Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
1.
Intest Res ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39155522

RESUMO

Background/Aims: Treatment using tumor necrosis factor-α (TNF-α) inhibitors is one of the risk factors for active tuberculosis (TB) in patients with Crohn's disease (CD). Biologics, such as ustekinumab (UST) and vedolizumab (VDZ), are less likely to cause opportunistic infections. However, large-scale studies for active TB and biologics other than TNF-α inhibitors are limited. We aimed to investigate the association between biologics and active TB utilizing a Japanese medical claims database. Methods: We analyzed retrospectively the association of the risk of active TB development with treatment using TNF-α inhibitors and other biologics (UST and VDZ) in patients with CD using the Japanese Medical Data Vision (MDV) database between April 2008 and June 2022. The durations of each biologic and biologic-free treatment were calculated for each patient. Univariate and multivariate analyses were performed using the Cox proportional hazards model, with the utilization of biologics considered as time-dependent covariates. Results: We included 28,811 patients with CD in MDV database. Finally, 17,169 patients were analyzed. In total, 7,064 patients were categorized as biologic-naïve, while 10,105 were classified as biologic-experienced. Seventeen patients developed active TB, including 7 on infliximab, 5 on adalimumab, and 5 on no biologics. None of the patients treated with UST and VDZ developed active TB. Multivariate analysis suggested that TNF-α inhibitors were the risk factors for active TB (hazard ratio, 3.66; P= 0.020). Conclusions: TNF-α inhibitors, but not UST or VDZ, are risk factors for active TB in Japanese patients with CD.

2.
J Gastroenterol Hepatol ; 38(6): 910-920, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36807301

RESUMO

BACKGROUND AND AIMS: Ustekinumab has been proven to be effective for treatment of patients with Crohn's disease; however, 30-40% of patients have been reported to lose clinical response within 2 years. We aimed to evaluate the efficacy of ustekinumab and identify predictors of short-term and long-term efficacy in Crohn's disease. METHODS: Patients with Crohn's disease receiving their first ustekinumab infusion in our hospital between June 2017 and September 2020 were prospectively enrolled. Concentrations of serum cytokines and chemokines were measured using a multiplex bead array assay. RESULTS: Fifty-nine Crohn's disease patients were enrolled in this study. Among 34 clinically active patients, 38.2% achieved a clinical response at week 8. None of the assayed factors were associated with short-term clinical response. Cumulative persistence rates of ustekinumab were 77.6% at 1 year and 58.9% at 2 years. Univariate Cox regression analysis revealed that Harvey-Bradshaw Index scores at baseline, concomitant immunomodulator treatment, and concentrations of interferon gamma-induced protein-10, monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-1RA, IL-4, IL-6, and IL-8 were significantly associated with loss of efficacy. Multivariate Cox regression analysis found that biologic naïve status (hazard ratio [HR]: 0.1191, 95% confidence interval [CI]: 0.02458-0.5774) and MCP-1 concentrations (HR: 1.038, 95% CI: 1.015-1.062) were significantly and associated with loss of sustained efficacy for ustekinumab treatment. CONCLUSIONS: Our findings suggest that pretreatment serum MCP-1 analysis, combined with a history of biologic use, could be a novel biomarker for predicting the long-term efficacy of ustekinumab in patients with Crohn's disease.


Assuntos
Produtos Biológicos , Doença de Crohn , Humanos , Ustekinumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Quimiocina CCL2 , Indução de Remissão , Produtos Biológicos/uso terapêutico , Resultado do Tratamento
3.
PLoS One ; 18(1): e0280252, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36634124

RESUMO

Endoscopic mucosal healing (MH) is an important treatment goal for patients with ulcerative colitis (UC). The neutrophil-to-lymphocyte ratio (NLR) reflects systemic inflammation and has been reported to be a useful predictive marker for UC. This study aimed to evaluate the clinical utility of the NLR for predicting clinical relapse in UC patients with MH. We retrospectively enrolled patients with UC who underwent colonoscopy at the Osaka City University Hospital between January 2010 and December 2010, whose Mayo Endoscopic Subscore was 0 or 1. The correlation between the incidence of relapse and demographic factors, including the NLR, was analyzed. We included 129 patients in the present study. The median NLR at the time of endoscopy was 1.98, and differences in the high NLR group and the low NLR group were compared. During a median follow-up period of 46.4 months, 58 patients (45.0%) experienced relapse. The cumulative relapse-free rate was significantly higher in the low NLR group than in the high NLR group (P = 0.03, log-rank test). Multivariate analysis identified high NLR as an independent prognostic factor for clinical relapse (hazard ratio, 1.74; 95% confidence interval, 1.02-2.98; P = 0.04). NLR is a novel and useful predictor of clinical relapse in UC patients with MH, and it can potentially be a strong indicator to determine the appropriate treatment strategy and decision-making in clinical practice.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Estudos Retrospectivos , Neutrófilos , Colonoscopia , Doença Crônica , Linfócitos , Mucosa Intestinal , Índice de Gravidade de Doença , Recidiva
4.
Drug Discov Today ; 28(2): 103429, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36334648

RESUMO

Gene therapy has been one of the most promising therapeutic approaches in recent years. This study analyzed a research and development (R&D) system for adeno-associated virus (AAV)-based gene therapies, and confirmed that there was a gap between the development and manufacturing capabilities. Although a start-up company that has no academic or manufacturing facilities can begin the clinical development process, it cannot successfully continue development activities without forming alliances and capital investment or, at a certain stage, without appropriate manufacturing and marketing strategies. We reviewed a series of case studies to categorize the acquisition patterns of pharmaceutical companies that are engaged in AAV gene therapy. These results provide insights into the R&D structures for AAV gene therapies from a technological management perspective.


Assuntos
Indústria Farmacêutica , Terapia Genética , Comércio , Terapia Genética/métodos , Vetores Genéticos , Investimentos em Saúde , Pesquisa , Dependovirus , Indústria Farmacêutica/organização & administração , Estudos de Casos Organizacionais
5.
Intern Med ; 61(12): 1835-1841, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34866098

RESUMO

Wilson disease is an inherited copper metabolism disorder. We herein report a novel endoscopic finding in three men with Wilson disease. These patients underwent upper endoscopy due to gastrointestinal symptoms or during follow-up. In each case, endoscopy revealed lustrous white erosions surrounded by an erythematous mucosa in the greater curvature of the gastric body. A biopsy of the lesions showed orcein-positive tissue, indicating copper deposition, in the interstitial stroma and fundic glands of the mucosa. All patients had been receiving treatment with zinc acetate. These endoscopic findings might have been related to the cytotoxicity of the accumulated copper and zinc acetate.


Assuntos
Degeneração Hepatolenticular , Gastropatias , Biópsia , Cobre , Mucosa Gástrica/patologia , Gastroscopia , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/patologia , Humanos , Masculino , Gastropatias/patologia , Acetato de Zinco
6.
Intern Med ; 61(4): 577-580, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34393163

RESUMO

Staphylococcus schleiferi has rarely been reported to cause pyogenic spondylitis. A 42-year-old man had been treated for Crohn's disease with immunosuppressive agents and home parenteral nutrition via a central vein (CV) port. The patient was admitted to our hospital, presenting with neck pain and a fever. A neurological examination showed slight weakness in his left-hand muscles, and he was diagnosed with pyogenic spondylitis of C6 and C7 vertebral bodies due to catheter-related blood stream infection caused by S. schleiferi. An early diagnosis by magnetic resonance imaging, CV port removal and antibiotic therapy targeting S. schleiferi improved his symptoms.


Assuntos
Doença de Crohn , Espondilite , Adulto , Vértebras Cervicais/patologia , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Humanos , Masculino , Espondilite/diagnóstico por imagem , Espondilite/etiologia , Staphylococcus
7.
Endosc Int Open ; 8(12): E1817-E1825, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33269315

RESUMO

Background and study aims Eosinophilic gastrointestinal disorders are classified into eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic colitis according to the site of eosinophilic infiltration. Although well established in eosinophilic esophagitis, endoscopic findings in eosinophilic gastritis and eosinophilic gastroenteritis with regard to gastric lesions have not been clearly described. The aim of this study was to identify endoscopic findings of gastric lesions associated with eosinophilic gastrointestinal disorders. Patients and methods Out of 278 patients with eosinophilic gastrointestinal disorders, 18 had eosinophilic gastritis or eosinophilic gastroenteritis confirmed by biopsy; their endoscopic images were analyzed retrospectively. The association between endoscopic findings and number of eosinophils in the gastric mucosa was investigated. Results Erythema was most frequently observed (72 %), followed by ulcers (39 %), discoloration (33 %), erosions (28 %), nodularity (28 %), and polyps (28 %). There were several unique endoscopic findings such as submucosal tumor-like deep large ulcers in three patients, antral Penthorum -like appearances (small nodules radially lined toward the pyloric ring) in three patients, "muskmelon-like appearances" (discolored mucosa-composed mesh pattern) in three patients, multiple white granular elevations in two patients, cracks (appearance of furrows similar to those in eosinophilic esophagitis) in five patients, and antral rings in one patient. No significant association was observed between endoscopic findings and number of gastric eosinophils. Conclusions Several unique endoscopic findings of gastric lesions were observed in patients with eosinophilic gastritis or eosinophilic gastroenteritis. Submucosal tumor-like ulcers, antral Penthorum -like appearances, muskmelon-like appearances, and cracks might be associated with eosinophilic gastrointestinal disorders.

8.
Sci Rep ; 10(1): 4883, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32184453

RESUMO

Loss-of-function mutations in the solute carrier organic anion transporter family, member 2a1 gene (SLCO2A1), which encodes a prostaglandin (PG) transporter, have been identified as causes of chronic nonspecific multiple ulcers in the small intestine; however, the underlying mechanisms have not been revealed. We, therefore, evaluated the effects of systemic knockout of Slco2a1 (Slco2a1-/-) and conditional knockout in intestinal epithelial cells (Slco2a1ΔIEC) and macrophages (Slco2a1ΔMP) in mice with dextran sodium sulphate (DSS)-induced acute colitis. Slco2a-/- mice were more susceptible to DSS-induced colitis than wild-type (WT) mice, but did not spontaneously develop enteritis or colitis. The nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 (NLRP3) inflammasome was more strongly upregulated in colon tissues of Slco2a-/- mice administered DSS and in macrophages isolated from Slco2a1-/- mice than in the WT counterparts. Slco2a1ΔMP, but not Slco2a1ΔIEC mice, were more susceptible to DSS-induced colitis than WT mice, partly phenocopying Slco2a-/- mice. Concentrations of PGE2 in colon tissues and macrophages from Slco2a1-/- mice were significantly higher than those of WT mice. Blockade of inflammasome activation suppressed the exacerbation of colitis. These results indicated that Slco2a1-deficiency increases the PGE2 concentration, resulting in NLRP3 inflammasome activation in macrophages, thus exacerbating intestinal inflammation.


Assuntos
Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Transportadores de Ânions Orgânicos/deficiência , Transportadores de Ânions Orgânicos/metabolismo , Animais , Western Blotting , Células Cultivadas , Colite/genética , Sulfato de Dextrana/toxicidade , Enterocolite/induzido quimicamente , Enterocolite/genética , Enterocolite/metabolismo , Enterocolite/patologia , Ensaio de Imunoadsorção Enzimática , Inflamassomos/imunologia , Inflamassomos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Modelos Teóricos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transportadores de Ânions Orgânicos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
9.
J Gastroenterol ; 55(6): 615-626, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31989252

RESUMO

BACKGROUND: Small bowel stricture is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD. METHODS: Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available. RESULTS: A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation. CONCLUSIONS: In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD.


Assuntos
Enteroscopia de Balão , Doença de Crohn/complicações , Obstrução Intestinal/etiologia , Intestino Delgado/patologia , Adulto , Constrição Patológica/etiologia , Doença de Crohn/terapia , Endoscopia/métodos , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Obstrução Intestinal/terapia , Masculino , Estudos Retrospectivos , Abandono do Hábito de Fumar , Fatores de Tempo , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/administração & dosagem
10.
Nihon Shokakibyo Gakkai Zasshi ; 115(9): 797-803, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30197393

RESUMO

We performed a retrospective analysis on three patients diagnosed with EGE (eosinophilic gastroenteritis) at our hospital and 90 cases obtained from a case database. The cases' genders, ages, peripheral eosinophils, ascites, endoscopic findings, biopsy findings, diagnostic scores, and rates of glucocorticoid use were evaluated. The gender ratio was 40 males to 53 females, and the median age was 50. 78.5% of cases had peripheral eosinophilia. The prevalence of allergic diseases was 31.2%, and the incidence of ascites was 34.4%. 83.9% of endoscopic findings were positive, and 92.5% of biopsies were positive. The total rate of glucocorticoid use was 77.4%. When both score <5 and age <33 conditions were met, the rate of glucocorticoid use was approximately 30%, meaning it was possible to avoid glucocorticoid use.


Assuntos
Enterite/terapia , Eosinofilia/terapia , Gastrite/terapia , Adulto , Ascite , Enterite/epidemiologia , Eosinofilia/epidemiologia , Feminino , Gastrite/epidemiologia , Gastroenterite , Humanos , Masculino , Estudos Retrospectivos
11.
Inflamm Bowel Dis ; 24(6): 1307-1315, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29668948

RESUMO

Background: Little is known about the prevalence and pathogenicity of human herpes viruses except for cytomegalovirus (CMV) in patients with inflammatory bowel disease (IBD). The aim of this study was to determine the prevalence of human herpes viruses on colonic mucosa in patients with IBD and assess the long-term outcomes in these patients. Methods: We examined the colonic mucosal specimens from 66 patients with ulcerative colitis (UC), 54 patients with Crohn's disease (CD), and 29 healthy patients to identify the 6 most common types of human herpes virus, using multiplex polymerase chain reaction (PCR) technique. Results: Herpes simplex virus (HSV)-1/2 and varicella-zoster virus (VZV) were not detected in any of the groups. There was a higher prevalence of Epstein-Barr virus (EBV) (21.2%) and CMV (15.1%) in patients with UC than in patients with CD (EBV 9.3%, CMV 0%) and patents in the healthy control group (EBV 0%, CMV 3.4%). The prevalence of human herpes virus (HHV)-6A/B and HHV-7 was not statistically different among the groups. Five UC patients with inflammation had coexisting CMV and EBV or HHV-6. The combined infection of CMV with EBV or HHV-6 was a significant and independent prognostic factor for subsequent colectomy in patients with UC. Conclusions: The increased prevalence of CMV coexisting with EBV/HHV-6 infection was associated with the clinical course in patients with UC. 10.1093/ibd/izy005_video1izy005_Video_15786489376001.


Assuntos
Colo/virologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/epidemiologia , Doenças Inflamatórias Intestinais/virologia , Adulto , Idoso , Estudos de Casos e Controles , Coinfecção/epidemiologia , Coinfecção/virologia , Colectomia , Colo/patologia , Colonoscopia , Citomegalovirus/isolamento & purificação , Feminino , Herpesvirus Humano 3/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Doenças Inflamatórias Intestinais/complicações , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Simplexvirus/genética
12.
Scand J Gastroenterol ; 53(5): 579-585, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29171305

RESUMO

OBJECTIVES: Infliximab is effective in patients with ulcerative colitis (UC); however, one-third of patients do not respond and require additional therapies such as other biologic agents. Therefore, the aim of this study was to analyze the association between pro-inflammatory molecules and clinical efficacy to elucidate possible mechanisms for the non-response to infliximab to aid in treatment selection. MATERIALS AND METHOD: Patients with moderate-to-severe active UC receiving infliximab in our hospital between 2010 and 2016 for whom pre-treatment serum samples were available were retrospectively evaluated. We analyzed the association between serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) and the clinical efficacy of infliximab. The primary endpoint was clinical response at the end of the induction period. RESULTS: Forty-one patients were included in this study. After induction therapy, 27 patients (65.9%) showed a clinical response. Serum IL-6 levels were significantly lower in responders than in non-responders (p = .012), whereas no significant differences were noted in other factors including sMAdCAM-1 and TNF-α. Multivariate analysis identified that serum IL-6 level (odds ratio = 0.72; 95% confidence interval, 0.54-0.96; p = .027) was independently associated with response to infliximab. CONCLUSIONS: Serum IL-6 level is associated with response to infliximab in UC. Elevated concentrations of IL-6 may provide insight to the mechanism of non-response to infliximab.


Assuntos
Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Interleucina-6/sangue , Adulto , Biomarcadores/sangue , Moléculas de Adesão Celular , Feminino , Humanos , Imunoglobulinas/sangue , Modelos Logísticos , Masculino , Mucoproteínas/sangue , Análise Multivariada , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
13.
Intern Med ; 56(17): 2245-2252, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28794359

RESUMO

Objective Balloon-assisted endoscopy enables access to and treatment of strictures in the small intestine using endoscopic balloon dilation (EBD); however, the long-term outcomes of EBD have not been sufficiently evaluated. This study evaluated the long-term outcomes of EBD in Crohn's disease to identify the risk factors associated with the need for subsequent surgical intervention. Methods We retrospectively analyzed patients with Crohn's disease who had undergone EBD with double-balloon endoscopy (DBE) for small intestinal strictures at a single center between 2006 and 2015. The long-term outcomes were assessed based on the cumulative surgery-free rate following initial EBD. Results Seventy-two EBD with DBE sessions and 112 procedures were performed for 37 patients during this period. Eighteen patients (48.6%) required surgery during follow-up. Significant factors associated with the need for surgery in a multivariate analysis were multiple strictures (adjusted hazard ratio, 14.94; 95% confidence interval, 1.91-117.12; p=0.010). One patient (6.7%) required surgery among 15 who had single strictures compared to 17 (77.3%) among 22 patients with multiple strictures. Conclusion In a multivariate analysis, the presence of multiple strictures was a significant risk factor associated with the need for surgery; therefore, a single stricture might be a good indication for EBD using DBE for small intestinal strictures in Crohn's disease patients.


Assuntos
Constrição Patológica/complicações , Constrição Patológica/cirurgia , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Dilatação/efeitos adversos , Obstrução Intestinal/complicações , Obstrução Intestinal/cirurgia , Adulto , Constrição Patológica/etiologia , Endoscopia Gastrointestinal/métodos , Feminino , Humanos , Obstrução Intestinal/etiologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
14.
PLoS One ; 12(1): e0169845, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28076386

RESUMO

OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) has been used to determine the outcome in malignancies and coronary heart disease. Some reports considered the value of NLR as a predictor of response to infliximab in patients with Crohn's disease or rheumatoid arthritis; however, no similar studies have been reported for ulcerative colitis (UC). This study aimed to evaluate the clinical significance of the baseline NLR in patients with UC treated by infliximab. MATERIALS AND METHODS: Patients with moderate-to-severe active UC who received the first infliximab infusion in our hospital between 2010 and 2015, who showed clinical response during the induction period, were retrospectively evaluated for long-term outcomes and risk factors for loss of response (LOR) during infliximab maintenance therapy. Baseline inflammatory markers including NLR were measured within one week before the initiation of infliximab. RESULTS: Fifty-nine patients with moderate-to-severe active UC started treatment with infliximab and 37 patients (62.7%) experienced clinical response after induction therapy. Fourteen of 37 patients on maintenance therapy lost the response during follow-up. Baseline NLR of patients with LOR was significantly higher than in patients with sustained response. The NLR cut-off value of 4.488 was predictive of LOR, using receiver operating characteristic analysis (sensitivity: 78.6%, specificity: 78.3%). A univariate analysis revealed a significant relationship between relapse-free survival and the NLR (P = 0.018). Multivariate analysis indicated the NLR as an independent prognostic factor for LOR (hazard ratio = 3.86, 95% confidence interval: 1.20-12.4, P = 0.023). CONCLUSIONS: Baseline NLR is a useful prognostic marker in patients with moderate-to-severe active UC treated with infliximab, and may contribute to appropriate use of infliximab.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Resistência a Medicamentos , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Linfócitos/citologia , Neutrófilos/citologia , Adulto , Contagem de Células Sanguíneas , Colite Ulcerativa/sangue , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Infliximab/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
Nanomedicine ; 12(1): 123-30, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26364795

RESUMO

Immunoinhibitory oligodeoxynucleotides (INH-ODNs) are promising inhibitors of Toll-like receptor 9 (TLR9) activation. To efficiently deliver INH-ODNs to TLR9-positive cells, we designed a Takumi-shaped DNA (Takumi) consisting of two partially complementary ODNs as the main component of a DNA hydrogel. Polyacrylamide gel electrophoresis showed that Takumi-containing INH-ODNs (iTakumi) and iTakumi-based DNA hydrogel (iTakumiGel) were successfully generated. Their activity was examined in murine macrophage-like RAW264.7 cells and DC2.4 dendritic cells by measuring tumor necrosis factor-α and interleukin-6 release after the addition of a TLR9 ligand (CpG ODN). Cytokine release was efficiently inhibited by the iTakumiGel. Flow cytometry analysis and confocal microscopy showed that cellular uptake of INH-ODN was greatly increased by the iTakumiGel. These results indicate that a Takumi-based DNA hydrogel is useful for the delivery of INH-ODNs to immune cells to inhibit TLR9-mediated hyperinduction of proinflammatory cytokines. From the Clinical Editor: Toll-like receptor 9 activation has been reported to be associated with many autoimmune diseases. DNA inhibition using oligodeoxynucleotides is one of the potential treatments. In this article, the authors described hydrogel-based platform for the delivery of the inhibitory oligodeoxynucleotides for enhanced efficacy. The positive findings could indicate a way for the future.


Assuntos
DNA/administração & dosagem , DNA/imunologia , Células Dendríticas/imunologia , Hidrogéis/química , Macrófagos/imunologia , Receptor Toll-Like 9/imunologia , Animais , Linhagem Celular , Cristalização/métodos , Células Dendríticas/efeitos dos fármacos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/imunologia , Macrófagos/efeitos dos fármacos , Camundongos , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Receptor Toll-Like 9/análise
16.
Nihon Shokakibyo Gakkai Zasshi ; 110(3): 441-8, 2013 03.
Artigo em Japonês | MEDLINE | ID: mdl-23459539

RESUMO

A man in his 70's was admitted to our hospital for treatment of a huge hepatocellular carcinoma (HCC) by transcatheter hepatic arterial embolization (TAE). After treatment, anuria occurred, and laboratory examinations revealed a diagnosis of tumor lysis syndrome (TLS). He underwent conservative therapy including hemodialysis, resulting in complete remission of TLS. On the other hand, poor hepatic functional reserve was seen temporarily. After conservative therapy, biochemical markers returned dramatically. TLS is a group of metabolic complications in cancer therapy. It may occur in highly sensitive tumors, resulting from a rapid release of cytoplasmic degradation products of malignant cells. Generally it is rare in the treatment of solid tumors. In the case of TAE for huge HCC, we should keep the possibility of TLS in mind.


Assuntos
Carcinoma Hepatocelular/terapia , Embolização Terapêutica/efeitos adversos , Neoplasias Hepáticas/terapia , Síndrome de Lise Tumoral/etiologia , Idoso , Humanos , Masculino , Diálise Renal , Síndrome de Lise Tumoral/terapia
17.
Clin J Gastroenterol ; 6(1): 46-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26181404

RESUMO

A 73-year-old male was admitted to our institution with complaints of nausea, vomiting, and abdominal distension. Plain abdominal computed tomography (CT) suggested intussusception in the jejunum. Enhanced abdominal CT revealed the 'target-like' sign and ultrasonography revealed the 'multiple concentric ring' sign; therefore, a diagnosis of entero-enteric intussusception was made. The small intestinal obstruction and cause of the intussusception were not evident. The patient was treated conservatively with fasting and transfusion therapy to prevent intestinal obstruction. However, with no spontaneous resolution of intussusception, surgical treatment was decided. The operative findings revealed a jejunal tumor about 30 cm from the Treiz ligament, and the jejunum including the tumor with a 5 cm margin were partially resected. The resected tumor was a 35 × 50 mm soft mass spreading laterally with nodules. The pathological examinations revealed tubulovillous adenocarcinoma in the adenoma. Intussusception is rare in adults compared to children. About 45 % of cases of intussusception in adults are due to small intestinal tumors such as malignant lymphoma or lipoma, but a tubulovillous adenocarcinoma with adenoma is a rare cause of intussusception. We present a rare case of jejunal tubulovillous adenocarcinoma in adenoma presenting with entero-enteric intussusception.

18.
Nihon Shokakibyo Gakkai Zasshi ; 109(10): 1760-9, 2012 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-23047634

RESUMO

We report here a case of intestinal obstruction occurring during anti-tuberculous therapy for tuberculous peritonitis. An 89-year-old woman, who had been treated for tuberculous spondylitis and operated for tuberculous mastitis and peritonitis, was transferred to our hospital with high grade fever, lower abdominal pain and vomiting. An enhanced abdominal computed tomography (CT) revealed ascites and hypertrophy of the parietal peritoneum. Puncture and drainage of ascites were performed and revealed that a smear examination of the specimen was positive for acid-fast bacilli (Gaffky 1). Treatment by rifampicin, isoniazid and ethambutol for tuberculous peritonitis was started then halted because of drug-induced liver injury. After recovery of the liver damage improved, anti-tuberculosis drugs (rifampicin and streptomycin) were restarted. However two days after recommencing administration, repeated vomiting occurred. An abdominal X-ray showed intestinal obstruction. An ileus tube was inserted and she was treated conservatively, but her symptoms did not improve. Injection of contrast medium through the ileus tube showed obstruction of the upper jejunum, so open surgery was performed. Disseminated yellowish miliary tubercles were seen on the peritoneum and severe inflammatory adhesions were found between the jejunum and the ileum. After ablation of the adhesions, partial resections of jejunum and ileum were performed. Histological examination confirmed the diagnosis of tuberculous peritonitis.


Assuntos
Íleus/etiologia , Doenças do Jejuno/etiologia , Peritonite Tuberculosa/complicações , Peritonite Tuberculosa/tratamento farmacológico , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Feminino , Humanos
19.
Gan To Kagaku Ryoho ; 39(2): 281-4, 2012 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-22333644

RESUMO

A 80-year-old female was referred to our hospital for hematomesis. An abdominal CT revealed a heterogeneous giant tumor of about 11 cm, rich in vascularity, extending from the gastric fundus, beyond the upper side of the spleen, to the left thoracic diaphragm. Gastroscopy showed a 5 cm submucosal tumor with a visible vessel at the gastric fundus. After biopsy was performed, she was diagnosed with a c-kit-positive gastrointestinal stromal tumor (GIST)of the stomach. Following endoscopic hemostasis for gastric bleeding, imatinib mesilate was administered. The tumor reduced markedly, and vascularity in the tumor was diminished, the visible vessels of the tumor disappeared. For curative resection, total gastrectomy with a distal pancreato -splenectomy and a left diaphgram resection is necessary, but surgery was high-risk for this patient because she was advanced in age. She is now achieving a good partial response without surgery.


Assuntos
Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Hemorragia/etiologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso de 80 Anos ou mais , Benzamidas , Feminino , Gastrectomia , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/patologia , Hemorragia/cirurgia , Humanos , Mesilato de Imatinib , Esplenectomia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X
20.
Gan To Kagaku Ryoho ; 38(8): 1337-40, 2011 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-21829076

RESUMO

A 65-year-old female was admitted to our hospital with abdominal distension. Abdominal CT and MRI revealed massive ascites and an omental cake, but the ovaries were of normal size. After an omentum biopsy was performed during open abdominal surgery, she was diagnosed as peritoneal serous papillary adenocarcinoma. After 6 courses of chemotherapy with paclitaxel and carboplatin, the massive ascites totally disappeared, and a second look operation could be performed. She is still alive with no sign of recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Papilar/tratamento farmacológico , Paclitaxel/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Membrana Serosa/patologia , Idoso , Biópsia , Carboplatina/administração & dosagem , Carcinoma Papilar/cirurgia , Terapia Combinada , Feminino , Humanos , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Tomógrafos Computadorizados
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA