Tehran University Medical Journal
Year:2017 | Volume:75 | Issue:3|Papers Count:15

Tumor necrosis factor-alpha (TNF-a) is a pro-inflammatory cytokine produced by a variety of cells, including hematopoietic and non-hematopoietic cells, malignant cells, macrophages, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, astrocytes, endothelial cells, and smooth muscle cells. TNF-a is a homo-trimeric molecular whose individual subunits are composed of antiparallel beta-sheets, forming a regular triangular prism shape. TNF-α binds to three receptor molecules through its receptor-binding sites, which are at the base of its pyramid structure. Biological responses to TNF-a are mediated through two different receptors: TNFR1 and TNFR2.These receptors are trans membrane glycoproteins with extracellular domains containing multiple cysteine-rich repeats that are structurally and functionally homologous, and the intracellular domains that are discrete and transduce their signals through both overlapping and distinct pathways. However, though TNF-a was initially discovered as an anti-tumor agent, it has been revealed that TNF-α and other ligands of this family are involved in some diseases like cancer, neurological, pulmonary, cardiovascular and autoimmune diseases and metabolic disorders. In general, TNF-aactivates the control systems involved in cell proliferation, differentiation, inflammation and cell death, and the regulation of immune system. Although a normal level of TNF-a is very important for the regulation of immune responses, the persistence of the immune response as a result of inappropriate and excessive production of TNF-α can cause some inflammatory or autoimmune diseases. Accordingly, either neutralization TNF-a or blockade of its receptors using TNF-a inhibitors can be an effective therapeutic strategy to prevent or treat such inflammatory diseases. Several methods have been used to inhibit TNF-a, including the production of chimeric or fully human antibodies, soluble TNF-a receptors, or anti-TNF-a small molecules. The two previous agents are mostly capable of inhibiting the binding of TNF-a to its associated receptors, while anti-TNF-a small molecules, in addition to the above, inhibit the biosynthesis of TNF-a by blocking TNF-a mRNA biosynthesis, through the inhibition of its post-translational processing, or by blocking TNF-a receptors. Therefore, in this review article, we discuss the structure and characteristics of TNF-a and its related receptors: TNF-a signaling, TNF-a-mediated inflammatory diseases as well as TNF-a inhibition strategies.

Background: HLA disease association was investigated in several autoimmune, cancer and infectious diseases. The outcome of tuberculosis (TB) infection may be influenced by host genetic factors like MMP-1, MCP-1, IL-10, IL-12, TNF-a, IFN-g and human leukocyte antigen (HLA). Given the paucity of information with regard to the association between the human leukocyte antigens (HLA) and TB infection among Iranians, we aimed to identify HLA polymorphisms that might confer susceptibility or protect against TB.Methods: In this case - control study, to investigate the association between the HLADRB1 and DQB1 alleles and TB, 50 patients with tuberculosis were selected from Sistani population in Golstan University of Medical Sciences, Golestan Province, North East of Iran, from September 2015 to February 2016. Allele frequencies in patients were compared with a 100 aged and sex match control group from healthy blood donor of that ethnic population. HLA-DRB1 and -DQB1 alleles were determined using polymerase chain reaction based on sequence specific primer (PCR-SSP) method by low to intermediate resolution kits supplied by CTS (Collaborative Transplant Study, Heidelber University, Germany). Using EPI-info statistical software Chi-square test and fisher exact test, 95% confidence interval and odd ratio were calculated and allele frequencies in patients and control subjects were compared. P-value less than 0.05 were considering statistically significant.Results: The results of this study showed a significant increase and positive association with -DRB1*04: 03 (OR=3.13, CI 95% (2.47-3.96), -DRB1*14: 04 (OR=3.13, CI 95% (2.47-3.96), -DQB1*0201 (OR=2.67, CI 95% (1.18-6.04), -DQB1*0601 (OR=3.16, CI 95% (1.36-7.73), while the frequency of -DRB1*07 (OR=0.16, CI 95% (0.05-0.52) were lower in patients than control group and shows negative association.Conclusion: The results of this study confirmed some of the previous positive and/or negative association, however it is suggested that HLA-DRB1*04: 03, -DRB1*14: 04, - DQB1*0201, -DQB1*0601- have an important role in susceptibility to tuberculosis infection and -DRB1*07 was associated with protection in Iranian Sistani population.Larger case-control sample size studies may be helpful to confirm our investigation. In addition population-specific studies is needed for evaluation of the role of HLA polymorphisms in tuberculosis in different ethnic groups.

Background: In recent years, use of powdered infant formula (PIF) milk for neonates feed is increasing; therefore, the quality control (QC) of PIF products is very important.The aim of present study was detection of toxigenic Bacillus cereus species in PIF milk using PCR assay.Methods: The cross-sectional study was carried out on 125 samples of powdered infant formula milk (PIF) purchased between March 2015 and April 2016 in Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Briefly, 0.1 dilutions were prepared and inoculated on Bacillus cereus selective media (MYP) and incubated at 30oC for 24 hours. The suspicious colonies were verified using biochemical tests based on standard methods. Final confirmation of studied isolates was carried out by ITS gene detection using polymerase chain reaction (PCR) assay. Presence of nonhemolytic enterotoxin (NHE) (linked to diarrhoea syndrome) and emetic toxin (EM) (linked to emetic syndrome) virulence genes were investigated using polymerase chain reaction assay.Results: In this study, of 125 PIF samples, 84 (67.2%) were contaminated. Of various recovered bacteria from these samples, 110 bacterial isolates were suspected to be Bacillus spp. using phenotypic methods. The ITS PCR results showed that 91.8% of the isolates were B. cereus. Respectively, 53.63 and 79% of B. cereus isolates possessed NHE and EM virulence genes.Conclusion: Our data revealed that near 80% of Bacillus cereus isolates have emetic toxin (EM) gene, as result virulence potency of this isolates is very high. However, the low number of this organisms in foods is very important and food safety protocols for these opportunistic toxigenic bacteria should be revised. Since the pasteurization process is ineffective on B. cereus spores; therefore, spores can remain in PIF milk and the vegetative bacterial cells can cause food poisoning in neonates. Therefore, modification of foods quality control protocols is essential in order to identify virulence genes in this bacterium.

Background: Lochia is the slight vaginal bleeding between 24 hour to 12 week after delivery. There isn' t any standard definition for difference between normal and abnormal lochia in post-partum period. The aim of this study was to determine the relationship between ultrasonic findings of the postpartum uterus after normal vaginal delivery with the duration of lochia discharge.Methods: In this cross-sectional study was done in Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran, from 2014 to 2015. In this study 160 women with non-complicated vaginal delivery were entered. Inclusion criteria were: Term pregnancy with gestational age>37, singleton fetus with cephalic presentation.Exclusion criteria were pre-term pregnancies, previous Cesarean section or other uterine surgeries and twin fetuses. Transvaginal ultrasound was done in first 48 hours after delivery, endometrial thickness echogenicity and uterine size was evaluated.Maternal age, parity, duration of labor and neonatal weight were evaluated. Then the mothers were followed for 6 weeks. The quality and the quantity of lochia discharge were asked by the phone.Results: Lochial discharge last more than 6 weeks in 96 out of 160 (60%). One had less than 4 weeks. The uterus length, thickness, height and endometrial length did not show any relationship with the duration of lochial discharge, but endometrial strip thickness significantly correlated with the duration of lochial discharge period (P=0.04). None of clinical variables like the number of gravidity, parity, live birth or child birth weight, were correlated to the duration of lochia discharge period, but the labor time was correlated to the duration of lochia discharge period (P=0.04). Although both endometrial thickness and labor time in univariate analysis were correlated to the lochia duration time but this was true just for endometrial thickness in multivariate analysis.Conclusion: The endometrial thickness in first 48 hours after normal vaginal delivery could predict the duration of lochia discharge, there wasn’t any correlation between lochia discharge period and other ultrasound parameters.

Background: Hypocalcemia is one of the most prevalent complications following total thyroidectomy. Over recent years, in addition to hormone parathyroid hormone (PTH), vitamin D has been also studied as a factor causing post-total thyroidectomy hypocalcemia.This survey seeks to study the relationship between the serum level of vitamin D before surgery and during post-total thyroidectomy hypocalcemia.Methods: A group of 57 patients volunteering for total thyroidectomy were studied on Vali-e-Asr Hospital, Tehran, Iran, from March 2013 to March 2015. In all these patients, pre-surgery calcium, vitamin D and parathyroid hormone (PTH) as well as the level of calcium during the post-surgery first two days were measured. Based on objectives of this study, the relationship be-tween pre-surgery vitamin D level and postsurgery hypocalcemia was examined.Results: The average age of patients participating in the survey was 24.1±13.3. They included 19 women (33.3%) and 38 men, total of 40 patients (70.2%). Their average post-surgery calcium level was 9.2±0.77 milligrams per deciliters (mg/dl) and their average vitamin D content before the surgery was 42±12.1 nanomole per liter (nmol/l).The average calcium level before the surgery and the first post-surgery day were meaningfully different in terms of statistics (P<0.001). In terms of vitamin D, 37 patients (64.9%) had pre-surgery vitamin D deficiency and 20 patients (35.1%) had vitamin D insufficiency. Of 37 patients with pre-surgery vitamin D deficiency, 26 were diagnosed with post-surgery first-day hypocalcemia and of 20 patients with vitamin D insufficiency, 14 suffered post-surgery first-day hypocalcemia. This difference was not statistically meaningful (P>0.001). Of 37 patients with pre-surgery vitamin D deficiency, 31 suffered post-surgery second-day hypocalcemia and of 20 patients with vitamin D insufficiency, 18 suffered second-day hypocalcemia. This difference was not statistically meaningful either (P>0.001).Conclusion: The current study showed that the serum level of vitamin D before total thyroidectomy does not have any role in the occurrence of post-surgery hypocalcemia which is almost common after this type of surgery.

Background: Blood transfusion is common in infants. Due to the weakened immune system of newborns and the risk of blood transfusion complications, it is necessary to pay more attention following or after to blood transfusion. The aim of this study was to evaluate the frequency and risk factors of blood transfusions in hospitalized neonates.Methods: A cross-sectional study was performed on 1106 infants admitted in the neonatal intensive care unit (NICU) of Mustafa Khomeini University Hospital, Tehran, Iran, from spring 2009 to 2012. Frequency and the reason for of blood components transfusion including fresh frozen plasma, platelets, whole blood, packed red blood cells, cryoprecipitate and relationship with gestational age, sex, birth weight, Apgar score, duration of hospitalization, use of mechanical ventilation were assessed.Statistical analysis was performed with SPSS statistical software, version 16 (IBM, Armonk, NY, USA) and statistical test, chi-square test, independent t-test and analysis of variance (ANOVA).Results: Among 1106 infants admitted to the neonatal intensive care unit, 221 infants (%19.98) received blood products.82 of all (37%) were female and 139 (%63) were female.113 (51%) of neonate were preterm and 108 (48%) were term. From 361 times of blood transfusions, 121 infant (54.75%) received at least one blood product. The frequency of blood transfusion was between 39 and 1 times, with an average of 3.65 times per infant. Frequency of fresh frozen plasma infusion was 173 (47.9%), packed cell 122 (33%), platelet 32 (8.8%), cryoprecipitate 20 (5.1%) and whole blood 3 unit (0.83%). The most common causes for fresh frozen plasma transfusion was replacement therapy 140 (80%), for packed cell, to correct symptomatic anemia 68 (55.6%), for platelet transfusions was to prevent bleeding in neonates with thrombocytopenia 20 (62.5%) and cryoprecipitate for bleeding caused by DIC in 18 infant (90%). There was significant relation between frequency of blood transfusions with gestational age (P=0.002), birth weight (P=0.01), cause of hospitalization (P=0.001) using of ventilator (P=0.002), and length of hospital stay (P=0.001).Conclusion: With attention to the guidelines of blood transfusions and controlling factors affecting premature birth and low weight infants, reducing length of hospital stay and duration of mechanical ventilation, frequency and complications of blood transfusion can be effectively decreased.

Background: Cardiovascular disease (CVD) is the most common cause of death in the world that is mostly due to vascular disease. Myocardial infarction (MI) is the most lethal form of coronary heart disease Which is increasing in developing countries. This study was done to calculate and compare lost years of life due to death and disability for the most important cause of death (myocardial infarction) in the studied population.Methods: This cross-sectional study was carried out in Urmia university of Medical Sciences in Western Azerbaijan Province, Iran during 2012 to 2013. Confirmation of the occurrence of myocardial Infarction in hospitalized patients was based on clinical symptoms, changes in electrocardiogram and increases of cardiac enzymes (CK-M Band Troponin). The burden of health from Myocardial Infarction was calculated using the disability adjusted life years index (DALY). The morbidity data of MI was collected from myocardial infarction Registration System Department of Health, and mortality data were extracted based on death registration ICD10 (I20-25).Results: The total occurrence of MI was 7235 patients (60.6% men and 39.4% women) with the mean ages of 69±15 years. Number of disability adjusted life years (DALY) caused by MI was 53804 years (17.7 per thousand people) and the portion of early death Years of Life Lost (YLL) due to premature death was 52170 years (17.1 per thousand people), and Years of Life Lost (YLD) due to disability resulting from the disease was 1634 years (0.54 per thousand people). The disease burden in men was more than in women, and the greatest burden was in the age group of 80 and above in both sexes. Prevalence rate of the MI was estimated 376 (Per hundred thousand people) and the MI accounted for 18.8% of all causes of death.Conclusion: The high burden of myocardial infarction, especially in men, raises the incidence of Myocardial Infarction a health priority and the need for proper planning in order to take effective measures for the prevention and treatment.

Background: Cancer is a major life-threatening disease that can evoke deep-rooted fear of death and sense of loss of hope. Even the word, cancer, has powerful connotations of anxiety, pain and suffering. Cancer has a great impact on patients’ lives, so the extent to which physicians should inform them of the diagnosis poses a difficult decision in clinical settings. Therefore, truth telling is one of the most important issues in patients physicians’ relationship. Besides the ethical aspect, telling or not telling the truth has some legal aspects, therefore, it is important to know the effective factors and understand how to deal with this issue especially for incurable diseases such as cancer.Therefore, the aim of this research was to analyses the effective factors in physician’s truth telling to cancer-patients.Methods: The samples of this descriptive and analytical study, (survey study) consist of 161 cancer-specialists from Tehran University of Medical Sciences who have been selected by simple random sampling method in 2015 and 2016. The data was obtained by survey approach and the data collected using a questionnaire. In order to evaluate the validity and reliability of the research, expert’s opinion and Cronbach alpha coefficient have been used. The questionnaire included scales designed to measure attitude, intention, subjective norms; perceived behavior control. Statistical package for social science software (SPSS) were used to analyses the data. T-test and ANOVA were used to compare groups.Results: Fifty-nine hudred percent male and 41% female physicians took part in this study. The average age of the participants was 43.4±11.27 years. The best person for truth-telling was physician and psychologist. Results showed that there was no significant difference between attitudes of male and female specialist but there was significant difference between oncologist and non-oncologist tendency to tell the truth.Results also showed that there was difference between physician’s behaviors (average 8.87). There was difference between behavior of private and public-private sectors physicians (62.8).Conclusion: Although the results show that there are differences in specialists’ attitude toward truth telling, it is not a good reason for not telling the truth. Although the physicians should consider several factors when telling the truth.

Background: Patient satisfaction is an important indicator of healthcare quality and effectiveness. Quality management as an organizational strategy enhances the quality of hospital services through continuously improving hospital structures and processes.This study aimed to examine the impact of quality management on patient satisfaction.Methods: A participatory action research was conducted in respiratory intensive care unit, at Labafinejad hospital, Tehran, Iran, in 2013. A quality improvement team was established. Operational processes were improved using a quality management model.The quality improvement team standardized processes, identified quality goals for the processes and improved them until achieved quality goals. Patients’ satisfaction data was collected before and after the intervention using a valid and reliable questionnaire.Results: Patients’ satisfaction was 75 percent at the beginning of the study. Patients were mostly dissatisfied with the nutrition services, amenities, lack of attention to their personal needs and lack of involving them in their treatment processes. An action plan was developed for improving patient satisfaction. After the quality management intervention, patient satisfaction reached to 81 percent at the end of this study. The quality management model improved the quality of services by 54.5 percent and consequently increased patient satisfaction by 7.2 percent. Almost half of the patients at the beginning of this study were definitely willing to recommend the hospital to their friends and relatives. This figure increased to 76 percent. The rest of patients stated that they may recommend the hospital to others.Conclusion: Implementing an appropriate quality management model appropriately in a supportive environment helps improve the quality of services and enhance patient satisfaction and loyalty.

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.