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1.
Thromb Res ; 176: 74-78, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30780007

RESUMO

BACKGROUND: Severe acute cholecystitis (AC) is defined by the association of organ dysfunction, including hematological dysfunction, with AC. Severe AC is often complicated by disseminated intravascular coagulation (DIC), the diagnostic criteria of which overlap with AC-associated hematological dysfunction. Since the diagnosis of DIC often delays definitive surgical management of severe AC, treatment of DIC in this setting is clinically important. Recombinant human soluble thrombomodulin (rTM) is a new agent that has proven clinically useful for treating DIC. However, the relevance of rTM to sepsis-induced DIC caused by AC has not been clinically evaluated. This retrospective multicenter study aimed to determine the clinical impact of rTM on sepsis-induced DIC caused by AC. METHODS: This retrospective multicenter study initially included 68 consecutive patients and proceeded between July 2014 and December 2017. The inclusion criterion was sepsis-induced DIC caused by severe AC due to benign disease. Sixteen of the 68 patients were excluded in this study due to having advanced malignant tumors. Finally, 42 patients were enrolled in this study. We treated DIC with AC using Recomodulin® Injection (rTM) at doses of 130 or 380 U/kg/day. RESULTS: 17 and 25 patients were treated with and without rTM, respectively. Values on days 3 and 7 did not significantly differ between the groups for PT-INR (P = 0.38 and P = 0.16, respectively) and FDP (P = 0.06 and P = 0.08, respectively), and PLT was significantly increased in the rTM group at day 7 (P = 0.03). Resolution rates of DIC on day 7 were significantly higher in the group treated with, than without rTM (94.1% [16/17] vs. 68.0% [17/25], P = 0.04). Two patients in each group died of sepsis-induced DIC associated with severe AC, and thus mortality rates did not significantly differ. CONCLUSIONS: rTM can may be improve the resolution rate of sepsis-induced DIC due to severe AC. Future studies should include more patients to validate our findings.


Assuntos
Colecistite Aguda/complicações , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/etiologia , Sepse/complicações , Trombomodulina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
2.
Int J Mol Sci ; 17(3): 350, 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-27005617

RESUMO

The restoration of innate immune responses has potential as a novel therapeutic strategy for chronic hepatitis C (CHC). We compared the efficacy and safety of induction therapy (IT) with natural interferon-ß (n-IFN-ß) followed by pegylated-IFN-α/ribavirin (PR) alone (group A, n = 30) and IT with a protease inhibitor (PI) (simeprevir or vaniprevir)/PR (group B, n = 13) in CHC patients with genotype 1b and high viral loads. During IT with nIFN-ß, virologic response rates in group A and group B were 10% and 8% (p = 0.6792) at week 4, 30% and 16% (p = 0.6989) at week 12 and 47% and 20% (p = 0.0887) at week 24 respectively. During and after the treatment with PR alone or PI/PR, virologic response rates in groups A and B were 50% and 82% (p = 0.01535) at week 4, 53% and 91% (p = 0.006745) at week 8, 57% and 91% (p = 0.001126) at week 12, 57% and 100% (p < 0.001845) at the end of the treatment and 57% and 80% (p < 0.005166) after treatment cessation. IT with PI/PR linked to the restoration of innate immune response was tolerated well, overcame virological breakthrough, enhanced early virologic responses, and resulted in a sustained virologic response in difficult-to-treat CHC patients. IT with PI/PR is beneficial for treating difficult-to-treat CHC patients.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Indóis/uso terapêutico , Interferon beta/uso terapêutico , Polietilenoglicóis/uso terapêutico , Inibidores de Proteases/uso terapêutico , Ribavirina/uso terapêutico , Simeprevir/uso terapêutico , Idoso , Antivirais/administração & dosagem , Ciclopropanos , Esquema de Medicação , Feminino , Genótipo , Hepacivirus/genética , Humanos , Indóis/administração & dosagem , Interferon beta/administração & dosagem , Isoindóis , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Prolina/análogos & derivados , Inibidores de Proteases/administração & dosagem , Ribavirina/administração & dosagem , Simeprevir/administração & dosagem , Sulfonamidas
3.
World J Gastroenterol ; 20(15): 4362-9, 2014 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-24764674

RESUMO

AIM: To evaluate the efficacy and safety of esomeprazole-based triple therapy compared with lansoprazole therapy as first-line eradication therapy for patients with Helicobacter pylori (H. pylori) in usual post-marketing use in Japan, where the clarithromycin (CAM) resistance rate is 30%. METHODS: For this multicenter, randomized, open-label, non-inferiority trial, we recruited patients (≥ 20 years of age) with H. pylori infection from 20 hospitals in Japan. We randomly allocated patients to esomeprazole therapy (esomeprazole 20 mg, CAM 400 mg, amoxicillin (AC) 750 mg for the first 7 d, with all drugs given twice daily) or lansoprazole therapy (lansoprazole 30 mg, CAM 400 mg, AC 750 mg for the first 7 d, with all drugs given twice daily) using a minimization method with age, sex, and institution as adjustment factors. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. H. pylori eradication was confirmed by a urea breath test from 4 to 8 wk after cessation of therapy. RESULTS: ITT analysis revealed the eradication rates of 69.4% (95%CI: 61.2%-76.6%) for esomeprazole therapy and 73.9% (95%CI: 65.9%-80.6%) for lansoprazole therapy (P = 0.4982). PP analysis showed eradication rate of 76.9% (95%CI: 68.6%-83.5%) for esomeprazole therapy and 79.8% (95%CI: 71.9%-86.0%) for lansoprazole therapy (P = 0.6423). There were no differences in adverse effects between the two therapies. CONCLUSION: Esomeprazole showed non-inferiority and safety in a 7 day-triple therapy for eradication of H. pylori compared with lansoprazole.


Assuntos
Quimioterapia Combinada/métodos , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Lansoprazol/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/administração & dosagem , Claritromicina/farmacologia , Esquema de Medicação , Farmacorresistência Bacteriana , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Adulto Jovem
4.
Hepatogastroenterology ; 54(79): 1941-4, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18251133

RESUMO

BACKGROUND/AIMS: Toll-like receptor 4 (TLR4), which requires a helper molecule, MD-2, is a main receptor for lipopolysaccharide (LPS) from gram-negative bacteria. The expression of TLR4 in H. pylori infection in human gastric mucosa, however, is unclear. The aim of this study was to determine the effect of H. pylori infection on the TLR4 and MD-2 expression in human gastric mucosa. METHODOLOGY: Biopsy samples from the antrum and corpus were obtained from 45 patients (25 patients without H. pylori infection including 5 patients with successful eradication of H. pylori, and 20 patients with H. pylori infection). These samples were used for TLR4, MD-2 mRNA expression study and immunohistochemical study. RESULTS: In patients without H. pylori infection, the expressions of TLR4 and MD-2 were bigger in the corpus mucosa than in the antral mucosa. In patients with H. pylori infection, the expressions of TLR4 and MD-2 significantly increased in the antral and corpus mucosa. Immunohistochemical study revealed similar results as the TLR4 mRNA expression. After the eradication of H. pylori, the expressions of TLR4 and MD-2 were the same levels in both sites as those in patients without H. pylori infection. CONCLUSIONS: The results indicated that H. pylori infection significantly increased TLR4 and MD-2 expressions in the antral and corpus mucosa.


Assuntos
Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori , Antígeno 96 de Linfócito/metabolismo , Receptor 4 Toll-Like/metabolismo , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Reação em Cadeia da Polimerase Via Transcriptase Reversa
5.
Clin Drug Investig ; 26(7): 403-14, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17163273

RESUMO

OBJECTIVE: Seven-day administration of omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day is currently approved in Japan for the eradication of Helicobacter pylori infection. We investigated the efficacy and safety of an omeprazole-based triple therapy regimen in combination with amoxicillin and low-dose clarithromycin in Japanese patients. METHODS: Patients were randomly assigned to either the low-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 400 mg/day) or the high-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day). A total of 288 patients were allocated to the low-dose (143) and high-dose (145) groups and were treated twice daily for 1 week. RESULTS: For the full-analysis set, H. pylori eradication rates were 81.1% (116/143 patients, 90% confidence interval [CI] 74.9, 86.3) in the low-dose group and 80.0% (116/145 patients, 90% CI 73.7, 85.3) in the high-dose group. Per-protocol eradication rates were 81.7% (103/126 patients, 90% CI 75.1, 87.2) and 84.1% (90/107 patients, 90% CI 77.1, 89.6), respectively. When patients with non-susceptibility to clarithromycin were excluded, eradication rates were >80% for both gastric and duodenal ulcers in the two groups. The results suggested that eradication rates were affected more by susceptibility to clarithromycin than to amoxicillin. Both regimens were well tolerated. CONCLUSION: This study demonstrated that an omeprazole-based triple-therapy regimen with clarithromycin 400 mg/day was as effective as that with clarithromycin 800 mg/day for H. pylori eradication.


Assuntos
Amoxicilina/administração & dosagem , Claritromicina/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Omeprazol/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/efeitos adversos , Hidrocarboneto de Aril Hidroxilases/genética , Claritromicina/efeitos adversos , Citocromo P-450 CYP2C19 , Método Duplo-Cego , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Omeprazol/efeitos adversos
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