Evaluation of MIC distribution and establishment of epidemiological cut-off values for Streptococcus parauberis isolated from aquatic animals.

AIMS: Streptococcus parauberis is responsible for the development of streptococcosis in marine fish. The aim of the current study was to determine the antimicrobial susceptibility of aquatic Strep. parauberis strains, thus establishing laboratory-specific epidemiological cut-off (COWT) values to distinguish wild-type (WT) and nonwild-type (NWT) strains. METHODS AND RESULTS: Using 220 Strep. parauberis isolates obtained from diseased Paralichthys olivaceus, Platichthys stellatus, and Sebastes schlegelii over 6 years from seven different locations in Korea, we established COWT values for eight common antimicrobial agents using the standard broth microdilution method. The COWT values calculated using MIC distribution with the NRI and ECOFFinder methods were the same or within one dilution step for the eight antimicrobials tested. Nine NWT isolates with decreased susceptibility to at least two antimicrobials and one of these isolates exhibited decreased susceptibility to six antimicrobial agents were identified using COWT values based on NRI. CONCLUSIONS: Interpretive criteria for Strep. parauberis have not yet been established, and the findings of this study provide putative COWT values for eight antimicrobial agents frequently used in aquaculture in Korea.

Establishment of Epidemiological Cut-Off Values and the Distribution of Resistance Genes in Aeromonas hydrophila and Aeromonas veronii Isolated from Aquatic Animals.

The emergence of antimicrobial-resistant bacteria is an enormous challenge to public health. Aeromonas hydrophila and Aeromonas veronii are opportunistic pathogens in fish. They exert tremendous adverse effects on aquaculture production, owing to their acquired antibiotic resistance. A few Clinical and Laboratory Standards Institute (CLSI) epidemiological cut-off values (ECVs) against Aeromonas spp. are available. We evaluated antimicrobial susceptibility by establishing 8 ECVs using two analytical methods, normalized resistance interpretation and ECOFFinder. We detected antimicrobial resistance genes in two motile Aeromonas spp. isolated from aquatic animals. Results showed that 89.2% of A. hydrophila and 75.8% of A. veronii isolates were non-wild types according to the oxytetracycline ECVCLSI and ECVNRI, respectively. The antimicrobial resistance genes included tetA, tetB, tetD, tetE, cat, floR, qnrA, qnrB, qnrS, strA-strB, and aac(6')-1b. The most common tet gene in Aeromonas spp. isolates was tetE, followed by tetA. Some strains carried more than one tet gene, with tetA-tetD and tetA-tetE found in A. hydrophila; however, tetB was not detected in any of the strains. Furthermore, 18.6% of A. hydrophila and 24.2% of A. veronii isolates showed presumptive multidrug-resistant phenotypes. The emergence of multidrug resistance among aquatic aeromonads suggests the spread of drug resistance and difficult to treat bacterial infections.

Antiparasitic potential of ethanolic extracts of Carpesii Fructus against Miamiensis avidus in hirame natural embryo cell line and their effects on immune response- and biotransformation-related genes.

Scuticociliatosis, caused by Miamiensis avidus, is a severe parasitic disease affecting marine organisms, particularly Paralichthys olivaceus. The aim of this study was to assess the antiparasitic potential of ethanolic extracts of Carpesii Fructus (EECF), the dried fruit of Carpesium abrotanoides L., which is used in traditional Chinese medicine, in vitro. We found that 50%, 70%, and 100% EECF induced morphological changes in M. avidus, including reduced motility, cell shrinkage, and lysis. Nearly 100% cell lysis was observed in M. avidus after 2 h of treating with 100% EECF. After 24 h, the survival rates of M. avidus treated with 100%, 70%, and 50% EECF were 10%, 20%, and 30%, respectively. Additionally, the mRNA levels of immune response-related (IL-1ß, IL-8, TNF-α, and CD8-α) and biotransformation-related (CYP1A, CYP1B, CYP3A4, and UGT2B19) genes increased with 70% and 100% EECF treatment and decreased with 50% EECF treatment following pretreatment with concanavalin A. The viability of hirame natural embryo (HINAE) cells was reduced by 50%, 70%, and 100% EECF (100 mg/L) and was between 67 and 80%. The IC50 values of 50%, 70%, 90%, and 100% EECF in HINAE cells were 102.3, 42.93, 39.15, and 38.39 mg/L, respectively. These results indicated that 50% EECF was less toxic to HINAE cells than 70% or 100% EECF, while still exhibiting antiparasitic activity against M. avidus. Therefore, we demonstrated the role of EECF as a natural antiparasitic agent against M. avidus. Our findings suggest that Carpesii Fructus has potential use as an antiparasitic agent in the aquaculture industry.

Fasting serum insulin levels and insulin resistance are associated with colorectal adenoma in Koreans.

AIMS/INTRODUCTION: Insulin has been associated with the risk of colorectal cancer (CRC). However, few studies have evaluated the association between insulin and colorectal adenoma. We investigated the relationship between fasting serum insulin levels or homeostasis model assessment of insulin resistance (HOMA-IR) and colorectal adenoma. MATERIALS AND METHODS: We retrospectively enrolled 15,427 participants who underwent both fasting serum insulin measurement and colonoscopy for a routine health examination at Asan Medical Center from January 2007 to December 2008. Participants with a history of any cancer, previous colectomy or polypectomy, those taking antidiabetic medications, and inflammatory bowel disease, non-specific colitis, non-adenomatous polyps only or CRC on colonoscopic findings were excluded. Finally, 3,606 participants with histologically confirmed colorectal adenoma and 6,019 controls with no abnormal findings on colonoscopy were included. Participants were categorized into quartiles (Q) based on fasting serum insulin levels and HOMA-IR. RESULTS: Fasting serum insulin and HOMA-IR were significantly higher in participants with colorectal adenomas compared with controls. Multivariate regression analysis adjusting for age, sex, smoking habits, drinking habits and family history of CRC showed that participants with higher quartiles of fasting serum insulin levels (odd ratio [OR] 1.17 for 2nd Q, 1.19 for 3rd Q, and 1.42 for 4th Q, P < 0.05) or HOMA-IR (OR 1.18 for 2nd Q and 1.45 for 4th Q, P < 0.05) showed significantly increased ORs of colorectal adenoma compared with the lowest quartiles. CONCLUSIONS: These findings showed that increased serum insulin levels and insulin resistance were significantly associated with the presence of colorectal adenoma.

Seroconversion rates of Helicobacter pylori infection in Korean adults.

BACKGROUND: Studies on seroconversion and its reversion rate in Korean adults with Helicobacter pylori infection are very rare. The purpose of this study was to evaluate the overall seroprevalence, seroconversion rate, and seroreversion rate of H. pylori infection in an adult population. MATERIALS AND METHODS: We performed this retrospective cohort study on healthy adults who had visited our health screening center at Asan Medical Center more than twice between January 2000 and December 2010. We reviewed the anti- H. pylori Ab IgG profiles of the enrolled people and their family members and the results of esophagogastroduodenoscopies and a self-reported questionnaire. RESULTS: A total of 67,212 people were enrolled in this study. The mean follow-up duration was 4.6 years, and each participant visited the center for a mean of 3.8 visits. The overall proportions of participants demonstrating persistent seropositivity, persistent seronegativity, seroconversion, and seroreversion were 53.1%, 32.5%, 4.3%, and 10.1%, respectively. The annual seroconversion rate was 2.79%. The annual crude and spontaneous seroreversion rates of the entire study population were 3.64% and 2.42%, respectively. According to multivariate logistic regression, old age (HR = 1.015), smoking (HR = 1.216), alcohol consumption more than four times per week (HR = 1.263), marriage (HR = 2.735), and living with H. pylori-infected family members (HR = 1.525) were identified as statistically significant risk factors associated with seroconversion. CONCLUSION: The annual seroconversion rate was 2.79% in our study population. Marriage and living with H. pylori-infected family members were important risk factors affecting seroconversion in our adult population.

Novel classification and pathogenetic analysis of hypoganglionosis and adult-onset Hirschsprung's disease.

BACKGROUND AND AIMS: Researchers have not clearly described the clinical and pathogenetic features of hypoganglionosis and adult-onset Hirschsprung's disease, which cause pseudo-obstruction or intractable constipation. We conducted this study to explore these features of hypoganglionosis and adult-onset Hirschsprung's disease in Korean patients. METHODS: We enrolled 24 patients pathologically confirmed as having hypoganglionosis and 11 as having adult-onset Hirschsprung's disease. We recruited 26 subjects who had undergone operation for nonobstructive colon cancer and 45 healthy volunteers as controls. We described their clinical features, investigated ganglion cells and interstitial cells of Cajal (ICC), and analyzed RET, EDNRB, EDN3, and SOX10 genes. RESULTS: We classified hypoganglionosis patients into two groups: type I (focal type, n = 13), with focally narrowed transition zone (TZ); and type II (diffuse type, n = 11), without transition zone. Hypoganglionosis patients had significantly fewer ganglion cells than the controls, and those cells were scarcer in the transition zone than in the proximal dilated area (P < 0.05). The ICC numbers in both diseases were significantly lower than in controls; however, they were similar between transition zone and the proximal dilated area in hypoganglionosis. In adult-onset Hirschsprung's disease, two significant intronic RET polymorphic variants, IVS14-24G>A and IVS19+47T>C, were significantly associated with adult-onset Hirschsprung's disease (P = 0.0122 and 0.0295, respectively), but not with hypoganglionosis. CONCLUSIONS: Hypoganglionosis and adult-onset Hirschsprung's disease have different pathophysiologic characteristics, although their clinical presentations are similar. We suggest that there are two subgroups of hypoganglionosis: those with or without a focally narrowed transition zone with a profoundly diminished number of ganglion cells.

Western-style diets induce macrophage infiltration and contribute to colitis-associated carcinogenesis.

BACKGROUND AND AIM: A Western-style diet (WD) is known to play an important role in inflammatory bowel disease and colon carcinogenesis. The purpose of this study was to understand the role of macrophages in WD-induced colitis associated with carcinogenesis. METHODS: Male BALB/c mice were fed a WD or a control diet (CD) for 4 weeks and exposed to azoxymethane (AOM) followed by 2% dextran sulfate sodium (DSS) for 7 days. RESULTS: The WD increased susceptibility to DSS-induced inflammation and accelerated the infiltration of macrophages. The incidence and multiplicity of colon tumors were higher in mice fed the WD than in those fed the CD (P < 0.05). Levels of prostaglandin-endoperoxide synthase (PTGS) 2 and prostaglandin (PG) E(2) in the colon were higher after treatment with AOM and DSS in mice fed the WD than in those fed the CD. In addition, WD consumption increased the DNA binding activity of nuclear factor-kappaB and the serum concentration of tumor necrosis factor (TNF)-α. Mice fed the WD had higher numbers of F4/80-positive cells surrounding cancer cells compared with mice fed the CD. These cells expressed PTGS2, TNF-α and ß-catenin, which are up-regulated by the WD. We also found that the WD increased unphosphorylated ß-catenin accumulation in the cytoplasm and nucleus of colon cancer cells. CONCLUSIONS: A WD increases the susceptibility to DSS-induced inflammation and accelerates the infiltration of macrophages. In turn, this resulted in the development and progression of colon cancer.

Near-infrared fluorescence imaging using a protease-specific probe for the detection of colon tumors.

BACKGROUND/AIMS: Early tumor detection is crucial for the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging using a target-activatable probe may permit earlier disease detection. Matrix metalloproteinases (MMPs) participate in tumorigenesis and tumor growth. The aim of this study was to determine whether NIRF imaging using an MMP-activatable probe can detect colon tumors at early stages. METHODS: WE UTILIZED TWO MURINE COLON CANCER MODELS: a sporadic colon cancer model induced by azoxymethane (AOM), and a colitis-associated cancer model induced by a combination of AOM and dextran sodium sulfate (DSS). Colonic lesions were analyzed by histologic examination, Western blotting, immunohistochemical staining, and NIRF imaging using an MMP-activatable probe. RESULTS: Multiple variable-sized tumors developed in both models and progressed from adenomas to adenocarcinomas over time. At the early stage of the AOM/DSS model, diffuse inflammation was observed within the tumors. MMP expression increased progressively through normal, inflammation, adenoma, and adenocarcionoma stages. NIRF signal intensities were strongly correlated with each tumor stage from adenoma to adenocarcinoma. NIRF imaging also distinguished tumors from inflamed mucosa. CONCLUSIONS: NIRF imaging using a protease-activatable probe may be a useful tool for early tumor detection. This approach could translate to improve the endoscopic detection of colon tumors, especially in patients with inflammatory bowel disease.

Usefulness of double balloon endoscopy in patients with surgically distorted intestinal anatomy.

BACKGROUND: Double balloon endoscopy (DBE) is a new endoscopic method with the capability for complete observation of whole small bowel. This study evaluated the feasibility and usefulness of DBE for the diagnosis and therapy of small bowel diseases in patients with distorted intestinal anatomy by previous surgeries. PATIENTS AND METHODS: From January 2005 to August 2007, 15 patients with Roux-en-Y anastomosis underwent DBE in Asan Medical Center. Eight were men and the median age was 57 years (range, 40 to 68 y). Indications of DBE were suspected small bowel bleeding, chronic diarrhea, and recurrent acute pancreatitis. The main outcome measurements included completeness of the observation of afferent loop and DBE findings. RESULTS: Because 1 patient underwent DBE twice separately owing to recurrent bleeding, a total of 16 cases were analyzed. The observation of afferent loop was complete in 13 (81%) of 16 cases. The overall diagnostic yield of DBE was 69% (11/16). Out of 11 cases in which DBE detected abnormalities, 6 (55%) showed definite lesions and 5 (45%) probable lesions. Of the 11 cases in which abnormalities were found, 7 (64%) showed lesions in afferent loop. Of the 6 cases in which definite lesions were found, 4 (67%) showed lesions in afferent loop. Therapeutic endoscopic procedures were performed in 4 cases, which include argon plasma coagulation, foreign body removal, and endoscopic nasobiliary drainage. CONCLUSIONS: DBE in patients with distorted intestinal anatomy such as Roux-en-Y anastomosis is a useful tool for the management of small bowel lesions, especially those in the afferent loop.

[The changes in prevalence and the related factors of Helicobacter pylori infection in Korean health check-up subjects during 8 years].

BACKGROUND/AIMS: The aim of this study was to evaluate the changes in prevalence and the related factors of Helicobacter pylori (H. pylori) infection in Korean health check-up subjects during the period of 8 years. METHODS: Among 89,231 subjects who visited the Health Promotion Centers of Severance hospital or Chung-Ang University hospital from Jan. 1998 through Dec. 2005, a total of 10,553 subjects who received esophagogastroduodenoscopy (EGD) and H. pylori test were enrolled. H. pylori infection was assessed by histologic examination. Changes of the prevalence of H. pylori infection during 8 years, and infection-related factors such as demographic characteristics, body mass index, ABO blood types, endoscopic findings (presence of peptic ulcer diseases), educational level, economic status, smoking habits, and alcohol intake in year 2005 were analyzed. RESULTS: The mean age of 10,553 subjects (7,329 men, 3,224 women) was 49.7+/-10.4 years (range from 17 to 92 years). The prevalence of H. pylori infection at the first, second, third, fourth, fifth, sixth, seventh, and eighth year were 64.7%, 58.1%, 54.2%, 50.4%, 48.9%, 49.5%, 39.6%, and 40.0%, respectively, and these serial decreases in prevalence over 8 years were statistically significant (p<0.001). Regardless of sex, age or EGD findings, the prevalence of H. pylori infection was significantly decreased. In the analysis of the H. pylori infection-related factors in 2005, only age and EGD findings (peptic ulcer diseases) were significant factors. CONCLUSIONS: The prevalence of H. pylori infection was significantly decreased during 8-year period in Korean health check-up subjects. Age and peptic ulcer diseases were the two significant factors related to H. pylori infection in Korea.

A pilot study about tolerability to double balloon endoscopy: comparison to esophagogastroduodenoscopy and colonoscopy.

BACKGROUND: Although the diagnostic and therapeutic values of double balloon endoscopy (DBE) have been investigated, the subjective tolerability to DBE has not been assessed. We aimed to evaluate patients' tolerability to DBE. METHODS: We prospectively enrolled patients who underwent DBE. For the comparison of tolerability to DBE with that to esophagogastroduodenoscopy (EGD) and colonoscopy, those who had not undergone EGD nor colonoscopy were excluded. A total of 52 patients were included. All procedures were performed under conscious sedation with midazolam with or without pethidine. Patients' tolerability to DBE, EGD, and colonoscopy was assessed through an interview with a questionnaire using a 10-point Likert scale. RESULTS: A total of 36 patients underwent both antegrade DBE and EGD under conscious sedation. The level of abdominal pain during procedures, the level of post-procedural abdominal discomfort, and the proportion of patients with persistent abdominal discomfort until the next morning were higher in antegrade DBE. However, when analyzed in 16 patients who had good quality of sedation, the differences in the level of abdominal pain during procedures and the persistent abdominal discomfort until the next morning disappeared. A total of 23 patients underwent both retrograde DBE and colonoscopy under conscious sedation. Tolerability parameters were not different between retrograde DBE and colonoscopy. Serious complications, including hemodynamic instability, did not occur during all procedures. CONCLUSION: Patients tolerated DBE well. DBE may be performed as comfortably as EGD and colonoscopy if the quality of sedation is good enough.

The long-term effects of rosiglitazone on serum lipid concentrations and body weight.

OBJECTIVE: Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentrations and low density lipoprotein (LDL) particle size, it has unwanted effects on total cholesterol (TC) and LDL cholesterol (LDL-C) concentrations and body weight in some short-term studies. The aim of this study was to evaluate the long-term effects of rosiglitazone on serum lipid levels and body weight. DESIGN: Open labelled clinical study. PATIENTS AND MEASUREMENTS: We prospectively evaluated fasting serum glucose, haemoglobin A(1c) (HbA(1c)), lipid profiles and body weight at baseline and every 3 months after the use of rosiglitazone (4 mg/day) for 18 months in 202 type 2 diabetic patients. RESULTS: TC levels increased maximally at 3 months and decreased thereafter. However, overall, TC levels remained significantly higher at 18 months than those at baseline. LDL-C levels from the 3-month to the 12-month timepoint were significantly higher than those at baseline. However, after 15 months, LDL-C concentrations were not significantly different from basal LDL-C concentrations. HDL-C levels increased after the first 3 months and these levels were maintained. The increment of change in HDL-C was more prominent in patients with low basal HDL-C concentrations than in patients with high basal HDL-C concentrations. Body weight increased after the first 3 months and these levels were maintained. CONCLUSIONS: HDL-C and body weight increased and remained elevated for the duration of the study. There was an initial increase in LDL-C but this attenuated and by the end of the study was not significantly elevated above baseline levels.

Hypercalcemia in hepatic tuberculosis: a case report in Korea.

Although primary hyperparathyroidism and malignant diseases account for approximately 90% of the causes of hypercalcemia, they could occur in association with granulomatous diseases such as tuberculosis or sarcoidosis, especially in developing countries. Hepatic tuberculosis is difficult to diagnosis without suspicion in cases with normal findings on chest radiographs. We report a 70-year-old woman who presented with hypercalcemia due to hepatic tuberculosis. The diagnosis was made by a computed tomography scan and laparoscopic evaluation. After treatment with anti-tuberculosis medication, her hypercalcemia resolved. Increased vitamin D synthesis by activated macrophages in the granuloma tissue is the major mechanism of hypercalcemia in tuberculosis.

Clinical features of bone metastases resulting from thyroid cancer: a review of 28 patients over a 20-year period.

Bone is the second most frequent site of metastasis resulting from thyroid cancer. Many studies have investigated clinical features and prognostic factors of distant metastases stemming from thyroid cancer in Western countries. The purpose of this study was to review clinical characteristics of Korean patients with bone metastasis originating from thyroid cancer. Between January 1985 and August 2004, 28 patients with thyroid cancer were diagnosed with bone metastases at the Yonsei Severance Hospital in Seoul, Korea. Their clinical characteristics were analyzed retrospectively. Incidence of bone metastasis from follicular thyroid cancer was 6.8% (9 of 132 patients), and 0.4% (13 of 3,154 patients) from papillary thyroid cancer, with an odds ratio of 17.67 (95% confidence interval; 7.41-42). Twelve patients had no symptoms of bone metastasis. Overall mean number of metastasis sites was 2.6 +/- 1.9, and 12 patients had a solitary bone metastasis. Survival rates between the synchronous and metachronous metastasis groups were not significantly different, and the number of metastasis sites did not affect survival. However, the survival of patients that underwent curative treatment was longer than those with palliation (P = 0.0317). In Korea, the overall incidence of bone metastasis resulting from thyroid cancer was less than our expectation. Many patients were asymptomatic, and had a tendency of undergoing less aggressive or palliative treatment, even though the long-term survival of distant metastasis resulting from thyroid cancer with active treatment is relatively good. Further studies of the prognostic factors and effectiveness of various treatments of these patients are needed to enhance survival.