Antibiotics resistance rate of Helicobacter pylori in Bhutan

AIM:To survey the antibiotic resistance pattern of Helicobacter pylori(H.pylori)strains isolated from Bhutanese population.METHODS:We isolated 111 H.pylori strains from the gastric mucosa of H.pylori-infected patients in Bhutan in 2010.The Epsilometer test was used to determine the minimum inhibitory concentrations(MICs)of amoxicillin(AMX),clarithromycin(CLR),metronidazole(MNZ),levofloxacin(LVX),ciprofloxacin(CIP),and tetracycline(TET).RESULTS:Nineteen of the isolated H.pylori strains were susceptible to all antibiotics tested.The isolated strains showed the highest rate of antibiotic resistance to MNZ(92/111,82.9%).Among the 92 MNZresistant strains,74 strains(80.4%)showed high-level resistance(MIC≥256 g/mL).Three strains were resistance to LVX(2.7%).These strains were also resistance to CIP.None of the strains showed resistance to CLR,AMX and TET.CONCLUSION:CLR-based triple therapy is a more effective treatment approach over MNZ-based triple therapy for H.pylori infection in Bhutan.     

Clinical usefulness of repeated pancreatic juice cytology via endoscopic naso-pancreatic drainage tube in patients with pancreatic cancer

Background

Cytological examination of pancreatic juice obtained during endoscopic retrograde cholangiopancreatography (ERCP) is well established, but its sensitivity for pancreatic cancer has not been satisfactory. The aim of this study was to evaluate the usefulness of repeated pancreatic juice cytology (PJC) via the endoscopic naso-pancreatic drainage (ENPD) tube in patients with pancreatic cancer compared with conventional PJC.

Methods

We retrospectively investigated 139 patients with pancreatic disease. Between April 2004 and November 2007, conventional PJC was performed in 56 patients with pancreatic cancer and 23 with benign pancreatic stricture. Between January 2008 and November 2010, ENPD was used in 40 patients with pancreatic cancer and 20 with benign pancreatic stricture. The ENPD tube was placed into the main pancreatic duct for up to 3 days, and cytological samples of pancreatic juice were collected up to 6 times in total.

Results

Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the ENPD method for pancreatic cancer were 80, 100, 100, 71, and 87 %, respectively, revealing significantly higher sensitivity than the conventional method (p = 0.0001). Sensitivities according to tumor location and size were 90 % (19/21), 69 % (9/13), and 67 % (4/6) in the head, body, and tail of the pancreas, 88 % (7/8), 79 % (19/24), and 75 % (6/8) in tumors with a diameter less than 20 mm including carcinoma in situ, 21–40, and greater than 41 mm, respectively.

Conclusions

The ENPD method was found to have high diagnostic yield, especially for tumors less than 20 mm or located in the pancreatic head, and might be useful for the diagnosis of early-stage pancreatic cancer.     

Effects of Transdermal Tulobuterol in Pediatric Asthma Patients on Long-Term Leukotriene Receptor Antagonist Therapy: Results of a Randomized,Open-Label,Multicenter Clinical Trial in Japanese Children Aged 4–12 Years

BackgroundFew studies have examined the efficacy or safety of a transdermal β2 agonist as add-on medicationto long-term leukotriene receptor antagonist (LTRA) therapy in pediatric asthma patients.MethodsIn this randomized, open-label, multicenter clinical trial, children aged 4-12 years on long-term LTRA therapy were treated with tulobuterol patches (1-2 mg daily) or oral sustained-release theophylline (usual dose, 4-5 mg_kg daily) for 4 weeks. LTRAs were continued throughout the trial. Outcomes included volume peak expiratory flow (% PEF), fractional exhaled nitric oxide (FeNO), clinical symptoms and adverse events.ResultsThirty-three and 31 patients were treated with tulobuterol patches and theophylline, respectively. % PEF measured in the morning and before bedtime was significantly higher at all times in the treatment period compared with baseline in the tulobuterol patch group (p < 0.001), and was significantly higher in the tulobuterol patch group compared with the theophylline group. FeNO was similar and unchanged from baseline in both groups. There were no drug-related adverse events in either group.ConclusionsThese results suggest that short-term use of a transdermal β2 agonist is an effective therapy for pediatric asthma without inducing airway inflammation in children on long-term LTRA therapy.     

Genetic reconstitution of tumorigenesis in primary intestinal cells

Animal models for human colorectal cancer recapitulate multistep carcinogenesis that is typically initiated by activation of the Wnt pathway. Although potential roles of both genetic and environmental modifiers have been extensively investigated in vivo, it remains elusive whether epithelial cells definitely require interaction with stromal cells or microflora for tumor development. Here we show that tumor development could be simply induced independently of intestinal microenvironment, even with WT murine primary intestinal cells alone. We developed an efficient method for lentiviral transduction of intestinal organoids in 3D culture. Despite seemingly antiproliferative effects by knockdown of adenomatous polyposis coli (APC), we managed to reproducibly induce APC-inactivated intestinal organoids. As predicted, these organoids were constitutively active in the Wnt signaling pathway and proved tumorigenic when injected into nude mice, yielding highly proliferative tubular epithelial glands accompanied by prominent stromal tissue. Consistent with cellular transformation, tumor-derived epithelial cells acquired sphere formation potential, gave rise to secondary tumors on retransplantation, and highly expressed cancer stem cell markers. Inactivation of p53 or phosphatase and tensin homolog deleted from chromosome 10, or activation of Kras, promoted tumor development only in the context of APC suppression, consistent with earlier genetic studies. These findings clearly indicated that genetic cooperation for intestinal tumorigenesis could be essentially recapitulated in intestinal organoids without generating gene-modified mice. Taken together, this in vitro model for colon cancer described herein could potentially provide unique opportunities for carcinogenesis studies by serving as a substitute or complement to the currently standard approaches.     

Cognitive dysfunction: An emerging concept of a new diabetic complication in the elderly

The incidence of type 2 diabetes mellitus (T2DM) has risen, and this trend is likely to continue. Recent advances suggest that T2DM is a risk factor for cognitive decline. We are now encountering novel complications of T2DM, namely cognitive dysfunction and dementia. Although the treatment strategy for diabetic patients with neurocognitive dysfunction has received a great deal of attention, the appropriate level of glycemic control for the prevention of the development and/or progression of cognitive decline in elderly diabetic patients remains to be elucidated. Another issue in diabetic treatment in patients with cognitive dysfunction is the selection of medicines. The best choice and combination of antidiabetic medications for the preservation of cognition should also be studied. Ample studies suggest that exercise helps to preserve cognitive function, although existing evidence does not necessarily indicate its effectiveness exclusively in diabetic patients. Exercise is a helpful non‐pharmacological therapy. Considering the progressive aging of the worldwide population, more research to investigate the best way to manage this population is important. Geriatr Gerontol Int 2012; ••: ••–•• .     

Marked improvement of platelet transfusion refractoriness after bortezomib therapy in multiple myeloma

We report a patient with refractory multiple myeloma (MM) who developed platelet transfusion refractoriness (PTR). A 61-year-old woman was diagnosed with MM in July 2003. She underwent high-dose chemotherapy followed by autologous stem cell transplantation, and achieved a very good partial response. However, she relapsed in June 2006, and was referred to our hospital in October of the same year. Laboratory examinations showed pancytopenia and increased plasma cells in the peripheral blood. Platelet transfusions from random donors became ineffective, and anti-HLA class I antibody (83.8% positive) was detected in the serum by flow cytometry assay (Flow PRA). Therefore, she was considered to have developed PTR due to anti-HLA class I antibody caused by the previous blood transfusions. She was transfused with HLA-matched platelets, and then treated with bortezomib plus dexamethasone (BD) for refractory MM. The serum IgG level decreased from 7,451 to 1,735 mg/dL, and HLA class I antibody was markedly decreased to 1.9%. In addition, platelet transfusion from random donors showed clinical effects after BD therapy. This case suggests that bortezomib might be effective in different types of immune disease by inhibiting allo-reactive antibody.     

Zinc deficiency delays gastric ulcer healing in rats

Zinc is an important element in wound healing. Zinc compounds hasten the healing of gastric ulcers, by an unknown mechanism(s). We studied the effect of the induction of zinc deficiency on gastric ulcer healing. Rats were given a control or zinc-deficient diet for six weeks and then subjected to the induction of acetic acid-induced chronic gastric ulcers. Four days later, zinc-deficient rats were divided into two groups. In the first group, the zinc-deficient diet was continued. In the second group, the diet was changed to the control diet. Zinc-deficient rats had a mean serum zinc concentration approximately 70% of that in controls. Zinc deficiency did not affect the formation of gastric ulcers; however, it reduced cell proliferation by day 4 and delayed ulcer healing. Zinc supplementation brought zinc to control levels within a week, but failed to reverse the delay in ulcer healing. We conclude that zinc is crucial for healing of gastric ulcers, especially at the early stage.An abstract of this study was presented at the Second Osaka International Symposium on Gastroenterology held in Osaka, Japan, on November 22–23, 1993.     

Glycosphingolipids in human pancreatic juice

Summary Glycosphingolipids in human pancreatic juice were isolated and purified by DEAE and silica gel column chromatographs, and further by HPLC on silica gel and reversed-phase columns. The structures of the glycosphingolipids were determined to be glucosylceramides and lactosylceramides by means of fast atom bombardment mass spectrometry,¹H-NMR spectroscopy, and component analysis involving GLC-mass spectrometry. The ceramide portions of the glucosylceramides consist of palmitic, tetracosanoic, and α-hydroxy tetracosanoic fatty acids, and d18:1 and t18:0 sphingosines. The ceramide portions of the lactosylceramides consist of palmitic, tetracosanoic, tetracosenoic, and tetracosadienoic fatty acids, and d18:1 sphingosine. The fatty acid compositions are different from the free fatty acid compositions of serum and pancreatic juice. The predominance of saturated, unsaturated, and hydroxy tetracosanoic fatty acids is quite unique, and the possibility that these glycosphingolipids may play a specific role in pancreatic juice deserves consideration. These glycosphingolipids were documented to be major components of the pancreatic juice from 15 patients with a variety of pancreatic diseases.     

Pulmonary alveolar proteinosis in a patient with Behcet's disease

Secondary pulmonary alveolar proteinosis (PAP) has been described in several clinical settings that can be grouped into three main categories: infections of the lung; haematological malignancies and other conditions that alter the patient's immune status; and exposure to inhaled chemicals and minerals. Recent studies reported that anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody was present in the serum of patients with idiopathic PAP but not in patients with secondary PAP or in normal subjects. The present report describes the interesting case of a patient with Behcet's disease and PAP. The absence of anti-GM-CSF antibodies in this patient suggested a diagnosis of secondary PAP.     

Identification of tumor-initiating cells in a highly aggressive brain tumor using promoter activity of nucleostemin

Controversy remains over whether the cancer stem cell (CSC) theory applies to all tumors. To determine whether cells within a highly aggressive solid tumor are stochastically or hierarchically organized, we combined a reporter system where the nucleostemin (NS) promoter drives GFP expression (termed NS-GFP) with a mouse brain tumor model induced by retroviral Ras expression on a p16^Ink4a/p19^Arf-deficient background. The NS-GFP system allowed us to monitor the differentiation process of normal neural stem/precursor cells by analyzing GFP fluorescence intensity. In tumor-bearing mice, despite the very high frequency of tumorigenic cells, we successfully identified the NS-GFP⁺ cells as tumor-initiating cells (T-ICs). The clonal studies conclusively established that phenotypical heterogeneity can exist among the cells comprising a genetically homogeneous tumor, suggesting that this aggressive brain tumor follows the CSC model. Detailed analyses of the NS-GFP⁺ brain tumor cells revealed that T-ICs showed activation of the receptor tyrosine kinase c-Met, which functions in tumor invasiveness. Thus, the NS-GFP system provides a powerful tool to elucidate stem cell biology in normal and malignant tissues.