PURPOSE: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. MATERIALS AND METHODS: Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. RESULTS: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). CONCLUSIONS: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.
Ascites ; Biomarkers ; Carcinoembryonic Antigen ; Carcinoma ; Cohort Studies ; Diagnosis ; Down-Regulation ; Exosomes ; Humans ; Liver ; MicroRNAs ; Prognosis ; RNA ; Stomach Neoplasms

BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSIONS: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.
Cell Transplantation ; Cytogenetics ; Humans ; Leukemia, Myeloid, Acute ; Multivariate Analysis ; Myelodysplastic Syndromes* ; Retrospective Studies ; Transplants

Butylated hydroxyanisole (BHA) is a synthetic phenolic compound consisting of a mixture of two isomeric organic compounds: 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole. We examined the effect of BHA against hydrogen peroxide (H2O2)-induced apoptosis in primary cultured mouse hepatocytes. Cell viability was significantly decreased by H2O2 in a dose-dependent manner. Additionally, H2O2 treatment increased Bax, decreased Bcl-2, and promoted PARP-1 cleavage in a dose-dependent manner. Pretreatment with BHA before exposure to H2O2 significantly attenuated the H2O2-induced decrease of cell viability. H2O2 exposure resulted in an increase of intracellular reactive oxygen species (ROS) generation that was significantly inhibited by pretreatment with BHA or N-acetyl-cysteine (NAC, an ROS scavenger). H2O2-induced decrease of cell viability was also attenuated by pretreatment with BHA and NAC. Furthermore, H2O2-induced increase of Bax, decrease of Bcl-2, and PARP-1 cleavage was also inhibited by BHA. Taken together, results of this investigation demonstrated that BHA protects primary cultured mouse hepatocytes against H2O2-induced apoptosis by inhibiting ROS generation.
Animals ; Apoptosis/*drug effects ; Butylated Hydroxyanisole/chemistry/*pharmacology ; Cell Survival/drug effects ; Cells, Cultured ; Hepatocytes/*drug effects ; Hydrogen Peroxide/*toxicity ; Male ; Mice ; Mice, Inbred ICR ; Molecular Structure

BACKGROUND: The number of patients diagnosed with hereditary hemolytic anemia (HHA) has increased since the advent of novel diagnostic techniques that accurately identify this disorder. Here, we report data from a survey on the prevalence and characteristics of patients diagnosed with HHA in Korea from 2007 to 2011. METHODS: Information on patients diagnosed with HHA in Korea and their clinical and laboratory results were collected using a survey questionnaire. Globin gene and red blood cell (RBC) enzyme analyses were performed. In addition, we analyzed data collected by pediatricians. RESULTS: In total, 195 cases of HHA were identified. Etiologies identified for HHA were RBC membranopathies, hemoglobinopathies, and RBC enzymopathies, which accounted for 127 (64%), 39 (19.9%), and 26 (13.3%) cases, respectively. Of the 39 patients with hemoglobinopathies, 26 were confirmed by globin gene analysis, including 20 patients with beta-thalassemia minor, 5 patients with alpha-thalassemia minor, and 1 patient with unstable hemoglobin disease. CONCLUSION: The number of patients diagnosed with hemoglobinopathies and RBC enzymopathies has increased considerably since the previous survey on HHA in Korea, dated from 1997 to 2006. This is likely the result of improved diagnostic techniques. Nevertheless, there is still a need for more sensitive diagnostic tests utilizing flow cytometry and for better standardization of test results to improve the accuracy of diagnosis of RBC membranopathies in Korea. Additionally, more accurate assays for the identification of RBC enzymopathies are warranted.
alpha-Thalassemia ; Anemia, Hemolytic, Congenital ; beta-Thalassemia ; Diagnostic Tests, Routine ; Erythrocytes ; Flow Cytometry ; Globins ; Hematology ; Hemoglobinopathies ; Hemoglobins ; Humans ; Korea ; Prevalence ; Spherocytosis, Hereditary ; Thalassemia ; Surveys and Questionnaires

Fever of unknown origin (FUO) is caused by infections (30-40%), neoplasms (20-30%), collagen vascular diseases (10-20%), and numerous miscellaneous diseases (15-20%). The literatures also reveal that 5-15% of FUO cases defy diagnosis, despite extensive studies. Diagnostic advances continuously modify the spectrum of FUO-causing diseases. Modern imaging techniques (e.g., ultrasound, CT scan, MRI) enable early detection of abscesses and solid tumors that used to be difficult to diagnose. But the correct diagnosis can be delayed because the tumor, such as rare hematologic malignancy, is difficult to be detected by various imaging studies. Intravascular lymphomatosis (IVL) is a rare form of non-Hodgkin's lymphoma and generally fatal disease characterized by extensive proliferation of neoplastic mononuclear cells within the lumina of blood vessels. The prognosis is usually extremely poor, with rapid death despite chemotherapy. The diagnosis is most frequently made after biopsy of skin or brain but is often established post mortem. Most patients with IVL present with FUO and nonspecific cutaneous and neurologic manifestations. Peripheral nerve system or pulmonary involvements are not common as initial menifestations. We report a case of intravascular lymphomatosis, presenting as FUO with peripheral polyneuropathy. We made early diagnosis of IVL by video-assisted thoracoscopic lung biopsy. She is improving with good performance after the 4th cycle of chemotherapy till now.
Abscess ; Biopsy ; Blood Vessels ; Brain ; Collagen ; Diagnosis ; Drug Therapy ; Early Diagnosis ; Fever of Unknown Origin* ; Fever* ; Hematologic Neoplasms ; Humans ; Lung ; Lymphoma ; Lymphoma, Non-Hodgkin ; Neurologic Manifestations ; Peripheral Nerves ; Polyneuropathies* ; Prognosis ; Skin ; Tomography, X-Ray Computed ; Ultrasonography ; Vascular Diseases

Fever of unknown origin (FUO) is caused by infections (30-40%), neoplasms (20-30%), collagen vascular diseases (10-20%), and numerous miscellaneous diseases (15-20%). The literatures also reveal that 5-15% of FUO cases defy diagnosis, despite extensive studies. Diagnostic advances continuously modify the spectrum of FUO-causing diseases. Modern imaging techniques (e.g., ultrasound, CT scan, MRI) enable early detection of abscesses and solid tumors that used to be difficult to diagnose. But the correct diagnosis can be delayed because the tumor, such as rare hematologic malignancy, is difficult to be detected by various imaging studies. Intravascular lymphomatosis (IVL) is a rare form of non-Hodgkin's lymphoma and generally fatal disease characterized by extensive proliferation of neoplastic mononuclear cells within the lumina of blood vessels. The prognosis is usually extremely poor, with rapid death despite chemotherapy. The diagnosis is most frequently made after biopsy of skin or brain but is often established post mortem. Most patients with IVL present with FUO and nonspecific cutaneous and neurologic manifestations. Peripheral nerve system or pulmonary involvements are not common as initial menifestations. We report a case of intravascular lymphomatosis, presenting as FUO with peripheral polyneuropathy. We made early diagnosis of IVL by video-assisted thoracoscopic lung biopsy. She is improving with good performance after the 4th cycle of chemotherapy till now.
Abscess ; Biopsy ; Blood Vessels ; Brain ; Collagen ; Diagnosis ; Drug Therapy ; Early Diagnosis ; Fever of Unknown Origin* ; Fever* ; Hematologic Neoplasms ; Humans ; Lung ; Lymphoma ; Lymphoma, Non-Hodgkin ; Neurologic Manifestations ; Peripheral Nerves ; Polyneuropathies* ; Prognosis ; Skin ; Tomography, X-Ray Computed ; Ultrasonography ; Vascular Diseases

The aim of this cross-over study was to investigate whether albumin infusion before furosemide administration could potentiate the diuretic action of furosemide. Seven patients with nephrotic syndrome were given the following infusions in random order on two separate days: 1) a sham solution followed by 160 mg of furosemide, 2) 100 ml of 20% human albumin followed by 160 mg of furosemide. Urine and serum furosemide concentrations were measured by high-performance liquid chromatography. The increment of urine volume was greater in albumin preinfusion than in furosemide alone. However, the increments of sodium and chloride excretions between furosemide alone and albumin preinfusion were not different. No significant differences in the pharmacokinetic parameters between the two treatments were observed: area under the concentration-time curve (AUC: 12.7+/-2.2 vs 15.1+/-4.4 g/ml hr), total plasma clearance (253+/-41 vs 256+/-54 ml/min), volume of distribution (341+/-34 vs 494+/-153 ml/kg), elimination half life (4.0+/-1.1 vs 4.6+/-0.8 hr), and urine furosemide excretion of the administered amount (16.5+/-7.3 vs 7.5+/-1.6%). In conclusion, these data show that albumin preinfusion potentiated diuresis, but not natriuresis, of furosemide without any change in the pharmacokinetics of the agent in patients with nephrotic syndrome.
Adolescence ; Adult ; Aged ; Albumins/*pharmacology ; Cross-Over Studies ; Diuretics/*pharmacology ; Drug Synergism ; Female ; Furosemide/*pharmacology ; Human ; Male ; Middle Age ; Nephrotic Syndrome/*drug therapy/metabolism ; Serum Albumin/analysis

PURPOSE: The purpose of this study was to establish, using computed tomography, the normal thickness of thepericardium in adults. MATERIALS AND METHODS: CT scans of 50 patients, including sections through the level of theheart, were reviewed. Patients were excluded if there were any suspicions of pericardial abnormality such asinfectious or neoplastic diseases. Twenty-four of the 50 were men and 26 were women; their mean age was 47.0(range,18-76) years. We measured pericardial thickness at the level of the right ventricle, interventricularseptum and left ventricle, and also compared pericardial thickness in terms of age and sex. RESULTS: In allpatients, the pericardium was observed in the right ventricular region; in 41 (82%) at the interventricularseptum; and in 41 (82%) along the left ventricle. The mean thickness of normal pericardium at the level of theright ventricle, interventricular septum, and left ventricle was 1.8 mm +/- 0.5 mm, 1.8 mm +/- 0.4 mm, and 1.7 mm +/-0.5 mm, respectively. No statistically significant correlation was apparent between pericardial thickness and agegroup (p > 0.63, ANOVA test). Mean pericardial thickness was 1.9 mm +/- 0.6 mm in males and 1.7 mm +/- 0.4 mm in females; thus, no statistically significant correlation was apparent between pericardial thickness and sex (p >0.29, Student's t-test). CONCLUSION: The pericardium was best visualized in sections through the right ventricle.The mean thickness of normal pericardium was 1.8 mm +/- 0.5 mm and pericardial thickness did not differ accordingto age or sex.
Adult* ; Female ; Heart Ventricles ; Humans ; Male ; Pericardium ; Tomography, X-Ray Computed

PURPOSE: To evaluate sequential changes in miliary nodules, as seen on chest radiographs in patients withmiliary tuberculosis. MATERIALS AND METHODS: We retrospectively analyzed sequential changes in miliary nodules,as seen on the chest radiographs of 13 patients with miliary tuberculosis who recovered completely ofterantituberculous medication. Two were children and 11 were adults, and their ages ranged from 2 monts to 73years(mean, 38 years). In cases in which miliary tuberculosis had been diagnosed from initial chest radiographs,follow-up chest radiographs were obtained 5 to 15(mean, 10) months later. After complete resolution of miliarynodules, as seen on chest radiographs, high-resolution CT scanning was performed in three patients. RESULTS: Asseen on follow-up chest radiographs obtained at one week, the number and size of miliary nodules had decreased ineight of nine patients (89%), and on those obtained at one month, these decreases were seen in all 13 patients.The mean duration of complete resolution of miliary nodules was 6.3 months ; in children, this was 3.5(range, 2-5)months, and in adults, 6.8 (range, 3-10) months. In all three patients involed, high-resolution CT scans obtainedafter complete radiographic resolution of miliary nodules showed no recurrence. CONCLUSION: In patients withmiliary tuberculosis, the size and number of nodules had decreased within one month of adequate chemotherapy andon chest radiographs, complete resolution was seen at 6.3 months, on average.
Adult ; Child ; Drug Therapy ; Follow-Up Studies ; Humans ; Radiography, Thoracic ; Recurrence ; Retrospective Studies ; Thorax ; Tomography, X-Ray Computed ; Tuberculosis ; Tuberculosis, Miliary ; Tuberculosis, Pulmonary*

PURPOSE: To determine through an analysis of the location of pleural effusion associated with ascites, as seen on abdominal CT scan, differences in the distribution of pleural effusion according to the etiology and distribution of ascites. MATERIALS AND METHODS: We retrospectively evaluated 77 consecutive patients in whom abdominal CT scan revealed pleural effusion associated with ascites. Patients with history of surgery or trauma and those with clinically and radiologically diagnosed lung or pleural diseases were excluded. We compared the location of pleural effusion with the etiology and distribution of ascites. RESULTS: Forty-two patients were suffering from hepatobiliary diseases, mainly right dominant pleural effusion (26/42, 62%). Fourteen had intraperitoneal carcinomatosis with no significant difference between the frequency of right dominant (5/14, 36%)and of left dominant (6/14, 43%) pleural effusion. Eleven patients had pancreatic diseases, with mainly left dominant pleural effusion (6/11, 55%). Patients with right dominant ascites usually had right dominant pleural effusion (22/24, 92%) and those with left dominant ascites had left dominant pleural effusion (9/10, 90%). CONCLUSION: Ascites-associated pleural effusion correlated with the anatomical location of the etiology of ascites ; its laterality was, in addition, usually the same as that of ascites.
Ascites* ; Carcinoma ; Humans ; Lung ; Pancreatic Diseases ; Pleural Diseases ; Pleural Effusion* ; Retrospective Studies ; Tomography, X-Ray Computed*