Background: The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics. Methods: We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor. Results: GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively). Conclusion GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

Background: The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics. Methods: We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor. Results: GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively). Conclusion GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

Regulation of matrix metalloproteinases (MMPs) is important for many physiological processes involving cancers, inflammation, tissue remodeling and skin aging. Here, we report the novel finding that the expression of MMP1 mRNA is downregulated by the overexpression of miR-526b which is a member of chromosome 19 microRNA cluster (C19MC). Our analysis using reporter constructs containing the 3' untranslated region (3' UTR) of MMP1 and its mutant form showed that the region from 377-383 in the 3' UTR of MMP1 is critical for targeting by miR-526b. In addition, the expression pattern of miR-526b and MMP1 mRNA showed reverse relation between adult dermal and neonatal fibroblasts. We show for the first time that miR-526b, an miRNA belonging to C19MC, can target the 377-383 region of the MMP1 3' UTR.
3' Untranslated Regions ; Adult ; Base Sequence ; Cell Line ; Down-Regulation ; Fibroblasts/metabolism ; *Gene Expression Regulation ; HeLa Cells ; Humans ; Matrix Metalloproteinase 1/*genetics ; MicroRNAs/*genetics ; RNA, Messenger/*genetics

BACKGROUND: Dialysis patients have impaired host defense mechanisms and frequently require antibiotics for various infective complications. In this study, we investigated whether dialysis patients have greater risk for Clostridium difficile-associated diarrhea (CDAD). METHODS: During the 4-year study period (2004-2008), 85 patients with CDAD were identified based on a retrospective review of C difficile toxin assay or histology records. Nosocomial diarrheal patients without CDAD were considered as controls (n=403). We assessed the association between renal function and the prevalence and clinical outcomes of CDAD. RESULTS: There was a significant difference in the prevalence rate of chronic kidney disease (CKD) between CDAD and non-CDAD patients (P<0.001). Sixteen patients (18.8%) of the CDAD group were treated with dialysis, whereas 21 patients (5.2%) of the non-CDAD group were treated with dialysis. There was a significant association between renal function and CDAD in patients on dialysis [odds ratio (OR)=4.44, 95% confidence interval (CI) 2.19-8.99, P<0.001], but not in patients with CKD stage 3-5 (OR=1.10, 95% CI 0.63-1.92, P=0.73). In multivariate analysis, CKD stage 5D was an independent risk factor for the development of CDAD (OR=13.36, 95% CI 2.94-60.67, P=0.001). CONCLUSION: Our data indicate that dialysis patients might be at a greater risk of developing CDAD, which suggests that particular attention should be provided to CDAD when antibiotic treatment is administered to dialysis patients.
Anti-Bacterial Agents ; Clostridium ; Clostridium difficile ; Defense Mechanisms ; Dialysis ; Diarrhea ; Humans ; Multivariate Analysis ; Prevalence ; Renal Insufficiency, Chronic ; Retrospective Studies ; Risk Factors

BACKGROUND: Dialysis patients have impaired host defense mechanisms and frequently require antibiotics for various infective complications. In this study, we investigated whether dialysis patients have greater risk for Clostridium difficile-associated diarrhea (CDAD). METHODS: During the 4-year study period (2004-2008), 85 patients with CDAD were identified based on a retrospective review of C difficile toxin assay or histology records. Nosocomial diarrheal patients without CDAD were considered as controls (n=403). We assessed the association between renal function and the prevalence and clinical outcomes of CDAD. RESULTS: There was a significant difference in the prevalence rate of chronic kidney disease (CKD) between CDAD and non-CDAD patients (P<0.001). Sixteen patients (18.8%) of the CDAD group were treated with dialysis, whereas 21 patients (5.2%) of the non-CDAD group were treated with dialysis. There was a significant association between renal function and CDAD in patients on dialysis [odds ratio (OR)=4.44, 95% confidence interval (CI) 2.19-8.99, P<0.001], but not in patients with CKD stage 3-5 (OR=1.10, 95% CI 0.63-1.92, P=0.73). In multivariate analysis, CKD stage 5D was an independent risk factor for the development of CDAD (OR=13.36, 95% CI 2.94-60.67, P=0.001). CONCLUSION: Our data indicate that dialysis patients might be at a greater risk of developing CDAD, which suggests that particular attention should be provided to CDAD when antibiotic treatment is administered to dialysis patients.
Anti-Bacterial Agents ; Clostridium ; Clostridium difficile ; Defense Mechanisms ; Dialysis ; Diarrhea ; Humans ; Multivariate Analysis ; Prevalence ; Renal Insufficiency, Chronic ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: The meaning of specialized intestinal metaplasia (SIM) in the diagnosis of Barrett's esophagus (BE) is not clear. This study was designed to determine the clinical significance of SIM in the diagnosis of Barrett's esophagus. MATERIALS AND METHODS: Biopsies were taken from 601 subjects with endoscopically suspected columnar-lined esophagus. Under light microscopy with Alcian-blue stain, SIM was identified. Demographic characteristics, gastroesophageal (GE) reflux symptoms and endoscopic findings were compared between the SIM-present group and the SIM-absent group. RESULTS: Among 601 subjects, 184 (30.6%) were confirmed by pathology to have SIM. Age over 40 years (P<0.001) and a medication history of proton pump inhibitor or H2 blocker were found more frequently in the SIM-present group (P=0.01) than in the SIM-absent group. Any of 7 GE reflux symptoms (heartburn, acid regurgitation, chest pain, hoarseness, globus sensation, cough and epigastric soreness) were more frequent in the SIM-present group than SIM-absent group (P<0.001). Specifically, heartburn, chest pain and cough were significantly more common in the SIM-present group. There was no clinically significant difference associated with endoscopic findings or other clinical characteristics. CONCLUSIONS: When subjects with endoscopically suspected BE are analyzed based on the presence or absence of SIM, the SIM-present group was significantly associated with GE reflux symptoms suggestive of frequent GE reflux. However, the presence of SIM did not correlate with endoscopic findings.
Barrett Esophagus ; Biopsy ; Chest Pain ; Cough ; Esophagus ; Gastroesophageal Reflux ; Heartburn ; Hoarseness ; Light ; Metaplasia ; Microscopy ; Prospective Studies ; Proton Pumps ; Sensation

BACKGROUND/AIMS: Chronic gastritis is a common finding during endoscopy and it is very important to describe it correctly. This study was designed to evaluate the distribution of endoscopic gastritis and the differences according to age, sex or area. MATERIALS AND METHODS: A clinical analysis was conducted on 25,536 subjects who had undergone an upper endoscopy for routine health check-up. Endoscopic gastritis was classified into four types, superficial gastritis, erosive gastritis, atrophic gastritis and intestinal metaplasia. The distribution of the four types of gastritis was evaluated according to sex, age and area. RESULTS: 51.6% of the patients had experienced at least one of the symptoms (epigastric pain or discomfort, soarness, dyspepsia, abdominal pain) on at least a few occasions during the previous year. The incidence of normal gastric finding was 3,593 (14.1%). 21,943 (85.9%) subjects have at least more than one of endoscopic gastritis. The number of cases with superficial gastritis was 7,983 (31.3%), erosive gastritis 6,054 (23.7%), atrophic gastritis 6,918 (27.1%), and intestinal metaplasia 1,181 (7.1%). Erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men than women (P<0.001) and in the older age group (> or =60 years) than younger age group (P<0.001). CONCLUSIONS: The prevalence of endoscopic gastritis was very common, 85.9%. In addition, erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men and in the older age group, which is similar to gastric cancer or peptic ulcer. Cautious regular endoscopic follow-up might be necessary regardless of gastrointestinal symptoms in Korea.
Dyspepsia ; Endoscopy ; Female ; Gastritis ; Gastritis, Atrophic ; Helicobacter pylori ; Humans ; Incidence ; Korea ; Male ; Metaplasia ; Peptic Ulcer ; Prevalence ; Stomach Neoplasms

BACKGROUND/AIMS: Chronic gastritis is a common finding during endoscopy and it is very important to describe it correctly. This study was designed to evaluate the distribution of endoscopic gastritis and the differences according to age, sex or area. MATERIALS AND METHODS: A clinical analysis was conducted on 25,536 subjects who had undergone an upper endoscopy for routine health check-up. Endoscopic gastritis was classified into four types, superficial gastritis, erosive gastritis, atrophic gastritis and intestinal metaplasia. The distribution of the four types of gastritis was evaluated according to sex, age and area. RESULTS: 51.6% of the patients had experienced at least one of the symptoms (epigastric pain or discomfort, soarness, dyspepsia, abdominal pain) on at least a few occasions during the previous year. The incidence of normal gastric finding was 3,593 (14.1%). 21,943 (85.9%) subjects have at least more than one of endoscopic gastritis. The number of cases with superficial gastritis was 7,983 (31.3%), erosive gastritis 6,054 (23.7%), atrophic gastritis 6,918 (27.1%), and intestinal metaplasia 1,181 (7.1%). Erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men than women (P<0.001) and in the older age group (> or =60 years) than younger age group (P<0.001). CONCLUSIONS: The prevalence of endoscopic gastritis was very common, 85.9%. In addition, erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men and in the older age group, which is similar to gastric cancer or peptic ulcer. Cautious regular endoscopic follow-up might be necessary regardless of gastrointestinal symptoms in Korea.
Dyspepsia ; Endoscopy ; Female ; Gastritis ; Gastritis, Atrophic ; Helicobacter pylori ; Humans ; Incidence ; Korea ; Male ; Metaplasia ; Peptic Ulcer ; Prevalence ; Stomach Neoplasms

PURPOSE: Malnutrition is a strong predictor of increased morbidity and mortality in patients on maintenance dialysis. Although a number of studies were performed to determine effective treatment, there is no proven medication for malnutrition. This study aimed to evaluate the effect of keto acids (ketosteril(R)) on serum albumin levels in hemodialysis patients with hypoalbuminemia. METHODS: Hemodialysis patients with hypoalbumineia (serum albumin < or = 3.8 g/dL) were enrolled. Exclusion criteria were previous supplementation of keto acids before the initiation of dialysis, acute infection, liver cirrhosis, malignancy and persistent hypercalcemia. Patients were treated with ketosteril for 6 months and serum albumin levels were compared to age- and gender-matched hemodialysis patients. RESULTS: There were no significant differences in the baseline serum albumin levels between ketosteril group (n=19) and the control group (n=19). After 6 months, the mean (+/-SD) serum albumin level in the ketosteril group rose from 3.46+/-0.40 g/dL to 3.66+/-0.37 g/dL (p=0.01), but not the control group. However, the difference between the two groups was not significant (p=0.06). Multivariate analysis showed that the ketosteril supplementation (p=0.03) and the baseline serum albumin level (< or = 3.4 g/dL, p=0.04) were predictors of increased serum albumin. There was no severe hypercalcemia during the study period. CONCLUSION: There was an improvement of serum albumin levels in hemodialysis patients with hypoalbuminemia after the supplementation of keto acids.
Amino Acids, Essential ; Dialysis ; Humans ; Hypercalcemia ; Hypoalbuminemia ; Keto Acids ; Liver Cirrhosis ; Malnutrition ; Multivariate Analysis ; Renal Dialysis ; Serum Albumin

PURPOSE: The incidence of complete remission is lower and the relapse is more frequent in adult-onset minimal change nephrotic syndrome (MCNS) are observed especially when compared with those in children. This study was designed to examine the effect of methylprednisolone pulse therapy in adultonset MCNS comparing to oral steroid as an initial therapeutic modality. METHODS: We have retrospectively reviewed the clinical data of 25 adult-onset MCNS patients. Twelve patients were treated with three intravenous pulses of methylprednisolone (1 g daily) followed by oral prednisolone 1 mg/kg daily for 4-8 weeks and also by low doses of oral prednisolone for 4-6 months (MP group) Thirteen patients were initially treated with oral prednisolone 1 mg/kg daily for 4-8 weeks and then with low doses of oral prednisolone (PD group). RESULTS: The response to therapy was similar between MP and PD group, with a complete remission obtained in 83.3% and 84.6%, respectively. No statistically significant difference between the two groups was observed in the rate of response at 8 weeks (58.3% versus 69.2%). The mean time to response was not different between MP group (37.9+/-28.0 days) and PD group (45.5+/-40.2 days). No difference was recognized between the two groups with respect to relapse rate. CONCLUSION: These data suggest that a short course of methylprednisolone pulse therapy followed by oral prednisolone is not superior to oral prednisolone therapy as an initial therapeutic modality in adult-onset MCNS.
Child ; Humans ; Incidence ; Methylprednisolone* ; Nephrosis, Lipoid* ; Prednisolone ; Recurrence ; Retrospective Studies