RESUMEN
BACKGROUND: A predisposition to exacerbations is being recognized as a distinct phenotype with "previous exacerbations" representing the strongest clinical factor associated with future exacerbation. Thus, to identify additional novel biomarkers associated with asthma exacerbations, "past exacerbation status" must be included as a confounding factor. OBJECTIVE: This study aimed to characterize the clinical and biomarker features associated with asthma exacerbations in severe asthma. METHODS: We evaluated clinical parameters from 105 severe asthmatics yearly for 3 years, as well as their exacerbation status. We classified the subjects into 3 groups: (i) consistent non-exacerbators (CNE, subjects who did not experience any exacerbation over the 3-year period); (ii) consistent frequent exacerbators (CFE, subjects with frequent exacerbation, defined as those who had 2 or more exacerbations within 1 year, throughout the 3-year period); and (iii) intermittent exacerbators (IE). We conducted multivariate analysis for comparisons among the groups for multiple factors, including several Th2-related biomarkers, in addition to the "past exacerbation status." RESULTS: Thirty-nine subjects were classified as CNE, 15 as CFE, and 51 as IE. Frequent exacerbations in the previous year predicted exacerbations for the following year (P < .001). Among the several Th2-related biomarkers, only FeNO was associated with exacerbation status. When we analysed the data after the second visit, the impact of FeNO on predicting future exacerbation remained significant, even after considering the exacerbation status during the first year (P < .05). CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of FeNO has a significant potential to predict future asthma exacerbation, which is independent of the "past exacerbation history."
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Asma/epidemiología , Adolescente , Adulto , Asma/diagnóstico , Biomarcadores , Niño , Preescolar , Comorbilidad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Óxido Nítrico , Fenotipo , Pronóstico , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Adulto JovenRESUMEN
BACKGROUND: We have recently reported that sensitization to food allergens and sensitization to airborne allergens had independent associations with increased fraction of exhaled nitric oxide (FeNO) and blood eosinophils in middle-aged adults and in young subjects with asthma. OBJECTIVE: To investigate the relation between IgE sensitization and several type 2 inflammation biomarkers in adult asthmatics. METHODS: FeNO, urinary eosinophil-derived neurotoxin (U-EDN), serum eosinophil cationic protein (S-ECP) and periostin were measured in 396 asthmatics, aged 17-76 years, from the Swedish GA2LEN study. Sensitization to airborne allergens was examined with skin prick tests (≥3 mm wheal) and sensitization to food allergens with measurement of specific IgE (≥0.35 kU/L). RESULTS: Asthmatics sensitized to food allergens had higher FeNO, 22.3 ppb (18.6, 26.7) vs 16.1 ppb (14.2, 18.2) (P = .005), S-ECP, 17.7 mg/L (14.8, 21.1) vs 12.8 mg/L (10.9, 14.9) (P = .01), and periostin, 73.7 (67.5, 80.3) ng/mL vs 59.9 (55.8, 64.2) ng/mL (P = .003), than non-sensitized subjects. Periostin levels in this group were also significantly higher than in the group sensitized only to airborne allergens (P = .01). Sensitization to food allergens related independently to FeNO (P = .02), S-ECP (P = .006) and periostin (P = .004), whereas sensitization only to airborne allergens related only to FeNO (P = .02) after adjustments for age, sex, height, weight and smoking history. FeNO correlated weakly with S-ECP (r = .17, P < .001), periostin (r = .19, P < .001) and U-EDN (0.16, P < .001). S-ECP also correlated weakly with U-EDN (r = .12, P = .02). None of the correlations between the remaining pairs of markers of type 2 inflammation were significant. CONCLUSIONS & CLINICAL RELEVANCE: Sensitization to food allergens related to several local and systemic type 2 inflammation markers, such as FeNO, S-ECP and periostin. Assessing the profile of allergic sensitization, including to food allergens, might improve the understanding and interpretation of inflammatory markers and potentially improve asthma management.
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Alérgenos/inmunología , Asma/inmunología , Asma/metabolismo , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/metabolismo , Alimentos/efectos adversos , Inmunoglobulina E/inmunología , Adulto , Asma/diagnóstico , Biomarcadores , Pruebas Respiratorias , Espiración , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Humanos , Inmunización , Masculino , Persona de Mediana Edad , Óxido Nítrico , Pruebas de Función Respiratoria , Pruebas Cutáneas , EspirometríaRESUMEN
BACKGROUND: Periostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear. AIM: To examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics. METHODS: Serum periostin was examined by ELISA in 1100 subjects aged 17-76 from the Swedish Global Allergy and Asthma European Network (GA(2)LEN) study, which included 463 asthmatics with/without chronic rhinosinusitis (CRS), 98 individuals with CRS only, and 206 healthy controls. Clinical tests included measurement of lung function, Fraction of exhaled NO (FeNO), IgE, urinary eosinophil-derived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication, and quality of life. RESULTS: Although median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN, and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower body mass index (BMI) related to higher periostin levels in subjects both with and without asthma. CONCLUSION: We confirm associations between periostin and markers of type 2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma.
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Asma/epidemiología , Moléculas de Adhesión Celular/sangre , Inflamación/etiología , Pulmón/fisiopatología , Adolescente , Adulto , Anciano , Asma/sangre , Asma/patología , Asma/fisiopatología , Estudios de Casos y Controles , Humanos , Pulmón/patología , Persona de Mediana Edad , Rinitis , Sinusitis , Suecia , Adulto JovenRESUMEN
BACKGROUND: People with Down syndrome (DS) often have sleep-disordered breathing (SDB). Unusual sleep postures, such as leaning forward and sitting, are observed in people with DS. This study aimed to clarify the prevalence of unusual sleep postures and their relationships with SDB-related symptoms (SDB-RSs), such as snoring, witnessed apnoea, nocturnal awakening and excessive daytime sleepiness. METHODS: A questionnaire, including demographic characteristics and the presence of unusual sleep postures, as well as SDB-RSs, was completed by 1149 parents of people with DS from Japan. RESULTS: Unusual sleep postures were recorded in 483 (42.0%) people with DS. These participants were significantly younger and had a history of low muscle tone more frequently than people without unusual sleep postures. In all ages, the leaning forward posture was more frequent than sitting. People with DS with unusual sleep postures suffered from SDB-RSs. Those who slept in the sitting posture had more frequent SDB-RSs than did those who slept with the leaning forward posture. Snoring, witnessed apnoea and nocturnal awakening were observed in 73.6, 27.2 and 58.2% of participants, respectively. Snoring increased with aging. Witnessed apnoea was more common in males and in those with hypothyroidism than in females and in those without hypothyroidism. CONCLUSIONS: Our study shows that there is a close relationship between unusual sleep postures and SDB-RSs. We recommend that all people with DS with unusual sleep postures should be checked for the presence of SDB.
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Trastornos de Somnolencia Excesiva/fisiopatología , Síndrome de Down/fisiopatología , Postura/fisiología , Síndromes de la Apnea del Sueño/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Ronquido/fisiopatología , Adolescente , Adulto , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Genetic markers of susceptibility to asthma exacerbations in adults remain unclear. OBJECTIVE: To identify genetic markers of asthma exacerbations, particularly in patients with type-2 inflammatory endotype. METHODS: In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin-4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type-2 inflammatory endotype) were considered in the analysis. RESULTS: Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type-2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37-18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47-11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05-7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type-2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type-2 and neutrophilic inflammations. CONCLUSIONS AND CLINICAL RELEVANCE: IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type-2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.
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Proteínas ADAM , Asma/sangre , Asma/genética , Subunidad alfa del Receptor de Interleucina-4 , Proteínas ADAM/sangre , Proteínas ADAM/genética , Adulto , Anciano , Asma/tratamiento farmacológico , Estudios de Seguimiento , Marcadores Genéticos , Humanos , Subunidad alfa del Receptor de Interleucina-4/sangre , Subunidad alfa del Receptor de Interleucina-4/genética , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Omalizumab, a humanized anti-IgE monoclonal antibody, has demonstrated efficacy in patients with severe allergic asthma. However, treatment responses vary widely among individuals. Despite a lack of data, free serum IgE levels following omalizumab treatment have been proposed as a marker of treatment responsiveness. METHODS: In this prospective, observational study, we assessed the utility of biomarkers of type 2 inflammation in predicting omalizumab treatment responses, as determined by the absence of asthma exacerbation during the first year of treatment. Free serum IgE levels were monitored for 2 years to examine their association with baseline biomarker levels and the number of exacerbations. RESULTS: We enrolled thirty patients who had been treated with omalizumab for at least 1 year, of whom 27 were treated for 2 years. Baseline serum periostin levels and blood eosinophil counts were significantly higher in patients without exacerbations during the first year of treatment than in patients with exacerbations. Baseline serum periostin levels, but not eosinophil counts, were negatively associated with free serum IgE levels after 16 or 32 weeks of treatment. Reduced free serum IgE levels during treatment from those at baseline were associated with reduced exacerbation numbers at 2 years. In 14 patients who continued to have exacerbations during the first year of treatment, exacerbation numbers gradually and significantly decreased over the 2-year study period, with concurrent significant reductions in free serum IgE levels. CONCLUSION: Baseline serum periostin levels and serum free IgE levels during treatment follow-up may be useful in evaluating responses to omalizumab treatment.
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Antiasmáticos/uso terapéutico , Asma/sangre , Asma/tratamiento farmacológico , Moléculas de Adhesión Celular/sangre , Inmunoglobulina E/sangre , Omalizumab/uso terapéutico , Adulto , Anciano , Antiasmáticos/farmacología , Asma/diagnóstico , Asma/inmunología , Biomarcadores , Progresión de la Enfermedad , Femenino , Humanos , Inmunoglobulina E/inmunología , Masculino , Persona de Mediana Edad , Omalizumab/farmacología , Curva ROC , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. METHODS: In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined. RESULTS: Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/µl) in the high serum periostin group. CONCLUSIONS: A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.
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Asma/genética , Asma/fisiopatología , Variación Genética , Receptores de Glucocorticoides/genética , Administración por Inhalación , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Anciano , Asma/tratamiento farmacológico , Asma/inmunología , Moléculas de Adhesión Celular/sangre , Eosinófilos/inmunología , Femenino , Volumen Espiratorio Forzado , Estudios de Asociación Genética , Proteínas de Choque Térmico/genética , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Pruebas de Función Respiratoria , Factores de RiesgoRESUMEN
BACKGROUND: Recent findings indicate that periostin, an extracellular matrix protein induced by T helper 2 cytokines, plays a critical role in the pathogenesis of atopic dermatitis (AD). OBJECTIVES: To determine whether serum periostin level is associated with clinical phenotype in adult patients with AD. METHODS: An enzyme-linked immunosorbent assay was performed to determine serum periostin levels in 257 adult patients with AD, 66 patients with psoriasis vulgaris (PV) as a disease control and 25 healthy controls. Serum periostin levels were analysed together with clinical characteristics and laboratory parameters, including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophil count and total IgE. Immunohistochemical analysis evaluated the expression of periostin in association with various clinical phenotypes of AD. The effect of treatment on serum periostin level was also assessed. RESULTS: Serum periostin was significantly higher in patients with AD than in patients with PV and healthy controls. Periostin level was found to be positively correlated with disease severity, TARC level, LDH level and eosinophil count, but not with IgE level. Higher serum periostin level was observed in patients with extrinsic AD compared with patients with intrinsic AD; the positive correlation of disease severity disappeared in patients with intrinsic AD. Robust expression of periostin was detected in the dermis of patients with AD with erythroderma, lichenification and, to a lesser extent, scaly erythema. Serial measurement of serum periostin revealed decreased levels of periostin after treatment for AD. CONCLUSIONS: Periostin may play a critical role in disease severity and chronicity in the pathogenesis of AD.
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Moléculas de Adhesión Celular/metabolismo , Dermatitis Atópica/etiología , Adulto , Estudios de Casos y Controles , Quimiocina CCL17/metabolismo , Enfermedad Crónica , Dermatitis Atópica/metabolismo , Ensayo de Inmunoadsorción Enzimática , Eosinófilos/fisiología , Femenino , Humanos , Inmunoglobulina E/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Recuento de Leucocitos , Masculino , Psoriasis/metabolismo , Piel/metabolismoAsunto(s)
Neurología/tendencias , Pediatría , Niño , Educación , Educación Médica/normas , Humanos , Japón , Neurología/ética , Médicos , Sociedades CientíficasRESUMEN
Pancreatic islet transplantation is an attractive therapy for the treatment of insulin-dependent diabetes mellitus. However, the low efficiency of this procedure necessitating sequential transplantations of islets with the use of 2-3 donors for a single recipient, mainly due to the early loss of transplanted islets, hampers its clinical application. Previously, we have shown in mice that a large amount of HMGB1 is released from islets soon after their transplantation and that this triggers innate immune rejection with activation of DC, NKT cells and neutrophils to produce IFN-γ, ultimately leading to the early loss of transplanted islets. Thus, HMGB1 release plays an initial pivotal role in this process; however, its mechanism remains unclear. Here we demonstrate that release of HMGB1 from transplanted islets is due to hypoxic damage resulting from Ca(2+) influx into ß cells through the Na(+) /Ca(2+) exchanger (NCX). Moreover, the hypoxia-induced ß cell damage was prevented by pretreatment with an NCX-specific inhibitor prior to transplantation, resulting in protection and long-term survival of transplanted mouse and human islets when grafted into mice. These findings suggest a novel strategy with potentially great impact to improve the efficiency of islet transplantation in clinical settings by targeting donor islets rather than recipients.
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Compuestos de Anilina/farmacología , Diabetes Mellitus Experimental/prevención & control , Diabetes Mellitus Tipo 1/inmunología , Rechazo de Injerto/inmunología , Trasplante de Islotes Pancreáticos/inmunología , Islotes Pancreáticos/inmunología , Éteres Fenílicos/farmacología , Intercambiador de Sodio-Calcio/antagonistas & inhibidores , Animales , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/inmunología , Citometría de Flujo , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/metabolismo , Proteína HMGB1/metabolismo , Humanos , Hipoxia/metabolismo , Hipoxia/patología , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Intercambiador de Sodio-Calcio/metabolismoRESUMEN
BACKGROUND: Periostin, a matricellular protein, serves as a regulator of wound healing and fibrosis. The role of periostin in the pathogenesis of systemic sclerosis (SSc) is unknown. OBJECTIVE: To determine periostin levels in association with severity of skin fibrosis in patients with SSc. METHODS: Expression of periostin was immunohistochemically examined in skin obtained from patients with SSc and healthy controls. Enzyme-linked immunosorbent assay was performed to evaluate serum periostin levels in association with clinical characteristics in 56 patients with SSc [diffuse cutaneous SSc (dSSc), n=16; and limited cutaneous SSc (lSSc), n=40] and 66 healthy controls. RESULTS: Periostin was strongly expressed in the affected dermis from patients with SSc. Periostin was colocalized in α-smooth muscle actin-positive myofibroblasts and platelet endothelial cell adhesion molecule-1-positive endothelial cells in SSc dermis. Serum levels of periostin in patients with dSSc were markedly elevated compared with those in patients with lSSc and control subjects. Patients with lSSc had increased periostin levels compared with healthy controls. In addition, significantly higher levels of periostin were observed in patients with dSSc with disease duration ≤5 years compared with those with disease duration >5 years. Furthermore, the modified Rodnan total skin thickness score (MRSS) was positively correlated with periostin levels in patients with SSc. Serial analysis revealed a correlation between periostin and MRSS; namely, MRSS decreased in line with decreased periostin levels in some patients with dSSc as the disease progressed. CONCLUSION: An elevated periostin level in patients with SSc is associated with severity of skin sclerosis. Periostin may be a potential biomarker for progressive skin fibrosis in SSc.
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Moléculas de Adhesión Celular/metabolismo , Esclerodermia Sistémica/sangre , Piel/patología , Área Bajo la Curva , Biomarcadores/metabolismo , Femenino , Humanos , Inmunohistoquímica , Pulmón/patología , Masculino , Persona de Mediana Edad , Esclerodermia Sistémica/patología , Esclerosis/sangre , Esclerosis/patologíaRESUMEN
BACKGROUND/OBJECTIVE: Focal papillary thyroid carcinoma (PTC) arising within a follicular adenoma (PTCFA) represents a clinically significant, but rare, histopathologic subset of papillary carcinomas whose cytologic features have not been well described. This uncommon presentation of PTC may contribute to a subset of thyroid aspirates interpreted as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS). STUDY DESIGN: Seventeen fine-needle aspiration biopsy (FNAB) cases diagnosed as 'PTCFA' on corresponding surgical excision were identified from the archival records of 2 large academic medical centers. A control group of 40 FNAB comprised of 20 follicular adenomas (FA) and 20 PTC was identified (based on the corresponding surgical pathology diagnosis) for comparison. All 57 FNAB were reviewed in a masked fashion and scored for a series of 31 cytomorphologic features. The intraclass correlation between diagnostic categories and overall agreement between cytopathologists was statistically evaluated. RESULTS: Aspirates of PTCFA were originally diagnosed as 'negative' (n = 3), 'AUS/FLUS' (n = 7), 'suspicious for a follicular neoplasm' (n = 3), 'suspicious for malignancy' (n = 3), and 'malignant' (n = 1). On masked review, the most common cytomorphologic features of PTCFA were a nonmacrofollicular cytoarchitectural pattern (71%), medium-large cell size (74%), and micronucleoli (79%). Intranuclear pseudoinclusions and a papillary architecture were absent in 85 and 88% of the cases, respectively. Relative to the 2 control groups, the PTCFA cases demonstrated overlapping features between FA and PTC for the majority of the 31 examined cytomorphologic features. CONCLUSION: PTCFA represent a rare subset of PTC that is difficult to recognize as PTC by FNAB. Most cases exhibit overlapping features between a benign thyroid nodule and conventional PTC, and they are often interpreted as 'AUS/FLUS'.
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Adenoma/patología , Carcinoma/patología , Neoplasias Complejas y Mixtas/patología , Glándula Tiroides/patología , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/patología , Adenoma/clasificación , Adenoma/diagnóstico , Adulto , Biopsia con Aguja Fina , Carcinoma/clasificación , Carcinoma/diagnóstico , Carcinoma Papilar , Reacciones Falso Negativas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Complejas y Mixtas/clasificación , Neoplasias Complejas y Mixtas/diagnóstico , Guías de Práctica Clínica como Asunto , Pronóstico , Estudios Retrospectivos , Riesgo , Terminología como Asunto , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/clasificación , Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/clasificación , Nódulo Tiroideo/diagnósticoRESUMEN
Idiopathic interstitial pneumonias (IIPs) are histopathologically classified into several types, including usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and cryptogenic organising pneumonia (COP). We investigated whether periostin, a matrix protein, could be used as a biomarker to assess histopathological types of IIPs. We performed immunohistochemical analyses in each histopathological type of IIP, examined serum levels of periostin in IIP patients and analysed the relationship between serum levels of periostin and the pulmonary functions in patients with idiopathic pulmonary fibrosis (IPF). Periostin was strongly expressed in lungs of UIP and fibrotic NSIP patients, whereas expression of periostin was weak in the lungs of cellular NSIP and COP patients, as well as in normal lungs. Serum levels of periostin in IPF were significantly higher than those of healthy subjects and COP patients. Furthermore, periostin levels in IPF patients were inversely correlated with their pulmonary functions. Thus, we have found that periostin is a novel component of fibrosis in IIP. Periostin may be a potential biomarker to distinguish IIP with fibrosis.
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Moléculas de Adhesión Celular/sangre , Neumonías Intersticiales Idiopáticas/sangre , Anciano , Biomarcadores/sangre , Femenino , Humanos , Neumonías Intersticiales Idiopáticas/patología , Neumonías Intersticiales Idiopáticas/fisiopatología , Pulmón/patología , Pulmón/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: The presence of a projection from the primary motor cortex to the ipsilateral muscles has been established in human, but whether this pathway contributes to functional recovery after stroke is unclear. We investigated whether the ipsilateral tract is activated in hemiparetic stroke. METHODS: Motor-evoked potentials (MEPs) were simultaneously recorded from the bilateral trapezius or abductor digiti minimi (ADM) muscles after magnetic stimulation to the motor cortex in 40 acute stroke patients. RESULTS: At rest, ipsilateral trapezius MEPs were recordable in none of the 24 normal controls, and in 38% of the patients after stimulation to the non-affected hemisphere (P < 0.001). With voluntary contraction, ipsilateral trapezius MEPs were elicited in 21% of the normal controls and 73% of the patients (P < 0.001). Ipsilateral ADM MEPs were rarely recordable in both controls (0%) and patients (3%). The presence of ipsilateral trapezius MEPs was associated with less severe paresis in the trapezius (P = 0.04) and deltoid (P = 0.07), but not in the more distal muscles. CONCLUSIONS: The ipsilateral cortico-spinal tract is acutely facilitated after stroke in the trunk or proximal muscles, but not in the hand muscles. Activation of such pathway appears to partly compensate motor dysfunction of the trunk/proximal muscles.
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Potenciales Evocados Motores/fisiología , Lateralidad Funcional , Tractos Piramidales/fisiología , Recuperación de la Función/fisiología , Accidente Cerebrovascular/fisiopatología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiología , Músculo Esquelético/fisiología , Paresia/fisiopatología , Estimulación Magnética TranscranealRESUMEN
OBJECTIVE: The purpose of this retrospective study was to evaluate results of a local treatment protocol using gamma knife surgery (GKS) for brain metastases without upfront whole brain radiation therapy (WBRT). METHODS: Results for 521 consecutive patients satisfying the following 3 criteria were analysed: 1) a maximum of 3 tumours with a diameter of 25 mm or more; 2) no prior WBRT; 3) no surgically in accessible large (>30 mm) tumours. Large tumours were surgically removed and all smaller lesions were treated by GKS without up front WBRT. New lesions, detected with follow-up MRI, were appropriately treated with repeat GKS. Overall survival (OS), neurological survival (NS), qualitative survival (QS) and new lesion-free survival (NLFS) curves were calculated and the prognostic values of covariates were obtained. OS and NS were compared according to tumour number. RESULTS: In total, 1023 separate sessions were required to treat 4562 lesions. The primary organs were lung in 369 patients, gastro-intestinal tract in 70, breast in 33, urinary tract in 24, and others/unknown in 25. The median OS period was 9.0 months. On multivariate analysis, the significant prognostic factors for OS were found to be extracranial disease (risk factor: active), Karnofsky performance status (KPS) score (<70) and gender (male). NS and QS at one year were 85.6% and 73.0%, respectively. The only significantly poor prognostic factor for NS was carcinomatous meningitis. NLFS at 6 months was 68.9%. For both OS and NS, the differences between a few (=3) and many (4-10) brain lesions were not significant (OS: p=0.3128, NS: p=0.5509). Patients with numerous (>10) tumours had a significantly poorer prognosis than those with =10. CONCLUSION: Our protocol, aggressively applying GKS, provides excellent results in selected patients with =10 brain lesions and no carcinomatous meningitis.
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Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Radiocirugia , Anciano , Daño Encefálico Crónico/diagnóstico , Daño Encefálico Crónico/mortalidad , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Causas de Muerte , Diagnóstico por Imagen , Supervivencia sin Enfermedad , Femenino , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/cirugía , Humanos , Estado de Ejecución de Karnofsky , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/mortalidad , Neoplasias Primarias Desconocidas/cirugía , Examen Neurológico , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/mortalidad , Pronóstico , Reoperación , Estudios Retrospectivos , Factores Sexuales , Tasa de Supervivencia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/cirugíaRESUMEN
SUMMARY: Endovascular embolization of the middle meningeal artery was performed in two cases of refractory chronic subdural haematoma (CSDH) after repeated burr hole and irrigation surgeries. The embolization prevented expansion of the CSDH in both cases, and the haematoma disappeared completely in one case. The expansion of CSDH is considered to result from repeated bleeding from the macrocapillaries on the haematoma capsule. Embolization of the middle meningeal artery appears to be useful to eliminate the blood supply to this structure.
RESUMEN
SUMMARY: Angioplasty with stent deployment is a promising option for the treatment of carotid stenosis. However, the definite treatment indication is still unknown through lack of scientific evidences in the randomized controlled trial, which is now on going. We compared the short-term outcome, such as periprocedural complication rate, cerebral blood flow, subsequent ischemic events and restenosis, between carotid stenting (CS) and carotid endarterectomy (CEA) in the same period to investigate the justice of our present indication for CS. Fifty-five patients with carotid stenosis greater than 70% were treated by CS or CEA in a constant indication. Twenty-five times of CEA were indicated in patients who satisfied the inclusion criteria of NASCET without the exclusion criteria, 30 times of CS in patients with the exclusion criteria. No major procedure-related complication was found in either group. One patient (3.3%) in CS group suffered a minor ischemic stroke during the procedure, just after postdilatation. One patient underwent myocardial infarction in CEA group, and one patient congestive heart failure in CS group within one week after the procedure. During a mean follow-up period of 19 months, no further stroke occurred in either group. There was no lesion-related mortality, but one patient in each group was dead of heart disease. As for restenosis, one patient in each group showed recurrent stenosis on angiogram 12 and 24 months after the treatment. Restenosis rate calculated by the personyear method in CEA and CS group was almost same, 2.3% per year. Stenting seemed to be so safe and effective for cases refractory to CEA that the present indication for CS is thought to be reasonable, though it is necessary to draw a decisive conclusion in randomized trials.
RESUMEN
To elucidate the association of lipoprotein(a) (Lp(a)) with diabetic retinopathy (DR), we studied the serum Lp(a) concentrations (n = 412), apolipoprotein(a) (apo(a)) phenotypes expressed by the number of kringle 4 (K4) repeats (n = 150), apo(a) gene genotypes (n = 161) of type 2 diabetes with or without DR. The 5'-untranslated region of apo(a) gene was classified into seven haplotypes (A to G) and 18 genotypes by PCR-RFLP at three distinct sites. The serum Lp(a) concentrations were significantly higher in diabetic patients than in normal controls. Furthermore, the patients with DR, especially proliferative retinopathy showed higher serum Lp(a) concentrations than those without DR. Although a negative correlation was found between the serum Lp(a) concentrations and the number of K4 repeats in total diabetic patients, no difference was seen in the distribution of the number of K4 repeats between those with and without DR. In the same apo(a) phenotypes, the patients with DR had higher Lp(a) concentrations than those without DR. Among the genotypes, type CC showed significantly higher serum Lp(a) concentrations than the other genotypes. However, there was no difference in the ratios of the type CC between the patients with and without DR. In conclusion, other factors than phenotypes and genotypes in the 5'-untranslated region of apo(a) may be responsible for the elevation of serum Lp(a) in diabetic patients with retinopathy.
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Apolipoproteínas/sangre , Apolipoproteínas/genética , Diabetes Mellitus Tipo 2/genética , Retinopatía Diabética/genética , Lipoproteína(a)/sangre , Lipoproteína(a)/genética , Regiones no Traducidas 5'/genética , Adulto , Anciano , Anciano de 80 o más Años , Apoproteína(a) , Diabetes Mellitus Tipo 2/sangre , Retinopatía Diabética/sangre , Femenino , Genotipo , Heterocigoto , Homocigoto , Humanos , Japón , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Juego de Reactivos para Diagnóstico , Valores de ReferenciaRESUMEN
The long-term effectiveness of zonisamide (ZNS) was evaluated in 11 patients with West syndrome (7 symptomatic) who had cessation of spasms with ZNS monotherapy. During the follow-up period (24 to 79 months, mean = 53 months), this response was maintained in 7 patients (3 symptomatic, relapse rate = 36%), including 2 children in whom ZNS was successfully discontinued. No serious adverse reactions were noted. ZNS may be both effective and well tolerated for the treatment of West syndrome.
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Anticonvulsivantes/uso terapéutico , Isoxazoles/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Adolescente , Anticonvulsivantes/efectos adversos , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Isoxazoles/efectos adversos , Cuidados a Largo Plazo/estadística & datos numéricos , Masculino , Estudios Prospectivos , ZonisamidaRESUMEN
We reported four children cases with reversible posterior leukoencephalopathy syndrome (RPLS). Magnetic resonance imaging (MRI) of the brain demonstrated reversible multiple cortical and subcortical lesions predominant in the occipital region. All patients presented with neurological symptoms associated with hypertension, such as headache, seizures and visual disturbances, which were successfully treated with antihypertensive therapy. Although RPLS is rare in childhood, characteristic lesions on MRI in the hypertensive children should be recognized as manifestations of RPLS. Subsequent clinical management should focus on the treatment of the hypertension and/or its underlying causes.