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Objective: To ascertain the clinical characteristics of anti-NMDA receptor encephalitis (NMDARE) in older patients. Method: A systematic literature review using PubMed and Scopus of all published case reports of NMDARE was undertaken, from database inception to June 2020. From this, cases reporting on patients older than 65 years of age and whose diagnosis was confirmed by the presence of anti-NMDAR antibodies in CSF were selected. Results: 23 case reports fulfilling the study's criteria were found. Median age was 70.1 years (range 65-84), fourteen were female (60.9%), and mostly presented with acute behavioral and cognitive changes (95.7%). Atypical psychosis occurred in eleven patients (47.8%) with a sudden onset and fluctuating clinical pattern of delusions (39.1%), hallucinations (30.4%), and motility disturbances (34.8%) including catatonia (17.4%). Nine patients presented with seizures (39.1%). Pleocytosis in CSF (>5 WBC) was described in twelve cases (52.2%). Eleven cases (47.8%) had abnormal brain magnetic resonance imaging (MRI) scans with limbic inflammatory lesions. Thirteen patients had an abnormal EEG (56.5%). Conclusion: NMDARE should be included in the differential diagnosis of older patients who present with new psychiatric episodes, especially when characterized by sudden onset psychotic polymorphic symptomatology, fluctuating course with marked cognitive decline, and with catatonic features.

Aims Atrial fibrillation (AF) is associated with abnormal sarcoplasmic reticulum (SR) calcium release, which is promoted by adenosine A(2A) receptor (A(2A)R) activation. Here, we tested the hypothesis that abnormal calcium release in AF is linked to A(2A)R remodelling. Methods and results Western blotting and quantitative real-time PCR were used to determine A(2A)R mRNA and protein levels in right atrial samples from patients with and without AF. Effects of A(2A)R activation on calcium handling were assessed with patch-clamp technique and confocal calcium imaging. A(2A)R mRNA levels and functional A(2A)Rs were moderately up-regulated in patients with atrial dilation and markedly up-regulated in those with AF. Accordingly, A(2A)R stimulation significantly increased ryanodine receptor phosphorylation in AF patients, and spontaneous calcium waves increased moderately in myocytes from patients with atrial dilation and strongly in patients with AF (2.2 +/- 2.1 to 14.3 +/- 8.8 min(-1), n = 6, P = 0.01). Moreover, the high baseline level of calcium waves in AF was reduced by A(2A)R antagonists (3.5 +/- 2.0 to 1.3 +/- 1.3 min(-1), n = 6, P = 0.007) or adenosine deaminase (1.7 +/- 1.5 to 0.5 +/- 0.6 min(-1), n = 10, P = 0.02) suggesting that A(2A)Rs are activated by endogenous adenosine. Indeed, intracellular perfusion with adenosine significantly increased the calcium wave frequency (1.1 +/- 0.8 to 8.2 +/- 3.3 min(-1), n = 8), whereas adenosine removal from the cytosol decreased it (2.1 +/- 0.9 to 0.3 +/- 0.3 min(-1), n = 8, P = 0.04). Conclusions Atrial fibrillation patients show increased A(2A)R expression that may account for the high baseline level of spontaneous SR calcium release seen in myocytes from these patients, and the ability of A(2A)R antagonists to reduce this abnormal calcium release points to the A(2A)R as a novel molecular target in AF.

In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim efficacy and safety results of the ongoing extension of this study. In the extension (months 7—36), placebo-treated patients were re-randomized to either dose of fingolimod; fingolimod-treated patients continued at the same dose. During months 15—24, all patients receiving fingolimod 5.0 mg switched to 1.25 mg. Of the 250 patients who entered the extension study, 173 (69%) continued to month 36. Most patients were free from gadolinium-enhanced lesions (88—89%) or new T2 lesions (70—78%) at month 36. Patients receiving continuous fingolimod treatment had sustained low annualized relapse rates of 0.20—0.21, and 68—73% remained relapse-free at month 36. Over 36 months, nasopharyngitis (34%), headache (30%), fatigue (19%) and influenza (18%) were the most commonly reported adverse events. Pulmonary function remained stable and blood pressure was stable after an initial increase (3—5 mmHg) during the first 6 months of fingolimod treatment; serious adverse events included infections and skin cancer. The low MRI and clinical disease activity at 6 months were maintained at 36 months with fingolimod, which was generally well tolerated by most patients. The efficacy and safety of oral fingolimod are being further evaluated in a large phase III MS study programme.

La enfermedad por reflujo gastroesofágico (ERGE) es una enfermedad crónica recurrente, que constituye uno de los trastornos gastrointestinales que afecta con mayor frecuencia a población mundial. Objetivo: Determinar la prevalencia de enfermedad por reflujo gastroesofágico en la población adulta venezolana. Pacientes y Métodos: Se realiza un estudio descriptivo, de corte transversal, multicéntrico durante los meses de abril y mayo de 2008. Se entrevistaron a individuos en edades comprendidas entre 15 - 65 años de diferentes estados del país (Aragua, Anzoátegui, Barinas, Carabobo, Delta Amacuro, Distrito Capital, Mérida, Miranda, Sucre, Zulia) escogidos a través del azar simple, realizándose un muestreo por conglomerados, de donde, en cada estado se seleccionó un Municipio y de éste, lugares como iglesias, centro comerciales, cines y paradas de autobuses. Se tomó en consideración la población de cada municipio según el Censo Nacional 2001. Resultados: Un total de 1318 individuos fueron encuestados en los estados incluidos, 814 mujeres (61,76%) y 504 Hombres (38,24%). En cuanto a la distribución por categoría de edad, el grupo de 25-35 años constituyó el de mayor predominio. Se obtuvo una Prevalencia Nacional de 11,54%, donde los síntomas cardinales pirosis y regurgitación ácida representaron 16,62% y 12,75% respectivamente. Conclusión: La prevalencia nacional de enfermedad por reflujo gastroesofágico en la población venezolana es del 11,54%. The gastroesophageal reflux disease (GERD) is a chronic recurrent illness that represents one of the most common gastrointestinal disorders that affects worldwide population. Aim: To determine the prevalence of gastroesophageal reflux disease in the Venezuelan adult population. Patients and Methods: A Descriptive, cross section, multicentric study was made. A survey was done to people in ages between 15 - 65 years of different states of the country (Aragua, Anzoátegui, Barinas, Carabobo, Delta Amacuro, Distrito Capital, Mérida, Miranda, Sucre, Zulia) chosen randomly. Cluster sampling was performed, where in each State was selected a municipality and, of which one places like churches, malls, cinemas and bus stops. To calculate de amount of people The National Census 2001 was taken in account in each municipality. Results: A total of 1318 individuals were surveyed in the mentioned States including, 814 women (61.76%) and 504 men (38.24%). The predominant distribution by age was the group of 25-35 years old. A National Prevalence of 11.54% was obtained, where the cardinal symptoms were heartburn and acid regurgitation represented 16.62% and 12.75% respectively. Conclusion: The national prevalence of gastroesophageal reflux disease in the Venezuelan adult population is 11.54%.

Functional interactions between the G protein-coupled dopamine D1 and histamine H3 receptors have been described in the brain. In the present study we investigated the existence of D1-H3 receptor heteromers and their biochemical characteristics.D1-H3 receptor heteromerization was studied in mammalian transfected cells with Bioluminescence Resonance Energy Transfer and binding assays. Furthermore, signalling through mitogen-activated protein kinase (MAPK) and adenylyl cyclase pathways was studied in co-transfected cells and compared with cells transfected with either D1 or H3 receptors.Bioluminescence Resonance Energy Transfer and binding assays confirmed that D1 and H3 receptors can heteromerize. Activation of histamine H3 receptors did not lead to signalling towards the MAPK pathway unless dopamine D1 receptors were co-expressed. Also, dopamine D1 receptors, usually coupled to G(s) proteins and leading to increases in cAMP, did not couple to G(s) but to G(i) in co-transfected cells. Furthermore, signalling via each receptor was blocked not only by a selective antagonist but also by an antagonist of the partner receptor.D1-H3 receptor heteromers constitute unique devices that can direct dopaminergic and histaminergic signalling towards the MAPK pathway in a G(s)-independent and G(i)-dependent manner. An antagonist of one of the receptor units in the D1-H3 receptor heteromer can induce conformational changes in the other receptor unit and block specific signals originating in the heteromer. This gives rise to unsuspected therapeutic potentials for G protein-coupled receptor antagonists.

Objective:: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS:: In the randomized, double-blind, placebo-controlled core study, 281 patients received placebo or FTY720, 1.25 or 5.0 mg/day, for 6 months. During the subsequent dose-blinded extension, patients assigned to placebo were re-randomized to either dose of FTY720; those originally assigned to FTY720 continued at the same dose. Patients receiving FTY720 5.0 mg were switched to 1.25 mg during the month 15 to month 24 study visits. RESULTS:: Of 281 patients randomized in the core study, 250 (89%) entered the extension phase, and 189 (75.6%) received treatment for 24 months. During the core study, FTY720 significantly reduced gadolinium-enhanced (Gd) lesions and annualized relapse rate (ARR) compared with placebo, with no differences between doses. During the extension phase, patients who switched from placebo to FTY720 showed clear reductions in ARR and lesion counts compared with the placebo phase; ARR and lesion counts remained low in patients who continued FTY720 treatment. After 24 months, 79 to 91% of patients were free from Gd lesions and up to 77% of patients remained relapse free. FTY720 was well tolerated; no new safety concerns emerged during months 7 to 24 compared with the 6-month core study. CONCLUSIONS:: Once-daily oral treatment with FTY720, 1.25 or 5.0 mg, for up to 2 years, was well tolerated and was associated with low relapse rates and lesion activity. © 2009 AAN Enterprises, Inc.

The objective of this study is to calculate direct, indirect and intangible costs of a relapse in multiple sclerosis (MS) in our cohort of patients.Data from patient questionnaires, hospital charts, Catalan Public Healthcare System tariffs and Catalan Statistics Institute. We employed a cost-of-illness method. The human capital approach was used to estimate indirect costs, and quality-of-life measurements were used to estimate intangible costs.148 MS patients monitored in our MS-Unit consecutively answered the questionnaire elaborated. We calculated 1,498.5-1,537.9 euros for direct costs (hospital admission and outpatient, respectively) and 1,530.6 euros for indirect costs. We estimated an average total cost of 3,048.8 euros per patient/relapse. We also calculated intangible costs, 539 euros per patient and relapse, which should be added to the previous figure.The total cost of a MS relapse in our population (3,048.8 euros) is lower than the cost reported in the literature. The economic impact of MS is due to its disabling progression rather than to relapses

RESUMEN La Colangitis Autoinmune es una enfermedad hepática de causa desconocida, con hallazgos clínicos, de laboratorio y cambios histológicos de colestasis. Algunos la consideran sinónimo de cirrosis biliar primaria con anticuerpos Anti mitocondriales (AMA) negativos. Aún no existe consenso en su definición como entidad individual. Sin embargo han sido publicados numerosos estudios con el objetivo de unificar criterios. Las pruebas de Inmunohistoquímica, la determinación de la expresión de moléculas de histocompatibilidad y recientemente la identificación de anticuerpos contra la enzima anhidrasa carbónica, han facilitado la caracterización de la Colangitis Autoinmune como una enfermedad hepática autoinmune distinguible de las otras y no simplemente un subtipo de Cirrosis biliar primaria con anticuerpos antimitocondriales negativos. Se presenta la clínica, el diagnóstico, hallazgos colangiográficos e histológico y el manejo terapéutico de una paciente de 33 años con diagnóstico histológico de Colangitis Autoinmune. ABSTRACT Autoimmune Cholangitis is a disease of unknown etiology, with clinical, biochemical and histological findings of colestasis.Autoimmune Cholangitis has been considered a Primary Biliary Cirrhosis without Antimitochondrial Antibodies. It is a disease that lacks uniform diagnostic criteria. Advances in biochemistry, inmmunology, and pathology has facilitated to determine the place of autoimmune colangitis in the spectrum of autoimmune liver disease.We report a case of a 33 year-old woman with symptoms, laboratory and histological features of Autoinmune Cholangitis.