Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH.
Animals ; DNA Methylation/drug effects ; Drug Discovery/methods ; *Epigenesis, Genetic/drug effects ; Genetic Therapy/methods ; Humans ; Hypertension, Pulmonary/*genetics/therapy ; MicroRNAs/*genetics

PURPOSE: Currently, holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP) are the standard surgical procedures used to treat benign prostatic hyperplasia (BPH). Several recent studies have demonstrated that the surgical management of BPH in patients with detrusor underactivity (DU) can effectively improve voiding symptoms, but comparative data on the efficacy of HoLEP and TURP are insufficient. Therefore, we compared the short-term surgical outcomes of HoLEP and TURP in patients with DU. METHODS: From January 2010 to May 2015, 352 patients underwent HoLEP or TURP in procedures performed by a single surgeon. Of these patients, 56 patients with both BPH and DU were enrolled in this study (HoLEP, n=24; TURP, n=32). Surgical outcomes were retrospectively compared between the 2 groups. DU was defined as a detrusor pressure at maximal flow rate of <40 cm H(2)O as measured by a pressure flow study. RESULTS: The preoperative characteristics of patients and the presence of comorbidities were comparable between the 2 groups. The TURP group showed a significantly shorter operative time than the HoLEP group (P=0.033). The weight of the resected prostate was greater in the HoLEP group, and postoperative voiding parameters, including peak flow rate and postvoid residual urine volume were significantly better in the HoLEP group than in the TURP group. CONCLUSIONS: HoLEP can be effectively and safely performed in patients with DU and can be expected to have better surgical outcomes than TURP in terms of the improvement in lower urinary tract symptoms.
Comorbidity ; Holmium* ; Humans ; Lasers, Solid-State* ; Lower Urinary Tract Symptoms ; Operative Time ; Prostate* ; Prostatic Hyperplasia ; Retrospective Studies ; Transurethral Resection of Prostate

BACKGROUND: Few studies have reported on breakthrough urinary tract infection (UTI) associated with the susceptibility of index UTI to prophylactic antibiotics in children with primary vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). We assessed the impact of the susceptibility of index UTI to prophylactic antibiotics in breakthrough UTIs in children with primary VUR receiving CAP. METHODS: We retrospectively reviewed the medical records of 81 children with primary VUR who were diagnosed after febrile or symptomatic UTI and subsequently received trimethoprim-sulfamethoxazole (TMP-SMX) as CAP between January 2010 and December 2013. We allocated children to a susceptible group or a resistant group based on the susceptibility of index UTI to TMP-SMX. We evaluated patient demographics and clinical outcomes after CAP according to the susceptibility of index UTI to TMP-SMX. Multivariate analysis was used to identify the predictive factors for breakthrough UTI. RESULTS: Of the 81 children, 42 were classified into the susceptible group and 39 into the resistant group. The proportion of breakthrough UTI was 31.0% (13/42) in the susceptible group and 53.8% (21/39) in the resistant group (P = 0.037). Progression of renal scarring was observed in 0% of children in the susceptible group and 15% in the resistant group (P = 0.053). Multivariate analysis showed that TMP-SMX resistance and initial renal scarring were significant predictors of breakthrough UTI. CONCLUSION: Susceptibility of index UTI to prophylactic antibiotics is a risk factor of breakthrough UTI and is associated with poor clinical outcomes in children with primary VUR receiving CAP.
Anti-Bacterial Agents ; Antibiotic Prophylaxis ; Child ; Cicatrix ; Demography ; Humans ; Medical Records ; Multivariate Analysis ; Retrospective Studies ; Risk Factors ; Trimethoprim, Sulfamethoxazole Drug Combination ; Urinary Tract Infections ; Urinary Tract ; Vesico-Ureteral Reflux

BACKGROUND/AIMS: According to recent prevalence of hepatitis A virus (HAV) infection, acute liver failure (ALF) due to HAV infection is observed frequently in parallel. The aim of this study was to elucidate the clinical, laboratory, and pathologic features of patients who have undergone emergency liver transplantation (LT) due to fulminant HAV infection. METHODS: Clinical, laboratory, and pathologic data of 11 transplant recipients with anti-HAV IgM-positive ALF between December 2007 and May 2009 were analyzed, and compared with data of 10 recipients who underwent LT for the management of ALF due to other causes. RESULTS: The median age of the patients with HAV-related ALF was 34 years (range: 15-43 years). The levels of hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were higher and the level of bilirubin was lower in the HAV-related ALF group than in the other group (P=0.005, 0.001, 0.001, 0.010, and 0.003, respectively). The time from the onset of initial symptoms to the development of encephalopathy was shorter in the HAV-related ALF group than in the other group (median 5 days, range: 4-13 days; P<0.001). In patients with HAV-related ALF, laboratory findings and clinical prognostic parameters including the Acute Liver Failure Study Group prognostic index, King's College criteria, and model for endstage liver disease (MELD) and Child-Pugh scores were not associated with the grade of hepatic encephalopathy or time of progression to encephalopathy. CONCLUSIONS: The results of this study indicate that the clinical condition of patients with HAV-related ALF requiring emergency LT aggravates rapidly. Prognostic parameters are not sufficient for discriminating transplant candidates in patients with fulminant hepatitis A.
Adolescent ; Adult ; Aged ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Bilirubin/blood ; Creatine/blood ; Emergencies ; Female ; Hemoglobins/analysis ; Hepatitis A/*complications ; Hepatitis A Antibodies/immunology/metabolism ; Humans ; Immunoglobulin M/metabolism ; Liver Failure, Acute/complications/*diagnosis/therapy ; *Liver Transplantation ; Male ; Middle Aged ; Prognosis ; Severity of Illness Index ; Time Factors

BACKGROUND/AIMS: The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH. METHODS: One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8+/-13.5 years, mean+/-SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea. RESULTS: According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis > or =2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH. CONCLUSIONS: Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.
Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase/blood ; Asian Continental Ancestry Group ; Aspartate Aminotransferases/blood ; Biological Markers/blood ; Fatty Liver/classification/metabolism/*pathology ; Female ; Ferritins/blood ; Fibrosis/complications ; Humans ; Keratin-18/analysis ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Republic of Korea ; Severity of Illness Index ; Young Adult

BACKGROUND/AIMS: The aims of this study were to determine subgoups of functional dyspesia and to evaluate the short-term effect of cisapride in patients with functional dyspepsia in Korea. METHODS: 1025 patients, with a mean age of 42.6 years, with symptoms of functional dyspepsia, were recruited consecutively and upper gastrointestinal symptoms were investigated by interview in 41 hospitals in Korea. In an open, multicenter trial, 1025 patients received Smg of cisapride three times a day (TID) for at least .2 weeks for the treatment of symptoms of functional dyspepsia. When necessary, the dose of cisapride was increased to 10mg TID and the duration of therapy was extended to 4 weeks. RESULTS: The most frequently reported symptoms of functional dyspepsia were epigastric discomfort or fullness (85%), bloating (70%), belching (53%), early satiety (52%) and epigastric pain (46%) retrospectively. Subgroups of functional dyspepsia were as follows; dysmotility-like 73.5%, ulcer-like 39.7%, reflux-like 13.0%, and unspecified dyspepsia 14.0%. However, 33.2% of subjects with functional dyspepsia could be classified into more than one subgroup. Upper gastrointestinal symptoms were decreased to average 50.3% (range; 42.2 to 59.2%) after 2 weeks of cisapride treatment and to 25% (19.2 to 29.9%) after 4 weeks. cisapride therapy resulted in good or excellent improvement in 59.0% of the patients after two weeks, in 75% of patients after 4 weeks. Adverse events were occurred in 52 patients (5.8% of all patients), most commonly, loose stools or diarrhea (3.5%), abdominal pain (1.1%), and dizziness (0.3%). The majority of adverse events was mild and transient in nature and led to premature discontinuation of treatment in 4 patients. CONCLUSIONS: Although the majorities of patients with functional dyspepsia have dysmotility like symptoms in Korea, there is such overlap among the dyspepsia subgroups. Most patients responded well to a short therapeutic trial with cisapride without significant side effects.
Abdominal Pain ; Cisapride* ; Diarrhea ; Dizziness ; Dyspepsia* ; Eructation ; Humans ; Korea* ; Retrospective Studies