Tehran University Medical Journal

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Background: Cutaneous leishmaniasis is a major health problem in Iran and especially Isfahan province is considered as an endemic area for this disease. Regarding the previous report of positive effects of Cassia fistula boiled extract in the treatment of cutaneous leishmaniasis, this study was designed to evaluate the effect of combination therapy with intralesional meglumine antimoniate and Cassia fistula fruit gel compared to placebo in this disease.
Methods: 140 patients with cutaneous leishmaniasis referring to Skin Disease and Leishmaniasis Research Center of Isfahan (SDLRC) were randomly allocated in two groups. One group received intralesional meglumine antimoniate injection and Cassia fistula fruit gel and the second group were treated with intralesional meglumine antimoniate and placebo gel. Improvement was defined as complete cure, partial cure and treatment failure.
Results: At 12 week, 47 patients treated with intralesional meglumine antimoniate and topical Cassia fistula fruit gel achieved complete cure (67.1%) compared to 29(41.4%) patients in placebo treated group. There was significant difference in cure rate between two treatment groups of this study (p<0.001). Nine patients (19%) in each group suffered from adverse effects of the treatment such as itching and erythema. There was no significant difference in this regard between two groups (p=0.82).
Conclusions: The results of this study shows the efficacy of Cassia fistula fruit gel in increasing the cure rate of cutaneous leishmaniasis lesions achieved by intralesional meglumine antimoniate. Combination therapy of intralesional meglumine antimoniate and Cassia fistula fruit gel could be suggested as a choice for the treatment of acute cutaneous leishmaniasis lesions.

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Background: Polycystic ovary syndrome (PCOS) is a common cause of ovulation insufficiency and then infertility. Therapeutic options to induce ovulation in anovulatory PCOS patients are clomiphene citrate, metformin, tamoxifen, dopamine agonists (bromocriptin), Gonadotrophin and laparoscopic ovarian electrocautery (LOE). Gonadotrophin and LOE are important options in anovulatory clomiphene citrate-resistant patients with PCOS. Literature data regarding compare of the efficacy of these two treatments are few. Therefore we aimed to study the pregnancy rates of these treatments in infertile clomiphene citrate-resistant patients with PCOS. Methods: A randomized clinical trial study was carried out in infertile clomiphene citrate-resistant patients with PCOS, referred to infertility clinic of Mirza Koochackhan Hospital of Tehran University of Medical Science in Tehran, Iran, between 2003 and 2008. Results: A total of 100 patients women were randomly allocated in two groups. There were no differences in age and pimary and secondary infertility duration. In LOE treatment group, eight cases (16%) were pregnant and all delivered at term. in gonadotrophin treatment 14 cases (28%) were pregnant, 10 cases (20%) delivered at term but four cases aborted. The cost in gonadotrophin treatment was significantly more than laparoscopic ovarian diathermy (p<0.001). In logistic regression analysis, age, BMI, cost and kind of treatment had no significant effect on pregnancy rate. Conclusions: Pregnancy and abortion rate in gonadotrophin treatment was more than LOE but the difference was not significant. More studies are needed.

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Background: Because bronchial hyper responsiveness (BHR) has been shown to be a risk factor for asthma and lung function decline, interest has focused on diagnosing BHR. The aim of our study was to measure the association between airway caliber relative to lung size expressed as the ratio between forced expiratory flow, mid expiratory phase, divided by forced vital capacity (FEF25-75/FVC) and BHR measured by methacholine challenge test (MCT) to obtain a cutoff for this ratio and positive MCT.
Methods: We carried out a cross- sectional study on general Iranian population in 376 subjects aged 7-73 years who were referred to Shariati hospital in Tehran, Iran in an outpatient setting. There were 190 male (50.5%) and 186 female (49.5%) subjects. They had chronic respiratory symptoms such as cough and dyspnea. The physical examination was normal. Baseline spirometry was normal or equivocal. MCT was done for all subjects over a two year period (2009- 2010). Positive MCT was defined by PC 20≤4mg/ml.
Results: The methacholine challenge test was positive in 191 (50.8%) and negative in 185 (49.2%) patients. The mean of FEF25-75/FVC in positive MCT was 0.86±0.27 Vs. 0.91±0.28 in the negative ones (p=0.070). The sensitivity and specificity of FEF25-75/FVC for prediction of MCT results were 57.1% and 60.2% based on cutoff point of 0.85 in all patients, and 87.5% and 70.7% based on cut off point of 1 in allergic patients, respectively.
Conclusion: The FEF25-75/FVC appears to be a useful predictive ratio in allergic patients but not in general population.

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Background: Human embryonic stem cells (hESCs) are capable of self-renewal and large-scale expansion. They also have the capacity to differentiate into a variety of cell types including liver, cardiac and neuron cells. However, it is not yet clear whether hESCs can differentiate to hemangioblasts under in-vitro conditions. Hemangioblasts are bipotential progenitors that can generate hematopoietic lineages and endothelial cells. The aim of this study was to identify the potential of human Royan H5 embryonic stem cells in differentiating into hemangioblast cells.

Methods: HESCs were cultured at suspension system in DMEM/F12 supplemented with bFGF. 7-day old cells differentiated into blast cells under defined condition consisting of hematopoietic cytokines including BMP4, VEGF, etc. Blast cell markers kinase insert domain receptor (KDR), CD31, and CD34 were evaluated by flow cytometry and blast gene expressions (TAL-1, Runx-1 and CD34) were detected by qRT-PCR. Clonogenic assays were performed in semisolid medium by colony forming unit-assays.

Results: The hESCs (Royan H5) had the capacity of differentiating into hemangioblast cells. We could detect colonies that expressed 79%±12.5 KDR+, 5.6%±2.8 CD31+-CD34+ and 6%±2.12 KDR+-CD31+ on day 8 in the hESCs. Up-regulation of TAL-1, Runx-1 and CD34 occurred during hemangioblast commitment (P≤0.05 and P≤0.01, respectively). Moreover, hemangioblast cells generated mixed-type and endothelial-like colonies in semi-solid media.

Conclusion: Our results showed that hESCs (Royan H5) were able to differentiate into hemangioblasts under in-vitro conditions. The hemangioblasts had the potential to generate two non-adherent (Mixed-type) and adherent (endothelial-like) cell populations.

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Background: Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorders that affect approximately 5-7% of women in reproductive age. There is not any consensus about the efficient in vitro fertilization (IVF) protocol for patients with PCOS. The aim of the present study was to compare the half and one-third dose depot gonadotropin-releasing hormone (GnRH) agonist protocols versus the GnRH antagonist protocol in PCOS patients.
Methods: In the present study, we retrospectively evaluated 119 infertile women with PCOS. The patients entered in the study in accordance with Rotterdam criteria. According to GnRH analogue used for pituitary suppression, patients were divided into three groups: half and one-third dose depot GnRH agonist protocols and GnRH antagonist protocol. In GnRH agonist protocol, half or one-third dose depot Decapeptyl (1.875 mg, 1.25 mg) was injected on 21st day of previous cycle. In GnRH antagonist cycles, cetrotide 0.25 mg were administered daily when the leading follicles reached 14 mm. All basal and controlled ovarian hyperstimulation (COH) characteristics were analyzed.
Results: Basal characteristics including: age, FBS, prolactin, hirsutism, length of menstrual cycle were similar between 3 groups. Statically significant decreases in days of stimulation, number of gonadotrophin ampoules and metaphase II (MII) oocytes were found in GnRH antagonist protocol (P<0.001, P<0.001 and P=0.045), while the decrease in biochemical pregnancy (P=0.083) and live birth rate (P=0.169) wasn't significant. Number of embryos transferred were similar in the half and one-third dose depot GnRH agonist and GnRH antagonist cycles (P=0.881). The incidence of OHSS weren't significantly different between 3 groups (5%, 4.9% and 12.8%, P=0.308).
Conclusion: Our study suggest that one-third dose depot GnRH agonist protocol could be a suitable choice for treatment of PCOS because of lower incidence of ovarian hyperstimulation syndrome (OHSS) as compared with half dose depot GnRH agonist and higher pregnancy rate as compared with GnRH antagonist.

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Background: Septate uterus is the most common congenital malformation of the uterus in normal population and also patients with recurrent abortions. Pathogenesis of the disease is incompletely elucidated. It is clarified that incomplete absorption of paramesonephric ducts in the first trimester is responsible for septum formation. Hysteroscopy is known as the standard diagnostic and therapeutic procedure for septate uterus. In this study, our aim was to evaluated the effects of hysteroscopic septal resection in improving pregnancy outcomes in patients with unexplained infertility or recurrent abortion. Methods: Prospective cohort study was conducted in a Tehran University Medical Sci-ences affiliated hospital from April 2012 to May 2013. Eight patients were excluded from the study because of non-reproductive related complains. The other 40 patients went through a prospective cohort study and were treated for septate uterus. All patients had complete history taken and underwent physical examination. Septum size was measured by hysteroscopy. Patients underwent hysteroscopic metroplasty with resectoscope with an equatorial semicircular loop cutting 12 with monopolar energy. Some septum resected by 5 french hysteroscopic scissor. The patients were visited 2 month later for evaluated surgical outcome. This assessment was done by hysterosalpingography (HSG). Patient’s reproductive outcome were followed for 10.33 (SD:±6.43) months. Results: The mean age in patients was 31.5 (SD±3.02) years. In whole, 48 patients un-derwent hysteroscopic metroplasty. In 52.1% length of septum occupied two third of uterine cavity. Eight patients were excluded from the study because of non-reproductive related complains. There were 29 pregnant patients (72.5%). Fifteen patients became pregnant without intervention (51.7%). 14 patients had pregnancy under ART, while the pregnancy did not occur in 11 patients (27.5%) during this period. Among pregnant population there were 9 miscarriage (31%), 3 preterm (13.3%) and 17 term delivery (50%). Live birth rate in our study was 68.9%. In control hysterosalpingography (HSG), no patients had adhesion or residual ridge. Conclusion: The findings of this study indicate that hysteroscopic septoplasty is ac-ceptable for improving reproductive outcomes in patients with septate uterus.

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Background: With introduction of intracytoplasmic sperm injection with testicular sperm extraction or precutaneouse epididymal sperm aspiration, effective treatment was provided for azoospermic men. The aim of present study was to compare clinical outcome following intracytoplasmic sperm injection using extracted testicular/epididymal sperm or ejaculated severe oligoasthenoteratozoospermic sperm. Methods: After retrospective evaluation of more than four hundred medical records of patients undergoing intracytoplasmic sperm injection Mehr medical institute (between 2011-2012), 45 cycles with severe eligoasthenoteratozoospermia and 34 cycles with azoospermia were included. Patients were treated with gonadotropin releasing hormone agonist. The clinical characteristics and intracytoplasmic sperm injection outcome such as the rate of fertilization, implantation and clinical pregnancy were compared between the two groups. Results were presented as mean±standard deviation and number (percent). Differences between variables were analyzed using student's t test and the chi-square test was used to examine differences between categorical variables. P value less than 0.05 were considered as statistically significant. Results: Mean of female age (29±4.9 vs. 30.2±5.8), body mass index (26.9±5.3 vs. 26.9±3.8), estradiol level on human chorionic gonadotropin administration day (1375.6±843.9 vs. 1181.8±673.1), total number of retrieved oocytes (9.7±5.3 vs. 9.2±5.9) and metaphase II oocytes (7.7±5.1 vs. 7.5±5.4) were similar between the two groups. Of 436 and 313 retrieved oocytes, respectively 232 and 163 oocytes were ferti-lized in oligoasthenoteratozoospermic and azoospermic groups (53.2% vs. 52.1%, P=0.214). There were not statistical differences between groups in number of trans-ferred top quality embryos (1.5±1.2 vs. 1±1.2, P=0.09), implantation rate (22.7% vs. 16.9%, P=0.238) and clinical pregnancy rate (21 (47.7%) vs. 11 (35.4%), P=0.199). Conclusion: Intracytoplasmic sperm injection with precutaneouse epididymal sperm aspiration and testicular sperm extraction are effective methods to treat azoospermic men and its clinical outcome were comparable to ejaculated sever oligoasthenoterato-zoospermic cycles. It can be concluded that the influence of sperm quality and origin on intracytoplasmic sperm injection outcome are the same.

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Background: Polymorphisms of the upstream transcription factor 1 (USF1) have been associated with familial combined hyperlipidemia (FCHL), type 2 diabetes and coronary heart diseases (CHD). In the current investigation, the association of USF1s2 variant of human USF1 gene with premature coronary artery disease (PCAD) was evaluated in a population from southern Iran. USF1s2 has the best potential as a functional variant .in the USF1 gene. Methods: In a case-control study USF1s2 variant of human USF1 gene was determined by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique using BsiHKA I restriction enzyme for 186 women under 55 years of age and 135 men less than 50 years of age who underwent diagnostic coronary angiography in Saadi, Nemazee and Kowsar Hospitals of Shiraz, between July 2009 and March 2012. Data on the history of familial myocardial infarction or other heart diseases, hypertension, and smoking habit were collected by a simple questionnaire. Blood sugar level and serum lipid profile of all participants were also obtained by measuring the levels of fasting blood sugar (FBS), total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and high-density lipoprotein cholesterol (HDL). Results: Frequencies of the major (G) and minor (A) alleles of usf1s2 gene variant were 0.74 and 0.26 in the whole population, respectively. Meanwhile, the prevalence of the minor allele was significantly higher in PCAD patients compared with control subjects. This difference remained significant even after adjustment for confounding parameters. Indeed, subjects with mutant homozygous genotype (AA) were about 5 times more likely to suffer from early-onset CAD than those with wild-type homozygous genotype (GG). Moreover, the baseline characteristics of the control subjects and patients were statistically similar for almost all parameters except for the number of male individuals there was no significant difference among various genotypes in the patient group for any of these investigated variables. Conclusion: It appears that the usf1s2 variant in upstream transcription factor 1 gene is an independent predictor of premature coronary artery disease in our population and applies its effects without affecting blood sugar and lipid levels.

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Background: Metastasis associated miRNA (metastamiR) opened a new field of anti-metastatic therapy which have a great potential of treatment for the most lethal aspect of cancer, metastasis. The pleiotropic nature of gene regulation exhibited by certain miRNAs that showed that miRNAs might be endowed with a capacity to function as crucial modulators of tumor metastasis. MiR-31 is a pleiotropic anti-metastatic miRNA whose expression decreased significantly in metastatic breast cancer cells. MiR-31 has multiple roles in metastasis cascade. Therefore, using the miR-31-restoration based therapy could be an efficient anti-metastatic strategy for cancer therapy. Methods: This research was performed from May 2014 to October 2015 in Tarbiat Modares University in Tehran, Iran. The double-strand oligo of mature miR-31 was cloned into pcDNA 6.2gw/EmGFP according to the manufacturer instruction. The MDA-MB231, MCF-7 breast cancer cell lines were cultured and their miRNAs have been extracted. The expression of miR-31 has been quantified by Real time-PCR be-fore transfection of construct contained miR-31 into two cell lines and in normal breast cells. Then the constructs contain miR-31 have been transfected in to two cell lines. The expression of miR-31 has been quantified after 48 hours. Scratch and invasion as-say have been carried out for assessing the level of migration and invasion. Results: The result of Real time-PCR before transfection of constructs contained miR-31 have been shown 4 fold and more than 100 fold reduction in expression of miR-31 in MCF-7 and MDA-MB231 respectively in comparison to miR-31 expression in nor-mal breast cells, but after transfection of miR-31 construct to MDA-MB231 the quan-tification of expression showed the significant increase in mir-31 expression and 20 fold reduction in invasive and 10 fold reduction in migratory characteristics of MDA-MB231 in comparison to MCF-7. Conclusion: Metastasis associated miRNA have been represented a promising candi-dates in the field of anti-metastatic therapy and miR-31 as a powerful member of this family can function very effectively in order to inhibit the metastasis and introduce the new possibility of metastasis inhibition.

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Background: One of the today most common and incurable diseases that is associated with central neural system is ‘MS’ disease. Multiple sclerosis (MS) is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. In this disease become apparent a wide spectrum of symptoms such as lose muscles control and their coordination and vision derangement. The goal of this research is to consider to two problems: 1- Recognition of effective clinical symptoms on MS disease and 2- Considering levels of effectiveness of age, sex and education levels factors on MS disease and association between these factors according to verity of categories of this disease. Methods: Data mining science in medicine is worthy of attention with main application in diagnosis, therapy and prognosis, respectively high volume of collected datum. The data that were used in this article are about patients of Chaharmahal and Bakhtiari Province and collected by cure assistance. In this paper classification and association methods in software engineering field are used. Classification is a general process related to categorization, the process in which ideas and objects are recognized, differentiated, and understood. Association rules are created by analyzing data for frequent if/then patterns and using the criteria support and confidence to identify the most important relationships. Results: In consideration of first problem in this paper, concluded vision-clinical symptoms are the most effective symptoms and in consideration of second problem, concluded that from 584 records, women affected four times more than men. In other word 70% of MS patients with high graduate are in relapsing-remitting category and 62.5% of MS patients are 20-40 years old. Conclusion: Some of symptoms are quite temporary and transitory and are ignored by people. Awareness of clinical-symptoms prevalence manner can be warning for people before starting critical cycle of illness. This would cause early diagnosis, effective therapy and even prevention of disease progress, respectively to MS chronicity.

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Background: Cerebral arteriovenous malformations are rare congenital anomalies presenting as different symptoms depending on their size and the age of patient. Congestive heart failure is a rare condition in neonatal period and is most common due to structural heart defects, but rarely may be a result of peripheral shunts such as cerebral arteriovenous malformation.

Case presentation: A term male newborn infant who was delivered by Caesarean Section in Chamran Hospital, Ferdows, South Khorasan Province, June 2016. The infant was admitted to neonatal care unit due to nonreactive nonstress (NST) with normal Apgar score. In first postpartum visit, a systolic heart murmur was detected. Echocardiography showed small atrial septal defect secundum type and patent foramen ovale (PFO). He presented clinical manifestations of heart failure after 72 hours of birth. Antibiotic and treatment of heart failure was started. Following excluding most common etiologies of heart failure such as sepsis, anemia and arrhythmias, for detecting less common conditions such as cerebral vascular aneurism a transfontanelle ultrasonography was performed which showed dilated cerebral venous system. Magnetic resonance imaging (MRI) and Magnetic resonance venography (MRV) revealed a large congenital cerebral arterio-venous malformation (CAVM), in right cerebral hemisphere. Finally, he was expired 9 days after birth due to severe heart failure before any definitive treatment for closing CAVM could be done. 

Conclusion: CAVM are extremely rare vascular anomalies in newborns which may present occasionally as congestive heart failure in neonatal period. So after excluding other most common etiologies of heart failure such as structural heart defects, screening CAVMs should be done. Inspite of early diagnosis, usually they have extremely poor prognosis.

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Results: The mean weight and BMI (P=0.002), hirsutism and irregular menstruation cycle in the study group were greater than the control (P<0.001). In the study group the mean score of the sleep questionnaire in three dimensions: sleep problems (P=0.024), drug use (P=0.048), and the sufficiency of sleep (P=0.049) were higher than control. Regression analysis showed that there is a significant relationship between quality of life and menstruation cycle (P=0.046), as well as the three dimensions of negative affecting situations with family income (respectively, 0.015, 0.016 and P=0.035). Conclusion: The environmental factors can easily affect the quality of life in PCO women. Sleep patterns were not favorable, and the effect of menstruation on mood and low family income caused negative emotions in women with PCOS.

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Results: In the position of the -513T/C (rs1028181) polymorphism, a significant difference in frequency of all genotypes (CC, CT and TT) (P=0.001) and both alleles (C and T) (P=0.002) between preeclampsia pregnant women and healthy pregnant women was observed. There was no significant relationship between the other parameters of the study with the mentioned polymorphism in the patient and control groups. Conclusion: Due to the significant relationship between (rs1028181) -513T/C polymorphism and the occurrence of preeclampsia, which emphasizes the role of genetic predisposition in the development of preeclampsia disease, the presence of this polymorphism can be considered as a predictor of preeclampsia and concluded that polymorphic genetic markers are good predictive strategies for early detection of preeclampsia before the twentieth week of pregnancy.

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