مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و چهارم شماره 10 (پیاپی 190، دی 1395)

Despite advances in the vaccinology and chemotherapy in the past century, tuberculosis is still responsible for two million deaths every year. Emergence of multi-drug resistant strain and coinfection of TB-HIV make it a serious concern. Treatment and control of tuberculosis is a great health burden in every community. Active tuberculosis in children has very severe consequences especially those who are under 5-years-old, therefore vaccine indication should be taken. Bacille Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used for providing immunity or protection against tuberculosis (TB). In addition, BCG provides relative protection against leprosy and Buruli ulcer, it also can be used for treatment of bladder cancer. BCG is the most widely administered vaccine around the world. It has been given to over three billion individuals over the past decades. At first it was developed in 1908 at the Pasteur Institute in Lille by Albert Calmette and Camille Guérin. In fact BCG is a strain of Mycobacterium bovis that bear deletion in its genome following too long subculture in special media. Deletion in region of deletion 1 (RD1), a specific region of Mycobacterium bovis genome, has decreased pathogenicity of BCG strain. Following culture of BCG on different media since 1921 make genetic variation in the BCG strains that have specific characteristics. BCG should begin given to only immune-competent individuals and should not be administered to immunocompromised people. This vaccine is not effective in people formerly infected or sensitized with environmental mycobacteria. Previous meta-analysis studies indicate that BCG has variable range of protection from 0 to 80 percent against pulmonary TB, but is very effective against severe disseminated forms such as meningitis and miliary form of TB. Despite many research and develop new generation vaccine against TB, BCG vaccine still remains as the only effective vaccine because many efforts to replace it with better ones were unsuccessful.

The use of random flaps is one of the most common methods of reconstructive surgery because they are easy to use and quick to do. However, the absence of axial vessels especially in the distal areas can cause ischemia and loss of total or part of the flap. Different methods and systemic and topical medications have been recommended to prevent ischemia in random flaps. The aim of this study was to evaluate the effect of stem cells derived from umbilical cord blood in random flap survival in rats.
This experimental study was conducted in Animal Laboratory of Hazrat Fatemeh Hospital in 2012. In this study twenty Sprague-Dawley male rats weighing approximately 300 to 350 g were selected and divided randomly into two groups. In both groups after anesthesia, a flap was created in the posterior part of each rat with a size of 2 x 6 cm. In the intervention group we injected stem cells derived from umbilical cord blood into the flap, and after eight days the effects on the survival of flaps were examined by digital photography and then pathological examination was performed.
The mean of viable flap in the stem cell group was 6.57 cm2 and in control group 4.71 cm2. The minimum and maximum flap survival in the intervention group were 4.71 and 8.75, and the minimum and maximum flap survived in control group were 1.86 and 7.77. This difference was significant and showed that the viable parts of flap were more in the intervention group (P=0.49). In pathologic examinations epidermal and muscle necrosis of the skin were reported in 3 cases in the intervention group and 5 cases in control group.
This study showed that cord blood stem cells can be effective somehow in reducing ischemia and increasing random flap survival. However, similar studies are recommended in order to compare the results of this drug and placebo or other proven effective drugs.

Researchers are always trying to find specific markers which express specifically in cancer. These specific markers help to diagnose and treat cancer without affecting normal tissues. Cancer-testis antigens are among the new promising biomarkers, especially for targeted therapy. These markers are specially expressed in testis. Various studies have been reported individual expression of these proteins in some tumor tissues. Since testis is an immune privilege organ, abnormal expression of the above mentioned genes raises immune response and the serum antibody against them (CT antigene) can be detected as a marker of cancer. However, understanding their differential role in normal and cancer tissues may introduce them as new candidates of cancer biomarkers. The aim of this study was to evaluate AKAP3 gene expression in breast cancer and its correlation with clinicopathologic features of the disease.
This study is a case-control study conducted at the Brest Cancer Research Center (BCRC)- Iran, between October 2014 to May 2016. AKAP3 gene expression was investigated with real-time PCR in breast samples including: 74 tumors, 73 normal adjacents and 15 normal tissues. On the other hand the correlation between gene expression, clinicopathologic features of the tumors and treatment regimen were evaluated.
Statistical analysis showed a significant correlation between lack of AKAP3 expression, tumor size (P=0.01) and stage (P=0.04). The association between poor prognosis and the absence of AKAP3 expression in normal adjacent tissues were observed. Kaplan Meier plot showed a significant better disease free survival in the normal adjacent patients group that are expressed AKAP3.
It was observed that the better free survival in the normal adjacent group is because of the different AKAP3 expression, not treatment variations between two patient groups. As a result, AKAP3 can be a suitable candidate biomarker for breast cancer patients. Also, the study of gene expression in normal tissue of patients may be used to predict response to therapy.

There is no need to explain the importance of collection, recording and analyzing the information of disease in any health organization. In this regard, systematic design of standard data sets can be helpful to record uniform and consistent information. It can create interoperability between health care systems. The main purpose of this study was design the core dataset to record colorectal cancer information in Iran.
For the design of the colorectal cancer core data set, a combination of literature review and expert consensus were used. In the first phase, the draft of the data set was designed based on colorectal cancer literature review and comparative studies. Then, in the second phase, this data set was evaluated by experts from different discipline such as medical informatics, oncology and surgery. Their comments and opinion were taken. In the third phase refined data set, was evaluated again by experts and eventually data set was proposed.
In first phase, based on the literature review, a draft set of 85 data elements was designed. In the second phase this data set was evaluated by experts and supplementary information was offered by professionals in subgroups especially in treatment part. In this phase the number of elements totally were arrived to 93 numbers. In the third phase, evaluation was conducted by experts and finally this dataset was designed in five main parts including: demographic information, diagnostic information, treatment information, clinical status assessment information, and clinical trial information.
In this study the comprehensive core data set of colorectal cancer was designed. This dataset in the field of collecting colorectal cancer information can be useful through facilitating exchange of health information. Designing such data set for similar disease can help providers to collect standard data from patients and can accelerate retrieval from storage systems.

Rheumatoid Arthritis (RA) is a chronic inflammatory disease presenting with inflammation, tenderness and destruction of the synovial joints, resulting in severe disability and early death due to complication of disease. Previous diagnostic criteria are not useful for identifying patients who need early treatment. Thus, new diagnostic criteria for faster diagnosis of disease are introduced in 2010. The aim of this study was to compared 1987 ACR (American College of Rheumatology) criteria and 2010 ACR/EULAR (European League Against Rheumatism) classification criteria for diagnosis of rheumatoid arthritis.
In this Cohort prospective study, patients with early arthritis were evaluated according to the old and new diagnostic criteria and followed-up every two monthly for one year (2012-2013) in Hazrat-e Rasool University Hospital, Tehran. Inclusion criteria of this study were age more than 18 year and indefinite diagnosis of arthritis. For all of patients physical examination by expert rheumatologist was done and lab data include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide (Anti-CCP) and rheumatoid factor was requested. The sensitivity, specificity, positive and negative predictive values were then determined for each diagnostic criteria.
In this study 104 patients including 28 males (26.9%) and 76 females (73.1%) with the mean age of 44.2±13.7 years were included. At the end of one year follow-up, 82 were diagnosed to have RA while other 22 patients were not categorized as RA. Sensitivity for ESR, CRP, Anti-CCP and rheumatoid factor in 2010 ACR/EULAR criteria was 52%, 19%, 48%, 28% and specificity for them was 45%, 71%, 27%, 79% respectively. Number of small and large joint arthritis were more in patients with Rheumatoid Arthritis (RA) rather than other arthritis (P=0.0001). Sensitivity and specificity for small joints involvement was 87% and 54% and for large joints involvement was 81% and 59%. The sensitivity, specificity, positive and negative predictive values for 2010 ACR/EULAR criteria were 65%, 40%, 81%, and 23%, respectively. The sensitivity, specificity, positive and negative predictive values for 1987 ACR criteria were 51%, 62%, 83%, and 25% respectively.
In comparison to the old diagnostic criteria, the new one has higher sensitivity and lower specificity.

Protective antigen of anthrax toxin, after touching the cell receptors, plays an important role in the pathogenesis of toxin. The purpose of this study was to investigate the interaction of anthrax toxin protective antigen and four great combination propolis included caffeic acid, benzyl caffeate, cinnamic acid and kaempferol using the softwares and bioinformatics web servers.
Three-dimensional structure of protective antigen (receptor) obtains from Protein Data Bank (PDB). Four of the main components from propolis were selected as ligand and their 3D-structures were obtained from ChemSpider and ZINC compound database. The interaction of each ligand and receptor was assessed by SwissDock server (http://www.swissdock.ch/) and BSP-SLIM server (http://zhanglab.ccmb.med.umich.edu/BSP-SLIM). Docking results appears with Fullfitness numbers (in kcal/mol). Identification of amino acids involved in ligand and receptor interaction, was performed using the Chimera software; UCSF Chimera program (http://www.cgl.ucsf.edu/).
The results of interaction between propolis components and protective antigen by BSP-SLIM server showed that the most interaction was related with benzyl caffeate, caffeic acid, kaempferol and cinnamic acid, respectively. Results for the desired ligand Interaction with protective antigen genes using SwissDock server showed that the caffeic acid had ΔG equals -9.10 kcal/mol and FullFitness equal to -993.16 kcal/mol respectively. The analysis of interaction between ligands with amino-acids of protective antigen indicated that the interaction of Caffeic acid whit Glutamic acid 117 had energy -15.5429 kcal/mol.
Finding strong and safe inhibitors for anthrax toxin is very useful method for inhibiting its toxicity to cell. In this study the binding ability of four flavonoids to protective antigen was studied. Glutamic acid 117 is very effective in protective antigen binding and cell receptor and subsequent in virulent of anthrax toxin. Effective interaction of caffeic acid in propolis and glutamic acid 117 can be as useful in preventing the toxic effect on cell. According to our results, all four flavonoids tested in this study have binding activity to protective antigen and are good choices for fighting against anthrax.

Studies show that aerobic exercise prevents osteoporosis in menopause by stimulating osteoblastic cells. Therefore, the purpose of this study was to investigate the effect of 12 weeks of moderate-intensity aerobic exercise on alkaline phosphatase gene expression, serum levels of alkaline phosphatase, parathyroid hormone, and calcium in sedentary women.
This investigation is a semi-experimental study that was performed in September 2015 at Urmia University, Iran. The statistical population was all healthy and sedentary postmenopausal women 50 to 65 years old in Urmia city. Twenty sedentary postmenopausal women with an average age 60.12±2.12 yr, weight 72.35±10.50 kg, and body mass index 29.46±3.24 kg/m2 voluntarily and bona fide participated in this study, and then subjects were randomly divided to the Exercise/E (10 women) and Control/C (10 women) groups by random sampling method. E group performed of 12 weeks walking and jogging moderate-intensity aerobic exercise at 65-70% maximal heart rate of training, three sessions per week and per session 50-60 (min), but the C group participated in no intervention. Twenty-four hours before and after the 12-week training program were taken blood samples in order to measure of alkaline phosphatase gene expression and serum markers of bone in the E and C Groups. Evaluation of gene expression and serum markers of bone were measured by real-time reverse transcription PCR (RT-PCR) and Auto-analyzer (Biotechnica, Italy)/ ELISA reader (Awareness Inc., USA) machines, respectively. Data analysis included descriptive and inferential (ANCOVA test) statistics using SPSS version 23 (Chicago, IL, USA) and a significance level of P≥0.05 was considered.
The results showed that alkaline phosphatase gene expression and parathyroid hormone after 12 weeks of moderate-intensity aerobic exercise in between-groups were significantly increased (P=0.027 and P=0.006, respectively), while serum levels of calcium and alkaline phosphatase were not significantly different (P=0.941 and P=0.990, respectively).
The results suggest that 12 weeks of aerobic exercise of walking and jogging at 65-70% maximal heart rate of training increases alkaline phosphatase gene expression and parathyroid hormone in sedentary postmenopausal women.

Hypertension is one of the most important chronic illness worldwide and one the major risk factors for cardiovascular diseases. Obesity and abdominal obesity are risk factors for high blood pressure. Population attributable fraction (PAF) answers the question of how much of the disease burden in a certain population may be reduced if a risk factor like obesity is removed from the population. It implies that reducing prevalence of obesity as a risk factor of hypertension, may reduce the burden of hypertension and its consequences. The aim of this study was to determine the population attributable fraction of hypertension associated with obesity, abdominal obesity and joint effect of them in the men of Mazandaran Province, North of Iran.
In this epidemiological study, the data of non-communicable disease surveillance system in 2009 has been achieved. Then measure of association between obesity and hypertension (Odds Ratio) was extracted from Tehran Lipid and Glucose Study (TLGS). After standardizing the data, the population attributable risk for men based on the above formula (Levin's attributable fraction formula) has been calculated.
In our study based on population attributable fraction, results in blood pressure caused by obesity were 14.5 (CI 95%: 10.7-17.2), the effect of abdominal obesity was 7.4 (CI 95%: 2.04-11.3) and deductions attributable joint effect both obesity and abdominal obesity was 22.6 (CI 95%: 9.7-25.6) respectively.
Given the high prevalence of hypertension and obesity in Mazandaran men and the impact of obesity on blood pressure is necessary to prevent the spread of the disease. It is recommended that health promotion programs focus on men with high blood pressure due to obesity could be performed.

Cancer diagnosis is the biggest stress for the child and his family. Diagnosis and treatment of cancer in children can cause stress, which often has a negative effect on the health of parents. Psychological reactions such as anxiety, depression, denial and loss of confidence in parents observed that because of the fear of recurrence and future of children. This study aimed to determine the level of stress and anxiety and depression in parents of children with leukemia who were in the maintenance phase of treatment.
This cross-sectional study has been conducted on 48 parents have referred to the clinic of Dr. Sheikh Hospital of Mashhad City, Iran, whom selected using easy sampling method. DASS-21 questionnaire was used for data collection. Another questionnaire containing demographic information such as age, sex, income, educational level and duration of illness was filled under supervision of the psychologist and pediatric physician. Data with SPSS software, ver. 20 (IBM, Armonk, NY, USA), descriptive statistics and Pearson correlation analysis was performed.
The results showed that in this study, 37% had abnormal stress levels (33% and 2% of mild stress, moderate stress and severe stress 2%) and 79% had abnormal anxiety level (mild 19%, moderate 31% and severe 29%) and 67% had abnormal depression level (mild 33%, moderate depression 33%) tests, respectively. In our study, there was no relationship between age, sex and duration of illness with these variables.
According to this study, in addition to the classic treatment of patients, parent’s mental performance should be paid attention.

Autosomal recessive polycystic kidney disorder (ARPCKD) is one of the most prevalent hereditary disorders in neonates and children. Its frequency is between 1/6000 to 1/55000 births. In the most severe cases, it can be diagnosed prenatally by the presence of enlarged, echogenic kidneys and oligohydramnios. However, in the milder forms, clinical manifestations are usually detected in neonatal and childhood period. PKHD1 gene located on chromosome 6 is linked with this disorder. About half of detected mutations in this gene are missense ones. The largest protein product of this gene is called the FPC/polyductin complex (FPC). It is a single-membrane spanning protein whose absence leads to abnormal ciliogenesis in the kidneys.
Here we present a 5-year-old female patient affected with ARPCKD. She has been born to a non-consanguineous healthy Iranian parents. No similar disorder has been seen in the family. Prenatal history has been normal. In order to find the genetic background, DNA was extracted from patient's peripheral blood lymphocytes. PKHD1 gene exons and exon-intron boundaries were sequenced using next generation sequencing platform. Two novel variants have been detected in compound heterozygote state in the patient (c.6591C>A, c.8222C>A). Bioinformatics tools predicted these variants to be pathogenic.
In the present study, we detected two novel variants in PKHD1 gene in a patient with ARPCKD. The relatively mild phenotype of this patient is in accordance with the missense mutations found. Molecular genetic tools can help in accurate risk assessment as well as precise genotype-phenotype correlation establishment in families affected with such disorder to decrease the birth of affected individuals through preimplantation genetic diagnosis or better management of disorder.