Tehran University Medical Journal

Implication of thymoglobulin in kidney transplant patients: review article

Gholamreza Pourmand

Thymoglobulin is a purified polyclonal immunoglobulin that has been used widely over the last decades in the prevention and treatment of rejection following renal transplantation. This immunoglobulin works against human thymocytes. Since thymoglobulin does not contain the nephrotoxic properties therefore it can be used in induction therapy especially in patients with higher risk of graft rejection such as patients who receive graft from cadavers. Recent research showed also its beneficial role in cross-match-positive transplantation, a role that is mediated through conjunction with inhibitors of terminal complement activation. This immunoglobulin has also been used for treatment of rejection following renal transplantation. Thymoglobulin can have various effects on various Immune system cells including T cells, B cells and also plasma cells. Thymoglobulin also affects the Tcell surface antigens, natural killer-cell antigens, B cell antigens, plasma cell antigens, adhesion molecules and chemokine receptors. Diverse effects of thymoglobulin on the immune system includes: T cell depletion, induce apoptosis in B cell lineage and interference with dendritic cell functional properties. Thymoglobulin can cause acute complications, delayed complications as well as infectious complications. Acute reaction events includes: anaphylaxis, fever, chills, dyspnea, nausea, vomiting and diarrhea. Thymoglobulin also induces cytokine release syndrome manifested by high grade fevers and chills and treated by steroid therapy. Delayed reactions events usually present as serum sickness and infections. Infectious complications are more important and include cytomegalovirus (CMV) infection, sepsis, candidiasis, herpes simplex and urinary infections. Thymoglobulin can also induce cytokine release syndrome. It has been thought that thymoglobulin increases the risk of post-transplant lymphoproliferative disorder (PTLD), however, debate still exists whether such an association is present when lower dosing regimens are used. In this review, we aimed to present first a brief history of thymoglobulin development and its mechanism of action and then assess the most recent published data regarding the role of thymoglobulin in following issues: immunological tolerance, ischemia-reperfusion injury, delayed graft function, prevention and treatment of acute allograft rejection, live donor transplantation, graft and patient survival and posttrans-plant lymphoproliferative disorder. This review can help specialist in transplant domain to appropriately used thymoglobulin in transplant patients.

Identification of toxic shock syndrom and exfoliative toxin genes of Staphylococcus aureus in carrier persons, resistant and susceptible methicillin

Mohammad Yousef Alikhani

Background: Staphylococcus aureus is one the most common pathogens causing community-acquired infections and a major concern for public health, and the other hands antibiotic resistance is also of great concern for public health authorities also Staphylococcus aureus produce a lot of virulence factors such as variety of exoproteins included toxic shock syndrome and exfoliative toxin which causes colonization and different infections in their host. The aims of current study were to evaluate the prevalence of Toxic shock syndrome toxin 1 (TSST-1) and ETs genes in isolated S. aureus strains using polymerase chain reaction (PCR) assay. Methods: This cross-sectional study was performed on 100 methicillin-resistant staphylococcal aureus (MRSA) and 100 methicillin-sensitive staphylococcal aureus (MSSA) isolated from clinical specimens of inpatients, outpatients hospitals and nasal carriers in Hamadan University from October 2013 to August 2014. Identified species by biochemical methods were confirmed by the PCR method. Antibiotic resistance was performance by disk diffusion and the presence of TSST-1 and ETs genes was investigated using PCR. Results: Of the 100 isolates MRSA examined, the most frequent resistance was observed to ciprofloxacin (95%), followed by tetracycline (91%), erythromycin (92%), Gentamicin (90%), Rifampin (85%), trimethoprim-sulfamethoxazole (85%), clindamycin (80%) and cefoxitin (100%). Of the 100 isolates MSSA examined, the most frequent resistance was observed to erythromycin (68%), ciprofloxacin (66%), followed by tetracycline (52%), gentamicin (25%), clindamycin (46%), rifampin (45%), trimethoprim-sulfamethoxazole (66%) and cefoxitin (0%). Prevalence of TSST-1 and ETs genes were determined 13% (n=26) isolates, totally. Also the prevalence of TSST-1 was 11% (n=22) and ETs genes was 2% (n=4) isolates and none of the investigated isolates carried eta gene. Conclusion: The increasingly prevalence of MRSA and emerging its antibiotic resistance in clinical isolates can be considered a serious problem for public health. Detection of the high rate prevalence of TSST genes in current study is considered as a serious problem and existing and circle of these strains in according to colonization in community especially old people and immunocompromised patients is very serious.

Protective effect of testosterone on cognitive deficits induced by ethidium bromide in experimental model of multiple sclerosis

Shiva Khezri

Background: Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). The hippocampus is a vital center for learning and memory it is extremely vulnerable to neurodegenerative diseases. The male hormones could be neuroprotective for the CNS. The current study is an attempt to investigate the effect of testosterone on learning and spatial memory following the demyelination of CA1 area by the injection of ethidium bromide in the rats' hippocampus. Methods: This experimental study has been conducted on healthy rats in the faculty of science of the Urmia University from September 2013 to February 2015. For demyelination in all previously gonadectomized healthy rats, 3µl ethidium bromide was injected into the CA1 area of rats by stereotaxic surgery. In addition, the treatment groups received 1µl testosterone (6µg/µl) during a 20-day timeframe on a daily basis after demyelination by the ethidium bromide. The control groups had no drug injection. The process of the learning and spatial memory of the rats were closely monitored by the radial Maze. The demyelination and remyelination in the hippocampus were checked by the myelin-specific coloring (Luxol fast blue and Cresyl violet). Results: The histological results suggest that the testosterone is capable of minimizing the destructive impacts of ethidium bromide in the treatment group as well as enhancing the remyelination process. In the group treated by testosterone, the percentage of the pyknotic cells 20 days after demyelination induction, represented a significant reduction compared to that of ethidium bromide group (P=0.008). The behavioral studies analyses show that the amount of the food finding time in those groups received ethidium bromide was significantly longer than those of the control groups (P=0.001). Furthermore, the application of the testosterone in the treatment groups reduced the extent of demyelination while the memory impairment induced by the ethidium bromide was significantly improved (P=0.001). Conclusion: Testosterone can act as a neuroprotective factor that reduces the extent of demyelination and the number of pyknotic cells. It also may improve the learning and memory impairment induced by ethidium bromide.

The correlation of serum S100β protein levels and hippocampal Seladin-1 gene expression in a rat model of sporadic Alzheimer's disease

Soheila Hosseinzadeh

Background: Seladin-1 protein protects the neural cells against amyloid beta toxicity and its expression decreased in vulnerable regions of Alzheimer's disease (AD) brains. On the other hand, changes in serum levels of S100 have been considered as a marker of brain damage in neurodegenerative diseases. Furthermore, this study was carried out to determine the relation between the change profile of serum S100&beta protein levels and hippocampal Seladin-1 gene expression in a rat model of sporadic AD. Methods: In this experimental study that established in Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Science, from March 2011 to April 2013, 72 animals were randomly divided into control, 4, 7, 14, and 21days ICV-STZ/Saline administrated rats. Alzheimer's model was induced by intracerebroventricular (ICV) injections of streptozotocin (STZ) [3 mg/kg] on days 1 and 3. Serum levels of S100&beta and hippocampal Seladin-1 gene expression were evalu-ated in experimental groups. The initial and step-through latencies (STL) were deter-mined using passive avoidance test. Results: Serum levels of S100&beta were significantly different between the STZ-7 day and STZ-14 day groups in comparison with the control, saline and STZ-4 day groups. As well as, there was a significant difference between the STZ-7 day group in comparison with the STZ-14 day and STZ-21 day groups (P=0.0001). Hippocampal Seladin-1 gene expression in STZ-14 day and STZ-21 day groups significantly decreased as compared to the control, saline and STZ-4 day groups (P=0.0001). However, significant correla-tion was detected between serum S100&beta protein decrement and Seladin-1 down regula-tion (P=0.001). Also, the STL was significantly decreased in 21 days ICV-STZ adminis-trated rats as compared to the control or saline groups (P=0.001). Conclusion: Monitoring the changes of serum S100&beta protein levels by relationship with changes in hippocampal Seladin-1 gene expression can be a useful indicator of neu-ronal damage in patients with Alzheimer's disease.

Utility of tumor marker HE4 and CA125 to predict staging in endometrioid adenocarcinoma of the uterus

Mitra Modaresgilani Modaresgilani

Background: Endometrial carcinoma is considered the most common gynecological cancer in the world. Pelvic and para-aortic lymphadenectomy is widely advised based on FIGO staging system. The purpose of this study was to determine whether the biomarker human epididymis protein 4(HE4) correlates with depth of myometrial invasion, histologic grade and metastases in patients with endometrioid adenocarcinoma of the uterus. Methods: This was a cross-sectional study in women with biopsy-proven endometrioid adenocarcinoma in the gynecological ward of Vali-e-Asr Hospital from October 2012 to October 2014. The concentrations of HE4 and CA125 were assessed before surgery and all surgical specimens were reviewed by dedicated gynecologic pathologists. The results were compared with the final histopathology report. Results: A total of 80 patients were initially entered in this study. Twelve patients were excluded because they didn’t have tumor marker. Most of patients (76%) was in stage I disease. Levels of serum HE4 greater than 140 PM and CA125 greater than 35 kU/L observed in 12(17%) and 26(38.2%) of patients, respectively. Of the 52 patients with satge I, 14(26.9%) had CA125&ge35 KU/L, compared with 6(66.7%) of the 9 patients with stage II and 6(85.7%) of the 7 patients with stage III (P<0.002). A significant increase in serum CA125 level was noted in patients with grade III tumors, deep myometrial invasion, cervical stromal involvement and nodal metastasis (P<0.001, P<0.0001, P<0.006, P<0.002). Among the group of patients with early stage disease a significant increase in serum CA125 was noted in patients with deep myometrial invasion. Five out of 52 patients (9.6%) in stage I had HE4 level&ge140 PM, compared with 3 patients (33.3%) with stage II and 4 patients (57.1%) with stage III disease (P<0.003). A significant increase in serum HE4 level was noted in patients with grade III tumors, deep myometrial invasion, cervical stromal involvement and nodal metastasis (P<0.035, P<0.001, P<0.012, P<0.007). Conclusion: Human epididymis protein 4 (HE4) and CA125 may be a useful markers preoperatively in the clinical decision making for determining the need for lymph node dissection in women with endometrial cancer.

Androgen receptor expression on breast cancer cells: a clinicopathologic and survival study

Hosein Kamranzadeh

Background: Breast cancer is the most common cancer in women around the world. It has been known for over a century that androgens and androgen receptor (AR) play a role in normal and neoplastic breast cells. The aim of this study was to determined the AR expression on tumor cells and its correlation with other prognostic and predictive factors as well as contribution of AR in patients overall survival (OS) and disease- free survival (DFS). Methods: This retrospective cross-sectional study performed on 189 patients who referred to Medical Oncology Ward of Cancer Institute, Tehran University of Medical Sciences, from April 2007 to February 2010. We performed an immunohistochemistry study for AR (AR441 clone, Dako, Germany) (10% cut-off point) and Ki-67 MIB-1 clone, Dako, Germany) on paraffin embedded blocks. Other data were extracted from patients’ documents. Results: Overall, AR expression was 49.1%. Mean age of the patients with and without AR was 47.86 and 48.49 years, respectively. AR positive tumors presented more in stage I/II than III/IV (P=0.02) and AR were more positive for estrogen receptor positive, lower grade of tumor (grade I/II versus III) and lower Ki-67 (P=0.01). AR positivity had neither correlation with progesterone receptor, HER2/neu, P53 expression or menopausal status. OS and DFS were higher in AR positive patients but did not reach statistical significance. In triple-negative breast cancer (TNBC) group, 25% of tumors showed AR expression. AR had non-significant positive correlation with OS in TNBC cancer patients. OS and DFS had significant statistic positive correlation with ER, PR and stage regardless of AR status. Conclusion: Based on this study, although androgen receptor expression showed correlation with other prognostic factors for survival in patients, we didn’t find statistically significant independent relationship between AR and overall survival in patients. As far as there isn’t any targeted therapy for triple-negative breast cancer (TNBC), prospective basic and clinical studies regarding AR inhibitors in the treatment of TNBC seems to be logical and valuable.

Assessment of time interval between tramadol intake and seizure and second drug-induced attack

Tayeb Ramim

Background: Tramadol is a synthetic drug which is prescribed in moderate and severe pain. Tramadol overdose can induce severe complications such as consciousness impairment and convulsions. This study was done to determine the convulsions incidence after tramadol use until one week after hospital discharge. Methods: This prospective study was done in tramadol overdose patients without uncontrolled epilepsy and head injury history. All cases admitted in Loghman and Rasol Akram Hospitals, Tehran, Iran from 1, April 2011 to 1, April 2012 were included and observed for at least 12 hours. Time interval between tramadol intake and first seizure were record. Then, patients with second drug-induced seizure were recognized and log time between the first and second seizure was analyzed. The patients were transferred to the intensive care unit (ICU) if clinical worsening status observed. One week after hospital discharge, telephone follow-up was conducted. Results: A total of 150 patients with a history of tramadol induced seizures (141 men, 9 women, age: 23.23±5.94 years) were enrolled in this study. Convulsion was seen in 104 patients (69.3%). In 8 out of 104 patients (7.6%) two or more convulsion was seen. Time interval between tramadol use and the onset of the first and second seizure were 0.93±0.17 and 2.5±0.75 hours, respectively. Tramadol induced seizures are more likely to occur in males and patients with a history of drug abuse. Finally, one hundred forty nine patients (99.3%) were discharged with good condition and the only one patient died from tramadol overdose. Conclusion: The results of the study showed tramadol induced seizure most frequently occurred within the first 4 hours of tramadol intake. The chance of experiencing a second seizure exists in the susceptible population. Thus, 4 hours after drug intake is the best time for patients to be hospital discharged.

The association between concentration of Uric Acid and metabolic syndrome among adolescents

Forogh Nokhostin

Background: Metabolic syndromes are known as a set of risk factors for the development of cardio-vascular disease and diabetes in the individual. The association between concentration of uric acid and metabolic syndrome in adolescents has yet to be established thoroughly. The aim of this study was to investigate the relationship between uric acid and metabolic syndrome in a sample of adolescents. Methods: This cross-sectional study was conducted from September 23, 2009 to September 22, 2010 in Jundishapur University of Medical Sciences, Ahvaz, Iran. In this study, 240 individuals aged 10-19 years were randomly selected among participants of the Ahvaz MetS study (120 subjects normal and 120 subjects MetS). The serum levels of UA were measured by a colorimetric method. In the normal group, anyone with abdominal obesity, high systolic or diastolic blood pressure, High-density lipoprotein (HDL)&le40 mg/dl, TG&le110 mg/dl, fasting blood sugar (FBS)&le100 mg/dl or diabetes was excluded from the study. History of Anticonvulsive drugs or steroids use was the criteria for exclusion for both groups. Results: Of the 240 subjects aged a mean of 14.95±2.64 years, mean of uric acid in metabolic syndrome group was 4.8±1.4 mg/dl and in the control group was 4.18±1.01 mg/d (P=0.001). Participants were divided into three groups based on uric acid levels: &le4.9 mg/dl, 4.9-5.7 mg/dl and >5.7 mg/dl. The risk of metabolic syndrome was significantly higher in third group of uric acid than the second and first group (odds ratio [OR], 3.7 95% confidence interval [CI], 1.70 - 8.04) and (OR, 5.9 95% CI, 2.42-14.35, P<0.001). In addition, uric acid level was inversely associated with hyperglycemia. The ORs of hypertriglyceridemia for the second and third group of uric acid were 4.36 (95% CI, 2.01- 9.47) 5.75 (95% CI, 2.43-13.61) respectively, compared with lowest group of UA. Conclusion: The results showed that hyperuricemia was significantly linked with increased risk for hypertriglyceridemia, low high-density lipoprotein cholesterol level, high blood pressure and waist circumference. Among Ahvaz adolescents, serum concentrations of uric acid strongly associated with the prevalence of metabolic syndrome and several of its components.

How long it takes patients' initial statements of concerns? brief report

Rasoul Masoomi

Background: There is a concern by some doctors that not interrupting the patients' initial statements of concerns can lead to too long medical visits. Therefore, in this study, the duration of the patients' initial statements of concerns was studied. Methods: This descriptive cross sectional study was conducted from August to October, 2011 in the Emergency Department of Imam Khomeini Hospital in Tehran. 100 patients entered the study through convenience sampling. Based on a 5 level triage system Emergency Severity Index (ESI), patients who were not life-threatening conditions (level 5) entered the study and critically ill patients and foreign patients were excluded from the study. Demographic data of the patients and durations the patients' initial statements of concerns were recorded and measured. Results: Fifty-six percent of patients were men. 79 percent of them had academic degree less than diploma and most of them have Persian ethnicity (60 percent). The mean age of the participants was 37.09 (SD, 1.68). The mean durations of patients' initial statements was 71.60±2.37 seconds. The minimum time was 22.51 seconds and the maximum time was 206.51 seconds. There was significant difference between age (P=0.001, r=0.382) and gender (P=0.032, df=98, t= -2.17) with the durations of patients' initial statements. But education level (P=0.996, F (2, 97)=0.004) and ethnicity (P=0.266, F (6, 93)=1.3) did not have a significant effect on the durations of patients' initial statements. Conclusion: According to the findings of this study, duration of patients' initial statements of concerns is less than what which leads to an increase the time of medical visits.