showed that AE9C90CB had greater affinity for M3muscarinic receptors with pKi of 9.90 ± 0.11 and was 20‐fold more selective for M3than for M2muscarinic receptors. AE9C90CB exhibited an unsurmountable antagonism on rat bladder strips (pKB, 9.13 ± 0.12). In anaesthetized rabbits after intravenous administration, AE9C90CB dose dependently inhibited carbachol‐induced increase in intravesicular pressure and salivary secretion, and exhibited functional selectivity for urinary bladder over salivary gland which was ninefold better than that of oxybutynin.Conclusions and implications: We have identified AE9C90CB, a compound exhibiting moderate selectivity for M3over M2receptors but greater selectivity for urinary bladder over salivary gland than oxybutynin, tolterodine, solifenacin and darifenacin. Therefore, AE9C90CB may be a promising compound for the treatment of overactive bladder with reduced potential to cause dry mouth than currently available antimuscarinic drugs.
Anti‐adhesive Membrane for Pleural Cavity
Authors: Noishiki Yasuharu , Shintani Noriyuki 
Published: March 2010

AbstractAn anti‐adhesive membrane containing a large amount of glycerin was developed for lung surgery and was tested in the pleural cavity of six dogs. The test membranes were put between the lung and the chest wound of the pleural cavity wall to separate them. In five of the animals, no adhesion was observed after 3 weeks in the area where the membrane had been inserted, but the area without the membrane showed firm adhesion between the lung and the pleural cavity wall. A sixth animal observed for 3 months also showed no adhesion. Seprafilm, which is the product of choice for peritoneal surgeries, was used as a control in six dogs. Seprafilm could not prevent adhesion in the pleural cavity of all six animals after 3 weeks observation. The new test membrane contained glycerin, which gathered and dispersed abundant water. Together with this, growth factors are also dispersed, resulting in dilution of excessive growth factors at the wound sites. In general, fibroblasts do not migrate in an extremely hydrous gel matrix. Migration of fibroblasts into the membrane is minimized, resulting in the prevention of formation of adhesion tissue composed of fibroblasts and collagen fibers. From the results, we assume that water can prevent adhesion after surgery.
Beating‐Heart Coronary Artery Bypass Grafting With Miniaturized Cardiopulmonary Bypass Results in a More Complete Revascularization When Compared to Off‐Pump Grafting
Authors: Reber Delawer , Brouwer René , Buchwald Dirk , Fritz Markus , Germing Alfried , Lindstaedt Michael , Klak Krzysztof , Laczkovics Axel 
Published: March 2010

AbstractThe technique of miniaturized cardiopulmonary bypass (M‐CPB) for beating‐heart coronary artery bypass grafting (CABG) is relatively new and has potential advantages when compared to conventional cardiopulmonary bypass (CPB). M‐CPB consists of less tubing length and requires less priming volume. The system is phosphorylcholine coated and results in minimal pump‐related inflammatory response and organ injury. Finally, this technique combines the advantages of the off‐pump CABG (OPCAB) with the better exposure provided by CPB to facilitate complete revascularization. The hypothesis is that CABG with M‐CPB has a better outcome in terms of complete coronary revascularization and perioperative results as that compared to off‐pump CABG (OPCAB). In a retrospective study, 302 patients underwent beating‐heart CABG, 117 (39%) of them with the use of M‐CPB and 185 (61%) with OPCAB. After propensity score matching 62 patients in both groups were demographically similar. The most important intra‐ and early‐postoperative parameters were analyzed. Endpoints were hospital mortality and complete revascularization. Hospital mortality was comparable between the groups. The revascularization was significantly more complete in M‐CPB patients than in patients in the OPCAB group. Beating‐heart CABG with M‐CPB is a safe procedure and it provides an optimal operative exposure with significantly more complete coronary revascularization when compared to OPCAB. Beating‐heart CABG with the support of a M‐CPB is the operation of choice when total coronary revascularization is needed.
Is It Possible to Create a “Mechanical” Arteriovenous Fistula in Hemodialysis Patients?
Authors: Lo Monte Attilio Ignazio , Buscemi Giuseppe 
Published: March 2010

AbstractManual suturing still remains the best technique for the creation of vascular anastomoses on uremic patients with excellent results, despite being time consuming, difficult to perform with small vessels, and associated with a significant learning curve. We created a full mechanical arteriovenous fistula on a 65‐year‐old uremic patient with a new device already used in cardiac bypass surgery. The fistula was created automatically and rapidly, without the need for temporary occlusion of the artery, reducing the risk of blood clotting. We believe that mechanical devices may be useful to produce precise and fast anastomoses requiring minimal training for the surgeon.
Recombinant Human Erythropoietin Treatment of Chronic Renal Failure Patients Normalizes Altered Phenotype and Proliferation of CD4‐positive T Lymphocytes
Authors: Lisowska Katarzyna A. , Debska‐Slizien Alicja , Radzka Monika , Witkowski Jacek M. , Rutkowski Boleslaw , Bryl Ewa 
Published: March 2010

AbstractPatients with chronic renal failure (CRF) receive recombinant human erythropoietin (rhEPO) for the correction of anemia. However, rhEPO also has an immunomodulatory effect. Detailed changes of phenotype and function of CD4+ T lymphocytes in CRF patients receiving rhEPO have not been reported yet; their study may bring insight into understanding of this immunomodulatory action of rhEPO. Two groups of CRF patients were included into the study: those treated; and those not receiving rhEPO. The expression of activation markers on CD4+ lymphocytes was measured with flow cytometry, both ex vivo and in vitro. The kinetics of CD4+ T lymphocytes proliferation was calculated using a dividing cells tracing method and numerical approach. Significantly higher percentages of CD4+CD95+, CD4+HLA‐DR+ cells, and lower percentages of CD4+CD69+ and CD4+CD28+ cells were observed in both rhEPO‐treated and untreated patients when compared with healthy controls. Changes in the proportions of CD4+CD28+ and CD4+HLA‐DR+ subpopulations were dependent on the type of rhEPO, being more pronounced for rhEPOβ. CD4+ lymphocytes from untreated patients exhibited decreased expression of CD28 and CD69 after stimulation in vitro, whereas the expression of these antigens on lymphocytes of rhEPO‐treated patients was similar to that observed in healthy controls. Fewer CD4+CD28+ T lymphocytes of untreated patients proliferated in vitro; these cells had longer G0→G1 time, which negatively correlated with surface expression of CD28. Our study confirms that rhEPO treatment normalizes activation parameters of CD4+ T lymphocytes and their proliferative capacity, which could explain earlier described immunomodulatory effects of rhEPO in patients suffering from CRF.
Propagation of Tears in Pericardium From Young Bulls: Influence of the Suture
Authors: García Páez José María , Jorge‐Herrero Eduardo , Claramunt Rafael , Millán Isabel , Rocha Aurora , Martínez Belén , Cordón Ángeles , Ros Antonio 
Published: March 2010

AbstractThe tearing of the collagen fibers of biological materials utilized in implants or bioprostheses is an important, and sometimes early cause of the failure of these devices. We studied the force necessary to propagate a tear in a biomaterial, pericardium from young bulls, and the influence of the suture. An Elmendorf pendulum capable of measuring the force necessary to tear a given length of tissue was employed. We analyzed 112 trials (70%) that proved valid after achieving the homogeneity of the samples according to their thickness, thus making the results comparable. Mean forces ranging between 19.87 and 150 N were required to propagate tears measuring from 0.25 to 2.0 cm. In the samples with a 1‐cm‐long suture, sewn using an edge‐to‐edge technique, the propagation of the tear required a mean force of 15.75 N when the suture was made of nylon and 28.73 N when Prolene was utilized. When these results were compared with the mean recorded in an unsutured control series (56.76 N), the loss of resistance was significant in both sutured series (P = 0.000 and P = 0.011, respectively). Finally, the equation that relates the force (y) with the length of the tear made in unsutured tissue (x) was also obtained: y = 58.14 + 9.62x2 (R2 = 0.924). The force necessary to produce a microtear, thus estimated, can be utilized as a parameter for comparison.
Aortic Valve Surgery in Congenital Heart Disease: A Single‐Center Experience
Authors: Coskun Kasim Oguz , Popov Aron Frederik , Tirilomis Theodor , Schmitto Jan Dieter , Coskun Sinan Tolga , Hinz Jose , Schoendube Friedrich Albert , Ruschewski Wolfgang 
Published: March 2010

AbstractThe optimal treatment of congenital aortic valve lesions is a controversial issue. This study was performed to evaluate the outcome after surgical treatment of aortic valve lesions in congenital aortic valve disease. Between the years of 2000 and 2008, 61 patients (mean age: 12.6 ± 9.6 years, range: 1 day to 40 years) underwent aortic valve surgery for congenital aortic valve disease. Twenty‐four patients had undergone previous cardiovascular operations. Indications for surgery were aortic regurgitation in 14.7% (n = 9), aortic stenoses in 26.2% (n = 16), and mixed disease in 59.1% (n = 36). The Ross procedure was performed in 37.7% (n = 23), aortic valve replacement with biological or mechanical prostheses in 29.5% (n = 18). Concomitant procedures were performed in 91.8% (n = 56) due to associated congenital cardiac defects. The overall mortality rate was 5%. Six patients needed reoperation. Implantation of permanent pacemakers occurred in six patients for permanent atrioventricular block. At the latest clinical evaluation, all survivors are in New York Heart Association class I–II and are living normal lives. Aortic valve surgeries in patients with congenital heart disease have had low mortality and morbidity rates in our series. Surgical technique as well as timing should be tailored for each patient. Aortic valve replacement should be delayed until the implantation of an adult‐sized prosthesis is possible.
Long‐term add‐on pregabalin treatment in patients with partial‐onset epilepsy: Pooled analysis of open‐label clinical trials
Authors: Uthman Basim M. , Bazil Carl W. , Beydoun Ahmad , Schulze‐Bonhage Andreas , Benabou Reina , Whalen Ed , Emir Birol , Griesing Teresa , Leon Teresa 
Published: March 2010

SummaryPurpose:  To evaluate the safety, tolerability, and efficacy of long‐term pregabalin as add‐on therapy for patients with poorly controlled partial seizures.Methods:  Analysis of data from six long‐term clinical trials involving 2,061 patients receiving open‐label pregabalin 75–600 mg/day adjunctive therapy for partial onset epilepsy refractory to multiple antiepileptic drugs.Results:  Total pregabalin exposure was 3,877 person‐years. The mean duration of pregabalin treatment was 534 days (range 0.3–8 years) and 59% completed 1 year. One‐third of patients discontinued for lack of efficacy. The most common dose was ≥300 mg/day; over half took ≥450 mg/day. There was a mean reduction in the 28‐day seizure rate of 25–40%, and more than 40% of all patients had a ≥50% reduction in seizures from baseline during the last 3 months of treatment. Twelve percent of all patients had a 6‐month period continuously free of seizures. In the last year, 6% were seizure‐free for the entire year. Pregabalin was generally well‐tolerated and the safety profile favorable in patients treated for up to several years, with an adverse event (AE) profile similar to short‐term placebo‐controlled trials. Common AEs included CNS symptoms (dizziness, somnolence, headache, and asthenia), accidental injury, and weight gain. CNS AEs tended to be mild and transient. Rates of sudden unexpected death in epilepsy (SUDEP), mortality, cancer, and status epilepticus were within the expected range for this population.Conclusions:  Adjunctive pregabalin was effective, generally well tolerated, and safe in the long‐term treatment of partial seizures, and provided clinically meaningful seizure reduction and freedom without evidence of tolerance over 2 years of follow‐up.
Infantile epileptic encephalopathy with late‐onset spasms: Report of 19 patients
Authors: Auvin Stéphane , Lamblin Marie‐Dominique , Pandit Florence , Vallée Louis , Bouvet‐Mourcia Agnès 
Published: March 2010

SummaryPurpose:  Late‐onset spasms (LOS) are epileptic spasms starting after the first year of life. Our aim was to assess the electroclinical features and the follow‐up of the patients with this particular type of epileptic seizure.Methods:  We retrospectively included all patients with LOS confirmed by electroencephalography between 1989 and 2008. Clinical and electroencephalographic findings at diagnosis and during follow‐up were collected. The Vineland scale was used to evaluate the neuropsychological outcome.Results:  We report 19 patients with LOS of 240 patients with recorded epileptic spasms. Eighteen patients had an epileptic encephalopathy with late‐onset spasms. The ictal electroencephalography (EEG) showed a focal or generalized discharge of triphasic slow‐waves, slow‐spikes, or slow spikes‐waves with fast activities. The interictal EEG usually showed focal or generalized slow‐waves or slow spikes‐waves without hypsarhythmia. LOS were controlled in only six patients. Three developed typical Lennox‐Gastaut syndrome and 10 had a severe epileptic encephalopathy. Neuropsychological outcome was evaluated in 15 patients with the Vineland scale. Cognitive functions were normal in only one patient, whereas severe cognitive delay was observed in 12 of 15.Conclusion:  Epileptic spasms may appear after the age of one. They are more frequently observed in patients with epileptic encephalopathy. In few patients this type of seizure was observed before the patients fulfill Lennox‐Gastaut syndrome criteria. In one patient, we diagnosed a focal epilepsy with seizures occurring in cluster. When LOS are related to an epileptic encephalopathy, this epileptic syndrome seems to be linked to refractory epilepsy and severe cognitive outcome unrelated to the etiology.
Febrile infection–related epilepsy syndrome (FIRES): A nonencephalitic encephalopathy in childhood
Authors: Van Baalen Andreas , Häusler Martin , Boor Rainer , Rohr Axel , Sperner Jürgen , Kurlemann Gerhard , Panzer Axel , Stephani Ulrich , Kluger Gerhard 
Published: March 2010

SummaryEncephalitis is generally presumed, even when seizures follow banal febrile infection, and pathogen detection in cerebrospinal fluid fails. This retrospective multicenter case series reports on 22 previously healthy children aged 3–15 years (median 6.5 years) with prolonged or recurrent seizures occurring 2–14 days (median 5 days) after fever onset (19 children with respiratory or nonspecific infections). Cerebrospinal fluid studies revealed 2–42 cells/μl (median 5 cells/μl) and no pathogens. Electroencephalography showed diffuse slowing or multifocal discharges. Neuroimaging demonstrated normal findings in 10 children. Brain biopsies were performed in seven children showing gliosis but no inflammation. Anesthetic barbiturates were used in 14 children with refractory status epilepticus, and immunotherapy in 9. Two children died, eight remained in a state of impaired consciousness, eight developed therapy‐refractory epilepsies, two had behavioral disturbances, and two recovered. The lack of evidence for encephalitis suggests another infection‐related pathogenesis of this disastrous epileptic encephalopathy. Therefore, we propose the term “febrile infection–related epilepsy syndrome” (FIRES).
Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy
Authors: Fisher Robert , Salanova Vicenta , Witt Thomas , Worth Robert , Henry Thomas , Gross Robert , Oommen Kalarickal , Osorio Ivan , Nazzaro Jules , Labar Douglas , Kaplitt Michael , Sperling Michael , Sandok Evan , Neal John , Handforth Adrian , Stern John , DeSalles Antonio , Chung Steve , Shetter Andrew , Bergen Donna , Bakay Roy , Henderson Jaimie , French Jacqueline , Baltuch Gordon , Rosenfeld William , Youkilis Andrew , Marks William , Garcia Paul , Barbaro Nicolas , Fountain Nathan , Bazil Carl , Goodman Robert , McKhann Guy , Babu Krishnamurthy K. , Papavassiliou Steven , Epstein Charles , Pollard John , Tonder Lisa , Grebin Joan , Coffey Robert , Graves Nina ,   the SANTE Study Group
Published: March 2010

SummaryPurpose:  We report a multicenter, double‐blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization‐related epilepsy.Methods:  Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3‐month blinded phase; then all received unblinded stimulation.Results:  One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and “most severe” seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure‐free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation‐associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events.Discussion:  Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.
Clinical features of seizures associated with parahippocampal/inferior temporal lesions compared to those with hippocampal sclerosis
Authors: Mirandola Laura , Badawy Radwa A. , Saunders Ann M. , McIntosh Anne , Berkovic Samuel F. , Jackson Graeme D. 
Published: March 2010

SummaryTemporal lobe epilepsy (TLE) is not a unitary electroclinical imaging syndrome. We asked if seizures arising from the parahippocampal‐inferior temporal (PIT) region differ from those associated with hippocampal sclerosis (HS). The electroclinical features of 22 patients with HS and 14 patients with lesions in the PIT region who underwent epilepsy surgery and were seizure free for at least 2 years postoperatively were analyzed retrospectively. Patients with PIT lesions had a higher frequency of hypermotor and bilateral features and a lower frequency of behavioral arrest at the onset of seizure compared to cases with HS, suggesting that TLE originating in the PIT area can mimic frontal lobe epilepsy or contralateral mesial TLE.
Surgery for medically intractable epilepsy due to postinfectious etiologies
Authors: Chandra P. S. , Bal Chandrashekar , Garg Ajay , Gaikwad Shailesh , Prasad Kameshwar , Sharma Bhawani S. , Sarkar Chitra , Singh M. B. , Padma Vasantha M. , Tripathi Manjari 
Published: March 2010

SummaryMedically intractable epilepsy (MIE) resulting from postinfectious etiologies requiring surgery have been uncommonly reported. A series of 28 cases are presented (hospital prevalence 5.7%). The mean duration of epilepsy prior to surgery was 8.2 ± 2.1 years. The mean time of onset of epilepsy after central nervous system infection was 1.4 ± 0.9 years (range 0–19 years). The pathologies included postpyogenic meningitic/encephalitic sequel (8), neurocysticercosis (6), tuberculomas/posttuberculous etiology (4), postpyogenic abscess of otogenic etiology (4), posttraumatic abscess–related gliosis (2), and gliosis of unknown infectious etiology (4) cases. Surgery included mesial temporal (11), lateral temporal (4), frontal (9), parietal (2) resections and hemispherotomy (1). Hippocampal sclerosis was seen in nine cases (4 neurocysticercosis) and this occurred in younger persons as compared to neocortical epilepsies. Good outcome (Engel class I and II) was seen in 23 of 28 cases (Engel class I in 17).