[Show abstract][Hide abstract] ABSTRACT: The prevalence of celiac disease (CD) among Japanese population has been unknown, whereas it has been increasingly recognized in the US and in the European countries. The aim of the present study is to identify possible cases with CD among Japanese population and clarify the relevance of screening for the disease. We conducted a serologic screening for the disease among 710 Japanese patients and 239 healthy volunteers at a local tertiary teaching hospital, using an anti-tissue transglutaminase IgA (TTG-IgA) test, and histological examination of the small intestines from the TTG-IgA positive subjects. There were no TTG-IgA positive sera among the healthy volunteers. Twenty of the patients (2.8%), including eight with malignant lymphoma, were tested positive for TTG-IgA. The histological examination of the eleven patients among those with positive TTG-IgA, seven showed villous atrophy and partial lymphocytes infiltration in the mucosa, which could be compatible to mucosal changes observed in CD. Five of them had non-Hodgkin lymphoma in the gastrointestinal tracts. Serologic tests using TTG-IgA might be relevant to screen for those with undiagnosed CD among Japanese population.
International journal of medical sciences 06/2014; 11(8):819-23. · 1.55 Impact Factor
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[Show abstract][Hide abstract] ABSTRACT: A spiral bacterium (SH9), morphologically different from Helicobacter pylori (H. pylori), was found in a 62-year-old woman's gastric mucosa. Gastroscopic examination revealed multiple gastric ulcers near the pyloric ring; mapping gastric biopsy showed mild mononuclear infiltration with large lymphoid follicles in the antrum, without corpus atrophy. Urea breath test and H. pylori culture were negative, but Giemsa staining of biopsies revealed tightly coiled bacteria that immunostained with anti-H. pylori antibody. Sequencing of SH9 16S rRNA and the partial urease A and B subunit genes showed that the former sequence had highest similarity (99%; 1302/1315 bp) to Helicobacter heilmannii (H. heilmannii) sensu stricto (H. heilmannii s.s.) BC1 obtained from a bobcat, while the latter sequence confirmed highest similarity (98.3%; 1467/1493 bp) to H. heilmannii s.s. HU2 obtained from a human. The patient was diagnosed with multiple gastric ulcers associated with H. heilmannii s.s. infection. After triple therapy (amoxicillin, clarithromycin, and lansoprazole) with regimen for eradicating H. pylori, gastroscopy showed ulcer improvement and no H. heilmannii s.s. upon biopsy.
World Journal of Gastroenterology 03/2014; 20(12):3376-82. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Although Helicobacter pylori eradication is a first-line treatment of gastric MALT lymphoma, roughly 25% of patients do not respond to treatment. CD4(+) FOXP3(+) regulatory T (Treg) cells regulate immune responses in physiological conditions and various inflammatory conditions, including H. pylori-associated diseases. Our goal was to determine how Treg cells affect responsiveness to H. pylori eradication therapy. MATERIALS AND METHODS: We performed dual immunohistochemistry for CD4 and FOXP3 to evaluate the prevalence of FOXP3(+) Treg cells in the stomach of 63 patients with MALT lymphoma and 55 patients with chronic active gastritis. Receiver operating characteristic analysis was carried out to determine the best cut-off point in differentiating H. pylori eradication responders from nonresponders. RESULTS: Both the FOXP3(+) /CD4(+) cell ratio and the absolute number of FOXP3(+) cells per high-power field in MALT lymphoma were significantly greater in H. pylori eradication responders compared with nonresponders, suggesting that Treg cells function in regression mechanisms of MALT lymphomas. Cut-off points with good sensitivities and specificities were obtained to predict eradication outcome. CONCLUSIONS: A high number of Treg cells or a high ratio of Treg cells to the total number of CD4(+) T cells in gastric MALT lymphoma could predict responsiveness to eradication therapy.
[Show abstract][Hide abstract] ABSTRACT: Background Recently, a significant relationship between gastric cancer and Helicobacter pylori infection has been proven. The purpose of this study was to elucidate the actual conditions of H. pylori infection in Japanese teenagers.
Methods The study subjects were students at a certain high school between 2007 and 2009. They were first examined with a urine-based
enzyme-linked immunosorbent assay (ELISA) for detection of the antibody to H. pylori (RAPIRAN®). Students who tested positive on this screening examination visited Shinshu University Hospital and received esophagogastroduodenoscopy,
and biopsy samples were taken to examine their H. pylori status. The resolution of H. pylori infection was assessed by urea breath test.
Results For 3 years, 1,224 of 1,232 students (99.4%) received a screening examination for H. pylori infection. Sixty-four of these 1,224 students (5.2%) were found to be positive for H. pylori. Thirty of these 64 H. pylori-positive students visited our hospital, and 24 of them (80%) were confirmed to be infected by H. pylori. The most common endoscopic findings for students with H. pylori infection were nodular gastritis (58.3%) and closed-type atrophic gastritis (45.8%). Histological findings showed no evidence
of intestinal metaplasia, except in one of the students. All 24 students were successfully cured of H. pylori infection. If this procedure were to be introduced into the nationwide health screening at Japanese high schools, we calculated
that the cost of the prevention of a gastric cancer would be 454,073 yen for each person.
Conclusions The low rate of prevalence of H. pylori infection in Japanese teenagers would make it possible to perform examinations and carry out treatment for this infection
in high school health screenings from the standpoint of medical economy.
Journal of Gastroenterology 09/2012; · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We here describe the clinical course of a 70-year-old male patient with Waldenström macroglobulinemia (WM) putatively transformed from refractory mucosa-associated lymphoid tissue lymphoma (MALTL).
Immunological staining was performed on formalin-fixed, paraffin-embedded tissue sections, and M-protein and cryoglobulin were identified by immunofixation electrophoresis and the cold precipitation method. Chromosome translocation was analyzed by the G-banded karyotype, and API2/MALT1 fusion gene underwent fluorescent in situ hybridization. Multiplex polymerase chain reaction was performed to analyze the VH-JH or DH-JH rearrangements of the IGH gene.
At diagnosis, the WM patient had monoclonal IgM with cryoglobulinemia and hyperviscosity syndrome. Eight years before developing WM, the patient experienced the onset of typical gastric MALT-L with H. pylori infection, but in spite of negative for chromosome translocation, t (11;18) and the successful eradication of H. pylori, the MALT-L relapsed repeatedly, and finally led to systemic metastasis. The lymphoma cells also infiltrated the large intestine and spleen. Immunoglobulin gene analyses of cellular clonality revealed that the same clone had been present in the stomach, bone marrow (BM) at the onset of MALT L, and in the BM at the diagnosis of WM.
In this case, lymphoma developed as H. pylori-associated gastric MALT-L with negative for t (11;18), and might be transformed into MW during the systemic metastasis.
Rinsho byori. The Japanese journal of clinical pathology 06/2012; 60(6):528-35.
[Show abstract][Hide abstract] ABSTRACT: Recently, a significant relationship between gastric cancer and Helicobacter pylori infection has been proven. The purpose of this study was to elucidate the actual conditions of H. pylori infection in Japanese teenagers.
The study subjects were students at a certain high school between 2007 and 2009. They were first examined with a urine-based enzyme-linked immunosorbent assay (ELISA) for detection of the antibody to H. pylori (RAPIRAN). Students who tested positive on this screening examination visited Shinshu University Hospital and received esophagogastroduodenoscopy, and biopsy samples were taken to examine their H. pylori status. The resolution of H. pylori infection was assessed by urea breath test.
For 3 years, 1,224 of 1,232 students (99.4%) received a screening examination for H. pylori infection. Sixty-four of these 1,224 students (5.2%) were found to be positive for H. pylori. Thirty of these 64 H. pylori-positive students visited our hospital, and 24 of them (80%) were confirmed to be infected by H. pylori. The most common endoscopic findings for students with H. pylori infection were nodular gastritis (58.3%) and closed-type atrophic gastritis (45.8%). Histological findings showed no evidence of intestinal metaplasia, except in one of the students. All 24 students were successfully cured of H. pylori infection. If this procedure were to be introduced into the nationwide health screening at Japanese high schools, we calculated that the cost of the prevention of a gastric cancer would be 454,073 yen for each person.
The low rate of prevalence of H. pylori infection in Japanese teenagers would make it possible to perform examinations and carry out treatment for this infection in high school health screenings from the standpoint of medical economy.
Journal of Gastroenterology 08/2011; 46(12):1353-60. · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The trefoil factor family (TFF) 2 protein is produced by gastric gland mucous cells (GMCs), and the secreted TFF2 shares a mucosal barrier function with GMC-type mucin. Recently, we presented an enzyme-linked immunosorbent assay (ELISA) method for measurement of GMC-type mucin in the gastric juice.
We aimed to develop an ELISA for TFF2 and to assess pathophysiological changes in the gastric surface mucous gel layer (SMGL) of patients with Helicobacter pylori infection.
The distribution of TFF2 and GMC-type mucin in the SMGL was immunohistochemically determined. The ELISA for TFF2 was based on a polyclonal goat antibody. Recombinant TFF2 was employed to prepare the calibrators. TFF2 and GMC-type mucin in the gastric juice in healthy individuals (n = 33) and patients with gastritis (n = 37), gastric ulcer (n = 16), and duodenal ulcer (n = 10) were assayed using ELISA.
TFF2 and GMC-type mucin were immunohistochemically co-localized in the gastric SMGL and GMCs. The TFF2 levels in the patients were significantly higher than those in the healthy individuals. Further, the TFF2 levels in the H. pylori-positive patients were significantly higher than those in the H. pylori-negative patients, and decreased after the eradication of the infection. GMC-type mucin levels showed a tendency similar to that of TFF2 levels.
The upregulation of TFF2 and GMC-type mucin secretion may reflect the response of the gastric mucosa to H. pylori-induced injuries. TFF2 and GMC-type mucin secreted into the SMGL may protect the gastric mucosa against H. pylori.
Digestive Diseases and Sciences 05/2011; 56(12):3498-506. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 38-year-old man presented to our hospital with abdominal pain and melena. Gastrointestinal endoscopy revealed a large gastric ulcer, and the pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) was made based on immunohistochemical findings. Left diplopia developed soon after commencement of chemotherapy. Despite normal findings from head MRI, orbital involvement in DLBCL was detected with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The patient was treated with salvage chemotherapy with success. Treatment analysis using FDG-PET for patients with DLBCL, especially for those with clinical symptoms and negative findings on conventional modalities, may be useful for assessing disease status and adjusting treatments.
Internal Medicine 01/2011; 50(18):1953-6. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Non-steroidal anti-inflammatory drug (NSAID)-related small intestinal complications exist, since developed new diagnostic modalities, such as balloon and capsule endoscopies. Some experiments have shown rebamipide to protect from NSAID-induced small intestinal complications. The purpose of this study is to investigate whether the effective concentrations of rebamipide (COR) are present in the small intestine after taking an ordinary clinical dose and double dose of this drug. Twelve healthy male subjects were enrolled. After taking 100 or 200 mg of rebamipide, balloon enteroscopy was performed at 1 and 3 h, and biopsy samples were obtained from the jejunum and the stomach. Venous blood samples were taken simultaneously. Samples were analyzed by high-performance liquid chromatography. The mean COR in the jejunum was higher than 100 µM at 1 h and higher than 10 µM at 3 h in both the 100 and 200 mg groups. Mean COR in the stomach was less than 100 µM at 1 h in the 100 mg group; however it was higher than 100 µM in the 200 mg group. In conclusion, the COR level in the jejunum was sufficient to protect for NSAID-induced gastrointestinal complications.
Journal of Clinical Biochemistry and Nutrition 11/2010; 47(3):256-60. · 2.29 Impact Factor
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[Show abstract][Hide abstract] ABSTRACT: Along with the growing elderly population, patients with gastric ulcers caused by low-dose aspirin have increased. Gastric cancer is also common among the elderly population, but is sometimes difficult to distinguish from gastric ulcers, especially those stemming from aspirin use. To differentiate the diagnostic symptoms of gastric ulcers and gastric cancers in elderly patients, we compared the endoscopic findings of 198 subjects (92 benign ulcers and 106 cancers) aged 65 years and older. Despite their benign nature, aspirin-induced ulcers tended to have more irregularity of the ulcer edge and heterogeneous formation of regenerating epithelium than ulcer unrelated to aspirin. Asking about the use of low-dose aspirin is therefore important when confronted with such lesions in elderly patients.
Nippon rinsho. Japanese journal of clinical medicine 11/2010; 68(11):2036-9.
[Show abstract][Hide abstract] ABSTRACT: Autoimmune pancreatitis (AIP) is a recently recognized disease entity. In some patients, this disease is associated with other inflammatory diseases. In this study, we aimed to elucidate the pathologic characteristics of AIP-associated gastritis (AIP-G). We evaluated and compared the pathologic findings and immunohistochemical expressions of immunoglobulin G (IgG)4 and IgG in gastric biopsy specimens from 13 AIP-G patients with those from patients of 2 control groups. We divided the AIP-G patients who did not receive steroid therapy [AIP-G-ST(-)] into the following 2 groups: without Helicobacter pylori (HP) infection [AIP-G-HP(-)] and with HP infection [AIP-G-HP(+)]. The control groups comprised 19 patients who were diagnosed with chronic active gastritis associated with HP infection and 7 patients with nonsteroidal anti-inflammatory drug-induced gastritis. We classified the findings for the gastric mucosa into those for the upper and the lower lamina propria. The characteristic finding of AIP-G groups was diffusely lymphoplasmacytic infiltration in the lamina propria. The IgG4-positive plasma cell/IgG-positive plasma cell ratios (IgG4/IgG ratios) in both the upper and lower lamina propria in the AIP-G-ST(-) groups were predominantly higher than the corresponding values in the other groups. In the AIP-G-ST(-) groups, the IgG4/IgG ratio in the lower lamina propria was predominantly higher than that in the upper lamina propria, irrespective of the HP status. In conclusion, diffuse lymphoplasmacytic infiltration in the lamina propria and increased IgG4/IgG ratio in the gastric mucosa (notably in the lower lamina propria) may be the characteristic findings of AIP-G.
The American journal of surgical pathology 09/2010; 34(9):1241-9. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Outcomes of endoscopic submucosal dissection (ESD) for early gastric neoplasms at low-volume centers have been unknown, because all previous reports have studied in advanced single centers. The aim of this study was to compare ESD outcomes between high- and low-volume centers.
A retrospective questionnaire survey was conducted and 30 centers (96.8%) responded. The complete en-bloc resection rate (CERR) and the incidence of complications were analyzed. Early gastric cancer (EGC) was divided into three categories on the basis of pathological diagnosis-standard indication (SI), expanded indication (EI) and out-of-indication (OI).
A total of 703 early gastric neoplasms (586 EGCs, 117 gastric adenomas) were treated with ESD from January to December 2005. The institutions that treated more than 30 cases a year were classified as high-volume centers, and those with less than 30 cases, low-volume centers. In SI, the CERRs at high- and low-volume centers were 92.1% and 91.1%, in EI, CERRs were 86.2% and 82.6% and in OI, CERRs were 80.3% and 88.0%. The perforation rates at high- and low-volume centers were 3.6% and 4.7%. The intra-operative bleeding rates at high- and low-volume centers were 0.26% and 0%, while the delayed bleeding rates were 0% and 0.63%.
There were no significant difference in the outcomes of ESD for early gastric neoplasms between high- and low volume centers.
Internal Medicine 01/2010; 49(4):253-9. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to evaluate the usefulness of double balloon enteroscopy (DBE) and video capsule endoscopy (VCE) in patients with primary follicular lymphoma (FL) of the gastrointestinal (GI) tract. Furthermore, we estimate the effectiveness of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) including rituximab for them.
Thirteen consecutive patients who were diagnosed of having FL in the duodenum between July 2005 and September 2008 were studied. All patients were given the conventional staging examinations, including total enteroscopy using DBE and/or VCE procedures. Chemotherapy was performed after written informed consent. Response assessment was performed every 6-12 months. The median follow-up period was 30.2 months.
FL was diagnosed in each patient as low grade (grade 1, n = 7; 2, n = 6) and, in all but 4 patients, localized lymphoma (stage I, n = 8; II(1), n = 1; II(2), n = 4). DBE revealed multifocal lesions in the jejunum in 10 of the patients, and in the ileum in 6. VCE showed similar findings in the jejunum in the recent 2 patients. Eleven of 13 patients finally received chemotherapy, and all of them achieved complete regression. They showed no evidence of recurrence after that.
Total examination of the small intestine using DBE should be performed before treatment to choose a suitable treatment procedure for primary FL of the GI tract. On the other hand, VCE is useful for screening and following the small intestine in the patients with it. Chemotherapy is effective to achieve complete regression of primary FL of the GI tract.
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori (H. pylori) is a gram-negative helical rod that colonizes human gastric mucosa. Its discovery has opened up new opportunities regarding the understating and management of gastrointestinal disorders. In humans, infection with H. pylori has been established as a major cause of chronic gastritis and peptic ulcer, and is important in the pathogenesis of gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Bacterial and host factors determine the outcome of H. pylori infection. The eradication of H. pylori can, therefore, contribute to the treatment and prevention of these diseases. H. pylori infection plays a critical role in gastric carcinogenesis through two major pathways: the indirect action of H. pylori on gastric epithelial cells through inflammation, and the direct action of the bacteria on epithelial cells through the induction of protein modulation and gene mutation. MALT lymphoma is a common low grade B-cell lymphoma arising from a background of chronic inflammatory disease at a number of mucosal sites. Those originating in the stomach are causatively linked to H. pylori infection, and eradication of the bacterium with antibiotics leads to the long-term complete regression of lymphoma. t (11;18)/API2-MALT1 and t(1;14)/IGH-BCL10 are specifically associated with the gastric MALT lymphoma entity, and the oncogenic products of these translocations have been shown to target a common molecular pathway, i.e., the nuclear factor-kappaB pathway. This paper reviews recent advances in our understanding of the association of H. pylori infection with gastric cancer and gastric MALT lymphoma and the molecular genetics underlying tumor development.
Rinsho byori. The Japanese journal of clinical pathology 09/2009; 57(9):861-9.
[Show abstract][Hide abstract] ABSTRACT: This is the first case of gastric schwannoma that exhibited increased accumulation of [(18)F] fluorodeoxyglucose (FDG) on positron emission tomography (PET) imaging. The patient was a 60-year-old woman in whom esophagogastroduodenoscopy showed a submucosal tumor, about 25 mm in size, in the upper body of the stomach, with ulceration at the top of the tumor. Endoscopic ultrasonography revealed a well-defined hypoechoic mass located in the proper muscle layer of the stomach. The specimen taken from the tumor showed only inflammatory degenerative tissue. Abdominal computed tomography revealed a tumor in the upper body of the stomach. FDG-PET showed FDG uptake (standardized uptake value [SUV] max 5.8) coincident with the tumor. Hence, the tumor was diagnosed initially as a gastrointestinal stromal tumor of the stomach. Laparoscopic partial gastrectomy was performed. Pathological examination showed that the tumor consisted of spindle cells with large nuclei, and mitosis was absent. The Ki-67 labeling index of the tumor cells was 4%. Immunohistochemically, the tumor cells showed a positive reaction for S-100 protein, whereas they were negative for KIT, CD 34, and alpha-smooth muscle actin protein. The tumor was diagnosed as a benign gastric schwannoma. Gastric schwannoma should be included in the differential diagnosis of submucosal tumors of the stomach with FDG uptake.
Gastric Cancer 01/2009; 12(4):225-8. · 4.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human serum sphingomyelin (SM) and phosphatidylcholine (PC) play important roles in the development of atherosclerosis. However, there are no rapid and sensitive methods for SM and PC measurement. The present report describes a novel enzymatic method for measuring SM, PC and lysophosphatidylcholine (lyso-PC) levels in plasma and lipid extracts.
The total choline-containing phospholipids (total PL), SM and PC were measured using a two-reagent system involving specific enzymes for choline-based phospholipids. The procedure was performed using either microplate or automatic analyzer technology. The concentration of lyso-PC was calculated by subtracting the concentration of SM plus PC from the total PL concentration.
Assay results showed linear correlations between sample concentration and absorbance. The within-run and between-run coefficients of variation for PC, SM, and lyso-PC concentrations were 2.0-4.4% for the microplate analyzer and 0.9-2.9% for the automatic analyzer. Analysis of normal human serum showed that the total PL concentration strongly correlated with the SM plus PC concentration (r=0.9850). There were moderate correlations between serum PC and SM levels (r=0.6228) and between serum PC and lyso-PC levels (r=0.7806). SM, PC, and lyso-PC levels in normal human serum (n=50) were 0.54+/-0.07, 1.99+/-0.22 and 0.60+/-0.15 mmol/L, respectively.
The present enzymatic method allowed for rapid, simple, and accurate measurement of SM, PC, and lyso-PC levels in lipid extracts and in serum. The method is suitable for both microplate and automatic analyzer assays.
[Show abstract][Hide abstract] ABSTRACT: The ulcer-associated cell lineage (UACL) induced at the site of ileac chronic ulceration in Crohn's disease has been reported to show histological differentiation resembling gastric pyloric mucosa. To clarify the significance of homeobox gene-encoded transcription factors in the formation of the UACL in Crohn's disease, we investigated the immunohistochemical expression of gastrointestinal mucins (MUC5AC for gastric surface mucous cells; MUC6 for gastric gland mucous cells, and MUC2 for intestinal goblet cells) and homeobox gene-encoded transcription factors (CDX-2 for intestinal mucosa and PDX-1 for pyloric mucosa) in the UACL. The analysis was undertaken on ileal mucosa obtained from ileal resections performed in 19 patients with active Crohn's disease of the small bowel. The UACL was observed in nine patients. In the UACL, expression of mucous cells with a foveolar-structure showed immunoreactivity to MUC5AC, and the mucous cells with a glandular structure showed immunoreactivity to MUC6, and the expression of MUC2 was decreased. In addition, we detected the decreased expression of CDX-2 along with the increased expression of PDX-1 in the UACL. The UACL showed histological differentiation simulating gastric pylori mucosa. The down-regulation of CDX-2 and the up-regulation of PDX-1 could be an important mechanism in the induction of the UACL.
Journal of Molecular Histology 05/2008; 39(2):161-8. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are successfully treated with Helicobacter pylori eradication alone. However, certain subsets of these tumors are resistant to the eradication treatment. As API2-MALT1 fusion is a feature of one of these subsets, we divided gastric MALT lymphomas into three groups: eradication-responsive and API2-MALT1 fusion-negative (Group A), eradication-resistant and fusion-negative (Group B), and eradication-resistant and fusion-positive (Group C). To characterize further gastric MALT lymphomas, we analyzed VH genes, which do not change in the course of tumor progression, by extensive subcloning of the monoclonal PCR products of 45 cases. VH3-23 and VH3-30 were preferentially used in Group A tumors (14/23 cases, 61%) as compared with Group B (1/10 cases, 10%, P=0.0094) and Group C (2/12 cases, 17%, P=0.017). Tumors of Groups B and C used variegated VH fragments, and no dominant VH fragments were noted. Somatic mutation was detected in most of the cases. Ongoing mutation was detected in 3/45 cases (7%), when assessed according to strict criteria for a confirmed mutation. These findings suggest that inflammation-dependent tumors (Group A) may be derived from a highly restricted, probably H. pylori-associated, B cell subset and may not often progress to those that are inflammation-independent (Groups B and C). Although considered to be common in this tumor, ongoing mutation may be infrequent when assessed by strict criteria.
Modern Pathology 05/2007; 20(4):460-6. · 6.36 Impact Factor