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1.
Phys Rev Lett ; 132(14): 146902, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38640398

RESUMEN

Spin defects in silicon carbide are promising candidates for quantum sensing applications as they exhibit long coherence times even at room temperature. However, spin readout methods that rely on fluorescence detection can be challenging due to poor photon collection efficiency. Here, we demonstrate coherent spin control and all-electrical readout of a small ensemble of spins in a SiC junction diode using pulsed electrically detected magnetic resonance. A lock-in detection scheme based on a three stage modulation cycle is implemented, significantly enhancing the signal-to-noise ratio. This technique enabled observation of coherent spin dynamics, specifically Rabi spin nutation, spin dephasing, and spin decoherence. The use of these protocols for magnetometry applications is evaluated.

2.
Scand J Rheumatol ; 53(2): 123-129, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38085537

RESUMEN

OBJECTIVE: The optimal strategy for difficult-to-treat (D2T) rheumatoid arthritis (RA) has not been identified, and the ultrasound characteristics of D2T RA have not been reported. We investigated the clinical characteristics and factors contributing to the outcome in D2T RA in a multicentre RA ultrasound observational cohort. METHOD: We reviewed 307 Japanese patients diagnosed with RA who underwent treatment with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). We compared the differences in patient characteristics between the D2T RA and non-D2T RA groups. We examined the factors contributing to a good response [defined as b/tsDMARD continuation and Clinical Disease Activity Index (CDAI) ≤ 10 at 12 months] in the D2T RA patient group. RESULTS: Forty-three patients (14%) were categorized as D2T RA and the remaining 264 (86%) as non-D2T RA at baseline. The grey-scale (GS) score, disease duration, and CDAI at the initiation of treatment were significantly higher in the D2T RA group than in the non-D2T RA group. In contrast, the power Doppler (PD) score was not significantly different between the two groups. Of the 43 D2T RA patients, 20 achieved a good response. The introduction of CTLA4-Ig (n = 5) was significantly associated with a good response in analysis based on inverse probability weighting with propensity score. GS and PD scores at baseline were not significantly associated with therapeutic response at 12 months in D2T RA patients. CONCLUSIONS: Patients with D2T RA had high clinical and ultrasound activity and poor responses to treatment with b/tsDMARDs. CTLA4-Ig was associated with a good response at 12 months in D2T RA patients.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Humanos , Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Estudios de Cohortes , Ultrasonografía , Ultrasonografía Doppler
3.
Scand J Rheumatol ; 51(4): 259-267, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34474646

RESUMEN

OBJECTIVE: This study investigated the effectiveness of treatment with Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA) assessed by ultrasonography (US) activity, and the influence of patient characteristics and previous treatments. METHOD: This prospective study assessed 60 treatment initiations among 53 Japanese patients diagnosed with RA who underwent treatment with JAK inhibitors during June 2013 to February 2020. Of the 53 patients, seven patients were enrolled in duplicate because they were treated with two different JAK inhibitors at different periods. For each case, the improvement rate on the power Doppler (PD) score was assessed at 6 month follow-up. Median improvement rate of PD score was used to classify cases as either US responders or non-responders, and patient characteristics were compared between the two groups. RESULTS: All indicators of clinical disease activity and US activity showed a significant improvement at 3 months compared with baseline. Although the JAK inhibitor-cycler group and the interleukin-6 (IL-6) inhibitor inadequate response (IR) group tended to show a later improvement for US activity, all indicators of clinical disease activity and US activity showed a significant improvement at 6 months compared with baseline for both groups. Multivariate analysis showed that concomitant methotrexate use and an IR to the previous biologic or targeted-synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) treatment were independently and significantly associated with US responders. CONCLUSION: Use of a JAK inhibitor in combination with methotrexate and an absence of IR to any previous b/tsDMARDs demonstrated superior effectiveness for patients with RA.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Humanos , Inhibidores de las Cinasas Janus/uso terapéutico , Japón , Metotrexato/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía
4.
Scand J Rheumatol ; 50(6): 436-441, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33719841

RESUMEN

Objectives: Using multicentre ultrasound (US) cohort data among patients with rheumatoid arthritis (RA), we aimed to identify baseline factors that permit differentiation between two patient cohorts achieving US remission and clinical remission, and to determine the factors contributing to the discrepancy.Method: We reviewed 248 Japanese patients diagnosed with RA who underwent treatment with biological disease-modifying anti-rheumatic drugs at 13 centres. We performed US assessments of the synovia of 22 joints. We assessed the percentages of patients with clinical remission and US remission, defined as total power Doppler scores of 0 at 12 months.Results: The 87 patients who achieved US remission were divided into a group that achieved both clinical and US remission (n = 53) and a group that achieved US remission only (n = 34). Baseline factors that were significantly and independently associated with clinical remission at 12 months among patients who also achieved US remission included short disease duration, the presence of concomitant methotrexate use, and low patient global assessment score (p < 0.05, p < 0.05, and p < 0.005, respectively).Conclusions: RA patients with baseline high patient global assessment scores and long disease duration at baseline were unlikely to achieve clinical remission even after achieving US remission. Objective joint assessments using US provide additional information of potential importance for the management of RA.


Asunto(s)
Artritis Reumatoide , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Estudios de Cohortes , Humanos , Japón , Inducción de Remisión , Resultado del Tratamiento , Ultrasonografía
5.
Scand J Rheumatol ; 50(1): 15-19, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32880228

RESUMEN

Objective: To determine whether the positivity of baseline anti-Ro/Sjögren's syndrome antigen A (SSA) antibodies influences the response to abatacept, we compared therapeutic responses between anti-Ro/SSA antibody-negative and -positive patients with rheumatoid arthritis (RA) using a multicentre RA ultrasonography prospective cohort. Method: We reviewed Japanese patients with RA who started abatacept as the first biological disease-modifying anti-rheumatic drug between June 2013 and April 2018. We assessed 28-joint Disease Activity Score-erythrocyte sedimentation rate (DAS28-ESR) change between baseline and 6 or 12 months after treatment in RA patients treated with abatacept, and European League Against Rheumatism (EULAR) response at 6 and 12 months. The Global OMERACT-EULAR Synovitis Score (GLOESS) was calculated at baseline and at 6 and 12 months. Results: Overall, 51 patients were enrolled and divided into anti-Ro/SSA antibody-negative and -positive groups of 35 and 16, respectively. Median age at baseline was significantly higher in the anti-Ro/SSA antibody-negative group (p = 0.04). The retention rate and percentage of EULAR good responders at 12 months were significantly higher in the anti-Ro/SSA antibody-negative group (both p = 0.02). Anti-Ro/SSA antibody-negative patients exhibited larger decreases in both DAS28-ESR and DAS28-C-reactive protein at 12 months than anti-Ro/SSA antibody-positive patients (p = 0.02 and 0.04, respectively). GLOESS decreased significantly at 6 months in anti-Ro/SSA antibody-negative patients (p = 0.03). Multivariate analyses showed that anti-Ro/SSA antibody positivity was an independent factor associated with change in the DAS28-ESR at 6 months (p < 0.05). Conclusion: Anti-Ro/SSA antibody positivity predicts a poor response to abatacept and low retention rate.


Asunto(s)
Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Autoantígenos/inmunología , ARN Citoplasmático Pequeño/inmunología , Ribonucleoproteínas/inmunología , Anciano , Artritis Reumatoide/inmunología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad
6.
J Intern Med ; 289(2): 206-220, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32691471

RESUMEN

BACKGROUND: Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers that can predict RPILD development remain unclear. OBJECTIVES: To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM-ILD. METHODS: In total, 49 patients with PM/DM-ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti-MDA5 antibody, compared them between the RPILD (n = 23) and non-RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL-15 expression in lung tissues. The IL-15 production was also investigated using A549 and BEAS-2B cells. RESULTS: The RPILD group had significantly higher IL-15, IL-1RA, IL-6, CXCL10, VCAM-1, anti-MDA5 antibody and ferritin serum levels than the non-RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti-MDA5 antibody, IL-15, CXCL8, CCL22, IL-1RA and ferritin were the best combination to distinguish the two groups. IL-15 and CCL22 were also predictive marker for RPILD development in anti-MDA5 antibody-positive patients. Additionally, the RPILD group had significantly high IL-15 levels in BALF. The lung tissues expressed IL-15, which increased after cytokine stimulation in the A549 cells. CONCLUSION: This study identified a combination of biomarkers predicting PM/DM-RPILD progression, and IL-15 is an important cytokine for predicting RPILD development and reflecting ILD severity.


Asunto(s)
Dermatomiositis/complicaciones , Interleucina-15/inmunología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/inmunología , Biomarcadores , Líquido del Lavado Bronquioalveolar/química , Quimiocinas/inmunología , Citocinas/inmunología , Progresión de la Enfermedad , Femenino , Ferritinas/inmunología , Humanos , Japón , Masculino
7.
Scand J Rheumatol ; 50(2): 95-103, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33084461

RESUMEN

Objectives: This study compared indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) and musculoskeletal ultrasound (MSUS), and explored the significance of the FOI findings based on the association between the FOI and MSUS findings and serum biomarkers in patients with rheumatoid arthritis (RA). The study also explored the association between the FOI findings and patients' joint destruction at the joint-area level.Method: We enrolled 50 consecutive patients with active RA from among the patients hospitalized from May 2014 to March 2016 at Nagasaki University Hospital, Japan. FOI images were acquired with the Xiralite® fluorescence imaging system and compared with the patients' clinical examination results and MSUS findings. On the same day, the patients' clinical disease activity and levels of serum biomarkers (including vascular endothelial growth factor) were obtained.Results: Although the FOI detected synovitis with high sensitivity, the frequency of positive findings and the diagnostic performance with MSUS as the reference standard for FOI differed considerably among the phases of FOI as well as among the affected joint regions. The FOI scores were positively correlated with clinical disease activity, MSUS scores, and serum biomarkers. The severity of FOI-proven synovitis was associated with the presence of MSUS-proven bone erosion.Conclusion: FOI is effective for detecting joint inflammation in RA patients, with high accuracy. The severity of the FOI score was closely associated with the joint destruction at the joint-area level. However, the significance of positive FOI findings differed depending on not only the phase of FOI but also the affected joint regions.


Asunto(s)
Artritis Reumatoide/diagnóstico por imagen , Articulaciones de la Mano/diagnóstico por imagen , Imagen Óptica/métodos , Ultrasonografía/métodos , Anciano , Biomarcadores , Femenino , Articulaciones de los Dedos/diagnóstico por imagen , Fluorescencia , Humanos , Masculino , Persona de Mediana Edad , Articulación de la Muñeca/diagnóstico por imagen
8.
Scand J Rheumatol ; 49(1): 13-17, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31402744

RESUMEN

Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment.Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation.Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months.Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.


Asunto(s)
Abatacept/administración & dosificación , Anticuerpos Antiproteína Citrulinada/sangre , Artritis Reumatoide/inmunología , Anciano , Anticuerpos Antiproteína Citrulinada/inmunología , Antirreumáticos/administración & dosificación , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Inyecciones Subcutáneas , Japón , Masculino , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía
9.
Lupus ; 28(3): 295-303, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30700214

RESUMEN

BACKGROUND: Lupus nephritis (LN) is a major determinant of mortality in systemic lupus erythematosus (SLE). Here we evaluated the association between complete renal response (CR) and mortality in LN. METHODS: We retrospectively analyzed the cases of 172 of 201 patients with LN for whom data on the therapeutic response at 6 and 12 months after induction therapy were available. The patients underwent a renal biopsy at Nagasaki University Hospital and community hospitals in Nagasaki between the years 1990 and 2016. We determined the CR rates at 6 and 12 months after induction therapy initiation and evaluated the predictive factors for CR and their relationship with mortality. We performed univariate and multivariable competing risks regression analyses to determine the factors predictive of CR. The patients' survival data were analyzed by the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up duration after renal biopsy was 120 months (interquartile range: 60.3-191.8 months). The 5-, 10-, 15- and 20-year survival rates of our cohort were 99.3, 94.6, 92.0 and 85.4%, respectively. During follow-up, nine patients (5.2%) died from cardiovascular events, infection, malignancy and other causes. The multivariate analysis revealed that the following factors were predictive of CR. At 6 months: male gender (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.08-0.65, p = 0.0028), proteinuria (g/gCr) (OR 0.83, 95% CI 0.71-0.97, p = 0.0098) and index of activity (0-24) (OR 0.84, 95% CI 0.71-0.99, p = 0.0382). At 12 months: male gender (OR 0.25, 95% CI 0.09-0.67, p = 0.0043) and index of activity (0-24) (OR 0.82, 95% CI 0.69-0.98, p = 0.0236). The Kaplan-Meier analysis showed that compared to not achieving CR at 12 months, achieving CR at 12 months was significantly correlated with the survival rate (OR 0.18, 95% CI 0.04-0.92, p = 0.0339). CONCLUSIONS: Our results suggest that the survival rate of patients with LN is associated with the achievement of CR at 12 months after induction therapy, and that male gender and a higher index of activity (0-24) are the common predictive factors for failure to achieve CR at 6 and 12 months.


Asunto(s)
Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/mortalidad , Prednisolona/uso terapéutico , Adulto , Edad de Inicio , Estudios de Casos y Controles , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Proteinuria , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores Sexuales
10.
Lupus ; 28(4): 501-509, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30755146

RESUMEN

BACKGROUND: Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE). METHODS: We retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993-2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares. RESULTS: Of the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5-154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01-1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44-0.90, p = 0.00048) and serum ß2 microglobulin (MG) (OR 0.26, 95% CI 0.06-0.74, p = 0.00098) levels. CONCLUSIONS: Among LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum ß2MG levels were negative predictive factors of CR at 12 months.


Asunto(s)
Hospitales Universitarios , Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/etiología , Adulto , Autoantígenos/sangre , Nitrógeno de la Urea Sanguínea , Femenino , Estudios de Seguimiento , Humanos , Japón , Estimación de Kaplan-Meier , Riñón/patología , Modelos Logísticos , Nefritis Lúpica/sangre , Nefritis Lúpica/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Fragmentos de Péptidos/sangre , Modelos de Riesgos Proporcionales , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Microglobulina beta-2/sangre
11.
Lupus ; 27(8): 1312-1320, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29665758

RESUMEN

Systemic lupus erythematosus (SLE) involves multiple organ systems and primarily affects women during their reproductive years. Pregnancy in a woman with SLE may lead to higher rates of disease flares. Little is known regarding which medications are safe to maintain remission and/or treat flares throughout such pregnancies. Here we retrospectively analyzed the efficacy of tacrolimus (TAC) in the pregnancy outcomes of SLE patients. We studied the 54 deliveries of 40 SLE patients over an eight-year period from 2008 to 2016. We used analyses of covariance with adjustments for the propensity score and inverse probability of treatment weights to compare the patient backgrounds between the TAC users and non-TAC users. TAC was administered to the patient in 15 of the 54 (27.8%) pregnancies, and these patients had a significantly higher dose of prednisolone, hypocomplementemia, lower estimated glomerular filtration rate, past history of lupus nephritis, and complication with antiphospholipid syndrome. In the adjusted background of the TAC deliveries, the risks of decreased fetal body weight, low birth weight infant, non-reassuring fetal status (NRFS), and preterm birth were not increased compared to the non-TAC deliveries. Thrombocytopenia and hypertension during the pregnancy were extracted as independent predictive risk factors for decreased fetal body weight and NRFS, respectively. We had anticipated that the maternal and fetal outcomes in the TAC-use deliveries would be poor before the analysis; however, the TAC-use group showed no significant difference in risks contributing to outcomes compared to the non-TAC group, suggesting that adjunct TAC treatment corrected various risk factors during the lupus pregnancies.


Asunto(s)
Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Resultado del Embarazo , Tacrolimus/uso terapéutico , Adolescente , Adulto , Síndrome Antifosfolípido/complicaciones , Femenino , Humanos , Japón , Prednisolona/uso terapéutico , Embarazo , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
14.
Diabetes Obes Metab ; 18(3): 249-57, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26661514

RESUMEN

AIMS: To examine the efficacy and safety of once-weekly dulaglutide 0.75 mg monotherapy compared with once-daily liraglutide 0.9 mg in Japanese patients with type 2 diabetes (T2D) for 52 weeks. METHODS: We conducted a phase III, randomized, 52-week (26-week primary endpoint), active- and placebo-controlled trial comparing 492 Japanese patients (dulaglutide, n = 281; liraglutide, n = 141; and placebo, n = 70). Participants and investigators were blinded to treatment assignment for dulaglutide and placebo but not for liraglutide (open-label comparator); after 26 weeks, patients randomized to placebo were switched to once-weekly dulaglutide 0.75 mg (open-label). The present paper reports results for patients treated with dulaglutide and patients treated with liraglutide for 52 weeks. RESULTS: At week 52, dulaglutide decreased HbA1c significantly from baseline compared with liraglutide [least squares mean difference: -0.20; 95% confidence interval (CI) -0.39, -0.01; p = 0.04]. At week 52 (last observation carried forward), dulaglutide significantly decreased pre- and post-dinner blood glucose (BG) levels, the mean of seven-point self-monitored BG profiles, the mean of all postprandial BG levels and circadian variation compared with liraglutide. Body weight was generally stable in both groups through 52 weeks. The most frequently reported adverse events were nasopharyngitis, constipation, nausea and diarrhoea. Eight dulaglutide-treated (2.9%) and four liraglutide-treated (2.9%) patients reported hypoglycaemia, with no event being severe. CONCLUSIONS: Monotherapy with once-weekly dulaglutide 0.75 mg was effective and safe in Japanese patients with T2D, with better glycaemic control compared with once-daily liraglutide 0.9 mg.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/análogos & derivados , Hemoglobina Glucada/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Liraglutida/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Anciano , Glucemia , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Esquema de Medicación , Femenino , Péptidos Similares al Glucagón/administración & dosificación , Humanos , Hipoglucemia/inducido químicamente , Japón , Masculino , Persona de Mediana Edad , Periodo Posprandial/efectos de los fármacos , Resultado del Tratamiento
15.
Diabetes Obes Metab ; 17(10): 974-83, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26179187

RESUMEN

AIMS: To examine the efficacy and safety of once-weekly dulaglutide monotherapy (0.75 mg) compared with placebo and once-daily liraglutide (0.9 mg) in Japanese patients with type 2 diabetes. METHODS: This was a phase III, 52-week (26-week primary endpoint), randomized, double-blind, placebo-controlled, open-label comparator (liraglutide) trial comparing 492 Japanese patients with type 2 diabetes (dulaglutide, n = 281; liraglutide, n = 141; and placebo, n = 70) who were aged ≥20 years. Patients and investigators were blinded to treatment assignment for dulaglutide and placebo but not for liraglutide. The primary objective evaluated the superiority of dulaglutide versus placebo on change from baseline in glycated haemoglobin (HbA1c) at 26 weeks. Analyses were performed on the full analysis set. RESULTS: At 26 weeks, once-weekly dulaglutide was superior to placebo and non-inferior to once-daily liraglutide for HbA1c change from baseline [least squares mean difference: dulaglutide vs placebo -1.57% (95% confidence interval -1.79 to -1.35); dulaglutide vs liraglutide -0.10% (95% confidence interval -0.27 to 0.07)]. The most frequently reported adverse events were nasopharyngitis, constipation, diarrhoea, nausea, abdominal distension and decreased appetite; only decreased appetite was different between the dulaglutide and liraglutide groups [dulaglutide, n = 2 (0.7%); liraglutide, n = 8 (5.8%); p = 0.003]. Nine (1.8%) patients experienced hypoglycaemia [dulaglutide, n = 6 (2.1%); liraglutide, n = 2 (1.5%); placebo, n = 1 (1.4%)], with no event being severe. CONCLUSIONS: In Japanese patients with type 2 diabetes, once-weekly dulaglutide (0.75 mg) was superior to placebo and non-inferior to once-daily liraglutide (0.9 mg) for reduction in HbA1c at 26 weeks. Dulaglutide was safe and well tolerated.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Liraglutida/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Anciano , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Esquema de Medicación , Femenino , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/efectos adversos , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Japón , Liraglutida/efectos adversos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/efectos adversos
16.
Nat Commun ; 6: 7783, 2015 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-26205309

RESUMEN

Electrically driven single-photon emitting devices have immediate applications in quantum cryptography, quantum computation and single-photon metrology. Mature device fabrication protocols and the recent observations of single defect systems with quantum functionalities make silicon carbide an ideal material to build such devices. Here, we demonstrate the fabrication of bright single-photon emitting diodes. The electrically driven emitters display fully polarized output, superior photon statistics (with a count rate of >300 kHz) and stability in both continuous and pulsed modes, all at room temperature. The atomic origin of the single-photon source is proposed. These results provide a foundation for the large scale integration of single-photon sources into a broad range of applications, such as quantum cryptography or linear optics quantum computing.

17.
Clin Exp Immunol ; 179(3): 392-7, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25286988

RESUMEN

Autoinflammatory diseases include a large spectrum of monogenic diseases, e.g. familial Mediterranean fever (FMF), as well as complex genetic trait diseases, e.g. adult-onset Still's disease (AOSD). In populations where FMF is common, an increased MEFV mutation rate is found in patients with rheumatic diseases. The aim of this study was to examine MEFV mutations in Japanese patients with AOSD. Genomic DNA was isolated from 49 AOSD patients and 105 healthy controls, and exons 1, 2, 3 and 10 of the MEFV gene genotyped by direct sequencing. MEFV mutation frequencies in AOSD patients were compared with controls. We found no significant difference in overall allele frequencies of MEFV variants between AOSD patients and controls. However, MEFV exon 10 variants (M694I and G632S) were significantly higher in AOSD patients than controls (6.1 versus 0%). In addition, there was no significant difference between MEFV variant carriers and non-carriers with clinical manifestations, but the monocyclic clinical course of the AOSD disease phenotype was observed less frequently in patients without MEFV variants. AOSD patients had significantly higher frequencies of MEFV exon 10 mutations, suggesting that low-frequency variants of MEFV gene may be one of the susceptibility factors of AOSD.


Asunto(s)
Proteínas del Citoesqueleto/genética , Mutación/genética , Enfermedad de Still del Adulto/genética , Adulto , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Exones/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Japón , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Pirina , Adulto Joven
18.
Diabet Med ; 28(1): 96-9, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21210542

RESUMEN

AIMS: Previous studies have implicated reduced serum bilirubin concentrations in the development of cardiovascular disease. The aim of this study was to examine whether bilirubin may explain the high incidence of vascular complications in haemodialysis patients with Type 2 diabetes. METHODS: We compared serum bilirubin concentrations, as well as other known aetiological risk factors for cardiovascular disease, in 206 Type 2 diabetes patients on haemodialysis with those in 741 Type 2 diabetes patients not receiving haemodialysis, and evaluated the association between serum bilirubin concentration and cardiovascular disease incidence. RESULTS: Incidences of cardiovascular disease and systolic blood pressure were higher; however, BMI and serum total cholesterol were lower in haemodialysis patients compared with those in patients without haemodialysis. Serum total (0.30 ± 0.10 vs. 0.74 ± 0.26 mg/dl, 0.005 ± 0.002 vs. 0.013 ± 0.004 mmol/l, P < 0.0001) and indirect (0.17 ± 0.08 vs. 0.70 ± 0.23 mg/dl, 0.003 ± 0.001 vs. 0.012 ± 0.004 mmol/l, P < 0.0001) bilirubin were lower in haemodialysis patients compared with those in patients without haemodialysis. Stepwise regression analysis demonstrated that age (ß = 0.109, F = 5.959, P < 0.05), duration of diabetes (ß = -0.112, F = 6.048, P < 0.05), sex (ß = -0.123, F = 8.623, P < 0.05), cardiovascular disease events (ß = -0.099, F = 5.131, P < 0.05) and presence of haemodialysis (ß = -0.626, F = 201.727, P < 0.01) were independent factors for serum total bilirubin. Logistic regression demonstrated that age (OR 1.089, 95% CI 1.044-1.136; P < 0.0001), duration of diabetes (OR 1.029, 95% CI 1.001-1.059; P = 0.0423), body mass index (OR 1.115, 95% CI 1.001-1.242; P = 0.0487), habit of smoking (OR 2.445, 95% CI 1.046-5.716; P = 0.0391) and serum total bilirubin (OR 0.192, 95% CI 0.037-0.989; P = 0.0484) were independent factors for cardiovascular disease events. CONCLUSIONS: Low serum bilirubin concentration could be one of the important factors for the high incidence of cardiovascular disease in Type 2 diabetes patients receiving haemodialysis.


Asunto(s)
Bilirrubina/sangre , Enfermedades Cardiovasculares/sangre , Diabetes Mellitus Tipo 2/sangre , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/terapia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal , Factores de Riesgo
19.
Trop Biomed ; 27(2): 177-84, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20962713

RESUMEN

Formalin-ether sedimentation (MGL) is a well-known technique for the examination of faeces for parasites, but some recent reports have indicated that its efficiency is not as high as originally thought. We reevaluated the recovery efficiency of the original MGL (O-MGL) technique to modify it. We subsequently adopted the following modified MGL technique (M-MGL): filtration by three layers of gauze and washing, adjustment to pH 3, retreatment of plug, and use of 1.5 g of faeces. We also compared five faecal examination techniques (including the O-MGL and the M-MGL) for three parameters: recovery efficiency, sensitivity, and mean number of eggs detected. The highest sensitivity was obtained by the M-MGL (95%), followed by the commercially available kit (Kit; 90%), O-MGL (76%), Kato-Katz (KK; 57%), and direct smear (DS; 50%). The mean numbers of Ascaris lumbricoides eggs recovered by the techniques were in order M-MGL (148 eggs), Kit (97), O-MGL (41), KK (11), and DS (6). This M-MGL technique has the advantage not only of the above-mentioned three parameters, but also the ease of microscopic observation and the concentration index. The parameters of the O-MGL technique were not necessarily sufficient compared with the other techniques. It seems that the improved M-MGL technique in the present study is applicable for field surveys, particularly when the survey is done in areas of low parasite endemicity.


Asunto(s)
Éter/química , Heces/parasitología , Formaldehído/química , Recuento de Huevos de Parásitos/métodos , Animales , Ascaris lumbricoides , Humanos , Masculino
20.
Transplant Proc ; 42(7): 2797-9, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20832591

RESUMEN

A 64-year-old man who suffered from human T-cell leukemia virus type I (HTLV-I)-associated myelopathy (HAM) after living-donor liver transplantation (LDLT) for liver cirrhosis due to hepatitis C virus infection complained of xerostomia. Although exocrine function test results were positive, autoantibodies including anti-SS-A/SS-B antibodies and sialography showed negative findings. Labial salivary gland biopsy revealing infiltration of 60 counts of mononuclear cells (MNCs) in minor salivary glands led to a diagnosis of Sjögren's syndrome-like sialadenitis. Immunohistochemistry demonstrated dominant CD68 staining and major histocompatibility complex class II on the surface of infiltrating MNCs. Herein we have reported a rare condition of macrophage-dominant sialadenitis in a patient with HAM after LDLT.


Asunto(s)
Leucemia-Linfoma de Células T del Adulto/etiología , Trasplante de Hígado/efectos adversos , Donadores Vivos , Sialadenitis/etiología , Alanina Transaminasa/sangre , Antivirales/uso terapéutico , Aspartato Aminotransferasas/sangre , Humanos , Inmunoglobulina G/sangre , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/patología , Cirrosis Hepática/cirugía , Macrófagos/patología , Masculino , Persona de Mediana Edad , Ribavirina/uso terapéutico , Sialadenitis/patología
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