Predictors of survival in oesophageal cancer patients in a high-risk area in Northern Iran: the role of health services utilisation.

We aimed to determine predictors of survival in oesophageal cancer (EC) patients in a high-risk area. This study was conducted on EC patients diagnosed in 2007-2008 in Golestan province, Iran. Diagnostic (DU) and Therapeutic (TU) services utilisation indices were determined. DU and TU indices of 1 were considered as good utilisation. EC-specific survival rates were calculated. Multivariate Cox-regression model was used to calculate adjusted hazard ratios (AHRs). Two hundred and twenty-three EC subjects were enrolled. The median survival time was 10.47 months and the 5-year survival rate was 11%. Cox-regression analysis suggested that stage of tumour (AHRregional  = 3.75, 95% confidence interval [CI]: 2.34-6.00; AHRmetastasis  = 12.21, 95% CI: 7.42-20.08) and TU (AHR = 1.78, 95% CI: 1.25-2.52) were the strongest variables related to EC survival. The median survival time in patients with good and poor TU were 14.37 and 8.53 months respectively (p < .01). There was no significant relationship between DU and EC survival. We found relatively low survival rates in our EC patients when compared with developed countries. Our results also suggested an increasing trend for EC survival rate during recent years. Good TU could predict higher survival rates. Patients' access to therapeutic services may be considered as an important indicator in decision-making for controlling EC.

Determinants of healthcare utilisation and predictors of outcome in colorectal cancer patients from Northern Iran.

We aimed to assess healthcare utilisation (HU), its determinants, as well as its relationship with survival in colorectal cancer (CRC) patients. This study was conducted on incident CRC cases from Northern Iran. Information on HU was collected using a valid questionnaire, considering eight diagnostic and four therapeutic services. The results were categorised as good and poor HU. Multivariate logistic regression analysis was used to assess the relationship between HU and other variables. Cox regression analysis was performed to determine major predictors of survival. In total, 227 new cases of CRC were enrolled. HU could be assessed in 218 subjects (96%). Living in rural areas was the strongest variable related to poor HU (adjusted OR, odds ratio = 2.65; CI, confidence interval: 1.30-5.40). The median survival time was 40.5 months. The 1-, 3- and 5-year survival rates were 71%, 52% and 44% respectively. Cox regression analysis showed a significant lower survival rate in patients with poor HU (HR = 2.3; CI: 1.46-3.64). HU was an independent predictor of survival in our CRC patients. Patients' place of residence was a significant determinant of HU. Regarding its effects on patients' outcome, HU and its determinants should be considered in designing CRC controlling programmes in our region and similar high-risk populations.

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.

Comparison of three with six regions of interest analyses in patients with idiopathic constipation undertaking colon transit scintigraphy using 67Ga-citrate.

UNLABELLED: OBJECTIVE AND INTRODUCTION: Preparation of data from 6 geometric regions of interest in the colon is time consuming, and can become impractical in the environment of busy Nuclear Medicine Departments. Therefore, we have investigated and demonstrated an alternative method for obtaining the same diagnostic information from an analysis of patients with idiopathic constipation who underwent colon transit scintigraphy using 67Ga-citrate. Data analysis methods using three regions of interest are compared to the results obtained using the more time consuming 6 regions of interest method to analyze the data. MATERIALS AND METHODS: In this study, we report our results of the comparative reanalysis of data obtained by more traditional methods. We compare 3 regions of interest (ROI) which were taken from areas including the right colon, left colon and the rectosigmoid colon, with original work using our alternative 6 (ROI) diagnostic methodology. In addition, the proximal colonic emptying (PCE) was determined at 24 hr post ingestion among members of 3 identified subject groups. RESULTS: The distribution of activity as the ingested 67Ga-citrate passes through the colon constitutes an activity profile. The mean activity position in the colon can be determined from subsequent radiographic images and from this the mean clearance time can be calculated.  In quantitative assessment, this represents the time at which half of activity was eliminated from colon (mean half clearance time - MCT) which did not appear different in the reanalysis. There is no significant difference in the current study in GMC 24h, GMC 48h and GMC 72h between two groups using the Man Whitney u test (p > 0.05), while in the previous work the results were statistically significant for the two later time periods GMC (GMC 48h and GMC 72h) (p = 0.016 and p = 0.027 respectively). The PCE in the group 1 was = 2.50 (0.37); group 2, 1.57 (0.47) and group 3, 2.97. The PCE was not different between the two groups (p = 0.21). CONCLUSIONS: This investigation demonstrated that the radionuclide colon transit study using 67Ga-citrate is a safe, physiologic, and quantitative method for evaluating the transit of fecal material from cecum to rectum. Although, the visual assessment of diagnosis of the subjects in the two analyses is the same, it was not completely supported by quantitative measurements. Therefore, further studies need to be done.

Aflatoxin contamination in wheat flour samples from golestan province, northeast of iran.

BACKGROUND: Due to the high toxicity of aflatoxin and its effects on public health, determination of aflatoxin level in Wheat flour samples in the Golestan province, north of Iran was investigated. To examine the effect of seasonal changes, summer and winter sampling was performed with standard sampling methods. METHODS: A total of 200 flour samples were collected from 25 factories. HPLC method with immunoaffinity chromatography was used to measure aflatoxin types (G2, G1, B2 and B1). Statistical analysis was performed by the Pearson correlation test, One-way ANOVA and multivariate regression analysis. RESULTS: Mean total aflatoxin levels of samples were 0.82 and 1.99 ng/g in summer and winter, respectively. Aflatoxin B1 levels were detected in 3.1%, 7.4% over permissible limits by worldwide regulations in samples collected in summer and winter, respectively. Aflatoxins in winter were higher than summer. The highest frequency of aflatoxin contamination in winter was B2 (98%) and in summer G1 (51%). The relationship between humidity and rate of aflatoxin B1 and total aflatoxin was significant in winter. Results of multivariate regression were showed the strongest relationship with humidity and aflatoxin level. Despite the contamination of flour samples, there was no contamination higher than the standard limit of Iran Standard Institute. But it was significantly higher than similar studies from other regions. CONCLUSIONS: Therefore, with regard to negative impacts of aflatoxin on health, aflatoxin contamination should be considered in future programs. Decrease of aflatoxin contamination may be made practical through reducing wheat storage duration and controlling humidity.

Complete improvement in a patient with multiple irreversible defects of the left ventricle on 99m technetium-sestamibi SPECT after percutaneous coronary intervention.

99mTc-sestamibi has been investigated as a potential viability marker; initial studies have shown good concordance between 201Tl and 99mTc-sestamibi activities in both viable and nonviable myocardium. However, assessment of myocardial viability by 99mTc-sestamibi remains controversial for tissue recovery after revascularization. Here, we present a patient with several regions of severely diminished and irreversible (defect persisting in both early and delay images of each set scanning) defects on initial scan which were dissolved completely on the follow up scan after an intervention. In a 75 year-old Asian woman with acute myocardial infarction who received thrombolytic therapy and subjected to percutaneous coronary angiography (PCI) on day 28 after acute myocardial infarction(MI), resting 99mTc-sestamibi SPECT was applied on day 4 (initial scan) and 138 (follow up scan) after acute MI at 30 and 180 min after injection of tracer (740 MBq); Two-dimensional echocardiography was carried out at the same time. On the initial image set, there was irreversible defects in the apex, anteroapical, inferoapical, anteroseptal, septal and also anterior walls, while the follow up image was normal in all regions.The angiography intervention showed just significant stenosis on left anterior descending (LAD) vessel (95%). This may highlight the failure of 99mTc-sestamibi as a marker of myocardial viability and also mandate further validating of the procedure with follow up scan or other modalities for myocardial viability investigation.

Gastric atrophy and oesophageal squamous cell carcinoma: possible interaction with dental health and oral hygiene habit.

BACKGROUND: Gastric fundal atrophy has been hypothesised to increase the risk of oesophageal squamous cell carcinoma (OSCC), but studies have shown inconsistent results. METHODS: We measured serum pepsinogen I (PGI) and pepsinogen II (PGII) among 293 incident cases and 524 matched neighbourhood controls in a high-risk area of Northern Iran. Conditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: After controlling for age, sex, residence area and other potential confounders, gastric atrophy (defined by a validated criterion, PGI <55 µg dl(-1)) was associated with a two-fold increased risk (OR=2.01, 95% CI: 1.18, 3.45) of OSCC in the absence of nonatrophic pangastritis (defined as PGII <11.8 µg dl(-1)). Stratification by PGII decreased the misclassification errors due to cancer-induced gastritis. Presence of both poor dental health, indicated by higher than median sum of decayed, missing, and filled teeth (DMFT score), and gastric atrophy further increased the risk of OSCC (OR=4.15, 95% CI: 2.04, 8.42) with relative excess risk due to interaction (RERI) of 1.47 (95% CI: -1.15, 4.1). Coexistence of poor oral hygiene habit with gastric atrophy elevated OSCC risk eight times (OR=8.65, 95% CI: 3.65, 20.46) and the additive interaction index was marginally statistically significant (RERI=4.34, 95% CI: -1.07, 9.76). CONCLUSION: Gastric atrophy is a risk factor for OSCC, and poor dental health and oral hygiene habit may act synergistically in increasing the risk.

Acute visual field defect in ulcerative colitis: a case report.

A cerebrovascular occlusive event is a rare complication of IBD, which usually occurs during its acute phase, shortly after diagnosis. This association seems to be a complex situation, affected by a combination of factors.

The association of rate pressure product (RPP) and myocardial perfusion imaging (MPI) findings: a preliminary study.

INTRODUCTION: The product of heart rate and systolic blood pressure, termed as rate-pressure product (RPP), is a very reliable indicator of myocardial oxygen demand and is widely used clinically. There have been previous attempts to describe the relationship between RPP and the onset of pain in angina pectoris. The current study aimed to evaluate the association between RPP results and scan findings. MATERIALS AND METHODS: In total, 497 patients with suspected coronary artery disease (CAD) underwent gated, single-photon emission computed tomography (SPECT) imaging with dipyridamole, exercise, or dobutamine stress, and were included in this study. Baseline and maximum heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and electrocardiogram (ECG) results were recorded. The rate-pressure product (RPP) was calculated as the product of heart rate and systolic arterial pressure for both baseline and maximum measures. The difference between the RPP max and the basal RPP is known as the RPP reserve. Researchers also obtained semi-quantitative analyses of myocardial perfusion imaging (MPI), using gated software, demographic information, risk factors of CAD, and pretest likelihoods of CAD using nomograms. RESULT: Four hundred and ninety-seven cases, including 426 patients with dipyridamole stress, 59 with exercise stress, and 12 with dobutamine stress, underwent myocardial perfusion imaging. Scan results were positive in 194 (45.5%) and negative in 232 (54.5%) patients with dipyridamole stress. In patients with exercise stress, the scan was positive in 24 (40.7%) cases and negative in 35 (59.3%) cases. In dobutamine stressed patients, the scan was positive in 6 (50%) cases and negative in the 6 remaining cases. Dipyridamole stress resulted in a significant difference between HR at rest and at maximum (28.95 ± 24.53, p-value<0.0001), between systolic BP at rest and maximum (6.75 ± 12.50, p-value<0.0001) and between diastolic BP at rest and maximum (1.45 ± 5.80; p-value<0.0001). There was a significant correlation between sum stress scores (SSS) and reserved RPP (r= -0.12, p-value<0.001) which, in dipyridamole patients, was r=-0.18, p-value=0.0001). In addition, there was a significant association between reserved RPP and risk of CAD (p-value<0.001). In the patients with dipyridamole stress, the ejection fraction (EF) change (odds ratio =0.92; 95% CI: 0.86-0.98; p=0.01), reserve RPP (odds ratio =1.00; 95% CI: 1.00-1.00; p=0.04), risk of CAD (odds ratio =5.80; 95% CI: 3.21-10.50; p<0.0001) and age (odds ratio =0.94; 95% CI: 0.89-0.98; p=0.01) were associated significantly with MPI results, using multiple logistic regressions. CONCLUSION: The study demonstrated that RPP is associated with MPI findings using gated SPECT imaging with dipyridamole stress. However, to confirm this preliminary result, further studies are mandatory.

Scintigraphic parameters with emphasis on perfusion appraisal in rest 99mTc-sestamibi SPECT in the recovery of myocardial function after thrombolytic therapy in patients with ST elevation myocardial infarction (STEMI).

INTRODUCTION: This study was performed to determine the clinical application of rest 99mTc-sestamibi in the assessment of viability and functional improvement of the left ventricle (LV) myocardium in the post-thrombolytic therapy of acute myocardial infarction (AMI). MATERIAL AND METHODS: In 37 patients with AMI who received thrombolytic therapy, 2-dimensional (2D) echocardiography, as well as the resting redistribution of 99mTc-sestamibi, was investigated, both within 1 week and 3-5 months after AMI. The predictive capacity of the perfusion percentage for myocardial function recovery was evaluated. Also, the capacities of the possible variables in the prediction of recovery of myocardial function resulting from a change in LV ejection fraction (EF) were evaluated using stepwise multiple regression analysis. RESULTS: Thirty-seven patients (30 men and 7 women; mean age: 58±14 years) with AMI were enrolled in the study. Redistribution was observed in 35 and 50 segments of the initial and follow-up scans, respectively. In addition, 146 segments with reverse redistribution (RR), both in the initial scan (118 segments) and the follow-up scan (86 segments), were also observed. An apparent difference in wall motion scores was seen between the initial and follow-up echocardiographs (p<0.001). Furthermore, using the optimal cut-off point of perfusion percentage in each image set, sensitivity as well as specificity and likelihood ratio (LR) for the improvement of regional wall motion after 3-5 months were defined. CONCLUSION: These data showed that redistribution and reverse redistribution of 99mTc-sestamibi post thrombolytic therapy can be used as a marker of viability to predict the recovery of segmental wall motion abnormality (stunning), as well as the improvement of segmental perfusion uptake. This study also demonstrates that the resting 99mTc-sestamibi SPECT can be used for an approximate assessment of LV function status and can predict the recovery of jeopardized myocardium function after thrombolytic therapy.

Esophagitis may not be a Major Precursor Lesion for Esophageal Squamous Cell Carcinoma in a High Incidence Area in North-Eastern Iran.

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is usually detected in advanced stages resulting in a very poor prognosis. Early diagnosis needs identification of clinically relevant precancerous lesions which could become the target of screening and early treatment. Our aim was to check whether esophagitis could serve as a relevant histological precursor of ESCC in Northern Iran. METHODS During 2001-2005, all adult patients who were referred to Atrak clinic for upper gastrointestinal endoscopy and biopsy were enrolled. Atrak clinic is a major center for upper gastrointestinal cancer research in eastern Golestan. All subjects had been complaining of upper GI symptoms and were under further investigation to rule out cancer. Biopsies from the endoscopically normal mid-esophagus and also just above the esophago-gastric junction were obtained in all subjects whose esophagus appeared normal during endoscopy and from endoscopically normal appearing mucosa at the proximal vicinity of any detected mass. Microscopic examinations for the verification of the presence or absence of esophagitis was performed by independant histological examination of the samples by two pathologists. All the discrepant diagnoses were resolved in joint diagnostic sessions. RESULTS During the study period 836 patients were enrolled including 419 non cancer patients (endoscopy clinic controls), 387 cancer patients, and 30 subjects with clinical diagnosis of malignancy referred for histological reconfirmation of diagnosis by repeated biopsy. Mild or marked mid-esophagitis was diagnosed in 39 (9.3%), 47 (12.5%) and 12 (40%) of endoscopy clinic controls, cancer patients and those who were suspicious for upper gastrointestinal malignancies. CONCLUSION Our observation does not show evidence for esophagitis to be a predisposing factor for ESCC in Gonbad region In North Eastern Iran.

A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy ('polypill') on cardiovascular risk factors.

AIM: Our objective was to investigate the effects and tolerability of fixed-dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels. METHODS: This was a double-blind randomised placebo-controlled trial in residents of Kalaleh, Golestan, Iran. Following an 8-week placebo run-in period, 475 participants, aged 50 to 79 years, without cardiovascular disease, hypertension or hyperlipidaemia were randomised to fixed-dose combination therapy with aspirin 81 mg, enalapril 2.5 mg, atorvastatin 20 mg and hydrochlorothiazide 12.5 mg (polypill) or placebo for a period of 12 months. The primary outcomes were changes in LDL-cholesterol, systolic and diastolic blood pressure and adverse reactions. Analysis was by intention-to-treat basis. RESULTS: At baseline, there were differences in systolic blood pressure (6 mmHg). Taking account of baseline differences, at 12 months, polypill was associated with statistically significant reductions in blood pressure (4.5/1.6 mmHg) and LDL-cholesterol (0.46 mmol/l). The study drug was well tolerated, but resulted in the modest reductions in blood pressure and lipid levels. CONCLUSION: The effects of the polypill on blood pressure and lipid levels were less than anticipated, raising questions about the reliability of the reported compliance. There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease.

Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran.

The very high incidence of oesophageal squamous cell carcinoma (ESCC) in Golestan Province in northeastern Iran was suggested by studies in the 1970s as partly due to opium use, which is not uncommon in this area, but based on limited numbers. From December 2003 to June 2007, we administered a validated structured questionnaire to 300 ESCC cases and 571 controls, matched on neighbourhood of residence, age (+/-2 years), and sex. We used conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. Compared with those who used neither tobacco nor opium, risk of ESCC was increased in those who used tobacco only (OR, 95% CI: 1.70, 1.05-2.73), in those who used opium only (2.12, 1.21-3.74), and in those who used both tobacco and opium (2.35, 1.50-3.67). All forms of tobacco use (cigarettes, hookah, and nass) were associated with higher ESCC risk. Similarly, use of both crude opium and other forms of opium were associated with higher risk. Alcohol consumption was seen in only 2% of the cases and 2% of the controls, and was not associated with ESCC risk.

Germline BRCA2 mutations and the risk of esophageal squamous cell carcinoma.

The incidence of esophageal squamous cell carcinoma (ESCC) is very high among the Turkmen population of Iran. Family studies suggest a genetic component to the disease. Turkmen are ethnically homogenous and are well suited for genetic studies. A previous study from China suggested that BRCA2 might play a role in the etiology of ESCC. We screened for mutations in the coding region of the BRCA2 gene in the germline DNA of 197 Turkmen patients with ESCC. A nonsense variant, K3326X, was identified in 9 of 197 cases (4.6%) vs 2 of 254 controls (0.8%) (OR=6.0, 95% CI=1.3-28; P=0.01). This mutation leads to the loss of the C-terminal domain of the BRCA2 protein, a part of the region of interaction with the FANCD2 protein. We observed nine other BRCA2 variants in single cases only, including two deletions, and seven missense mutations. Six of these were judged to be pathogenic. In total, a suspicious deleterious BRCA2 variant was identified in 15 of 197 ESCC cases (7.6%).

Validity and reliability of a new food frequency questionnaire compared to 24 h recalls and biochemical measurements: pilot phase of Golestan cohort study of esophageal cancer.

BACKGROUND: A pilot study was carried out to evaluate validity and reproducibility of a food frequency questionnaire (FFQ), which was designed to be used in a prospective cohort study in a population at high risk for esophageal cancer in northern Iran. METHODS: The FFQ was administered four times to 131 subjects, aged 35-65 years, of both sexes. Twelve 24-h dietary recalls for two consecutive days were administered monthly during 1 year and used as a reference method. The excretion of nitrogen was measured on four 24-h urine samples, and plasma levels of beta-carotene, retinol, vitamin C and alpha-tocopherol was measured from two time points. Relative validity of FFQ and 24-h diet recall was assessed by comparing nutrient intake derived from both methods with the urinary nitrogen and plasma levels of beta-carotene, retinol, vitamin C and alpha-tocopherol. RESULTS: Correlation coefficients comparing energy and nutrients intake based on the mean of the four FFQ and the mean of twelve 24-h diet recalls were 0.75 for total energy, 0.75 for carbohydrates, 0.76 for proteins and 0.65 for fat. Correlation coefficients between the FFQ-based intake and serum levels of beta-carotene, retinol, vitamin C and vitamin E/alpha-tocopherol were 0.37, 0.32, 0.35 and 0.06, respectively. Correlation coefficients between urinary nitrogen and FFQ-based protein intake ranged from 0.23 to 0.35. Intraclass correlation coefficients used to measure reproducibility of FFQ ranged from 0.66 to 0.89. CONCLUSION: We found that the FFQ provides valid and reliable measurements of habitual intake for energy and most of the nutrients studied.

Golestan cohort study of oesophageal cancer: feasibility and first results.

To investigate the incidence of oesophageal cancer (EC) in the Golestan province of North-East Iran, we invited 1349 rural and urban inhabitants of Golestan province aged 35-80 to undergo extensive lifestyle interviews and to provide biological samples. The interview was repeated on a subset of 130 participants to assess reliability of questionnaire and medical information. Temperature at which tea was consumed was measured on two occasions by 110 subjects. Samples of rice, wheat and sorghum were tested for fumonisin contamination. An active follow-up was carried out after 6 and 12 months. A total of 1057 subjects (610 women and 447 men) participated in this feasibility study (78.4% participation rate). Cigarette smoking, opium and alcohol use were reported by 163 (13.8%), 93 (8.8%) and 39 (3.7%) subjects, respectively. Tobacco smoking was correlated with urinary cotinine (kappa = 0.74). Most questionnaire data had kappa > 0.7 in repeat measurements; tea temperature measurement was reliable (kappa = 0.71). No fumonisins were detected in the samples analysed. During the follow-up six subjects were lost (0.6%), two subjects developed EC (one dead, one alive); in all, 13 subjects died (with cause of death known for 11, 84.6%). Conducting a cohort study in Golestan is feasible with reliable information obtained for suspected risk factors; participants can be followed up for EC incidence and mortality.

Epidemiologic features of upper gastrointestinal tract cancers in Northeastern Iran.

Previous studies have shown that oesophageal and gastric cancers are the most common causes of cancer death in the Golestan Province, Iran. In 2001, we established Atrak Clinic, a referral clinic for gastrointestinal (GI) diseases in Gonbad, the major city of eastern Golestan, which has permitted, for the first time in this region, endoscopic localisation and histologic examination of upper GI cancers. Among the initial 682 patients seen at Atrak Clinic, 370 were confirmed histologically to have cancer, including 223 (60%) oesophageal squamous cell cancers (ESCC), 22 (6%) oesophageal adenocarcinomas (EAC), 58 (16%) gastric cardia adenocarcinomas (GCA), and 58 (16%) gastric noncardia adenocarcinomas. The proportional occurrence of these four main site-cell type subdivisions of upper GI cancers in Golestan is similar to that seen in Linxian, China, another area of high ESCC incidence, and is markedly different from the current proportions in many Western countries. Questioning of patients about exposure to some known and suspected risk factors for squamous cell oesophageal cancer confirmed a negligible history of consumption of alcohol, little use of cigarettes or nass (tobacco, lime and ash), and a low intake of opium, suggesting that the high rates of ESCC seen in northeastern Iran must have other important risk factors that remain speculative or unknown. Further studies are needed to define more precisely the patterns of upper GI cancer incidence, to test other previously suspected risk factors, and to find new significant risk factors in this high-risk area.

Effects of adenosine receptor agonists and antagonists on physostigmine-induced yawning.

The effect of adenosine receptor agonists and antagonists on physostigmine-induced yawning was investigated in intact or cannulated rats. Intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of physostigmine to rats induced yawning dose dependently. I.p. or i.c.v. treatment of the animals with atropine, theophylline, 5-N-ethylcarboxamidoadenosine (NECA) or N6-cyclohexyladenosine reduced the yawning induced by i.p. injection of physostigmine. I.p. administration of theophylline decreased the yawning induced by i.c.v. injection of physostigmine. The inhibitory action of N6-cyclohexyladenosine (i.p.) also was decreased by 8-phenyltheophylline (i.p.) pretreatment. It is concluded that yawning induced by a central cholinergic mechanism and a central adenosine mechanism interacts with the cholinergic-induced behaviour.