Deformation of quay walls is one of the main sources of damage to port facility while liquefaction of backfill and base soil of the wall are the main reasons for failures of quay walls. During earthquakes, the most susceptible materials for liquefaction in seashore regions are loose saturated sand. In this study, effects of enhancing the wall width and the soil improvement on the behavior of gravity quay walls are examined in order to obtain the optimum improved region. The FLAC 2D software was used for analyzing and modeling progressed models of soil and loading under difference conditions. Also, the behavior of liquefiable soil is simulated by the use of “Finn” constitutive model in the analysis models. The “Finn” constitutive model is especially created to determine liquefaction phenomena and excess pore pressure generation.
Despite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this doubleblind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI).
Methods and results
A total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6–8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6–8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size −0.7% 95% CI: −2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6–8 days and at 6 months and final infarct size (FIS) measured at 6 months.
Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size.
Acute myocardial infarction; Ischaemia-reperfusion injury; Cardioprotection; Nitrite
Malignancy and its treatments could cause disturbance in homeostasisof body such as cortisol secretion. The present study has investigated the effects of cortisol level imbalance in behavioral and emotional adjustments.
Seventy-eight children with Acute Lymphoblastic Leukemia (ALL) have involved in this study. Their salivary cortisol level, which were sensitive to pain and disruptive behaviors, have measured.
Cortisol level effect in different periods: within duration of reaction to pain, sensitivity to pain and disruptive behaviors have evaluated. In addition abnormal regulation of cortisol levels have shown a very strong relationship between sensitivity to pain and the disruptive behaviors. Cortisol suppression was responsible for adjustment by the participants to stressful conditions.
Previous investigations have shown that there is a low reaction to stressor which decreases the vitality as well as impairing a negative memory in low cortisol levels. The findings of the present study demonstrated a nonlinear relation between cortisol level and sensitivity to pain as well as disruptive behaviors. Therefore, regulation of cortisol- up and down- is predisposed to maladjustment.
Child; Cancer; Cortisol; Pain; Disruptive behavior disorder
Although percutaneous coronary intervention (PCI) improves outcomes compared to thrombolysis, a substantial number of ST-elevation myocardial infarction (STEMI) patients do not achieve optimal myocardial reperfusion. This study was designed to evaluate factors related to suboptimal myocardial reperfusion after primary PCI in patients with STEMI.
Totally, 155 patients (124 men; mean age = 56.6 ± 11.03 years, range = 31– 85 years) with STEMI undergoing primary PCI were retrospectively studied. Additionally, the relationships between the occurrence of reperfusion failure and variables such as age, sex, cardiac risk factors, family history, Body Mass Index, time of symptom onset, ejection fraction, previous PCI, coronary artery bypass graft surgery or previous myocardial infarction, and angiographic data were analyzed.
Procedural success was 97.1% and complete ST resolution occurred in 43.2%. Age; cardiac risk factors; family history; body mass index; previous MI, coronary artery bypass graft surgery, or PCI; and use of thrombectomy device and GPIIb/IIIa inhibitor were not the determining factors (p value > 0.05). According to our multivariate analysis, time of symptom onset (OR [95% CI]: 045 [0.2 to 0.98]; p value = 0.044) and ejection fraction (OR [95% CI]:0.37 [0.26 to .091]; p value = 0.050) had reverse and male gender had direct significant associations with failed reperfusion (OR [95% CI]: 0.34 [0.11 to 1.08]; p value = 0.068). More degrees of ST resolution occurred when the right coronary artery was the culprit vessel (p value = 0.001). The presence of more than three cardiac risk factors was associated with failed reperfusion (p value = 0.050).
Considering the initial risk profile of patients with acute STEMI, including time of symptom onset and ejection fraction, as well as the accumulation of cardiac risk factors in a given patient, we could predict failed myocardial reperfusion to design a more aggressive therapeutic strategy.
Myocardial infarction; Myocardial reperfusion; Electrocardiography
Children with cancer should deal with difficult situations such asundergoing multimodal treatment. Emotion Regulation Mechanisms (ERM) could be more effective for childhood cancer adaptation. The main purpose of this study was examination a number of the biological, psychological and social emotion regulators on adjustment to pediatric oncology.
In this study, 98 children (39 girls and 59 boys) have participated that diagnosed as Acute Lymphoblastic Leukemia (ALL) cases along with their mothers. The participants were between 8 to 12 years old. Salivary cortisol, cognitive emotion regulation, children's level of inhibition, maternal positivity and Beck Depression Inventory have been applied for evaluation of Emotion Regulation (ER) while Cancer-Specific Stress and Coping, Connor-Davidson Resilience Scale, anxiety-depression scales and vitality test have all used for assessing the Emotional Adjustment (EA).
Using the canonical correlation has been showing significant relation between predictors of ER and EA. Cortisol level and mother's depression have played the most important role in above correlation.
Variation of cortisol level has identified by its various effects on the mother's behavioral system depression, cognitive strategies and emotional inhibition; would determine the rate of coping with cancer, resiliency and vitality.
Child; Malignancy; Emotions; Adaptation
Little is known about the natural history of aortic regurgitation (AR) in patients undergoing mitral valve procedures for mitral stenosis.
The aim of this study was to evaluate the short- and long-term effects of percutaneous mitral valvuloplasty (PMV) on coexisting AR.
Materials and Methods:
A total of 327 patients with rheumatic mitral stenosis (282 females and 45 males; mean age at the time of intervention = 47 ± 11 years) were followed up for between 48 hours and 13 years after PMV. At the time of PMV, 142 (43.3%) patients had no AR, 124 (37.9%) had mild AR, and 61 (18.7%) had moderate AR. After PMV, the follow-up showed that 120 (36.6%) patients had no AR, 103 (31.5%) had mild AR, and 104 (31.8%) had moderate AR.
AR progression after PMV and during the follow-up was significant (P < 0.00), but there was no significant increase in aortic valve replacement (AVR) procedures. The rate of AVR was higher in the moderate AR group (3.8%). There were no significant changes in the left atrial size (LA) (P = 0.6), ejection fraction (EF) (P = 0.4), and rhythm (P = 0.4) before and after PMV, respectively.
Our findings indicate that among patients with rheumatic mitral stenosis, a considerable number have concurrent AR. Concomitant AR at the time of PMV does not influence procedural success and is not associated with inferior outcomes. Rheumatic aortic insufficiency progresses slowly by nature, and patients with AR and mitral stenosis can safely tolerate PMV without the possibility of undergoing AVR in the near future. Patients with moderate degrees of AR remain good candidates for PMV.
Percutaneous; Balloon Dilation; Mitral Valve Stenosis; Aortic Valve Insufficiency
This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha × piperita (M. × piperita) in preventing chemotherapy-induced nausea and vomiting (CINV).
This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. × piperita. Statistical analysis included the χ2 test, relative risk, and Student’s t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. × piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time.
There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. × piperita in both treatment groups (p < 0.05) when compared with the control and no adverse effects were reported. The cost of treatment was also reduced when essential oils were used.
M. spicata or M. × piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective.
chemotherapy-induced nausea and vomiting (CINV); essential oils; Mentha spicata; Mentha × piperita; Lamiaceae
Nowadays, hand transplantation is a very challenging procedure for surgeons and researchers worldwide. Despite many problems that may occur after this surgery, some centers continue to practice this highly sophisticated procedure. Herein, we report on a 38-year-old man who received hand transplant from a 24-year-old brain-dead man. This patient had lost his right hand from the lower one-third of forearm six years before after a trauma from a mincing machine. Team members organized pre-operative research, cadaver dissection, legal consultation, religious permission and discussion to patient. This procedure was done by 15 Khordad Plastic Surgery Transplant team on February 27, 2013 for the first time in Iran.
Hand; hand transplant; Iran; composite tissue allotransplantation; allotransplant; forearm amputation
In spite of dozens of clinical trials to establish effective therapeutic and/or preventive vaccine to resolve HCV infection, no real vaccine has been proved to date. Genetic vaccines based on replication-defective adenoviruses have proved to elicit strong and long lasting T-cell responses against a number of viral antigens and are even currently being used for vaccine trials in humans. According to the controversy in the immune modulatory effects of both core and NS3 full length genes, it seemed more practical to employ some parts of these HCV proteins for vaccine design.
To generate recombinant Adenoviral vectors containing new overlapping-truncated region of NS3 gene or both the N- and C-terminal deleted parts of core gene, as well as a fusion fragment derived from both of them.
Materials and Methods
The corresponding transfer vectors expressing truncated fragments of core, NS3 or a fusion fragment of both genes were prepared. The integrity and sequence of the transfer vectors were confirmed, and followed by experiments involving homologous recombination between them and the adenovirus backbone plasmid in the bacterial host. Recombinant Ad-pNS3, Ad-pCore and Ad-pNS3pCore viruses were prepared by transfection of these new recombined constructs into 293 packaging cell lines. The virus titer was then calculated by an immunohistochemistry based method. The RT-PCR, Real-Time PCR and western blotting were used to evaluate gene expression by all recombinant constructs. The production of complete virion particles was evaluated by detailed electron microscopy in addition to the appearance of typical cytopathic effects (CPE) and GFP expression patterns in 293 cells. The RT-PCR and GFP detection were employed to monitor the integrity as well as infectivity potency of the viral particles in Hep-G2 cells.
RT-PCR, Real-Time PCR or western blotting confirmed expression of truncated fragment of NS3, core or a fusion fragment of theirs by newly constructed Ad-pNS3, Ad-pCore, Ad- pNS3pCore particles. Electron microscopy, which revealed many adenovirus-like particles and characteristics of CPE in infected cells in addition to GFP detection, confirmed the infectivity, potency and integrity of recombinant adenoviral particles.
These adenoviruses expressing novel fragments of NS3 and core genes may be suitable tools to overcome shortcomings associated with full gene expression in the setting of HCV vaccine therapy.
Vaccines; Genetic Vector; Genes
There are many physiological and psychological factors, which affect sensitivity to pain in children afflicted with ALL. The main purpose of this study was to evaluate the relation between salivary cortisol and sensitivity to pain, and also study the role of age and gender.
Seventy eight children (33 girls and 45 boys, aged 3 to 12 years) with ALL participated in this study. Morning salivary cortisol was measured and Behavior Scales of Sensitivity to Pain for Children (BSSPC) and Pre-Linguistic Behavioral Pain Reactivity Scale (PL-BPRS) were applied.
The results showed a high significant correlation between cortisol levels and pain sensitivity. Cortisol suppression was observed in some participants. The roles of gender and age in relation between cortisol levels and sensitivity to pain were assessed by using moderated regression. Gender and age moderated the relation between sensitivity to pain and cortisol level.
Conditional fear can explain for high sensitivity to pain amongst the participants; chemotherapy drugs might play a role in cortisol suppression and parenthood style perhaps determines sex difference in reaction to pain.
Child; Leukemia; Cortisol; Pain
Premenstrual syndrome is a common disorder experienced by up to 50% of women during reproductive age. The prevalence of severe form of PMS (PMDD) is 3% to 8 %. Psychiatric disorders in PMS patients have resulted in significant morbidity and in some cases caused resistance to the treatment process.
Material and Method
390 participants (264 with PMS/PMDD, and 126 healthy students of University of Guilan) who completed the demographic questionnaire, daily symptom rating (DSR) and the checklist 90-revised (SCL-90-R) took part in this study. This study was conducted using a cross sectional method.
According to repeated measure variance, the mean scores of psychiatric symptoms (Depression, Anxiety, Aggression, Interpersonal sensitivity) in the PMS group were significantly higher than the healthy group (p< 0/05), and increase in severity of PMS from mild to severe was accompanied by increase in mean score of these subscales. There was a significant difference in mean score of depression, anxiety, aggression and interpersonal sensitivity between the 3rd and the 13th day of the cycle. Significant effect of the DSR grouping (PMS and Healthy group) and time interaction emerged in interpersonal sensitivity and aggression, significant effect on the DSR grouping (Mild, Moderate, Severer) and time interaction demonstrated in interpersonal sensitivity.
Patients with prospective confirmed PMDD seemed to suffer from psychiatric symptoms. Therefore, recognizing co-morbid psychiatric symptoms in patients with PMDD is of prime importance. All healthcare providers should be sensitive to mental status of women with PMS.
Premenstrual syndrome; Psychiatric symptoms; Severity of illness
The symptoms of irritable bowel syndrome (IBS) are common in the general population. The aim of this population-based study was to determine the prevalence of IBS and describe the associated factors including demographic, life style and health-seeking behaviors in Shiraz city, southern Iran.
From April to September 2004, 1978 subjects aged > 35 years old completed a validated and reliable questionnaire on IBS.
The prevalence rate of IBS was 10.9%, higher in females, in 35-44 years old age group and among subjects eating fast food (14.1%) but was lower in those taking more fruits and vegetables (10.5%). The occurrence of anxiety, nightmare and restlessness was also significantly higher in subjects with IBS. It had an association with psychological distress and recurrent headaches but not with drinking tea/coffee, smoking or physical activity.
In our area, IBS was correlated with gender, age, psychological distress, recurrent headaches and consumption of fast foods that necessitate health planning programs by health policy makers.
Irritable Bowel Syndrome; Prevalence; Demography; Life Style; Health Behavior
The use of administrative databases to perform epidemiological studies in asthma has increased in recent years. The absence of clinical parameters to measure the level of asthma severity and control is a major limitation of database studies. A study was undertaken to develop and validate two database indexes to measure the control and severity of asthma.
Database indexes of asthma severity and control were derived from definitions in the Canadian Asthma Consensus Guidelines based on dispensed prescriptions and on medical services recorded in two large administrative databases from the Canadian province of Québec (Régie de l'Assurance Maladie du Québec (RAMQ) and MED‐ECHO) over 12 months. The database indexes of asthma severity and control were validated against the pulmonary function test results of 71 patients with asthma randomly selected from two asthma clinics, and they were also applied to a cohort of patients with asthma followed up for 139 283 person‐years selected from the RAMQ and MED‐ECHO databases between 1 January 1997 and 31 December 2004.
According to the database indexes, 49.3%, 29.6% and 21.1% of patients recruited at the asthma clinics were found to have mild, moderate and severe asthma, respectively, while 53.5% were found to have controlled asthma. The mean predicted value of the forced expiratory volume in 1 s (FEV1) ranged from 89.8% for mild asthma to 61.5% for severe asthma (p<0.001), whereas the range from controlled to uncontrolled asthma was 89.5% to 67.3% (p<0.001). The ratio of the FEV1 to the forced vital capacity (FEV1/FVC ratio) measured in 56 patients ranged from 75.8% for mild asthma to 61.8% for severe asthma (p = 0.030), whereas the range from controlled to uncontrolled asthma was 75.3% to 65.7% (p<0.001).
In the absence of clinical data, these database indexes could be used in epidemiological studies to assess the severity and control of asthma.
Dyspepsia is a common disorder that can present many clinical dilemmas in patient management. Although not life-threatening, the symptoms are long-lasting, interfere with daily activities and have a significant impact upon quality of life. The aim of this study was to determine prevalence of dyspepsia and its relationship with demographic and socioeconomic factors, and lifestyle in an apparently healthy population in Shiraz, southern Iran.
In a population-based study, 1978 subjects aged 35 years or older were interviewed from April to September 2004. A questionnaire consisting of demographic factors, lifestyle data and gastrointestinal symptoms was completed for each participant. The validity and reliability of the questionnaire were determined.
The prevalence of dyspepsia was 29.9%. The dyspeptic patients were classified as having ulcer-like (27.9%), dysmotility-like (26.2%) or unspecified dyspepsia (45.9%). The prevalence was higher in females, water-pipe smokers, NSAIDs users, and in those with psychological distress, recurrent headache, anxiety, nightmares and past history of gastrointestinal disease. Dyspepsia had an inverse relationship with consumption of pickles, fruits and vegetables, and with duration of meal ingestion. Subjects with dyspepsia symptoms were more likely to restrict their diet, take herbal medicine, use over-the-counter drugs, consult with physicians and consume medication advised by their friends.
This study reveals that dyspepsia has a high prevalence in Shiraz, southern Iran and is associated with several demographic factors, lifestyle and health-seeking behavior.
Dyspepsia; Prevalence; Epidemiology; Lifestyle
Mutations and promoters' methylation of a set of candidate cancer genes (CAN genes) are associated with progression of colorectal cancer (CRC). We hypothesized that these genes' promoters are inactivated through epigenetic silencing and may show a different profile in high-risk populations. We investigated the status of CAN gene methylation and CHD5 protein expression in African American CRC tissue microarrays (TMA) using immunohistochemical staining.
The promoter methylation status of the CAN genes was studied by methylation-specific PCR (MSP) in 51 Iranians (a white population) and 51 African Americans (AA). Microsatellite instability (MSI) was analyzed as well. The differential frequency of methylation for each gene was tested by chi-square analysis between the two groups based on matched age and sex. CHD5 protein expression was evaluated in moderate to well differentiated and poorly differentiated carcinomas compared to matched normal tissue using TMA. In addition, the correlation between these epigenetic biomarkers and various clinicopathological factors, including, age, location, and stage of the disease were analyzed.
Seventy-seven and 34% of tumors were distal in Iranian and African American patients, respectively. In both populations, the percentage of methylation was >65% for SYNE1, MMP2, APC2, GPNMB, EVL, PTPRD, and STARD8, whereas methylation was <50% for LGR6, RET, CD109, and RNF. The difference in methylation between the two populations was statistically significant for CHD5, ICAM5 and GPNMB. Thirty-one percent AA tumors showed MSI-H, compared to 28% in Iranians.
A significantly higher methylation rate was found for GPNMB, ICAM5, and CHD5 genes in AA patients compared to Iranians. These genes might play a role in the high incidence and aggressiveness of CRC in the AA population. The hypermethylation of the CAN genes can be considered as a marker of colon carcinogenesis.
AIM: To investigate the prevalence and risk factors of gastroesophageal reflux disease (GERD) symptoms in Qashqai migrating nomads with a different life style in Fars province, southern Iran.
METHODS: In summer 2006, 748 Qashqai migrating nomads aged 25 years or more were enrolled using a multiple-stage stratified cluster random sampling method. A questionnaire consisting of demographic characteristics, lifestyle and GERD symptoms (heartburn, regurgitation, chest pain, dysphagia, hoarseness and cough) as completed for each subject.
RESULTS: The questionnaire was completed in 717 subjects. The prevalence rate of GERD, defined as reflux occurring at least one time per week in the preceding year, was 33% (237 subjects). The prevalence was higher in older individuals (36.0% vs 28.9%, P < 0.05) and in those with other gastrointestinal complaints (51.0% vs 27.8%, P < 0.001), but not different in obese and non-obese subjects. It was also higher in those consuming fruits and vegetables more than once a week (36.2% vs 17.3%, P < 0.001). GERD had a positive correlation with smoking (42.1% vs 27.8%, P < 0.001), but a negative relation with non-alcoholic beverages. The association between GERD and non-steroidal anti-inflammatory drugs (NSAIDs) consumption was also significant (40.2% vs 25.4%, P < 0.001).
CONCLUSION: The prevalence of GERD (33%) is very high in Qashqai migrating nomads which may be due to a lower socioeconomic and educational level of these people and difference in the life style. Older age, frequent consumption of fruits and vegetables, smoking and NSAIDs are risk factors for GERD in this population.
Gastroesophageal reflux disease; Preva-lence; Risk factors; Nomads; Iran
In the title compound, (C4H14N2)[Cd(C7H3NO4)2]·2H2O, the CdII ion is coordinated by four O atoms [Cd—O = 2.2399 (17)–2.2493 (17) Å] and two N atoms [Cd—N = 2.3113 (15) and 2.3917 (15) Å] from two tridentate pyridine-2,6-dicarboxylato ligands in a distorted octahedral geometry. The uncoordinated water molecules are involved in O—H⋯O and N—H⋯O hydrogen bonds, which contribute to the formation of a three-dimensional supramolecular structure, along with π–π stacking interactions [centroid–centroid distances of 3.5313 (13) and 3.6028 (11) Å between the pyridine rings of neighbouring dianions].
AIM: To study halothane hepatitis (HH) in Iran and its associated risk factors.
METHODS: We retrospectively studied files of all cases diagnosed with HH referred to three referral hospitals and four private centers in Iran from April 1994 to September 2006. Information on age at surgery, gender, medications history, obesity, history of previous exposure, previous reaction to halothane, familial history, type of surgery, perioperative hypoxia or sepsis, morbidity and mortality were recorded and analyzed.
RESULTS: A total of 59 cases were identified. Forty-eight (81%) were women. The median age at the time of surgery was 44 years (range, 18 to 80 years). Sixty percent of patients were above 40-year-old. Obesity was observed in 22.2%. Previous history of exposures to halothane was noted in 61% of which 50% had history of post-exposure reaction. Coronary artery bypass graft (CABG), cholecystectomy, and cosmetic surgeries (mainly weight reduction) were the most frequent surgeries. The mortality rate was 12.2%. In patients developing encephalopathy, it was as high as 50%.
CONCLUSION: HH remains an important cause of morbidity and mortality in centers still using this anesthetic. However, a large percentage of these cases could have been avoided. To lessen occurrence of further cases of HH, the authors suggest that in female patients having a history of surgery (or delivery) with general anesthesia, the use of halothane should be absolutely avoided. Utilization of proper substitutes in adults’ anesthesia is advocated.
Anesthesia; Inhalation; Halothane; Hepatitis; Drug-induced
The reaction of chromium(III) nitrate hexahydrate, pyridine-2,6-diamine and 4-hydroxypyridine-2,6-dicarboxylic acid in a 1:2:2 molar ratio in aqueous solution resulted in the formation of the title compound, (C5H8N3)[Cr(C7H3NO5)2]·2H2O or (pydaH)[Cr(hypydc)2]·2H2O (where pyda is pyridine-2,6-diamine and hypydcH2 is 4-hydroxypyridine-2,6-dicarboxylic acid). Each CrIII atom is hexacoordinated by four O and two N atoms from two (hypydc)2− fragments, which act as tridentate ligands, in a distorted octahedral geometry. The O—Cr—O—C torsion angles between the two planes of the (hypydc)2− fragments [−99.81 (17) and 97.77 (17)°] indicate that these two units are almost perpendicular to one another. In the crystal structure, extensive O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds with D⋯A distances ranging from 2.560 (2) to 3.279 (3) Å, ion pairing, C—O⋯π [O⋯π = 3.166 (2) Å] and π–π stacking interactions between (hypydc)2− and (pydaH)+ rings [with a centroid–centroid distance of 3.3353 (14) Å] contribute to the formation of a three-dimensional supramolecular structure.
We have identified an alternative pathway of tumorigenesis in sporadic colon cancer, involving microsatellite instability due to mismatched repair methylation, which may be driven by mutations in the BRAF gene (V600E). Colorectal cancer (CRC) is the most common cancer in the world, and African Americans show a higher incidence than other populations in the United States. We analyzed sporadic CRCs in Omani (of African origin, N = 61), Iranian (of Caucasian origin, N = 53) and African American (N = 95) patients for microsatellite instability, expression status of mismatched repair genes (hMLH1, hMSH2) and presence of the BRAF (V600E) mutation. In the Omani group, all tumors with BRAF mutations were located in the left side of the colon, and for African Americans, 88%  of tumors with BRAF mutations were found in the right side of the colon. In African Americans, 31% of tumors displayed microsatellite instability at two or more markers (MSI-H), while this rate was 26% and 13% for tumors in the Iranian and Omani groups, respectively. A majority of these MSI-H tumors were located in the proximal colon (right side) in African American and Iranian subjects, whereas most were located in the distal colon (left side) in Omani subjects. Defects in hMLH1 gene expression were found in 77% of MSI-H tumors in both African Americans and Iranians and in 38% of tumors in Omanis. BRAF mutations were observed in all subjects: 10% of tumors in African Americans (8/82), 2% of tumors in Iranians (1/53), and 19% of tumors in Omanis (11/59). Our findings suggest that CRC occurs at a younger age in Omani and Iranian patients, and these groups showed a lower occurrence of MSI-H than did African American patients. Our multivariate model suggests an important and significant role of hMLH1 expression and BRAF mutation in MSI-H CRC in these populations. The high occurrence of MSI-H tumors in African Americans may have significant implications for treatment, since patients with MSI-H lesions display a different response to chemotherapeutic agents such as 5-fluorouracil.
Background: Twenty four hour oesophageal pH monitoring is frequently used to quantify the association between a patient’s symptom and gastro-oesophageal reflux. Three indices (symptom association probability (SAP), symptom index (SI), and symptom sensitivity index (SSI)) are used to quantify and establish this relation.
Aims: The aim of the present study was to compare these indices against the omeprazole test (OT) as an objective indicator of reflux induced symptoms.
Methods: Fifty two patients with a predominant symptom of heartburn were enrolled from gastroenterology and primary care clinics. Baseline symptom score was calculated at the fist visit. All patients underwent 24 hour oesophageal pH monitoring, and symptom-reflux association indices were calculated. All patients were placed on high dose omeprazole (40 mg in the morning, 20 mg at night) after completion of pH monitoring and symptom score was recorded again after one week.
Results: Thirty eight patients completed the study. All three indices were significantly related to each other (p<0.001). SAP and SSI (with a new cut off of 1.3, but not with the commonly used 5%) had statistically significant relations with OT (p<0.05 for both). SSI had the highest positive and negative predictive values and sensitivity. The specificity of SSI and SAP was equal and lower than SI. Areas under the receiver operating characteristic (ROC) curve for the three indices were not significantly different from each other or from a hypothetical non-discriminating test. Per cent time pH <4, sex, and age had no relation to OT and no effect on its correlation with association indices. No cut off point could be found at which the results of SI could be related significantly to the OT results.
Conclusion: SAP and SSI are significantly related to symptomatic response to high dose omeprazole; however, they are far from perfect, with a significant number of discordant cases as well as relatively small areas under the ROC curves. We suggest that the new cut off of 1.3 be used for SSI in the future. Further research is needed to identify possible methods to improve the discrimination power of these indices or to identify possible patient characteristics that may affect this relation.
gastro-oesophageal reflux; heartburn; symptom index; symptom association probability; symptom sensitivity index
AIM: To evaluate joint effects of Methylentetrahydrofolate reductase (MTHFR) C677T genotypes, and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients.
METHODS: We examined the associations between MTHFR C677T genotype, and promoter methylation of P16, hMLH1, and hMSH2 tumor-related genes among 151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit.
RESULTS: We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison, we did not find a significant association between methylation in tumors and any single genotype. However, in comparison to controls with the CC genotype, an increased risk of tumor methylation was associated with the CT genotype (OR = 2.5; 95% CI, 1.1-5.6). In case-case comparisons, folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high (above median) versus low (below median) serum folate/vitamin B12 levels were 4.9 (95% CI, 1.4-17.7), and 3.9 (95% CI, 1.1-13.9), respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group, especially in those with MTHFR CT (P = 0.01), and CT/TT (P = 0.002) genotypes, but not in those with the CC genotype (P = 1.0).
CONCLUSION: We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes, and this relationship is modified by MTHFR C677T genotypes.
Methylentetrahydrofolate reductase; Folate; Vitamin B12; Methylation; Colorectal cancer
In the title compound, (C4H14N2)[Cu(C7H3NO4)2]·3H2O or (bdaH2)[Cu(pydc)2]·3H2O (where bda is butane-1,4-diamine and pydcH2 is pyridine-2,6-dicarboxylic acid), the CuII atom is coordinated by four O atoms [Cu—O = 2.0557 (16)–2.3194 (16) Å] and two N atoms [Cu—N = 1.9185 (18) and 1.9638 (18) Å] from two chelating rings of the pydc2− anions, which act as tridentate ligands. The geometry of the resulting CuN2O4 coordination can be described as distorted octahedral. The the two pydc2− fragments are almost perpendicular to one another [77.51 (11)°]. To balance the charges, two centrosymmetric protonated butane-1,4-diammonium, (bdaH2)2+ cations are present. In the crystal structure, extensive O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds [D⋯A = 2.720 (2)–3.446 (3) Å], ion pairing, C—O⋯π [O⋯π = 3.099 (2) Å] and π–π stacking interactions between the pydc2− rings [centroid–centroid distance = 3.5334 (15) Å] contribute to the formation of a three-dimensional supramolecular structure.