Association Between SLC6A4 Serotonin Transporter Gene Linked Polymorphic Region and ADRA2A -1291C>G and Irritable Bowel Syndrome in Korea

BACKGROUND/AIMS: Despite numerous studies on the relation of genetic polymorphisms with irritable bowel syndrome (IBS), the results still remain inconclusive. The aim of this study was to assess the possible association between SLC6A4 serotonin transporter gene linked polymorphic region (5-HTTLPR), ADRA2A -1291C>G, GNB3 825C>T, CCK1R intron 779T>C and TRPV1 945G>C polymorphisms and IBS based on Rome III criteria in Korea. METHODS: Study subjects were prospectively recruited from visitors to Seoul National University Bundang Hospital between July 2009 and January 2014. Ninety-nine IBS patients and 171 healthy controls were enrolled. Polymorphisms of above-mentioned 5 genes were genotyped. Serum serotonin from 101 participants was measured by ELISA and compared according to SLC6A4 5-HTTLPR polymorphisms and IBS subtypes. RESULTS: Regarding SLC6A4 5-HTTLPR polymorphism, L/L genotype was significantly associated with the total IBS, constipation predominant IBS (IBS-C) and mixture of diarrhea and constipation IBS (IBS-M) (adjusted OR: 4.35, 95% CI: 1.04-16.67; adjusted OR: 11.11, 95% CI: 1.69-50.00 and adjusted OR: 5.56, 95% CI: 1.05-33.33, respectively). Carrying ADRA2A -1291G allele was significantly associated with total IBS and diarrhea predominant IBS (adjusted OR: 3.37, 95% CI: 1.16-9.77 and adjusted OR: 5.64, 95% CI: 1.18-27.01, respectively). IBS-C patients showed reduced level of serum serotonin compared to controls and patients with diarrhea predominant IBS (50.2 ng/mL vs. 69.0 ng/mL and 92.9 ng/mL, P = 0.017 and P = 0.001, respectively). CONCLUSIONS: Genetic polymorphisms of SLC6A4 5-HTTLPR and ADRA2A -1291C>G could be one of the pathophysiological factors of IBS in Korea. Reduced serum serotonin shown in the IBS-C group suggested a role of serotonin in IBS, but large study is needed for confirming genotypic difference in serum serotonin level.

Association Between Halitosis Diagnosed by a Questionnaire and Halimeter and Symptoms of Gastroesophageal Reflux Disease

BACKGROUND/AIMS: The relationship between halitosis and gastroesophageal reflux disease (GERD) remains controversial. The aim of this study was to investigate an association between subjective and objective halitosis and GERD. METHODS: The subjects were enrolled from participants who visited a health promotion center at Seoul National University Bundang Hospital. For diagnosis of halitosis, a questionnaire was requested, and volatile sulfur compounds (VSCs) were measured by Halimeter. Self-conscious halitosis was defined as halitosis perceived by himself or herself. Informed halitosis was defined as halitosis perceived by others. Objective halitosis was defined when mean VSCs values were > 100 parts per billion. GERD was defined based on a questionnaire and endoscopy, including erosive esophagitis and non-erosive reflux disease (NERD). RESULTS: A total of 54 subjects (male:female = 33:21) with mean age of 46.0 +/- 11.4 years were analyzed. The mean VSCs values were not significantly different between presence and absence of self-conscious halitosis (P = 0.322), but significantly different between presence and absence of informed halitosis (P = 0.021). Informed halitosis was associated with objective halitosis (P = 0.039). GERD, erosive esophagitis and NERD did not correlate with objective halitosis (P = 0.556, 0.206 and 0.902, respectively). In multivariable analysis, the relationship between objective halitosis and GERD symptoms including chest pain, heart burn, acid regurgitation, epigastric pain, hoarseness, globus sensation and coughing was not significant. Besides, GERD was not associated with self-conscious halitosis, informed halitosis and objective halitosis, respectively. CONCLUSIONS: GERD might not be associated with self-conscious, informed halitosis and objective halitosis indicated by Halimeter results. Informed halitosis could be correlated with objective halitosis determined by the Halimeter.

Predictable Marker for Regression of Barrett's Esophagus by Proton Pump Inhibitor Treatment in Korea

BACKGROUND/AIMS: There has been no report regarding the regression of Barrett's esophagus (BE) by continuous treatment of proton pump inhibitor (PPI). The aim of this study was to determine the regression rate of BE by PPI and predictable markers related to regression. METHODS: Thirty-five patients diagnosed as BE were consecutively enrolled and most of them took continuous PPI. The 25 patients underwent endoscopic surveillance and received biopsy. If the specialized intestinal metaplasia (SIM) was lost at any point of surveillance and did not recur, the case was regarded as the regression group. The proportion of SIM was graded and the mucin phenotype was decided using immunohistochemistry for MUC2, MUC5AC and MUC6. To assess the cell proliferation indexes and the degree of intestinal maturation, immunohistochemistry for Ki67 and CDX2 were performed. RESULTS: The regression of BE occurred in the 11 (44%) patients. The clinical and demographic factors showed no difference between the regression (n = 11) and persistence group (n = 14). The lower grade of SIM (P < 0.001) and gastric predominant mucin phenotype (P = 0.018) were more frequent, and the number of Ki67 positive cell per gland (P = 0.008) and the mean extent of CDX2 (P = 0.022) were lower in the regression group than in the persistence group. CONCLUSIONS: The regression of BE by PPI treatment was frequent in Korea. The immunohistochemical detection of mucin phenotype, grade of SIM, Ki67 and CDX2 expression in Barrett's mucosa could be useful as a predictable marker for regression of SIM in BE.

The Long-term Clinical Efficacy of Biofeedback Therapy for Patients With Constipation or Fecal Incontinence

BACKGROUND/AIMS: There has been a controversy regarding the usefulness of biofeedback therapy for functional constipation or fecal incontinence. This study was performed to investigate the long-term clinical efficacy of biofeedback therapy. METHODS: Sixty-four patients with constipation or fecal incontinence received biofeedback therapy for 4 weeks. Symptom improvements were evaluated immediately after the completion of biofeedback therapy and during the follow-up period of about 12 to 64 months. RESULTS: Twenty-five patients in the constipation group [mean age of 52.1 years, 16 men (64.0%)] received 6.2 sessions of biofeedback therapy. Improvement of constipation after the completion of biofeedback therapy was as follows: major response (or improvement) in 3 patients (12.0%), fair in 6 (24.0%), minor in 11 (44.0%) and none in 5 (20.0%). Among 9 patients who showed major or fair improvement, 8 patients (88.9%) maintained the symptom improvement through the long term follow-up periods. Thirty-nine patients in the fecal incontinence group [59.7 years old, 15 men (38.5%)] received 6.8 sessions of biofeedback therapy. Improvement of incontinence after the completion of biofeedback therapy was as follows: major improvement in 6 patients (15.4%), fair in 14 (35.9%), minor in 14 (35.9%), and none in 5 (12.8%). All 11 patients with major or fair improvement maintained the symptom improvement to the end of follow-up periods. CONCLUSIONS: Symptom improvements after biofeedback therapy were disappointing in both the constipation and incontinence group. However, when the symptom improvements were classified as major or fair, the improvements continued for at least a year.

Comparison of Direct Medical Care Costs Between Erosive Reflux Disease and Non-erosive Reflux Disease in Korean Tertiary Medical Center

BACKGROUND/AIMS: Gastroesophageal reflux disease is one of the most common and frequent chronic disease requiring considerable cost. We investigated the medical care costs in the erosive reflux disease (ERD) and non-erosive reflux disease (NERD). METHODS: The risk factors and the direct medical care costs were analyzed retrospectively in the ERD (178 patients) and NERD (183 patients) groups for a follow up period of 2 years. RESULTS: Logistic regression analysis showed that the ERD was more frequent in the groups of male gender, alcohol consumption, higher body mass index (> or =25 kg/m2), hiatal hernia, and higher triglyceride levels (> or =150 mg/dL). The direct medical care costs per person for 2 years were found to be $384.8 (ERD) and $412.9 (NERD) without statistically significant differences (p = 0.364). However, 9.3% (17/183) of the NERD patients had visited the emergency room compared to 3.4% (6/178) of the ERD patients (p = 0.029). In addition, more NERD patients were hospitalized than ERD patients (p = 0.006), and because of the longer hospitalization period, the medical costs in NERD patients were higher than ERD patients (p = 0.038). CONCLUSIONS: In spite of the different risk factors for ERD and NERD, total direct medical care costs were similar between the ERD and NERD group. However, more visits to emergency room and longer hospitalization period with more hospitalization costs in NERD patients account for the differences in medical service and usage distribution between the 2 groups.

Two Cases of Chronic Idiopathic Intestinal Pseudo-obstruction with Different Clinical Features

Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterized by a severe impairment of gastrointestinal propulsion in the absence of mechanical obstruction. We experienced a case of chronic pseudo-obstruction in the initial phase mimicking acute pseudo-obstruction, which was treated medically. This ongoing case was compared to another recurrent and intractable case successfully treated with surgery and diagnosed as hypoganglionosis. These two cases showed different clinical features and therapeutic approaches for CIPO; one with the first episode of CIPO mimicking Ogilvie's syndrome; the other with recurrent episodes of CIPO with typical features. In conclusion, CIPO is a difficult disorder with various clinical manifestations and different treatment modalities, therefore individualized diagnostic and therapeutic approaches are needed.

A Case of Gastric Metastasis from Small Cell Lung Carcinoma / 대한소화기학회지

Gastric metastasis of lung carcinoma is a rare entity which is detected mostly at autopsy. Patients diagnosed as having those on lifetime are extremely rare. In addition to our case, 54 cases of lung carcinoma metastasis to the gastro-intestinal tract have been reported in the literature since 1961. We report a case of gastric metastasis originated from small cell lung carcinoma. The patient was a 87-year-old man. He refused lung biopsy and further treatment and died 2 months after the diagnosis. This is the case of gastric metastsis originated from lung carcinoma, which was confirmed by immunohistochemical staining.

Activation of calcium signaling by hepatitis B virus-X protein in liver cells

Hepatitis B virus x gene product (HBx) is known to be a transactivator of transcriptional elements that regulate the expression of a variety of genes associated with the growth, differentiation, survival and the apoptosis of cells. However, the exact mechanism of the activation and inhibition of cellular events by HBx remains uncertain. The present study was designed to measure the effect of HBx, on the signal transduction pathways associated with intracellular Ca(2+)mobilization following HBx transfection in the stable Chang liver cells (CHL-X). Enhanced cell proliferation by HBx in CHL-X was confirmed by MTT assay and by the immunodetection of PCNA. The transactivation of AP-1 by HBx induced in CHL-X was inhibited by cyclosporin A (CsA), a mitochondrial Ca(2+)channel blocker and by BAPTA-AM, a cytosolic Ca(2+)blocker. Activation of the SAPK/JNK signaling pathway by HBx was evidenced by the increased phosphorylations of c-Jun (Ser63) and of JNK (Thr183/Tyr185). Increased phospho-Erk/Erk and phospho-Raf1/Raf in HBx-induced CHL-X indicated that HBx might stimulate the MAPK pathway. PI3K activity and cytosolic free Ca(2+)levels were elevated in HBx-induced CHL-X. These results imply that HBx transactivates both JNK and MAPK signal transduction pathways in association with the mobilization of cytosolic Ca(2+).

Successful Treatment of Cisplatin Overdose with Plasma Exchange

We report a 48-year-old man with laryngeal cancer who received a massive cisplatin toxic overdose without intravenous prehydration through an error in prescription. He received 400 mg/m2 of cisplatin over a 4-day period. On day 4, he exhibited a broad range of cisplatin toxicities and emergency plasma exchange was started. From day 5 through 19, he underwent 9 cycles of plasma exchange and his plasma cisplatin concentration decreased from 2,470 ng/ml to 216 ng/ml. He completely recovered without any sequelae. No previous reports exist in the English literature of survival without complication after the administration of such a high cisplatin dosage without prehydration.

A Case of Percutaneous Transluminal Coronary Angioplasty with Stent in a Patient of Acute Myocardial Infarction with Situs Inversus Totalis

Situs inversus totalis with dextrocardia is a rare congenital anomaly and its incidence is approximately 1: 6,000-35,000 in general population. Such patients usually have structurally normal hearts and are expected to have normal life span. Coronary angioplasty in such patients have previously been reported, but reported cases in literature are scanty. This report describes our experience of successful percutaneous transluminal coronary angioplasty with stent in acute myocardial infarction patient with situs inversus totalis and dextrocardia who exhibited total occlusion of the mid left anterior descending coronary artery.

Clinical Study of the Intravenous Amiodarone in Acute Myocardial Infarction with Life-Threatening Refractory Ventricular Tachyarrhythmias

BACKGROUND: Recently, the amiodarone has emerged as a promising antiarrhythmic agent and its efficacy and safety has been widely accepted with many literatures. But there was no general agreement regarding the dosage and indication of intravenous (IV) amiodarone in acute myocardial infarction with life-threatening refractory ventricular tachyarrhythmias. METHOD: From October 1995 through October 1997, we recruited retrospectively 9 patients of acute myocardial infarction who had received IV amiodarone for life-threatening refractory ventricular tachyarrhythmias and analyzed the initial response, adverse effect, and loading dose. RESULTS: 1) Acute efficacy:Eight of 9 patients promptly restored normal sinus rhythm immediately after intravenous amiodarone administration. 2) In-Hospital Mortality:One patients died due to ventricular tachyarrhythmias refractory to aggressive management and 5 in 8 patients who had responded promptly with IV amiodarone discharged alive and other 3 patients died due to cardiogenic shock with normal sinus rhythm. 3) Immediate adverse effects:Five patients experienced immediate adverse effects after IV amiodarone; 3 patients of hypotension, 1 patient of first degree AV block, and the other of Morbitz type 2 AV block. 4) Long term follow-up:Among 5 patients discharged alive, one died as unexpected consequence. Other 4 patients have been still alive without maintenance medication. CONCLUSION: The IV amiodarone for suppression of life-threatening ventricular tachyarrhythmias in patients with acute myocardial infarction seemed to be an effective second-line therapeutic drug and have acceptable adverse effects. In the future, the large scale study regarding the dosage and indication might be warrented.