Endoscopic duodenal stent versus surgical gastrojejunostomy for gastric outlet obstruction in patients with advanced pancreatic cancer

Background

Malignant gastric outlet obstruction (GOO) often develops in patients with advanced pancreatic cancer (APC). It is not clear whether endoscopic duodenal stenting (DS) or surgical gastrojejunostomy (GJJ) is preferable as palliative treatment.

Right atrial thrombosis as a complication of arrhythmogenic right ventricular cardiomyopathy

A 65-year-old woman was admitted to our hospital due to palpitation. Electrocardiogram (ECG) showed ventricular tachycardia originating from the right ventricle, and transthoracic echocardiography revealed dilatations of the right atrium and ventricle. The diagnosis of arrhythmogenic right ventricular cardiomyopathy was made. Eleven months later, echocardiography revealed a solid thrombus (36x32 mm) attached to the free wall of the right atrium, and it was surgically resected. Four months after the operation, a solid thrombus (48x30 mm) appeared again at the same site despite anticoagulant treatment. The patient died of both left and right heart failure 33 months after the operation.     

Esophageal duplication cyst continuously extending into the peritoneal cavity on the proximal portion of the stomach

Although bronchogenic or esophageal duplication cysts are foregut-derived developmental anomalies most commonly encountered in the mediastinum and rarely in the abdomen, a cyst continuously extending into the abdomen via the esophageal hiatus has not been reported previously. We report a case of esophageal duplication cyst that occurred in the distal esophagus and extended continuously into the proximal portion of the stomach via the esophageal hiatus. A 62-year-old Japanese man was admitted to a local hospital complaining of dysphagia and upper abdominal pain. Abdominal ultrasound and CT scan revealed a cystic mass dorsal to the lateral segment of the liver that extended continuously into the mediastinum via the hiatus. The upper gastrointestinal series and endoscopic examination revealed extramural compression of the distal esophagus without mucosal lesions. Resection of the cystic lesion was performed by thoracotomy followed by laparotomy. The upper part of the cyst originated in the submucosal layer, extending into the muscularis propria of the distal esophagus. Histology of the resected specimen indicated that the cystic wall was composed of two smooth muscle layers and that the inner cystic wall was lined with pseudostratified columnar ciliated and/or squamous epithelium associated without cartilage or respiratory gland, indicating esophageal differentiation. These histological characteristics indicated that the cyst was an esophageal duplication cyst, rather than a bronchogenic cyst. This is the first case of a large esophageal duplication cyst of the distal esophagus continuously extending into the abdomen via the esophageal hiatus. The atypical location of this esophageal duplication cyst provides an insight into the pathogenesis of esophageal duplication cysts.     

Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder

BACKGROUND: Methamphetamine (MAP) is one of the most frequently used illegal substances in Japan, and family and twin studies have suggested that genetic factors contribute to psychostimulant dependence, including MAP dependence. Organic cation transporter 3 (OCT3) has been reported to be involved in the disposition of MAP as well as MAP-induced behavioral changes in animals. Moreover, SLC22A3 (which encodes OCT3) is a candidate gene for MAP dependence because it is located within a chromosomal region associated with substance dependence. METHODS: Using 96 healthy control subjects, linkage disequilibrium (LD) within the SLC22A3 was investigated, and 5 single-nucleotide polymorphisms (SNPs) were selected as haplotype tag SNPs to search for an association with MAP dependence. Single-marker analyses and haplotype analyses of these SNPs were performed in 213 subjects with MAP dependence and 443 healthy controls. RESULTS: SLC22A3 polymorphisms were not significantly associated with MAP dependence in any of the single-marker and haplotype analyses. When subjects with MAP dependence were divided into polysubstance and single-MAP users, genotype and allele frequency of SNP2 (p=0.024, p=0.011, respectively), allele frequency of SNP3 (p=0.037), and haplotypic frequencies for these 2 SNPs (p=0.0438) differed significantly between groups. CONCLUSIONS: These results suggest that polymorphisms of SLC22A3 are related to the development of polysubstance use in Japanese patients with MAP dependence.     

Developmental stage-specific biphasic roles of Wnt/beta-catenin signaling in cardiomyogenesis and hematopoiesis

Although Wingless (Wg)/Wnt signaling has been implicated in heart development of multiple organisms, conflicting results have been reported regarding the role of Wnt/beta-catenin pathway in cardiac myogenesis: Wg/armadillo signaling promotes heart development in Drosophila, whereas activation of Wnt/beta-catenin signaling inhibits heart formation in avians and amphibians. Using an in vitro system of mouse ES cell differentiation into cardiomyocytes, we show here that Wnt/beta-catenin signaling exhibits developmental stage-specific, biphasic, and antagonistic effects on cardiomyogenesis and hematopoiesis/vasculogenesis. Activation of the Wnt/beta-catenin pathway in the early phase during embryoid body (EB) formation enhances ES cell differentiation into cardiomyocytes while suppressing the differentiation into hematopoietic and vascular cell lineages. In contrast, activation of Wnt/beta-catenin signaling in the late phase after EB formation inhibits cardiomyocyte differentiation and enhances the expression of hematopoietic/vascular marker genes through suppression of bone morphogenetic protein signaling. Thus, Wnt/beta-catenin signaling exhibits biphasic and antagonistic effects on cardiomyogenesis and hematopoiesis/vasculogenesis, depending on the stage of development.     

TRPC4 expression determines sensitivity of the platelet-type capacitative Ca2+ entry channel to intracellular alkalosis

The present study was designed to analyze the molecular basis of the intracellular pH-dependent capacitative Ca2+ entry (CCE) of human platelets and megakaryocytic cells, specifically to test the hypothesis that members of the classical transient receptor potential (TRPC) protein family are involved in the CCE pathway that is promoted by intracellular alkalosis. Human platelets as well as the tested megakaryocytic cell lines (CMK cells, MEG-01 cells) and HEK293 cells displayed thapsigargin-induced CCE and responded to monensin with comparable elevation in intracellular pH. Promotion of CCE by monensin-induced intracellular alkalosis, however, was profound in mature platelets, moderate in CMK cells and lacking in MEG-01 cells as well as in HEK293 cells. Analysis of the TRPC expression pattern by immunoblotting revealed that mature platelets and CMK cells express TRPC4 along with TRPC1 and TRPC3, while TRPC4 is lacking in MEG-01 cells. HEK293 cells displayed CCE characteristics as well as lack of TRPC4 expression similar to MEG-01 cells. Over-expression of TRPC4 in HEK293 cells was found to result in a gain of pH-sensitivity of CCE with clearly detectable promotion of CCE in response to monensin. These results suggest that platelet CCE channel complexes contain TRPC4 as a molecular component that determines sensitivity of CCE to intracellular alkalosis.     

Is admission hyperglycaemia in non-diabetic patients with acute myocardial infarction a surrogate for previously undiagnosed abnormal glucose tolerance?

AIMS: To investigate whether admission hyperglycaemia in non-diabetic patients with acute myocardial infarction (AMI) is a surrogate for previously undiagnosed abnormal glucose tolerance. METHODS AND RESULTS: Two hundred non-diabetic patients with AMI were divided into three groups: 81 patients with admission glucose < 7.8 mmol/L (group 1), 83 patients with admission glucose > or = 7.8 mmol/L and < 11.1 mmol/L (group 2), and 36 patients with admission glucose > or = 11.1 mmol/L (group 3). Abnormal glucose tolerance, diabetes, or impaired glucose tolerance (IGT) was diagnosed by oral glucose tolerance test (OGTT). OGTT identified diabetes in 53 patients (27%) and IGT in 78 patients (39%). When the fasting glucose criteria were applied, however, only 14 patients (7%) were diagnosed as having diabetes. The prevalence of abnormal glucose tolerance was similar among the three groups: 67% in group 1, 63% in group 2, and 69% in group 3 (P = 0.74). The relation of fasting glucose (r2 = 0.50, P < 0.001) and HbA1c (r2 = 0.34, P < 0.001) to 2-h post-load glucose was significant, but the relation of admission glucose to 2-h post-load glucose was not significant (r2 = 0.02, P = 0.08). Multivariable analysis showed that fasting glucose and HbA1c were independent predictors of abnormal glucose tolerance, but admission glucose was not. CONCLUSION: Admission hyperglycaemia in non-diabetic patients with AMI does not represent previously undiagnosed abnormal glucose tolerance. Fasting glucose and HbA1c, rather than admission glucose, may be useful to predict abnormal glucose tolerance. However, these parameters lacked sensitivity. OGTT should be considered in all non-diabetic patients with AMI.     

Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores

The replication timing of some genes is developmentally regulated, but the significance of replication timing to cellular differentiation has been difficult to substantiate. Studies have largely been restricted to the comparison of a few genes in established cell lines derived from different tissues, and most of these genes do not change replication timing. Hence, it has not been possible to predict how many or what types of genes might be subject to such control. Here, we have evaluated the replication timing of 54 tissue-specific genes in mouse embryonic stem cells before and after differentiation to neural precursors. Strikingly, genes residing within isochores rich in GC and poor in long interspersed nuclear elements (LINEs) did not change their replication timing, whereas half of genes within isochores rich in AT and long interspersed nuclear elements displayed programmed changes in replication timing that accompanied changes in gene expression. Our results provide direct evidence that differentiation-induced autosomal replication-timing changes are a significant part of mammalian development, provide a means to predict genes subject to such regulation, and suggest that replication timing may be more related to the evolution of metazoan genomes than to gene function or expression pattern.     

Acute myocardial infarction associated with myocardial bridging in a young adult

A 28-year-old man was admitted because of chest pain. Emergency coronary angiography showed a massive thrombus in the proximal segment and another occlusive thrombus in the distal segment of the left anterior descending artery. He was treated with thrombolytic therapy. Repeat coronary angiography showed disappearance of the thrombi in the proximal and distal segments and obvious myocardial bridging in the mid segment. Intravascular ultrasound revealed an atherosclerotic plaque in the segment immediately proximal to the myocardial bridging, but did not reveal any plaque within or distal to the site. He was discharged 12 days later.     

Relationships of body mass index with blood pressure and serum cholesterol concentrations at different ages

BACKGROUND AND AIMS: Only limited information has been available on the effects of age on the relationship between obesity and other atherosclerotic risk factors, such as blood pressure and serum lipids. The purpose of this study was to investigate the effects of age on the relationships of obesity with blood pressure and serum cholesterol concentrations. METHODS: A community-based cross-sectional study was performed on 157,902 workers in Yamagata, Japan. Blood pressure and serum total and HDL cholesterol concentrations were measured, and body mass index (BMI) and atherogenic index were calculated. The correlations of BMI with blood pressure, serum cholesterol concentrations and atherogenic index in different age groups were compared. RESULTS: BMI showed significant positive correlations with systolic and diastolic blood pressures, serum total cholesterol level and atherogenic index, and showed a significant negative correlation with serum HDL cholesterol level. The relationships of BMI with systolic and diastolic blood pressures became weaker with advancing age in both men and women after 30 and 40 years of age, respectively. The relationships of BMI with serum total cholesterol level and atherogenic index also became weaker with advancing age after 30 years of age in men and after 40 years of age in women. There was no age-dependent tendency in the relationship between BMI and HDL cholesterol, however. The above age-dependent changes were more prominent in men than in women. CONCLUSION: The relationships of obesity with blood pressure, serum total cholesterol level and atherogenic index in the elderly are much weaker than in the young.