Specific causes of recurrence after surgery and mortality in patients with colorectal cancer: A competing risks survival analysis.

BACKGROUND: In situation where there are more than one cause of occurring the outcome such as recurrence after surgery and death, the assumption of classical survival analyses are not satisfied. To cover this issue, this study aimed at utilizing competing risks survival analysis to assess the specific risk factors of local-distance recurrence and mortality in patients with colorectal cancer (CRC) undergoing surgery. MATERIALS AND METHODS: In this retrospective cohort study, 254 patients with CRC undergoing resection surgery were studied. Data of the outcome from the available documents in the hospital were gathered. Furthermore, based on pathological report, the diagnosis of CRC was considered. We model the risk factors on the hazard of recurrence and death using competing risk survival in R3.6.1 software. RESULTS: A total of 114 patients had local or distant recurrence (21 local recurrences, 72 distant recurrences, and 21 local and distant recurrence). Pathological stage (adjusted hazard ratio [AHR] = 4.28 and 5.37 for stage 3 and 4, respectively), tumor site (AHR = 2.45), recurrence (AHR = 3.92) and age (AHR = 3.15 for age >70) was related to hazard of death. Also based on cause-specific hazard model, pathological stage (AHR = 7.62 for stage 4), age (AHR = 1.46 for age >70), T stage (AHR = 1.8 and 2.7 for T3 and T4, respectively), N stage (AHR = 2.59 for N2), and white blood cells (AHR = 1.95) increased the hazard of recurrence in patients with CRC. CONCLUSION: This study showed that older age, higher pathological, rectum tumor site and presence of recurrence were independent risk factors for mortality among CRC patients. Also age, higher T/N stage, higher pathological stage and higher values of WBC were significantly related to higher hazard of local/distance recurrence of patients with CRC.

A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes.

BACKGROUND: Studies of dipeptidyl peptidase (DPP)-4 inhibitors report heterogeneous effects on endothelial function in patients with type 2 diabetes (T2D). This study assessed the effects of the DPP-4 inhibitor linagliptin versus the sulphonylurea glimepiride and placebo on measures of macro- and microvascular endothelial function in patients with T2D who represented a primary cardiovascular disease prevention population. METHODS: This crossover study randomised T2D patients (n = 42) with glycated haemoglobin (HbA1c) ≤7.5%, no diagnosed macro- or microvascular disease and on stable metformin background to linagliptin 5 mg qd, glimepiride 1-4 mg qd or placebo for 28 days. Fasting and postprandial macrovascular endothelial function, measured using brachial flow-mediated vasodilation, and microvascular function, measured using laser-Doppler on the dorsal thenar site of the right hand, were analysed after 28 days. RESULTS: Baseline mean (standard deviation) age, body mass index and HbA1c were 60.3 (6.0) years, 30.3 (3.0) kg/m2 and 7.41 (0.61)%, respectively. After 28 days, changes in fasting flow-mediated vasodilation were similar between the three study arms (treatment ratio, gMean [90% confidence interval]: linagliptin vs glimepiride, 0.884 [0.633-1.235]; linagliptin vs placebo, 0.884 [0.632-1.235]; glimepiride vs placebo, 1.000 [0.715-1.397]; P = not significant for all comparisons). Similarly, no differences were seen in postprandial flow-mediated vasodilation. However, under fasting conditions, linagliptin significantly improved microvascular function as shown by a 34% increase in hyperaemia area (P = 0.045 vs glimepiride), a 34% increase in resting blow flow (P = 0.011 vs glimepiride, P = 0.003 vs placebo), and a 25% increase in peak blood flow (P = 0.009 vs glimepiride, P = 0.003 vs placebo). There were no significant differences between treatments in postprandial changes. Linagliptin had no effect on heart rate or blood pressure. Rates of overall adverse events with linagliptin, glimepiride and placebo were 27.5, 61.0 and 35.0%, respectively. Fewer hypoglycaemic events were seen with linagliptin (5.0%) and placebo (2.5%) than with glimepiride (39.0%). CONCLUSIONS: Linagliptin had no effect on macrovascular function in T2D, but significantly improved microvascular function in the fasting state. Trial registration ClinicalTrials.gov identifier-NCT01703286; registered October 1, 2012.

Estimation of treatment effect in presence of noncompliance and competing risks: a simulation study.

A randomized controlled trial is commonly designed to assess the treatment effect in survival studies, in which patients are randomly assigned to the standard or the experimental treatment group. Upon disease progression, patients who have been randomized to standard treatment are allowed to switch to the experimental treatment. Treatment switching in a randomized controlled trial refers to a situation in which patients switch from their randomized treatment to another treatment. Often, the switchis from the control group to the experimental treatment. In this case, the treatment effect estimate is adjusted using either convenient naive methods such as intention-to-treat, per-protocol or advanced methods such as rank preserving structural failure time (RPSFT) models. In previous simulation studies performed so far, there was only one possible outcome for patients. However, in oncology in particular, multiple outcomes are potentially possible. These outcomes are called competing risks. This aspect has not been considered in previous studies when determining the effect of a treatment in the presence of noncompliance. This study aimed to extend the RPSFT method using a two-dimensional G-estimation in the presence of competing risks. The RPSFT method was extended for two events, the event of interest and the competing event. For this purpose, the RPSFT method was applied based on the cause-specific hazard approach, the result of which is compared to the naive methods used in simulation studies. The results show that the proposed method has a good performance compared to other methods.

Determining the Risk Factors Affecting on Death Due to Colorectal Cancer Progression: Survival Analysis in the Presence of Competing Risks.

PURPOSE: In survival analysis, some patients may be at risk of more than one event, for example cancer-related death and cancer-unrelated death. In this case, if the aim of study becomes to assess the impact of risk factors on different causes of death, the competing risk model should be used rather than classical survival model. The aim of the present study is to determine the risk factors for related and unrelated mortality in patients with colorectal cancer using competing risk regression models. METHODS: The present retrospective cohort study was carried out on 310 CRC patients. Death due to cancer progression was considered as the interest event, and death due to unrelated cancer was considered as a competing event. Two most popular methods, cause-specific and subdistribution hazard regression model, were used to determine the effect of covariates on incidence and cause-specific hazard. Data analysis was performed using R3.6.2 software and cmprsk and survival packages. RESULTS: The mean (SD) of patients' age was 55.84 ± 13.2 years and 53.9% of them were male. BMI, T and N stage had a significant effect on both incidence and cause specific hazard of cancer-related death. CONCLUSION: The results of this study showed that cancer-related death is strongly correlated with under-weight (BMI < 18.5) and advanced clinical stage of the disease in patients with colorectal cancer. So, in the presence of competing events, both types of regression hazard models should be applied to permit a full understanding of the impact of covariates on the incidence and the rate of occurrence of each outcome.

Association between 45T/G polymorphism of adiponectin gene and coronary artery disease in an Iranian population.

A single nucleotide polymorphism (SNP) in the adiponectin gene, 45T/G, has been reported in relation to a number of metabolic disorders, including obesity, insulin resistance, and diabetes. However, previous studies on the association between this SNP and the presence of coronary artery disease (CAD) have been few, with no report from Iranian subjects. The present study set out to investigate the association between this SNP and CAD in an Iranian population. Among 464 patients (age: 18-75 years), recruited from individuals who underwent coronary angiography, 135 patients had less than 50% reduction of coronary artery diameter and were classified as the CAD- group and 329 patients had more than 50% reduction of coronary artery diameter and were classified as the CAD+ group. The last group was divided into single-vessel disease (n = 86), two-vessel disease (n = 111), and three-vessel disease (n = 132). Healthy subjects (n = 106) who did not have any history of heart diseases were also recruited as the control group. All subjects were genotyped for the 45T/G polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. A significantly higher frequency of the TG genotype and G allele, which was paralleled by a lower frequency of the TT genotype and T allele, was observed in both CAD+ and CAD- patients when compared with the control group (p ≤ 0.001). There was no significant difference in the genotype distribution and allele frequencies between CAD+ and CAD- patients, and also between different subgroups of patients based on the number of stenosed vessels (p > 0.05). Our findings indicate that the presence of the G allele at the position +45 of the adiponectin gene may be associated with the risk of CAD in our study population. While we found no significant difference in the genotype distribution and allele frequencies between patients with angiography+ and angiography, this may be because the 50% stenosis cut-off does not discriminate sufficiently between individuals with and without significant coronary disease.

Estimating the treatment effect in patients with gastric cancer in the presence of noncompliance.

AIM: In this study, these methods were used to estimate the treatment effect in patients with gastric cancer in the presence of noncompliance. BACKGROUND: In medical sciences, simple and advanced methods are used to estimate treatment effects in the presence of noncompliance. METHODS: This historical cohort study surveyed 178 patients with gastric cancer underwent chemotherapy alone (chemotherapy alone group) and 193 patients underwent surgery and chemotherapy (surgery plus chemotherapy group) from 2003 to 2007 at the Cancer Institute of Imam Khomeini Hospital (Tehran). Demographic and clinical characteristics were extracted from patients' hospital records. The survival of patients was calculated as being from diagnosis to death or to the end of the study. The treatment effect was estimated using three methods: treatment as a time-dependent covariate, IPCW, and Structural Nested Models using STATA and R software. RESULTS: Fifty-six patients (31.5%) who underwent chemotherapy and 69 patients (35.8%) who underwent surgery and chemotherapy died by the end of the study. The hazard ratio in group I compared to group II was estimated between 1.5 to 2.07 times based on the simple analysis method. The modified hazard ratio was estimated to be 1.21 (95% CI: 1.11-1.32) based on the SNM method. Surgery plus chemotherapy is superior to chemotherapy alone, and it improves the overall survival (OS) rate of gastric cancer patients. CONCLUSION: Survival was improved in patients undergoing chemotherapy and surgery together compared to those undergoing chemotherapy alone. The results of the current study suggest that treatment effect can be estimated unbiasedly using the appropriate method.

Antibody titres to heat shock protein 27 are elevated in patients with acute coronary syndrome.

IgG antibody titres to heat shock protein 27 (anti-Hsp27) were measured to determine whether these titres were affected in patients admitted with acute coronary syndrome. Blood samples were taken from 94 patients admitted with acute coronary syndrome. Anti-Hsp27 IgG titres were determined using an in-house enzyme-linked immunosorbent assay (ELISA) in the first and second 12 h after the onset of symptoms and compared with values for 81 age- and sex-matched control subjects. Median antibody titres to Hsp27 in the first sample from patients whose diagnosis was a myocardial infarction (n = 42) was 0.41 absorbancy units (range 0.28-0.57) and for those with unstable angina (n = 52) was 0.31 (range 0.20-0.42), both being significantly higher than for controls (n = 81), which was 0.08 (range 0.05-0.15) (P < 0.05). However, titres fell in the second samples collected in the coronary syndrome patients and were then no longer significantly different from controls (P > 0.05). Myocardial infarction patients also had significantly higher anti-Hsp27 titres in the first 12 h than patients with unstable angina (P < 0.05), but again the difference in the second sample did not reach statistical significance (P > 0.05). Serum antibody titres to Hsp27 rise and fall rapidly after the onset of acute coronary syndrome, and may be an early marker of myocardial ischaemia as patients with myocardial infarction or unstable angina both had high titres.

Ranking Factors Affecting the Attraction of Foreign Medical Tourists in Hospitals Affiliated to Mashhad University of Medical Sciences Based on Marketing Mix Model.

BACKGROUND: This study was designed to rank factors affecting attraction of foreign medical tourists based on marketing mix model. METHODS: In this descriptive study, data were collected through a questionnaire. Foreign patients, hospitalized from Jan 2015 to Sep 2016 in all hospitals of Mashhad were chosen as the study population (13 hospitals). Data analysis was conducted using Friedman test and Wilcoxon test in SPSS 21 at a significance level of 0. 05. RESULTS: Factors of staff, service and process gained the highest score from the perspective of patients; while price, facilities and promotion scored the lowest among parameters affecting the attraction of medical tourists to hospitals of Mashhad. In this context, factors of staff (96%) and price (66%) had the highest and lowest effect on absorption of tourists, respectively. CONCLUSION: To promote medical tourism, important factors such as staff, service, and process should be further stressed and variables of price, facilities and promotion demand for a revision by the authorities in this industry.

Pharmacokinetics/Pharmacodynamics of Dabigatran 75 mg Twice Daily in Patients With Nonvalvular Atrial Fibrillation and Severely Impaired Renal Function.

INTRODUCTION: Dabigatran etexilate is an oral direct thrombin inhibitor. Dabigatran excretion is 80% renal, so exposure increases with severity of renal failure. The US Food and Drug Administration-approved dabigatran etexilate 75 mg twice daily (BID) for patients with nonvalvular atrial fibrillation (NVAF) having severely impaired renal function (creatinine clearance: 15-30 mL/min), based on post hoc pharmacokinetic modeling. We assessed dabigatran exposure at trough and peak levels in patients with NVAF and severely impaired renal function and compared with model predictions. METHODS: Patients received dabigatran etexilate (75 mg BID) for ≥7 days before blood sampling; Cpre,ss (steady-state predose concentration; trough) was taken 10 to 16 hours postdose (prior to next dose), and C2,ss (steady-state concentration; peak) was taken 2 hours (± 30 minutes) postdose. Pharmacodynamic parameters at baseline (Ebase), trough concentrations (Epre,ss), and peak concentrations (E2,ss) were assessed by established coagulation assays. RESULTS: Of the 150 patients screened, 60 were treated, of which 40% were male and 78.3% were white; median age was 84 years. Cpre,ss values (n = 51) were close to pharmacokinetic modeling predictions with a geometric mean (gMean) of 155 ng/mL, geometric coefficient of variation (gCV) of 76.9%, and range of 15.6 to 498 ng/mL. The C2,ss values (n = 59) had a gMean of 202 ng/mL, gCV of 70.6%, and range of 42.0 to 680 ng/mL. Pharmacodynamic effects on coagulation paralleled dabigatran concentrations. Eleven (18.3%) patients had ≥1 adverse event (AE); pharmacokinetic results for these patients versus those without AEs (n = 49) were Cpre, ss: gMean = 206 versus 145 ng/mL, gCV = 64.0% versus 78.3%; C2,ss: gMean = 243 versus 193 ng/mL, gCV = 68.9% versus 70.8%. All bleeding events (8 events in 5 patients) were considered minor by the investigators. CONCLUSION: Dabigatran exposure levels largely confirmed earlier pharmacokinetic predictions, supporting the use of dabigatran etexilate 75 mg BID in patients with NVAF and severely impaired renal function. Pharmacodynamic results were also in agreement with earlier studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01896297.

C-reactive protein associated with coronary artery disease in Iranian patients with angiographically defined coronary artery disease.

INTRODUCTION: Several cross-sectional and cohort studies have reported an association between serum markers of inflammation such as C-reactive protein, and coronary heart disease in Caucasian populations. We aimed to investigate the relationship between levels of serum C-reactive protein (hs-CRP) and the presence of coronary artery disease (CAD) in Iranian patients undergoing coronary angiography. METHODS: Serum hs-CRP, fasting lipid profile and blood glucose levels were measured in 110 patients (61 males and 49 females) undergoing routine coronary angiography. Anthropometric features including blood pressure were determined using standard procedures. Demographic characteristics, including post-menopausal status and smoking habit were assessed by questionnaire. RESULTS: Of the 110 subjects undergoing angiography, 74 (67.28%) had significant CAD (CAD+) and 36 (32.72%) were classified as having insignificant CAD (CAD-). Mean age (p<0.01), waist circumference (p<0.01) and LDL (p<0.05) and median values of hs-CRP (p<0.01) and triglycerides (p<0.05) were higher in the patients CAD+ than in the subjects CAD-. The proportion of women who were postmenopausal was also significantly higher in the CAD+ group. Age (p<0.01), waist circumference (p<0.05) and hs-CRP (p<0.05) were significant CAD predictive factors from logistic regression analysis. Serum hs-CRP concentrations were significantly higher in smokers compared to non-smokers (p<0.05), low density lipoprotein (LDL) (r=0.31, p<0.001), and serum triglycerides (r=0.191, p<0.05) correlated with serum hs-CRP. The median value of serum hs-CRP increased with the severity of the disease, but failed to reach statistical significance. CONCLUSION: Serum hs-CRP is an independent predictor of angiographically defined CAD in an Iranian population. Measurement of the serum hs-CRP level may improve risk stratification among patients suspected of having CAD. The strong correlations between serum hs-CRP with LDL and smoking may be due to the putative pro-inflammatory effects of these two parameters. The association with serum triglycerides may be indirect and related to insulin resistance and adiposity.

Serum copper and zinc concentrations are lower in Iranian patients with angiographically defined coronary artery disease than in subjects with a normal angiogram.

BACKGROUND: An imbalance between zinc and copper metabolism has been reported to predispose to coronary artery disease (CAD) in Western populations, but there are little data for other racial groups. We have therefore investigated the association between serum copper and zinc, and CAD in Iranian subjects undergoing coronary angiography. METHODS: Serum copper, zinc, fasting lipid profile, and blood glucose levels were measured in 114 patients (67 male and 47 female) undergoing routine coronary angiogram. Anthropometric features including blood pressure were determined using standard procedures. Demographic characteristics, including menopausal status and smoking habit, were assessed by questionnaire. RESULTS: Male patients had lower serum copper (p<0.05), lower serum zinc (p<0.05), and higher serum zinc/copper ratio (p<0.05) than females. Serum copper and zinc concentrations were significantly lower in the subjects with angiographically defined CAD than those patients with a normal angiogram, although the zinc/copper ratio was higher in these patients (p<0.001). Serum copper (r=-0.303, p<0.001) and zinc (r=-0.250, p<0.01) concentrations were both inversely related to age, and copper was positively associated with fasting serum triglycerides (r=0.188, p<0.05). CONCLUSION: Serum copper and zinc concentrations were significantly lower in Iranian patients with abnormal versus those with a normal angiogram. However, the zinc/copper ratio was higher in patients with CAD compared to subjects without CAD. Serum zinc and copper concentrations appear to be influenced by several physiological factors including age and gender.

Levels of physical activity are correlated with intima media ratio in subjects without but not with metabolic syndrome: A study of Iranians without a history of cardiovascular events.

AIM: We aimed to investigate the relationship between carotid Intima Media Thickness (CIMT) and physical activity levels (PAL), in subjects with and without metabolic syndrome (MetS) and in indidiviuals with and without carotid artery plaque (CAP) defined using high-resolution ultrasound. METHOD: A sample of 506 subjects [215 (42.5%) males], aged 35-64 years was recruited from an urban population in Mashhad, Iran, using a stratified-cluster method as part of the Mashhad Stroke Heart Atherosclerosis Disorder (MASHAD) study cohort. This sub-sample was selected randomly from a cohort of 9765 individuals for carotid duplex ultrasound. Comparisons were made between individuals with and without CAP on the one hand, and between participants with and without MetS on the other hand with regard to physical activity and cardiometabolic risk level, as well as their correlation with CIMT. RESULT: PAL was positively and significantly correlated with CIMT in the total sample (r=0.132, p<0.001). The correlation coefficient was 0.132 (p=0.426) in the MetS+ participants and 0.440 (p<0.001) in the MetS- participants. The correlation of PAL with CIMT was also positive and significant in CAP+ participants (r=0.150, p<0.001), but not in the CAP- participants (r=-0.001, p=0.621), with however a non-significant difference between the two estimates (p=0.374). Hip circumference was correlated with CIMT in MetS- but not MetS+ participants. CONCLUSION: physical activity in the current study appeared to be a correlate of infraclinical CVD risk in participants without metabolic syndrome, but not in those without.

Cardiovascular Risk Factors and Nutritional Intake are not Associated with Ultrasound-defined Increased Carotid Intima Media Thickness in Individuals Without a History of Cardiovascular Events.

BACKGROUND: Carotid ultrasound appears to be useful in the assessment of cardiovascular risk. In this study, we have assessed the carotid intima-media thickness (CIMT) in a group of individuals without a history of cardiovascular events. METHODS: A sample of 431subjects (189 [43.9%] males and 242 [56.1%] females) was obtained from an urban population using a stratified-cluster method in Mashhad stroke and heart atherosclerosis disorder study. None of the subjects had a history of the cardiovascular event. Carotid artery duplex ultrasound was used to determine the CIMT in all subjects, and to identify those with an abnormal value (CIMT [+]; i.e., CIMT ≥ 0.8 mm). Dietary intake of participants was assessed using a questionnaire for 24-h dietary recall. The relationship between anthropometric, biochemical and dietary data and CIMT were assessed. RESULTS: The mean age of subjects was 48.7 ± 8.0 years. Of the 431 patients, 118 (27.4%) were found to be CIMT (+). Of the cardiovascular parameters assessed, only age (odds ratio [OR] [95% confidence interval (CI)], 1.11 [0.56-4.34]; P < 0.01) and male gender (OR [95% CI], 1.14 [0.63-2.23]; P < 0.05) were significant independent predictors of ultrasound defined CIMT. Crude and total energy adjusted intake were not associated with the presence of CIMT (+). CONCLUSIONS: It appears that within a relatively young Iranian population of individuals without a history of cardiovascular event, the presence of CIMT (+) defined by duplex ultrasound cut-off value of ≥0.8 mm, did not associate with several modifiable cardiovascular risk factors or measures of dietary intake.

Association of angiotensin II type 1 receptor gene A1166C polymorphism with the presence of diabetes mellitus and metabolic syndrome in patients with documented coronary artery disease.

BACKGROUND: There are relatively limited data available on the genetic susceptibility to diabetes mellitus and metabolic syndrome in the Iranian population. We have therefore investigated the association between the angiotensin II type I receptor gene polymorphism (AT(1)R/A1166C) and the presence of diabetes mellitus and metabolic syndrome in a well defined group of patients. METHODS: Patients with angiographically defined coronary artery disease (CAD) (n=309) were evaluated for the presence of AT(1)R/A1166C polymorphism. These patients were classified into subgroups with (n=164, M/F: 109/55) and without (n=145, M/F: 84/61) diabetes mellitus. The AT(1)R polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based method. RESULTS: There was a higher frequency of polymorphic genotypes (AC+CC) in the diabetic compared with the non-diabetic group (p=0.01). When determined for each gender separately, this difference remained significant in the males (p=0.04) but not in females (p=0.09). With regard to the allele frequencies, the C allele was significantly higher and the A allele frequency was lower in the diabetic group (p=0.01). This remained significant after gender segregation for males (p=0.01) but not females. In the binary logistic regression analysis, only serum fasting glucose was found as the independent predictor for the presence of diabetes in the CAD patients (ß=1.16, p<0.001 for total population and ß=1.29, p<0.001 for male subjects). There was no significant difference in genotype or allele frequencies between subgroups with and without metabolic syndrome, this being unaffected by gender or the definition of metabolic syndrome used apart from a significantly lower frequency of C allele in male subjects with metabolic syndrome defined by the NCEP ATP III criteria (p=0.04). CONCLUSION: The AT(1)R/A1166C polymorphism may be associated with the presence of diabetes mellitus in male subjects with documented CAD.

Serum inflammatory and immune marker response after bare-metal or drug-eluting stent implantation following percutaneous coronary intervention.

We assessed the changes in serum antiheat shock protein (HSP)-27 antibody and high-sensitivity C-reactive protein (hsCRP) levels, following the placement of a drug-eluting stent (DES) or bare-metal stent (BMS) in patients with stable coronary artery disease. Either a BMS or DES was implanted in 137 patients (82 BMS; 55 DES). Anti-HSP27 and hsCRP levels were measured 24 hours before and 24 hours after stenting. Median hsCRP serum levels increased significantly to 60.78 (10.13-84.87) and 77.80 (50.00-84.84) mg/L for BMS and DES groups (P = .006 and P = .000, respectively); this increase did not differ significantly between the 2 groups. Median anti-HSP27 antibody levels decreased to 0.26 (0.17-0.49) and 0.21 (0.16-0.29) absorbency units in BMS and DES groups (P = .045 and P = < 0.001, respectively). The changes in anti-HSP27 antibody titers were significant between the 2 groups (P = .015). Bare-metal stent and DES differ in stimulation of immune rather than inflammatory responses. Less stent restenosis after DES compared with BMS implantation could, in part, be attributed to differences in immune responses.

Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers.

Saffron (Crocus sativus) stigma tablets were evaluated for short-term safety and tolerability in healthy adult volunteers. The study was a double-blind, placebo-controlled design consisting of a 1 week treatment of saffron tablets. Volunteers were divided into 3 groups of 10 each (5 males and 5 females). Group I received placebo; groups 2 and 3 received 200 and 400mg saffron tablets, respectively, for 7 days. General measures of health were recorded during the study such as hematological, biochemical and electrocardiographic parameters done in pre- and post-treatment periods. Clinical examination showed no gross changes in all volunteers after intervention. Saffron with higher dose (400mg) decreased standing systolic blood pressure and mean arterial pressures significantly. Saffron decreased slightly some hematological parameters such as red blood cells, hemoglobin, hematocrit and platelets. Saffron increased sodium, blood urea nitrogen and creatinine. This study showed that saffron tablets may change some hematological and biochemical parameters. However, these alterations were in normal ranges and they were not important clinically.

Glucokinase gene promoter -30G>A polymorphism: a cross-sectional association study with obesity, diabetes Mellitus, hyperlipidemia, hypertension and metabolic syndrome in an Iranian hospital / Polimorfismo -30G

OBJECTIVE: A -30G>A single nucleotide polymorphism in the promoter region of the glucokinase gene has been previously associated with obesity, insulin resistance and diabetes. The present study aimed to evaluate the association of this polymorphism with obesity and its comorbidities in a population from Northeast Iran. METHODS: Five hundred and forty-two subjects aged 18 to 65 years were included in the study and divided into normal (BMI<25, n=220), overweight (2530, n=187) groups. All subjects were genotyped for the -30G>A polymorphism using the polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The genotypes and allele frequencies of the three groups did not differ significantly (p>0.05). When the study population was categorized according to diabetes mellitus, hyperlipidemia, hypertension and metabolic syndrome status, no significant difference in -30G>A genotypes and alleles was found between the subgroups with and without these disorders (p>0.05), apart from a significantly higher frequency of the G allele in the hyperlipidemic vs. non-hyperlipidemic subgroup (p<0.05). CONCLUSION: The findings of the present study do not support an association between the -30G>A polymorphism and high body mass index in the Iranian population.

OBJETIVO: O polimorfismo de nucleotídeo único -30G>A, na região promotora do gene da glucoquinase, já foi associado à obesidade, resistência insulínica e diabete. O objetivo deste estudo foi avaliar a associação deste polimorfismo com a obesidade e suas comorbidades em uma população do nordeste iraniano. MÉTODOS: Quinhentos e quarenta e dois indivíduos com idades entre 18 e 65 anos foram divididos em três grupos: normal (BMI<25, n=220), sobrepeso (2530, n=187). Todos os indivíduos foram genotipados para o polimorfismo -30G>A através da técnica da reação em cadeia da polimerase - polimorfismo do comprimento do fragmento de restrição. RESULTADOS: As frequências dos genótipos e alelos dos 3 grupos não diferiram entre si (p>0,05). Quando a população de estudo foi categorizada de acordo com a presença de diabete, hiperlipidemia, hipertensão arterial e síndrome metabólica, os genótipos e alelos -30G>A dos subgrupos com e sem essas doenças não diferiram entre si (p>0,05), exceto por uma frequência maior do alelo G no grupo de hiperlipidêmicos quando comparados aos não hiperlipidêmicos (p<0,05). CONCLUSÃO: Os achados do presente estudo não confirmam uma associação entre o polimorfismo -30G>A e excesso de peso na população iraniana.