Evaluation of the depth score of type V pit patterns in crypt orifices of colorectal neoplastic lesions

Background We developed and evaluated the clinical usefulness of a scoring system that subclassified type Vi pit patterns. Methods We studied 119 colon cancer lesions (pTis, n = 26; pT1, n = 93) and 22 tubular adenoma lesions with severe atypia in which a type Vi pit pattern was visible under a stereomicroscope. Four type Vi pit pattern formation appearances (existing pits, marginal irregularities of the gland duct, narrowing of the gland duct lumen, and unclear outline of the gland duct) were defined, and the relationship between each appearance and the invasive depth of the cancer was evaluated. Results When the four type Vi pit pattern appearances were considered in a logistic regression analysis, the odds of a more invasive submucosal cancer were significantly increased by the appearance of marginal irregularities, a narrowed lumen, and an unclear outline. In the logistic regression analysis results, when 0.63 was used as the cutoff score for prediction of a more invasive submucosal cancer, 80 cases in the less invasive group were classified correctly (specificity, 1.0), whereas 53 (86.9%) of the 61 cases in the more invasive group were classified correctly (sensitivity, 0.869). Conclusions It is important first to understand the usability and limitations of objective scoring of type V pit pattern findings and then to apply this score to the determination of cancer depth in order to accurately identify lesions suitable for endoscopic treatment.     

Splenic artery ligation: A protection against hepatic ischemia/reperfusion injury in partially hepatectomized rats

Aim: In liver resection, the temporary occlusion of the hepatoduodenal ligament (Pringle maneuver) is often used. However, the maneuver causes ischemia/reperfusion (I/R) injury in the remnant liver. Heme oxygenase (HO)‐1 has a cytoprotective role against this injury. Our aim is to investigate whether splenic artery ligation induces HO‐1 expression in the liver and ameliorates the hepatic I/R injury in partially hepatectomized rats. Methods: Rats underwent splenic artery ligation by occluding the main splenic artery. Two days later, the total hepatic ischemia (Pringle maneuver) was conducted, and then a two‐thirds partial hepatectomy (PH) was performed just before the start of reperfusion. HO inhibitor was twice injected s.c. at 3 and 16 h before the Pringle maneuver. HO‐1 levels were determined by western blotting. Liver injury was biochemically assessed. Results: In normal rats, HO‐1 was highly expressed in the spleen, but not in the liver. Splenic artery ligation induced HO‐1 in the livers. When rats underwent 20 and 30 min of Pringle maneuver/PH, survival rates were 28% and 8%, respectively. Splenic artery ligation significantly improved both the survival rates: 73% and 56%, respectively. Under these conditions, administration of HO‐1 inhibitor at least partly negated the efficacy of splenic artery ligation. Splenic artery ligation also increased the recovery rate of the remnant liver mass and platelet counts in Pringle maneuver/PH‐treated rats. Conclusion: Splenic artery ligation was significantly effective on the hepatic I/R injury in partially hepatectomized rats. Induction of HO‐1 may be at least partly involved in the improvement of this injury.     

Occurrence of clinical depression during combination therapy with pegylated interferon alpha or natural human interferon beta plus ribavirin

Aim: The onset of depression symptoms during pegylated interferon α plus ribavirin (PEG‐IFN/RBV) combination therapy has led to treatment discontinuation in some cases. In the present study, we conducted a questionnaire survey during treatment to determine whether natural human interferon β plus ribavirin (IFNβ/RBV) therapy is associated with a lower incidence of depression symptom onset compared with PEG‐IFN/RBV therapy. Methods: Seventy‐seven patients with chronic hepatitis C received PEG‐IFN/RBV (PR) or IFNβ/RBV (FR) therapy. A questionnaire survey was administered at the start of treatment, and at 4 and 12 weeks, using the Beck Depression Inventory II (BDI‐II) and the Pittsburgh Sleep Quality Index (PSQI). Results: BDI‐II scores in the PR group increased at 4 and 12 weeks, but remained unchanged in the FR group. At 12 weeks, the mean BDI‐II score and incidence of abnormalities with a BDI‐II score of ≥14 were significantly lower in the FR group than in the PR group. BDI‐II scores during IFNβ/RBV therapy in 11 patients currently using antidepressants remained unchanged up to 12 weeks. None of these 11 patients required addition or dose increases of antidepressants, and there was no evidence of worsened depression symptoms. Nine PR patients had BDI‐II scores of ≥14 and PSQI scores of ≥11 at 12 weeks. Conclusions: IFNβ/RBV therapy was associated with a lower incidence of depression symptom onset during treatment. In patients already diagnosed with depression, there was no evidence that IFNβ/RBV therapy caused any worsening of symptoms, indicating that IFNβ/RBV therapy is safe for patients with depression.     

Interferon-beta reduces the mouse liver fibrosis induced by repeated administration of concanavalin A via the direct and indirect effects

Type I interferons (IFNs), IFN-alpha and IFN-beta, are widely used for treating chronic hepatitis C. Although retrospective studies have suggested that type I IFNs have direct antifibrotic effects, little is known about these mechanisms. The present study was designed to clarify the preventive mechanisms of type I IFNs in the progression of fibrosis for the establishment of a more effective therapy. A murine fibrosis model comprising immunological reactions was induced by the administration of concanavalin A (0.3 mg/body) into mice once a week for 4 weeks. Liver injury and the degree of fibrosis were determined by measuring the serum alanine aminotransferase activities and liver hydroxyproline contents with or without IFN-beta pretreatment. IFN-beta suppressed the hepatocellular injury and increased the hydroxyproline content induced by repeated concanavalin A injections, but had no effect on established fibrosis. Furthermore, IFN-beta reduced the expressions of transforming growth factor-beta, basic fibroblast growth factor, collagen type I A2 and tissue inhibitor of metalloproteinase 1 messenger RNAs, which are related to the progression of liver fibrosis. The IFN-beta reduced the liver injury and fibrosis induced by immunological reactions. These data suggest that type I IFNs suppress the progression of cirrhosis through inhibition of repeated hepatocellular injury and/or factors that promote the liver fibrosis induced by hepatitis virus infection.     

The feasibility of a bed net impregnation program to enhance control of Malayan filariasis along a swamp forest in southern Thailand

The purpose of this study is to document the potential feasibility of using a bed net impregnation program to enhance the control of Malayan filariasis in southern Thailand. A survey was conducted in one Muslim and one Buddhist village along the swamp forest in Narathiwat Province. Face-to-face interview was employed to collect data on practice of bed net use, knowledge and attitudes on filarial control and acceptance if a bed net impregnation program were to be introduced. Bed nets were used by 98.5% of the study households. Both Muslims and Buddhists were all in bed by 23.00 hrs. By 03.00 hrs, more than 20% of Buddhists were out of bed for rubber tapping, whereas more than 90% of the Muslim were still in bed until 04.30 hrs. Combining our data with biting rate from a previous study, approximately one-third of Mansonia bites were protected by the current bed net practice. The impregnation program was potentially welcome by both groups of villagers. From this study, we conclude that a bed net impregnation program in this area is feasible.     

Transferrin is not involved in initial uptake process of iron in rat duodenal mucosa

The role of transferrin in iron absorption by the duodenal mucosa in rats with iron deficiency and controls was evaluated immunohistochemically. Ferric iron was administered to each rat using a metallic gastric tube. Transferrin was stained by an immunoperoxidase method and iron with Prussian blue in the same duodenal sections and observed by light microscopy. The localization of transferrin differed from that of ferric iron both in rats with iron deficiency and in controls. In iron-deficient rats, transferrin was weakly stained after iron administration but was strongly stained after saline administration. In contrast, in controls, transferrin was weakly stained after saline administration but was strongly stained after iron administration. By electron microscopy, x-ray energy spectrometric analysis of the transferrin-positive areas showed no iron peak. In iron-deficient rats, accumulation of electron-dense transferrinnegative microgranules was observed in some of the duodenal columnar epithelium. X-ray energy spectrometric analysis of this area revealed iron, indicating iron absorption. These results suggest that mucosal transferrin does not act as a shuttle protein in iron absorption via the rat duodenal columnar epithelium, and the function of this protein may be to inform the absorptive cells of the iron status of the body as observed in other organs.     

Semiquantitative analysis of integrated genomes of human T-lymphotropic virus type I in asymptomatic virus carriers.

A semiquantitative estimation of human T-lymphotropic virus type I (HTLV-I) integration by peripheral blood mononuclear cells (PBMC) was performed. Genomic DNA samples derived from 134 HTLV-I carriers were subjected to 40 or 60 cycles of the polymerase chain reaction to amplify the pol region of HTLV-I. The HTLV-I genome was detected by dot hybridization using a 32P-labeled oligonucleotide probe for the pol region. The radioactivity of hybridized dot membranes was then counted with an RI Imaging System (Ambis Inc, San Diego, CA) and the HTLV-I genome dose was determined by comparison with standard curve for serially diluted HTLV-I genome-positive DNA. A wide range of variation of HTLV-I genome integration was observed. When the integrated genome dose was calculated as the number of HTLV-I copies per 100 PBMC, 7 carriers (5%) had more than 10 copies, 56 (42%) had 1 to 10 copies, 46 (34%) had 0.1 to 1 copy, and 24 (18%) had less than 0.1 copy. In one sample, the HTLV-I genome was undetectable, which may indicate that the integrated genome was present at less than 0.01 copies per 100 PBMC. Age- or sex-related variations in the distribution of individuals with different HTLV-I genome were rather limited. However, carriers with a high level of the HTLV-I genome were always more than 30 years old and were predominantly male (six of seven).     

Right bundle branch block without overt heart disease predicts higher risk of pacemaker implantation: The study of atomic-bomb survivors

Background

We investigated the clinical course of complete right bundle branch block (RBBB) or RBBB with axis deviation (AD) in terms of subsequent pacemaker implantation for high-degree atrioventricular (AV) block or sick sinus syndrome (SSS).

Methods and results

Among the 16,170 atomic-bomb survivors in our biennial health examination between July 1967 and December 2010, we detected 520 newly-acquired RBBB subjects with no organic heart disease, and selected 1038 age- (at RBBB diagnosis) and sex-matched subjects without RBBB to serve as comparison subjects. Multivariate Cox regression analysis was used to estimate the hazard ratios (HRs) for the risk of pacemaker implantation due to all causes, AV block or SSS between RBBB and comparison subjects and between RBBB subjects with and without AD. The risk of pacemaker implantation for RBBB was 4.79 (95% confidence interval [CI] 1.89–12.58; P = 0.001), 3.77 (95% CI, 1.09–13.07; P = 0.036), and 6.28 (95% CI, 1.24–31.73, P = 0.026) when implantation was for all causes, AV block and SSS, respectively. RBBB subjects with AD had a higher risk for all-cause pacemaker implantation than subjects without AD (HR, 3.03; 95% CI, 1.00–9.13, P = 0.049). RBBB subjects with AD were younger than subjects without AD at the time of RBBB diagnosis (59.4 ± 7.6 vs 74.4 ± 3.1 years old, P = 0.019), and their progression from diagnosis to pacemaker implantation took longer (15.1 ± 6.6 vs 6.4 ± 3.0 years, P = 0.032).

Conclusions

RBBB, especially with AD, progresses to AV block and SSS that requires pacemaker implantation; the mechanisms by which the conduction defect progresses differ among patients with and without AD.