مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و سوم شماره 4 (پیاپی 172، تیر 1394)

Cancer/Testis antigens (CTAs) as a group of tumor antigens are the novel subjects for developing cancer vaccine and immunotherapy approaches. They aberrantly express in tumors with highest normal expression in testis, and limited or no expression in normal tissues. There are important similarities between the processes of germ-cell and cancer cell development Spermatogenesis begins at puberty when expression of novel cell-surface antigens occurs when the immune system has been refined the ability to distinguish self from non-self. Whereas macrophage and lymphocytes are commonly found within interstitial spaces of the testis, these antigen-presenting cells are rarely seen within the seminiferous tubules. These observations have led to the concept of the immune privileged site for testis. Localized normal expression of the CT genes in testis that makes them immunogenic for immune system, in one side, and their abnormal expression in different kinds of cancer cells, in the other side, has make them as promising target for developing cancer vaccines and new cancer therapeutics approaches. In malignancies, gene regulation is disrupted which results aberrant expression of CT antigen in a proportion of tumors of various types. For some CTAs, data support their fundamental role in tumorigenesis. Several authors believe it is not clear whether they have an essential role in tumorigenesis or they are by-products of chromatin variations in cancer. There is a growing list of CTAs within them advanced clinical trials are running by using some of them in cancers like lung cancer, malignant melanoma and neuroblastoma. In this review we discuss the gene TSGA10 as an example of CT genes. TSGA10 expresses in its highest levels in elongating spermatids and localized in the fibrous sheath of mature sperm. This gene is proposed as a serological biomarker in cutaneous lymphoma. Its abnormal expression has been reported in different cancers such as acute lymphoblastic leukemia, breast, brain, gastrointestinal and a range of other cancers either in mRNA or protein levels. It has an important role in angiogenesis in cancer tumors because of its effects in the gene hypoxia-inducible factor (HIF1). Absence or lack of TSGA10 expression has been reported in ascosporic infertile men.

Bone is a hard and dynamic tissue, which continually undergoes remodeling process. Longitudinal growth of bone is mediated by growth plate that is a cartilage structure at the end of long bones. During puberty, along with the closure (ossification) of growth plate, the longitudinal growth of bone will stop. Diazinon is one of the widely used organophosphorus pesticides that have been known to cause damage to the cells and tissues of the body by enhancing oxidative stress. Due to the dynamism and active process, bone and growth plate tissues are suitable models to investigate the effect of diazinon on bone development and bone growth. The aim of this study was to investigate the effects of diazinon on the epiphyseal growth plate width (including the proliferating cells zone and hypertrophy cells zone) of immature rat. This is an experimental study. This study was performed on 12 immature male in Ferdowsi University of Mashhad in May 2014, Wistar rats that randomly divided into 2 groups: control group and diazinon group. All treatments were done by oral gavage during 28 days. The animals were sacrificed on day 28 and left femur bones were removed for histomorphometric studies of epiphyseal growth plate width. Assessments were done by ImageJ software, version 1.40g (Wayne Rasband, NIH, USA) and the significance of the results were performed by ANOVA analysis and Tukey’s test. Epiphyseal growth plate width of diazinon group was significantly reduced (P=0.0126) in compared to control group. This reduction was associated with reduced of width of the proliferating zone (P=0.0001) and increased width of the hypertrophy zone (P=0.0166). Diazinon leads to reduction in the Epiphyseal growth plate width of immature male rats. Therefore it could be a factor in the impairment of bone longitudinal growth and premature closure of the growth plate.

Pregnancy in women with systemic lupus erythematosus (SLE) is still introduced as a major challenge. Consulting before pregnancy in these patients is essential in order to estimating the risk of undesirable maternal and fetal outcomes by using appropriate information. The purpose of this study was to develop an artificial neural network for prediction of pregnancy outcomes including spontaneous abortion and live birth in SLE. In a retrospective study, forty-five variables were identified as effective factors for prediction of pregnancy outcomes in systemic lupus erythematosus. Data of 104 pregnancies in women with systemic lupus erythematosus in Shariati Hospital and 45 pregnancies in a private specialized center in Tehran from 1982 to 2014 in August and September, 2014 were collected and analyzed. For feature selection, information of the 149 pregnancies was analyzed with a binary logistic regression model in SPSS software, version 20 (SPSS, Inc., Chicago, IL, USA). These selected variables were used for inputs of neural networks in MATLAB software, version R2013b (MathWorks Inc., Natick, MA, USA). A Multi-Layer Perceptron (MLP) network with scaled conjugate gradient (trainscg) back propagation learning algorithm has been designed and evaluated for this purpose. We used confusion matrix for evaluation. The accuracy, sensitivity and specificity were calculated from the confusion matrix. Twelve features with P<0.05 and four features with P<0.1 were identified by using binary logistic regression as effective features. These sixteen features were used as input variables in artificial neural networks. The accuracy, sensitivity and specificity of the test data for the MLP network were 90.9%, 80.0%, and 94.1% respectively and for the total data were 97.3%, 93.5%, and 99.0% respectively. According to the results, we concluded that feed-forward Multi-Layer Perceptron (MLP) neural network with scaled conjugate gradient (trainscg) back propagation learning algorithm can help physicians to predict the pregnancy outcomes (spontaneous abortion and live birth) among pregnant women with lupus by using identified effective variables.

The incidence rate of gastric cancer in Western countries has shown a remarkable decline in recent years although it is still the almost common cancer between men in Iran. The proto-oncogene MYC, located at 8q24.1, regulates almost 15% of human genes and is activated in 20% of all tumors. MYC amplification and overexpression of its protein product are observed in 15-30% of gastric neoplasia. The objective of this study was to find the preference of CISH or IHC in the diagnosis and prognosis of gastric cancer. In this cross-sectional investigation, 102 paraffin blocks samples of Iranian patients with gastric cancers were studied. All the patients had undergone primary surgical resection at the Cancer Institute Hospital, Tehran University of Medical Sciences from 1987 to 1993. CISH and IHC techniques were applied to the samples. CISH was carried out on 3-µm-thick tissue sections and with a ZytoDot CISH Implementation Kit (ZytoVision GmbH, Germany). IHC was down using the HRP method with the monoclonal antibody. A universal peroxidase-conjugated secondary antibody kit was used for the detection system. All samples were gastric adenocarcinoma and were selected randomly. Our data revealed that both diffuse and intestinal types of gastric cancer occurred significantly in men more than women. Our results showed an indication of some correlation between grades and CISH results, although the difference was not significant. Our data also showed that CISH+ patients (43.1%) were more frequent in comparison with IHC+ patients (14.7%). There was a correlation between CISH and IHC. This result revealed that there was a significant difference between grades and IHC. There was also no statistically significant difference between CISH amplification in diffuse and intestinal types. Our conclusion is that for the treatment, management of stomach cancer, and monitoring of progress and prognosis of the tumor that is almost important for patients and clinicians, CISH test is a better and feasible to IHC test, with regards to sensitivity and specificity.

Warfarin is the most common oral anticoagulant. This drug is used for the prevention and treatment of thromboembolic patients. It is difficult for physician to predict the results of warfarin prescriptions because there is narrow boundary between therapeutic range and complications of warfarin. Therefore drug dose adjustment is normally performed by an expert physician. Decision support systems that use extracted knowledge from experts in the field of drug dose adjustment would be useful in reducing medical errors, especially in the clinics with limited access to experts. The aim of this study was to propose a method for boosting the maintenance dose of warfarin for a maximum period of three days to eliminate disruptions in International Normalized Ratio (INR). In a retrospective study, from December 2013 to February 2014 in Shahid Rajaee Heart Center, Tehran, Iran, 84 patients with International Normalized Ratio below (INR) the therapeutic range was selected who was undergone a boosting dose during three days. Patients with unstable maintenance dose were excluded from the study. In this study, data from 75 patients receiving warfarin therapy were used for developing and evaluation of the proposed model. The INR target range for 37 patients out of remaining 75 cases was between 2.5 and 3.5, while for 38 patients the intended INR range was between 2 and 3. A separate fuzzy model was designed for each of the above-mentioned therapeutic ranges. The recommended dose for 37 patients having INR therapeutic range of 2.5 to 3.5 has mean absolute error and root mean squared error of 1.89 and 2.78 respectively for three days. These error rates are 1.97 and 2.88 respectively for 38 patients who are in therapeutic range 2 to 3. The results are promising and encourage one to consider this system for more study with the aim of possible use as a decision support system in the future.

In this study were focused on corneal cells changes in keratoconus disease, as there are differences between results of other studies that were done on keratokonic eyes. And the chief purpose was a comparison between keratoconus and normal population based corneal endothelium (in cell density, pleomorphism and polymegethism of cells). This study is an observational study and is a case-control type. This study was done in Farabi Ophthalmology Hospital, Tehran, from September 2013 to February 2014. In this study, 26 mild (corneal power is lower than 48 diopter) and moderate (corneal power is between 48 to 54 diopter) keratoconic eyes (case group) with no history of contact lenses wear or eye surgeries were compared with 25 normal eyes (control group) that corneal power based topographic images is lower than 47.2 diopter. This comparison were done based specular microscopy images which were taken by Noncontact (Topcan Sp-2000 P) specular microscope in 5 corneal regions (central, superior, inferior, nasal, temporal). Then the information related to the cell density, Coefficient of Variation (CV) of polymegethism and pleomorphism of cells were analyzed by SPSS software, version 21 (SPSS, Inc., Chicago, IL, USA). Superior corneal region has the largest amount of endothelial cell density in case and control groups (P<0.001). But the effects of keratoconus on the cell density was not significant (P=0.96). And also CV of polymegethism in two groups (case and control groups), was similar (P=0.828). Pleomorphism was seen in 7 eyes of 26 eyes in case group (26.9%) and 6 eyes of 25 eyes in control group (24%). Keratoconus does not have any considerable effect on cell density, polymegethism and pleomorphism, in mild and moderate stages and corneal opacity risk caused by intraocular surgeries (such as: Cataract or Glaucoma surgeries) and some diseases (such as diabetes and uveitis) is similar in keratoconic and normal eyes.

Helicobacter pylori (HP) infection may be having no clinical symptoms and if not treated will be persisting. This infection was considered as gastric diseases even during pregnancy. During the last decade its relationship with pregnancy related- disorders has been strongly reported in literature. In this study we evaluated the effect of positive IgG and CagA strains helicobacter pylori on incidence of early spontaneous abortions. A cross-sectional study was carried out on 100 women were referred to health centers and Motahari Hospital, Urmia, Iran, from October 2012 to March 2013. Fifty women with first miscarriage as cases and 50 women with previous normal delivery as controls were studied. A 2-cc blood sample was taken from each patient to evaluate the specific IgG titer by ELISA method. All results of samples with positive H. pylori IgG, were assayed for anti-CagA, IgG antibodies. A questionnaire was filled for each subject. The associations between CagA positive cases with odds of spontaneous abortion incidence were analyzed by using SPSS software, ver. 19 (Chicago, IL, USA). Mean (±SD) of age were 21.0±5.78 and 30.78±5.10 years for cases and controls group respectively. There was no significant difference in mean of age (P=0.25), and parity (P=1) between two groups. H. pylori IgG antibodies were positive among 23 and 24 (46% vs. 48%) in women with aborted and normal pregnancy respectively. Relationship between IgG status and miscarriage was not significant (OR=0.92, CI95%: 0.39-2.17, P=0.84). In particular anti-CagA antibodies were positive among 18 and 13(78.3% vs. 54.2%) in women with aborted and normal pregnancy respectively. Among women with CagA positive strains had higher odds of miscarriage (OR=3.05, CI95%: 0.73-13.76, P=0.08), but it wasn’t significant. According to the result of this study there was not any association between HP infection and miscarriage. We recommend more studies with larger sample size for determining the effect of CagA positive strains on miscarriage.

Antimicrobial resistance is a growing problem in many bacterial pathogens and is of particular concern for hospital-acquired nosocomial infections. Klebsiella pneumonia is an important cause of nosocomial infections has rapidly become the most common extended spectrum beta-lactamases (ESBLs) producing organism. ESBL are defined as the enzymes capable of hydrolyzing oxyimino-cephalosporins. The aim of this study was to compare phenotypic detection of ESBL using two phenotypically method among the clinical isolates of Klebsiella pneumoniae. In this cross-sectional study a total of 144 isolates from clinical samples Urine, sputum, wound, blood, throat and body fluids isolated and identified as K. pneumoniae in a teaching hospitals in Shiraz within a six months period from December 2012 to May 2013. Antibacterial susceptibility test performed to 14 antibiotics by the disk diffusion method according to CLSI guideline and then isolates that were resistant to at least one of the beta-lactam antibiotics evaluated for the production of beta-lactamase enzymes by using E-test ESBL and combined disk method. Totally 38 (26.3%) isolates produced ESBLs. All ESBL producing isolates were susceptible to imipenem and meropenem and resistant to aztreonam. The highest antibiotic resistance was observed for amoxicilin (100%) and the lowest antibiotic resistance was observed for meropenem (9.7%). The number of 38 (100%) isolates were identified as ESBL producer by using E-test ESBL ceftazidime. It was while using the combined disks; ceftazidime/clavulanic acid, cefotaxime/clavulanic acid and cefpodoxime/clavulanic acid, respectively 35 (92.1%), 34 (89.4%) and 31 (81.5%) of isolates identified as beta-lactamase producing isolates. Considering the high prevalence of bacteria producing ESBL, screening for infections caused by ESBL-producing isolates may be lead to the most effective antibiotics therapies.

Chronic obstructive pulmonary disease (COPD) and heart failure are prevalent comorbidities affecting a vast proportion of the world population, responsible for significant morbidity and mortality, their coexistence is more frequent than previously recognized that poses important diagnostic and therapeutic challenges. We intend to determine the prevalence of concomitant left ventricular dysfunction in COPD patients. We performed a cross-sectional study in patients who had referred to Firuzgar University Hospital in Tehran from March 2011 to March 2013 in period of 2 years. All participants were compatible for including and excluding criteria’s. In all cases of COPD, pulmonary function test was done; also Echocardiography was performed as the diagnostic assessment of heart failure. Out of 74 participants there was 56(75.7%) male and 18(24.3%) female with the mean age of 67.712.9 (SD), the prevalence of left ventricular systolic dysfunction (LVSD) was 25.70%, also the prevalence of left ventricular diastolic dysfunction (LVDD) was 74.60% among 71 patients. The prevalence of LVSD in patients with and without history of coronary artery disease (CAD) was 33.30% and 15.60% respectively. The prevalence of LVDD was 85.40% in patient with history of CAD and 60% in patients without it. The presence of ventricular dysfunction (neither systolic nor diastolic) in COPD patients was not statistically associated with presence of CAD or the intensity of underlying COPD disease. Knowledge about the prevalence of concomitant left side heart failure in COPD patients is limited, but it seems the presence is rather common, so more attention should be paid to coexistence of ventricular dysfunction in COPD patients disregarding presence of CAD or COPD intensity in clinical practice.

One of the main reasons of hemorrhagic fevers is Ebola. The high rate of mortality and lack of definite treatment have been caused this infection to be a serious problem in the world. Ebola, especially in the early stages, when causes symptoms such as fever, anorexia and nausea, can be confused with malaria infection and conversely, severe malaria with Ebola. Plasmodium falciparum is an important cause of severe malaria that more than other types of plasmodium confused with Ebola. The patient is a 54-year-old man who had gone to Sudan about 8 months ago. The patient reported that fever, chills and headache had been started one week before traveling from Sudan to Iran and hematuria was added to his symptoms in third week of illness in Iran. He was referred to the emergency department with probable diagnosis of Ebola. Plasmodium falciparum gametocytes were revealed in his peripheral blood smear. Finally, he was treated with Coartem (artemether/lumefantrine) for malaria and after clinical improvement discharged to home with good condition. Ebola should be suspected in every patient with fever and a history of traveling to endemic areas. Considering the fact that in most areas where Ebola is endemic also malaria is common, lack of clinical suspicion to malaria causes that clinicians mistake malaria with Ebola. Necessary laboratory tests to rule out important differential diagnoses in patients with suspected Ebola virus contains: Peripheral blood smear for malarial parasite and blood culture and blood cell counts to investigate typhoid fever and other bacterial infections. Therefore, malaria should be considered as an important differential diagnosis in every patient suspected with Ebola.