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BACKGROUND: Albinism is a group of genetic disorders characterized by general skin and retinal hypopigmentation. It is in most cases an autosomal recessive condition. Foveal hypoplasia (FH) is one of the main criteria for the diagnosis of albinism. The aim of this study was to analyze the macular profile of the parents of patients with albinism. METHODS: This study included a case series of 27 patients with albinism seen in Rothschild Foundation between April 2017 and February 2020. Spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCT-A) were performed in every patient when possible and in every available parents. FH was graded according to Thomas' classification based on OCT. Next generation sequencing-based gene panel testing was performed in parents and children when a FH was detected on OCT in a parent. RESULTS: Twenty-seven patients with albinism were examined. Nine parents had FH based on the OCT B-scan (33%). In parents without FH based on the SD-OCT B-scan (67%), OCT-A showed a reduced avascular zone in the deep vascular plexus in 4 parents. Six parents carried variants that could explain their phenotype, including TYR R402Q hypomorphic alleles. CONCLUSION: This study showed the presence of FH in parents of patients with albinism, and aimed to genetically explain this phenotype.
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Albinismo Ocular , Albinismo Oculocutáneo , Albinismo , Humanos , Fóvea Central/anomalías , Retina , Albinismo/genética , Albinismo Oculocutáneo/diagnóstico , Albinismo Oculocutáneo/genética , Albinismo Ocular/diagnóstico , Albinismo Ocular/genética , Trastornos de la Visión/diagnóstico , Tomografía de Coherencia Óptica/métodosRESUMEN
BACKGROUND: Response to antidepressant therapy is highly variable among individuals. Pharmacogenomic (PGx) testing presents an opportunity to guide drug selection while optimizing therapy outcomes and/or decreasing the risk for toxicity. CASE PRESENTATION: A patient with multiple comorbidities, including severe major depressive disorder (MDD), experienced adverse drug events and undesirable response to multiple antidepressant medications (i.e., bupropion, escitalopram, and venlafaxine). A clinical pharmacist assessed significant drug-gene, drug-drug, and drug-drug-gene interactions as well as other clinical factors to provide recommendations for antidepressant therapy optimization. CONCLUSION: This case highlights the importance of PGx testing and the key role of pharmacists in identifying and mitigating drug-related problems and optimizing drug therapy in patients with MDD.
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Trastorno Depresivo Mayor , Antidepresivos/efectos adversos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Humanos , Farmacéuticos , Farmacogenética , Clorhidrato de Venlafaxina/efectos adversosRESUMEN
INTRODUCTION: Many endoscopists do not use split-dose bowel preparation (SDBP) for morning colonoscopies. Despite SDBP being recommended practice, they believe patients will not agree to take early morning bowel preparation (BP). We assessed patients' opinions about waking early for BP. METHODS: A self-administered survey was distributed between 08/2015 and 06/2016 to patients in Winnipeg, Canada when they attended an outpatient colonoscopy. Logistic regression was performed to determine predictors of reluctance to use early morning BP. RESULTS: Of the 1336 respondents (52â% female, median age 57 years), 33â% had used SDBP for their current colonoscopy. Of the 1336, 49â% were willing, 24â% neutral, and 27â% reluctant to do early morning BP. Predictors of reluctant versus willing were number of prior colonoscopies (OR 1.20; 95â%CI: 1.07â-â1.35), female gender (OR 1.65; 95â%CI: 1.19â-â2.29), unclear BP information (OR 1.86; 95â%CI: 1.21â-â2.85), high BP anxiety (OR 2.02; 95â%CI: 1.35â-â3.02), purpose of current colonoscopy being bowel symptoms (OR 1.40; 95â%CI: 1.00â-â1.97), use of 4âL of polyethylene glycol laxative (OR 1.45; 95â%CI: 1.02â-â2.06), not having SDBP (OR 1.96; 95â%CI: 1.31â-â2.93), and not having finished the laxative for the current colonoscopy (OR 1.66; 95â%CI: 1.01â-â2.73). Most of the same predictors were identified when reluctance was compared to willing or neutral, and in ordinal logistic regression. CONCLUSIONS: Almost three-quarters of patients do not express reluctance to get up early for BP. Among those who are reluctant, improving BP information, allaying BP-related anxiety, and use of low volume BP may increase acceptance of SDBP.
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BACKGROUND: Previous research has assessed anxiety around colonoscopy procedures, but has not considered anxiety related to different aspects related to the colonoscopy process. AIMS: Before colonoscopy, we assessed anxiety about: bowel preparation, the procedure, and the anticipated results. We evaluated associations between patient characteristics and anxiety in each area. METHODS: An anonymous survey was distributed to patients immediately prior to their outpatient colonoscopy in six hospitals and two ambulatory care centers in Winnipeg, Canada. Anxiety was assessed using a visual analog scale. For each aspect, logistic regression models were used to explore associations between patient characteristics and high anxiety. RESULTS: A total of 1316 respondents completed the questions about anxiety (52% female, median age 56 years). Anxiety scores > 70 (high anxiety) were reported by 18% about bowel preparation, 29% about the procedure, and 28% about the procedure results. High anxiety about bowel preparation was associated with female sex, perceived unclear instructions, unfinished laxative, and no previous colonoscopies. High anxiety about the procedure was associated with female sex, no previous colonoscopies, and confusing instructions. High anxiety about the results was associated with symptoms as an indication for colonoscopy and instructions perceived as confusing. CONCLUSIONS: Fewer people had high anxiety about preparation than about the procedure and findings of the procedure. There are unique predictors of anxiety about each colonoscopy aspect. Understanding the nuanced differences in aspects of anxiety may help to design strategies to reduce anxiety, leading to improved acceptance of the procedure, compliance with preparation instructions, and less discomfort with the procedure.
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Ansiedad/etiología , Colonoscopía/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atención Ambulatoria , Ansiedad/diagnóstico , Ansiedad/prevención & control , Enfermedades del Colon/diagnóstico , Enfermedades del Colon/psicología , Enfermedades del Colon/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/psicología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
This study was conducted from 2008 to 2013 to determine the animal health status of Ivory Coast and neighboring countries (Burkina Faso, Ghana, Togo and Benin) for African swine fever (ASF) and classical swine fever (CSF), and to assess the risk factors for ASF introduction in Ivory Coast. Ivory Coast had probably been free from ASF from 1998 to 2014 when it was re-introduced in this country. However, the ASF virus was found in all neighboring countries. In contrast, no evidence of CSF infection was found so far in Ivory Coast and neighboring countries. To assess the risk of ASF reintroduction in Ivory Coast, we surveyed 59 modern pig farms, and 169 pig owners in 19 villages and in two towns. For the village livestock, the major risk factor was the high frequency of pig exchanges with Burkinabe villages. In the commercial sector, many inadequate management practices were observed with respect to ASF. Their identification should enable farmers and other stakeholders to implement a training and prevention program to reduce the introduction risk of ASF in their farms.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana/sangre , Peste Porcina Clásica/sangre , Sus scrofa/virología , Fiebre Porcina Africana/epidemiología , Animales , Benin/epidemiología , Burkina Faso/epidemiología , Peste Porcina Clásica/epidemiología , Côte d'Ivoire/epidemiología , Ghana/epidemiología , Factores de Riesgo , Porcinos , Togo/epidemiologíaRESUMEN
PURPOSE: Rosuvastatin disposition is modulated by the expression and activity of several membrane transporters including BCRP (ABCG2). The objective of our study was to investigate the effects of pantoprazole, a previously proposed BCRP inhibitor, on the disposition of rosuvastatin. METHODS: The impact of pantoprazole (40 mg ID for 2 days) on rosuvastatin pharmacokinetics was evaluated in healthy volunteers (n = 16) who received a single oral dose of rosuvastatin (10 mg) either alone or with pantoprazole. Rosuvastatin, N-desmethylrosuvastatin, and rosuvastatin lactone levels were quantified in plasma while rosuvastatin and N-desmethylrosuvastatin excretion were measured in urine. RESULTS: Ratios and 90 % standard confidence interval of geometric means for C max (1.03 [0.91-1.16]), AUC0-∞ (1.03 [0.89-1.19]) and renal clearance (0.96 [0.85-1.09]) were all within the pre-specified range of 0.8-1.25, indicating a lack of drug-drug interaction between pantoprazole and rosuvastatin. CONCLUSIONS: Concomitant administration of pantoprazole with rosuvastatin did not affect rosuvastatin plasma concentrations. The use of pantoprazole as a BCRP inhibitor should be revisited when characterizing BCRP-mediated transport in humans.
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2-Piridinilmetilsulfinilbencimidazoles/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacocinética , Inhibidores de la Bomba de Protones/farmacología , Rosuvastatina Cálcica/farmacocinética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/antagonistas & inhibidores , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Adolescente , Adulto , Estudios Cruzados , Citocromo P-450 CYP2C19/genética , Interacciones Farmacológicas , Genotipo , Voluntarios Sanos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/sangre , Lactonas/sangre , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Pantoprazol , Polimorfismo de Nucleótido Simple , Pirimidinas/sangre , Rosuvastatina Cálcica/sangre , Sulfonamidas/sangre , Adulto JovenRESUMEN
The performance of Whatman 3-MM filter papers for the collection, drying, shipment and long-term storage of blood at ambient temperature, and for the detection of African swine fever virus and antibodies was assessed. Conventional and real-time PCR, viral isolation and antibody detection by ELISA were performed on paired samples (blood/tissue versus dried-blood 3-MM filter papers) collected from experimentally infected pigs and from farm pigs in Madagascar and Côte d'Ivoire. 3-MM filter papers were used directly in the conventional and real-time PCR without previous extraction of nucleic acids. Tests that performed better with 3-MM filter papers were in descending order: virus isolation, real-time UPL PCR and conventional PCR. The analytical sensitivity of real-time UPL PCR on filter papers was similar to conventional testing (virus isolation or conventional PCR) on organs or blood. In addition, blood-dried filter papers were tested in ELISA for antibody detection and the observed sensitivity was very close to conventional detection on serum samples and gave comparable results. Filter papers were stored up to 9 months at 20-25°C and for 2 months at 37°C without significant loss of sensitivity for virus genome detection. All tests on 3-MM filter papers had 100% specificity compared to the gold standards. Whatman 3-MM filter papers have the advantage of being cheap and of preserving virus viability for future virus isolation and characterization. In this study, Whatman 3-MM filter papers proved to be a suitable support for the collection, storage and use of blood in remote areas of tropical countries without the need for a cold chain and thus provide new possibilities for antibody testing and virus isolation.
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Fiebre Porcina Africana/diagnóstico , Recolección de Muestras de Sangre/instrumentación , Clima Tropical , Virus de la Fiebre Porcina Africana/genética , Virus de la Fiebre Porcina Africana/aislamiento & purificación , Animales , Ensayo de Inmunoadsorción Enzimática , Madagascar , Reacción en Cadena en Tiempo Real de la Polimerasa , PorcinosRESUMEN
Efavirenz increases CYP2C19- and CYP3A-mediated omeprazole metabolism. We hypothesized that CYP2C19 and CYP2B6 genetic polymorphisms influence the extent of induction of omeprazole metabolism by efavirenz. Healthy subjects (n=57) were administered a single 20 mg oral dose of omeprazole on two occasions: with a single 600 mg efavirenz dose; and after a 17-day treatment with efavirenz (600 mg per day). DNA was genotyped for CYP2C19*2, *3 and *17 alleles and CYP2B6*6, *4 and *9 alleles using Taqman assays. Omeprazole, its enantiomers and metabolites were measured by liquid chromatography/tandem mass spectrometry. Our results showed that efavirenz increased omeprazole clearances in all CYP2C19 genotypes in non-stereoselective manner, but the magnitude of induction was genotype dependent. Metabolic ratios of 5-hydroxylation of omeprazole were reduced in extensive and intermediate metabolizers of CYP2C19 (P<0.05). No significant associations were observed between CYP2B6 genotypes and induction by efavirenz on omeprazole metabolism. Our data indicate how interplays between drug interactions and CYP2C19 genetic variations may influence systemic exposure of CYP2C19 substrates.
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Benzoxazinas/administración & dosificación , Citocromo P-450 CYP2C19/genética , Interacciones Farmacológicas/genética , Omeprazol/administración & dosificación , Adulto , Alquinos , Ciclopropanos , Citocromo P-450 CYP3A/genética , Estudios de Asociación Genética , Genotipo , Humanos , Hidroxilación , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
African swine fever (ASF) is a major limiting factor for pig production in most of the countries in Sub-Saharan Africa and the Indian Ocean. In the absence of vaccine, a good understanding of the ecology and epidemiology of the disease is fundamental to implement effective control measures. In selected countries of Southern and East Africa, the association between Ornithodoros moubata ticks and warthogs has been described in detail in the literature. However, for many other countries in the region, information related to the sylvatic cycle is lacking or incomplete. In West African countries, for instance, the role of wild pigs in the epidemiology of ASF has never been demonstrated and the existence and potential impact of a sylvatic cycle involving an association between soft ticks and warthogs is questionable. In other countries, other wild pig species such as the bushpigs (Potamochoerus spp.) can also be asymptomatically infected by the virus but their role in the epidemiology of the disease is unclear and might differ according to geographic regions. In addition, the methods and techniques required to study the role of wild hosts in ASF virus (ASFV) epidemiology and ecology are very specific and differ from the more traditional methods to study domestic pigs or other tick species. The aim of this review is (i) to provide a descriptive list of the methodologies implemented to study the role of wild hosts in African swine fever, (ii) to compile the available knowledge about the sylvatic cycle of ASFV in different regions of Sub-Saharan Africa and the Indian Ocean in addition to the one that has been described for East and Southern Africa, and (iii) to discuss current methodologies and available knowledge in order to identify new orientations for further field and experimental surveys.
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Fiebre Porcina Africana/epidemiología , Fiebre Porcina Africana/transmisión , África del Sur del Sahara/epidemiología , Animales , Animales Domésticos , Animales Salvajes , Argasidae , Islas del Oceano Índico/epidemiología , PorcinosRESUMEN
Drug-drug interactions involving efavirenz are of major concern in clinical practice. We evaluated the effects of multiple doses of efavirenz on omeprazole 5-hydroxylation (CYP2C19) and sulfoxidation (CYP3A). Healthy volunteers (n = 57) were administered a single 20 mg oral dose of racemic omeprazole either with a single 600 mg oral dose of efavirenz or after 17 days of administration of 600 mg/day of efavirenz. The concentrations of racemic omeprazole, 5-hydroxyomeoprazole (and their enantiomers), and omeprazole sulfone in plasma were measured using a chiral liquid chromatography-tandem mass spectrometry method. Relative to single-dose treatment, multiple doses of efavirenz significantly decreased (P < 0.0001) the area under the plasma concentration-time curve from 0 to infinity (AUC(0-∞)) of racemic-, R- and S-omeprazole (2.01- to 2.15-fold) and the corresponding AUC(0-∞) metabolic ratio (MR) for 5-hydroxyomeprazole (1.36- to 1.44-fold) as well as the MR for omeprazole sulfone (â¼2.0) (P < 0.0001). The significant reduction in the AUC of 5-hydroxyomeprazole after repeated efavirenz dosing suggests induction of sequential metabolism and mixed inductive/inhibitory effects of efavirenz on CYP2C19. In conclusion, efavirenz enhances omeprazole metabolism in a nonstereoselective manner through induction of CYP3A and CYP2C19 activity.
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Hidrocarburo de Aril Hidroxilasas/biosíntesis , Benzoxazinas/administración & dosificación , Citocromo P-450 CYP3A/biosíntesis , Omeprazol/farmacocinética , Adulto , Alquinos , Área Bajo la Curva , Ciclopropanos , Citocromo P-450 CYP2C19 , Interacciones Farmacológicas , Inducción Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/sangre , Inhibidores Enzimáticos/farmacocinética , Femenino , Humanos , Hidroxilación , Masculino , Omeprazol/análogos & derivados , Omeprazol/sangre , Inhibidores de la Transcriptasa Inversa/farmacologíaRESUMEN
We previously demonstrated that injection of IL-2-activated natural killer (NK) cells contribute to vascular remodeling via a4b7 integrin and killer cell lectin-like receptor (KLRG) 1 and promote cardiac repair following myocardial infarction (MI). The aim of the present study is to test the hypothesis that injection of recombinant human interleukin (rhIL)-2 improves angiogenesis and preserves heart function after MI. A single IV injection of rhIL-2 two days following MI improved by 27.7% the left ventricular (LV) fractional shortening of immune competent (C57Bl6) mice, but had no effect on cardiac function of immune-deficient (NOD-SCID IL2Rγnull) mice. Immunohistochemical analysis of C57Bl6 cross sections of heart revealed that collagen deposition was reduced by 23.1% and that capillary density was enhanced in the scar area and the border zone of the infarct respectively by 22.4% and 33.6% following rhIL-2 injection. In addition, rhIL-2 enhanced 1.6-fold the in vivo endothelial cell proliferation index and 1.8-fold the number of NK cell infiltrating the infarcted heart, but had no effect on the number of cardiac CD4 and CD8 cells. In vitro, rhIL-2 activated NK cells enhanced cardiac endothelial cell proliferation by 17.2%. Here we show that a single IV injection of rhIL-2 positively impacted cardiac function by improving angiogenesis through a process involving NK cells.
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Pruebas de Función Cardíaca/efectos de los fármacos , Corazón/fisiopatología , Interleucina-2/farmacología , Infarto del Miocardio/fisiopatología , Neovascularización Fisiológica/efectos de los fármacos , Animales , Recuento de Células , Proliferación Celular/efectos de los fármacos , Colágeno/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Citometría de Flujo , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Humanos , Subunidad gamma Común de Receptores de Interleucina/deficiencia , Subunidad gamma Común de Receptores de Interleucina/metabolismo , Interleucina-2/uso terapéutico , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Activación de Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones SCID , Infarto del Miocardio/patología , Tamaño de los Órganos/efectos de los fármacosRESUMEN
Since its introduction in Madagascar in 1998, African swine fever (ASF) has severely affected national pig production and persists as a common disease in that country. Two of its natural hosts in the African continent, the bushpig (Potamochoerus larvatus) and tick vectors of the Ornithodoros moubata complex, are reported in west and central regions of the island. However, their role in the maintenance and transmission of the virus has been insufficiently studied. In this work, we tried to assess their potential role in the epidemiology of the disease in Madagascar, by assessing the levels of interaction between (i) ASF virus (ASFV) and bushpigs and (ii) between soft ticks and domestic and wild suids in north-western Madagascar. Twenty-seven sera and 35 tissue samples from bushpigs were collected and analysed for the presence of anti-ASF antibodies and viral DNA. In addition, the sera from 27 bushpigs and 126 domestic pigs were analysed with an ELISA test for the detection of antibodies against salivary antigens from Ornithodoros ticks. No circulation of ASFV or anti-ASFV antibodies nor anti-tick antibodies were detected in bushpigs. However, seven of the domestic pig sera (5.6% of the total sample population) were antibody positive for O. moubata antigens. The probability of freedom from ASFV in the bushpig population using Bayesian statistical methods ranged between 73% and 84%. The probabilities of absence of anti-tick antibodies in domestic and wild pigs were estimated at 63% and 71%, respectively. These preliminary results suggest that bushpigs are unlikely to play a significant role in the maintenance and transmission of ASFV in Madagascar. Nevertheless, further ASFV surveys are needed on that species to confirm this assumption. In addition, the presence of antibodies against O. moubata in domestic pigs suggests that soft ticks may be able to maintain ASFV within a domestic pig cycle in areas of Madagascar where they remain present.
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Virus de la Fiebre Porcina Africana/aislamiento & purificación , Fiebre Porcina Africana/transmisión , Ornithodoros/virología , Porcinos/virología , Fiebre Porcina Africana/epidemiología , Virus de la Fiebre Porcina Africana/inmunología , Animales , Animales Salvajes/virología , Anticuerpos Antivirales/análisis , Vectores Arácnidos/virología , Ensayo de Inmunoadsorción Enzimática , Madagascar/epidemiología , Saliva/virología , Sus scrofa/virologíaRESUMEN
Wooden racket paddles were modified with rubber and carbon fibre laminates and their differences tested in terms of flexural, damping, and coefficient of restitution properties. Four rackets types were designed: a wood reference, wood with rubber, carbon fibre 0°, and carbon fibre 90°. Seven expert and eight intermediate tennis players tested the rackets. To determine which of the four rackets suited the players best, we asked the players to compare the rackets two by two. After each pair tested, participants had to fill out a 4-item questionnaire in which different aspects of the rackets' performance were judged. The most preferred racket was the 0° carbon fibre racket, followed by the 90° carbon fibre racket, the wood racket and, finally, the 1-mm rubber racket. Thus, rackets with the highest stiffness, least damping, and highest coefficient of restitution were the most preferred. Interestingly, although experts and intermediate players overall judged the rackets in very similar ways according to force, vibration, and control, they were sensitive to quite different physical characteristics of the rackets.
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Carbono , Comportamiento del Consumidor , Equipo Deportivo , Tenis , Madera , Atletas , Diseño de Equipo , HumanosRESUMEN
The relative contribution of phenotypic measures and CYP2C9-vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphisms to warfarin dose requirements at day 14 was determined in 132 hospitalized, heavily medicated patients. Phenotypic measures were (1) the urinary losartan metabolic ratio before the first dose of warfarin, (2) the S:R-warfarin ratio at day 1, and (3) a dose-adjusted international normalized ratio (INR) at day 4. CYP2C9 and VKORC1 genotypes were determined by gene chip analysis. In multivariate analyses, the dose-adjusted INR at day 4 explained 31% of variability observed in warfarin doses at day 14, whereas genotypic measures (CYP2C9-VKORC1) contributed 6.5%. When S:R-warfarin ratio was used, genotypes contributed more significantly (23.5%). Finally, urinary losartan metabolic ratio was of low predictive value. The best models obtained explained 51% of intersubject variability in warfarin dose requirements. Thus, combination of a phenotypic measure to CYP2C9-VKORC1 genotypes represents a useful strategy to predict warfarin doses in patients receiving multiple drugs (11+/-4 drugs/day).
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Anticoagulantes/administración & dosificación , Hidrocarburo de Aril Hidroxilasas/genética , Oxigenasas de Función Mixta/genética , Warfarina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/sangre , Hidrocarburo de Aril Hidroxilasas/metabolismo , Fibrilación Atrial/sangre , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/enzimología , Fibrilación Atrial/genética , Citocromo P-450 CYP2C9 , Relación Dosis-Respuesta a Droga , Humanos , Persona de Mediana Edad , Oxigenasas de Función Mixta/metabolismo , Fenotipo , Polimorfismo de Nucleótido Simple , Análisis de Regresión , Vitamina K Epóxido Reductasas , Warfarina/sangreRESUMEN
In tropical countries the diagnosis of viral infections of humans or animals is often hampered by the lack of suitable clinical material and the necessity to maintain a cold chain for sample preservation up to the laboratory. This study describes the use of filter papers for rapid sample collection, and the molecular detection and genotyping of viruses when stored over long periods at elevated temperatures. Infected blood was collected on filter papers, dried and stored at different temperatures (22, 32 and 37 degrees C) for various periods (up to 9 months). Two animal viruses, African swine fever, a large double-stranded DNA virus and Peste des Petits Ruminants, a negative single-stranded RNA virus, were used to validate the method. Filter papers with dried blood containing virus or control plasmid DNA were cut in small 5mm(2) pieces and added directly to the PCR tube for conventional PCR. Nucleic acid from both viruses could still be detected after 3 months at 32 degrees C. Moreover, the DNA virus could be detected at least 9 months after conservation at 37 degrees C. PCR products obtained from the filter papers were sequenced and phylogenetic analysis carried out. The results were consistent with published sequences, demonstrating that this method can be used for virus genotyping.
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Virus de la Fiebre Porcina Africana/aislamiento & purificación , Recolección de Muestras de Sangre/métodos , Calor , Virus de la Peste de los Pequeños Rumiantes/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , África , Fiebre Porcina Africana/virología , Virus de la Fiebre Porcina Africana/clasificación , Virus de la Fiebre Porcina Africana/genética , Animales , Genotipo , Peste de los Pequeños Rumiantes/virología , Virus de la Peste de los Pequeños Rumiantes/clasificación , Virus de la Peste de los Pequeños Rumiantes/genética , Filogenia , Sensibilidad y Especificidad , Factores de Tiempo , Clima TropicalRESUMEN
The objective was to identify the major cytochrome P450 enzyme(s) involved in the metabolism of domperidone. Experiments were performed using human liver microsomes (HLMs), recombinant human cytochrome P450 enzymes, cytochrome P450 chemical inhibitors and monoclonal antibodies directed against cytochrome P450 enzymes. Four metabolites were identified from incubations performed with HLMs and excellent correlations were observed between the formation of domperidone hydroxylated metabolites (M1, M3 and M4), N-desalkylated domperidone metabolite (M2) and enzymatic markers of CYP3A4/5 (r2 = 0.9427, 0.951, 0.9497 and 0.8304, respectively). Ketoconazole (1 microM) decreased the formation rate of M1, M2, M3 and M4 by 83, 78, 75 and 88%, respectively, whereas the effect of other inhibitors (quinidine, furafylline and sulfaphenazole) was minimal. Important decreases in the formation rate of M1 (68%), M2 (64%) and M3 (54%) were observed with anti-CYP3A4 antibodies. Formation of M1, M2 and M3 in HLMs exhibited Michaelis-Menten kinetics (Km: 166, 248 and 36 microM, respectively). Similar Km values were observed for M1, M2 and M3 when incubations were performed with recombinant human CYP3A4 (Km: 107, 273 and 34 microM, respectively). The data suggest that CYP3As are the major enzymes involved in the metabolism of domperidone.
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Sistema Enzimático del Citocromo P-450/análisis , Sistema Enzimático del Citocromo P-450/metabolismo , Domperidona/farmacocinética , Microsomas Hepáticos/metabolismo , Mapeo de Interacción de Proteínas , Células Cultivadas , Domperidona/farmacología , HumanosRESUMEN
A BALB/c mouse model of enhanced pulmonary pathology following vaccination with formalin-inactivated alum-adsorbed respiratory syncytial virus (FI-RSV) and live RSV challenge was used to determine the type and kinetics of histopathologic lesions induced and chemokine gene expression profiles in lung tissues. These data were compared and contrasted with data generated following primary and/or secondary RSV infection or RSV challenge following vaccination with a promising subunit vaccine, BBG2Na. Severe peribronchiolitis and perivascularitis coupled with alveolitis and interstitial inflammation were the hallmarks of lesions in the lungs of FI-RSV-primed mice, with peak histopathology evident on days 5 and 9. In contrast, primary RSV infection resulted in no discernible lesions, while challenge of RSV-primed mice resulted in rare but mild peribronchiolitis and perivascularitis, with no evidence of alveolitis or interstitial inflammation. Importantly, mice vaccinated with a broad dose range (20 to 0.02 microg) of a clinical formulation of BBG2Na in aluminium phosphate demonstrated histopathology similar to that observed in secondary RSV infection. At the molecular level, FI-RSV priming was characterized by a rapid and strong up-regulation of eotaxin and monocyte chemotactic protein 3 (MCP-3) relative gene expression (potent lymphocyte and eosinophil chemoattractants) that was sustained through late time points, early but intermittent up-regulation of GRO/melanoma growth stimulatory activity gene and inducible protein 10 gene expression, while macrophage inflammatory protein 2 (MIP-2) and especially MCP-1 were up-regulated only at late time points. By comparison, primary RSV infection or BBG2Na priming resulted in considerably lower eotaxin and MCP-3 gene expression increases postchallenge, while expression of lymphocyte or monocyte chemoattractant chemokine genes (MIP-1beta, MCP-1, and MIP-2) were of higher magnitude and kinetics at early, but not late, time points. Our combined histopathologic and chemokine gene expression data provide a basis for differentiating between aberrant FI-RSV-induced immune responses and normal responses associated with RSV infection in the mouse model. Consequently, our data suggest that BBG2Na may constitute a safe RSV subunit vaccine for use in seronegative infants.
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Quimiocinas/genética , Pulmón/patología , Vacunas contra Virus Sincitial Respiratorio/inmunología , Animales , Quimiocina CCL2/genética , Quimiocina CCL4 , Quimiocina CCL5/genética , Quimiocina CXCL2 , Femenino , Inmunización , Pulmón/metabolismo , Proteínas Inflamatorias de Macrófagos/genética , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vacunas de Productos Inactivados/inmunología , Vacunas de Subunidad/inmunologíaRESUMEN
OBJECTIVE: To investigate the nature and extent of gambling problems in a region of Canada in which legalized gambling activities were expanded during the 1990s. METHOD: A standardized telephone interview was conducted with a random sample of 738 community-dwelling adults (response rate 74%) in Winnipeg, Manitoba. RESULTS: According to traditional classification criteria, the lifetime prevalence of "probable pathological gambling" was 2.6%. A further 3.0% of the sample met criteria for traditionally defined "problem gambling," and evidence suggests that both types of gamblers share several characteristics. Social or recreational gamblers significantly differed on several variables from individuals who reported gambling problems. CONCLUSIONS: The 2.6% prevalence figure is the highest yet reported in a Canadian epidemiological survey and was obtained in a region that developed a more liberal attitude toward gambling in the 1990s. Further, a continuum of severity was demonstrated by scores on the South Oaks Gambling Screen (SOGS), and a clear and consistent distinction between problem and probable pathological gambling was not apparent. Frequenting casinos and using video poker and slot machines, rather than buying lottery tickets, distinguishes problem or pathological gamblers from recreational gamblers.
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Trastornos Disruptivos, del Control de Impulso y de la Conducta/epidemiología , Juego de Azar/psicología , Adulto , Anciano , Estudios Transversales , Trastornos Disruptivos, del Control de Impulso y de la Conducta/psicología , Femenino , Humanos , Incidencia , Masculino , Manitoba/epidemiología , Persona de Mediana EdadRESUMEN
BACKGROUND: Hemangiomas are frequent in childhood. Their association with dysmorphic anomalies is rare. Recently, the acronym "PHACES syndrome" was proposed to emphasize the association of Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta and cardiac defects, Eye abnormalities, and Sternal malformations. CASE REPORT: A female child, 3 months old, had a large facial hemangioma. The physical examination was normal otherwise. A choroidal hemangioma and a papillary abnormality, causing amblyopia, were detected. The brain magnetic resonance imaging was normal. A subglottic hemangioma was found at endoscopy. At the age of 16 months, physical examination disclosed a heart murmur and coarctation of the aorta was detected. Moreover, the cardiac angiography showed diffuse arterial lesions. Strict surveillance was decided as there were no manifestations. DISCUSSION: Different abnormalities have been described to be associated with large facial hemangiomas. Frieden has grouped these abnormalities under the acronym PHACES. She described 43 hemangiomas and found 74 p. 100 Dandy Walker malformations and other posterior fossa malformations, 41 p. 100 arterial anomalies, 26 p. 100 cardiac or aortic malformations, 23 p. 100 ophthalmologic abnormalities. There is a high risk for the hemangiomas to develop in an airway localization. The prevalence of facial hemangiomas associated with other malformations is, to our knowledge, not known. In our department, 56 children were treated with corticosteroid therapy for severe facial hemangioma. 11 p. 100 had a cerebral abnormality. There were no cases with cardiac malformation or dysmorphism. PHACES syndrome is very rare but easy to remember. Thus in patients presenting a large facial hemangioma, it is important to conduct an attentive neurological examination completed by brain imaging and an extensive cardiovascular exploration. Special attention should be given to the ophthalmologic and sternal examinations as well as the search for hemangiomas in an airway localization.
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Coartación Aórtica/diagnóstico , Neoplasias de la Coroides/congénito , Neoplasias Faciales/congénito , Hemangioma/congénito , Neoplasias Primarias Múltiples/congénito , Neoplasias Cutáneas/congénito , Aortografía , Neoplasias de la Coroides/diagnóstico , Neoplasias Faciales/diagnóstico , Femenino , Estudios de Seguimiento , Hemangioma/diagnóstico , Humanos , Lactante , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Cutáneas/diagnóstico , SíndromeRESUMEN
BACKGROUND: Recent investigation into the push-pull effect (PPE), the reduction of +Gz tolerance when preceded by less than +1 Gz, has focused on centrifuge studies to demonstrate the presence of adverse cardiovascular responses. Maneuvers found to cause the Push-Pull Effect (PPEM) have not been studied previously in U.S. Air Force (USAF) fighter aircraft. The frequency of and extent to which PPEMs are performed in fighter aircraft are unknown. METHODS: Head-up display (HUD) videotapes from F-15 and F-16 air combat training missions were reviewed for the presence of PPEMs. The frequency of engagements containing PPEMs and the magnitude of the Gz profiles were noted. RESULTS: PPEMs were found in 11 to 67%, of engagements reviewed, depending on the nature of the training mission, with an overall average of 32%. The PPEMs that were observed contained segments of less than +1 Gz, ranging on average from 0.0 to 0.5 Gz for an average of 3.5 to 5 s duration. CONCLUSIONS: PPEMs are present in air combat training missions performed by today's USAF fighter aircraft and represent an operationally significant source of risk for accidents. These findings support continued research into the physiologic response to PPE and the development of countermeasures.