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Background: The stool color card has been the primary tool for identifying acholic stools in infants with biliary atresia (BA), in several countries. However, BA stools are not always acholic, as obliteration of the bile duct occurs gradually. This study aims to introduce Baby Poop (Baby unchi in Japanese), a free iPhone application, employing a detection algorithm to capture subtle differences in colors, even with non-acholic BA stools., Methods: The application is designed for use by caregivers of infants aged approximately 2 weeks-1 month. Baseline analysis to determine optimal color parameters predicting BA stools was performed using logistic regression (n = 50). Pattern recognition and machine learning processes were performed using 30 BA and 34 non-BA images. Additional 5 BA and 35 non-BA pictures were used to test accuracy., Results: Hue, saturation, and value (HSV) were the preferred parameter for BA stool identification. A sensitivity and specificity were 100% (95% confidence interval 0.48-1.00 and 0.90-1.00, respectively) even among a collection of visually non-acholic, i.e., pigmented BA stools and relatively pale-colored non-BA stools., Conclusions: Results suggest that an iPhone mobile application integrated with a detection algorithm is an effective and convenient modality for early detection of BA, and potentially for other related diseases.

Studies on ecology of medical care can provide valuable information on how people seek healthcare in a specific geographic area. The objective of this study was to update a 2003 report on the ecology of medical care in Japan, identifying relevant changes in healthcare patterns. We collected information based on a prospective health diary recorded for a month in 2013 (n = 4548; 3787 adults and 797 children) using a population-weighted random sample from a nationally representative panel. We compared our overall and stratified findings with a similar study conducted in 2003. During a one-month period, per 1000 adults and children living in Japan, we estimated that 794 report at least one symptom, 447 use an over-the-counter (OTC) drug, 265 visit a physician's office, 117 seek help from a professional provider of complementary or alternative medicine (CAM), 70 visit a hospital outpatient clinic (60 community-based and 10 university-based), 6 are hospitalized, and 4 visit a hospital emergency department. After adjusting for demographic variables, we found that healthcare seeking behaviors were influenced by age, gender and area of living. Compared with the 2003 study, participants in this study had fewer symptoms, fewer physician and emergency room visits, and less OTC use, but reported higher frequency of CAM use (p < .01 for all). Compared with 2003, reported symptoms, physician visits and OTC use has decreased, while CAM use has increased. Our findings may be useful to policymakers in Japan in a context where healthcare expenditure and a rapidly aging population are two challenging issues.

Knowledge about the arrangement of visual elements is an important aspect of perception. This study investigates whether humans learn rules of two-dimensional abstract patterns (exemplars) generated from Reber's artificial grammar. The key question is whether the subjects can implicitly learn them without explicit instructions, and, if so, how they use the acquired knowledge to judge new patterns (probes) in relation to their finite experience of the exemplars. The analysis was conducted using dissimilarities among patterns, which are defined with n-gram probabilities and the Levenshtein distance. The results show that subjects are able to learn rules of two-dimensional visual patterns (exemplars) and make categorical judgment of probes based on knowledge of exemplar-based representation. Our analysis revealed that subjects' judgments of probes were related to the degree of dissimilarities between the probes and exemplars. The result suggests the coexistence of configural and element-based processing in exemplar-based representations. Exemplar-based representation was preferred to prototypical representation through tasks requiring discrimination, recognition and working memory. Relations of the studied judgment processes to the neural basis are discussed. We conclude that knowledge of a finite experience of two-dimensional visual patterns would be crystalized in different levels of relations among visual elements.

The present study used functional near-infrared spectroscopy (fNIRS) to measure 5- to 6-month-old infants' hemodynamic response in the prefrontal cortex (PFC) to visual stimuli differing in saliency and social value. Nineteen Japanese 5- to 6-month-old infants watched video clips of Peek-a-Boo (social signal) performed by an anime character (AC) or a human, and hand movements without social signal performed by an AC. The PFC activity of infants was measured by 22-channel fNIRS, while behaviors including looking time were recorded simultaneously. NIRS data showed that infants' hemodynamic responses in the PFC generally decreased due to these stimuli, and the decrease was most prominent in the frontopolar (FP), covering medial PFC (MPFC), when infants were viewing Peek-a-Boo performed by an AC. Moreover, the decrease was more pronounced in the dorsolateral PFC (DLPFC) when infants were viewing Peek-a-Boo performed by an AC than by a human. Accordingly, behavioral data revealed significantly longer looking times when Peek-a-Boo was performed by an AC than by a human. No significant difference between Peek-a-Boo and non-Peek-a-Boo conditions was observed in either measure. These findings indicate that infants at this age may prefer stimuli with more salient features, which may be more effective in attracting their attentions. In conjunction with our previous findings on responses to self-name calling in infants of similar age, we hypothesize that the dynamic function of the MPFC and its vicinity (as part of default mode network (DMN): enhanced by self-focused stimuli, attenuated by externally focused stimuli), which is consistently observed in adults, may have already emerged in 5- to 6-month-old infants.

As a consequence of global climate-driven changes, marine ecosystems are experiencing polewards redistributions of species - or range shifts - across taxa and throughout latitudes worldwide. Research on these range shifts largely focuses on understanding and predicting changes in the distribution of individual species. The ecological effects of marine range shifts on ecosystem structure and functioning, as well as human coastal communities, can be large, yet remain difficult to anticipate and manage. Here, we use qualitative modelling of system feedback to understand the cumulative impacts of multiple species shifts in south-eastern Australia, a global hotspot for ocean warming. We identify range-shifting species that can induce trophic cascades and affect ecosystem dynamics and productivity, and evaluate the potential effectiveness of alternative management interventions to mitigate these impacts. Our results suggest that the negative ecological impacts of multiple simultaneous range shifts generally add up. Thus, implementing whole-of-ecosystem management strategies and regular monitoring of range-shifting species of ecological concern are necessary to effectively intervene against undesirable consequences of marine range shifts at the regional scale. Our study illustrates how modelling system feedback with only limited qualitative information about ecosystem structure and range-shifting species can predict ecological consequences of multiple co-occurring range shifts, guide ecosystem-based adaptation to climate change and help prioritise future research and monitoring., (© 2016 John Wiley & Sons Ltd.)

Patients with cancer exhibit various symptoms induced by cancer itself and its therapy leadingto fatigue; however, their vital energy can be restored by administration of Kampo, which is a traditional Japanese herbal medicine. Restoration and maintenance of mental and physical energy are important for successful cancer treatment. For this purpose, appropriate use of Kampo formulas, such as"Ho-zai", formulas to vitalize fatigued patients (eg, Hochu-ekki-to, Juzen-taiho-to, Ninjin-yoeito), "Hojin-zai", formulas to restore energy (eg, Gosha-jinki-gan), and"Kuoketsu-zai ", formulas to resolve stagnant blood flow (eg, Keishi-bukuryo-gan, Tokaku-joki-to, Toki-shakuyaku-san) are administered in combination. Consequently, basic autonomic functions, such as appetite, sleep, defecation, and urination normalize and the nutritional and mental conditions are restored. These favorable changes in the patients' condition allow completion of the standard cancer therapy course, resultingin an improved outcome of cancer therapy and successful treatment. Kampo therapy can be administered as the final treatment option for patients with last-stage cancer who do not have any other effective therapy options. If patients with cancer are administered Kampo formulas, their vital energy is restored, and they develop a will to fight the cancer. As a result, communication becomes easier.

Placental growth factor (PlGF) contributes to atherogenesis through vascular inflammation and plaque destabilization. High levels of PlGF may be associated with mortality and cardiovascular disease, but the relationship between PlGF level and adverse outcomes in patients with CKD is unclear. We conducted a prospective cohort study of 1351 consecutive participants with CKD enrolled in the Novel Assessment of Risk management for Atherosclerotic diseases in CKD (NARA-CKD) study between April 1, 2004, and December 31, 2011. During a median follow-up of 3 years, 199 participants died and 383 had cardiovascular events, defined as atherosclerotic disease or heart failure requiring hospitalization. In adjusted analyses, mortality and cardiovascular risk increased in each successive quartile of serum PlGF level; hazard ratios (HRs) (95% confidence intervals [95% CIs]) for mortality and cardiovascular risk, respectively, were 1.59 (0.83 to 3.16) and 1.55 (0.92 to 2.66) for the second quartile, 2.97 (1.67 to 5.59) and 3.39 (2.20 to 5.41) for the third quartile, and 3.87 (2.24 to 7.08) and 8.42 (5.54 to 13.3) for the fourth quartile. The composite end point of mortality and cardiovascular events occurred during the study period in 76.4% of patients in both the highest PlGF quartile (≥19.6 pg/ml) and the lowest eGFR tertile (<30 ml/min per 1.73 m(2)). The association between PlGF and mortality or cardiovascular events was not attenuated when participants were stratified by age, sex, traditional risk factors, and eGFR. These data suggest elevated PlGF is an independent risk factor for all-cause mortality and cardiovascular events in patients with CKD., (Copyright © 2015 by the American Society of Nephrology.)

We describe a Japanese autopsy case of familial amyotrophic lateral sclerosis (FALS) with a TARDBP Q343R mutation. This male patient developed dysarthria at the age of 52 years, and bulbar symptoms progressed, with weakness and atrophy in the extremities. His mental status was normal, but he became bedridden, received artificial respiratory support at 54 years of age, and gradually acquired a locked-in state and died at 58 years of age. Microscopically, marked diffuse myelin pallor was observed in the anterolateral columns of the spinal cord. The remaining anterior horn cells contained Bunina bodies and phosphorylation-dependent transactivation response DNA-binding protein of 43 kDa (pTDP-43)-positive neuronal cytoplasmic inclusions (NCIs). Glial cytoplasmic inclusions (GCIs) were also observed. The number of ubiquitin- and p62-positive inclusions was markedly lower than that of pTDP-43-positive inclusions. NCIs and many fine dot-like pTDP-43-positive granules in the neuropil were mainly seen in the temporal and motor cortices, and striatum. NCIs were rare in hippocampal granular cells. Immunoblotting of samples from the cerebral cortex using an anti-pTDP-43 antibody was slightly different from previous TDP-43 pathological subtypes., (© 2015 Japanese Society of Neuropathology.)

Complementary and alternative medicine (CAM) including Japanese Kampo is known to have anticancer potential. An increasing number of cancer survivors are using CAM for disease prevention, immune system enhancement, and symptom control. Although there have been abundant previous clinical reports regarding CAM, scientific investigations aimed at acquiring quantifiable results in clinical trials, as well as basic research regarding CAM, have only recently been undertaken. Recent studies suggest that CAM enhancement of immune function is related to cytokines. This review provides a translational aspect of CAM, particularly Hozai in Kampo from both scientific and clinical points of view for further development of CAM for cancer treatment.

Three novel coelenterazine (CTZ) derivatives with extension at the C-6 position of the imidazopyrazinone structure show significant bioluminescence emission with known renilla luciferase variants, indicating a promising method to develop CTZ derivatives with superior optical properties compared to hitherto reported compounds.

In 1988, the late Prof. Rikimaru Hayashi had first proposed "Use of High Pressure in Food", introducing his views, i.e., "heat and pressure are independently capable of transforming the state of a substance, and such state transforming factors are only heat and pressure in nature." Sc. D. Masaru Nakahara stated in his note that he had been impressed by the unique starting point of Prof. Hayashi's idea. Prof. Hayashi had explored some good method for food processing without using heat, so he alternatively thought of high-pressure treatment (Hayashi R (1989) Use of high pressure to food processing and preservation. In: Hayashi R (ed) Use of high pressure in food. San-Ei Publishing Co, Kyoto, pp 1-30; Nakahara M (1990) Water and ions at high pressure: their fundamental properties relevant to the pressure treatment to food. In: Hayashi R (ed) Pressure-processed food--research and development. San-Ei Publishing Co, Kyoto, pp 3-21). Since the start-up of Japanese research group of high pressure in biological field (the present "Japanese Research Group of High Pressure Bioscience and Biotechnology (JHPBB)") and "International Association of High Pressure Bioscience and Biotechnology (IAHPBB)", we have continued to research into the industrial use of high-pressure treatment over a period of 25 years to realize our dream, that is, the same as Prof. Hayashi's dream. Although heat and pressure were found to be independent factors capable of transforming the state of a substance, use of heat has been overwhelmingly more frequent in food processing up to now. However, the pressure treatment has the advantages of instantaneous transmission, uniform distribution in vessels, and ability of inducing uniform change in quality. The high-pressure treatment does not cause cleavage of the covalent bond in the substance, thereby lessening the decomposition of nutrients, the generation of offensive smell, and the production of abnormal materials when compared with the heat application. In addition, energy consumption in the high-pressure treatment is less than that in the heat treatment. For the reasons mentioned above, the high-pressure treatment has thus been regarded as suitable for future food processing, and much attention has been paid to the researches of high-pressure treatment again. Then, we reviewed the previous researches in which little interest had been taken because of imperfectness of non-heat sterilization. Surprisingly, we discovered some novel findings about the effect of high-pressure treatment, that is, pressure history on the subsequent event. Then, we decided to present two theses on the themes, "Application of High-pressure Treatment to Enhancement of Functional Components in Agricultural Products" and "Application of High-pressure Treatment to Development of Sterilized Foods".

Loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We retrospectively evaluated 78 consecutive HIV-uninfected patients who underwent LAMP method for diagnosing Pneumocystis pneumonia (PCP). Diagnosis of PCP was made by the detection of Pneumocystis jirovecii (P. jirovecii) with positive LAMP or conventional staining (CS) (Grocott methenamine silver staining or Diff-Quick™) on the basis of compatible clinical symptoms and radiologic findings. Additionally, we reviewed HIV-uninfected immunocompromised patients who underwent subcontract PCR as a historical control. LAMP was positive in 10 (90.9%) of 11 positive-CS patients. Among 13 negative-CS patients with positive LAMP, 11 (84.6%) had PCP, and the remaining 2 were categorized as having P. jirovecii colonization. LDH levels in negative-CS PCP were higher than in positive-CS PCP (p = 0.026). (1 → 3)-β-D-glucan levels in negative-CS PCP were lower than in positive-CS PCP (p = 0.011). The interval from symptom onset to diagnosis as PCP in LAMP group (3.45 ± 1.77 days; n = 22) was shorter than in subcontract PCR group (6.90 ± 2.28 days; n = 10; p < 0.001). As for patients without PCP, duration of unnecessary PCP treatment in LAMP group (2; 2-3 days; n = 10) was shorter than in subcontract PCR group (7; 7-12.25 days; n = 6; p = 0.003). LAMP showed higher sensitivity (95.4%) and positive predictive value (91.3%) than subcontract PCR did. Pneumocystis LAMP method is a sensitive and cost-effective diagnostic method and is easy to administer in general hospitals. In-house LAMP method would realize early diagnosis of PCP, resulting in improving PCP prognosis and reducing unnecessary PCP-specific treatment., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI) identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical.

Background: Saving more limbs of patients with peripheral arterial disease (PAD) from amputation by accelerating angiogenesis in affected limbs has been anticipated for years. We hypothesized that an anti-Alzheimer drug, donepezil (DPZ), can activate angiomyogenic properties of satellite cells, myogenic progenitors, and thus be an additional pharmacological therapy against PAD. METHODS AND RESULTS: In a murine hindlimb ischemia model, we investigated the angiogenic effects of a clinical dose of DPZ (0.2 mg·kg(-1)·day(-1)) and its combination with cilostazol, a platelet aggregation inhibitor and a conventional therapeutic drug against PAD. The combination therapy most effectively improved skin coldness and most effectively upregulated vascular endothelial growth factor (VEGF)-producing satellite cells in ischemic hindlimbs. Computed tomography revealed that DPZ remarkably attenuated ischemic muscle atrophy and induced super-restoration in affected hindlimbs. The in vitro study with human aortic endothelial cells showed that DPZ or its combination with cilostazol effectively upregulated the expression of pAkt, hypoxia inducible factor-1α, and VEGF protein. Likewise, in primary cultured satellite cells, DPZ, alone or in combination, upregulated the expression of VEGF, interleukin-1β, and fibroblast growth factor 2 protein., Conclusions: The present results suggest that a clinical dosage of DPZ accelerates angiomyogenesis by directly acting on both endothelial and satellite cells. Therefore, DPZ is a potential additional choice for conventional drug therapy against PAD.

Background: Prorenin, the precursor of renin, binds to the (pro)renin receptor [(P)RR] and triggers intracellular signaling. The ligand binding sites of (P)RR are disconnected and are present in the soluble form of the receptor in serum. Given that the clinical significance of serum prorenin and soluble (P)RR in chronic kidney disease (CKD) is unclear, we investigated the relationship between serum prorenin, soluble (P)RR, and various clinical parameters in patients with CKD., Methods: A total of 374 patients with CKD were enrolled. Serum samples were collected, and the levels of soluble (P)RR and prorenin were measured using ELISA kits. Serum creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin (Hb), soluble secreted α-Klotho, and the urine protein/Cr ratio were also measured. Similarly, clinical parameters were also evaluated using serum and urine sample collected after 1 year (n = 204)., Results: Soluble (P)RR levels were positively associated with serum Cr (P < 0.0001, r = 0.263), BUN (P < 0.0001, r = 0.267), UA (P < 0.005, r = 0.168) levels, CKD stage (P < 0.0001, r = 0.311) and urine protein/Cr ratio (P < 0.01, r = 0.157), and inversely with estimated glomerular infiltration rate (eGFR) (P < 0.0001, r = -0.275) and Hb (P < 0.005, r = -0.156). Soluble (P)RR levels were inversely associated with α-Klotho levels (P < 0.001, r = -0.174) but did not correlate with prorenin levels. With respect to antihypertensive drugs, soluble (P)RR levels were significantly lower in patients treated with an angiotensin II receptor blocker (ARB) than in those without ARB therapy (P < 0.005). Soluble (P)RR levels were significantly lower in CKD patients with diabetes mellitus or primary hypertension than in those without these conditions (P < 0.05). In contrast, serum levels of prorenin did not correlate with parameters related to renal function. Serum prorenin levels were significantly higher in CKD patients with diabetes mellitus than in nondiabetic patients (P < 0.05), but not in CKD patients with hypertension (P = 0.09). Finally, with respect to the relationship between basal soluble (P)RR levels and the progression rates of renal function, soluble (P)RR levels were positively associated with ΔCr (P < 0.05, r = 0.159) and inversely associated with ΔeGFR (P < 0.05, r = -0.148)., Conclusion: Serum levels of soluble (P)RR correlated with the stage of CKD. Our findings suggest that soluble (P)RR may be involved in renal injury and influence the progression of CKD.

Background: In recent years, endoscopic submucosal dissection (ESD) has often been used for the treatment of laterally spreading tumors (LST) of the rectum. The present study was carried out with the aim of clarifying the characteristics of each of the subtypes of LST in the rectum that are often treated by ESD., Patients and Methods: This study involved 141 rectal LST that were initially treated at our hospital between March 2005 and December 2010 and whose endoscopic images and histopathological specimens could be re-examined. The LST were divided into LST-G-H (homogeneous type), LST-G-MIX (nodular mixed type), LST-NG-F (flat type) and LST-NG-PD (pseudo-depressed type) type lesions, and tumor diameter and depth of invasion of each of these tumor types were investigated., Results: Regarding the depth of invasion, the proportion of submucosa-massive (SM-m) lesions was high in the LST-NG-PDtumors, even among tumors measuring <20 mm in diameter; both the rate of cancer and proportion of SM-m lesions were significantly higher in the LST-NG-PD tumors than in the LST-NG-F tumors (P < 0.05). In both LST-NG-MIX and LST-NG-PD tumors, the proportion of SM-m lesions was significantly higher in the lower rectum than in the upper rectum (P < 0.05)., Conclusion: For LST of the rectum (particularly of the lower rectum), it is necessary to carefully select the treatment considering LST subclass and tumor diameter from the standpoint of the presence of malignancy, quality of life, and prognosis of patients., (© 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.)

Background: This study aims to evaluate the safety and efficacy of simultaneous endoscopic submucosal dissection (ESD) for synchronous double early gastric cancers., Methods: We retrospectively evaluated 832 single gastric cancers from 789 patients treated by single ESD (single group) and 124 synchronous double cancers from 62 patients treated by simultaneous ESD (simultaneous group)., Results: The overall rate of en bloc resection and curative resection was comparable between the two groups. Procedure time was significantly longer in the simultaneous group than in the single group (131.0 ± 66.5 and 94.8 ± 64.1 min, respectively, P < 0.001). White blood cell count on the day after ESD was significantly higher in the simultaneous group (9310 ± 2774/μl) than in the single group (8633 ± 2341/μl) (P = 0.032). Length of fasting period after ESD was 1.1 ± 0.5 days in the single group and 1.4 ± 1.1 days in the simultaneous group (P = 0.082). Complications were more frequent in the simultaneous group than in the single group (11.3 vs. 5.4 %, respectively), but the difference was not significant (P = 0.082). Complication rate per one lesion did not differ between the two groups (5.6 vs. 5.4 %, respectively, P = 0.914). Multivariate analysis showed procedure time longer than 150 min was independently predictive for complications of simultaneous ESD (P < 0.042, odds ratio = 6.094). Large tumors, upper portion location and tumors not in the standard guideline criteria were significantly associated with long procedure time., Conclusions: Simultaneous ESD for synchronous early gastric cancer can be a feasible and safe option, and it can reduce hospital stay. These results need to be validated by further studies.

A 73-year-old woman underwent esophagogastroduodenoscopy (EGD) at a local hospital, which revealed a flat elevated lesion, approximately 15 mm in diameter, in the posterior wall of the lower gastric body. At our hospital, a repeat EGD and biopsy led to a diagnosis of moderately dysplastic adenoma. The patient requested endoscopic submucosal dissection (ESD). Histopathology revealed a gastric adenoma with negativity for tumor at the vertical margin; however, the horizontal margin was positive for cancer with an undifferentiated carcinoma surrounding the adenoma. EGD was repeated, and a discolored area was found around the ESD scar. Biopsy revealed an undifferentiated carcinoma. Laparoscopic distal gastrectomy was performed, and postoperative histopathology also revealed an undifferentiated carcinoma (50 mm in diameter) surrounding the ESD scar; this lesion was an undifferentiated adenocarcinoma that was colocalized with and spread out to surround the original adenoma. This case is important for consideration of the pattern of development and progression of superficial spreading gastric cancer.

Background: Early esophagogastric junction (EGJ) cancer is currently being treated in the same way as early gastric cancer, by endoscopic submucosal dissection (ESD), but long-term outcomes are still unknown. Our aim was to retrospectively evaluate the safety and efficacy of ESD in treating early EGJ cancer and compare risk factors in curative and non-curative resection cases., Methods: Forty-four cases of early EGJ cancer, defined as a Siewert's type II tumor, in 44 patients with a mean age of 70.0 years and a male/female ratio of 90.9:9.1 % were treated by ESD between January 2004 and June 2010. There were 30 standard indication cases; the remaining 14 cases were expanded indication cases., Results: Mean resected specimen and tumor sizes were 35 and 17 mm, respectively, and median procedure time was 121 min, with no bleeding or perforation complications. All cases were resected en bloc with an 84.1 % curative resection rate (37/44). The curative resection rates in the standard and expanded indication cases were 90.0 % (27/30) and 71.4 % (10/14), respectively. There were no significant differences in tumor location, tumor morphology, tumor size, histology of biopsy specimens, or standard versus expanded indication cases with regard to risk factors for curative and non-curative resections. However, submucosal invasion, positive tumor margins, lymphovascular invasion, and some components of poorly differentiated adenocarcinomas in just the submucosal layer were significantly more common in the non-curative resection cases., Conclusions: ESD was a safe, effective, and minimally invasive treatment for early EGJ cancer. For tumors without any submucosal invasion findings, therefore, ESD is an acceptable treatment option, in addition to also being suitable for diagnostic purposes in evaluating the need for surgery.

Objective: The aim of our study was to investigate the natural course of silicosis in terms of radiographic progression among Japanese tunnel workers., Methods: Tunnel workers with silicosis were included in our study between January 2008 and June 2011. We retrospectively assessed workers' radiographs from their first through last visits to see whether there was progression. All films were interpreted by two physicians, who had been specially trained in using the ILO (2000) International Classification of Radiographs of Pneumoconioses (ILO/ICRP). We classified the radiographic findings according to the ILO/ICRP. Survival analysis was performed and then presented as time to progression. Subgroup analysis among the progressed group was performed to demonstrate duration of progression., Results: A total of 65 patients, who were no longer exposed to silica for the duration of the study, were included. The mean age at the first visit was 58.60 ± 7.10 years. The incidence rate of progression was 42 per 1,000 person-years with a median time to progression of 17 years. Progression was demonstrated among 33 cases (51%). The mean durations of progression from category 1 to category 4 and category 2 to category 4 were 14.55 and 10.65 years, respectively. Most patients (86%) had radiographic change from category 1 or 2 directly to category 4., Conclusion: Silicosis progressed at a relatively high rate among tunnel workers without further silica exposure. The high probability of progression directly from category 1 to category 4 may lead to further investigation for the improvement of disease prevention.

Background: Serum N-terminal pro-brain natriuretic peptide (NTproBNP) is often elevated in patients with acute Kawasaki disease (KD), but the NTproBNP level in normal children is higher than in adults. Thus, characterization of the normal levels and cut-off values of NTproBNP according to age is warranted for proper diagnosis of acute KD in children., Methods and Results: Six hundred and fifty-five patients aged 1 month-15 years (median, 2.9 years) were included. Patients were admitted to the NTT East Japan Sapporo Hospital between October 2007 and October 2011. Serum NTproBNP level was examined in 149 patients with KD (median, 2.1 years) and 506 control patients with acute infectious disease (median, 3.2 years). In the control group, a Z-score curve of NTproBNP was generated for each age group using least mean square-based methods. The Z-score distribution of KD patients was then compared with that of the control group. The specificity and sensitivity of NTproBNP for diagnosing acute KD were 97.8% and 47.0%, respectively, at Z-score >2.0. Additionally, simple cut-offs every 100 pg/ml according to age were established for more convenient use at the bedside., Conclusions: The Z-score curve for NTproBNP in children was characterized. A Z-score >2.0 or the cut-off for children may be used to diagnose acute KD.

We experienced a case of gastric cancer that was prospectively followed up for 8 years. With severe heart disease, the patient did not wish surgery or anticancer drug treatment. After informed consent was obtained, he was followed up for 8 years. He received upper gastrointestinal endoscopy every year, which revealed IIc early gastric cancer, and biopsy showed well differentiated adenocarcinoma. A flat and mildly depressed lesion with redness was observed on endoscopy, exhibiting typical morphology of IIc-type early gastric cancer. The appearance of IIc M cancer was observed macroscopically from 2000 to 2003. Four years later, surface irregularity with ulceration appeared. Then, the whole lesion was elevated, which suggested submucosal invasion, and the tumor exhibited the morphology of IIa + IIc or type 3. The ulcer became deeper and elevated boundaries were formed. Horizontal expansion of the flat lesion was mild, while invasion to deeper layers was predominant. Eventually, he died of heart failure. Estimated M cancer was observed for about 3 years, followed by invasion to deeper layers. Taken together, this is a valuable case that followed up the manner of invasion to deeper layers over time from early to advanced gastric cancer.

Aim: The aim of this study was to elucidate characteristics of gastric lesions that are initially diagnosed as low-grade adenomas and to establish appropriate treatment., Methods: We retrospectively reviewed 231 lesions initially diagnosed as gastric adenomas. All forceps biopsy samples were histologically diagnosed as category 3 low-grade adenomas according to the revised Vienna Classification. All patients underwent endoscopic resection with endoscopic findings and post-resection diagnoses evaluated subsequently., Results: Sixty-three lesions were initially diagnosed as depressed adenomas, and 168 lesions were diagnosed as protruding adenomas. The depressed lesions were significantly smaller (11.6 ± 5.0 mm) than the protruding lesions (17.0 ± 10.8 mm) (P < 0.001). Diagnoses reclassified to category 4 mucosal high-grade neoplasia (i.e. high-grade adenoma, adenocarcinoma in adenoma and adenocarcinoma) were more frequent among depressed lesions (52.4%) than among protruding lesions (31.0%) (P = 0.004). Multivariate analysis of all 231 lesions showed that lesion size larger than 20 mm (P < 0.001) and depressed appearance (including central depression) (P < 0.001) were significant independent factors suggesting cancer. For the 168 protruding lesions, lesion size larger than 20 mm (P < 0.001) and central depression (P < 0.001) were significant independent factors suggesting cancer. For the 63 depressed lesions, lesion size larger than 15 mm (P = 0.016) and a moth-eaten appearance (P = 0.017) were significant independent factors in the pre-treatment diagnosis of cancer., Conclusions: Adenocarcinoma lesions were often found in depressed lesions and protruding lesions with central depression. Endoscopic resection for total biopsy is recommended, even if forceps biopsy indicates low-grade adenoma, as pre-treatment biopsy may be inadequate for an accurate histological diagnosis., (© 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.)

Background and Study Aim: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are being used increasingly to treat superficial oropharyngeal and hypopharyngeal carcinomas. The aim of this study was to clarify whether ESD provided better results than EMR for en bloc and complete resection of superficial pharyngeal carcinomas., Patients and Methods: A total of 76 superficial pharyngeal carcinomas in 59 consecutively treated patients were included. Patients underwent either conventional EMR (using a transparent cap or strip biopsy) (n = 45 lesions) or ESD (n = 31 lesions) between October 2006 and January 2011. The rates of en bloc resection, complete resection (defined as en bloc resection with tumor-free margins), major complications, and local recurrence were evaluated retrospectively as the therapeutic outcomes., Results: ESD yielded significantly higher rates of both en bloc and complete resection compared with EMR (en bloc 77.4 % [24/31] vs. 37.8 % [17/45], P = 0.0002; complete 54.8 % [17/31] vs. 28.9 % [13/45], P = 0.0379). ESD was more frequently complicated by severe laryngeal edema (4/21 [19.0 %] vs. 1/31 [3.2 %], P = 0.1446) and was also more time-consuming (124.9 ± 65.1 minutes vs. 57.2 ± 69.6 minutes; P = 0.0014). Local recurrence was observed more often after EMR than after ESD (3/45 [6.7 %] vs. 0/31 [0 %]), although this difference did not reach statistical significance (P = 0.2658)., Conclusions: ESD appears to be a superior method of endoscopic resection of superficial pharyngeal carcinomas for achieving both en bloc and complete resection, although these benefits were also associated with a higher incidence of complications and a significantly longer procedure time. Large prospective studies are needed to compare ESD with conventional EMR for superficial pharyngeal carcinomas., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Study Aim: Endoscopic submucosal dissection (ESD) of undifferentiated-type early gastric cancer (UD-EGC) is technically feasible; however, the long-term clinical outcomes of the procedure have not yet been fully investigated. The aim of our study was to elucidate long-term outcomes of ESD for UD-EGC., Patients and Methods: Between September 2003 and October 2009, a total of 153 patients were diagnosed endoscopically as having UD-EGC fulfilling the expanded criteria for ESD. After informed consent was obtained, 101 patients were selected to undergo ESD and 52 to undergo surgical operation. We assessed the clinical outcomes of ESD in 101 consecutive patients with 103 UD-EGC lesions who were undergoing ESD for the first time. The overall mortality and disease-free survival rates after ESD were evaluated as the long-term outcomes., Results: The rates of en bloc and curative resection were 99.0% (102/103) and 82.5% (85/103), respectively. We encountered one patient with nodal metastasis detected by computed tomography before diagnostic ESD, although curative resection of the primary lesion was achieved based on routine histological examination. Among the 78 patients without a past history of malignancy within the previous 5 years in whom curative resection of the primary lesion was achieved, no cases of local recurrence or distant metastasis were observed during follow-up; however, 1 synchronous and 2 metachronous lesions were detected in 2 patients (2.6%) after primary ESD. Thus, estimated over a median follow-up period of 40.0 months (range 19-92 months) and 36.0 months (range 9-92 months), the 3-and 5-year overall mortality rates were 1.9% and 3.9%, respectively, and the 3-and 5-year overall disease-free survival rates were both 96.7%., Conclusions: Although our single-center retrospective study may be considered to be only preliminary, our data indicate that ESD for UD-EGC may yield good long-term outcomes., (© Georg Thieme Verlag KG Stuttgart · New York.)

The poor management of natural resources has led in many cases to the decline and extirpation of populations. Recent advances in fisheries science could revolutionize management of harvested stocks by evaluating management scenarios in a virtual world by including stakeholders and by assessing its robustness to uncertainty. These advances have been synthesized into a framework, management strategy evaluation (MSE), which has hitherto not been used in terrestrial conservation. We review the potential of MSE to transform terrestrial conservation, emphasizing that the behavior of individual harvesters must be included because harvester compliance with management rules has been a major challenge in conservation. Incorporating resource user decision-making required to make MSEs relevant to terrestrial conservation will also advance fisheries science., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background and Aims:   The diagnostic use of magnification endoscopy with narrow-band imaging (ME-NBI) to assess histopathologically undifferentiated-type early gastric cancers (UD-type EGCs) is not well elucidated. The purpose of this study was to examine the comparative relationship between ME-NBI images and histopathological findings in UD-type EGCs., Methods:   We analyzed 78 consecutive cases of UD-type EGCs ≤ 20 mm in diameter that underwent ME-NBI ≤ 2 weeks prior to resection. The ME-NBI images were compared with histopathological findings following either endoscopic submucosal dissection (ESD) or surgery. Applying the comparative results, we prospectively evaluated the success of identifying the lateral extent of UD-type EGCs resected by ESD in additional consecutive cases., Results:   Lesions with preserved but irregular surface microstructures (S-type based on ME-NBI) showed mucosal atrophy and corresponded histologically to the non-whole-layer type of intramucosal cancer (24/24, 100%). Lesions with an irregular microvasculature type (V-type, for example, corkscrew pattern) or mixed type upon ME-NBI corresponded histopathologically to the non-whole-layer type of intramucosal cancer (15/54, 27.8%), the whole-layer type of intramucosal cancer (27/54, 50.0%) or submucosal (sm) invasion cancer (12/54, 22.2%). Applying these comparative results, we used ME-NBI to successfully predict the lateral extent of cancer, which corresponded to the histopathological lateral extent in all 18 additional consecutive UD-type EGCs resected by ESD., Conclusions:   ME-NBI images of UD-type EGCs were very closely related to the histopathological findings. Thus, ME-NBI can be useful in the pretreatment assessment of the histopathological patterns of cancer development and the lateral extent of such lesions., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: Endoscopic ultrasonography (EUS) has become a reliable method for predicting the invasion depth of early gastric cancer (EGC). This study evaluated the accuracy of EUS in identifying lesions meeting expanded-indication criteria for endoscopic submucosal dissection (ESD) and analyzed clinicopathologic factors influencing the diagnostic accuracy of EUS in assessing tumor invasion depth., Methods: This study investigated 542 EGCs of 515 patients who underwent EUS pretreatment. The pretreatment EUS-determined diagnosis was compared with the final histopathologic evaluation of resected specimens, and the impact of various clinicopathologic parameters on diagnostic accuracy was analyzed., Results: The diagnostic accuracy of EUS in identifying lesions meeting expanded-indication criteria for ESD was 87.8% (259/295) for differentiated adenocarcinoma (D-type) 30 mm in diameter or smaller, 43.5% (10/23) for D-type tumor larger than 30 mm in diameter, and 75% (42/56) for undifferentiated adenocarcinoma (UD-type) 20 mm in diameter or smaller. Using multivariate analysis, the diagnostic accuracy of EUS in predicting tumor invasion depth was determined to be decreased significantly by ulcerous change and large tumor size (diameter, ≥30 mm)., Conclusion: For patients with EGC, D-type lesions 30 mm in diameter or smaller and UD-type lesions 20 mm in diameter or smaller can be diagnosed with high accuracy by EUS, but larger D-type lesions (diameter, >30 mm) should be considered carefully in terms of EUS-based treatment decisions. Findings of ulceration and large tumors are associated with incorrect diagnosis of tumor invasion depth by EUS.

Objectives: Although sporadic nonampullary duodenal adenoma (SNDA) is regarded as a precancerous lesion, its natural course is uncertain. The aim of this study was to evaluate the risk of development of adenocarcinoma in SNDA lesions initially diagnosed as showing low-grade dysplasia (LGD; category 3) or high-grade dysplasia (HGD; category 4.1)., Methods: We analyzed 68 SNDAs, diagnosed based on initial and subsequent biopsies, in 66 consecutive patients. Of these, 46 (43 LGD lesions, 3 HGD lesions) were followed up for ≥6 months without treatment (mean 27.7±16.9 months; range 6-72 months), including 8 lesions that were eventually resected during follow-up. Sixteen lesions (eight LGD lesions, eight HGD lesions) were resected immediately, either endoscopically or surgically, and six lesions were excluded because of a short follow-up (<6 months). The histopathological diagnoses and macroscopic changes were evaluated., Results: Among the 43 LGD lesions followed up for ≥6 months, 34 (79.1%) showed no histopathological changes during follow-up, whereas the remaining 9 (20.9%) showed progression to HGD, including 2 (4.7%) that progressed eventually to noninvasive carcinoma (category 4.2). Macroscopically, 76.7% (33 of 43) of the LGD lesions showed no notable changes in size, 16.3% (7 of 43) became undetectable, 4.7% (2 of 43) reduced in size, and 2.3% (1 of 43) became larger in size. In contrast, all the three HGD lesions that were followed up for ≥6 months remained unchanged histologically, based on biopsy, and showed no notable macroscopic changes, although one of these HGD lesions resected endoscopically revealed evidence of noninvasive carcinoma. Although we diagnosed all lesions as HGD from biopsy samples, a high percentage of cancers (54.5%, 6 of 11) were diagnosed from resected specimens. A multivariate analysis identified HGD diagnosed at first biopsy and a lesion diameter of ≥20 mm as being significantly predictive of progression to adenocarcinoma., Conclusions: LGD lesions show a low risk of progression to adenocarcinoma, but some risk of progression to HGD, which warrants careful follow-up biopsy. However, HGD lesions and large SNDAs≥20 mm in diameter show a high risk of progression to adenocarcinoma. Therefore, they should be treated immediately.

Background: Delayed bleeding is one of the major complications of endoscopic submucosal dissection (ESD). The aim of this study is to determine the incidence rate and clinical factors associated with delayed bleeding, as well as the time interval between bleeding and ESD for gastric neoplasm., Methods: We investigated 647 lesions in 582 consecutive patients undergoing ESD for gastric neoplasm., Results: Delayed bleeding after ESD was evident in all 28 lesions from 28 patients (4.33% of all specimens, 4.81% of patients), and all achieved endoscopic hemostasis. Resected specimen width (≥40 mm) was the only significant factor associated with delayed bleeding on univariate and multivariate analysis. In early delayed bleeding (bleeding occurring on or before the fourth postoperative day), wide resected specimen and tumor location in the lower third of the stomach were significant risk factors. In late delayed bleeding (bleeding occurring after the fifth operative day), wide resected specimen, tumor location in the middle third of the stomach, hypertension, and high body mass index (≥25 kg/m(2)) were significant factors. Delayed bleeding in patients with tumors in the upper and middle third of the stomach (median 8.0 days; range 1-20 days) occurred significantly later as compared with patients who had tumors in the lower third (median 2.0 days; range 1-34 days)., Conclusions: Risk factors for delayed bleeding, and the probable underlying mechanism involved, differed depending on the time elapsed between surgery and the bleeding episode.

To date, there have been no reports showing the efficacy of nonsecosteroidal vitamin D receptor (VDR) agonists in a benign prostatic hyperplasia (BPH) animal model. To examine the efficacy of CH5036249, a novel nonsecosteroidal VDR agonist, we orally administered the compound at 0.03 microg/kg to a beagle model with spontaneous BPH. Prostate volume was checked by rectal ultrasonic probe periodically during 11 months of administration and the prostate tissues histologically examined. CH5036249 inhibited prostate growth in two out of three dogs compared with vehicle-treated dogs. In the prostate specimens, substantial atrophy of the epithelium was observed in all dogs administered CH5036249. At the dose given, serum calcium levels slightly increased in the CH5036249-treated dogs but stayed within a normal range. We next examined the cell growth inhibition of CH5036249 using human prostate stromal cells and found the cell growth inhibitory activity of CH5036249 to be comparable to that of 1alpha,25(OH)2D3. The bioavailability from oral administration in rats was 95.1% with a t1/2 of 17.6 h. Both micro-AMES and micronucleus tests were negative. Although the results are still preliminary, we consider the novel nonsecosteroidal VDR agonist CH5036249 to be a possible new drug candidate for the treatment of BPH in humans., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to pathologically investigate the developmental pattern of undifferentiated mucosal gastric cancer and to determine safe surgical margins for curative resection by endoscopic resection., Results: Intramucosal cancer spread, or the width of the proliferative zone, was pathologically investigated in 47 cases of undifferentiated mucosal gastric cancer of size 20 mm or smaller without ulceration (scars). The 47 cases comprised 40 IIc and 7 IIb cases. The IIc cases consisted of 5 (12.5%) of intermediate-layer type (cancer localized at the intermediate layer of the mucosa), 31 (77.5%) of superficial type, and 4 of whole-layer type (10%). The IIb cases consisted of six of intermediate-layer type (85.7%) and one of superficial type (14.3%). The width of the proliferative zone in the 40 IIc cases ranged from 0 to 2,390 microm (average 605.5 microm). There was no significant correlation between width of proliferative zone and background mucosa. With regard to lesion size, average width was 243.6 microm in cases with longest diameter 5 mm., Conclusions: In endoscopic treatment of undifferentiated mucosal gastric cancer of size 20 mm or smaller without ulceration (scars), the lateral safety margin should be 3 mm or more.

Aim: To clarify the gender differences about the clinical features and risk factors of low-dose aspirin (LDA) (81-100 mg daily)-associated peptic ulcer in Japanese patients., Methods: There were 453 patients under treatment with LDA (298 males, 155 females) who underwent esophagogastroduodenoscopy at the Department of Gastroenterology and Hepatology of Hiratsuka City Hospital between January 2003 and December 2007. They had kept taking the LDA or started treatment during the study period and kept taking LDA during the whole period of observation. Of these, 119 patients (87 males, 32 females) were diagnosed as having LDA-associated peptic ulcer. We examined the clinical factors associated with LDA-associated peptic ulcer in both sexes., Results: A history of peptic ulcer was found to be the risk factor for LDA-associated peptic ulcer common to both sexes. In female patients, age greater than 70 years (prevalence ORs 8.441, 95% CI: 1.797-33.649, P = 0.0069) was found to be another significant risk factor, and the time to diagnosis as having LDA-associated peptic ulcer by endoscopy was significantly shorter than that in the male patients (P = 0.0050)., Conclusion: We demonstrated gender differences about the clinical features and risk factors of LDA-associated peptic ulcer. Special attention should be paid to aged female patients taking LDA.

Aim: The aim of the present study was to examine therapeutic outcomes of endoscopic submucosal dissection (ESD) of undifferentiated-type intramucosal gastric cancer and the problems of diagnosis., Methods: We reviewed 58 patients with preoperatively diagnosed undifferentiated-type intramucosal early gastric cancer (EGC) without ulceration with a diameter of 20 mm or smaller (expanded-indication lesion) who underwent ESD at the Cancer Institute Hospital between September 2003 and August 2008., Results: The overall rates of one-piece resection and complete resection were 98% and 90% respectively, and the median operation time was 70 min. Bleeding was seen in 8.6% and perforation in 3.4%. The curative resection rate was low at 79%. Factors responsible for non-curative resection were most commonly submucosal invasions. If limited to pathologically diagnosed expanded-indication lesions, the curative resection rate was 98%. The difference in tumor size between a macroscopic diameter and a histological diameter was within +/-5 mm in 96% of expanded-indication lesions, with none of these cases having a histological diameter that exceeded the macroscopic diameter by more than 5 mm., Conclusion: ESD was technically feasible for expanded-indication lesions of undifferentiated-type EGC. We achieved a high rate of curative resection by the markings at sites 5 mm beyond the preoperatively determined lesion area. Factors responsible for non-curative resection were most commonly submucosal invasions. We should diagnose the depth of such lesions more carefully.

Retaining experienced nurses is an indispensable part of securing the safety and reliability of medical care. In this study, we investigate how the working conditions affect staff nurses' intention to remain in their current employment positions (intention to remain employed). A total of 319 staff nurses working for three private hospitals were given a questionnaire in order to evaluate their working conditions. A stepwise multiple logistic regression analysis selected 5 out of 44 question items as significant independent variables for their intention to remain employed; they were assumed to directly affect their intentions (direct modulators). From the remaining 39 items, seven meaningful factors were extracted via factor analysis. We constructed a path network model so that these factors would indirectly affect the intention to remain employed via any of the five direct modulators (indirect modulators). In this network, the factor, "Rapport with coworkers" had the strongest positive effect on three of the five direct modulators (beta = 0.28-0.55, p < 0.05). According to factor loadings, positive teamwork together with appropriate supervision and recognition from superiors and colleagues seems to characterize this factor, and therefore, may play a key role in retaining staff nurses in their current positions. Two indirect modulators related to "Management by Objectives" (MBO)--"Understanding MBO" and "Clear personal objectives" also played negligible roles in this path model. These findings could be helpful in improving management systems of the nursing sections of hospitals, which could contribute to retaining staff nurses in their current employment positions.

Background and Objective: Leukocytes and epithelium are the first line of defense in preventing bacterial invasion into periodontium. Some of these cells die in gingival crevicular fluid, whereupon their DNA is spilled out. The present study was designed to investigate the profile of host beta-globin gene fragments in the gingival crevicular fluid of various periodontal conditions., Material and Methods: Gingival crevicular fluid from 40 teeth with chronic periodontitis, 30 with gingivitis and 22 that were clinically healthy were centrifuged (3,000 g, 10 min). The supernatant (cell-free gingival crevicular fluid) was centrifuged again (13,000 g, 10 min), resulting in the pellet and the supernatant as debris and debris-free fractions, respectively. Specific primers for amplifying 110 bp, 536 bp and 2 kb amplicons of human beta-globin gene were used to investigate host DNA by quantitative and qualitative polymerase chain reaction., Results: The periodontitis group showed the largest amount of host beta-globin gene fragments, while the healthy group had the lowest. In the debris and debris-free fractions, the 536 bp and 2 kb amplicons were more often detected in the periodontitis group than in the other groups. Interestingly, the presence of 2 kb amplicon in the debris fraction could be used to discriminate periodontitis from gingivitis and healthy groups because we found it in 85% of periodontitis samples but only in 13% of gingivitis samples, and it was absent in the healthy group., Conclusion: This study shows the different DNA profiles of cell-free gingival crevicular fluid in periodontal health and disease. It suggests that the quantity and quality of host DNA are dependent on the disease conditions. Therefore, the beta-globin gene fragments in cell-free gingival crevicular fluid may be a potential biomarker of periodontal disease progression.

Background/aims: The aim of this study was to clarify the prevalence and various clinical factors of upper gastrointestinal bleeding (UGIB) associated with low-dose aspirin (LDA) treatment., Methodology: There were 6,807 patients who were under treatment with LDA at our hospital between January 2003 and November 2007. They had kept taking the LDA or started treatment in the study period and kept taking the whole period of observation. Esophagogastroduodenoscopy (EGD) was performed 453 patients of these patients, and 71 were diagnosed as LDA-associated UGIB. We examined the prevalence and various clinical factors of UGIB associated with LDA treatment., Results: The occurrence rate of UGIB was 0.209 UGIB per 100 patient-years at least. The multivariate odds ratio of LDA-associated UGIB was 3.318 (95% confidence interval (CI) 1.650-6.671, p = 0.0008) for a history of peptic ulcer, 0.086 (95% CI: 0.011-0.652, p = 0.0176) for the use of a proton pump inhibitor (PPI) with LDA, and 0.253 (95% CI: 0.113-0.569, p = 0.0009) for the use of a histamine type 2 receptor antagonist (H2RA) with LDA., Conclusions: Our results suggest that a history of peptic ulcer significantly increases the risk of LDA-associated UGIB. Regular use of a PPI or a H2RA effectively decreases the risk.

Knee pain is extremely common among the elderly, particularly women. Hence, there is an urgent need for applicable community-based intervention models for halting the progression of knee pain and related disabilities in elderly women. We aimed to assess the efficacy of home-visit physiotherapy as a new intervention model. This non-randomized 5-month-long controlled trial enrolled elderly community-dwelling women (aged 60-83 years) with mild knee pain. The intervention consisted of two home visits by a physiotherapist, with instructions on routinely performing muscle-strengthening exercises at home and implementing simple environmental modifications when necessary. Outcome measures were assessed at baseline and 5 months later. The primary outcomes were measured as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a newly devised seiza-style sitting score. People in Japan, especially elderly women, are accustomed to seiza-style sitting that involves kneeling on one's lower legs while resting the buttocks on the heels. The secondary outcomes included quadriceps isometric strength, knee alignment in the frontal and sagittal planes, and passive knee extension range. Forty-two subjects (20 in the intervention group and 22 in the control group) completed the study. At baseline, characteristics and the primary outcomes did not significantly differ between the 2 groups. At 5 months, the primary outcomes improved significantly in the intervention group. Estimated differences in the change from baseline for each outcome between the 2 groups were computed, adjusting for outcome variables imbalanced at baseline. Even after the adjustment, the home-visit physiotherapy regimen provides favorable improvement in the seiza-style sitting score.

Currently, transnasal esophagogastroduodenoscopy using an ultrathin endoscope is being widely carried out as a screening test for early gastric cancer. We compared the diagnostic utility of ultrathin esophagogastroduodenoscopy with that of conventional esophagogastroduodenoscopy in detecting 42 lesions of early gastric cancer that had a diameter of

The present patient developed a severe rectal ulcer more than 1 month after having received external beam radiation therapy for prostate cancer. Surveillance endoscopy every 3 months demonstrated healing of this rectal ulcer using a novel therapy. He was given enemas with ecabet sodium, which provides physical protection and promotes healing by increasing prostaglandin E(2), and this process induced squamous metaplasia that halted the progression of the ulcer of radiation proctitis as a late-phase reaction. Intrapapillary capillary loops were visualized with magnified narrow band imaging at the healing ulcer site as seen via the esophagus and, moreover, demonstrated histologically.

Background/aims: Iodine staining of the esophagus has been shown to be useful in detecting esophageal cancer. Narrow band imaging (NBI), a new endoscopic lighting system, visualizes the microvasculature of the gastrointestinal (GI) mucosa. To evaluate the detectability of early esophageal cancer by screening endoscopy assisted with NBI as compared with that assisted with iodine staining., Design: A prospective comparative study. Setting A single endoscopy unit., Patients: Forty-nine consecutive patients, consisting of 40 males and 9 females with a mean age of 67, most of whom were at high risks for esophageal cancer (heavy drinker and smoker, history of cancer especially of head and neck, etc.)., Intervention: Following conventional endoscopic observation, the esophagus was observed with NBI for possible cancerous lesions. Dark-brown areas on NBI were defined as NBI-positive areas. Esophageal mucosa was subsequently stained with 1.5% iodine, and both findings were compared. Finally, the areas discolored by iodine stain were biopsied for histological evaluation., Main Outcome Measurements: The sensitivity, specificity, and positive predictive value (PPV) of endoscopic detection of esophageal cancer., Results: Squamous cell carcinoma was detected in 5 out of 118 areas. Esophageal cancers detected were all both NBI-positive and discolored by iodine staining. Sensitivity, specificity, and PPV of NBI-positive areas for cancer were 100%, 59%, and 9.8%, respectively. On the other hand, the discolored areas with iodine staining for cancer were 100%, 4.4%, and 4.4%, respectively. NBI observation was significantly superior to iodine staining for detecting esophageal cancer (p < 0.02)., Limitation: In this study, the endoscopist engaged was not blinded and the assessment was not standardized., Conclusions: Esophageal endoscopy assisted with NBI was more useful for detecting early esophageal cancer than that assisted with iodine staining.

Background: Although proximal gastrectomy has been performed more as a function-preserving surgery, reflux esophagitis can occur postoperatively, resulting in poor postoperative quality of life. To date, only a few reports have compared the methods of reconstruction performed after proximal gastrectomy, and the method most likely to prevent postoperative reflux esophagitis remains undetermined., Methods: A retrospective review of 76 patients who underwent proximal gastrectomy with jejunal interposition (JI) or esophagogastrostomy (EG) at the Cancer Institute Hospital between April 1996 and August 2005 was performed. Preoperative characteristics, operative findings, and postoperative gastrointestinal fiberoscopy findings were reviewed and compared between JI and EG patients. Furthermore, we investigated the relationship between the length of interposed segment and operative and postoperative findings., Results: The frequency of grade C or D reflux esophagitis was lower in the JI group than in the EG group (p = 0.001), although the former required a longer operation time (256.5 +/- 10.2 min) than the latter (195.8 +/- 8.2 min; p < 0.001). Other characteristics and postoperative clinical course did not differ between the groups. In the JI group, interposed segments 10 cm or shorter were advantageous in evaluating the remnant stomach when compared with interposed segments longer than 10 cm. No relationship was observed between the length of the interposed segment and clinical findings, except operation time., Conclusion: Jejunal interposition helps prevent reflux esophagitis after proximal gastrectomy. The optimal length of the interposed segment is undetermined; however, a length of 10 cm or shorter is preferred for endoscopic evaluation of the remnant stomach.

Background/aims: Microorganisms of Peptostreptococcus micros are asaccharolytic, anaerobic gram-positive cocci that are frequently isolated from human oral sites such as periodontal pockets. Preliminary study showed that several amino acids, including serine, enhanced slightly the growth of P. micros. Therefore, we investigated the degradation of serine and serine-containing oligopeptides., Methods: Metabolic end products were determined with high-performance liquid chromatography. The related enzymatic activities in cell-free extract were also assayed., Results: Washed P. micros degraded serine-tripeptides (Ser-Ser-Ser), and produced formate, pyruvate, acetate, and ammonia. They also degraded serinyl-tyrosine (Ser-Tyr) to the same products. Related enzymatic activities, such as serine dehydratase, pyruvate formate-lyase, formate dehydrogenase, pyruvate oxidoreductase, phosphate acetyltransferase, and acetate kinase, were detected in the cell-free extract, indicating that the organisms produced ATP in the serine metabolism., Conclusion: P. micros utilized serine-containing oligopeptides as exogenous metabolic substrates rather than serine itself, and degraded Ser-Ser-Ser and Ser-Tyr to formate, pyruvate, acetate, and ammonia with ATP generation.

Slackia exigua ATCC 700122(T) and Cryptobacterium curtum ATCC 700683(T) were our isolates from infected root canal and human periodontal pocket, respectively; they are asaccharolytic anaerobic gram-positive rods, which are predominant in the oral cavity. They utilize arginine, so our aim was to investigate the pathway of arginine degradation. Metabolic end products were determined with high-performance liquid chromatography. The related enzymatic activities in cell-free extract were also assayed. Both S. exigua and C. curtum degraded arginine and produced substantial amounts of citrulline, ornithine and ammonia. Arginine and citrulline supported the growth of both strains. As the related enzymatic activities, arginine deiminase, ornithine carbamoyltransferase and carbamate kinase activities were detected in the cell-free extract of S. exigua and C. curtum. Arginase and urease activities were not detected in either organism. These results suggest that arginine was metabolized by the arginine deiminase pathway. Both S. exigua and C. curtum degrade arginine via the arginine deiminase pathway.

Background/aims: Culture-difficult bacteria, including asaccharolytic anaerobic gram-negative coccobacilli (AAGNC), may constitute a predominant group of organisms in oral sites. This study aimed to characterize phylogenetically 10 AAGNC isolated from endodontic lesions and periodontal pockets., Methods: 16S rDNA sequence and G + C content were determined. Strains sharing more than 98% sequence similarities and similar G + C content were considered the same bacterial species., Results: One isolate resembled Dialister pneumosintes (the type species of the genus Dialister) with 35 mol% G + C content and 97% sequence similarity. Of eight isolates having 45-47 mol% G + C content, seven were identified as D. invisus and one resembled Dialister invisus with 97% sequence similarity. However the 16S rDNA sequence similarities with D. pneumosintes were relatively low, indicating the strains may belong to a new genus. The last isolate revealed 35 mol% G + C content, but had higher 16S rDNA sequence similarity with D. invisus than with D. pneumosintes., Conclusion: The group of oral AAGNC isolates need to be reclassified.

Aim: This study was performed to clarify the optimum condition of argon plasma coagulation (APC) to treat hemorrhagic radiation proctitis., Subjects: Among 25 patients with hemorrhagic radiation proctitis treated in the Cancer Institute Hospital between December 2000 and May 2004, 18 were followed-up for more than 6 months. The clinical courses of these 18 patients were analyzed retrospectively., Methods: Proctoscopic findings of the hemorrhagic lesions were categorized as type-A (localized dilated veins, n = 6) , type-B (diffuse dilated veins, n = 6), and type-C (dilated veins associated with ulcers orerosions, n = 6). APC was applied for 5-10 seconds with the power of 40 W and the argon flow of 1.0 l/min (high power APC), or for 1-2 seconds with the power of 40 W and the argon flow of 0.6 l/min (low power APC)., Results: Type-A and B patients were successfully treated with either low or high power APC without any serious complications. But some type-C patients treated with high power APC showed serious complications such as proctovaginal fistula or prolonged ulceration. No recurrence patients were 89% (16/18) during the mean follow up period of 18 +/- 9.9 months., Conclusion: APC therapy for hemorrhagic radiation-proctitis was useful, but the pathologic healing process and consequence were different by rectal mucosal weakness. It is necessary for the therapeutic strategy to be put up and down according to proctoscopic findings. As for the optimum condision APC short cauterization by low power setting was more recommended.

Background: The polymorphic enzyme cytochrome P450 2C19 affects omeprazole metabolism. This influence on metabolism might affect serum gastrin levels, and safety, during long-term treatment of reflux oesophagitis., Aim: To examine the relationship between cytochrome P450 2C19 genotype and the safety profile of long-term omeprazole treatment., Methods: A total of 119 Japanese patients with recurrent reflux oesophagitis underwent cytochrome P450 2C19 genotyping prior to receiving daily omeprazole 10 mg or 20 mg for 6-12 months, during which adverse event frequency, serum gastrin levels and endoscopic findings were monitored., Results: The incidences of adverse events, serious adverse events and adverse events leading to withdrawal did not differ between homozygous extensive metabolizer (n = 46), heterozygous extensive metabolizer (n = 53) or poor metabolizer (n = 20) groups. In all genotype groups, serum gastrin increased during the first 3 months of dosing but stabilized thereafter. No significant differences were seen either in the rate of reflux oesophagitis healing or symptom improvement among genotype groups., Conclusions: Long-term treatment with omeprazole was well-tolerated in Japanese patients, irrespective of their cytochrome P450 2C19 metabolic genotype, indicating that dose adjustment depending on metabolic genotype is not required during treatment with omeprazole.

Although acupuncture has a significant clinical benefit, the mechanism of acupuncture remains unclear. Vasopressin, a posterior pituitary hormone, is involved in nausea and vomiting in humans and dogs. To investigate the antiemetic effects of acupuncture on vasopressin-induced emesis, gastroduodenal motor activity and the frequency of retching and vomiting were simultaneously recorded in conscious dogs. In seven dogs, four force transducers were implanted on the serosal surfaces of the gastric body, antrum, pylorus, and duodenum. Gastroduodenal motility was continuously monitored throughout the experiment. Vasopressin was intravenously infused at a dose of 0.1 U x kg(-1) x min(-1) for 20 min. Electroacupuncture (EA, 1-30 Hz) at pericardium-6 (PC6), bladder-21 (BL21), or stomach-36 (ST36) was performed before, during, and after the vasopressin infusion. To investigate whether the opioid pathway is involved in EA-induced antiemetic effects, naloxone (a central and peripheral opioid receptor antagonist) or naloxone methiodide (a peripheral opioid receptor antagonist) was administered before, during, and after EA and vasopressin infusion. Intravenous infusion of vasopressin induced retching and vomiting in all dogs tested. Retrograde peristaltic contractions occurred before the onset of retching and vomiting. EA (10 Hz) at PC6 significantly reduced the number of episodes of retching and vomiting. EA at PC6 also suppressed retrograde peristaltic contractions. In contrast, EA at BL21 or ST36 had no antiemetic effects. The antiemetic effect of EA was abolished by pretreatment with naloxone but not naloxone methiodide. It is suggested that the antiemetic effect of acupuncture is mediated via the central opioid pathway.