Gastroenterology and Hepatology from Bed to Bench

Aim: To investigate the ATP7B gene in ethnically different Iranian patients with Wilson disease.

Background: Copper transporting beta polypeptide, ATP7B or WND gene is predominantly expressed in liver and has been identified as the defective gene. WND gene is located on Chr13q14.3 and consists of 21 expressed exons.

Patients and methods: Diagnosis of WD was verified according to the biochemical characterizations including serum ceroluplasmin (<0.2g/l), 24-hour urine copper after challenging by D-penicillamine (>25mmol/24h), liver copper (>250µg/g dry weight), Kayser-Fleischer rings, Cu-ATPase activity, and liver and brain imaging features. A total of 70 patients aged 5-40 years, were included. Patients were classified in three different categories; hepatic, neurologic and combined based on their clinical presentations. Bi-directional sequencing was performed using the ABI 3130xl, Genetic analyzer (Applied-Biosystem).

Results: Totally, 12 different mutations have been found in 18 patients with Wilson's disease. Of these, T788I, 2803-2805 ACG>-TG, 2532delA and H1069N were novel mutations. Meanwhile, we have found 4 polymorphisms.

Conclusion: Mutations are highly distributed among the different exons of ATP7B gene in Iranian patients with WD.

Amebiasis is the infection of the human gastrointestinal tract by Entamoeba histolytica, a protozoan parasite that is capable of invading the intestinal mucosa and may spread to other organs, mainly the liver. The detection of Entamoeba histolytica from the nonpathogenic but identically appearing parasites Entamoeba dispar and Entamoeba moshkovskii is an important goal of the clinical microbiology laboratory. Currently, there is no low-cost laboratory test available for the differentiation of E. histolytica from E. dispar infections. It is likely that at least 90% of the infections previously ascribed to E. histolytica are actually E. dispar, while only the remaining 10% are infected with E. histolytica in its new sense. The present manuscript review recent advances in this regard. The purpose of this study is to alert physicians (and perhaps with their help, laboratories) to the importance of distinguishing between the two species of amoebae.

Aim: To evaluate antimicrobial resistance pattern of Shigella spp. isolated from patients with acute diarrhea in Tehran, Iran.

Background: Infectious diarrheal diseases caused by Shigella spp. are significant health concern world wide. They are responsible for considerable morbidity and mortality especially in developing countries.

Patients and methods: A total of 1120 fecal samples from patients with acute diarrhea from May 2003 to May 2005 were investigated to evaluate antimicrobial susceptibility patterns of predominant isolates from different hospitals in Tehran, Iran. Identification of isolates was carried out according to standard methods.

Results: Among isolated enteropathogens, Shigella spp. were found in 14%. Shigella sonnei was commonest (56.1%) followed by Shigella flexneri, boydii and dysenteriae that were found in 30.6%, 8.3% and 5.1% of isolates, respectively. Of all isolates, 66.3% were detected in patients less than 5 years old. Resistance pattern was as follow: tetracycline 95.5%, ampicillin 51.5% and trimethoprim-sulfamethoxazole 91.7%. None of the isolates were resistant to ciprofloxacin, ceftriaxone and ceftazidime. An interesting finding in our study was a high degree of multidrug resistance to 3 and more antibiotics among isolates 91%.

Conclusion: In conclusion, Shigella species isolated from acute diarrhea in Iran have a high degree of resistance to commonly used antibiotics. The emergence of multidrug-resistance demands continues monitoring of susceptibility pattern of Shigella isolates. The changing of resistance pattern to common antibiotics in Iran indicates that designing a monitoring system for detection of antimicrobial resistance and guidelines for the appropriate use of antibiotics are urgently needed.

Aim: To gain recent characteristic information about inflammatory bowel disease (IBD) in Iran.

Background: Inflammatory bowel disease (IBD) was believed to be infrequent in Iran; however, during the recent years its prevalence has been continuing in our country.

Patients and Method: Between 1992 and 2007, a total of 803 IBD patients (671 ulcerative colitis (UC), 109 Crohn's disease (CD) and 23 indeterminate colitis (IC)) referred to our research centre. We evaluated the demographic data, extraintestinal manifestations, chief complaints and extension of disease in this group of patients.

Results: The mean age at diagnosis was 33.01, 33.18, and 34.52 years in UC, CD, and IC patients, respectively. The male to female ratio was 0.78 for UC patients while it was 1.18 in CD patients. Patients with UC chiefly presented by hematochezia (54.24%), whereas those with CD and IC complained of abdominal pain (55.96% and 47.82%, respectively). Totally, 67.51% UC patients, 70.64% CD patients and 73.90% IC patients reported extra intestinal manifestations. The most involved section was left colon in UC (90.49%) and colon in CD patients (75%).

Conclusion: The demographic and clinical picture of IBD is more or less the same as other developing countries; however, the rarity of CD in Iran is noted. Although the true epidemiologic profile of IBD in Iran is still unknown, it is not as rare as previously thought and it seems as if gradual adoption of a western lifestyle may be associated with continuing rise in IBD.

Aim: To evaluate endoscopic results of a large number of Iranian patients with dyspepsia.

Background: Dyspepsia is quite common among adults and has a great impact on the patient's quality of life. The present study was designed to investigate the structure of dyspepsia and to determine existing symptoms and endoscopic findings.

Patients and methods: Over a period of 14 months (April 2003- June 2004), 940 consecutive outpatients referred for upper gastrointestinal endoscopy because of dyspepsia. The value of the criteria distinguishing between the two major diagnostic groups, peptic ulcer and non-ulcer dyspepsia, was assessed by comparing the group of non-ulcer dyspepsia with the group of patients with peptic ulcer.

Results: Ulcer-like presentation (69.3%) was the predominant symptom. Totally, 133 (14.1%) have peptic ulcer disease (PUD). Alcohol use and smoking were significantly higher in PUD group. H.Pylori was higher in PUD (68.4% in PUD versus 41.5% in NUD, p=0.000).

Conclusion: Regardless of numerous studies and trials, dyspepsia still remains a controversial issue. The analysis of the data of the overall patient population remains the subject of future research

Aim: To determine the expression of DNA MMR proteins, including hMLH1 and hMSH2, in gastric epithelial cells of patients with or without H. pylori infected gastritis.

Background: Impairment of DNA mismatch repair (MMR) system is a known mechanism of carcinogenesis and tumor progression in both sporadic and hereditary human cancers.

Patients and methods: Fifty H.pylori-positive patients and 50 H.pylori-negative subjects were enrolled in the study. During endoscopy of patients with non-ulcer dyspepsia, 2 antral and 2 corpus biopsies were taken for histologic examination (Giemsa stain) and immunohistochemical staining on hMLH1 and hMSH2.

Results: The percentage of epithelial cell nuclei demonstrating positivity for hMLH1 staining was 84.14±7.32 in H.pylori-negative subjects in comparison of 73.34±10.10 in H.pylori-positive patients (p<0.0001). The percentage of epithelial cell nuclei demonstrating positivity for hMSH2 staining did not differ significantly (81.16±8.32 in H.pylori-negative versus 78.24±8.71 in H.pylori-positive patients; NS).

Conclusion: Study indicates that H.pylori might promote development of gastric carcinoma at least in part through the ability to affect the DNA MMR system.

Aim: To comparing furazolidone and tetracycline in quadruple therapy for eradication of helicobacter pylori in dyspepsia patients.

Background: Helicobacter pylori eradication is the main step in dyspepsia and peptic ulcer management. In Iran different regimens have been proposed, however, most of our patients are resistant to metronidazole. In the current study we compared furazolidone- and tetracycline-based quadruple therapy for eradication of H.pylori in a group of Iranian patients with dyspepsia.

Patients and methods: Dyspeptic patients were randomly assigned in 2 groups and received omeprazole 20mg/twice a day, bismuth subcitrate 200mg/q6h, amoxicillin 1000mg/twice a day in association with furazolidone 100mg/ twice a day (OAB-F regimen) or tetracycline 500mg/ twice a day (OAB-T regimen). Stool antigen test was used to detect H. pylori eradication.

Results: Totally, 100 patients completed the desired regimen including 49 in OAB-F and 51 in OAB-T regimen. Following the first week, H. pylori was eradicated in 97.9% of OAB-F and 96% of OAB-T subjects, however, the difference did not reach a statistical significant level. These figures were 85.7% and 80.4% following the 4th week, respectively (NS).

Conclusion: Both furazolidone-and tetracycline-based quadruple therapy were revealed to be effective for eradication of H.pylori, however, furazolidone is suggested for population resistant to metronidazole since it is cheaper and more available.

Background: Primary liver lymphoma (PLL) is a rare disease. Patients usually present with abdominal problems and liver mass without any extrahepatic tumor. PLL usually responds well to chemotherapy, while chemotherapy±radiation is the standard treatment of choice.

Case report: A 42 year-old man was presented because of abdominal pain, 8.5kg weight loss and fever for 3 months. There was not lymphadenopathy, splenomegaly, abdominal mass or hepatomegaly in physical examination. A computed tomography (CT) scan of the abdomen disclosed multiple large liver masses without adenopathy. Patient responded well to CHOP chemotherapy regimen. Three months later, he was visited because of headache, dizziness and convulsion. A brain CT scan showed a mass in brain. He was treated by brain radiation plus intrathecal injection of methotrexate (MTX) (15mg) followed by 6 cycles of ICE protocol.

Conclusion: PLL is a rare disease that responds well to multi-agent chemotherapy. CNS metastasis should be considered in the affected patients.