Association between waterpipe smoking and lung cancer: a multicentre case-control study in Iran.

OBJECTIVES: This study investigated the association between lung cancer and waterpipe smoking, which is an emerging global public health concern. STUDY DESIGN: Multicentre case-control study. METHODS: This study included 627 cases and 3477 controls from the Iranian Study of Opium and Cancer (IROPICAN) study, which was conducted between 2017 and 2020. One frequency-matched control for each lung cancer patient was selected by age, gender and residential place; however, this study used controls of four cancer types in the analyses. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence intervals (CIs). Additional analyses were performed among 181 lung cancer cases and 2141 controls who were not cigarette smokers or opium or nass/pipe users. RESULTS: The odds of lung cancer were higher among waterpipe smokers than never-smokers (OR = 1.3, 95% CI: 1.0-1.7). Results showed a higher OR of lung cancer for those who smoked the waterpipe daily (OR = 2.1, 95% CI: 1.4-3.0), smoked more than two heads per day (OR = 2.7, 95% CI: 1.8-4.0), had smoked for >20 years (OR = 1.9, 95% CI: 1.3-2.7), smoked more than 20 head-years (OR = 2.8, 95% CI: 1.9-4.1) and initiated smoking before the age of 30 years (OR = 1.7, 95% CI: 1.1-2.5). The association was only statistically significant for squamous cell carcinomas (OR = 1.8, 95% CI 1.2-2.7). Furthermore, this study observed a higher OR of lung cancer among exclusive waterpipe smokers (OR = 2.3, 95% CI: 1.6, 3.5). CONCLUSIONS: Waterpipe smoking was associated with an increased risk of lung cancer. The association was stronger with higher frequency, duration and intensity of exposure to waterpipe smoking. The association increases in exclusive waterpipe smokers, which is likely due to controlling for residual confounding by cigarette smoking and opium consumption, and higher exposure levels in this subpopulation.

International cancer seminars: a focus on esophageal squamous cell carcinoma.

The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts.

Polymorphisms in EGFR and IL28B are associated with spontaneous clearance in an HCV-infected Iranian population.

Although most hepatitis C virus (HCV)-infected individuals develop chronic infection, about 25% of them are able to clear the virus spontaneously without any therapeutic intervention. The aim of the present study was to identify genes associated with spontaneous HCV clearance in a population of Iranian patients. We genotyped 110 single-nucleotide polymorphisms (SNPs) in 59 selected--candidate--genes in a cohort of 107 HCV-infected participants who spontaneously cleared the infection and 176 participants whose infection persisted. Three out of the 110 SNPs were found to be associated with HCV outcome (P-values<0.03). rs11506105 in EGFR (epidermal growth factor receptor gene), and rs11881222 and rs12979860 in IL28B (interferon-λ3 gene). Multivariate logistic regression of the three markers showed that the A/A genotypes in both rs11506105 (EFGR) and rs11881222 (IL28B), and the C/C genotype in rs12979860 (IL28B) are associated with HCV clearance (recessive model: odds ratio (OR)=2.06, 95% confidence interval (95% CI)=1.09-3.88, P=0.025; OR=2.09, 95% CI=1.23-3.60, P=0.007; and OR=1.95, 95% CI=1.15-3.35, P=0.014 for rs11506105, rs12979860 and rs11881222, respectively). In conclusion, EGFR and IL28B SNPs are strong independent predictive markers of spontaneous viral clearance.

Pilot study of cytological testing for oesophageal squamous cell dysplasia in a high-risk area in Northern Iran.

BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is a fatal disease with 5-year survival rates of <5% in Northern Iran. Oesophageal squamous dysplasia (ESD) is the precursor histologic lesion of ESCC. This pilot study was conducted to assess the feasibility, safety, and acceptability of non-endoscopic cytological examination of the oesophagus and to provide initial data on the accuracy of cytological atypia for identifying patients with ESD in this very-high-risk area. METHODS: Randomly selected asymptomatic participants of the Golestan Cohort Study were recruited. A cytological specimen was taken using a capsule sponge device and evaluated for atypical cells. Sections of the cytological specimen were also stained for p53 protein. Patient acceptability was assessed using a visual analogue scale. The cytological diagnosis was compared with a chromoendoscopic examination using Lugol's solution. RESULTS: Three hundred and forty-four subjects (43% male, mean (s.d.) age 55.6 (7.9) years) were referred to the study clinic. Three hundred and twelve met eligibility criteria and consented, of which 301 subjects (96.5%) completed both cytological and endoscopic examinations. There were no complications. Most of the participants (279; 92.7%) were satisfied with the examination. The sensitivity and specificity of the cytological examination for identifying subjects with high-grade ESD were 100 and 97%, respectively. We found an accuracy of 100% (95% CI=99-100%) for a combination of cytological examination and p53 staining to detect high-grade ESD. CONCLUSIONS: The capsule sponge methodology seems to be a feasible, safe, and acceptable method for diagnosing precancerous lesions of the oesophagus in this population, with promising initial accuracy data for the detection of high-grade ESD.

[Vasovagal syncope: diagnosis and management]. / Syncope vasovagale: test diagnostique et prise en charge.

Vasovagal syncope is the main cause of syncope. The mechanism behind this syncope has not been clearly identified, but the main hypothesis is a paradoxical reaction of the autonomic nervous system leading to hypotension and/or bradycardia. According to the recommendations of the European Society of Cardiology, the diagnosis can be made only on the basis of history. In patients where the diagnosis is not clear, we can offer to make a tilt test, which is, however, limited in terms of sensitivity and does not represent the gold standard. The initial management is primarily conservative. Pacing should still be revisit by future studies.

Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Large body size and sedentary lifestyle during childhood and early adulthood and esophageal squamous cell carcinoma in a high-risk population.

BACKGROUND: Little is known about the association of obesity and physical activity at young ages with subsequent risk of esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Between 2003 and 2007, we conducted a case-control study in a high-risk population in northeastern Iran. Three hundred ESCC cases and 571 matched controls were recruited. Each individual was shown a standard pictogram, to report body size at ages 15 and 30. Demographic and health-related information, including physical activity at these ages was also collected. RESULTS: In the fully adjusted models, very obese body size (last two pictograms) at age 15 [odds ratio (OR) 3.2, 95% confidence interval (CI) 1.3-7.7] and age 30 (OR 3.1; 95% CI 1.1-8.5) were associated with ESCC in women, but not in men. Sedentary work at age 15 (OR 3.3, 95% CI 1.3-8.3) and 30 (OR 18.2, 95% CI 3.9-86.2) were also associated with ESCC risk in women only. The increased risk in women at age 15 remained high after later reduction in body size, while women who became very obese only at age 30 did not show a significantly increased risk. CONCLUSION: These results highlight the importance of early lifestyle modifications in the context of cancer prevention, particularly in women.

Development of New Modified Simple Polymerase Chain Reaction and Real-time Polymerase Chain Reaction for the Identification of Iranian Brucella abortus Strains.

Brucellosis is primarily a worldwide zoonotic disease caused by Brucella species. The genus Brucella contains highly infectious species that are classified as biological threat agents. In this regard, the identification of Brucella can be a time-consuming and labor-intensive process posing a real risk of laboratory-acquired infection to the laboratory staff. This study aimed to present a novel conventional and real-time polymerase chain reaction (PCR) assay for the identification of Brucella abortus strains. Regarding this, two primers (bru ab2) were designed based on the unique loci encoding autotransporter-associated beta strand repeat-containing protein (ID:YP00113760). A total of 56 Brucella strains (e.g., reference, vaccinal, and field isolates) and Yersinia enterocolitica, as a non-Brucella isolate, were evaluated in conventional and real-time PCR systems. The results of the study indicated that 0.4 ng and 400 FG of genomic DNA of B. abortus strains can be detected by conventional and real-time PCR, respectively. The primers, bru ab2, were suitable for both PCR methods. Both methods were specific for the detection of all strains of the bacterium; however, real-time PCR assay was 1000-fold more sensitive than the conventional PCR method. Therefore, this new detection system could be a suitable selective modified method for the accurate identification of all B. abortus strains.

A Case of Identity Confirmation of Brucella abortus S99 by Phage Typing and PCR Methods.

Brucellosis is a zoonotic infection that is associated with fever in humans and abortion in animals. The agent of this disease is a facultative intracellular gram-negative coccobacillus called Brucella. There are six classic species, including B. abortus, B. melitensis, B. suis, B. canis, B. neotomae, and B. ovis. In recent years, four new species have been reported, including Brucella ceti, B. microti, B. pinnipedialis, and B. inopinata. Human disease causes hygienic and economic losses, including inactivity of workforces in the community and high cost of treatment. The disease also causes catastrophic losses in the livestock industry. There is no effective vaccine against human brucellosis. Hence, attempts to prevent human infection with Brucella are focused on preventative measures, including control of infection in livestock, which lead to a reduction in its incidence in humans. The common methods for diagnosis of this disease are serologic methods including Rose Bengal, Wright -2 ME and the ring test. B. abortus strain S99 is used to produce these diagnostic antigens. The production of these antigens requires the presence of a well-characterized seed with full identity. The aim of this work was confirmation of the identity of B. abortus S99 by phage typing, AMOS and multiplex PCR techniques. Therefore, it is essential to carry out the identification of the strains used as seed for the production of the brucellosis diagnostic antigens. In this project, B. abortus strain 99 was supplied by the bacterial collection of the Brucellosis Department of Razi Vaccine and Serum Research Institute. Then, the main aim of the present study was the confirmation of the seed identity by doing the tests through the standard phage typing method, AMOS PCR and multiplex PCR (Brucladder) methods. Results were in support of the identity of the studied strain, and the molecular methods could also be used as the sensitive approaches for validation of antigenic seed.

Hypertension and mortality in the Golestan Cohort Study: A prospective study of 50 000 adults in Iran.

High blood pressure has been the second most important determinant of disease burden in Iran since the 1990s. Despite well-recognized evidence on the association of high blood pressure and mortality in other countries, this relationship has not been fully investigated in the demographic setting of Iran. The current study is the first large-scale longitudinal study of this association in Iran. Briefly, 50 045 subjects between 40 and 75 years of age have been recruited and followed. Blood pressure measurements were carried out at baseline. Causes of death were reported and verified by verbal autopsy throughout the follow-up period. The outcomes of interest were all-cause deaths and deaths due to ischemic heart disease (IHD) or stroke. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). A total of 46 674 subjects free from cardiovascular disease at baseline were analyzed. Absolute mortality rates increased along with increasing systolic or diastolic blood pressure above 120 and 80 mm Hg, respectively. Adjusted HRs (95% confidence intervals) for each 20 mm Hg increase in systolic blood pressure in all age groups were 1.18 (1.13-1.23) for all-cause mortality, 1.21 (1.13-1.31) for deaths due to IHD and 1.50 (1.39-1.63) for deaths due to stroke. Unadjusted and adjusted HRs were higher in younger subjects and decreased with increasing age of the participants. High blood pressure is a serious threat to the health of Iranians. The entire health-care system of Iran should be involved in a comprehensive action plan for controlling blood pressure.

Membrane asymmetry. A survey and critical appraisal of the methodology. I. Methods for assessing the asymmetric orientation and distribution of proteins.

This and the companion article are aimed at surveying the methods used for the study of membrane asymmetry. The techniques employed for the assessment of the asymmetric distribution and orientation of membrane proteins are reviewed in this article, whereas those pertaining to the unequal distribution of lipids are detailed in the companion paper. The use of immunological techniques and lectins, functions of proteins and their perturbations, chemical reagents, enzymatic isotopic labeling and enzymatic cleavage of membrane proteins and physical techniques are discussed and illustrated using recent examples of their application. Whenever appropriate, problems involving crypticity and non-availability or non-reactivity of functional sites, relevant chemical functions or protein fragments to appropriate ligands, reagents or modifying enzymes are envisaged and possible modification of the exposure of proteins during preparation of ghosts and other drawbacks are discussed, the use of different techniques and control experiments in conjunction is recommended for a more realistic assessment of the distribution and orientation of proteins.

Membrane asymmetry. A survey and critical appraisal of the methodology. II. Methods for assessing the unequal distribution of lipids.

In the companion paper, I have reviewed the techniques employed for assessment of the asymmetric distribution and orientation of membrane proteins. This article deals with methods applicable to the investigation of the unequal distribution of lipids between the two membrane leaflets. Among the techniques I will discuss are the use of immunological techniques and lectins, chemical reagents, enzymatic isotopic labeling and degradation of membrane lipids, exchange proteins and physical techniques. Whenever appropriate, problems of crypticity and non-availability of lipids to interact with the appropriate ligands, reagents, modifying enzymes or exchange proteins have been envisaged. It appears that in many case, highly discordant results, sometimes with the same biological material, have been obtained. Some of the difficulties encountered presumably stem from the reported existence of non-bilayer arrangements and isotropic movement of lipids as evidenced by freeze-fracture and NMR studies. Other problems may be related to the induction of such arrangements, especially the inverted micellar arrangement, by the modifying agents, particularly degradation enzymes or exchange proteins when they cause severe unilateral modification of the lipids of the exposed leaflet. In addition, the situation is complicated by the role of the induced increase in the flip-flop rate under different experimental conditions and by modification of the rearrangement of lipid molecules as a result of the metabolic state of the cell or ghost preparation and of the reactivity of lipids as a consequence of temperature changes. Here, more so than with proteins, one must be cautious in interpreting experimental results. Moreover, it would appear that the use of different techniques in conjunction and the consequent comparison of results should be recommended. It has been emphasized that 'general rules' do not hold and that each new material should be assay again. To give one example, it is not pertinent to state that proteins enhance the flip-flop rate in lipid vesicles (and hence in membranes). This holds true for glycophorin from erythrocyte membrane, but could not be proved when mitochondrial cytochrome oxidase was used. There seems to be no rule for the distribution of lipids between the two leaflets of different membranes. For example, even for different strains of the same bacterial species, highly divergent results have been reported. It is generally (and probably under the influence of different studies with erythrocytes) believed that in mammalian plasma membranes, choline phospholipids are enriched in the outer leaflet and aminophospholipids in the inner leaflet. Though this contention may prove to be correct, different instances of contradictory results have been given in the text. This shows that if rules do exist, they remain to be discovered or established...

Presence of two forms of palmityl-CoA-ACP-transacylase in homogenates of Mycobacterium smegmatis, purification using the monomer-polymer interconvertibility.

Homogenates of Mycobacterium smegmatis have been shown to contain, among other acyl-transfer enzymes, two entities endowed with palmityl-CoA-ACP-transacylase activity (1973, this journal, 55, 1381-1394). The present report demonstrates that these two entities, now called palmityl-CoA-ACP-transacylase I and palmityl-CoA-ACP-transacylase II, following their elution rate from a Sephadex G-150 column, are two interconvertible forms of the same enzyme. Form II, apparently predominant in the crude homogenates, is converted, during the purification steps, into Form I. The latter is convertible into Form II. It is observed that when the concentration of the enzyme increases, Form I becomes predominant. A purification of 800-fold was achieved, particularly by taking advantage of this convertibility properties. Parallel experiments conducted on S. cerevisiae and E. coli homogenates show the presence of the enzyme in the former and its absence in the latter microorganism.

Further analysis of acyl-CoA-ACP-transacylases of mycobacterium smegmatis. Identification of a long chain alkyl malonyl-CoA-ACP-transacylase.

Homogenates were prepared from three sources, Mycobacterium smegmatis Saccharomyces cerevisiae and Escherichia coli and tested for docosyl malonyl-CoA-ACP transacylase activity, using ACP purified from E. coli strain B and [2R, 2S, 1, 3-14C2] docosyl malonyl-CoA synthesized chemically, as substrates. Only homogenates of M. semegmatis showed positive transacylase activity. Successive chromatographies on Sephadex G-150 and then on DEAE-Sephadex A-50 prove that neither the palmityl-CoA-ACP-transacylase nor the malonyl-CoA-ACP-transacylase of M. smegmatis are responsible for this activity. The question concerning the identity of the enzyme with one of the two entities exhibiting acetyl-CoA-ACP-transacylase activity, previously identified in homogenates of this microorganism (1973 this journal, 55, 1381-1394), remains open for further experimentation. The physiological significance of the presence of a long chain alkyl malonyl-CoA-ACP-transacylase in homogenates of M. smegmatis, a representative of the Actinomycetales, is discussed in relation to the mechanism of the biosynthesis of mycolic acids. Chromatography on Sephadex G-100 showed that the substrate of the enzyme, docosyl malonyl-CoA, exists, in 50 mu molar aqueous solution, mostly in an aggregated state. A factor has been identified in the homogenates, which in the presence of radioactive docosyl malonyl-CoA, leads to the formation of a radioactive material showing an apparent molecular weight less than 10000. The nature of this material is discussed.

Immobilized ACP and electrofocusing used to purify the palmityl-CoA-ACP-transacylase from Mycobacterium smegmatis.

This paper describes the first purification to electrophoretic and chromatographic homogeneity of a palmityl-CoA-ACP-transacylase. Palmityl-CoA-ACP-transacylase of Mycobacterium smegmatis shows two interconvertible forms in monomer-oligomer correlation. Taking advantage of this interconvertibility properties a 800-fold purification of the enzyme was recently achieved (Kervabon et al (1976) Biochimie, 58, 647-656). The present report describes the use of immobilized ACP and electrofocusing to obtain a 880-fold and a 5 500-fold purification respectively. The enzyme thus purified, pI 4.7, showed a single band upon polyacrylamide gel electrophoresis. Chromatography on Sephadex G-150 revealed only the peak of the monomer. When the enzyme solution containing 200 microng/ml of protein was concentrated by vacuum dialysis to approximatively 1 mg/ml, gel electrophoresis showed two bands one corresponding to the monomer and the other to the oligomer formed.

In vivo depigmentation by hydroxybenzene derivatives.

Certain mono- and dihydroxybenzene derivatives are selectively cytotoxic for melanocytes in vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxicity/hair depigmentation in C57Bl mice by injection of 0.032-1.0% p-t-butylcatechol (tBC) or p-hydroxyanisole (MMEH) in physiological saline. No depigmentation occurred on injection of 3,4-dihydroxyphenylalanine (DOPA) or 3,4-dihydroxyphenylacetic acid (DOPAC). Light- and electron-microscopic examination of biopsy specimens taken from depigmented areas indicates selective melanocyte damage as early as 2 h post-injection. Melanocytes from anagen hair are most susceptible to depigmentation. All four compounds are substrates for tyrosinase, but only tBC and MMEH generate their respective isolable 1,2-benzoquinones, tBCQ and MMEHQ. These caused depigmentation in C57Bl mice to a comparable degree to the parent compounds. DOPA- and DOPAC-quinones (DOPAQ and DOPACQ) are not spectroscopically detectable in solution, suggesting extremely low steady-state levels of these compounds. The net observed rate of reaction of the respective 1,2-quinone with 300 microM bovine serum albumin (BSA) in vitro varies widely, with tBCQ >> MMEHQ = DOPACQ >> DOPAQ. The results are consistent with a mechanism involving attack of -SH on melanosomal proteins and/or enzymes by tyrosinase-generated 1,2-quinones. This mechanism evidently differs from that involved in in vitro hydroxybenzene melanocytotoxicity of melanoma cells, in which active oxygen intermediates generated by hydroxybenzene autoxidation play a significant role. The most reliable prognosticator of in vivo depigmentation appears to be the ability of the depigmenter to form a spectroscopically stable 1,2-quinone which is capable of reacting with protein -SH.

Does immunotherapy with heat-killed Mycobacterium vaccae offer hope for the treatment of multi-drug-resistant pulmonary tuberculosis?

The ability of immunotherapy with heat-killed Mycobacterium vaccae (NCTC 11659), as an addition to the available chemotherapy, to improve the outcome in patients with multi-drug-resistant tubercle bacilli (MDRTB) who had not been cured by chemotherapy alone was evaluated in tuberculosis centres in Estonia, Iran, Kuwait, New Zealand, Romania, Vietnam and the U.K. A total of 337 patients in the above countries received intradermal injections of M. vaccae in addition to chemotherapy. Patients were grouped according to the length of their histories of disease: less than or greater than 2 years duration. Initially, single doses of M. vaccae were given but subsequently up to 12 doses at 2-month intervals were given. Chemotherapy varied from isoniazid alone to drugs selected according to susceptibility tests. Most patients had failed to respond to repeated courses of chemotherapy and the majority, were expected to die from their disease. Results were assessed by sputum smear and culture and by clinical observations. Cured patients were followed for 18-24 months to exclude relapse. Eighteen of 22 (82%) patients with disease for less than 2 years were bacteriologically cured by one or two doses of M. vaccae. Among 315 chronic patients, 24 (7.6%) were cured after one dose, 37.9% after seven doses and 41.6% after 12 doses. Sixty-six chronic patients were lost to follow-up, or died, during the multi-dose regimens. Nine of 33 patients (27%) with advanced disease unaffected by several courses of chemotherapy and discharged on isoniazid alone in Vietnam were cured by 3-12 injections of M. vaccae. The data provide preliminary evidence that the addition of immunotherapy with M. vaccae to chemotherapy improves the rate of cure of MDRTB, most effectively in patients with short histories of disease, but multiple dosing can have beneficial effects in chronic patients in whom chemotherapy has failed. A randomized clinical trial of this immunotherapy in MDRTB patients is therefore required.

Demographic, clinical features and treatment outcomes in 700 achalasia patients in iran.

BACKGROUND Achalasia is the most recognized motor disorder of the esophagus. Because it is an uncommon disease, most studies have reviewed small numbers of patients. Here, we report demographic, clinical features and treatment outcomes in 700 achalasia patients. METHODS In all patients, diagnosis was established based on clinical, radiological, endoscopic and manometric criteria. A questionnaire was completed for each patient and included the patient's age, gender, initial symptoms, frequency of different symptoms, presence of positive family history for achalasia, other accompanying diseases and treatment outcomes. RESULTS In our study men were affected more than women (54.3% vs. 45.7%). Patients' mean age was about 38 years. The most frequent symptoms noted were: dysphagia to solids and liquids, active regurgitation, passive regurgitation and weight loss, respectively. Women complained of chest pain more than men (59% vs. 47.1%, p=0.04). The vast majority of our patients were treated by pneumatic dilation (PD) of the LES and in long-term follow-up, 67% were in the responder group. Females responded better than males to PD. CONCLUSION Dysphagia to solids is the most common symptom in patients with achalasia. Chest pain was significantly higher among women. PD is an effective treatment for achalasia with long-term efficacy in the majority of patients.

Genetic susceptibility to Graves' ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes.

PURPOSE: In order to investigate the underlying genetic mechanisms of Graves' ophthalmopathy (GO), we examined the association between single-nucleotide polymorphisms in five important proinflammatory cytokines, namely IL-12, TNF-alpha, IFN-gamma, IL-2, and IL-6, with GO in a sample of Iranian adults. METHODS: A total of 57 patients with Graves' disease without GO, 50 patients with GO, and 140 healthy controls were enrolled. Patients were recruited consecutively from the outpatient endocrine clinic of a large university general hospital. Genotype and allele frequencies of the following proinflammatory cytokines were compared between the groups: IL-12 (-1188A/C), TNF-alpha (-308A/G, -238A/G), INF-gamma (UTR 5644A/T), IL-2 (-330T/G, 166G/T), and IL-6 (-174C/G, nt565A/G). A corrected (for multiple testing) P-value (Pc) less than 0.05 was considered statistically significant. RESULTS: The IL-12 -1188C allele (odds ratio (OR)=2.65, Pc<0.01) and CC genotype (OR=7.58, Pc<0.01) were significantly more common in patients with GO than in patients without GO. The TNF-alpha-238A allele was more frequent in patients with GO than in patients without GO (OR=2.99, Pc<0.05). The frequency of the IFN-gamma UTR 5644T allele (OR=2.67, Pc<0.05), AT genotype (OR=13.33, Pc<0.05), and TT genotype (OR=18.46, Pc<0.01) was significantly higher among patients with GO than patients without GO. No significant association was found for other polymorphisms. CONCLUSIONS: We demonstrated that specific polymorphisms in IL-12, IFN- gamma, and TNF-alpha genes are associated with susceptibility to GO in the Iranian population. Our results open a new perspective to genetic correlates of GO.