مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و ششم شماره 11 (پیاپی 215، بهمن 1397)

Considering the advancement of medical sciences, diagnostic tests have been developed to distinguish patients from healthy population. Therefore, Determining and evaluation of the diagnostic accuracy tests is of great importance. The accuracy of a test under evaluation is determined through the amount of agreement between its results with the results of the gold standard, and this test accuracy can be defined based on sensitivity, specificity, positive predictive value, negative predictive value and the area under the receiver operative characteristic curve (AUC). Gold standard is an accurate and error- free method to determine the presence or absence of disease of interest and classify patients, which is not available in some diseases and situations as this method is costly or invasive. In these cases, reference standard is a best available replacement method to be used by physicians to diagnostic disease. However, in some situation, the acceptable reference standard is invasive or costly and does not exist or unreliable. It can be imperfect and results of the reference standard method are not necessarily error- free and cannot be applied to everyone in the study; all these cases point to the conditions in which the gold standard is not available. The use of reference standard including error causes to incorrect separation of patients from healthy population and thus, it cannot be a comparing measure for other diagnostic tests and its results are inaccurate. Therefore, other alternatives methods are needed for evaluation and determine the diagnostic accuracy tests when the gold standard does not exist. Imputation method, correct imperfect reference standard method, the construct reference standard method, latent class models, differential verification, composite reference standard and discrepant analysis are of these alternative methods. Each of these methods, considering its features, advantages, and limitations can be used to evaluate the accuracy of diagnostic test in the absence of gold standard. The present study gave an overview of methods to evaluation of diagnostic accuracy tests when there is no gold standard and the focus of this study was on explain the concept of these solutions, review and compare them and their strengths and weaknesses.

Chronic lymphocytic leukemia (CLL) is a malignancy of B CD5+cells and is the most common type of leukemia in adults. The disease is more common in men over 50 years in western countries. CLL is associated with defective apoptosis in B cells. CLL was traditionally regarded as a disease that occurs before naïve B cells meet the antigen in the lymph nodes. Laboratory diagnosis requires white blood cell count, blood smear and immunophenotyping of lymphoid cells by flow cytometry. The disease most often associated with the accumulation of CD5+ CD19+ and CD23+ B cell with reduced number of surface membrane immunoglobulin in peripheral blood, bone marrow, and lymph nodes. Clinical progression of CLL is heterogeneous, some patients need treatment immediately after diagnosis, and others do not require treatment for many years after diagnosis. Over the past decades, considerable effort has been made to understanding the molecular mechanisms underlying the heterogeneous clinical course of the disease and finding prognostic markers for clinical classification. Patients with advanced Binet or Rai stages of disease require treatment. In addition to the interactions that exist between CLL cells, number of non-tumor cell types such as bone marrow stromal cells (BMSCs), nurse like cells (NLCs), follicular dendritic cells (FDCs), T cells, and some cytokines like IL-4 in tumor microenvironment play an important role in the CLL pathogenesis. Various factors including: IGVH mutation status, genetic variation, patient age and presence of other disorders are important for disease management and the type of treatment. CLL patients carrying p53 pathway dysfunction have poor prognosis and poor responses to therapy and very short survival. Available treatments include chemotherapy, chemoimmunotherapy, or drugs targeting B cell receptor signaling, Bruton's tyrosine kinase (BTK) or inhibitors of apoptosis, such as BCL2 and new class of small molecules. Understanding the CLL biology is important in identifying high-risk patients as well as the drug and relevant therapeutic methods for better management of patients. In this review paper, the microenvironment and genetic abnormalities in the CLL as well as new diagnostic and therapeutic approaches based on the new understanding of molecular biology of CLL are discussed.

Probiotics are living organisms that are beneficial for human health. Lactobacillus species has been considered as probiotic bacteria due to their adjustment of human immune responses and therapeutic effects in inflammatory disorders. The aim of the present study was to evaluate the effects of Lactobacillus probiotic strains on toll-like receptors (TLR2 and TLR4) expression in HT29 cell line (a human colon cancer cell line) infected with S. enteritidis. This experimental study was done in Food Microbiology Research Center of Tehran University of Medical Sciences, Iran, from March 2016 to February 2017. In this study, two strains of Lactobacillus acidophilus PTCC 1643 and Lactobacillus casei PTCC 1608 were used. HT29 cells were cultured in RPMI medium containing fetal bovine serum and antibiotics. Then, the cells were treated with the Lactobacillus strains, after or before challenge with S. enteritidis. After total RNA extraction and cDNA synthesis, the capacity of probiotic lactobacilli to modulate TLR2 and TLR4 expression on treated and un-treated HT29 cells were assessed quantitatively using Real-time polymerase chain reaction technique with specific primers. Our findings indicated that after treatment of non-infected HT29 cells, with both the probiotics, the expression of TLR2 and TLR4 genes significantly increased. In contrast, the expression of these two genes in HT29 cells which were infected with S. Enteritidis was significantly reduced before and after treatment with each one of the probiotic bacteria. The anti-inflammatory effect of probiotic lactobacilli on S. enteritidis were confirmed in tests. This study showed that L. acidophilus and L. casei play a major role in boosting the innate immune responses, the TLR2 and TLR4 expression levels also decreased, pre and post-infection with S. enteritidis. According to the results, both Lactobacillus strains have remarkable anti-inflammatory effect in pathogenicity of S. enteritidis, but L. acidophilus display greater anti-inflammatory activity than L. casei in this work. Additional in vivo and in vitro studies are required to further elucidate the mechanisms underlying this anti-inflammatory effect.

Papilloma viruses are pathogenic double-strand DNA viruses that genotypes 16 and 18 are the cause of more than 50 percent of cancers as cervical cancer. Although vaccination is one of the best options for the papilloma cancer prevention but that is the most of world healthy problem, it is attempted to evaluate both naloxone (NLX) and alum mixture used as adjuvants together with HPV16 E7d vaccine to change the tumor microenvironment for the benefit of the immune system. The aim of this study was to investigate the effect of naloxone and alum mixture as adjuvants in HPV16 E7d vaccine on C57BL/6 female mouse in tumor microenvironment. This study is a descriptive and cross-sectional study type, which was conducted on 80 case of C57BL/6 female mouse in Pasteur institute of Iran, Tehran over a period of six months in 2016. In this study, mice were vaccinated with dose of vaccine containing naloxone and alum mixture and alum as adjuvants and proper phosphate buffered saline (PBS) as control groups are considered. Tumor bearing mouse vaccinated by vaccine containing naloxone and alum mixture as adjuvants and phosphate buffered saline (PBS) as control group. Tumor model created through surgery and then tumor measurement done, the homogenate was created and protein concentration measured by Bradford system. Finally, assessment of IL-17, IL-4, IFN-γ and TGF-β cytokines concentration were performed by capture ELISA kit (mybiosource company) according to the company manual. It was observed that utilization of naloxone and alum mixture as adjuvant in the HPV16-E7d vaccine formulation significant reduction in the tumor growth (P≤0.0001) and reinforced meaningfully the cellular immunity reaction in tumor microenvironment. The results of our study show that vaccine formulated with the naloxone and alum mixture as adjuvant in the HPV16-E7d vaccine increase the cellular immunity reaction on C57BL/6 female mouse in tumor microenvironment compared to phosphate buffered saline (PBS) control group in this new formulation as a papilloma viruses vaccine on C57BL/6 female mouse.

Campylobacter genus is considered some of the most important agents of bacterial gastroenteritis worldwide. Campylobacter coli (C. coli) is accounted to at least 25% of all Campylobacter related diarrheal diseases moreover, C. coli infections can result in severe complications, such as bacteremia, sepsis, meningitis and spontaneous abortion. Finally, there is evidence that the frequency of antimicrobial resistance is higher in C. coli, when compared to C. jejuni. There is no data regarding the frequency and antibiotic resistance profile of C. jejuni isolated from human gastroenteritis samples. The present study aimed to determine the frequency and antibiotic resistance patterns of Campylobacter coli isolated from infectious diarrhea samples. In a descriptive cross-sectional study, 200 infectious diarrhea samples collected in Arak University of Medical Sciences Hospitals, Markazi Province, Iran, from May to November 2015 were subjected to the study. In order to identify C. coli modified Gram stain, modified charcoal-cefoperazone-deoxycholate agar (mCCDA) and Brucella agar media with filter and CeuE gene polymerase chain reaction (PCR) were accomplished. Antibiotic resistance against tetracycline, erythromycin, ciprofloxacin, ampicillin and gentamicin was evaluated phenotypically and genotypically. In total, out of 200 modified gram stained samples, 2 cases (1%) of C. coli were identified. Cultivating methods using mCCDA medium found 2 isolates (1%), 3 isolates (1.5%) were grown on Brucella agar with filter and 5 cases (2.5%) were determined as C. coli using PCR assay. Antibiotic resistance was observed in 5 cases against tetracycline, erythromycin and ciprofloxacin (100%), in 4 cases against ampicillin (80%), in 2 cases against gentamicin (40%), in 5 cases with CmeB, 23srRNA mutation in, qnrS, tet (o) (100%), in 4 cases with gyrA4 (80%), in 3 cases with gyrA5 (60%), in 5 cases with gyrA6 (100%), in 4 cases with Oxa61 (60%) and in 1 case with aphA-3-1 (20%). In this present study C. coli with low prevalence and entire resistance to ciprofloxacin and erythromycin which are the first line antibiotic for the treatment of campylobacter gastroenteritis is introduced as a causative agent of gastroenteritis in patients at central part of Iran.

Coronary artery bypass surgery is one of the surgeries in which high blood transfusions are needed. About 20% of all surgical operations require a blood transfusion. Packed cell administration increases perioperative morbidity and mortality. In the United States, from every 1000 people, one has undergone a coronary artery bypass graft surgery, and it is estimated that around 800,000 coronary artery bypass grafts undergo each year. Knowledge about relative blood administration during coronary artery bypass graft surgery improves the ability of blood transfusion centers in healthy and adequate blood donations. For this purpose, this study was conducted to determine the effective factors in the need for blood in a coronary artery bypass graft surgery. This cross-sectional study was performed on 317 patients undergoing coronary artery bypass graft surgery in the heart surgery operating room of Imam Khomeini Hospital in Tehran, Iran, from September 2017 to February 2018. Sampling method has been available. The data of this study were extracted from patient files. The products analyzed in the study included packed cell, fresh frozen plasma and platelets. Demographic data, type of surgery, transfusion of blood and products, and hemoglobin level have been reported. P-value less than 0.05 was reported as meaningful. In this study, 317 patients underwent coronary artery bypass graft surgery. 236 cases (74.4%) were male and the rest were women. The mean of administration of packed cell in women was 2.74±1.3 and in men it was 2.29±1.09 (P<0.001). The mean packed cell administration in patients with hemoglobin levels less than 10 g/dl was 3.27±1.8 and in patients with hemoglobin levels greater than 10 g/dl was 0.99±2.25 (P<0.0001). The present study showed that the mean transfusion of packed cells in women were more than men in coronary artery bypass graft surgery. Also, hemoglobin levels were the only factor that had a significant effect on infusion of packed cells.

Chronic inflammation and oxidative stress are the two essential factors determining ulcerative colitis (UC) onset and severity status. In present study, we aimed to investigate short-term effects of ginger (Zingiber officinale) as a well-known antioxidant and anti-inflammatory agent on the quality of life, disease activity index and some of inflammatory and oxidative stress factors in patients with active mild to moderate UC. This study was a double blind placebo controlled randomized clinical trial conducted in nutrition and diet therapy clinic of Shahid Beheshti University of Medical Science, Tehran, Iran, from October 2017 to June 2018. Forty-six patients with active mild to moderate UC daily consumed four capsules of 500 mg dried ginger powder or similar placebo through eating their meals for 6 weeks. Before and after intervention, we analyzed patient´s scores of disease activity index, by simple clinical colitis activity index questionnaire (SCCAIQ) as well as their quality of life using inflammatory bowel disease questionnaire-9 (IBDQ-9). We also measured serum concentrations of total antioxidant capacity (TAC), malondialdehyde (MDA), tumor necrosis factor (TNF-α), high sensitive (hs)-CRP and nuclear factor κB (NF-κB) in fasted blood samples of each participant. Additionally, anthropometric and dietary intake values of energy, macro/micronutrients and minerals of all of participants were assessed at the same time. While the mean of anthropometric measures and dietary intake values remained unchanged during the study, MDA level decreased in ginger group (P=0.04) compared with placebo group. Additionally, ginger supplementation successfully lowered serum levels of TNF-α and disease activity index after 6 weeks of intervention compared with baseline in ginger consumer group, however the increase of quality of life score was not statistically significant in mentioned group versus baseline values. No significant change in other study outcomes was observed at the end of 6 weeks within and between groups. Our data indicates that two grams per day supplementation with dried ginger powder can reduce oxidative stress level of patients with active mild to moderate UC.

Although the treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is very difficult, it can be prevented. The aim of this study was to investigate the knowledge and practice of oral and maxillofacial surgeons in the treatment of bisphosphonates user patients. This was a cross-sectional study carried out by census sampling of oral and maxillofacial surgeons in Tehran, Iran from March to June 2016. The employed instrument was a questionnaire including 4 sections. The first section was to collect the demographic information of the participants. In the second part including 7 questions, the knowledge of the participants was measured. The third section with 6 questions was to assess the participants’ practice in the treatment of patients using bisphosphates. Finally, the last sections contained 4 questions. The content validity of the questionnaire was evaluated by 5 specialists in the field (two oral and maxillofacial surgeons, two periodontists, and one endodontist). To assess the reliability of the questionnaire, it was given twice with a 10-day interval to 10 of target group members. The calculation of Spearman-Brown formula revealed a correlation coefficient of 0.79. In the treatment of BRONJ, most subjects responded to risk, 1 and 2 stages patient education and symptom relief. Treatment with antibiotics and debridement surgery was chosen for patients with higher stages. From 123 oral and maxillofacial surgeons, 102 answered the questionnaires. 77.2% of the surgeons answered correctly to questions about implant insertion. This percentage was higher than other therapeutic procedures. The knowledge of oral and maxillofacial surgeons as final line of referral and treatment of patients using bisphosphonates should be increased.

Hydatid cyst is an endemic disease in Iran and many middle eastern countries. The clinical presentation of Echinococcus granulosus infection depends upon the site of the cysts and their size. Small and/or calcified cysts may remain asymptomatic indefinitely. However, symptoms due to mass effect within organs, obstruction of blood or lymphatic flow, or complications such as rupture or secondary bacterial infections can result. The most common involved organs with this parasite are the liver and lung. Unusual areas of the disease include breast, adrenal, appendix, peritoneum, omentum and mesenteric. The purpose of this study was to report a rare case of abdominal hydatid cyst with presentation of ovarian cyst in ultrasonography. A 26-year-old virgin woman with abdominal pain in the hypogastric region and lower and right quadrant of the abdomen, with gastric fullness and without nausea and vomiting referred to an emergent unit of Ghaem Hospital (an academic hospital of Mashhad University of Medical Sciences) in June 2017. In an ultrasound, a cyst of 95×105 mm in right adnexa of uterus was seen. Due to continued abdominal pain, laparotomy was performed for the patient. At the time of laparotomy, the ovaries, uterus and adnexa were completely normal. A 10×15 cm cyst was seen with a thin wall which adhering to the omentum and the small end of the stomach. Frozen section biopsy reported hydatid cyst. Considering that hydatid cyst is endemic in Iran, the presence of cystic mass in the peritoneal cavity, hydatid cyst should be considered. To prevent complications and relapse, it is best to avoid cyst rupture during surgery as much as possible.