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To propose a style transfer model for multi-contrast magnetic resonance imaging (MRI) images with a cycle-consistent generative adversarial network (CycleGAN) and evaluate the image quality and prognosis prediction performance for glioblastoma (GBM) patients from the extracted radiomics features. Style transfer models of T1 weighted MRI image (T1w) to T2 weighted MRI image (T2w) and T2w to T1w with CycleGAN were constructed using the BraTS dataset. The style transfer model was validated with the Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) dataset. Moreover, imaging features were extracted from real and synthesized images. These features were transformed to rad-scores by the least absolute shrinkage and selection operator (LASSO)-Cox regression. The prognosis performance was estimated by the Kaplan-Meier method. For the accuracy of the image quality of the real and synthesized MRI images, the MI, RMSE, PSNR, and SSIM were 0.991 ± 2.10 × 10 - 4 , 2.79 ± 0.16, 40.16 ± 0.38, and 0.995 ± 2.11 × 10 - 4 , for T2w, and .992 ± 2.63 × 10 - 4 , 2.49 ± 6.89 × 10 - 2 , 40.51 ± 0.22, and 0.993 ± 3.40 × 10 - 4 for T1w, respectively. The survival time had a significant difference between good and poor prognosis groups for both real and synthesized T2w (p < 0.05). However, the survival time had no significant difference between good and poor prognosis groups for both real and synthesized T1w. On the other hand, there was no significant difference between the real and synthesized T2w in both good and poor prognoses. The results of T1w were similar in the point that there was no significant difference between the real and synthesized T1w. It was found that the synthesized image could be used for prognosis prediction. The proposed prognostic model using CycleGAN could reduce the cost and time of image scanning, leading to a promotion to build the patient's outcome prediction with multi-contrast images., (© 2024. The Author(s).)

Purpose: The thoracic inlet space might influence the blood vessel perfusion in the gastric conduit. The purpose of this study was to clarify the impacts of the thoracic inlet space on blood vessel perfusion in the gastric conduit and anastomotic leakage after esophagectomy., Methods: One hundred and forty-two esophageal cancer patients underwent esophagectomy followed by gastric conduit reconstruction via the retrosternal route. The blood flow speed in the gastric conduit was measured using indocyanine green fluorescence before and after reconstruction. Parameters at the thoracic inlet space were measured using CT. We then investigated the correlation between these two parameters and whether they could predict anastomotic leakage after esophagectomy., Results: Blood flow speed in the gastric conduit was slower after reconstruction than before reconstruction (P < 0.001). The incidence of anastomotic leakage (n = 23) was higher among patients with a delayed blood flow speed before reconstruction (n = 27) than among those with a non-delayed blood flow speed before reconstruction (n = 115) (P < 0.001). Among the patients with a non-delayed blood flow speed before reconstruction, the thoracic inlet area (TIA, sternum-tracheal distance × clavicle head distance) was positively correlated with the blood flow speed after reconstruction (P = 0.023) and was identified as an independent predictor of anastomotic leakage (P < 0.001)., Conclusion: A narrow TIA was associated with a delayed blood flow speed in the gastric conduit after reconstruction and was capable of predicting anastomotic leakage in the patients with a non-delayed blood flow speed before reconstruction., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Lead (Pb) causes developmental neurotoxicity. Developmental exposure to Pb acetate (PbAc) induces aberrant hippocampal neurogenesis by increasing or decreasing neural progenitor cell (NPC) subpopulations in the dentate gyrus (DG) of rats. To investigate whether hippocampal neurogenesis is similarly affected by PbAc exposure in a general toxicity study, 5-week-old Sprague-Dawley rats were orally administered PbAc at 0, 4000, and 8000 ppm (w/v) in drinking water for 28 days. After exposure to 4000 or 8000 ppm PbAc, Pb had accumulated in the brains. Neurogenesis was suppressed by 8000 ppm PbAc, which was related to decreased number of type-2b NPCs, although number of mature granule cells were increased by both PbAc doses. Gene expression in the 8000 ppm PbAc group suggested suppressed NPC proliferation and increased apoptosis resulting in suppressed neurogenesis. PbAc exposure increased numbers of metallothionein-I/II + cells and GFAP + astrocytes in the DG hilus, and upregulated Mt1, antioxidant genes (Hmox1 and Gsta5), and Il6 in the DG, suggesting the induction of oxidative stress and neuroinflammation related to Pb accumulation resulting in suppressed neurogenesis. PbAc at 8000 ppm also upregulated Ntrk2 and increased the number of CALB2 + interneurons, suggesting the activation of BDNF-TrkB signaling and CALB2 + interneuron-mediated signals to ameliorate suppressed neurogenesis resulting in increased number of newborn granule cells. PbAc at both doses increased the number of ARC + granule cells, suggesting the facilitation of synaptic plasticity of newborn granule cells through the activation of BDNF-TrkB signaling. These results suggest that PbAc exposure during the young-adult stage disrupted hippocampal neurogenesis, which had a different pattern from developmental exposure to PbAc. However, the induction of oxidative stress/neuroinflammation and activation of identical cellular signals occurred irrespective of the life stage at PbAc exposure., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study examined the ameliorating effect of alpha-glycosyl isoquercitrin (AGIQ), an antioxidant, on disrupted hippocampal neurogenesis in the dentate gyrus (DG) in a rat model of autism spectrum disorder induced by prenatal valproic acid (VPA) exposure. Dams were intraperitoneally injected with 500 mg/kg VPA on gestational day 12. AGIQ was administered in the diet at 0.25 or 0.5% to dams from gestational day 13 until weaning at postnatal day (PND) 21 and then to pups until PND 63. At PND 21, VPA-exposed offspring showed decreased numbers of type-2a and type-3 neural progenitor cells (NPCs) among granule cell lineage subpopulations. AGIQ treatment at both doses rescued the reduction in type-3 NPCs. AGIQ upregulated Reln and Vldlr transcript levels in the DG at 0.5% and ≥ 0.25%, respectively, and increased the number of reelin + interneurons in the DG hilus at 0.5%. AGIQ at 0.25% and/or 0.5% also upregulated Ntrk2, Cntf, Igf1, and Chrnb2. At PND 63, there were no changes in the granule cell lineage subpopulations in response to VPA or AGIQ. AGIQ at 0.25% increased the number of FOS + granule cells, accompanied by Gria2 and Gria3 upregulation and increasing trend in the number of FOS + granule cells at 0.5%. There was no definitive evidence of VPA-induced oxidative stress in the hippocampus throughout postnatal life. These results indicate that AGIQ ameliorates the VPA-induced disruption of hippocampal neurogenesis at weaning involving reelin, BDNF-TrkB, CNTF, and IGF1 signaling, and enhances FOS-mediated synaptic plasticity in adulthood, potentially through AMPA-receptor upregulation. The ameliorating effects of AGIQ may involve direct interactions with neural signaling cascades rather than antioxidant capacity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To predict the gamma passing rate (GPR) of the three-dimensional (3D) detector array-based volumetric modulated arc therapy (VMAT) quality assurance (QA) for prostate cancer using a convolutional neural network (CNN) with the 3D dose distribution. One hundred thirty-five VMAT plans for prostate cancer were selected: 110 plans were used for training and validation, and 25 plans were used for testing. Verification plans were measured using a helical 3D diode array (ArcCHECK). The dose distribution on the detector element plane of these verification plans was used as input data for the CNN model. The measured GPR (mGPR) values were used as the training data. The CNN model comprises eighteen layers and predicted GPR (pGPR) values. The mGPR and pGPR values were compared, and a cumulative frequency histogram of the prediction error was created to clarify the prediction error tendency. The correlation coefficients of pGPR and mGPR were 0.67, 0.69, 0.66, and 0.73 for 3%/3-mm, 3%/2-mm, 2%/3-mm, and 2%/2-mm gamma criteria, respectively. The respective mean±standard deviations of pGPR-mGPR were -0.87±2.18%, -0.65±2.93%, -0.44±2.53%, and -0.71±3.33%. The probabilities of false positive error cases (pGPR < mGPR) were 72%, 60%, 68%, and 56% for each gamma criterion. We developed a deep learning-based prediction model of the 3D detector array-based VMAT QA for prostate cancer, and evaluated the accuracy and tendency of prediction GPR. This model can provide a proactive estimation for the results of the patient-specific QA before the verification measurement., (© 2022. Australasian College of Physical Scientists and Engineers in Medicine.)

The purpose of this study was to extract the three-dimensional (3D) vector of the baseline drift baseline drift vector (BDV) of the specific points on the body surface and to demonstrate the importance of the 3D tracking of the body surface. Our system consisted of a near-infrared camera (NIC: Kinect V2) and software that recognized and tracked blue stickers as markers. We acquired 3D coordinates of 30 markers stuck on the body surface for 30 min for eight healthy volunteers and developed a simple technique to extract the BDV. The BDV on the sternum, rib, and abdomen was extracted from the measured data. BDV per min. was analyzed to estimate the frequency to exceed a given tolerance. Also, the correlation among BDVs for multiple body sites was analyzed. The longitudinal baseline drift was observed in the BDV of healthy volunteers. Among the eight volunteers, the maximum probability that the BDV per min. exceeded the tolerance of 1 mm and 2 mm was 30% and 15%, respectively. The correlation among BDVs of multiple body sites suggested a potential feasibility to distinguish the translational movement of the whole area and the respiratory movement. In conclusion, we constructed the 3D tracking system of multiple points on the body surface using a noninvasive NIC at a low cost and established the method to extract the BDV. The existence of the longitudinal baseline drift showed the importance of the 3D tracking in the body surface., (© 2022. Australasian College of Physical Scientists and Engineers in Medicine.)

Background: The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes annually., Methods: We analyzed the data of patients who had visited the participating hospitals in 2014. We collected the data with a web-based data collection system using the National Clinical Database. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification 7th edition by the Union of International Cancer Control (UICC) for cancer staging., Results: A total of 9026 cases were registered from 344 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.9% and 7.1%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.1%, 33.7%, 25.3%, and 59.3%, respectively. Esophagectomy was performed in 5204 cases. Concerning the approach used for esophagectomy, 48.1% of the cases were treated thoracoscopically. The operative mortality (within 30 days after surgery) was 0.75%, and the hospital mortality was 2.0%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system, because pStage IV included the patients with supraclavicular lymph-node metastasis (M1 LYM)., Conclusion: We hope that this report contributes to improving all aspects of diagnosing and treating esophageal cancer in Japan., (© 2021. The Author(s).)

Purpose: The study aimed to evaluate the usefulness of prone-position computed tomography (CT) for predicting relevant thoracic procedure outcomes in minimally invasive esophagectomy (MIE) for thoracic esophageal cancer., Materials and Methods: A total of 59 patients underwent esophagectomy between May 2019 and December 2020 in Tokai University Hospital. Preoperative CT imaging was conducted with the patient in both the supine and prone positions, and the magnitude of change in the intramediastinal space was calculated. In the 56 patients (94.9%) who had undergone MIE, the effects of such a difference on the surgical outcomes were analyzed., Results: A significant correlation of the magnitude of change in VE (distance between ventral aspect of the vertebral body and the midpoint of the esophagus) with the surgical outcome was revealed in the 17 patients (30.4%) in whom the magnitude of change in VE was over the 75th percentile. That is, in this subgroup, the magnitude of change in VE showed a negative correlation with the thoracic operation time (rs = - 0.57, p = 0.01) and blood loss during the thoracic procedure (rs = - 0.46, p = 0.01). Multivariate analysis identified a magnitude of change in VE ≥ 9 mm (OR = 0.14, p = 0.03) as an independent risk factor for postoperative pneumonia., Conclusions: This study indicates that preoperative prone-position CT imaging is useful for predicting the level of ease or difficulty of securing an adequate operative field, surgical outcomes, and the risk of postoperative pneumonia in MIE., (© 2021. The Japan Esophageal Society.)

Purpose: The study aimed to determine whether magnetic resonance thoracic ductography (MRTD) is useful for preventing injury to the thoracic duct (TD) during thoracoscopic esophagectomy and for reducing the incidence of postoperative chylothorax., Materials and Method: A total of 389 patients underwent thoracoscopic esophagectomy between September 2009 and February 2019 in Tokai University Hospital. Of them, we evaluated 228 patients who underwent preoperative MRTD (MRTD group) using Adachi's classification and our novel classification (Tokai classification). Then, the clinicopathological factors of the MRTD group (n = 228) were compared with those of the non-MRTD group (n = 161), and comparative analyses were conducted after propensity score matching (PSM)., Results: The TD could be visualized by MRTD in 228 patients. The MRTD findings were divided into 9 classifications including normal findings and abnormal TD findings (Adachi classification vs Tokai classification; 5.3% vs 16.2%). After PSM, both groups consisted of 128 patients. The rate of postoperative chylothorax after thoracoscopic esophagectomy was significantly lower in the MRTD group (0.8%) than in the non-MRTD group (6.3%) (p = 0.036). In the multivariate analysis for risk factors for chylothorax, the independent prognostic factors were preoperative therapy and the presence of MRTD., Conclusions: This study revealed that MRTD was useful for preventing of chylothorax after thoracoscopic esophagectomy for esophageal cancer., (© 2021. The Japan Esophageal Society.)

Background: Near-infrared fluorescence using indocyanine green (ICG) has been applied as a real-time navigation tool to observe blood flow in gastric conduit wall after esophagectomy. Atherosclerosis might impair the blood flow of the systemic organs. The aim of the study was to investigate the significances of ICG blood flow speed in the gastric conduit wall and atherosclerotic calcification for the prediction of anastomotic leakage after esophagectomy., Methods: The 109 esophageal cancer patients were prospectively enrolled. ICG fluorescence blood flow speed in the gastric conduit wall and abdominal aortic calcification index (ACI), celiac artery (CA) calcification, and superior mesenteric artery (SMA) calcification were determined. Then, the correlation between ICG fluorescence blood flow speed and anastomotic leakage as well as ACI, CA, and SMA calcification were evaluated., Results: Anastomotic leakage occurred in 15 patients. ACI ranged from 0 to 65. CA calcification and SMA calcification were present in 25 and 12 patients. Multivariate analysis demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall of 2.07 cm/s or less (P < 0.001) and SMA calcification (P = 0.026) were the significant independent predictors of anastomotic leakage. Only SMA calcification was significantly associated with ICG fluorescence blood flow speed in the gastric conduit wall (P = 0.026)., Conclusions: This study demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall can predict anastomotic leakage after esophagectomy and microvascular perfusion of capillary vessels of the gastric conduit might be impaired by systemic atherosclerosis.

Background: Esophageal cancer is the eighth most common cause of cancer mortality in Japan. More than 11,000 people had died from esophageal cancer in 2018. The Japan Esophageal Society has collected the data on patients' characteristics, performed treatment, and outcomes annually., Methods: We analyzed the data of patients who had first visited the participating hospitals in 2013. In 2019, the data collection method was changed from an electronic submission to a web-based data collection using the National Clinical Database (NCD). Japanese Classification of Esophageal Cancer 10th by the Japan Esophageal Society (JES) and UICC TNM Classification 7th were used for cancer staging RESULTS: A total of 8019 cases were registered from 334 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.8% and 6.3%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, or esophagectomy were 88.3%, 32.4%, 24.4%, and 59.3%, respectively. Esophagectomy was performed in 4910 cases. The operative and the hospital mortality rates were 0.77% and 1.98%, respectively. The survival curves showed a good discriminatory ability both in the clinical and pathologic stages by the JES system. The 5-year survival rate of patients with pStage IV in the UICC classification that included patients with supraclavicular node metastasis was better than that of patients with pStage IVb in JES classification., Conclusion: We hope this report contributes to improving all aspects of the diagnosis and treatment of esophageal cancer in Japan.

Background: Vasohibins (VASH), which are angiogenesis regulators, consist of Vasohibin-1 (VASH1) and Vasohibin-2 (VASH2). VASH1 is an angiogenesis inhibitor, while VASH2 is a proangiogenic factor. Patients with esophageal squamous cell carcinoma (ESCC) with high tumor expression levels of VASH1 and VASH2 have been reported to show a poor prognosis. The clinical significance of VASH concentrations in the blood of patients with ESCC has not yet been investigated., Methods: Plasma samples from 89 patients with ESCC were analyzed, and the relationships between the plasma VASH concentrations and the clinicopathological factors of the patients were evaluated. Immunohistochemical examination (IHC) of the resected tumor specimens for VASH was performed in 56 patients, and the correlation between the plasma VASH concentrations and tumor expression levels of VASH was analyzed., Results: The patient group with high plasma concentrations of VASH1 showed a higher frequency of lymph node metastasis (P = 0.01) and an invasive growth pattern (P = 0.05). Furthermore, poorly differentiated cancer occurred at a higher frequency in the patient group with high plasma concentrations of VASH2 (P < 0.01). High tumor expression levels of VASH1 were encountered more frequently in the patient group with high plasma concentrations of VASH1 (P = 0.03), and high tumor expression levels of VASH2 were encountered more frequently in the patient group with high plasma concentrations of VASH2 (P = 0.04)., Conclusions: In patients with ESCC, high plasma concentrations were associated with poor clinical outcomes for both VASH1 and VASH2. We propose that results indicate that plasma VASH1 and VASH2 are useful biomarkers in patients with ESCC.

The aim of our study is to evaluate the metal artefact reduction techniques with the same contrast scale for different vendors' dual-energy CT (DECT): kV-CT image with metal artefact reduction method and monoenergetic CT image using Canon's DECT, and monoenergetic CT image with metal artefact reduction method using GE's DECT. The kV-CT image and DECT scans were performed with the water-based polymethyl methacrylate phantom with various metal materials (brass, aluminium, copper, stainless steel, steel, lead, and titanium). Two types of metal artefact reduction (MAR) algorithm with the monoenergetic CT images were used. Smart MAR implemented by GE and the kV-CT images with MAR algorithms. Single-energy metal artefact reduction (SEMAR), implemented by Canon, was reconstructed. The artefact index was evaluated using the converted electron density values from the kV-CT and DECT images. The artefact index with all material inserts in the monoenergetic CT images were smallest at 70-90 keV for Canon and 140 keV for GE. The artefact index without SEMAR was larger than that with SEMAR for the 80 and 135-kV CT images. In the comparison of the artefact index for the converted electron density images from the 80 and 135-kV CT images with SEMAR, as well as the monoenergetic CT images with and without MAR, the monoenergetic CT image at 140 keV with MAR showed a reduction. In the comparison of the monoenergetic CT images at 140 keV and other energy ranges without and with Smart MAR, there was no statistically significant difference (P < 0.05) for all-metal inserts at more than 100 keV for Canon's DECT and 70 keV for GE's DECT. The metal artefact could be reduced by using a monoenergetic CT image at high energy with MAR algorithm. The metal artefact for the different-contrast-scale images can be compared on the same contrast scale by the electron density conversion method.

Purpose: We aimed to evaluate the magnetic resonance imaging (MRI) appearance changes during stereotactic radiotherapy (SRT) for large sized brain metastases, and analyze the lesions necessitating treatment plan modification., Materials and Methods: A total of 23 patients (27 lesions, >2 cm in tumor diameter) underwent SRT and all lesions were evaluated the appearance changes which had the necessity of the treatment plan modification. The appearance change of tumor during SRT was evaluated using gadolinium-enhanced MRI. The reasons of the modification were classified into tumor reduction, tumor enlargement, displacement, and shape change., Results: Among the 27 lesions, 55.6% required the treatment plan modification. The reasons were tumor reduction in six lesions, tumor enlargement in three lesions, displacement in three lesions, and shape change in three lesions. The planning target volume (PTV) size changed up to 43.0% and the shift of center of PTV was a maximum of 1.7 mm. The pathological status (adenocarcinoma vs others) and timing of steroid administration (prior vs after SRT start) were the predictive factors of tumor changes required the modification., Conclusions: As tumor changes might occur even during short period of SRT, the treatment plan evaluation and modification were important in SRT for large brain metastases.

Background: The present study investigated prognostic factors in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC) among various clinicopathological features related to neoadjuvant chemotherapy (NAC) and surgery, and the indications for additional treatment after surgery were considered., Methods: A total of 113 patients with clinical stage II or III ESCC, who had undergone NAC followed by a thoracic esophagectomy with a three-field lymphadenectomy were retrospectively reviewed. NAC consisted of either two courses of cisplatin and 5-fluorouracil or three courses of docetaxel, cisplatin and 5-fluorouracil, with a new course beginning every 3 weeks., Results: The overall survival (OS) rate was poorer in the pN-positive group than in the pN-negative group (P < 0.001). In terms of the histological therapeutic effect, the OS rate was poorer in the worse pathological responder group than in the better pathological responder group (P = 0.001). A multivariate analysis examining overall survival suggested that only pN (HR 3.204, P = 0.007) and worse pathological responder (HR 2.347, P = 0.041) were independent prognostic factors. The OS rate was compared among four groups classified according to the different combinations of pN and pathological response. A group of patients with pN-positive and worse pathological response had a significantly poorer outcome than the other groups., Conclusions: The present study suggested that patients with resectable advanced ESCC undergoing NAC followed by surgery, who have both pN and worse pathological response, have a poor prognosis.

In a previous study, a phantom study of a contrast agent extraction system with computed tomography (CT) number and raw-data-based electron density (ED) was described. The current study improved this system with monochromatic CT (mCT) number and evaluated an anthropomorphic phantom for delineation of the contrast-enhanced region. Dual-energy CT images were scanned with a tissue-equivalent phantom and an anthropomorphic phantom with an iodinated contrast agent (1-130 mg/mL). The 40, 70, and 130 keV mCT images were reconstructed with 80 and 135 kV CT images. The contrast agent was separated from other materials using the gradient of the mCT number (GmCT) and the threshold mCT numbers. The system was analyzed using in-house software with Python. The evaluation of the accuracy for the contrast agent extraction was performed by measuring the ratio of the volume (ROV). The mCT number of the contrast agent and bone materials, liver, and muscle in the tissue-equivalent phantom was obviously greater than - 78 HU. The deviation of the mCT numbers between bone materials in tissue-equivalent phantom and the contrast agent were larger than 8 HU. The GmCT was within 4.0 in the tissue-equivalent phantom and more than 6.0 in the contrast agent. The ROV was 0.97-1.00 at more than 1 mg/mL contrast agent. Improved the contrast agent extraction system could be used for a patient's CT image. It could extract the iodinated tumor or lesion automatically. The contrast agent extraction system was improved by the mCT number. It is expected to only extract the contrast-enhanced region automatically.

Purpose: We previously demonstrated that the rational pediatric dosage of warfarin can be well-described by a SIZE parameter that includes an allometry exponent of weight. On the other hand, allometry alone is considered to be insufficient to predict drug clearance in neonates and infants. The primary purpose of the present study was to evaluate the effects of incorporation of the maturation process into the analysis model for the dose-response relationship of warfarin in Japanese children. In addition, we evaluated the effect of chronic heart failure (CHF) on the response to warfarin as an independent risk factor for increased anticoagulant effects., Methods: Thirty-eight patients with stable anticoagulation by warfarin were enrolled. During a mean follow-up period of 4.74 ± 3.51 years, 1092 data points including prothrombin time-international normalized ratio (PT-INR) were obtained. The data were subjected to multiple regression analysis to identify covariates related to the anticoagulant effects., Results: Two different models describing the maturation process did not improve the predictive performance for the dose-response relationship in pediatric patients. In addition to the SIZE-normalized daily dose, the vitamin K epoxide reductase complex 1 (VKORC1) genotype, and concomitant use of bosentan, CHF was identified as a covariate increasing the anticoagulant effects of warfarin to 118%., Conclusion: The SIZE parameter was useful even without incorporation of maturation models to describe the response to warfarin in pediatric patients, and our longitudinal follow-up study design with multiple observations was beneficial to detect changes within individual subjects.

Background: This study aimed to compare the extent of lateral thermal spread of surrounding tissues after the use of advanced bipolar and ultrasonic coagulation and shearing devices. Association between recurrent laryngeal nerve paralysis (RLNP) and such devices was assessed in patients who underwent minimally invasive esophagectomy (MIE)., Methods: LigaSure ™ (LS) and Sonicision ™ (SONIC) were used. In ex vivo experiments using the porcine muscle, blade temperature and tissue temperature were measured using a thermometer after the activation of both devices. For the clinical assessment, 46 consecutive patients who received MIE were retrospectively assessed., Results: The temperature generated at the blade of both devices increased with the activation time. The blade temperature of LS was significantly lower than that of SONIC (P < 0.001). The blade temperature of SONIC exceeded 100 °C after 3-s activation. The temperature of surrounding tissues after a single activation of the devices decreased with the tissue distance from activation blade. The temperatures of tissues at 1 and 2 mm away from the blade side of LS were significantly lower than those of SONIC (P = 0.001 and P < 0.001, respectively). The temperature of tissue 2 mm away from the blade side of LS increased 6.4 °C from the baseline temperature. Furthermore, the incidence of RLNP in the LS group was lower than that in the SONIC group (P = 0.044)., Conclusion: This study highlights the necessity of spatial and temporal recognition of the thermal spread of coagulation and shearing devices to reduce the thermal injuries following MIE.

In the original publication of the article, the below name of institutions were not included in the table of Institution-registered cases in 2011.

Background: The aim of the study was to assess serum C-reactive protein (CRP) level immediately after minimally invasive esophagectomy (MIE) as a surrogate of surgical invasiveness in patients who underwent esophagectomy., Methods: In total, 104 patients were enrolled in the study: 37 patients underwent MIE in the left lateral decubitus position (MIE-LP) and 67 patients underwent MIE in the prone position (MIE-PP). Serum CRP levels were assessed on POD 1, 3, 5, and 7 after MIE, and were compared with surgical outcomes and duration of systemic inflammatory response syndrome (SIRS) to investigate less invasiveness of the MIE., Results: Reduced serum CRP level on POD 1 was associated with PP during MIE (P < 0.001) and decreased blood loss (P = 0.03). MIE-PP was identified as a significant independent predictor of reduced CRP level on POD 1 (odds ratio 3.65, P = 0.042). CRP level on POD 7 was associated with gender (P = 0.02), position of MIE (P = 0.011), blood loss (P = 0.02), and respiratory complications and/or anastomotic leakage (P < 0.001). Postoperative respiratory and/or anastomotic complication was identified as a significant predictor of elevated serum CRP level on POD 7 (odds ratio 3.44, P = 0.048). Shorter duration of SIRS was shown in the patients with reduced serum CRP level on POD 1 and 7 (P = 0.03 and P < 0.001, respectively)., Conclusion: Serial assessments of serum CRP level immediately after MIE may be a possible indicator that can reflect surgical invasiveness and postoperative complications.

Patient motion monitoring systems play an important role in providing accurate treatment dose delivery. We propose a system that utilizes a web camera (frame rate up to 30 fps, maximum resolution of 640 × 480 pixels) and an in-house image processing software (developed using Microsoft Visual C++ and OpenCV). This system is simple to use and convenient to set up. The pyramidal Lucas-Kanade method was applied to calculate motions for each feature point by analysing two consecutive frames. The image processing software employs a color scheme where the defined feature points are blue under stable (no movement) conditions and turn red along with a warning message and an audio signal (beeping alarm) for large patient movements. The initial position of the marker was used by the program to determine the marker positions in all the frames. The software generates a text file that contains the calculated motion for each frame and saves it as a compressed audio video interleave (AVI) file. We proposed a patient motion monitoring system using a web camera, which is simple and convenient to set up, to increase the safety of treatment delivery.

Purpose: This study aimed to compare short-term outcomes of minimally invasive esophagectomy (MIE) with those of open esophagectomy (OE) for thoracic esophageal cancer using a nationwide Japanese database., Methods: Overall, 9584 patients with thoracic esophageal cancer who underwent esophagectomy at 864 hospitals in 2011-2012 were evaluated. We performed one-to-one matching between the MIE and OE groups on the basis of estimated propensity scores for each patient., Results: After propensity score matching, operative time was significantly longer in the MIE group (n = 3515) than in the OE group (n = 3515) [526 ± 149 vs. 461 ± 156 min, p < 0.001], whereas blood loss was markedly less in the MIE group than in the OE group (442 ± 612l vs. 608 ± 591 ml, p < 0.001). The populations of patients who required more than 48 h of postoperative respiratory ventilation was significantly less in the MIE group than in the OE group (8.9 vs. 10.9%, p = 0.006); however, reoperation rate within 30 days was significantly higher in the MIE group than in the OE group (7.0 vs. 5.3%, p = 0.004). There were no significant differences between the MIE and OE groups in 30-day mortality rates (0.9 vs. 1.1%) and operative mortality rates (2.5 vs. 2.8%, respectively)., Conclusions: MIE was comparable with conventional OE in terms of short-term outcome after esophagectomy. It was particularly beneficial in reducing postoperative respiratory complications, but may be associated with higher reoperation rates.

Background: The extent of node dissection in esophageal cancer surgery is usually estimated by the number of resected nodes, irrespective of the area of dissection. The efficacy of lymph node dissection by area was evaluated according to the location of the primary tumor., Methods: The study group comprised the 3827 patients who underwent R0 esophagectomy with three-field lymph node dissection for squamous cell carcinoma, registered in a nationwide registry in Japan. The areas of lymph node were classified into zones according to AJCC Staging Manual. The Efficacy Index (EI) calculating the frequency and patient survival of metastases to each zone was investigated according to tumor location., Results: The EI was high in supraclavicular and upper mediastinal zones in patients with upper esophageal tumors, highest in upper mediastinal zone followed by supraclavicular and perigastric zones in patients with middle esophageal tumors, and highest in perigastric zone followed by upper and lower mediastinal zones in patients with lower esophageal tumors. In patients with middle and lower esophageal cT1 tumors, the EIs of upper mediastinal and perigastric zones were higher than middle and lower mediastinal zones., Conclusion: The EIs of each zone were differed by tumor location. The extent of lymph node dissection should be estimated by the dissected zones and modified by the tumor location. Supraclavicular dissection is indispensable for patients with upper esophageal tumors, and recommended for patients with middle esophageal tumors. Upper mediastinal dissection is recommended for all patients with thoracic esophageal squamous cell carcinoma, irrespective of the location.

Light energy drives photosynthesis, but it simultaneously inactivates photosynthetic mechanisms. A major target site of photo-damage is photosystem II (PSII). It further targets one reaction center protein, D1, which is maintained efficiently by the PSII repair cycle. Two proteases, FtsH and Deg, are known to contribute to this process, respectively, by efficient degradation of photo-damaged D1 protein processively and endoproteolytically. This study tested whether the D1 cleavage accomplished by these proteases is affected by different monochromic lights such as blue and red light-emitting-diode light sources, remaining mindful that the use of these lights distinguishes the current models for photoinhibition: the excess-energy model and the two-step model. It is noteworthy that in the two-step model, primary damage results from the absorption of light energy in the Mn-cluster, which can be enhanced by a blue rather than a red light source. Results showed that blue and red lights affect D1 degradation differently. One prominent finding was that D1 fragmentation that is specifically generated by luminal Deg proteases was enhanced by blue light but not by red light in the mutant lacking FtsH2. Although circumstantial, this evidence supports a two-step model of PSII photo-damage. We infer that enhanced D1 fragmentation by luminal Deg proteases is a response to primary damage at the Mn-cluster.

Background: In 2009, the rate of thoracoscopic esophagectomy for esophageal cancer was about 20% in Japan. This low rate may be due to the difficulty in maintaining a good surgical field and the meticulous procedures that are required. The purpose of this study was to establish and evaluate a new procedure for performing a thoracoscopic esophagectomy while the patient is in a prone position using a preceding anterior approach to make the esophagectomy easier to perform., Methods: We have performed thoracoscopic esophagectomy using our new procedure in 60 patients with esophageal cancer. Each patient was placed in a prone position and five trocars were inserted; only the left lung was ventilated and a pneumothorax was maintained. The esophagus was mobilized from the anterior structure during the first step and from the posterior structure during the second step. The lymph nodes around the esophagus were also dissected anteriorly and posteriorly. The patients were sequentially divided into two groups and their clinical outcomes were evaluated., Results: The mean operative time for the thoracoscopic procedure for the latter 30 cases (203 min) was shorter than that for the former 30 cases (260 min) (P = 0.001). Among the 52 cases without pleural adhesion, the mean blood loss in the latter 26 cases (18 mL) was also less than that in the former 26 cases (40 mL) (P = 0.027). There were no conversions to a thoracotomy and no operative deaths in this series. Postoperative complications related to the thoracoscopic procedure occurred in 8 cases (27%) in the former group and in 4 cases (13%) in the latter group., Conclusions: Thoracoscopic esophagectomy with the patient in the prone position using a preceding anterior approach is a safe and feasible procedure. As experience performing the procedure increases, the performance of the procedure stabilizes. This method seems to make the esophagectomy easier to perform.

Background: Postoperative delirium is a common complication after major surgery and is characterized by acute confusion with fluctuating consciousness. The aim of this study was to investigate the incidence and risk factors of postoperative delirium in patients with esophageal cancer., Methods: We conducted a retrospective cohort analysis of 306 consecutive patients who had undergone an esophagectomy at Keio University Hospital from January 1998 to December 2009. All data were assessed by psychiatrists, and delirium was diagnosed according to criteria of the Diagnostic and Statistical Manual Disorder, fourth edition. Univariate and multivariate analyses were performed., Results: Postoperative delirium developed in 153 (50.0 %) of 306 patients. One hundred fourteen (37.3 %) of the 306 patients required psychoactive medication for symptoms associated with delirium. Univariate analyses showed that older age, male gender, additional flunitrazepam for sedation in intensive care unit (ICU) after surgery, longer periods of time under mechanical ventilation after surgery, longer ICU stays, occurrence of postoperative complications, and longer hospital stays were significantly associated with postoperative delirium. Multivariate analysis revealed that development of delirium was linked to older age, additional flunitrazepam in ICU, and occurrence of postoperative complication., Conclusions: The development of postoperative delirium in patients with esophageal cancer is a problem that cannot be ignored. Our results suggest that the risk of developing delirium is associated with older age, use of flunitrazepam in ICU, and postoperative complications.

Background: Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing-that is, before or after surgery-for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma., Methods: Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival., Results: We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P = 0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54-0.99, P = 0.04), where the median follow-up of censored patients was 61.6 months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1., Conclusions: Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.

Background: The recurrence of hepatocellular carcinoma is still high even after surgery. Two general recurrence patterns occur: intrahepatic metastasis (IM) and multicentric carcinogenesis (MC). The aim of this study was to investigate the effectiveness of adjuvant chemolipiodolization for reducing IM or MC recurrences after surgery., Methods: A retrospective case-control study was carried out. From April 2005, adjuvant chemolipiodolization was performed in 63 initial hepatocellular carcinoma patients 3 months after surgery. Sixty-four patients who underwent surgery between April 2001 and March 2005 were analyzed as the control group. Recurrence-free and overall survival as well as prognostic factors were analyzed univariately and multivariately., Results: The 2-year recurrence-free survival was 57% in the chemolipiodolization group and 37% in the control group (P = 0.02). However, there was no significant difference at 5 years after surgery (P = 0.09). The 5-year overall survival rates in the chemolipiodolization and the control groups were 82.4 and 55.7%, respectively (P = 0.04). Cox proportional multivariate analysis revealed that adjuvant chemolipiodolization was an independent favorable prognostic factor for 2-year recurrence-free survival, and the odds ratio [95% confidential interval] was 0.55 [0.34-0.90] (P = 0.02). However, adjuvant chemolipiodolization was not an independent favorable prognostic factor for 5-year overall survival., Conclusions: Adjuvant chemolipiodolization can reduce the risk of early recurrences, which would be mainly IM derived. However, chemolipiodolization did not reduce late phase recurrences after surgery, which would be mainly MC derived. To prevent late phase recurrences, another novel strategy would be needed.

A 48-year-old woman presented with a 15-cm diameter tumor in her left breast with fixation to the chest wall and palpable axillary lymph nodes. Pathology study showed pure-type mucinous carcinoma. Pretreatment staging investigations showed multiple lung metastases, which resulted in the diagnosis of T4N2M1 breast cancer. Four cycles of cyclophosphamide 700 mg/m(2)/epirubicin 70 mg/m(2) (CE) were performed initially, but the tumors decreased only within the treatment response criteria of stable disease (SD). The second regimen of docetaxel could not continue due to drug allergy. Two more cycles of CE did not improve the situation. Then, treatment was continued with full-dose capecitabine with local radiotherapy. She received radiotherapy to the left breast and axillary region with 60 Gy/30 fractions/6 weeks and concomitant capecitabine 2400 mg/body twice daily for 21 days; the cycles were repeated every 28 days. After radiotherapy, tumors decreased in size, and the skin ulceration disappeared. She continued to receive capecitabine on the same schedule. She now has no palpable tumor in her left breast and no tumor in the axilla or lung on CT. She is alive and well 6 years after radiotherapy.

HisJ is a histidine binding subunit of the histidine permease, which exists in the outer membrane of Gram-negative bacteria. In order to incorporate the periplasmic histidine into the cell, HisJ captures histidine in the periplasm, and transfers the histidine to the transmembrane complex of histidine permease that is an ABC transporter. We established the backbone resonance assignments of (1)H/(13)C/(15)N-labeled HisJ from Escherichia coli, in the histidine-bound and unbound states.

The long-term outcomes of 97 consecutive patients with hepatolithiasis, who underwent treatment from January 1971 to June 2006, were analyzed. The short-term outcomes included the rate of residual stones and complications after treatment, whereas the long-term results included the stone recurrence rate. In 22 of the 97 (22.7%) patients, residual stones were found after treatment for hepatolithiasis. The incidence of residual stones was 0% in hepatectomy patients, 48.6% in cholangioenterostomy patients (p < 0.001, compared with hepatectomy), 25.0% in T-tube drainage patients (p = 0.015, compared with hepatectomy), and 10.0% in percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) patients. In 15 of the 66 (22.7%) patients who were treated for hepatolithiasis, recurrent stones were found after intervals of 5 to 24 years. The incidence of recurrent stones was 13.9% in hepatectomy patients, 28.5% in cholangioenterostomy patients, 25.0% in T-tube drainage patients, and 50.0% in PTCSL patients (p = 0.021, compared with hepatectomy). Hepatectomy appears to be the most effective treatment for selected patients with isolated left hepatolithiasis (L). In PTCSL procedures, favorable results have been obtained when the stones were completely cleared; however, the incidence of recurrent stones is high in patients after PTCSL.

Objective: Microsomal epoxide hydrolase (mEH) is an enzyme that detoxifies reactive epoxides and catalyzes the biotransformation of carbamazepine-10,11-epoxide (CBZ-epoxide) to carbamazepine-10,11-diol (CBZ-diol). Utilizing single nucleotide polymorphisms (SNPs) of the EPHX1 gene encoding mEH, we identified the haplotypes of EPHX1 blocks and investigated the association between the block haplotypes and CBZ-epoxide metabolism., Methods: SNPs of EPHX1 were analyzed by means of polymerase chain reaction amplification and DNA sequencing using DNA extracted from the blood leukocytes of 96 Japanese epileptic patients, including 58 carbamazepine-administered patients. The plasma concentrations of CBZ and its four metabolites were determined using high-performance liquid chromatography., Results: From sequencing all 9 exons and their surrounding introns, 29 SNPs were found in EPHX1. The SNPs were separated into three blocks on the basis of linkage disequilibrium, and the block haplotype combinations (diplotypes) were assigned. Using plasma CBZ-diol/CBZ-epoxide ratios (diol/epoxide ratios) indicative of the mEH activity, the effects of the diplotypes in each EPHX1 block were analyzed on CBZ-epoxide metabolism. In block 2, the diol/epoxide ratios increased significantly depending on the number of haplotype *2 bearing Y113H (P=0.0241). In block 3, the ratios decreased depending on the number of haplotype *2 bearing H139R (P=0.0351). Also, an increasing effect of a *1 subtype, *1c, was observed on the ratio., Conclusion: These results show that some EPHX1 haplotypes are associated with altered CBZ-epoxide metabolism. This is the first report on the haplotype structures of EPHX1 and their potential in vivo effects.

Apoptosis can be induced by various stimuli such as the ligands of death receptors, chemotherapeutic drugs and irradiation. It is generally believed that chemotherapeutic drugs induce mitochondrial damage, cytochrome c release and activation of caspase-9, leading to apoptosis. Here, we found that an isoprenoid antibiotic, 4-O-methyl ascochlorin, significantly induces typical apoptotic events in Jurkat cells including the degradation of poly (ADP-ribose) polymerase, DNA fragmentation, activation of caspase-3, -9 and -8, and cytochrome c release from mitochondria. Similar to Fas stimulation, 4-O-methyl ascochlorin but not staurosporine, cycloheximide and actinomycin D, induced apoptosis in SKW6.4 cells, in which apoptosis is strongly dependent on death-inducing signaling-complex. Bcl-2 overexpression in Jurkat cells completely suppressed the apoptosis, but procaspase-9 processing was partially induced. A caspase-8 inhibitor, IETD-fmk, effectively suppressed poly (ADP-ribose) polymerase cleavage and cytochrome c release. However, 4-O-methyl ascochlorin induced apoptosis in Jurkat cells deficient of caspase-8 or Fas-associated death domain protein. These results suggest that 4-O-methyl ascochlorin induces apoptosis through the mechanism distinct from conventional apoptosis inducers., (Copyright 2004 Kluwer Academic Publishers)

A probabilistic test (FUMI theory) for GeneChip experiments has been proposed for selecting the genes which show significant differences in the gene expression levels between a single pair of treatment and control. This paper describes that the reliability of the judgment by the FUMI theory can be enhanced, when the selected genes are referred to biomolecular-functional networks of a commercial database. The genes judged as being differently expressed are grouped into a cluster in the biomolecular networks. It is also demonstrated that false positive genes have a trend in the networks to be isolated from each other, and also away from the clustered genes, since the false positive genes are randomly selected.

The clinical significance of micrometastasis in sentinel nodes (SNs) may differ in various organs. In particular, the prognostic value of SN micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) is still controversial. We investigated the diagnostic and therapeutic significance of nodal molecular metastasis detected by nested RT-PCR for cytokeratin (CK) 19 mRNA in gastrointestinal cancer. In 51 cases with GI tract cancer treated by standard curative resection, SNs were identified by a radio-guided method. In 10 of 51 patients, 25 SNs and 3 non-SNs were histologically negative and RT-PCR positive. Three non-SNs with positive CK19 mRNA were randomly sampled from the same basin where histologically positive SNs were identified. Immunohistochemical analysis of six additional step sections obtained at 30- micro m intervals with use of an anticytokeratin antibody showed clearly recognizable histological metastases in 4 of 25 histologically negative/RT-PCR-positive SNs (16%). In one case of esophageal squamous cell carcinoma with nodal micrometastasis identified by CK19 RT-PCR, extranodal local recurrence in the SN basin (left supraclavicular basin) was observed 6 months postoperatively. These findings suggest that nodal micrometastasis detected by nested RT-PCR has some clinical significance in GI cancer. Molecular assessment of the SN may be a valuable tool to complement routine histological examination for GI cancers.

A traditional method for comparing two expression levels of genes in microarray experiments is the two-sample t-test. Because of the difficulty in using a large number of microarrays, an alternative method is required which can provide a reliable judgment of the comparison from a small number of replicates, even from a single pair of control and treatment. We present a method for detecting the changes in the gene expression levels under two different conditions in microarray experiments. Our method targets a single experiment for each condition, while retaining the statistical advantages of the t-test. The new proposals are: 1) standard deviation (SD) estimates of the expression levels which are an indicator for significant differences are given a priori as a function of the expression levels; 2) the limit of detection (LOD) for the expression levels is used to eliminate the majority of genes expressed at extremely low levels. The a priori SD estimates are obtained from six replicates under a fixed condition and are shown to be the approximate, but proper description of the expression uncertainty covering diverse conditions (e.g., different samples (human and rat) and different DNA chips). The LOD is defined as three times blank SD according to the IUPAC recommendation. A cell line (HL60) which will undergo macrophage differentiation on treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) is taken as an example. Our method is compared with the t-test for the data on duplicate TPA experiments and the former alone is evaluated with the data on a single TPA experiment. The errors from sample preparation and instrumental analysis are discussed.

Background: We investigated whether aberrant p53 and p16 expression, the Ki-67 labeling index (LI), and int-2/cyclin D1 gene amplification predict the response to chemoradiotherapy (CRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC)., Methods: p53 and p16 expression status, the Ki-67 LI, and int-2/cyclin D1 amplification were assessed by immunohistochemical staining and slot blot analysis in pretreatment endoscopic biopsy specimens of 41 patients with T4 or M1 Lym (distant lymph node metastasis) ESCC. All patients received a course of chemotherapy (5-fluorouracil and cisplatin) with radiotherapy., Results: The CRT therapeutic response rate was 71%, and resection after CRT was successful in 15 of the cases in which the CRT effect was significant. The cumulative survival rate after CRT in the p53-negative patients was significantly higher than in the p53-positive patients (P =.037). The mean Ki-67 LI in the CRT response cases was significantly higher than in the CRT no-response cases (P =.023). Multivariate regression analysis revealed high Ki-67 LI to be an independent variable linked to a pathologic complete response to CRT (P =.033). The cumulative survival rate after CRT in the group that was p53-negative and int-2/cyclin D1 amplification-positive was significantly higher than in the other groups (P =.008)., Conclusions: Evaluating predictive factors in pretreatment endoscopic biopsy specimens may allow selection of more suitable multimodal treatment for ESCC patients and improve their quality of life.

Although the sentinel node (SN) concept has been validated in malignant melanoma and breast cancer, the application of this concept for other solid tumors, including gastrointestinal (GI) cancer, is still controversial. We have demonstrated the feasibility of radioguided SN mapping during laparotomy in patients with esophageal, gastric, and colorectal cancers. In 188 patients, the SNs identified by this technique had an overall diagnostic accuracy of 96% for regional lymph node metastasis. Aberrant drainage sites that have been called skip metastasis from the primary lesion were detectable using this method. More recently, we have undertaken SN mapping during laparoscopic surgery. A combination of radiotracer and blue dye optimized the identification of SNs that drained GI cancers. Our preliminary data indicate that laparoscopic mapping of the SN is a sensitive intraoperative technique for identifying lymph node micrometastasis, and we believe that it will become an important component of a minimally invasive approach to early-stage GI cancers.

Background: It has been reported that nicorandil restores blood flow to reperfused myocardium in patients with acute myocardial infarction. However, whether nicorandil might decrease infarct size remains unclear. The aim of this study was to assess the effect of nicorandil on infarct size with thallium-201/beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) dual-isotope single photon emission computed tomography., Methods: A total of 62 patients were randomly assigned to receive intravenous nicorandil (4 mg in 5 minutes at admission, immediately followed by 6 mg/hr over a 24-hour period) or placebo. All patients were divided into 4 groups: Group N-a, 16 patients with preexisting angina treated with nicorandil; N-b, 15 patients without preexisting angina treated with nicorandil; C-a, 14 patients with preexisting angina given placebo; C-b, 17 patients without preexisting angina given placebo. Tl-201/BMIPP imaging was performed in the 62 patients within 7 days after admission. Dual-isotope single photon emission computed tomographic images were quantified by severity index with a polar map., Results: The BMIPP severity index was similar among the 4 groups. Only the thallium severity index in the N-a group was significantly less (P<.05). The ratio of the thallium severity index to that of BMIPP in the N-a group was significantly decreased compared with those of the other groups., Conclusion: Nicorandil has a protective effect in patients with acute myocardial infarction and preexisting angina treated with primary balloon angioplasty.

Background: Angiotensin-converting enzyme (ACE) inhibitor therapy has an early mortality benefit in unselected patients with acute myocardial infarction (AMI). However, the effects of ACE inhibition on myocardial fatty acid metabolism in this patient population have not been studied. We tested the hypothesis that ACE inhibitor therapy improves myocardial fatty acid metabolism and decreases mortality rate in patients after AMI., Methods: Forty-two patients after first anterior AMI and primary angioplasty were randomly assigned to titrated oral enalapril (n = 24) or placebo therapy (n = 18). Iodine 123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) single photon emission computed tomography imaging was performed an average of 4.8 days after AMI and 1 month after AMI. BMIPP abnormalities were quantified as a severity index by a polar map., Results: There were no significant changes in baseline characteristics, cardiac function, and angiographic findings between patients in the enalapril group and patients in the placebo group. However, BMIPP severity index from acute phase to chronic phase was significantly decreased in the enalapril-treated group (118+/-48 to 82+/-36, P<.05), but not in the placebo group (123+/-65 to 115+/-58, P not significant)., Conclusion: ACE inhibition therapy improved myocardial fatty acid metabolism and regional left ventricular function in patients after anterior AMI. BMIPP single photon emission computed tomography findings imply that this better outcome may be attributable to an improvement of cellular function with ACE inhibitors.

Ion permeation properties of the mouse e2/zeta1 NMDA receptor channel expressed in Xenopus oocytes were studied using the outside-out patch-clamp technique. In symmetrical Na+ solutions, the single-channel I-V relations were almost linear at low electrolyte concentrations, but rectified inwardly for Na+ concentrations above 50 mm. In symmetrical Na+ solutions, the "zero-current conductance" increased with Na+ concentration and saturated according to a hyperbolic curve, the half-maximal saturating activity, KM(Na), being 14.2 mm and the maximal conductance, Gmax(Na), 53.9 pS. When Ca2+ was present with Na+ in the external solution, the single-channel current was lower than in pure Na+, although the reversal potential indicated a higher permeability for Ca2+ than for Na+. Using ion activities, PCa/PNa was found to be about 17. The I-V data were fitted with a model based on the Eyring's rate theory, assuming a one-ion pore with three energy barriers and two sites. The KM(Ca) and Gmax (Ca) were 76.5 microm and 21.2 pS, respectively. According to the estimated rate constants, KM for Ca2+ is mainly determined by the binding strength of a site located 80% away from the channel opening at the external membrane-solution interface, a position similar to that postulated previously for the Mg2+ blocking site.

Field and intracellular potentials were recorded in the vestibular nuclei of the lizard following stimulation of the ipsi- and contralateral vestibular nerves. The field potentials induced by ipsilateral VIIIth nerve stimulation consisted of an early negative or positive-negative wave (presynaptic component) followed by a slow negativity (transsynaptic component). The spatial distribution of the field potential complex closely paralleled the extension of the vestibular nuclei. Mono- and polysynaptic EPSPs were recorded from vestibular neurons after ipsilateral VIIIth nerve stimulation. In some neurons early depolarizations preceded the EPSPs. These potentials may be elicited by electrical transmission. Often spikelike partial responses were superimposed on the EPSPs. It is assumed that these potentials represent dendritic spikes. Contralateral VIIIth nerve stimulation generated disynaptic and polysynaptic IPSPs in some neurons and EPSPs in others. The possible role of commissural inhibition in phylogeny is discussed. In a group of vestibular neurons stimulation of the ipsilateral VIIIth nerve evoked full action potentials with latencies ranging from 0.25-1.1msec. These potentials are caused by antidromic activation of neurons which send their axons to the labyrinth.