Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized,double-blind,active-controlled,multicenter phase 3 trial

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are −19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and −11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.     

A case of transradial carotid stenting in a patient with total occlusion of distal abdominal aorta.

We report a case with severe carotid stenosis in which carotid stenting was performed via the radial artery due to total occlusion of distal abdominal aorta. The radial approach offers a potential alternative in cases in which the femoral approach is problematic.     

Control of alkaline reflux esophagitis after total gastrectomy by a percutaneous jejunostomy tube

Postoperative alkaline reflux esophagitis is a potentially devastating complication after total gastrectomy. The advent of the Roux-en-Y reconstruction has significantly decreased the incidence of this complication. However, when reflux esophagitis occurs, it is often refractory to medical treatment. Even though surgical revision of the Roux-en-Y anastomosis is the management option of choice, affected patients (especially those with advanced metastatic cancers) are often poor surgical candidates. We describe a novel treatment of refractory alkaline reflux esophagitis in a patient after radical total gastrectomy with Roux-en-Y reconstruction for advanced gastric carcinoma. Radiologic placement of a percutaneous jejunostomy tube into the proximal jejunal limb resulted in significant symptomatic relief by external diversion of the pancreaticobiliary drainage, and the procedure was associated with minimal discomfort. Nonsurgical pancreaticobiliary diversion should be considered in those patients with refractory alkaline reflux esophagitis that occurs after total gastrectomy.     

Prenatal diagnosis of anomalous origin of the right pulmonary artery from the ascending aorta

We report a case of anomalous origin of the right pulmonary artery from the ascending aorta that was diagnosed by fetal ultrasound at 21 weeks of gestation. The clue to the diagnosis was present in the three-vessel view, this being one of the views that we use for fetal cardiac screening. The anomaly was corrected surgically at 11 days of age. We discuss the importance of prenatal diagnosis in the management of this rare anomaly.     

Treatment of high-risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by co-infusion of T cell-depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched human leucocyte antigen haplotype

A 20-year-old woman with high-risk acute myelogenous leukaemia was transplanted with granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood CD34+ haematopoietic stem cells and bone-marrow-derived mesenchymal stem cells (MSC) from her human leucocyte antigen haplotype-mismatched father after myeloablative conditioning therapy. The patient engrafted rapidly and had no acute or chronic graft-versus-host disease. Since transplantation, the patient has shown an enduring trilineage haematological complete response without any evidence of leukaemia relapse at 31 months. We suggest that MSC can be used effectively for genetically haploidentical haematopoietic stem cell transplantation for acute leukaemia.     

Melatonin suppresses NO-induced apoptosis via induction of Bcl-2 expression in PGT-beta immortalized pineal cells

In the present study, we investigated whether melatonin would prevent nitric oxide (NO)-induced apoptotic death of PGT-beta immortalized pineal cells. To examine the protective effect of melatonin, cytotoxicity assay, DNA fragmentation analysis, caspase-3 activity assay, and Western blotting for caspase-3 and poly(ADP-ribose) polymerase (PARP) were performed. Treatment of cells with S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, was shown to induce apoptotic cell death in a dose-dependent manner, and pretreatment with melatonin (0.1 mm) attenuated the occurrence of NO-induced apoptotic cell death. DNA fragmentation in response to NO was also arrested by melatonin. Caspase-3 activity induced by NO was decreased with melatonin treatment. Furthermore, the active fragments of caspase-3 and PARP were almost completely absent following exposure to melatonin. To elucidate the protective mechanisms of action of melatonin, Western blot analyses for Bcl-2 expression and cytochrome c release were carried out. Pretreatment with melatonin (0.1 mm) induced the expression of Bcl-2 and suppressed the release of cytochrome c into the cytosol, thereby arresting NO-induced apoptotic cell death. These results suggest that the antiapoptotic effect of melatonin is associated with induction of Bcl-2 expression in PGT-beta cells, which in turn blocks caspase-3 activation and inhibits cytochrome c release into the cytosol.     

A case of limb-girdle muscular dystrophy with serum anti-nuclear antibody which led to a mistaken diagnosis of polymyositis

A 45-year-old woman had first been diagnosed with polymyositis because of the presence of focal necrosis, regeneration and inflammatory infiltration in the muscle fibers, and elevated creatinine phosphokinase levels. However, a pathological re-evaluation and family history led to the definite diagnosis of limb-girdle muscular dystrophy (MD). This case suggests that MD should be taken into consideration in the differential diagnosis of the inflammatory myopathies and genetic surveys including dystrophin molecule may be necessary if the condition manifests during or after adolescence, or when the family history is uninformative. In this case, the serum anti-nuclear antibody was positive, and it may represent the first time that ANA positivity has been found in limb-girdle MD.     

SLC11A1 gene polymorphisms in Korean patients with Behçet's disease

OBJECTIVE: To investigate the potential susceptibility to the solute carrier family 11 member 1 (SLC11A1) gene polymorphisms of Korean patients with Beh?et's disease (BD). METHODS: Ninety-nine patients with BD and 98 controls were recruited. Analyses of three polymorphisms of the SLC11A1 gene [the 5'-promoter (GT)n, D543N and A318V] were performed, either by denaturing high-performance liquid chromatography for D543N and A318V or by using automatic DNA sequencing for the (GT)n. The genotypes and alleles between patients with BD and the controls were compared using the chi2 test and Yate's correction test. RESULTS: No significant differences were found in the distribution of genotypes and alleles of the (GT)n polymorphism between BD patients and the controls. However, subjects with the allele 3 or the genotype allele 3/allele 3 of this polymorphism had a significantly lower risk of developing BD than those without this allele or genotype [allele: p = 0.029, pc = 0.039, odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.37-0.95; genotype: p = 0.036, pc = 0.048, OR = 0.54, 95% CI 0.31-0.96]. In addition, the distributions of genotypes and alleles of D543N were similar between BD patients and controls (p>0.05). In the case of A318V, all of the BD patients and controls had a wild-type genotype. CONCLUSION: The allele 3 and the genotype allele 3/allele 3 of the 5'-promoter (GT)n in the SLC11A1 gene may have a protective effect for the development of BD in the Korean population. Further studies in other populations are required to confirm our results.     

The local prevalence of COPD by post-bronchodilator GOLD criteria in Korea.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a disease characterised by not fully reversible airflow limitation. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee decided to diagnose COPD using post-bronchodilator spirometry values. We aimed to examine the prevalence and risk factors of COPD in Ansan, an industrialised city of Korea, by using the post-bronchodilator GOLD criteria. We then investigated the implications of brenchodilation on the prevalence of COPD. DESIGN: A total of 3642 participants in the Korean Health and Genome Study were interviewed about age, income, smoking status and respiratory symptoms and completed pulmonary function tests, including postbronchodilator spirometry. RESULTS: COPD prevalence by post-bronchodilator spirometry was 3.7% (134/3642), which was significantly different from that estimated using pre-bronchodilator criteria (7.7%, 282/3642). Exclusion of subjects with significant bronchodilator response (BDR) significantly lowered the prevalence of COPD to 3.3% (117/3572), compared with including subjects with post-bronchodilatory residual obstruction with significant BDR. Prevalence was associated with old age, smoking history, male sex and respiratory symptoms. CONCLUSION: COPD prevalence by post-bronchodilator GOLD criteria was 3.7%, which was much lower than that of pre-bronchodilator criteria. The bronchodilator reversibility test substantially affects estimations of COPD prevalence.