Analysis of Gene Mutations Associated with Antibiotic Resistance in Helicobacter pylori Strains Isolated from Korean Patients

BACKGROUND/AIMS: This study aims to identify the gene mutation pattern associated with antibiotic resistance for mainly used antibiotics in Helicobacter pylori strains isolated from Koreans. MATERIALS AND METHODS: Seventy-one H. pylori strains were isolated from gastric mucosal biopsy specimens. The specimens were cultivated and the resistance to 5 antibiotics were assessed by using agar gel dilution method. DNA sequencing was carried out to detect the resistance-related gene mutations. RESULTS: A point mutation at A2143G of 23S rRNA was observed in all of the clarithromycin resistant strains, but tetracycline resistant strains were not found. Substitution N562Y in penicillin binding protein 1 were observed in an amoxicillin resistant strain (minimum inhibitory concentration [MIC] 2.0microg/mL). Eleven (57.8%) out of 19 levofloxacin resistant strains showed amino acid substitution at N87K (8 strains), N87I, A88V and D91N in GyrA. The truncation in rdxA was detected in 8 (25.0%) out of 32 metronidazole resistant strains. Two out of the 7 patients who failed in first-line treatment of clarithromycin and amoxicillin showed A2143G mutation. CONCLUSIONS: 23S rRNA mutation is closely related to the failure of eradication, however, the fact that five people who have no gene mutation failed eradication implies that other factors are related. As MIC levels in clarithromycin and levofloxacin resistance strains are getting higher, their appropriate gene mutation is more correlated.

Analysis of Gene Mutations Associated with Antibiotic Resistance in Helicobacter pylori Strains Isolated from Korean Patients

BACKGROUND/AIMS: This study aims to identify the gene mutation pattern associated with antibiotic resistance for mainly used antibiotics in Helicobacter pylori strains isolated from Koreans. MATERIALS AND METHODS: Seventy-one H. pylori strains were isolated from gastric mucosal biopsy specimens. The specimens were cultivated and the resistance to 5 antibiotics were assessed by using agar gel dilution method. DNA sequencing was carried out to detect the resistance-related gene mutations. RESULTS: A point mutation at A2143G of 23S rRNA was observed in all of the clarithromycin resistant strains, but tetracycline resistant strains were not found. Substitution N562Y in penicillin binding protein 1 were observed in an amoxicillin resistant strain (minimum inhibitory concentration [MIC] 2.0microg/mL). Eleven (57.8%) out of 19 levofloxacin resistant strains showed amino acid substitution at N87K (8 strains), N87I, A88V and D91N in GyrA. The truncation in rdxA was detected in 8 (25.0%) out of 32 metronidazole resistant strains. Two out of the 7 patients who failed in first-line treatment of clarithromycin and amoxicillin showed A2143G mutation. CONCLUSIONS: 23S rRNA mutation is closely related to the failure of eradication, however, the fact that five people who have no gene mutation failed eradication implies that other factors are related. As MIC levels in clarithromycin and levofloxacin resistance strains are getting higher, their appropriate gene mutation is more correlated.

Antibiotic Resistance in Helicobacter pylori Strains and its Effect on H. pylori Eradication Rates in a Single Center in Korea

BACKGROUND: Clarithromycin, amoxicillin, metronidazole, tetracycline, and levofloxacin have been commonly used for the eradication of Helicobacter pylori. We compared the change in antibiotic resistance of H. pylori strains during two separate periods and investigated the effect of antibiotic resistance on H. pylori eradication. METHODS: H. pylori strains were isolated from 71 patients between 2009 and 2010 and from 94 patients between 2011 and 2012. The distribution of minimal inhibitory concentration (MIC) of 5 antibiotics was assessed using the agar dilution method, and H. pylori eradication based on the antimicrobial susceptibility of the isolates was investigated retrospectively. RESULTS: Antibiotic resistance rate against clarithromycin, amoxicillin, tetracycline, metronidazole, and levofloxacin for the 2009-2010 isolates were 7.0% (5/71), 2.8% (2/71), 0% (0/71), 45.1% (32/71), and 26.8% (19/71), respectively, and for the 2011-2012 isolates were 16.0% (15/94), 2.1% (2/94), 0% (0/94), 56.3% (53/94), and 22.3% (21/94), respectively. Multi-drug resistance for 2 or more antibiotics increased slightly from 16.9% (12/71) in the 2009-2010 isolates to 23.4% (22/94) in the 2011-2012 isolates. In follow-up testing of 66 patients, first-line treatment successfully eradicated H. pylori in 50 patients (75.8%) and failed in 4 of 7 patients (57.1%) in a clarithromycin-resistant and amoxicillin-susceptible group. CONCLUSIONS: We observed an increase in resistance to clarithromycin and an overall increase in multi-drug resistance during the 2 study periods. The effectiveness of the eradication regimen was low with combinations of clarithromycin and amoxicillin, particularly in the clarithromycin-resistant group. Thus, eradication of H. pylori depends upon periodic monitoring of antimicrobial susceptibility.

Reversible Pituitary Dysfunction in a Patient with Cushing's Syndrome due to Adrenal Adenoma / 대한내분비학회지

A 45-year-old woman who complained of weight gain and irregular menstruation was diagnosed as having Cushing's syndrome due to a 3 cm sized left adrenal adenoma. She underwent left adrenalectomy, and she also underwent combined anterior pituitary tests before and 9 months after the surgery. The growth hormone and adrenocorticotropic hormone levels failed to respond to hypoglycemia before the surgery, but their responses recovered after the surgery. Cortisol and thyroid stimulating hormone failed to respond to hypoglycemia and thyrotropin releasing hormone (TRH) before the surgery, respectively, but these were improved after the surgery. Luteinizing hormone, follicle stimulating hormone, and prolactin adequately responded to gonadotropin-releasing hormone and TRH, respectively, before and after the surgery. However, the basal levels of these hormones were higher after adrenalectomy, suggesting that hypercortisolemia had a significant influence on all the pituitary hormones.

Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p=0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0-->> 4.2, p=0.000) ; lactulose group (11.3-->> 5.0, p=0.000) ). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.

Migration of Pyloric Self-Expanding Metallic Stent to the Esophagus / 대한소화기내시경학회지

Self-expandable metallic stent (SEMS) has been reported to provide effective treatment alternatives with minimal morbidity for patients with malignant gastroduodenal obstruction. Limitations of SEMSs are stent occlusion due to tumor ingrowth or overgrowth and stent migration. Migrated stents may remain in the stomach or travel distally. To our knowledge, however, migration of pyloric SEMS to the esophagus has not been reported. We experienced such a case in a 65-year-old woman who had undergone a gastrojejunostomy and choledochojejunostomy due to unresectable pancreatic head cancer. Pyloric SEMSs (Niti-S Pyloric Bare Stent, 18x60 mm, Taewoong Medical, Korea) were deployed at the obstructed efferent and afferent loops. After severe vomiting, a pyloric SEMS placed at the afferent loop migrated into the esophagus, which caused severe chest pain and intractable hiccup. It was removed endoscopically. This case illustrates that pyloric SEMS can migrate to the esophagus through the lower esophageal sphincter.

Efficacy and Safety of Short-term Administration of Rifaximin in the Treatment of Hepatic Encephalopathy / 대한간학회지

BACKGROUND/AIMS: A prospective, randomized study was performed to evaluate the efficacy and safety of the short-term administration of rifaximin in the treatment of hepatic encephalopathy. METHODS: Of the 64 patients diagnosed as having decompensated liver cirrhosis with hepatic encephalopathy, 39 patients were randomized to receive rifaximin and 25 patients to receive lactulose for seven days. Before and after the treatment we assessed changes in the level of serum ammonia, flapping tremor, patient's mental status, number connection test (NCT), and hepatic encephalopathy indices. RESULTS: In rifaximin-treated group, the mean grade of serum ammonia (1.8->0.9), mental status (1.3->0.3), NCT (3.0->2.0), and flapping tremor (1.7->0.4) were improved after treatment. In the lactulose-treated group, the mean grade of serum ammonia (1.9->1.0), mental status (1.5->0.5), NCT (3.3->2.1), and flapping tremor (1.4->0.3) were improved after treatment. Side effects of abdominal pain (rifaximin group) and excessive diarrhea (lactulose group) were noted in 2 cases. The efficacy of treatment was not significantly different between rifaximin and lactulose-treated groups (84.3% vs. 95.3%). CONCLUSION: Rifaximin was as efficient and safe in the treatment of hepatic encephalopathy as lactulose in terms of efficacy. Rifaximin may be useful drug for the short-term treatment of hepatic encephalopathy.

An ischemic skin lesion after chemoembolization of the right internal mammary artery in a patient with hepatocellular carcinoma

A huge nodular hepatocellular carcinoma located at the anterior superior portion of the left lobe in a patient with hepatocellular carcinoma was treated with transcatheter arterial chemoembolization through the left hepatic artery. Three months later, however, there was a re-elevation of the serum alpha-fetoprotein level and evidence of a marginal recurrence at the left side of the previously embolized tumor was noted on the postembolization computed tomographic scan. Although the hepatic artery was intact in the second hepatic arteriography, we found that the right internal mammary artery was feeding the recurred hepatocellular carcinoma. This internal mammary artery was successfully treated with Lipiodol-transcatheter arterial chemoembolization. However, an ischemic lesion occurred in the skin of the anterior chest and abdominal wall several days after internal mammary artery embolization. We report here a very rare case of ischemic skin lesion on the anterior chest and abdominal wall following transcatheter arterial chemoembolization of the right internal mammary artery. This internal mammary artery was embolized because it had developed a collateral tumor feeding vessel following the initial chemoembolization of a hepatocellular carcinoma.

Long-term Efficacy and Durability of Lamivudine Therapy in Patients with Chronic Hepatitis B / 대한간학회지

BACKGROUND/AIMS: It has been reported in patients with chronic hepatitis B, that the response rate of lamivudine therapy increases in proportion to the duration of the therapy. What was not well known was the durability of the therapeutic response after the cessation of lamivudine therapy. The aim of this study was to evaluate the long-term efficacy and durability of lamivudine therapy in patients with chronic hepatitis B. Patients and METHODS: We retrospectively analyzed 73 patients with chronic hepatitis B who were treated with lamivudine 100 mg orally once daily and followed up for more than 12 months between April 1997 and March 1999. Sixty-three patients were initially hepatitis B e antigen (HBeAg) positive and Hepatitis B virus (HBV) DNA positive (group I). Ten patients were HBeAg negative and HBV DNA positive (group II). The responders were those who had negative conversion of HBV DNA and normalization of alanine aminotransferase (ALT). Treatment was stopped after HBeAg seroconversion in group I and after thaerapeutic response in group II. RESULTS: The response rates of group I and group II were 68.3% and 70.0% at 12 months, respectively (P = NS). In group I, cumulative HBeAg seroconversion rates at 1 year, 2 years, and 3 years were 30.2%, 38.8%, and 42.4%, respectively. The cumulative durability of response was higher in group I than in group II (64.6% vs. 33.3% at 1 year; 35.4% vs. 22.2% at 2 years; P = .079). The cumulative durability of response was significantly higher in patients who received additional lamivudine therapy for more than 6 months after HBeAg seroconversion than for less than 6 months (90.0% vs. 40.0% at 1 year; 90.0% vs. 20.0% at 2 years; P = .013). CONCLUSIONS: The long-term response to lamivudine therapy showed no difference between HBeAg-negative/HBV DNA-positive and HBeAg-positive patients. The HBeAg seroconversion rate increased in proportion to the duration of lamivudine therapy. The Continuation of treatment for more than 6 months after HBeAg seroconversion might increase the durability of response.

Successful Treatment of Multiple Superficial Gastric Antral Bleeding with Alto Shooter(TM) in a Patient with End Stage Renal Disease / 대한소화기내시경학회지

Diffuse or multifocal superficial gastrointestinal bleeding can be treated by endoscopic laser, argon plasma coagulation, heater probe, or electrocoagulation. However, these methods need relatively expensive equipments and clinical experience. Recently, Alto Shooter(TM) (Kaigen Co. Ltd., Osaka, Japan) which can spray 100% sodium alginate was developed to control gastrointestinal bleeding as a topical therapy. We herein present a 47-year-old man with end stage renal disease in whom multiple superficial gastric antral bleeding was successfully managed by the use of Alto Shooter(TM). This method is easy and relatively cheap to use and seems to control superficial bleeding effectively from vascular lesions or after endoscopic biopsy.

An Impacted Distal Common Bile Duct Stone Mimicking a Tumor: An Unusual Manifestation of Gallstone Disease / 대한소화기내시경학회지

Patients with bile duct stones usually present with biliary pain, obstructive jaundice, ascending cholangitis, or pancreatitis. When endoscopic retrograde cholangiopancreatography (ERCP) is performed, bile duct stones are usually movable and thus easily detected. If a stone in the bile duct presents unusually, it may pose some diagnostic challenges. Recently, we experienced a case of an impacted distal common bile duct (CBD) stone mimicking a tumor which resulted in performing a pylorus-preserving pancreaticoduodenectomy in an asymptomatic 56-year-old man. On ERCP, an obstructing distal CBD lesion did not move even by doing brush cytology. Moreover, the result of brush cytology was positive for atypical cells. A major resective surgery performed after recovery from severe post-ERCP pancreatitis confirmed the diagnosis. Interestingly, this stone caused erosion with acute and chronic inflammation and fibrosis containing foci of mild epithelial dysplasia. We herein report an unusual manifestation of gallstone disease with a review of the literature.

Comparison of Somatostatin and Vasopressin in the Control of Acute Esophageal Variceal Hemorrhage: A Prospective Randomized Trial / 대한간학회지

BACKGROUND/AIMS: Although endoscopic band ligation or injection sclerotherapy are the current standard therapies for bleeding esophageal varices, the best method for initial control is unclear. The aim of this prospective study was to compare the efficacy and toxicity of somatostatin and vasopressin in the management of esophageal variceal hemorrhage. METHODS: From March, 1997 to September, 1998, 28 consecutive cirrhotic patients admitted to the Yonsei Medical Center because of active variceal bleeding were included in this trial. The patients were randomized to receive either somatostatin (15 patients) or vasopressin (13 patients) for 48 hours. RESULTS: There were no significant differences between the two treatment groups in relation to Child's classification, amount of bleeding before randomization and units of blood transfused during therapy. Initial control of bleeding was achieved in 13 (86.7%) patients receiving somatostatin and in 10 (76.9%) of those treated with vasopressin. However, two patients in the somatostatin group and two in the vasopressin group bled again during treatment. Therefore complete control of bleeding during the 48 hours of therapy was achieved in 11 (73.4%) patients treated with somatostatin and in eight (61.5%) of those receiving vasopressin. Differences were observed in complications associated with each therapy. Vasopressin produced complications in four patients (chest pain in two, hypertension in one and hyponatremia-induced seizure in one) while somatostatin produced minor complication in one patient. CONCLUSIONS: This study suggests that somatostatin is efficacious in controlling acute hemorrhage from esophageal varices and has a lower risk of adverse effects than vasopressin.

Cystic Duct Insertion at the Ampulla of Vater and Acute Pancreatitis: A Case Report / 대한소화기내시경학회지

The two most common causes of acute pancreatitis are alcohol and cholelithiasis. Acute recurrent pancreatitis can result from a variety of abnormalities involving the terminal end of the distal choledochus, pancreatic duct, ampulla of Vater and the major duodenal papilla, which in turn may include a papillary stenosis, periampullary neoplasm, choledochocele, sphincter of Oddi dysfunction, and pancreatic ductal adenocarcinoma. Recently a case of recurrent acute pancreatitis associated with aberrant cystic duet insertion at the ampulla of Vater was experienced. Biliary-pancreatic reflux was speculated to be the mechanism responsible for causing this anomalous, recurrent, acute pancreatitis. Another case of acute pancreatitis associated with aberrant cystic duct insertion at the ampulla of Vater was also experienced in a 29-year-old man, 1Jnlike the previous report, our case showed cholestatic features on the initial blood chemistry. An endoscopic retrograde cholangiopancre-atography performed after recovry revealed only aberrant cystic duct insertion at the ampulla of Vater. This anomaly also seems to have played a role in causing acute pancreatitis in this patient. This interesting case is herein reported with a review of the relevant literature.

A Case of Intraductal Papillary Mucinous Tumor of the Pancreas Presenting with Refractory Acute Pancreatitis / 대한소화기내시경학회지

The clinical presentation of intraductal papillary mucinous tumor (IPMT) of the pancreas is characterized by chronic or recurrent attacks of abdominal discomfort often in association with low level pancreatic enzyme elevations. The episodes of pancreatitis due to IPMT of the pancreas are usually mild in severity. Recently, however, we experienced a case of IPMT of the pancreas causing severe acute pancreatitis with a protracted course in a 65 year-old woman. Initially, she presented with pancreatic ascites and hyperenzynemia without duct ectasia and mucus extrusion through the papillary orifice. Refeeding caused aggravation of hyperenzynemia and abdominal pain. The 4th follow-up abdominal computed tomography taken about 2 months after admission only revealed marked dilatation of the main pancreatic duct. Distal pancreatectomy disclosed IPMT, combined type and carcinoma in situ histologically. The patient has been followed for 2 years after operation with an uneventful clinical course. We herein report a case of IPMT of the pancreas with an unusual presentation.

The functional relationships between hiatal hernia and reflux esophagitis

The purpose of this research was to investigate functional studies by which the hiatal hernia (HH) may be relevant to a reflux esophagitis (RE). Group I consisted of healthy controls who were endoscopically normal (n = 21). Group II consisted of patients with hiatal hernia but no reflux esophagitis (n = 8). Group III had patients with hiatal hernia with reflux esophagitis (n = 9). Group IV had patients with reflux esophagitis but no hiatal hernia (n = 16). Esophageal manometry, ambulatory 24 hour intraesophageal pH monitoring, acid clearance test, and gastric emptying scan were performed in each of the patients. The contraction amplitude at 3 cm above the lower esophageal sphincter did not differ significantly among the four groups, but the mean lower esophageal sphincter pressure was significantly decreased in group II. The DeMeester score in ambulatory 24 hour intraesophageal pH monitoring was significantly higher in group III compared with the controls. No significant difference among the groups was found with respect to acid clearance. Total and proximal gastric emptying times (T1/2) were significantly delayed in group III. We found that hiatal hernia combined with delayed gastric emptying may bear a relationship to the multifactorial origins of reflux esophagitis, and we suggest a rationale for using prokinetic agents as the therapeutic regimen in patients with HH complicated by RE.

Measurement of Trachea with MRI in the Normal Korean Adults / 대한마취과학회지

It is clinically important to know the size of normal trachea for airway management and respiratory care. The knowledge is useful for avoiding many possible complications due to tracheal intubation by appropriate choice of endotracheal tube size. Therefore, we investigated antero-posterior(A-P) diameter, transverse diameter and cross- sectional area(CSA) of trachea at various level with MRI(magnetic resonance imaging) in 70 males and 79 females who were divided into three age groups(group 1: 16-39 year of age, group 2: 40-59 year of age, group 3: 60-83 year of age), and they had no abnormalities in cardiopulmonary system. The results were as follows; 1. A-P 2. Transverse 3. Narrowing portion 4. CSA 1. A-P diameter of trachea was 17.1+/-1.4 mm in male and 13.9+/-1.3 mm in female. Transverse diameter of trachea was 15.1+/-1.6 mm in male and 13.3+/-1.5 mm in female(Table 1). A-P and Transverse diameters were greater in male than in female (P<0.05). 2. C-7 was the narrowest portion of A-P diameter in both sex (P<0,05). C-5 was the narro- west portion of transverse diameter in both sex (P<0.05). 3. A-P diameters of trachea among male patients were 17.1+/-1.2 mm, 17.41.6 mm, and 16.6+/- 1.3 mm in group 1, 2 and 3 (Table 3, Fig. 4). A-P diameters of trachea in female age group 1, group 2 and group 3 were 13.7+/-1.2 mm, 14.3+/-1.3 mm, and 13.6+/-1.5 mm(Table 3, Fig. 4). Transverse diameters of trachea in male age group 1, group 2 and group 3 were 14.8+/-1.4 mm, 15.1+/-1.7 mm, and 15.4+/-1.6 mm(Table 3, Fig. 4). Transverse diameters of trachea in female age group 1, group 2 and group 3 were 13.0+/- 1.2 mm, 13.6+/-1.9 mm and 13.5+/-1.4 mm(Table 3, Fig. 4). 4. CSA(cross sectional area) of trachea were 201.1+/-31.3 mm(2) in male and 145.4+/-27.7(2) mm in female(Table 4). 5. CSA at C5, C6, C7 and Tl in male were 175.9+/-61.1 mm(2), 201.1+/-43.8 mm(2), 196.2+/-36.2 mm(2) and 230.9+/-463 mm(2) (Table 4, Fig. 5). CSA at C5, C6, C7 and Tl in female were 127.0+/- 33.4 mm(2), 138.434.6 mm(2), 140.734.7 mm(2) and 171.7+/-42.0 mm(2) (Table 4, Fig. 5). 6. CSA of trachea among male patients were 198.1+/-28,5 mm(2), 206.2+/-33.0 mm(2) and 198.3+/-33.1 mm(2) in group 1, 2 and 3 (Table 5, Fig. 6). CSA of trachea in female age group 1, group 2 and group. 3 were 140.2+/-25.0 mm(2), 152.8+/-32.4 mm(2) and 145.6+/-25.1 mm(2) (Table 5, Fig. 6). But there was no significant difference between groups according to the sex. 7. CSA of trachea in age groups were stastically insignificant for both sex.

A Study of Allergy Skin Tests with Korean Pollen Extracts

In Korea, there are two descrite pollen seasons: a tree pollen season and a weed pollen season. In order to investigate the incidence of sensitization to the major pollens and to evaluate is clinical significance in respriatory allergic disease, skin prick tests were performed using 7 species of Korean pollen extracts (K-P extracts) and specific IgE was measured by the Phadebas radioallergosorbent test (RAST) in patients with positive skin prick tests. Of the 317 patients with respiratory allergic diseases 73 patients (23.0%) were skin prick test positive to one or more K-P extracts and the positive reactions to individual pollens were as follows: 14.2% (45/317) positive to sagebrush 10.4% to ragweed, 5.0% to grass, 4.1% to oak, 3.8% to alder, 1.9% to poplar; and 0% to pine. The 30-39yr old group manifested the highest skin test positivity 36.7%. There was no difference in the skin reactivity according to the patient's sex and the kinds of allergic disease. Also there was no relationship between birth season and skin test positivity. The agreement between the results of the skin prick test with K-P and commercially prepared Bencard's pollen extracts (B-P extracts) was good. There were good correlations between the strongly positive skin prick test and a posivite RAST and also between a netative skin prick test and a negative RAST. From this study, it can be concluded that overall sensitization rate of respiratory allergy patients to K-P exstracts was 23.0%, and that weed pollens such as sagebrush and ragweed were major pollens.