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Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is its most important extra-articular manifestation. Evidence-based recommendations are available only to a limited extent and therefore JIA associated uveitis management is mostly based on physicians experience. Consequently, treatment practices differ widely, both nationally and internationally. Therefore, an effort to optimize and publish recommendations for the care of children and young adults with rheumatic diseases was launched in 2012 as part of the international project SHARE (Single Hub and Access Point for Pediatric Rheumatology in Europe) to facilitate clinical practice for paediatricians and (paediatric) rheumatologists. The aim of this work was to translate published international SHARE recommendations for the diagnosis and treatment of JIA associated uveitis and to adapt them for use in the Czech and Slovak Republics. International recommendations were developed according to the standard methodology of the European League against Rheumatism (EULAR) by a group of nine experienced paediatric rheumatologists and three experts in ophthalmology. It was based on a systematic literature review and evaluated in the form of an online survey and subsequently discussed using a nominal group technique. Recommendations were accepted if > 80% agreement was reached (including all three ophthalmologists). A total of 22 SHARE recommendations were accepted: 3 on diagnosis, 5 on disease activity assessment, 12 on treatment and 2 on future recommendations. Translation of the original text was updated and modified with data specific to the czech and slovak health care systems and supplemented with a proposal for a protocol of ophthalmological dispensarization of paediatric JIA patients and a treatment algorithm for JIA associated uveitis. Conclusion: The aim of the SHARE initiative is to improve and standardize care for paediatric patients with rheumatic diseases across Europe. Therefore, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated based on the evidence and agreement of leading European experts in this field.
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Artritis Juvenil , Uveítis , Artritis Juvenil/complicaciones , Artritis Juvenil/diagnóstico , Artritis Juvenil/terapia , Niño , República Checa/epidemiología , Europa (Continente) , Humanos , Eslovaquia/epidemiología , Uveítis/diagnóstico , Uveítis/epidemiología , Uveítis/etiología , Adulto JovenRESUMEN
Resumen Introducción: El cáncer laríngeo es una de las neoplasias de cabeza y cuello más frecuentes, asociado al envejecimiento y a los hábitos de vida. Los análisis de supervivencia de cáncer laríngeo en Chile son escasos. Objetivo: Calcular y analizar la supervivencia y las características clínicas del cáncer laríngeo en pacientes del Servicio de Otorrinolaringología del Hospital Carlos Van Buren, Valparaíso, Chile. Material y Método: Se realizó un estudio retrospectivo de cohorte, incluyendo pacientes diagnosticados con carcinoma escamoso de laringe entre 2007 y 2018. Se calculó la supervivencia con el método de Kaplan-Meier. Se aplicaron las pruebas de log rank, t de Student y exacta de Fisher. Resultados: Se incluyeron 211 pacientes, 90,52% hombres, con un promedio de edad de 68 años. El factor de riesgo más frecuente fue el tabaquismo. La ubicación tumoral más frecuente fue la glotis (59,44%) y el motivo de consulta más común la disfonía (52,66%). Un 70,48% presentó estadios avanzados. En 23,92% se realizó laringectomía total como tratamiento primario. La supervivencia global a 2 años fue de 86,6% en estadio precoz y 45,2% en estadio avanzado, mientras que a 5 años fue de 77,4% y 33%, respectivamente. Conclusión: La supervivencia estimada fue menor que en otros estudios nacionales, lo que puede asociarse al tamaño de la muestra analizada, a factores etarios y/o a mayor latencia de inicio de tratamiento. Se enfatiza el mejoramiento de los registros clínicos y la gestión sanitaria para un manejo oportuno.
Abstract Introduction: Laryngeal carcinoma is one of the most frequent head and neck neoplasms, being associated with ageing and lifestyles. In Chile, survival analyses of laryngeal carcinoma are scarce. Aim: To estimate and analyze the survival and clinical characteristics of laryngeal carcinoma in patients attended at the Otorhinolaryngology Department of the Carlos Van Buren Hospital, Valparaíso, Chile. Material and Method: We conducted a retrospective cohort study, including patients diagnosed with laryngeal squamous cell carcinoma between 2007 and 2018. Kaplan-Meier estimator was applied for survival analysis. Log rank test, Student's t-test and Fisher's exact test were applied. Results: 211 patients were included, 90,52% were men, with an average age of 68 years. The main risk factor was smoking (80%). The most frequent tumor location was in the glottis (59,44%) and the most frequent reason for consultation was dysphonia (52,66%). Most cases (70,48%) presented at advanced stages. Laryngectomy was performed as a primary treatment in 23,92%. The 2-year overall survival rate was 86,6% for early stages and 45,2% for advanced stages; the 5-year overall survival rate was 77,4% and 33%, respectively. Conclusion: The estimated survival rate was lower than those referred by other national studies, which may be associated with the analyzed sample size, age-related factors and/or period of latency until the beginning of treatment. We emphasize the necessity of an improvement in clinical records and the health management to the timely treatment.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/epidemiología , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/epidemiología , Chile/epidemiología , Neoplasias Laríngeas/terapia , Tasa de Supervivencia , Estudios RetrospectivosRESUMEN
BACKGROUND: Neuroprotective effects of recombinant human activated Protein C (rhAPC) in models of Spinal Cord Injury (SCI) and ischemic stroke have been reported in rodents. To rule out immunogenicity of rhAPC and to possibly maintain the physiological PC/thrombin balance the use of zymogen PC in SCI might be preferable. Although activation of Protein C (PC) has been demonstrated in rats, the efficacy and drug safety of NON activated PC has not been previously tested in experimental SCI. METHODS: Twelve rats were subjected to 40 g compression of the spinal cord at TH11 for 20 minutes and randomly allocated to either the NON activated PC (25 IU/kg) or the Placebo group (saline).Results. 25 IU treatment yielded improved recovery from SCI compared to placebo and the triple fold dose of PC (75 IU/kg) was subsequently tested to detect treatment associated complications (TAC). Treatment was administered as a single shot via the right vena jugularis forty minutes after onset of compression. The observation period was 5 weeks in 25 IU treated and 1 week in the 75 IU treated rats. Improvement of motor function recovery was measured with behaviour tests and electrophysiology. FINDINGS: Single shot treatment with 25 IU/kg of NON activated PC led to improved recovery in terms of behaviour and electrophysiology. TACs neither occurred in the 25 IU nor in the 75 IU group within one week. CONCLUSION: NON activated PC is a potent and safe drug in experimental SCI and should be considered for treatment in neurotrauma.
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Antiinflamatorios/farmacología , Anticoagulantes/farmacología , Proteína C/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Médula Espinal/efectos de los fármacos , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/uso terapéutico , Anticoagulantes/metabolismo , Anticoagulantes/uso terapéutico , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Potenciales Evocados Somatosensoriales/fisiología , Inyecciones Intravenosas , Masculino , Parálisis/tratamiento farmacológico , Parálisis/etiología , Parálisis/fisiopatología , Proteína C/metabolismo , Proteína C/uso terapéutico , Ratas , Ratas Sprague-Dawley , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Médula Espinal/metabolismo , Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Resultado del TratamientoRESUMEN
The importance of the brain A2A adenosine receptor (A(2A)AR) in movement disorders urges the development of radiolabeled ligands for imaging those receptors by positron emission tomography (PET). This study evaluated one class of A(2A)AR antagonists, derivatives of 4-amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-2H-1-one, 10a, as agents for imaging brain A(2A)ARs by PET.. Modifications of a literature synthesis of 10a efficiently generated analogs 10b-s for pharmacological evaluation. Radioligand binding experiments showed affinities for the rat brain A(2A)AR in the low nanomolar range but similar affinities for the A1AR and substantial unspecific binding. Autoradiography employing [3H]10a, showing that high unspecific binding obscured specific binding to both the A1AR and A(2A)AR. Thus, compounds 10b-s are unsuitable as ligands for imaging brain A(2A)ARs by PET.
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Antagonistas del Receptor de Adenosina A2 , Quinoxalinas/síntesis química , Triazoles/síntesis química , Animales , Autorradiografía , Unión Competitiva/fisiología , Encéfalo/diagnóstico por imagen , Ligandos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Tomografía de Emisión de Positrones/métodos , Quinoxalinas/química , Quinoxalinas/farmacología , Ensayo de Unión Radioligante , Ratas , Espectrometría de Masa por Ionización de Electrospray , Triazoles/química , Triazoles/farmacología , TritioRESUMEN
BACKGROUND: Several findings suggest that nitric oxide (NO) plays a significant role in the regulation of the Th1/Th2 balance and contributes to the development of allergic diseases. Our study investigates a possible association of C/T transition located 276-bp downstream from the translation termination site in exon 29 of the human nitric oxide synthase type 1 (NOS1) gene with immunoglobulin E (IgE)-mediated allergic diseases in the Czech population. METHODS: The study included 688 subjects - 368 patients with clinically manifested allergic diseases and 320 unrelated controls with negative familial history of asthma/atopy. The NOS1 genotypes were determined by polymerase chain reaction (PCR) and restriction analysis by Eco72I. RESULTS: No significant differences were found for allele or genotype frequencies of the 5266 C/T polymorphism in exon 29 of the NOS1 gene between IgE-mediated allergic diseases (or asthma alone) and healthy subjects. However, this common polymorphism showed a significant association with signs of atopy, especially with total serum IgE levels [log(e) IgE levels (mean +/- SD): CC genotype = 4.34 +/- 1.40; CT genotype = 4.58 +/- 1.53; TT genotype = 5.01 +/- 1.61; P < 0.05). CONCLUSIONS: Our findings suggest that NOS1 gene may participate in the pathogenesis of high total serum IgE levels in allergic diseases in our population. These findings provide support for NOS1 as a candidate gene for IgE-mediated allergy.
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Hipersensibilidad/genética , Hipersensibilidad/inmunología , Inmunoglobulina E/inmunología , Óxido Nítrico Sintasa/genética , Polimorfismo Genético , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Citosina , República Checa , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Hipersensibilidad/sangre , Inmunoglobulina E/sangre , Masculino , Óxido Nítrico Sintasa de Tipo I , TiminaRESUMEN
BACKGROUND: Immunoglobulin E (IgE)-mediated allergy belongs to common chronic disorders resulting from an interaction between both genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localized on chromosome 5q31.1, a region that is linked to asthma and bronchial hyperresponsiveness. Recently, several polymorphisms in the promoter region of this gene have been associated with atopic phenotypes in various populations. METHODS: We investigated relationship among atopic phenotypes and two polymorphisms [C(-159)T and G(-1359)T] in the promoter of the CD14 gene in the Czech population. Polymerase chain reaction with restriction fragment length polymorphism analyses was used to determine the CD14 genotypes in subjects with IgE-mediated allergic diseases (n = 562) and random controls (n = 320). RESULTS: The CD14 allele or genotype distributions were similar in patients and control group. However, the frequency of the C allele of the C(-159)T polymorphism was higher in patients with positive skin prick tests for moulds than in patients without reactivity to this antigen (P < 0.002, Pcorr<0.01). In addition, we found that patients with homozygous genotype (GG) of the G(-1359)T polymorphism had marginally lower percentage of positive skin prick tests compared with the other genotypes (P < 0.029, Pcorr > 0.05). CONCLUSIONS: Our study supports the idea that CD14 gene variants may act as disease modifiers of IgE-mediated allergic diseases.
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Hipersensibilidad Inmediata/genética , Receptores de Lipopolisacáridos/genética , Polimorfismo Genético , Adulto , Alérgenos/sangre , Alérgenos/inmunología , Anafilaxia/sangre , Anafilaxia/inmunología , Asma/diagnóstico , Asma/genética , Asma/inmunología , Estudios de Casos y Controles , República Checa , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hipersensibilidad Inmediata/diagnóstico , Hipersensibilidad Inmediata/inmunología , Inmunoglobulina E/inmunología , Masculino , Fenotipo , Regiones Promotoras GenéticasAsunto(s)
Hipersensibilidad Inmediata/enzimología , Hipersensibilidad Inmediata/genética , Óxido Nítrico Sintasa/genética , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Alelos , Niño , Protección a la Infancia , Estudios Transversales , República Checa/epidemiología , Femenino , Genotipo , Humanos , Hipersensibilidad Inmediata/tratamiento farmacológico , Corea (Geográfico)/epidemiología , Masculino , Óxido Nítrico Sintasa de Tipo III , Polimorfismo Genético/genéticaRESUMEN
Several proteins from nacre of the oyster Pinctada maxima and the abalone Haliotis tuberculata were extracted and partly characterized. Proteins dispersed in aragonite were solubilized during demineralization with acetic acid whereas proteins adsorbed on conchiolin were extracted with sodium dodecyl sulfate and beta-mercaptoethanol. The matrix of Pinctada maxima nacre is composed of one main protein with an apparent molecular weight of 20 kDa (p20). This protein was found in the acetic acid soluble fraction of nacre, as well as in the Laemmli-solubilized extract of conchiolin. In addition, the p20 solubilized with acetic acid can form oligomers made of 6 monomers linked together by disulfide bridges. The first N-terminal 21 amino acids of p20 were determined and no homology with known proteins was found. In Haliotis tuberculata nacre, 5 main proteins were solubilized during demineralization and 3 glycoproteins were detected. Stains-all and Alcian blue staining revealed polyanionic proteins in the extracts isolated from Pinctada maxima and Haliotis tuberculata nacre.
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Glicoproteínas/aislamiento & purificación , Músculos/química , Ostreidae/química , Secuencia de Aminoácidos , Animales , Cromatografía Líquida de Alta Presión , Electroforesis en Gel de Poliacrilamida , Glicoproteínas/análisis , Datos de Secuencia Molecular , Peso Molecular , Solubilidad , Sulfatasas/farmacología , Tripsina/farmacologíaRESUMEN
Managed care offers many career opportunities to HIM professionals. If you're interested in making a transition to this area, the first step is understanding the ways HIM adds value to managed care processes. This article kicks off the first in a series on HIM opportunities in managed care.
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Movilidad Laboral , Gestión de la Información/organización & administración , Programas Controlados de Atención en Salud/organización & administración , Administradores de Registros Médicos , Programas Controlados de Atención en Salud/normas , Sistemas de Registros Médicos Computarizados , Gestión de la Calidad Total , Estados UnidosRESUMEN
PURPOSE: To compare hematologic recovery in patients receiving allogeneic blood cell transplantation (BCT) with those receiving allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: One hundred eleven patients with leukemia in the early stages and with HLA-matched sibling donors were randomized in this study. One hundred one underwent transplantation. Standard procedures for collection and transplantation were used. Patients did not receive prophylactic granulocyte colony-stimulating factor after undergoing transplantation. In addition to clinical end points being established, a prospective and comparative economic evaluation of the first 6 months after transplantation was performed. RESULTS: Groups were balanced for patient, donor, and transplant characteristics. Blood cell collection led to the collection of a higher number of CD34(+) and CD3(+) cells than did bone marrow collection (P < 10(-6)) without reported side effects for the donor. Patients in the BCT group reached platelet counts of 25 and 50 x 10(9) platelets/L 8 and 11 days earlier than did the BMT group (P < 10(-4) and P < 10(-5)), respectively. This resulted in fewer platelet transfusions during the first 180 days after transplantation (P =.002) for the former group. The time to reach neutrophil counts of 0.5 and 1 x 10(9) neutrophils/L was 6 and 7 days shorter, respectively, in the BCT group than in the BMT group (P < 10(-5)). This quicker hematologic recovery was associated with a shorter length of hospitalization and a decrease in total cost of procedure during the first 6 months. CONCLUSION: This study establishes that allogeneic BCT results in quicker hematologic recovery but is associated with a higher occurrence of chronic graft-versus-host disease.
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Adyuvantes Inmunológicos/uso terapéutico , Trasplante de Médula Ósea/métodos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia/terapia , Enfermedad Aguda , Adulto , Trasplante de Médula Ósea/economía , Trasplante de Médula Ósea/inmunología , Femenino , Trasplante de Células Madre Hematopoyéticas/economía , Humanos , Lenograstim , Leucemia/sangre , Leucemia/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide/sangre , Leucemia Mieloide/inmunología , Leucemia Mieloide/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Estudios Prospectivos , Proteínas Recombinantes/uso terapéuticoRESUMEN
The immunogenicity of two meningococcal outer membrane vesicle (OMV) vaccines, namely the Norwegian wild-type OMV vaccine and the Dutch hexavalent PorA OMV vaccine, were examined in infant cynomolgus monkeys. For the first time, a wild-type- and a recombinant OMV vaccine were compared. Furthermore, the induction of memory and the persistence of circulating antibodies were measured. The Norwegian vaccine contained all four classes of major outer membrane proteins (OMP) and wild-type L3/L8 lipopolysaccharide (LPS). The Dutch vaccine consisted for 90% of class 1 OMPs, had low expression of class 4 and 5 OMP, and GalE LPS. Three infant monkeys were immunised with a human dose at the age of 1.5, 2.5 and 4.5 months. Two monkeys of each group received a fourth dose at the age of 11 months. In ELISA, both OMV vaccines were immunogenic and induced booster responses, particularly after the fourth immunisation. The Norwegian vaccine mostly induced sero-subtype P1.7,16 specific serum bactericidal antibodies (SBA), although some other SBA were induced as well. The antibody responses against P1.7,16, induced by the Norwegian vaccine, were generally higher than for the Dutch vaccine. However, the Dutch vaccine induced PorA specific SBA against all six sero-subtypes included in the vaccine showing differences in the magnitude of SBA responses to the various PorAs.
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Vacunas Bacterianas/inmunología , Polisacáridos Bacterianos/inmunología , Porinas/inmunología , Animales , Anticuerpos Antibacterianos/análisis , Cápsulas Bacterianas , Fenómenos Fisiológicos Sanguíneos , Ensayo de Inmunoadsorción Enzimática , Ingeniería Genética , Inmunidad , Macaca fascicularis , Vacunas Meningococicas , Neisseria meningitidis , Polisacáridos Bacterianos/genética , Porinas/genéticaRESUMEN
Patients with mesial temporal lobe epilepsy (mTLE) exhibit marked depressions of the regional cerebral glucose metabolism (rCMRGlu) in the mesiotemporal region. We hypothesised that patients with temporal lobe epilepsy (TLE) who have a bilateral somatosensory or acoustic ( = temporolateral/SII-) aura can be differentiated from mTLE by rCMRGlu depressions primarily involving temporo-perisylvian locations. We therefore used this ictal semiology as a clinical criterion to define a subgroup of such patients and measured the rCMRGlu in 16 patients with TLE as evident from interictal and ictal EEG-video monitoring. Clinically, they presented with medically refractory complex partial seizures and were subjected to presurgical evaluation. The pattern of the interictal rCMRGlu in the TLE patients was different from that observed in patients with mTLE and showed significant depressions ipsilateral to the epileptic focus in mesial temporal and lateral temporal regions but spared the thalamus. The neocortical metabolic depressions were spatially more extended in right than in left TLE patients. Magnetic resonance images (MRI) were either normal (n = 5) or revealed unilateral or bilateral hippocampal atrophy/sclerosis (n = 7), or temporal or extratemporal focal cortical dysplasia (n = 4). The selected TLE patients presented here comprise a heterogeneous group showing most pronounced metabolic depressions in the lateral temporal cortex. Thus, our data suggest that non-invasive metabolic imaging can assist in identifying the neocortical symptomatogenic zone in putative temporo-perisylvian lobe epilepsy.
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Trastornos de la Percepción Auditiva/etiología , Epilepsia Parcial Compleja/metabolismo , Epilepsia Parcial Sensorial/metabolismo , Epilepsia del Lóbulo Temporal/metabolismo , Glucosa/metabolismo , Lóbulo Temporal/metabolismo , Abdomen , Adolescente , Adulto , Atrofia , Corteza Auditiva/diagnóstico por imagen , Corteza Auditiva/metabolismo , Corteza Auditiva/patología , Niño , Dominancia Cerebral , Epilepsia , Epilepsia Parcial Compleja/diagnóstico por imagen , Epilepsia Parcial Compleja/patología , Epilepsia Generalizada/diagnóstico por imagen , Epilepsia Generalizada/metabolismo , Epilepsia Generalizada/patología , Epilepsia Parcial Sensorial/diagnóstico por imagen , Epilepsia Parcial Sensorial/patología , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/patología , Epilepsia Tónico-Clónica/diagnóstico por imagen , Epilepsia Tónico-Clónica/metabolismo , Epilepsia Tónico-Clónica/patología , Femenino , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Parestesia/etiología , Esclerosis , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/patología , Tomografía Computarizada de EmisiónRESUMEN
In refractory temporal lobe epilepsy (TLE) temporal lobe structures and functions are continuously or intermittently affected by abnormal brain electrical events, noxious neurochemical agents, and metabolic disturbances. There is conflicting evidence regarding the relationship between the duration of refractory mesial TLE and quantitative measures of temporal lobe functions and volumes of the hippocampi. Twenty patients (aged 28 +/- 7 years, 14 males) with an initial precipitating injury before the age of 5 years were subjected to high-resolution magnetic resonance imaging, fluoro-2-deoxy-d-glucose positron-emission tomography (PET), and the Wada test. We investigated whether the duration of unilateral refractory TLE (12 left, 8 right) affects hippocampal volume, glucose metabolism, or Wada hemispheric memory performance. Ipsilateral to the epileptogenic zone the hippocampal volume, metabolism, and Wada hemispheric memory performance were reduced compared to the corresponding contralateral measures. The duration of epilepsy controlled for age at investigation, side of seizure origin, underlying cause, and sex were negatively correlated with ipsi- and contralateral hippocampal volume, hippocampal metabolism, and Wada hemispheric memory performance. Moreover, ipsilateral Wada hemispheric memory performance and contralateral hippocampal glucose metabolism were correlated with the frequency of habitual seizures. Refractory TLE seems to be associated with a slow but ongoing bilateral temporal lobe damage. These cross-sectional results require verification by longitudinal studies carried out over a period of more than two decades.
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Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/metabolismo , Glucosa/metabolismo , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Memoria , Adolescente , Adulto , Estudios Transversales , Epilepsia del Lóbulo Temporal/psicología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Radiografía , Radiofármacos , Factores de Tiempo , Tomografía Computarizada de EmisiónAsunto(s)
Asma/genética , Población Negra/genética , Región Variable de Inmunoglobulina/genética , Polimorfismo Genético/genética , Receptores de IgE/genética , Población Blanca/genética , Checoslovaquia , Predisposición Genética a la Enfermedad/genética , Genética de Población , Humanos , Reacción en Cadena de la Polimerasa , Hipersensibilidad Respiratoria , SudáfricaRESUMEN
In this study we compare different vaccine formulations containing meningococcal PorA outer membrane protein; purified PorA, outer membrane vesicles (OMV) and immune-stimulating complexes (iscom). Bactericidal antibodies could be generated by the OMV and iscom formulation but not with purified PorA using either A1PO4 or Quil-A as adjuvant. OMV and iscom formulations revealed similar immunogenicity when tested in a dose response manner, with respect to bactericidal as well as OMV-binding antibodies. The anti-OMV IgG subclass response induced by PorA in OMV formulation was found in all subclasses IgG1, IgG2a, IgG2b, IgG3. OMP-iscoms induced very high IgG1 anti-OMV antibodies but almost no IgG3 response. Also, OMP-iscoms appeared to be a potent inducer of antibodies directed against linear peptides corresponding to surface exposed loops of PorA. In addition, iscoms as well as purified PorA with Quil-A as adjuvant (but not with A1PO4) induced high levels of antibodies against purified PorA. In summary, in addition to the OMV formulation, only iscoms containing PorA are able to generate an anamnestic and bactericidal antibody response.
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Vacunas Bacterianas/administración & dosificación , Neisseria meningitidis/inmunología , Porinas/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Vacunas Bacterianas/inmunología , Actividad Bactericida de la Sangre , Femenino , ISCOMs/administración & dosificación , Sueros Inmunes/inmunología , Immunoblotting , Ratones , Datos de Secuencia Molecular , Porinas/administración & dosificaciónRESUMEN
BACKGROUND: Various countries require blood donor screening using assays applying specific HTLV-I and HTLV-II antigens. We evaluated the sensitivity and specificity of 4 anti-HTLV-I + II ELISAs (Abbott, Murex, Organon Teknika and Ortho). METHODS: Panel A consisted of HTLV-I-positive individuals (n = 41), panel B of Mixed Titer Performance Panel 204 (Boston Biomedica Inc. panels C and D of dilution series from HTLV-I-positive (n= 30) and HTLV-II-positive (n =20) individuals and panel E of sera from first-time blood donors (n = 1,055). RESULTS: In HTLV-I- and -II-positive samples, a sensitivity of 100% could be observed in all 4 ELISAs. In diluted HTLV-I- and -II-positive samples, probit analysis revealed that the Murex assay had the highest analytical sensitivity, followed by the ELISAs from Ortho, Abbott and Organon Teknika. In specimens from first-time donors, a specificity of 100% was observed in ELISAs from Murex, Organon Teknika and Ortho, and of 99.7% in the assay from Abbott. CONCLUSION: The 4 anti-HTLV-I + II ELISAs studied were appropriate as screening tests.
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Donantes de Sangre , Ensayo de Inmunoadsorción Enzimática , Antígenos HTLV-I/sangre , Antígenos HTLV-II/sangre , Tamizaje Masivo/métodos , Humanos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: The French drug authorities audited first-time prescription of hematopoietic growth factors using a prescription follow-up survey. Data collected between April 1995 and March 1996 were analyzed then criticized by three clinical experts working in three different areas where lenograstime is most widely used. METHODS: First-time prescription data and follow-up information were recorded on separate inclusion and follow-up diaries by the prescribing physicians. The delivering pharmacies complete the diaries and addressed them to the INSERM unit 330 for analysis. RESULTS: There were 7,102 inclusion diaries and 1376 follow-up diaries from 234 different hospital facilities. Lenograstime was most frequently prescribed in patients with lymphoma (19%), breast cancer (16.4%), and lung cancer (13.8%). Prescriptions involved 377 different chemotherapy protocols, including 196 which concerned a single patient. At the first prescription, lenograstime was given as a preventive measure in 61% of the cases and for curative therapy in 25.3%. The planned duration of preventive treatment was longer than the true period of treatment. DISCUSSION: Pr Rossi, hematologist, Pr Misset, cancerologist and Pr Lebeau, pneumologist criticized the findings.
Asunto(s)
Prescripciones de Medicamentos/estadística & datos numéricos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias/terapia , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/terapia , Femenino , Estudios de Seguimiento , Francia , Registros de Hospitales/estadística & datos numéricos , Humanos , Lenograstim , Neoplasias Pulmonares/terapia , Linfoma/terapia , Proteínas Recombinantes/uso terapéuticoRESUMEN
Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Factor Estimulante de Colonias de Granulocitos/farmacología , Neoplasias Hematológicas/terapia , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Femenino , Prueba de Histocompatibilidad , Humanos , Lenograstim , Masculino , Persona de Mediana Edad , Proyectos Piloto , Proteínas Recombinantes/farmacología , Análisis de Supervivencia , Donantes de Tejidos , Trasplante HomólogoRESUMEN
BACKGROUND: Prostaglandins of the E type are potent endogenous vasodilators that also interfere with the activity of the sympathetic nervous system. Thus treating patients with end-stage heart failure with prostaglandin E1 (PGE1) infusions seems to accord well with the hypothesis that neurohumoral imbalance rather than hemodynamic derangements should be the priority in the treatment of heart failure. METHODS: We sought to investigate neurohumoral in addition to hemodynamic changes during long-term PGE1 infusion and determined plasma renin activity, atrial natriuretic peptide, norepinephrine, and big endothelin plasma levels in 13 male patients with heart failure whose symptoms remained severe in spite of optimized oral therapy with digitalis, nitrates, furosemide (185 +/- 72 mg/d) and enalapril (33 +/- 3 mg/d). PGE1 infusion rate was started with 2.5 ng/kg/min and stepwise increased to the maximum tolerated dose (26 +/- 4 ng/kg/min), which was halved for continuous infusion through the following 12 hours and further stepwise reduced to an average dose of 8 +/- 1 ng/kg/min. Right heart catheterization was performed for acute hemodynamic studies and after 4 weeks. All patients were discharged with a catheter that was connected to a portable pump for home therapy. RESULTS: Acute effects of PGE1 were reductions in systemic blood pressure, (p < 0.05), right atrial pressure (p < 0.001), pulmonary artery pressure (p < 0.05), pulmonary capillary wedge pressure (p < 0.01), systemic and pulmonary vascular resistance index (both p < 0.01) and an increase in cardiac and stroke volume index (both p < 0.001) without a change in heart rate. After 4 weeks a persistent increase from baseline in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.2 L/min/m2; p < 0.01) and in pulmonary vascular resistance index (from 479 +/- 50 to 331 +/- 29 dynes x sec/cm5 x m2; p < 0.05) was observed. Atrial natriuretic peptide (p < 0.05) decreased, and norepinephrine and big endothelin showed a tendency to a lower level. Concomitantly, New York Heart Association functional class changed (p = 0.0001), with one patient's condition remaining class IV, the conditions of seven patients decreasing to class II, and the conditions of five patients decreasing to class III. CONCLUSION: Thus long-term parenteral home therapy with PGE1 infusions in patients with severe end-stage heart failure elicited beneficial clinical and hemodynamic effects without activating neurohumoral counterregulatory systems.