Overlapping gastroesophageal reflux disease and irritable bowel syndrome:Increased dysfunctional symptoms

AIM:To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.METHODS: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4±11.5 years) met Rome or Rome criteria(depending on the year of diagnosis)for IBS.2658 patients were diagnosed with GERD based on clinical presentation and endoscopic findings.We assessed other functional symptoms(epigastric pain,nausea,vomiting,belching,constipation and diarrhea)in patients suffering from GERD,IBS or both.RESULTS: Among IBS subjects, 63.6% (69.0% women, 31.0% men; mean age: 36.4±10.3 years) also hadGERD, whereas 34.7% of the non-IBS patients had GERD [odds ratio (OR) =3.2, 95% confidence interval (CI): 2.9-3.7, P<0.0001]. Among patients with GERD, 33.9% of subjects met Rome criteria compared to 13.5% of non-GERD patients (OR=3.6, 95% CI: 3.1-4.3, P<0.0001). Prevalence of all functional symptoms was higher in overlapping GERD and IBS subjects, when compared with their prevalence in the IBS subjects without GERD or GERD only subjects (P<0.05).CONCLUSION: This finding shows that in overlapping GERD and IBS, other functional abnormalities of the GI tract are also highly prevalent, suggesting a common underlying dysfunction.

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage

AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH).

The effect of NAFLD (non-alcoholic fatty liver disease) on long-term outcome of chronic hepatitis B in Iranian patients

Background: The influence of Non-Alcoholic Fatty Liver Disease on the outcome of chronic hepatitis B disease, including viral, biochemical and histologic characteristics, in Iranian patients is not yet fully un- derstood. Aim: To evaluate the effect of Non-Alcoholic Fatty Liver Disease (NAFLD) on long-term histology- cal, biochemical and viral outcome of chronic he- pa-tictis B in Iranian patients. Methods: We retro- spec-tively evaluated 94 “e Ag” negative chronic hepatitis B patients (with NAFLD: 44, without NAFLD: 50). Non-Alcoholic Fatty Liver Disease was diagnosed based on liver biopsy according to Kleiner classifica-tion. Liver biopsy was done for all patients. Serologi-cal and biochemical variables were evaluated with repeated measure analysis. Results: Non-Alcoholic Fat- ty Liver Disease (NAFLD) was present in 47% of the patients (44 out of 94 patients). In the NAFLD group, increase in AST, ALT, stage (P = 0.002), grade, and total score of liver biopsy were independently related to non-alcoholic fatty liver disease, while HBV-DNA viral load did not correlate with the presence of a fatty liver. Conclusion: Abnormalities of liver enzymes and liver histopathology are more prevalent in concurrent chronic hepatitis B and Non-Alcoholic Fatty Liver Disease (NAFLD).

Antibiotic resistance analysis and coping strategies of helicobacter pylori

Helicobacter pylori(H.pylori)is a Gram-negative bacterium that mainly colonizes the stomach and duodenum,and it can cause gastrointestinal diseases such as gastric inflammation,peptic ulcer and gastric cancer,and eradication of H.pylori can effectively stop the occurrence and development of gastrointestinal diseases.Antibiotics are one of the main drugs used to treat H.pylori.Due to the long-term application of antibiotics,the resistance rate of H.pylori to antibiotics increases year by year,which greatly reduces the eradication rate of H.pylori and increases the difficulty of re-treatment and the economic burden of patients.In this paper,we will review three aspects of H.pylori resistance status,resistance mechanism and treatment to provide reference for the progress of H.pylori resistance research and its treatment strategy.

Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis

AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.

Premedication with pronase or N-acetylcysteine improves visibility during gastroendoscopy: An endoscopist-blinded, prospective, randomized study

AIM： To assess the efficacy of premedicaton with pronase or N-acetylcysteine （NAC） at 20 min before upper gastrointestinal （UGI） endoscopy and to determine whether pronase or NAC pretreatment influences the reliability of the rapid urease test. METHODS： A total of 146 patients were prospectively and randomly assigned into the study groups according to different premedications before endoscopy. One endoscopist assessed mucosal visibility （MV） with scores ranged from 1 to 4 at four sites in the stomach. The sum of the MV scores from these four locations was defined as the total mucosal visibility （TMV） score. Identification of Hpylori was performed using CLO test, histology, and serology. RESULTS： The Group with pronase premedication had a significantly lower TMV score than did the groups with gascon and gascon water （P 〈 0.001 and P 〈 0.01, respectively）. The group with NAC had a significantly lower TMV score than the group with gascon （P 〈 0.01） and a trend of a lower MV score than the group with gascon water （P = 0.06）. The THV score did not significantly differ between the group with pronase and the group with NAC （P = 0.39 and P = 0.14, respectively）. The sensitivity and specifidty of the CLO test were 92.5% and 93.9%, respectively, in groups premedicated with pronase and NAC together.CONCLUSION： Premedication with pronase or NAC at 20 min before UGI endoscopy improves the mucosal visibility of the stomach. Neither pronase nor NAC produces any obvious interference with the CLO test for the identification of H pylori infection.

Association of p53/p21 expression with cigarette smoking and prognosis in esophageal squamous cell carcinoma patients

【Abstract】factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P【0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P【0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.

Human papillomavirus in squamous cell carcinoma of esophagus in a high-risk population

AIM: To investigate the relation of human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in Iranian patients as compared to normal controls. METHODS: Using MY09/MY11 consensus primers, we compared the prevalence of a HPV L1 gene in tumor tissues from 38 ESCC cases and biopsied tissues from 38 endoscopically normal Iranian individuals. We also compared the presence of HPV16 and HPVA18 in the same samples using type-specific E6/E7 primers. RESULTS: Fourteen (36.8%) of the 38 ESCC samples but only 5 (13.2%) of the 38 control samples were positive for the HPV L1 gene (P= 0.02). Five (13.2%) of the ESCC samples but none of the control samples were positive for the HPV16 E6/E7 gene (P= 0.05). Three (7.9%) of the ESCC samples and 5 (13.2%) of the control samples were positive for the HPV18 E6/E7 gene (P= 0.71). CONCLUSION: Our data are consistent with HPV DNA studies conducted in other high-risk areas for ESCC. HPV should be considered as a potential factor contributing to the high incidence of ESCC in Iran and other high-incidence areas of the world.

Sex hormones in the modulation of irritable bowel syndrome

Compelling evidence indicates sex and gender differences in epidemiology, symptomatology, pathophysiology, and treatment outcome in irritable bowel syndrome (IBS). Based on the female predominance as well as the correlation between IBS symptoms and hormonal status, several models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function including differences in GI symptoms expression in distinct phases of the menstrual cycle, in pre- and post-menopausal women, during pregnancy, hormonal treatment or after oophorectomy. Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa. Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, neuroimmune interactions triggered by stress, as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized. A concept of &#x0201c;microgenderome&#x0201d; related to the potential role of sex hormone modulation of the gut microbiota is also emerging. Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders, together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder.

Healthy ranges of serum alanine aminotransferase levels in Iranian blood donors

AIM: The healthy ranges for serum alanine aminotransferase(ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors. METHODS: A total of 1 939 blood donors were included.ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels werecomputed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels.RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L,and for non-overweight men was 40 U/L.CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.

Achalasia: A review of Western and Iranian experiences

Achalasia is a primary motor disorder of the eso-phagus, in which esophageal emptying is impaired. Diagnosis of achalasia is based on clinical fi ndings. The diagnosis is confirmed by radiographic, endoscopic, and manometric evaluations. Several treatments for achalasia have been introduced. We searched the PubMed Database for original articles and meta-analyses about achalasia to summarize the current knowledge regarding this disease, with particular focus on different procedures that are used for treatment of achalasia. We also report the Iranian experience of treatment of this disease, since it could be considered as a model for medium-resource countries. Myotomy, particularly laparoscopic myotomy with fundoplication, is the most effective treatment for achalasia. Compared to other treatments, however, the initial cost of myotomy is usually higher and the recovery period is longer. When performing myotomy is not indicated or not possible, graded pneumatic dilation with slow rate of balloon inflation seems to be an effective and safe initial alternative. Injection of botulinum toxin into the lower esophageal sphincter before pneumatic dilation may increase remission rates. However, this needs to be conf irmed in further studies. Due to lack of adequate information regarding the role of expandable stents in the treatment of achalasia, insertion of stents does not currently seem to be a recommended treatment. In summary, laparoscopic myotomy can be considered as the procedure of choice for treatment of achalasia. Graded pneumatic dilation is an effective alternative when the performance of myotomy is not possible for any reason.

Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer

AIM： To assess the proteome of normal versus tumor tissue in squamous cell carcinoma of the esophagus （SCCE） in Iranian patients and compare our results with former reports by using proteomics. METHODS： Protein was extracted from normal and tumor tissues. Two dimensional electrophoresis was carried out and spots with differential expression were identified with mass spectrometry. RNA extraction and RT-PCR along with immunodetection were performed. RESULTS： Fourteen proteins were found whose expression levels differed in tumor compared to normal tissues. Mass spectrometric analysis resulted in the identification of β-tropomyosin （TMβ）, myosin light chain 2 （and its isoform）, myosin regulatory light chain 2, peroxyredoxin 2, annexin I and an unknown polypeptide as the down regulated polypeptides in tumor tissue. Heat shock protein 70 （HSP70）, TPM4-ALK fusion oncoprotein 2, myosin light polypeptide 6, keratin I, GH16431p and calreticulin were the up-regulated polypeptides found in tumor tissue. Several of these proteins, such as TMβ, HSP70, annexin Ⅰ, calreticulin, TPM4-ALK and isoforms of myosins, have been well recognized in tumorigenesis of esophageal or other types of cancers. CONCLUSION： Our study not only supports the involvement of some of the formerly reported proteins in SCCE but also introduces additional proteins found to be lost in SCCE, including TMβ.

Involvement of cholangiocyte proliferation in biliary fibrosis

Cholangiocytes are the epithelial cells that line the biliary tree.In the adult liver,they are a mitotically dormant cell population,unless ductular reaction is triggered by injury.The ability of cholangiocytes to proliferate is important in many different human pathological liver conditions that target this cell type,which are termed cholangiopathies(i.e.primary biliary cirrhosis,primary sclerosing cholangitis and biliary atresia).In our article,we provide background information on the morphological and functional heterogeneity of cholangiocytes,summarize what is currently known about their proliferative processes,and briefly describe the diseases that target these cells.In addition,we address recent findings that suggest cholangiocyte involvement in epithelial-to-mesenchymal transformation and liver fibrosis,and propose directions for future studies.

Persistent alanine aminotransferase elevation among the general Iranian population: Prevalence and causes

AIM: To determine the prevalence and causes of persistently elevated alanine aminotransferase (ALT) levels among the general population in northern Iran. METHODS: A total of 2292 (1376 female, aged 18-75 year), were selected by systematic clustered random sampling from the cities and villages of Gonbad and Kalaleh in Golestan Province and invited to participate in the study. A comprehensive history regarding alcohol drinking and medication was taken. Body mass index (BMI), viral markers and ALT levels were measured. If ALT level was ≥ 40 U/L, it was rechecked twice within 6 mo. Those with ≥ 2 times elevation of ALT were considered as having persistently elevated ALT level. Non-alcoholic fatty liver disease (NAFLD) was diagnosed based on evidence of fatty liver upon sonography and excluding other etiology. RESULTS: A total of 2049 (1351 female) patients participated in the study, 162 (7.9%) had elevated ALT level at the first measurement. Persistently elevated ALT level was detected in 64 (3.1%) participants, with51 (79.6%) with no obvious etiology, six (9.3%) with Hepatitis B, four (6.2%) with Hepatitis C virus (HCV) infection and three (4.6%) with alcoholic hepatitis. The prevalence of NAFLD and alcoholic hepatitis was 2.04% (42 patients) and 0.1% (three), respectively. There was correlation between NAFLD and male gender, overweight, diabetes and living in an urban area [odds ratio = 3.03 (95% CI: 1.6-5.72), 4.21 (95% CI: 1.83-9.68), 2.86 (95% CI: 1.05-7.79) and 2.04 (95% CI: 1.00-4.16) respectively]. CONCLUSION: NAFLD is the most common cause of persistently elevated serum ALT level among the general population of Iran.

Eradication of Helicobacter pylori significantly reduced gastric damage in nonsteroidal anti-inflammatory drug-treated Mongolian gerbils

AIM: To examine the effect of eradication of Hellcobacter pylori prior to usage of NSAIDs, by investigating gastric inflammatory activity, myeloperoxidase (MPO) activity, prostaglandin (PG) E_2 synthesis in H Pylori-infected, and H pylori-eradicated gerbils followed by administration of indomethacin and rofecoxib. METHODS: Six-week-old male gerbils were orally inoculated with H pylori. Seven weeks later, anti-H pylori triple therapy and vehicle were given to gerbils respectively and followed by oral indomethacin (2 mg/kg·d) or rofecoxib (10 mg/kg·d) for 2 wk. We examined the area of lesions, gastric inflammatory activity, PGE_2 synthesis and MPO activity in the stomach. RESULTS: In indomethacin and rofecoxib-treated gerbils, the following results were obtained in H pylori-infected group vs H pylori-eradicated group respectively: hyperplasia area of the stomach (mm^2): 82.4±9.2 vs 13.9±3.5 (P＜0.05), 30.5±5.1 vs 1.3±0.6 (P＜0.05); erosion and ulcer area (mm^2): 14.4±4.9 vs 0.86±0.5 (P＜0.05), 1.3±0.6 vs0.4±0.3 (P＜0.05); score of gastritis: 7.0±0.0 vs3.6±0.5 (P＜0.05), 7.0±0.0 vs 2.7±0.5 (P＜0.05); MPO activity (μmol H_2O_2/min/g tissue): 104.7±9.2 vs9.0±2.3(P＜0.05), 133.5±15.0 vs2.9±0.7 (P＜0.05); PGE_2 synthesis (pg/mg wet weight/min): 299.2±81.5 vs102.8±26.2 (P＜0.05), 321.4±30.3 vs 11.9±4.8(P＜0.05). CONCLUSION: Eradication of H pylori reduced gastric damage of NSAID-treated Mongolian gerbils. Rofecoxib caused less severe gastric damage than indomethacin in H pylori-eradicated gerbils.

Central role of Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif in pancreatic cancer development

Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive PDAC.Additional genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflammation, are required for full PDAC formation. We hypothesize that oncogenic KRAS increases the intensity and duration of the growth-promoting signaling network.Recent exciting studies from different laboratories indicate that the activity of the transcriptional co-activators Yes-associated protein(YAP) and WW-domaincontaining transcriptional co-activator with PDZ-binding motif(TAZ) play a critical role in the promotion and maintenance of PDAC operating as key downstream target of KRAS signaling. While initially thought to be primarily an effector of the tumor-suppressive Hippo pathway, more recent studies revealed that YAP/TAZ subcellular localization and co-transcriptional activity is regulated by multiple upstream signals. Overall, YAP has emerged as a central node of transcriptional convergence in growth-promoting signaling in PDAC cells. Indeed, YAP expression is an independent unfavorable prognostic marker for overall survival of PDAC. In what follows, we will review studies implicating YAP/TAZ in pancreatic cancer development and consider different approaches to target these transcriptional regulators.

A novel device for endoscopic submucosal dissection,the Fork knife

AIM： To introduce and evaluate the efficacy and technical aspects of endoscopic submucosal dissection （ESD） using a novel device, the Fork knife. METHODS： From March 2004 to April 2008, ESD was performed on 265 gastric lesions using a Fork knife （Endo FS） （group A） and on 72 gastric lesions using a Flexknife （group B） at a single tertiary referral center. We retrospectively compared the endoscopic characteristics of the tumors, pathological findings, and sizes of the resected specimens. We also compared the en b/oc resection rate, complete resection rate, complications, and procedure time between the two groups. RESULTS： The mean size of the resected specimens was 4.27 ± 1.26 cm in group A and 4.29 ± 1.48 cm in group B. The en b/oc resection rate was 95.8% （254/265 lesions） in group A and 93.1% （67/72） in group B. Complete ESD without tumor cell invasion of the resected margin was obtained in 81.1% （215/265） of group A and in 73.6% （53/72） of group B. The perforation rate was 0.8% （2/265） in group A and 1.4% （1/72） in group B. The mean procedure time was 59.63 ± 56.12 min in group A and 76.65 ± 70.75 min in group B （P 〈 0.05）. CONCLUSION： The Fork knife （Endo FS） is useful for clinical practice and has the advantage of reducing the procedure time.

Treatment of upper gastrointestinal fistula and leakage with personal stage nutrition support

AIM： To investigate the feasibility of treatment for upper gastrointestinal fistula and leakage with personal stage nutrition support. METHODS： Forty-three patients with upper gastrointestinal fistula and leakage were randomly divided into two groups. Patients in group A were treated with personal stage nutrition support and patients in group B were treated with total parental nutrition （TPN） in combination with operation. Nutritional states of the candidates were evaluated by detecting albumin （AIb） and pre-AIb. The balance between nutrition and hepatic function was evaluated by measurement of aspartate aminotransferase （AST）, alanine aminotransferase （ALT） and total bilirubin （Tbill） before and after operation. At the same time their complications and hospitalized time were surveyed. RESULTS： Personal stage nutrition support improved upper gastrointestinal fistula and leakage. The nutrition state and hepatic function were better in patients who received personal stage nutrition support than in those who did not receive TPN. There was no significant difference in the complication and hospitalized time in the two groups of patients. CONCLUSION： Upper gastrointestinal fistula and leakage can be treated with personal stage nutrition support which is more beneficial for the post-operation recovery and more economic than surgical operation.

Deformity of duodenal bulb, gastric metaplasia of duodenal regenerating mucosa and recurrence of duodenal ulcer: A correlated study

AIM: To investigate the correlation among the presence and degree of gastric metaplasia of duodenal regenerating mucosa, the deformity of bulb and the recurrence of duodenal ulcer.METHODS: A total of 99 patients with duodenal ulcer were treated with H2-antagonist with or without antimicrobial therapy. All patients received follow-up endoscopic examinations 6 wk after treatment. When the ulcer(s) were noted to be healed, two biopsies were taken from the ulcer scar for histological study of gastric metaplasia, and 4 biopsies were taken from antrum for Helicobacter pylori(H pylori) study. Out of these cases,44 received further follow-up endoscopic examinations after 3, 6 and 12 mo respectively for studying the recurrence rate of duodenal ulcers. The correlation among ulcer recurrence, degree of gastric metaplasia of regenerating mucosa, bulbar deformity, and colonization of Hpylori in the stomach was then studied.RESULTS: The results showed that there was a strong correlation between the deformity of duodenal bulb and the degree of gastric metaplasia of regenerating duodenal mucosa. The recurrence rate of duodenal ulcer had a significant difference between patients with and without Hpyloricolonization in the stomach (P＜0.001). The greater the degree of gastric metaplasia of duodenal regenerating mucosa, the higher the recurrence rate of duodenal ulcer (P= 0.021). The more deformed the duodenal bulb, the higher the incidence of recurrence of duodenal ulcer (P = 0.03).CONCLUSION: There is a correlation among deformity of duodenal bulb, gastric metaplasia of duodenal regenerating mucosa and recurrence of duodenal ulcer.A more severely deformed duodenal bulb is closely related to a greater extent of gastric metaplasia. Both factors contribute to the recurrence of duodenal ulcer.

Ecologic study of serum selenium and upper gastrointestinal cancers in Iran

AIM:Both observational and experimental studies have shown that higher selenium status reduces the risk of upper gastrointestinal cancers in selenium deficient populations. Recent cancer registry data have shown very different rates of esophageal cancer(EC)and gastric cancer(GC)in four Provinces of Iran,namely Ardabil,Mazandaran,Golestan, and Kerman.The aim of this study was to have a preliminary assessment of the hypothesis that high rates of EC in Golestan and high rates of GC in Ardabil may be partly attributable to selenium deficiency. METHODS:We measured serum selenium in 300 healthy adults from An:labil(n=100),Mazandaran(n=50),Golestan (n=100),and Kerman(n=50),using inductively coupled plasma,with dynamic reaction cell,mass spectrometry(ICP- DRC-MS)at the US Centers for Disease Control(Atlanta, Georgia). RESULTS:The median serum selenium concentrations were very different in the four Provinces.The medians(IQR)for selenium in Ardabil,Mazandarn,Golestan,and Kerman were 82(75-94),123(111-132),155(141-173),and 119 (110-128)μg/L,respectively(P<0.001).The results of linear regression showed that the Province variable,by itself, explained 76% of the variance in log selenium(r^2=0.76). The proportion of the populations with a serum selenium more than 90 μg/L(the concentration at which serum selenoproteins are saturated)was 100% in Golestan, Kerman,and Mazandaran but only 29% in Ardabil. CONCLUSION:Our findings suggest that selenium defidency is not a major contributor to the high incidence of EC seen in northeastern Iran,but it may play a role in the high incidence of GC in Ardabil Province. Nouarie M,Pourshams A,Kamangar F,Sotoudeh M,Derakhshan MH,Akbari MR,Fakheri H,Zahedi MJ,Caldwell K,Abner CC, Taylor PR,Malekzadeh R,Dawsey SM.Ecologic study of serum