This study compared results from Gd-EOB-DTPA on two different phases of 3T MRI with those from Tc-99m-GSA hepatic scintigraphy and hepatic function tests. Twenty-four patients with liver tumor were included in this study. All patients underwent Gd-EOB-DTPA-enhanced-MRI and Tc-99m-GSA hepatic scintigraphy. Clearance index (HH15) and receptor index (LHL15) were calculated for the Tc-99m-GSA, while signal intensities (SI) of liver at pre-injection and at 4/20min post-injection, and of spleen at 4 min/20min were measured (SIpre, SI_4min, SI_20min, SI_sp4min, SI_sp20min, respectively) for the Gd-EOB-DTPA-MRI. Liver activity at 15min by Tc-99m-GSA scintigraphy or biochemical liver function values were compared with liver spleen contrast at 4min (LSC_4min = SI_4min/SI_sp4min) or 20min post-injection (LSC_20min = SI_4min/SI_sp20min), and the increase in ratio at 4min (IR_4min = SI_4min/SI_sp4min) or _20min (IR_20min = SI_20min/SIpre). Total bilirubin levels (T-bil), serum albumin levels (Alb), prothrombin activity, and the indocyanine green clearance test (ICG) results were also analyzed. There were statistically significant correlations in all comparisons between Gd-EOB-DTPA and Tc-99m-GSA. The highest coefficient of correlation was obtained in IR_4min (LHL15: r = 0.795, P < 0.001; HH15: r = -0.782, P < 0.001), with IR_20min (LHL15: r = 0.690, P < 0.01; HH15: r = -0.528, P < 0.05), LSC_4min (LHL15: r = 0.458, P < 0.05; HH15: r = -0.626, P < 0.05), and LSC_20min (LHL15: r = 0.443, P < 0.05, HH15: r = -0.609, P < 0.05) also significantly correlated. Correlations in hepatic function data were observed between IR_4min and T-bil/Alb, and IR_20min and Alb. In 3T-MRI using Gd-EOB-DTPA, the SI of liver at pre- to post-injection (especially at 4 min) significantly correlated with the corresponding Tc-99m-DTPA scintigraphy results, and with some biochemical liver function data.

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To identify risk factors for restenosis after percutaneous coronary intervention with sirolimus (SES)- or paclitaxel (PES)-eluting stents. The clinical outcomes of 894 patients treated with either SES (n = 462) or PES (n = 432) between January 2005 and January 2010 were evaluated. Multivariate logistic regression analysis showed that long ( > 20mm)(odds ratio [OR], 1.87; 95% confidence interval [CI], 1.07∼3.33; P = 0.03) or bent (angle > 45°) lesions (OR, 2.57; 95% CI, 1.47∼4.49; P < 0.01) were independent risk factors for restenosis with SES, and that hemodialysis (OR, 7.61; 95% CI, 2.78∼20.85; P < 0.01) and long (OR, 2.63; 95% CI, 1.18∼5.84; P = 0.02) or bent lesions (OR, 3.47; 95% CI, 1.65∼7.27; P < 0.01) were independent risk factors for target lesion revascularization (TLR) with SES. In contrast, no independent risk factors for restenosis and TLR were found for lesions treated with PES. The rate of TLR was significantly higher in patients on hemodialysis or in those with long lesions in the SES group (hemodialysis, 30.4% vs. 11.1%, P = 0.02; long lesions, 13.2% vs. 4.4%, P < 0.01; for SES vs. PES, respectively). Rates of restenosis and TLR were significantly higher in patients with bent lesions in the SES group (restenosis, 30.8% vs. 15.6%, P < 0.01; TLR, 20.0% vs. 5.8%, P < 0.01; for SES and PES, respectively). Most clinical studies have described better angiographic results for SES compared to PES. However, PES might result in better clinical outcomes than SES for patients on hemodialysis or for those with long or bent lesions.

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Abstract: The present study investigated the tonic vibration reflex (TVR) in humans elicited by vibratory stimulation applied to the muscle of the triceps brachii and examined the effects of rotation of the neck on misperception of movement of the elbow. Fifteen healthy subjects actively flexed their elbows from 0° to 90° for 3 s with their eyes closed. During the time that the elbow was flexed, vibratory stimulation (100 Hz) was applied to the tendon of the right triceps brachii. In the first experiment, only the right elbow was flexed (one-arm experiment), whereas in the second experiment both elbows were flexed simultaneously (two-arm experiment). In the two-arm experiment with vibratory stimulation, the mean ( ± SD) angle of the elbow was 63.2 ± 11.2° with neck rotation at 0°, which decreased significantly to 53.0 ± 15.5° (P < 0.05) when the neck was rotated back to 0° from the position of maximal right rotation. This suggests that there is an asymmetric tonic neck reflex as a result of neck movement, with the pathways involved in the crossed extension reflex enhanced by the simultaneous movement of both elbows. The TVR is an effective tool with which the convergence of various reflexes on α-motor neurons innervating the muscles of the extremity can be examined.

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First-generation drug-eluting stents (DESs) have reduced angiographic and clinical restenosis rates compared to bare-metal stents (BMSs). Zotarolimus-eluting stents (ZESs) are second-generation drug-eluting stents: however, the clinical efficacy of ZES implantation is unclear because late loss associated with ZESs is reportedly higher than that observed for other DESs. The aim of this study was to evaluate the clinical efficacy of ZESs compared to paclitaxel-eluting stents (PESs). We retrospectively evaluated the angiographic and clinical outcomes of 431 lesions in 342 patients treated with PESs and 153 lesions in 121 patients treated with ZESs in our hospital between May 2007 and December 2010. Follow-up angiographic examinations were performed eight months post-treatment and clinical outcomes were assessed one year after the procedure. Quantitative coronary angiographic analyses showed that late loss was significantly higher for ZESs than PESs (0.82 ± 0.73 mm vs 0.47 ± 0.68 mm; P = 0.003). However, there was no significant difference in target lesion revascularization (TLR) between the two groups (ZES: 15 lesions, 9.8% vs PES: 25 lesions, 5.8%; P = 0.092). When comparing stents according to the American College of Cardiology/American Heart Association (ACC/AHA) lesion type, the TLR rate in the ZES group was significantly lower than in the PES group (0% vs 7.0%; P = 0.038) for Type A/B1 lesions, but the TLR rate for type B2/C lesions in the ZES group was significantly higher than in the PES group (15.8% vs 5.3%; P = 0.009). Multivariate logistic regression analysis showed that dialysis (OR: 35.54; 95% CI: 3.15-400.67; P = 0.039) and pre-minimal lumen diameter (OR: 0.036; 95% CI: 0.002-0.541; P = 0.016) were independent predictors of TLR in ZES-treated lesions. However, no factors predicted TLR in PES-treated lesions. Our study demonstrated excellent outcomes with ZESs for simple lesions, but it is necessary to carefully implant ZESs in complex lesions, such as ACC/AHA type B2/C lesions..

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Interleukin (IL)-4 exhibits strong antitumor effects and IL-4 gene therapy has been used clinically in the treatment of some types of cancer. In the present study, we evaluated the efficacy of IL-4-transduced tumor cell vaccines in combination with blockade of programmed cell death 1 (PD-1) and investigated the mechanisms underlying the antitumor effects of this therapy. A poorly immunogenic murine colorectal cancer cell line (i.e. MC38) was transduced to overexpress IL-4. In a therapeutic model, MC38-IL4 cells and anti-PD-1 antagonistic antibodies (Ab) were inoculated into parental tumor-bearing mice. Immunohistochemical analyses and tumor-specific lysis were also performed. Additive antitumor effects were observed when mice were treated with IL-4 in combination with an anti-PD-1 Ab. Immunohistochemical analysis of the therapeutic model showed marked infiltration of CD4⁺ and CD8⁺ cells into established MC38 tumors of mice treated with anti-PD-1 Ab. Significant tumor-specific cytolysis was detected when the splenocytes of mice treated with both IL-4 and anti-PD-1 Ab were used as effector cells. These results suggest that blockade of the interaction between PD-1 and programmed death ligand 1 (PD-L1) enhances the antitumor immune responses induced by IL-4. Thus, IL-4 gene-transduced tumor cell vaccines in combination with PD-1 blockade may be considered as possible candidates for clinical trials of new cancer vaccines.

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Diabetes mellitus (DM) is observed in patients with autoimmune pancreatitis (AIP). The development of DM in AIP is believed to be due to blood flow obstruction of the endocrine gland that accompanies pancreatitis, as well as injury to the islets caused by inflammation. The latter is called insulitis and the detailed mechanisms underlying its development are not yet clear. The aim of the present study was to elucidate the mechanisms involved in the development of insulitis in AIP using aly mice as an animal model of AIP: results in aly/aly male mice, as the AIP group, were compared with those in aly/⁺ male mice as a control group. Mice in both groups were killed between 16 and 48 weeks of age, and pancreatitis and insulitis were evaluated histologically. Inflammatory and endocrine cells were evaluated by immunofluorescence staining with anti-CD4, anti-CD8, anti-CD11b, and anti-CD11c antibodies, as well as immunohistochemical analyses using insulin and glucagon antibodies. Plasma levels and the pancreatic content of interferon (IFN)-γ (as a Th1-secreted cytokine) and interleukin (IL)-4 (as a Th2-secreted cytokine) were determined. Pancreatitis was seen in aly/aly mice from 16 weeks of age and it developed gradually thereafter. Insulitis also developed gradually and was seen in mice after 24 weeks of age in association with a decrease in the number of islets. CD11c⁺ cells and CD4⁺ T cells were seen to infiltrate into the islets. Although the number of β-cells decreased with time, the number of α-cells was maintained until mice were 48 weeks of age. IFN-γ content peaked in mice at 16 weeks of age and declined rapidly from 20 weeks. There were two peaks in IL-4 content, one at 16 weeks and the other at 32 weeks, suggesting an association between IL-4 content and advanced insulitis after 32 weeks. In conclusion, the results suggest that insulitis in AIP is induced predominantly by the infiltration of CD11c⁺ cells and CD4⁺ T cells into the islets, and progression is facilitated by the imbalance of the activation of Th2 rather than Th1. Furthermore, insulitis in AIP predominantly involves β-cells rather than α-cells.

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Alcohol-induced liver injury is linked to oxidative stress and increased production of reactive oxygen species (ROS). Oxidative stress is an early event in the process of apoptosis. However, it is not completely understood how ethanol-induced oxidative stress induces apoptosis. In contrast, nicotinamide adenine dinucleotide phosphate oxidase (NOX) is known to generate ROS in hepatocytes. The purpose of the present study was to determine whether or not ethanol-induced ROS generation stimulates the death receptor or mitochondrial pathways of apoptosis in alcohol dehydrogenase containing human liver adenocarcinoma (SK-HEP-1) cells. Treatment with ethanol increased the generation of ROS and expression of NOX4 mRNA, and also induced mitochondrial dysfunction in SK-HEP-1 cells. Moreover, ethanol induced the activation of caspase-8 and -3 in hepatocytes. These activities were suppressed by pretreatment with N-acetyl-cysteine, an antioxidant, or apocynin, an inhibitor of NOX activity. These results suggested that ethanol induces an increase in NOX-derived ROS generation upstream of caspase-8 activation and in the mitochondria in SK-HEP-1 cells. In conclusion, this study demonstrated that ethanol increases the generation of ROS and subsequently induces apoptosis using a mechanism involving mitochondrial dysfunction and caspase activation in SK-HEP-1 cells.

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There are no reports reviewing the various types of dysphagia that occur after surgery for esophageal cancer and the rehabilitation approaches appropriate for each type. Herein, we classified various types of dysphagia after esophageal cancer surgery according to cause and examined the rehabilitation approaches for each type, as well as the outcomes. The study was performed on 31 patients who were tested postoperatively for swallowing function and underwent rehabilitation for dysphagia during their hospitalization. In patients with decreased swallowing ability due to recurrent laryngeal nerve injury associated with lymph node dissection, oral intake ability was improved by basic and feeding exercises. In patients with markedly reduced laryngeal elevation detected by videofluoroscopic examination of swallowing, feeding exercises were performed in addition to basic exercises that centered on stretching the perilaryngeal muscles. Improvements in laryngeal elevation were observed in some patients. In patients with dysphagia caused by postoperative gastrointestinal (GI) anastomotic stricture, the balloon dilatation method using an upper GI endoscope was applied at the anastomotic site. Finally, in patients with retention and reflux of GI tract contents in whom the reflux of contents into the pharynx caused aspiration, postures unlikely to cause reflux were maintained. Thus, dysphagia after esophageal cancer surgery may be due to not only swallowing dysfunction, but also impairments of the GI tract. When ingestion and swallowing abilities are assessed, simultaneous videofluoroscopic examination of swallowing and an upper GI series are important. In some cases, standard rehabilitation techniques alone may not be sufficient, requiring a multimodal approach for effective treatment.

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A 57-year-old woman was admitted to our hospital with abdominal pain and vomiting. Her abdomen was distended, and obstructive bowel sounds were discovered on examination. Diffuse abdominal tenderness was present, but no palpable masses were apparent. Abdominal computed tomography confirmed a large gallstone obstructing the small bowel. Colonoscopy revealed a large gallstone lodged at the terminal ileum, which was subsequently fragmented using electronic hydraulic lithotripsy (EHL). The patient has remained asymptomatic for over 3 years of follow-up after the EHL treatment. Here, we present this case of small intestinal obstruction caused by a large gallstone in the lower ileum.

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