Comparison of Targeted vs Random Biopsies for Surveillance of Ulcerative Colitis-Associated Colorectal Cancer

Background & AimsA random biopsy is recommended for surveillance of ulcerative colitis (UC)-associated colorectal cancer. However, a targeted biopsy might be more effective. We conducted a randomized controlled trial to compare rates of neoplasia detection by targeted vs random biopsies in patients with UC.MethodsWe performed a study of 246 patients with UC for 7 years or more, seen at 52 institutions in Japan from October 1, 2008 through December 31, 2010. Patients were randomly assigned to the random group (4 random biopsies collected every 10 cm in addition to targeted biopsies, n = 122) or the target group (biopsies collected from locations of suspected neoplasia, n = 124). The primary end point was the number of neoplastic lesions detected in a single surveillance colonoscopy. We estimated the ratio and difference in the mean number of neoplastic lesions between the groups. We also evaluated the non-inferiority between the groups as an exploratory study. A non-inferiority margin of 0.65 (0.13 of 0.20) was considered for the ratio of the mean number of neoplastic lesions between groups.ResultsThe mean number of biopsies found to contain neoplastic tissue per colonoscopy was 0.211 (24 of 114) in the target group and 0.168 (18 of 107) in the random group (ratio of 1.251; 95% confidence interval, 0.679–2.306). The lower limit was above the non-inferiority margin of 0.65. Neoplasias were detected in 11.4% of patients in the target group and 9.3% of patients in the random group (P = .617). Larger numbers of biopsy samples per colonoscopy were collected in the random group (34.8 vs 3.1 in the target group; P < .001), and the total examination time was longer (41.7 vs 26.6 minutes in the target group; P < .001). In the random group, all neoplastic tissues found in random biopsies were collected from areas of the mucosa with a history or presence of inflammation.ConclusionsIn a randomized controlled trial, we found that targeted and random biopsies detect similar proportions of neoplasias. However, a targeted biopsy appears to be a more cost-effective method. Random biopsies from areas without any signs of present or past inflammation were not found to contain neoplastic tissues. Clinical Trial Registry: UMIN000001608

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

R: Conditioned-fear stress increases Fos expression in monoaminergic and GABAergic neurons of the locus coeruleus and dorsal raphe nuclei. Synapse 2002

ABSTRACT Many studies have demonstrated that physical or psychological stress can increase Fos expression in brainstem monoaminergic nuclei. Little is known, however, about the extent to which stress increases the expression of Fos in monoaminergic and nonmonoaminergic neurons in the brainstem. We examined the effects of conditioned-fear (CF) stress following mild footshock (FS) as unconditioned stress on Fos expression in the monoaminergic and GABAergic neurons of the ventral tegmental area (VTA), locus coeruleus (LC), and dorsal raphe nucleus (DR) in rats. The CF stress significantly increased the number of Fos-positive (Fosϩ) cells in both the LC and DR, whereas it did not increase the number in the VTA. Using a double-labeling technique, we combined Fos immunostaining with that for tyrosine hydroxylase (TH), serotonin (5-HT), or GABA for histochemical identification of the CF stress-induced Fosϩ neurons. The percentage of TH/Fos double-labeled cells resulting from CF stress was 63% of the Fosϩ cells in the LC, whereas 52% of the Fosϩ cells contained 5-HT in the DR. We also found that approximately 60% of the CF stress-induced Fosϩ cells were GABAergic neurons in these brain regions. These results indicate that CF stress induces intense Fos expression in the noradrenergic LC and serotonergic DR neurons, but not in the dopaminergic VTA neurons. They also indicate that not only monoaminergic neurons but also GABAergic neurons within the LC and DR are activated by the stress. Synapse 45: 46 -51, 2002

Pentraxin 3 Is a New Inflammatory Marker Correlated With Left Ventricular Diastolic Dysfunction and Heart Failure With Normal Ejection Fraction

ObjectivesThis study investigated the clinical significance of plasma pentraxin 3 (PTX3) levels in patients with heart failure with normal ejection fraction (HFNEF) and whether PTX3 is produced from coronary circulation.BackgroundPentraxin 3 is a novel inflammatory marker and a member of pentraxin superfamily including C-reactive protein (CRP). The relationship between inflammatory markers and HFNEF remains unclear.MethodsWe measured peripheral blood levels of PTX3, high-sensitivity CRP, tumor necrosis factor-alpha, and interleukin-6 in 323 patients comprising 82 HFNEF, 70 heart failure (HF) with reduced EF, and 171 non-HF patients. Levels of PTX3 were also measured at the aortic root and the coronary sinus in 75 patients.ResultsThe levels of PTX3, tumor necrosis factor-alpha, and interleukin-6, but not high-sensitivity CRP, were significantly higher in HFNEF patients than in non-HF patients. Multivariate logistic regression analysis identified only high levels of PTX3 as the independent inflammatory marker correlated with the presence of HFNEF in patients with normal left ventricular (LV) EF (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.11 to 1.98, p < 0.01) and with the presence of left ventricular diastolic dysfunction (LVDD) in non-HF patients (OR: 1.23, 95% CI: 1.02 to 1.50, p < 0.05). Levels of PTX3 at the coronary sinus were significantly higher than at the aortic root in HFNEF patients (p < 0.05) and in non-HF patients with LVDD (p < 0.01), but not different in non-HF patients without LVDD (p = 0.33).ConclusionsPentraxin 3 is significantly elevated in HFNEF patients and produced in the coronary circulation in patients with LVDD. Pentraxin 3, but not high-sensitivity CRP, is an independent inflammatory marker correlated with the presence of LVDD and HFNEF. (The Clinical Significance of Plasma Pentraxin 3 levels for Patients with Diastolic Heart Failure; UMIN000002170