Serum interleukin (IL)-10 and IL-12 levels and IL28B gene polymorphisms: pretreatment prediction of treatment failure in chronic hepatitis C

Background: Both IL28B gene polymorphisms and serum levels of interleukin (IL)-10, IL-12p40 and IL-18 have been reported to affect the outcome of natural and pegylated interferon and ribavirin-treated HCV infection. Methods: To clarify their association and predictive value in treatment outcome of genotype 1 HCV-infected patients, we measured pretreatment serum IL-10, IL-12p40 and IL-18 levels using multiplex assays and determined IL28B gene polymorphisms (rs 8099917) in 52 cases with chronic hepatitis C. Results: High baseline levels of IL-10 (P<0.001) and low levels of IL-12p40 (P<0.001) were significantly associated with a non-virological response (NVR) in our cohort. The IL28B polymorphism was tested and TT, TG or GG genotypes were found in 60%, 38% and 2% of patients, respectively, with corresponding NVR rates of 10%, 60% and 100% (P<0.001). Serum cytokine levels were significantly correlated with IL28B gene polymorphisms. When serum IL-10 levels were stratified at 5.0 pg/ml, NVR rates were 50% versus 0% (P=0.004) for the IT genotype and 87% versus 0% (P=0.001) for the TG or GG genotypes. Similarly, low IL-12p40 levels were associated with an NVR in patients with TG or GG genotypes (P=0.006). In multivariate analysis, high IL-10, low IL-12p40 and IL28B TG or GG genotypes were independently associated with an NVR. Conclusions: Serum IL-10 and IL-12p40 levels in combination with IL28B genotype, especially G-allele carriage, are strong predictive markers of an NVR to HCV treatment with pegylated interferon and ribavirin.ArticleANTIVIRAL THERAPY. 16(7):1073-1080 (2011)journal articl

Serum chemokine levels are associated with the outcome of pegylated interferon and ribavirin therapy in patients with chronic hepatitis C

Aim: Serum chemokine levels and amino acid substitutions in the interferon-sensitivity determining region (ISDR) and core region have been associated with treatment outcome of pegylated interferon and ribavirin therapy in genotype 1 hepatitis C virus (HCV)-infected patients. The present study was conducted to clarify the association between serum chemokines and treatment outcome in patients with chronic HCV-1 infection in a Japanese cohort. Methods: A total of six serum chemokines were quantified before, during and after pegylated interferon and ribavirin treatment in 79 genotype 1 chronic HCV patients using a multiple bead array system. Viral ISDR and core region variants were determined by direct sequencing. Results: The baseline serum levels of eotaxin, IP-10 and RANTES were significantly higher in chronic HCV patients than in controls. High levels of eotaxin and macrophage inflammatory protein (MIP)-1 beta before therapy and more than two mutations in the ISDR were associated with a sustained virological response, and patients with more than two mutations in the ISDR also had significantly higher MIP-1 beta levels. Receiver-operator curve analysis showed a 77% sensitivity and 73% specificity for predicting an SVR using MIP-1 beta values. Conclusion: Serum MIP-1 beta levels may predict the response to HCV treatment with pegylated interferon and ribavirin and are associated with amino acid substitutions in the ISDR.ArticleHEPATOLOGY RESEARCH. 41(6):587-593 (2011)journal articl

Three-dimensional imaging of thoracic diseases with multidetector row CT

The benefits of multi-detector row CT (MDCT) relative to single-detector row helical CT are considerable. Multi-detector row CT allows shorter acquisition times, greater coverage, and superior image resolution. These factors substantially increase the diagnostic accuracy of the examination. Three-dimensional (3D) volume data from MDCT provides various unique applications on thoracic diseases. These includes isotropic viewings, use of multi planar reformation (MPR), maximum and minimum intensity projections (MIP and min IP), and volume rendering performed from external and internal perspectives allowing the user to “fly around” and “fly through” the structures. Recent advances in 3D volume rendering put real-time, interactive virtual reality guidance of the procedures such as bronchoscopy and surgery into practice

Association of Serum Cytokine Levels With Treatment Response to Pegylated Interferon and Ribavirin Therapy in Genotype 1 Chronic Hepatitis C Patients

Methods. We quantified a total of 8 serum cytokines before, during, and after treatment in 79 genotype 1 chronic HCV patients. Viral ISDR and core region variants were determined by direct sequencing. Results. High levels of interleukin (IL)-12 and IL-18 and more than 2 mutations in the ISDR were associated with a sustained virological response (SVR). Conversely, high baseline IL-10 levels and glutamine at amino acid 70 of the HCV core protein (Gln70) were significantly associated with a nonresponse to treatment, and patients with Gln70 had significantly higher IL-10 levels. In multivariate analysis, low IL-10, high IL-12, and high IL-18 levels were independently associated with an SVR. These 3 cytokine levels were decreased from baseline levels 4 weeks into treatment and remained low in patients with an SVR. Conclusion. Serum IL-10, IL-12, and IL-18 levels are predictive of the response to HCV treatment with pegylated interferon and ribavirin and are associated with amino acid substitutions in the ISDR and core region.ArticleJOURNAL OF INFECTIOUS DISEASES. 203(8):1087-1095 (2011)journal articl

Comparison of carbon dioxide and air insufflation use by non-expert endoscopists during endoscopic retrograde cholangiopancreatography

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is subject to several complications that include a lengthy procedure time, technical difficulty, and active bowel movement induced by air insufflation. In ERCP carried out by non-expert endoscopists who are prone to excessive luminal insufflation, insufflation with carbon dioxide (CO2) may provide better and safer outcomes. We aimed to assess the efficacy and safety of CO2 insufflation during ERCP by non-expert endoscopists. Methods: This study included 208 consecutive patients who received ERCP, excluding those in poor general health or with obstructive lung disease. The first operator for each patient was a non-expert endoscopist having done 50 or fewer ERCP procedures. Primary outcomes were the changes in cardiopulmonary state during ERCP. Secondary outcomes were ERCP complications. We designed a single-center, randomized, prospective, double-blind, controlled trial with CO2 and air insufflation during ERCP. Results: CO2 insufflation did not affect overall procedure progression or results. A positive correlation was observed between procedure time and change in maximal systolic blood pressure from baseline among patients in the air insufflation group, but not in the CO2 insufflation group (correlation coefficient 0.408 vs 0.114, change in the maximal systolic blood pressure from baseline +4.2 vs+1.2mmHg/10min). This was consistent with our findings in patients treated by the first operator alone. The occurrence rate of post-ERCP pancreatitis tended to be lower in the CO2 group than the air group (4/102 [3.9%]vs 0/106 [0%], P=0.056). Conclusions: CO2 insufflation during ERCP by non-expert endoscopists is recommended from the standpoints of efficacy and safety.ArticleDIGESTIVE ENDOSCOPY. 25(2):189-196 (2013)journal articl

Risk factors for pancreatic stone formation in autoimmune pancreatitis over a long-term course

Autoimmune pancreatitis (AIP) has the potential to progress to a chronic state that forms pancreatic stones. The aim of this study was to clarify the risk factors underlying pancreatic stone formation in AIP. Sixty-nine patients with AIP who had been followed for at least 3 years were enrolled for evaluation of clinical and laboratory factors as well as computed tomography and endoscopic retrograde cholangiopancreatography findings. During the course of this study, increased or de novo stone formation was seen in 28 patients, who were defined as the stone-forming group. No stones were observed in 32 patients, who were defined as the non-stone-forming group. Nine patients who had stones at diagnosis but showed no change during the course of this study were excluded from our cohort. Univariate analysis revealed no significant differences in clinical or laboratory factors associated with AIP-specific inflammation between the two groups. However, pancreatic head swelling (P = 0.006) and narrowing of both Wirsung's and Santorini's ducts in the pancreatic head region (P = 0.010) were significantly more frequent in the stone-forming group. Furthermore, multivariate analysis identified Wirsung and Santorini duct narrowing at diagnosis as a significant independent risk factor for pancreatic stone formation (OR 4.4, P = 0.019). A primary risk factor for pancreatic stone formation in AIP was narrowing of both Wirsung's and Santorini's ducts, which most presumably led to pancreatic juice stasis and stone development.ArticleJOURNAL OF GASTROENTEROLOGY. 47(5):553-560 (2012)journal articl

Hydro-bio-geomechanical properties of hydrate-bearing sediments from Nankai Trough

This paper is not subject to U.S. copyright. The definitive version was published in Marine and Petroleum Geology 66 (2015): 434-450, doi:10.1016/j.marpetgeo.2015.02.033.Natural hydrate-bearing sediments from the Nankai Trough, offshore Japan, were studied using the Pressure Core Characterization Tools (PCCTs) to obtain geomechanical, hydrological, electrical, and biological properties under in situ pressure, temperature, and restored effective stress conditions. Measurement results, combined with index-property data and analytical physics-based models, provide unique insight into hydrate-bearing sediments in situ. Tested cores contain some silty-sands, but are predominantly sandy- and clayey-silts. Hydrate saturations Sh range from 0.15 to 0.74, with significant concentrations in the silty-sands. Wave velocity and flexible-wall permeameter measurements on never-depressurized pressure-core sediments suggest hydrates in the coarser-grained zones, the silty-sands where Sh exceeds 0.4, contribute to soil-skeletal stability and are load-bearing. In the sandy- and clayey-silts, where Sh < 0.4, the state of effective stress and stress history are significant factors determining sediment stiffness. Controlled depressurization tests show that hydrate dissociation occurs too quickly to maintain thermodynamic equilibrium, and pressure–temperature conditions track the hydrate stability boundary in pure-water, rather than that in seawater, in spite of both the in situ pore water and the water used to maintain specimen pore pressure prior to dissociation being saline. Hydrate dissociation accompanied with fines migration caused up to 2.4% vertical strain contraction. The first-ever direct shear measurements on never-depressurized pressure-core specimens show hydrate-bearing sediments have higher sediment strength and peak friction angle than post-dissociation sediments, but the residual friction angle remains the same in both cases. Permeability measurements made before and after hydrate dissociation demonstrate that water permeability increases after dissociation, but the gain is limited by the transition from hydrate saturation before dissociation to gas saturation after dissociation. In a proof-of-concept study, sediment microbial communities were successfully extracted and stored under high-pressure, anoxic conditions. Depressurized samples of these extractions were incubated in air, where microbes exhibited temperature-dependent growth rates.PCCTs were developed with funding to Georgia Tech from the DOE/Chevron Joint Industry Project (JIP), with additional funds from the Joint Oceanographic Institutions, Inc. The JIP also funded the Georgia Tech participation in Sapporo. USGS participation in Sapporo was funded through a technical assistance agreement with Chevron (TAA-12-2135/CW928359). Some USGS developments on the IPTC were funded under Interagency Agreement DE-FE0002911 with the U.S. Department of Energy, with additional support from the U.S. Geological Survey. Core acquisition and Japanese participation in this study was supported by the Research Consortium for Methane Hydrate Resources in Japan (MH21 Research Consortium) to carry out Japan's Methane Hydrate R&D Program conducted by the Ministry of Economy, Trade and Industry (METI)

Serum interleukin (IL)-10 and IL-12 levels and IL28B gene polymorphisms: pretreatment prediction of treatment failure in chronic hepatitis C

Background: Both IL28B gene polymorphisms and serum levels of interleukin (IL)-10, IL-12p40 and IL-18 have been reported to affect the outcome of natural and pegylated interferon and ribavirin-treated HCV infection. Methods: To clarify their association and predictive value in treatment outcome of genotype 1 HCV-infected patients, we measured pretreatment serum IL-10, IL-12p40 and IL-18 levels using multiplex assays and determined IL28B gene polymorphisms (rs 8099917) in 52 cases with chronic hepatitis C. Results: High baseline levels of IL-10 (P<0.001) and low levels of IL-12p40 (P<0.001) were significantly associated with a non-virological response (NVR) in our cohort. The IL28B polymorphism was tested and TT, TG or GG genotypes were found in 60%, 38% and 2% of patients, respectively, with corresponding NVR rates of 10%, 60% and 100% (P<0.001). Serum cytokine levels were significantly correlated with IL28B gene polymorphisms. When serum IL-10 levels were stratified at 5.0 pg/ml, NVR rates were 50% versus 0% (P=0.004) for the IT genotype and 87% versus 0% (P=0.001) for the TG or GG genotypes. Similarly, low IL-12p40 levels were associated with an NVR in patients with TG or GG genotypes (P=0.006). In multivariate analysis, high IL-10, low IL-12p40 and IL28B TG or GG genotypes were independently associated with an NVR. Conclusions: Serum IL-10 and IL-12p40 levels in combination with IL28B genotype, especially G-allele carriage, are strong predictive markers of an NVR to HCV treatment with pegylated interferon and ribavirin.ArticleANTIVIRAL THERAPY. 16(7):1073-1080 (2011)journal articl

Two cases of retroperitoneal hematoma caused by combination of anticoagulant therapy and 5-fluorouracil

We reported two cases of retroperitoneal hematoma in patients who received a combination of anticoagulant therapy and5-fluorouracil (5-FU). We should be aware of the possible interaction of this combination therapy and monitor prothrombin time (PT) prolongation. CT is useful for evaluation of the disease