Medical and Societal information from the Research Community	Number of Articles: 17,750,454 Number of Contributors: 57 Number of Queries: 12,901,669
	Save this page:  Send this page	Login  or Create a Free Account

GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Humans or Animals Humans Animals Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Results(1-25 of 719) Sort By: Publication Date Relevance Took: 1.159 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 29 1 2 3 4 > Last >> (719 articles found) Risk of gastric cancer in asymptomatic, middle-aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels. Aug 15, 2008 Kimihiko Yanaoka,Masashi Oka,Noriko Yoshimura,Chizu Mukoubayashi,Shotaro Enomoto,Mikitaka Iguchi,Hirohito Magari,Hirotoshi Utsunomiya,Hideyuki Tamai,Kenji Arii,Nobutake Yamamichi,Mitsuhiro Fujishiro,Tatsuya Takeshita,Osamu Mohara,Masao Ichinose A total of 5,209 asymptomatic, middle-aged subjects, whose serum pepsinogen (PG) and Helicobacter pylori antibody levels had been assessed, were followed for 10 years. Subjects with positive serum H. pylori antibodies (>50 U/mL) had an increased cancer risk (HR = 3.48, 95% CI = 1.26-9.64). Risk of ... ( view more )gastric cancer increased as the antibody level increased; the H. pylori-positive group with antibody levels >500 U/mL had the highest incidence rate (325/100,000 person-years). Cancer development also increased with a reduced serum PG I level or a reduced PG I/II ratio; the risk was significantly elevated with serum PG I level or=30 ng/mL (HR = 3.81, 95% CI = 1.10-13.21). Using H. pylori antibody and PG levels, subgroups with an especially high or low cancer incidence rate could be identified. H. pylori-negative or indeterminate subjects with low PG level (PG I 500 U/mL and a low PG level were among the subgroups with a high cancer incidence rate (over 400/100,000 person-years). In contrast, H. pylori-negative subjects with a PG I level >70 ng/mL or a PG I/II ratio >3.0 had the lowest risk; none of these subjects developed cancer. Thus, serum PG levels and/or H. pylori antibody levels can be used to predict the risk of cancer in individuals with H. pylori-related gastritis from the general population. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Evaluation of lateral instability of the atlanto-axial joint in rheumatoid arthritis using dynamic open-mouth view radiographs. Jul 2008 Daigo Taniguchi,Daisaku Tokunaga,Hitoshi Hase,Yasuo Mikami,Tatsuya Hojo,Takumi Ikeda,Ryo Oda,Ryota Takatori,Kan Imai,Yoshikazu Kida,Eigo Otakara,Hirotoshi Ito,Tsunehiko Nishimura,Toshikazu Kubo Upper cervical involvement is common in patients with rheumatoid arthritis (RA). Anterior atlanto-axial subluxation (aAAS) sometimes occurs at an early stage of the disease. We hypothesized that not only antero-posterior instability but lateral instability may occur with atlanto-axial involvement i... ( view more )n RA. To prove this hypothesis, we evaluated the lateral instability of the atlanto-axial joint in RA, using dynamic open-mouth view radiographs. Thirty RA patients and a control group of 22 non-RA outpatients were enrolled in this study. The patients underwent lateral view radiographs of the cervical spine during flexion and extension, and antero-posterior (AP) open-mouth views during maximum right and left bending of the neck. The anterior atlanto-dental interval (AADI) was measured to evaluate antero-posterior instability of the atlanto-axial joint, and atlanto-dental lateral shift (ADLS) was defined to evaluate dynamic lateral instability. In the RA group, AADI averaged 3.2 mm in flexion, and in eight patients, it exceeded 3 mm in flexion (aAAS). In the control group, the AADI averaged 1.0 mm in flexion. The ADLS in the RA group averaged 14.8%, and this was significantly greater than in the control group, in which it averaged 6.1%. The ADLS averaged 20.6% in the RA subgroup with aAAS, and 12.7% in the RA subgroup without aAAS. In both subgroups, the ADLS was significantly greater than that of the control group. In this study, dynamic lateral instability of the atlanto-axial joint in RA was demonstrated. The results suggest that an evaluation of the dynamic lateral instability of the atlanto-axial joint can be useful for early diagnosis of atlanto-axial lesions in RA. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Molecular characterization of Streptococcus mutans strains isolated from the heart valve of an infective endocarditis patient. Jul 2008 Hirotoshi Nemoto,Kazuhiko Nakano,Ryota Nomura,Takashi Ooshima Streptococcus mutans, known to be an aetiological agent of dental caries, is occasionally isolated from patients with infective endocarditis (IE). S. mutans strains with a defect in all three types of glucosyltransferase (GTF) obtained from an infected heart valve extirpated from an IE patient have... ( view more ) been reported previously. In this study, molecular analyses of strains detected in heart valve (strain V1) and dental plaque (strain P1) samples taken from the same patient were performed. Complete nucleotide alignments of the gtfB, gtfC and gtfD regions in strains V1 and P1, as well as in the reference strain MT8148, were determined, which revealed the existence of alignments with a high similarity to erythromycin- and spectinomycin-resistance genes in the middle of the gtfB-gtfC and gtfD genes, respectively, of V1. Strain V1 also showed a higher MIC for these two antibiotics compared with strain P1. Next, primers to detect the specific sequences of the antibiotic-resistance genes in strain V1 were constructed and PCR amplification was performed with template DNA from dental plaque and infected valve tissue samples taken from the patient. Attenuated expression of GTFs in V1 caused a significantly lower susceptibility to phagocytosis by human polymorphonuclear leukocytes compared with the reference strain. These results suggest that the blood isolate V1 found in the oral cavity invaded and survived in the bloodstream for a long duration and that this was related to its virulence in IE in our patient. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Reproductive isolation among cryptic species in the ectomycorrhizal genus Strobilomyces: Population-level CAPS marker-based genetic analysis. Jul 2008 Hirotoshi Sato,Noriaki Murakami Among the higher fungi, reproductively isolated cryptic species exist that are morphologically difficult to distinguish owing to a lack of taxonomically useful morphological characters. Mating tests are helpful for detecting reproductive isolation between cryptic species, but are often difficult to... ( view more ) perform for higher fungi, especially ectomycorrhizal fungi. In order to identify cryptic species of the ectomycorrhizal genus Strobilomyces more efficiently, lineages were defined based on the nucleotide sequence of two mitochondrial genes. Then the gene flow among lineages was measured using cleaved amplified polymorphic sequences (CAPS) markers designed for single copy nuclear genes. No heterozygosity was observed between different lineages, but within the same lineage heterozygosity was present at the ratio expected given Hardy Weinberg equilibrium. These results show that the mtDNA lineages are separate Mendelian populations, possibly cryptic species that are reproductively isolated from each other. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Role of the hinge region of glucocorticoid receptor for HEXIM1-mediated transcriptional repression. Jun 20, 2008 Noritada Yoshikawa,Noriaki Shimizu,Motoaki Sano,Kei Ohnuma,Satoshi Iwata,Osamu Hosono,Keiichi Fukuda,Chikao Morimoto,Hirotoshi Tanaka We previously reported that HEXIM1 (hexamethylene bisacetamide-inducible protein 1), which suppresses transcription elongation via sequestration of positive transcription elongation factor b (P-TEFb) using 7SK RNA as a scaffold, directly associates with glucocorticoid receptor (GR) to suppress gluc... ( view more )ocorticoid-inducible gene activation. Here, we revealed that the hinge region of GR is essential for its interaction with HEXIM1, and that oxosteroid receptors including GR show sequence homology in their hinge region and interact with HEXIM1, whereas the other members of nuclear receptors do not. We also showed that HEXIM1 suppresses GR-mediated transcription in two ways: sequestration of P-TEFb by HEXIM1 and direct interaction between GR and HEXIM1. In contrast, peroxisome proliferator-activated receptor gamma-dependent gene expression is negatively modulated by HEXIM1 solely via sequestration of P-TEFb. We, therefore, conclude that HEXIM1 may act as a gene-selective transcriptional regulator via direct interaction with certain transcriptional regulators including GR and contribute to fine-tuning of, for example, glucocorticoid-mediated biological responses. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Role of Fgf receptor 2c in adipocyte hypertrophy in mesenteric white adipose tissue. Jun 11, 2008 Morichika Konishi,Hirotoshi Nakamura,Hiroyuki Miwa,Pierre Chambon,David M Ornitz,Nobuyuki Itoh Fgf receptor 2c (Fgfr2c) was expressed in mature adipocytes of mouse white adipose tissue (WAT). To examine the role of Fgfr2c in mature adipocytes, we generated adipocyte-specific Fgfr2 knockout (Fgfr2 CKO) mice. The hypertrophy impairment of adipocytes in the mesenteric WAT but not in the subcuta... ( view more )neous WAT and decreased plasma free fatty acid (FFA) levels were observed in Fgfr2 CKO mice. Although the expression of genes involved in adipocyte differentiation and lipid metabolism in the mesenteric WAT was essentially unchanged, the expression of uncoupling protein 2 potentially involved in energy dissipation was significantly increased. Among potential Fgf ligands for Fgfr2c, Fgf9 was preferentially expressed in the mesenteric WAT. The present findings indicate that Fgfr2c potentially activated by Fgf9 plays a role in the adipocyte hypertrophy in the mesenteric WAT and FFA metabolism and/or energy dissipation in the mesenteric WAT might be involved in the hypertrophy impairment. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Development of a DNA Microarray for Authentication of Ginseng Drugs Based on 18S rRNA Gene Sequence. Jun 11, 2008 Shu Zhu,Hirotoshi Fushimi,Katsuko Komatsu Ginseng drugs, derived from underground parts of Panax species (Araliaceae), are the most important group of herbal medicines in the Orient. Previously, the nucleotide sequences of the nuclear 18S rRNA gene of 13 Panax taxa were determined, as were the specific polymorphic nucleotides for identific... ( view more )ation of each species. On the basis of the nucleotide difference, a DNA microarray (PNX array) was developed for the identification of various Panax plants and drugs. Thirty-five kinds of specific oligonucleotide were designed and synthesized as probes spotting on a decorated glass slide, which included 33 probes corresponding to the species-specific nucleotide substitutions and 2 probes as positive and negative controls. The species-specific probes were of 23-26 bp in length, in which the substitution nucleotide was located at the central part. Triplicate probes were spotted to warrant accuracy by correcting variation of fluorescent intensity. Partial 18S rRNA gene sequences amplified from Panax plants and drugs as well as their derived health foods were fluorescently labeled as targets to hybridize to the PNX array. After hybridization under optimal condition, specific fluorescent patterns were detected for each Panax species, and the analyzed results could be indicated as barcode patterns for quick distinction. The developed PNX array provided an objective and reliable method for the authentication of Panax plants and drugs as well as their derived health foods. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Sagittal alignment changes after thoracic laminectomy in adults. Jun 2008 Toshimi Aizawa,Tetsuro Sato,Hiroshi Ozawa,Naoki Morozumi,Fujio Matsumoto,Hirotoshi Sasaki,Takeshi Hoshikawa,Chikashi Kawahara,Shoichi Kokubun,Eiji Itoi OBJECT: The increased kyphosis after thoracic laminectomy in adult patients was retrospectively evaluated and various factors affecting this spinal deformity were analyzed. METHODS: The authors conducted a retrospective study of 58 cases in which laminectomy was performed and more than half of the ... ( view more )facet joints were left intact. The study group included 44 men (mean age 59 years) and 14 women (mean age 61 years) with thoracic myelopathy due to ossifications of the ligamentum flavum and/or the posterior longitudinal ligament or due to posterior bone spurs. Patients were followed up for a minimum of 2 years. Their neurological condition was evaluated using the Japanese Orthopaedic Association (JOA) scale (a full score is 11), and the magnitude of local kyphosis in the laminectomized area was determined using the Cobb angle method. RESULTS: The mean preoperative JOA score was 5.4; the mean postoperative score was 8.3. No relationship was found between postoperative JOA score and increased kyphotic angle. The mean preoperative kyphotic angle was 7.0 degrees . The mean postoperative kyphotic angle was 10.8 degrees . Thus local kyphosis in the treated area increased by only 3.8 degrees . The mean increase in kyphosis per spinal segment, calculated by dividing the kyphotic angle of the surgically decompressed area by the number of resected laminae, was 1.9 degrees . Female patients with >or= 3-level laminectomies showed a significant increase of kyphosis in both the laminectomized area and each spinal segment. CONCLUSIONS: The increase in kyphosis after thoracic laminectomy is not large and thus spinal fusion is usually not necessary. In cases involving female patients who undergo long-segment laminectomies, however, careful radiographic follow-up is recommended. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Antiviral activities of coffee extracts in vitro. Jun 2008 Hirotoshi Utsunomiya,Masao Ichinose,Misao Uozaki,Kazuko Tsujimoto,Hisashi Yamasaki,A Hajime Koyama Both hot water extracts of coffee grinds and instant coffee solutions inhibited the multiplication of herpes simplex virus type 1, a representative enveloped DNA virus, when they were added to the culture medium of the virus-infected cells at a dose of one fifth the concentration suitable for drink... ( view more )ing. The antiherpetic activity was independent of the suppliers (companies) of the coffee grinds and of the locations where the coffee beans were produced. Further characterization revealed that there are two different mechanisms, by which the coffee extracts exert inhibitory activities on the virus infection; (1) a direct inactivation of the infectivity of virus particle (i.e., a virucidal activity) and (2) the inhibition of progeny infectious virus formation at the late stage of viral multiplication in the infected cells. Caffeine, but not quinic acid and chlorogenic acid, inhibited the virus multiplication to some extent, but none of them showed the virucidal activity, suggesting that other component(s) in the coffee extracts must play a role in the observed antiviral activity. In addition, the coffee extracts inhibited the multiplication of poliovirus, a non-enveloped RNA virus, but showed no virucidal effect on this virus. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles SSA/Ro52 autoantigen interacts with Dcp2 to enhance its decapping activity. May 23, 2008 Tadanori Yamochi,Kei Ohnuma,Osamu Hosono,Hirotoshi Tanaka,Yoshiyuki Kanai,Chikao Morimoto We identified human decapping enzyme 2 (hDCP2) as a binding protein with Ro52, being colocalized in processing bodies (p-bodies). We also showed that the N-terminus and C-terminus of Ro52 bound to hDCP2. Moreover, Ro52 enhanced decapping activity of hDCP2 in a dose-dependent manner. Our data suppor... ( view more )t the novel notion of the association between Ro52 with hDCP2 protein in cytoplasmic p-bodies, playing a role in mRNA metabolism in response to cellular stimulation. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Role of cadherin-mediated cell-cell adhesion in pancreatic exocrine-to-endocrine transdifferentiation. May 16, 2008 Kohtaro Minami,Hirotoshi Okano,Akinori Okumachi,Susumu Seino Although pancreatic exocrine acinar cells have the potential to transdifferentiate into pancreatic endocrine cells, the mechanisms are poorly understood. Here we report that intracellular signaling pathways, including those involving MAPK and phosphatidylinositol 3 (PI3)-kinase, are activated by en... ( view more )zymatic dissociation of pancreatic acinar cells and that spherical cell clusters are formed by cadherin-mediated cell-cell adhesion during transdifferentiation. Inhibition of PI3-kinase by LY294002 prevents spheroid formation by degrading E-cadherin and beta-catenin, blocking transdifferentiation into insulin-secreting cells. In addition, neutralizing antibody against E-cadherin suppresses the induction of genes characteristic of pancreatic beta-cells. We also show that loss of cadherin-mediated cell-cell adhesion induces and maintains a dedifferentiated state in isolated pancreatic acinar cells. Thus, disruption and remodeling of cadherin-mediated cell-cell adhesion is critical in pancreatic exocrine-to-endocrine transdifferentiation, in which the PI3-kinase pathway plays an essential role. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Surgical outcomes in esophageal cancer patients with tumor recurrence after curative esophagectomy. May 2008 Chikara Kunisaki,Hirochika Makino,Ryo Takagawa,Naoto Yamamoto,Yasuhiko Nagano,Syoichi Fujii,Takashi Kosaka,Hidetaka A Ono,Yuichi Otsuka,Hirotoshi Akiyama,Yasushi Ichikawa,Hiroshi Shimada This study aimed to identify predictive factors and to evaluate appropriate treatments for recurrence of esophageal cancer after curative esophagectomy. About 166 consecutive patients, who underwent curative esophagectomy, were enrolled between April 1994 and March 2003. Recurrence was classified a... ( view more )s loco-regional or distant. Logistic regression analysis was used to identify predictive factors for recurrence. Prognostic factors were evaluated by Log-rank test and Cox proportional hazard regression analysis. The disease-specific 5-year survival was 56.8%. Recurrence was observed in 72 patients (43.4%), with 64 of these occurring within 3 years. The number of metastatic lymph nodes and lymphatic invasion independently predicted recurrence. There were significant differences in time to recurrence and survival time between loco-regional, distant recurrence, and combined recurrence. The 5-year survival time in patients with recurrence was 11.9%, and median survival time was 24 months. There was also a significant difference in survival after recurrence between treatment methods (no treatment vs chemo-radiotherapy, p=0.0063; chemotherapy, p=0.0247; and radiotherapy, p<0.0001). Meticulous, long-term follow-up is particularly necessary in patients with four or more metastatic lymph nodes to achieve early detection of recurrence. Randomized controlled trials should be used to develop effective modalities for each recurrence pattern to improve therapeutic outcomes. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A novel molecular mechanism for anticancer drug-induced ovarian failure: Irinotecan HCl, an anticancer topoisomerase I inhibitor, induces specific FasL expression in granulosa cells of large ovarian follicles to enhance follicular apoptosis. May 2008 Tomoko Utsunomiya,Tetsuji Tanaka,Hirotoshi Utsunomiya,Naohiko Umesaki Clinical use of CPT-11 combination chemotherapy frequently induces ovarian dysfunction in premenopausal and perimenopausal cancer patients, but its mechanism remains unclear. Mouse experiments were performed to clarify the molecular mechanism of CPT-11-induced ovarian dysfunction. Clinically therap... ( view more )eutic doses of CPT-11 were injected intraperitoneally into 8-week-old female MCH mice, and their ovaries were examined by the TUNEL assay to detect dead cells. Immunohistochemical examinations were simultaneously performed to detect the expression of activated caspase 3, Fas antigen and Fas ligand (FasL). Furthermore, normal murine ovarian tissue fragments were incubated with recombinant soluble FasL in organ cultures and stained by the TUNEL assay to detect apoptotic cells. Intraperitoneal CPT-11 injections induced specific TUNEL-positive cells and cell death with cleaved caspase 3 expression among large ovarian follicular granulosa cells. Apoptotic follicles (follicles containing >/=10 TUNEL-positive cells per ovarian section) were only found among large follicles. The final apoptotic follicle ratios were approximately 30% of the total follicles independent of the CPT-11 dose, while CPT-11 dose-dependently enhanced apoptotic processes in murine ovarian follicles. Fas antigen was expressed in most ovarian cells, with extremely high expression levels detected in luteal cells. CPT-11 injections did not significantly increase the Fas expression levels in ovarian cells. Although no FasL expression was detected in normal ovarian tissues, CPT-11 injections significantly induced specific FasL expression in granulosa cells. Incubation of organ-cultured normal murine ovarian tissue fragments with recombinant mouse soluble FasL significantly increased the numbers of TUNEL-positive granulosa and luteal cells. In conclusion, CPT-11 dose-dependently induced specific FasL expression in granulosa cells of developing ovarian follicles. The induced FasL reacted with the Fas antigen constitutively expressed on granulosa cells, such that apoptosis can only be enhanced and induced in granulosa cells in an autocrine and/or paracrine manner. This cell lineage-specific and differentiation stage-specific apoptosis in granulosa cells is thought to be the main molecular mechanism of the ovarian dysfunction induced by CPT-11 combination chemotherapy. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Irinotecan HCl, an anticancer topoisomerase I inhibitor, frequently induces ovarian failure in premenopausal and perimenopausal women. May 2008 Tetsuji Tanaka,Tomoko Utsunomiya,Hirotoshi Utsunomiya,Naohiko Umesaki The effects of irinotecan HCl (CPT-11) combination chemotherapies on the hypothalamus-pituitary-ovary endocrine system were examined clinically. The incidences of typical menopausal malaises and/or endocrinological findings were investigated in 32 gynecological cancer patients treated by CPT-11 com... ( view more )bination chemotherapies. Patients who complained of menopausal malaises or had been treated by hormone replacement therapy before chemotherapy were excluded from the study. Menopausal malaise-like symptoms (MMLS) appeared in 6 of 32 patients (18.8%) during CPT-11 combination chemotherapy, and these symptoms were completely cured within a few days by administration of conjugated estrogen tablets (0.625 mg/day). All the MMLS cases were perimenopausal patients (47-57 years of age), and MMLS were not found in any of the postmenopausal patients who had exceeded 3 years since endocrinological menopause or patients who had recurrent cancer after pelvic radiotherapy. After exclusion of these 3-year-postmenopausal patients and postirradiation patients, 6 of 7 patients aged 45-59 years complained of MMLS during CPT-11 combination chemotherapy. The incidence of CPT-11-induced MMLS showed no relationships with the anticancer drugs combined with CPT-11, mean total CPT-11 dose, mean number of CPT-11 injections, mean individual CPT-11 dose, grade of CPT-11-specific diarrhea or anticancer effects of each CPT-11 combination chemotherapy. The perimenopausal cancer patients with CPT-11-induced MMLS showed decreased serum estradiol and increased serum FSH and LH levels accompanying the CPT-11 injections. A young patient with CPT-11-induced secondary amenorrhea showed decreased serum estradiol and increased serum FSH and LH levels accompanying the CPT-11 injections. None of the postmenopausal patients with high FSH and LH levels showed any significant differences in their serum FSH, LH, PRL and TSH levels during CPT-11 combination chemotherapy. No differences in the results of LHRH and TRH tests during chemotherapy were found for postmenopausal patients. Histopathological examinations of normal ovarian tissues surgically removed from 4 young cervical cancer patients treated with preoperative CPT-11 combination chemotherapies revealed no growing ovarian follicles in the ovarian tissues. CPT-11 injections can induce estrogen-rescued MMLS in cancer patients aged approximately 50 years at a very high rate and may induce secondary amenorrhea in young women. The endocrinological and histopathological studies revealed that CPT-11 causes ovarian follicular loss and ovarian failure within a short time without affecting hypothalamic and pituitary hormone secretion. These clinical results indicate that CPT-11 has strong ovarian toxicity and that repeated CPT-11 administrations may frequently induce ovarian follicular loss and premature ovarian failure, even in young women. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Effect of vascular stenosis on perfusion-weighted imaging; differences between calculation algorithms. May 2008 Shigenori Matsushima,Takao Kubota,Kei Yamada,Kentaro Akazawa,Terutoshi Masunami,Hirotoshi Ito,Yo Ushijima,Kei Owada,Hiroyasu Sasajima,Katsuyoshi Mineura,Tsunehiko Nishimura PURPOSE: To determine the most suitable postprocessing technique for magnetic resonance (MR) perfusion imaging in patients with vascular stenosis, by comparing the cerebral blood flow (CBF) maps of single photon emission tomography (SPECT) and perfusion MR imaging (MRI). MATERIALS AND METHODS: In 1... ( view more )5 consecutive patients (14 men and one woman, mean age 73.9 +/- 6.0 years) with stenosis of common carotid artery (CCA) or internal carotid artery (ICA) of more than 75%, both brain perfusion MRI and brain perfusion SPECT were performed. From perfusion MR images, CBF maps were calculated with the first moment, singular value decomposition (SVD), and block circulant SVD (b-SVD) methods, and CBF maps from each algorithm were compared with those from SPECT. RESULTS: The b-SVD method had the best correlation with SPECT (R = 0.814), followed by the first moment method (R = 0.776) and the SVD method (R = 0.723). The b-SVD method has the least mean difference with SPECT (0.118), the first moment method also had less difference (0.121), and the SVD had greatest mean difference (0.164). CONCLUSION: Our results suggest that in patients with vascular impairment the b-SVD method will be the technique of choice rather than SVD or first moment method. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Non-small-cell lung cancer] May 2008 Hirotoshi Akita,Ichiro Kinoshita Molecular targeted therapy in combination with chemotherapy or thoracic radiotherapy has been studied in clinical trials. Gefitinib or erlotinib in combination with standard chemotherapy did not improve efficacy on survival over standard chemotherapy alone in chemotherapy-naive patients with advanc... ( view more )ed NSCLC. On the other hand, bevacizumab in combination with standard chemotherapy improved survival in chemotherapy-naive patients with advanced NSCLC, excluding squamous cell carcinoma. Multi-target tyrosine kinase inhibitors in combination with standard chemotherapy, and anti-EGFR antibodies and EGFR tyrosine kinase inhibitors in combination with thoracic radiotherapy, are under clinical trials. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Identification and in vitro expansion of functional antigen-specific CD25+ FoxP3+ regulatory T cells in hepatitis C virus infection. May 2008 Hirotoshi Ebinuma,Nobuhiro Nakamoto,Yun Li,David A Price,Emma Gostick,Bruce L Levine,J Tobias,William W Kwok,Kyong-Mi Chang CD4(+)CD25(+) regulatory T cells (CD25(+) Tregs) play a key role in immune regulation. Since hepatitis C virus (HCV) persists with increased circulating CD4(+)CD25(+) T cells and virus-specific effector T-cell dysfunction, we asked if CD4(+)CD25(+) T cells in HCV-infected individuals are similar to... ( view more ) natural Tregs in uninfected individuals and if they include HCV-specific Tregs using the specific Treg marker FoxP3 at the single-cell level. We report that HCV-infected patients display increased circulating FoxP3(+) Tregs that are phenotypically and functionally indistinguishable from FoxP3(+) Tregs in uninfected subjects. Furthermore, HCV-specific FoxP3(+) Tregs were detected in HCV-seropositive persons with antigen-specific expansion, major histocompatibility complex class II/peptide tetramer binding affinity, and preferential suppression of HCV-specific CD8 T cells. Transforming growth factor beta contributed to antigen-specific Treg expansion in vitro, suggesting that it may contribute to antigen-specific Treg expansion in vivo. Interestingly, FoxP3 expression was also detected in influenza virus-specific CD4 T cells. In conclusion, functionally active and virus-specific FoxP3(+) Tregs are induced in HCV infection, thus providing targeted immune regulation in vivo. Detection of FoxP3 expression in non-HCV-specific CD4 T cells suggests that immune regulation through antigen-specific Treg induction extends beyond HCV. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles High levels of saturated very long-chain fatty acid (hexacosanoic acid; C26:0) in whole blood are associated with metabolic syndrome in Japanese men. May 2008 Atsumi Kume,Tetsuro Miyazaki,Yohei Kitamura,Kyoichi Oshida,Naotake Yanagisawab,Hirotaka Takizawa,Kiyotaka Fujii,Takashi Kiyanagi,Katsuhiko Sumiyoshi,Hirotoshi Ohmura,Hiroshi Mokuno,Kazunori Shimada,Hiroyuki Daida OBJECTIVE: Hexacosanoic acid (C26:0) is a saturated very long-chain fatty acid and high levels of C26:0 in red blood cells are reported to be closely related with risk factors of atherosclerosis. However, the relationship between absolute levels of C26:0 in whole blood and metabolic syndrome (MS) h... ( view more )as not been determined. MATERIALS AND METHOD: We divided 218 consecutive apparently healthy male subjects into an MS group (n=78) and a non-MS group (n=140) according to the definition of the International Diabetes Federation. The levels of C26:0 in whole blood were measured by gas liquid chromatography-mass spectrometry. RESULTS: The MS group had significantly higher levels of C26:0 than the non-MS group (2.42+/-0.31mug/ml vs. 2.25+/-0.29mug/ml, P=0001). There was a significant association between the levels of C26:0 and the number of factors of MS. The levels of C26:0 positively correlated with age, blood pressure, triglyceride and fasting plasma glucose. Multivariate analysis revealed that the level of C26:0 is still an independent variable for the presence of MS after adjustment for age and each criterion of MS. CONCLUSION: The absolute levels of C26:0 in whole blood appear to be associated with MS independent of its component parts. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Possible involvement of heparin-binding protein in transfusion-related acute lung injury. May 2008 Kazuta Yasui,Rika A Furuta,Nobuki Matsuyama,Yasuo Fukumori,Takafumi Kimura,Yoshihiko Tani,Hirotoshi Shibata,Fumiya Hirayama BACKGROUND: In antibody-mediated nonhemolytic transfusion reactions, transfusion-related acute lung injury (TRALI) tends to occur typically within 2 hours after a blood transfusion. White cell antibodies or immune complexes have been frequently shown to be associated with the syndrome, although the... ( view more ) mechanisms by which they induce TRALI are poorly understood. The aim of this study was to characterize soluble mediators that are released from cells at an early stage after immune stimulation. STUDY DESIGN AND METHODS: To explore the mechanism of TRALI, an in vitro whole-blood cell culture assay was established in which cells were stimulated by human antibodies and the activation of neutrophils was monitored by a cell surface marker (Mac-1) with flow cytometry and by measurement of the release of soluble factors, including perforin, interleukin-6, tumor necrosis factor-alpha, and heparin-binding protein (HBP) with enzyme-linked immunosorbent assays. In addition, the involvement of two neutrophil FcgammaRs (FcgammaRIIIb and FcgammaRIIa, also known as CD16 and CD32, respectively) was examined during antibody-induced cell activation with anti-FcgammaR blocking antibodies. RESULTS: Substantial amounts of HBP were released within 30 minutes of stimulation by human antibodies, although other soluble mediators were not released within the same period. Furthermore, the release of HBP was mediated via signals through both FcgammaRIIIb and FcgammaRIIa. CONCLUSION: HBP appears to be one of the primary effector molecules of antibody-mediated nonhemolytic transfusion reactions including TRALI. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Modulation of redox potential and alteration in reactivity via the peroxide shunt pathway by mutation of cytochrome P450 around the proximal heme ligand. Apr 22, 2008 Hirotoshi Matsumura,Masahiro Wakatabi,Sayaka Omi,Akashi Ohtaki,Nobuhumi Nakamura,Masafumi Yohda,Hiroyuki Ohno In the thermophilic cytochrome P450 from the thermoacidophilic crenarchaeon Sulfolobus tokodaii strain 7 (P450st), a phenylalanine residue at position 310 and an alanine residue at position 320 are located close to the heme thiolate ligand, Cys317. Single site-directed mutants F310A and A320Q and d... ( view more )ouble mutant F310A/A320Q have been constructed. All mutant enzymes as well as wild-type (WT) P450st were expressed at high levels. The substitution of F310 with Ala and of A320 with Gln induced shifts in redox potential and blue shifts in Soret absorption of ferrous-CO forms, while spectral characterization showed that in the resting state, the mutants almost retained the structural integrity of the active site. The redox potential of the heme varied as follows: -481 mV (WT), -477 mV (A320Q), -453 mV (F310A), and -450 mV (F310A/A320Q). The trend in the Soret band of the ferrous-CO form was as follows: 450 nm (WT) < 449 nm (A320Q) < 446 nm (F310A) < 444 nm (F310A/A320Q). These results established that the reduction potential and electron density on the heme iron are modulated by the Phe310 and Ala320 residues in P450st. The electron density on the heme decreases in the following order: WT > A320Q > F310A > F310A/A320Q. The electron density on the heme iron infers an essential role in P450 activity. The decrease in electron density interferes with the formation of a high-valent oxo-ferryl species called Compound I. However, steady-state turnover rates of styrene epoxidation with H2O2 show the following trend: WT approximately equal to A320Q < F310A approximately equal to F310A/A320Q. The shunt pathway which can provide the two electrons and oxygen required for a P450 reaction instead of NAD(P)H and dioxygen can rule out the first and second heme reduction in the catalytic process. Because the electron density on the heme iron might be deeply involved in the k cat values in this system, the intermediate Compound 0 which is the precursor species of Compound I mainly appears to participate dominantly in epoxidation with H2O2. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Nonadiabatic couplings from time-dependent density functional theory. II. Successes and challenges of the pseudopotential approximation. Apr 21, 2008 Chunping Hu,Hirotoshi Hirai,Osamu Sugino We present extensive calculations of nonadiabatic couplings (NACs) between the electronically ground and excited states of molecules, using time-dependent density functional theory (TDDFT) within (modified) linear response [C. Hu et al. J. Chem. Phys. 127, 064103 (2007)]. Our approach is implemente... ( view more )d in the pseudopotential framework, with the consideration of nonlinear core corrections. The features of either the ordinary Jahn-Teller conical intersections in X(3) (X=Li, Na, K, Cu, Ag, Au) trimers, or the elliptic Jahn-Teller conical intersections in NaH(2), have been well reproduced. In particular, anticipated results for the H-H(2) collision near the avoided crossing are obtained, showing appealing improvement over the first, real-time, TDDFT calculation. The other important type of intersections, Renner-Teller glancing intersection, has also been studied for several typical molecular systems (BH(2), AlH(2), CH(2)(+), SiH(2)(+)), giving results in reasonable agreement with the theoretical model. Despite these successes, it is found that for some systems, including both Jahn-Teller and Renner-Teller systems, the pseudopotential scheme might give inaccurate results for some NAC components on nonhydrogen atoms. By trying different construction schemes of pseudopotentials, e.g., using local pseudopotentials, the results of NACs are found scheme-dependent and show improvement for some cases. Since there is much freedom in constructing ab initio nonlocal pseudopotentials, our findings on TDDFT calculation of NACs in the pseudopotential scheme might be helpful to give clues for constructing more "realistic" pseudopotentials. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Endoscopic deployment of multiple JOSTENT SelfX is effective and safe in treatment of malignant hilar biliary strictures. Apr 2008 Hirofumi Kawamoto,Koichiro Tsutsumi,Ryo Harada,Masakuni Fujii,Hironari Kato,Ken Hirao,Naoko Kurihara,Takashi Nakanishi,Osamu Mizuno,Etsuji Ishida,Tsuneyoshi Ogawa,Hirotoshi Fukatsu,Kohsaku Sakaguchi BACKGROUND & AIMS: For the treatment of unresectable biliary tract carcinoma with hilar biliary stricture, antitumor therapy and biliary stenting should be addressed in terms of prolonged survival with a good quality of life. However, the endoscopic management of malignant hilar biliary strictures ... ( view more )is difficult even for an expert endoscopist. We evaluated the efficacy and safety of the endoscopic deployment of multiple JOSTENT SelfX units in patients with hilar biliary strictures treated with or without chemotherapy. METHODS: Between November 2003 and December 2006, endoscopic deployment of multiple JOSTENT SelfX units in hilar biliary strictures by using a partial stent-in-stent procedure was performed on 41 consecutive patients with primary cholangiocarcinoma (n = 34) and gallbladder carcinoma (n = 7) at a gastroenterologic center of Okayama University Hospital. Thirty-three patients were treated with gemcitabine (n = 25) or S-1 (n = 8). RESULTS: Metallic stent deployment was successfully accomplished in all cases via only endoscopic procedures. During the follow-up period (mean, 210 days), mean patency time was 150 days, and metallic stent obstruction occurred in 15 cases (37%). Although a repeat intervention was required in all metallic stent obstructed cases, the deployment of the second metallic or plastic stent was completed successfully. The remaining 26 cases (63%) required no interventions. The median overall survival period was only 235 days. However, that of the patients receiving chemotherapy was 392 days. CONCLUSIONS: Endoscopic partial stent-in-stent deployment with multiple JOSTENT SelfX prostheses is effective and safe for the treatment of malignant hilar biliary stricture even in patients receiving chemotherapy. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Messenger RNA expression of vascular endothelial growth factor and its receptors in primary colorectal cancer and corresponding liver metastasis. Apr 2008 Hirotoshi Kobayashi,Kenichi Sugihara,Hiroyuki Uetake,Tetsuro Higuchi,Masamichi Yasuno,Masayuki Enomoto,Hidekazu Kuramochi,Heinz-Josef Lenz,Kathleen D Danenberg,Peter V Danenberg BACKGROUND: Antiangiogenic therapies have been developed recently in combination with traditional chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to clarify the association between messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and it... ( view more )s receptors (VEGFR) in primary colorectal cancer and those in corresponding liver metastasis. METHODS: Thirty-one paired formalin-fixed, paraffin-embedded tumor tissues of colorectal cancer and liver metastasis were dissected by laser capture microdissection. After the mRNA was isolated, a quantitative fluorescent dye real-time reverse transcription-polymerase chain reaction system was used for gene expression measurement. RESULTS: There was a positive correlation between VEGF mRNA levels in primary colorectal cancer and those in matched liver metastasis (P = .0083, r (s) = 0.48). However, there was no association between mRNA levels of VEGFRs in primary tumor and those in liver metastasis. The mRNA levels of VEGF were associated with those of VEGFR-1 (P = .0026, r (s) = 0.39) but not with those of VEGFR-2. The mRNA levels of VEGF were higher than that of either of the VEGFRs (P < .0001). CONCLUSIONS: We can predict VEGF mRNA levels, but not those of VEGFRs, in liver metastasis by measuring those in primary colorectal cancer. The mRNA expression of VEGFRs may be more dependent on the surrounding environment than that of VEGF. These results should be useful for the formulation of antiangiogenic therapies for metastatic colorectal cancer. Further studies will be necessary to validate these preliminary data. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A Phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable advanced pancreatic cancer after vascular supply distribution via superselective embolization. Apr 2008 Koji Miyanishi,Hirotoshi Ishiwatari,Tsuyoshi Hayashi,Minoru Takahashi,Yutaka Kawano,Kohichi Takada,Hideyuki Ihara,Toshinori Okuda,Kunihiro Takanashi,Sho Takahashi,Yasushi Sato,Takuya Matsunaga,Hisato Homma,Junji Kato,Yoshiro Niitsu BACKGROUND: We previously reported that arterial infusion chemotherapy improved the response rate and survival of the patients with pancreatic cancer at advanced stages in an open trial. We conducted a Phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for advanced ... ( view more )pancreatic cancer after vascular supply distribution via superselective embolization. METHODS: Patients were treated after arterial embolization for hemodynamic change to restrict the blood flow into the pancreas (mainly to the great pancreatic artery and the caudal pancreatic artery). Arterial infusion chemotherapy consisted of gemcitabine in doses that were increased from 600 to 1000 mg/m(2) in subsequent cohorts on Day 1 plus continuous infusion of 5-fluorouracil 300 mg/m(2)/day on Days 1-5 every 2 weeks. Result Twelve patients were enrolled. The maximum tolerated dose of gemcitabine was determined to be Level 3 (1000 mg/m(2)). Only very mild hematological and non-hematological toxicities were noted. The overall response rate was 33.3%. The median survival time was 22.7 (95% CI; 9.5-24.5) months and the 1- and 2-year overall survival rates were 83.3 and 25.0%, respectively. CONCLUSION: Arterial infusion chemotherapy using 1000 mg/m(2) gemcitabine on Day 1 and 300 mg/m(2)/day 5-fluorouracil on Days 1-5 every 2 weeks warrants a Phase II study. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Cancer high-risk subjects identified by serum pepsinogen tests: outcomes after 10-year follow-up in asymptomatic middle-aged males. Apr 2008 Kimihiko Yanaoka,Masashi Oka,Chizu Mukoubayashi,Noriko Yoshimura,Shotaro Enomoto,Mikitaka Iguchi,Hirohito Magari,Hirotoshi Utsunomiya,Hideyuki Tamai,Kenji Arii,Hiroshi Ohata,Mitsuhiro Fujishiro,Tatsuya Takeshita,Osamu Mohara,Masao Ichinose BACKGROUND: Gastric cancer screening using the pepsinogen filter test is receiving wide recognition in Japan owing to convenience, freedom from discomfort or risk, efficiency, and economy. Because the long-term outcomes of cancer development in extensive atrophic gastritis detected by pepsinogen te... ( view more )st are unclear, test-positive and test-negative subjects were investigated in a longitudinal cohort study. METHODS: Subjects comprised 5,209 middle-aged men with measured serum pepsinogen levels who were followed for 10 years. Cancer development based on "atrophy-positive" and "atrophy-negative" criteria used for cancer screening was investigated. RESULTS: During the study, 63 cases of cancer developed in the cohort, representing an incidence rate of 125 per 100,000 person-years. Pepsinogen test screening using the most widely used atrophy-positive criterion (pepsinogen I, < or =70 ng/mL; pepsinogen I/II ratio, < or =3.0) displayed 58.7% sensitivity, 73.4% specificity, and 2.6% positive predictive value. Cancer incidence rate was 276 per 100,000 person-years for the atrophy-positive group and 70 per 100,000 person-years for the atrophy-negative group. Incidence rate was higher in groups fulfilling stricter positive criteria detecting more extensive atrophy, reaching 424 per 100,000 person-years. In addition, 9.2% of atrophy-negative subjects with pepsinogen I of >70 ng/mL and pepsinogen I/II ratio of < or =3.0 (reflecting putative inflammation-based high pepsinogen II level) are at high risk for cancer, particularly diffuse-type cancer, with a cancer incidence rate comparable with atrophy-positive subjects (216 per 100,000 person-years). CONCLUSION: Atrophy-positive subjects by pepsinogen filter test, particularly those fulfilling stricter criteria, and atrophy-negative subjects with low pepsinogen I/II ratio reflecting putative extensive active inflammation constitute populations at high risk for gastric cancer, requiring thorough endoscopic examination. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 29 1 2 3 4 > Last >> (719 articles found)

      
 ESRNexus is provided as a service by TrialStat Corporation. ESRNexus is a registered trademark of TrialStat Corporation. Copyright 2008. View a list of all articles here