Tehran University Medical Journal

---

Background: Childhood nephrotic syndrome is frequently characterized by a relapsing course. Due to their adverse effects, the use of corticosteroids for the management of frequently relapsing nephrotic syndrome is limited. Levamisole, a steroid sparing agent, has been found to have low toxicity. This study was conducted to evaluate the efficacy of levamisole in steroid-sensitive nephrotic syndrome (SDNS). 

Methods: In this retrospective study from January 1988 to September 2006, we included data from 305 pediatric SDNS patients at the Children's Medical Center clinics in Tehran, Iran. Nephrotic syndrome was diagnosed using classic criteria. None of the patients had any signs or symptoms of secondary causes of nephrotic syndrome. All had received prednisolone 60 mg/m²/day. After remission, prednisolone administration was reduced to every other day and the steroid was tapered over the next three months. With every recurrence, prednisolone was prescribed with the same dosage, but after remission it was continued at a lower dosage for another six months or longer if there was risk of recurrence. Levamisole was administered to all patients at a dose of 2 mg/kg every other day.         

Results: Patients ranged in age from 1 to 20 years (mean±SD: 4.84 ±3.1) and 70.8% were male. At the last follow up, 84 (27.5%) were in remission, while 220 (72.1%) patients had relapsed or needed a low dose of steroid. Levamisole was effective in reducing the prednisolone dosage and long-term remission in 68 (22.3%) and 90 (29.5%) cases, respectively. A comparison of before vs. after levamisole treatment revealed a had significant decrease in the number of relapses (2.05±0.88 vs. 1.1±1.23 P<0.0001) and the prednisolone dosage (0.74±0.39 vs. 0.32±0.38 mg/kg/day P<0.0001). Only one patient developed levamisole-induced neutropenia.

Conclusions: In childhood steroid-dependent nephrotic syndrome, levamisole is an efficacious, safe initial therapy in maintaining remission while decreasing steroid dose, in addition to reducing the rate of relapse.

---

Background: Alkaloids are a group of nitrogenous compounds with potential effects on the physiological behavior of human and animals. Some of these compounds are considered important drugs in modern medicine, such as atropine and morphine. Plants are considered the most important source of alkaloids. Therefore, investigating the presence of alkaloids in different plants is very important. Usually, alkaloids in plants are identified by methods such as those of Dragendorf, Wagner and Meyer, among others, which require milligrams of alkaloids for identification. In the present study, a fast and sensitive procedure for detecting of alkaloids in plants is presented.
Methods: Twelve dried plants samples were investigated for the presence alkaloids. After extracting the total alkaloid into methanol using a Soxhlet extractor, a few milligrams of the extract was transferred to a separatory funnel, buffered to pH 4.7, the bromocresol green (BCG) solution (10-4 M) was added, mixed and extracted with CHCl3 until a yellow color was observed in the CHCl3 layer, indicating the presence of the alkaloid. The crude extracts were also investigated by the standard methods of Dragendorf, Wagner and Meyer for the presence of alkaloids.
Results: Investigation of the 12 plant samples for the presence of alkaloids by the standard reagents of Dragendorf, Wagner, and Meyer showed that only Camelia sinensis (flowers), Echium amoenum Fisch & Mey (flowers), and Stachys (aerial parts) are devoid of alkaloids, with all other samples positive for alkaloids. By the BCG procedure, similar results were obtained, except for the E. amoenum flower, which was positive. The minimum detectable limit for alkaloids by the BCG method is the equivalent of approximately 40μg atropine.
Conclusions: According to previous reports, only one of these plants does not contain alkaloids. All studied plants positive for alkaloids by standard reagents were positive by the BCG procedure. Stachys was negative for alkaloids by both the standard reagents and the BCG method, in agreement with previous reports. However, black tea, reported to contain xanthine alkaloids, was negative for alkaloids by both the standard reagents and the BCG method. Therefore, the BCG method is not suitable for the detection of xanthine alkaloids. Nevertheless, the microgram detectable limit for alkaloids indicates that the BCG method is very sensitive.

---

Background: Early diagnosis of renal parenchymal involvement in children with acute pyelonephritis (APN) using isotope scan and early treatment may decrease or prevent development of renal parenchymal lesions. We designed this study to assess the diagnostic value of certain biologic parameters in children with first- episode of acute pyelonephritis (APN) documented by 99m Tc-dimercaptosuccinic acid (DMSA) scintigraphy.
Methods: We compared the laboratory findings of leukocyte count, erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) levels with the results of the DMSA scans obtained within three days of admission. One hundred-two children (93 girls and 9 boys aged 1 month–12 years (mean 2.85±2.92 years) were enrolled in the study. Of these patients, 203 renal units, were investigated using scintigraphy. Voiding cystourethrography (VCUG) was performed in 98 children (195 renal unit) when urine culture became negative.
Results: In all children one or both of kidneys had parenchymal involvement on scintigraphy. Changes on the DMSA scan were found in 178(88%) renal units during the acute phase. The extent of changes in DMSA scan were mild in 113/178(55.7%) renal units, moderate in 40/178(19.7%) and severe in 25/178(12.3%). When inflammatory markers were correlated with the development of the severe renal lesions, as assessed with DMSA scan, a highly significant correlation with both ESR (p=0.007) and leukocyte counts (p=0.02) were found.
conclusions: We conclude that the incidence of renal parenchymal involvement in Iranian children with APN is very high. Although increased ESR and leucocytosis may be valuable markers for determination of severe renal parenchymal involvement, but these parameters and also CRP, were inadequate in distinguishing mild to moderate renal parenchymal involvement.

---

Background: Increased rate of oxidative stress have important role in diabetic nephropathy. Oxidative stress induces the synthesis of antioxidant enzymes. One of them, Extracellular- SOD (EC–SOD) is a major anti-oxidative enzyme and the only one that neutralizes superoxide ion, a precursor of reactive oxygen species (ROS). The aim of this study was to evaluate the correlation between diabetes- associated oxidative stress and antioxidative defense in macroalbuminuric type 2 diabetic patients.

Methods: One hundred and thirty three patients (74 women, 59 men) with type 2 diabetes were studied during 1385-86. According to level of urinary protein, two groups of patients normoalbuminuric (urinary protein excertion below 30mg/24h) and macroalbuminuric (urinary protein excretion more than 300mg/24) were recognized. In each group serum level of oxidized- LDL and EC-SOD were measured.

Results: The mean age of patients and the mean duration of diabetes was 59.09±8.26 years and 137.92±65.91 months, respectively. The plasma oxidized-LDL level and extracellular- superoxide dimutase level were significantly higher in macroalbuminuric than normoalbuminuric group (88.57±33.36 versus 78.24±27.59u/l, p=0.039 for oxidized-LDL and 87.60±21.18 versus 76.25±16.25mu/l, p<0.001 for EC-SOD). Oxidized- LDL was significantly correlated to EC-SOD in macroalbuminuric patients (r=0.425, p<0.0001). Oxidized-LDL and EC-SOD does not correlate to Fasting Plasma Glucose and HbA1c in each two groups.
Conclusion: The significantly elevated plasma oxidized-LDL in patients with macroalbuminuria suggests that, oxidized-LDL may play an important role in the progression of diabetic nephropathy. Besides severity of oxidative stress in macroalbuminuic patients, increase level of EC-SOD enzyme could be a compensatory mechanism to prevent tissue damage.

---

Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Multiple myeloma is a plasma cell dyscrasia characterized by proliferation of plasma cells in bone marrow associated with the production of monoclonal immunoglobulins. In recent years, the use of arsenic trioxide, formerly approved for treatment of acute promyelocytic leukemia has been considered for refractory myeloma treatment. This study was designed and carried out to evaluate the efficacy and possible side effects of ATO on patients with refractory multiple myeloma.

Methods: This study carried out on myeloma patients whose diseases were at least refractory to two standard treatment regimens conducted in Ghazi Tabatabaei Hospital in Tabriz- Iran. Arsenic trioxide was administered as an intravenous infusion at a dose of 0.25 mg/kg/d for 5 d/week during the first two consecutive weeks of each 4-week cycle with two week rest. Patients who completed one 4-weak cycle were evaluated for response to treatment.

Results: Twelve patients with refractory disease to conventional treatment regimens received arsenic trioxide. The response to the treatment assessed based on the amount of serum proteins electrophoresis of the 10 patients. Stable disease observed in four patients (33%), progressive disease in five patients (41.6%), complete response in one (3.8%) and the remaning two patients could not be assessed for response (because of increased liver enzymes after the first week). One patient completed six cycles. Some adverse events such as: increase liver enzymes and serum creatinine, neutropenia, pruritus, nausea, vomiting, lower extremities edema, and noninfectious diarrhea were observed.

Conclusions: The use of arsenic trioxide is promising in treatment of refractory multiple myeloma.

---

Background: The current standard of adjuvant management for gastric cancer after curative resection based on the results of intergroup 0116 is concurrent chemoradiation. Current guidelines for designing these challenging fields still include two-dimensional simulation with simple AP-PA parallel opposed design. However, the implementation of radiotherapy (RT) remains a concern. Our objective was to compare three-dimensional (3D) techniques to the more commonly used AP-PA technique.
Methods: A total of 24 patients with stages II-IV adenocarcinoma of the stomach were treated with adjuvant postoperative chemoradiation with simple AP-PA technique, using Cobalt-60. Total radiation dose was 50.4Gy. Landmark-based fields were simulated to assess PTV coverage. For each patient, three additional radiotherapy treatment plans were generated using three-dimensional (3D) technique. The four treatment plans were then compared for target volume coverage and dose to normal tissues (liver, spinal cord, kidneys) using dose volume histogram (DVH) analysis.
Results: The three-dimensional planning techniques provided 10% superior PTV coverage compared to conventional AP-PA fields (p<0.001). Comparative DVHs for the right kidney, left kidney and spinal cord demonstrate lower radiation doses using the 3D planning techniques (p<0.0001), the liver dose is higher (p=0.03), but is still well below liver tolerance.
Conclusion: Despite the department protocol using conventional planning, 3D radiotherapy provides 10% superior PTV coverage. It is associated with reduced radiation doses to the kidneys and spinal cord compared to AP-PA techniques with the potential to reduce treatment toxicity.

---

Background: Many chemotherapeutic regimens used in the treatment of cancer generate free radicals that may be a part of their beneficial effects. The aim of this study was to assess the oxidative status in patients undergoing chemotherapy for acute myeloid leukemia (AML).

Methods: Thirty-eight patients with AML (17 female and 21 male patients) with a mean age 34.05±12.49 years were included in the study. All the patients received cytarabine and daunorubicin as their standard induction therapy. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and also the erythrocyte superoxide dismutase and glutathione peroxidase activities were measured before and 14 days after chemotherapy.

Results: Plasma malondialdehyde concentrations increased significantly (from a former 2.68±0.89 nmol/ml to 3.14±1.29 nmol/ml) 14 days post chemotherapy (p=0.04). Moreover, the total plasma antioxidant capacity changed from 1.09±0.15 mmol/L to 1.02±0.14 mmol/L (p=0.005). Erythrocyte superoxide dismutase and glutathione peroxidase activity decreased over time from 1157.24±543.61 U/gHb to 984.01±419.09 U/gHb (p=0.04) and 46.96±13.70 U/gHb to 41.40±6.44 U/gHb (p=0.02), respectively.

Conclusion: In this study, an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant capacity were observed. It seems that chemotherapy by cytarabine and daunorubicin generates enormous amounts of free radicals in patients undergoing the treatment for AML. Use of antioxidant supplementation during chemotherapy i is discouraged as it may interfere with the generation of free radicals that may be a part of the therapeutic efficacy of these drugs.

---

Background: Recurrent aphthous stomatitis (RAS) is a common disease with unknown etiology. There is no curative treatment. Purslane is considered as a rich source of antioxidants with anti-inflammatory effects. The purpose of this study is to evaluate the effect of Purslane in the treatment of RAS.
Methods: A total of 50 patients were selected for this randomized triple-blind placebo-controlled clinical trial from School of Dentistry of Tehran University of Medical Sciences in 2011. All subjects were randomly divided into two groups. Groups A and B received placebo and Purslane, respectively, for three months. Pain intensity based on the visual analogue scale (VAS), the mean intervals of lesions occurrence, number of lesions and the mean duration of complete healing at baseline and at months 1, 2 and 3 were recorded. 
Results: While no patient complained from increased severity of pain, decreased severity of pain for 4, 3, 2, and 1 grades were recorded in %16, %20, 20%, and 40%, respectively, which were much higher than 4%, 8%, 8%, and 28%, respectively, in the control group. A significant decrease in pain intensity in VAS scores were seen after treatment in group B (P<0.001). The mean duration of complete healing showed significant differences (P<0.001) between groups A (-1.52±4.07 days) and group B (-6.56±4.50 days). The mean intervals between lesions also showed significant differences (P<0.001) between group A (17.88 days) and group B (33.12 days). No significant differences were found between group A and group B regarding to number of lesions. No serious side-effects occurred in either group.
Conclusion: According to our study, Purslane is clinically effective in treatment of RAS and considering the lack of side-effects during the study period, this medicine may be a favorable alternative treatment for recurrent aphthous stomatitis.

---

Background: Bone is one of the most common sites of metastatic disease in malignancies. Many of the cases are asymptomatic and may be diagnosed in primary or secondary follow-up, but in symptomatic cases pain is the prominent symptom which is mostly exaggerated at nights. The improved survival of cancer patients with bony metastases in recent years, specially in breast and prostate cancer, has given a greater importance to the careful choice of treatments in this setting. This can lead to a better quality of life, lower treatment cost, prevention of disabilities, less delay in primary cancer therapies, and decrease of life-threatening events for the patients. Here we review the metastatic disease of the bone and its treatments, with emphasis on local and systemic radiation therapy. Current literature about bone metastasis and its treatments was reviewed through a search of available databases on internet for papers published in 1995-2013. Special attention was given to the research trials and studies performed by the authors on this setting. Treatment of bone metastases consist of analgesics, radiotherapy, surgery and bisphosphonates. Control of bone metastases is a challenging process, necessitating a multi-disciplinary approach and teamwork between the treating physicians. Radiotherapy is the most useful modality for this purpose in oncology, given both as a local and systemic therapy. We hope that this review would be able to help in choosing the best treatment option for this common palliative situation in Iranian cancer patients.

---

Background: Colorectal carcinoma is a common malignancy, in treatment of which pelvic radiotherapy plays an important role. But this may lead to azospermia. We designed a study to determine the delivered dose to the testis with thermoluminescence dosimetry (TLD) and compare it to the dose calculated by the Three-dimensional planning software. Methods: We measured the testicular doses by TLD the TLDs were fixed to the scrotum in six points anteriorly and posteriorly in two random fractions of the radiation course. All patients received a 50-50.4 Gy radiation dose to the pelvis in a prone position with standard fractionation and 3-dimensional planning, through three or four fields. The average dose of the TLD measurements was compared to the average of 6 relevant point doses calculated by the planning software. Results: In 33 patients with a mean age of 56 years, the mean testis dose of radiation measured by TLD was 3.77 Gy, equal to 7.5% of the total prescribed dose. The mean of point doses calculated by the 3-dimensional planning software was 4.11 Gy, equal to 8.1% of the total prescribed dose. A significant relationship was seen between the position of the inferior edge of the fields and the mean testis dose (P= 0.04). Also body mass index (BMI) was inversely related with the testicular dose (P= 0.049). Conclusion: In this study, the mean testis dose of radiation was 3.77 Gy, similar to the dose calculated by the planning software (4.11 Gy). This dose could be significantly harmful for spermatogenesis, though low doses of scattered radiation to the testis in fractionated radiotherapy might be followed with better recovery. Based on above findings, careful attention to testicular dose in radiotherapy of rectal cancer for the males desiring continued fertility seems to be required.

---

Background: The mortality due to Coronary Artery Bypass Graft (CABG) in patients with chronic renal failure is more common than normal population. This study evalu-ates the impacts of prophylactic dialysis on decreasing mortality and morbidity of non- dialysis-dependent patients with renal failure after CABG surgery. Methods: In this study, fifty non-dialysis-dependent patients who were suffering from renal failure and needed to CABG, were selected by convenience sampling method. Se-quentially, they were allocated to prophylactic dialysis (n=20) and no prophylactic dialysis (n=30) groups, using a randomized block design. Exclusion criteria were under 18 year old patients and doing CABG for second time. Mortality rate and some complications such as acute renal failure, brain accident and atrial arrhythmias were compared between two groups after CABG. All cardiac surgeries were performed in a single centre and through a median sternotomy. P value less than 0.05 was considered as significant. Results: The mean age of patients was (65.3±9.9). The patients included %16 (n.8) of women and %84 (n.42) of men. There were 20 patients in intervention and 30 patients in control groups. Baseline characteristics were similar in two groups. Comparison be-tween intervention and control groups after surgery did not show any difference in mortality (P=0.14), acute renal failure (P=0.4), cerebrovascular accidents (P=1) and atrial arrhythmias (P=0.3), need to second surgery due to bleeding (P=1), need to dialysis (P=0.14), need to rehospitalization (P=1), duration of ventilator use (P=0.4), duration of need to hospitalization (P=0.11), duration of a patients stay in the Intensive Care Unit (P=0.4) and deep sternal infection (P=0.7) rates. Conclusion: According the results of this study, prophylactic dialysis, before conduct-ing CABG, does not have any significant effect on mortality and other complications. The only exception is lung complications in non-dialysis-dependent patients with renal failure.

---

Background: The relationship of the base of appendix to the cecum remains constant, whereas the tip can be found in a retrocecal, pelvic, subcecal, preileal, or right pericolic position. These anatomic considerations have significant clinical importance in the context of acute appendicitis. The knowledge about the correct anatomical position of appendix may facilitate in generating an accurate diagnosis of appendicitis as well as assist in achieving a better prognosis and early treatment. The present study aimed to determine the anatomical location of the appendix in Iranian cadavers. Methods: This descriptive cross-sectional study was conducted on 200 cadavers who were referred to the Forensic Center of Tehran from March to September 2013. The data including age, sex, weight, and appendix length and position were collected and analyzed using SPSS software, version 16 (SPSS, Inc., Chicago, IL, USA). Results: In the present study, 200 cadavers were evaluated accidentally, of which 173 (86.5%) were males and 26 (13%) were females, and the mean age was 39.96 years±16.31 (SD). The mean wall thickness of the appendix was 9.78 cm±16.31 (SD). The mean appendix length was 9.86 cm±1.79 (SD) in men and 9.30 cm±1.56 (SD) in women. The appendix height was long in 20 cadavers (10%), short in 3 cadavers (1.5%), and moderate in 177 cadavers (88.55%) cadavers. The appendix position was posterior in 120 (60%), ectopic in 32 (16%), and pelvic in 48 (24%) cadavers. Conclusion: Majority of appendices examined in the present study were positioned at the posterior (Retrocecal) of pelvis. According to different positions of appendices in different populations and different races, the knowledge of appendix position in various populations is necessary for early diagnosis and treatment and fewer complications for related disease.

---

Background: Small molecule Purmorphamin (PMA) is the agonist of smoothened protein in Sonic hedgehog (Shh) signaling pathway. Effect of purmorphamin small molecule on differentiation of mesenchymal cells into bone tissue has been studied previously. Use of Shh causes progression of neural differentiation, and the differentiated cells express specific neural markers. Neurofilament (NF) and acetylcholine esterase (Chat) are specific markers of motor neurons and their expression in differentiated cells indicates their conversion into motor neurons. The aim of this study was to evaluate the ability of PMA to differentiate the human endometrial stem cells (hEnSCs) into motor neurons.

Methods: This analytical study was done in Tehran University of Medical Sciences laboratory on September of 2015. In this study hEnSCs were enzymatically extracted from endometrial tissue. After third passages, the flow cytometry was done for mesenchymal stem cells markers. The mesenchymal stem cells were divided into control and differentiated groups. FBS 10%+DMEM/F12 was added to the culture medium of control group and the differentiating group was treated with differentiating medium containing N2, PMA, DMEM/F12, FBS, B27, IBMX, 2ME, FGF2, RA, BDNF. After 21 days immunocytochemistry (ICC) test was done for the expression of NF and Chat proteins and Real-time PCR analysis for expression of neural markers such as NF, Chat, Nestin and GFAP (as glial marker) at mRNA level.

Results: The flow cytometry analysis showed that hEnSCs were positive for mesenchymal markers CD90, CD105 and CD146 and negative for endothelial marker CD31, and hematopoietic marker CD34. The immunocytochemistry and Real time-PCR results showed that the cells treated with PMA expressed motor neuron markers of NF and Chat. Conclusion: According to the results of this study, it can be concluded that small molecule PMA has the potency to induce the differentiation of hEnSCs into neural cells, specifically motor neurons by activating Shh signaling pathway.

---

---

---

---

Results: Dose distribution uniformity was acquired in the order of -1.01% to +11.82% relative to the prescribed dose at the umbilicus. The difference between the calculated and measured dose at the umbilicus level was -2.73%. The radiation absorbed dose to the lung with blocks was 127.53cGy in one fraction which resulted in 756.18cGy in six fractions.

---

Background: Among all types of cancers, pancreatic cancer has poor prognosis with 5-year survival below 10%. In theory, alcohol intake may be a modifiable risk factor for pancreatic cancer due to its role in multiple carcinogenic and metabolic signaling pathways. In addition, alcohol consumption may lead to chronic pancreatitis which is underlying cause of pancreatic cancer. However, little is known about whether this factor is associated with pancreatic cancer. This study aimed to systematically review the cohort studies investigating the possible link between alcohol consumption and the morbidity or mortality of pancreatic cancer.
Methods: This study was carried out based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). All of cohort studies that assessed the association between alcohol intake and the risk of pancreatic cancer or death were included in this systematic review without a language restriction. Electronic databases including PubMed, Web of science, Scopus, and Google scholar were searched using the keywords "pancreatic cancer" and "alcohol" and similar words from 1990 to April 2021 to find the cohort studies.

Results: 858 articles were identified, of which 806 were excluded and the full-text of 52 papers were evaluated for the eligibility. Eventually, 22 articles were eligible and were included in this study. Many of the articles assessed the impacts of low to moderate alcohol intake. A comprehensive review of these studies showed that low to moderate alcohol consumption had a non-significant correlation with pancreatic cancer, while high alcohol consumption was significantly associated with the risk of pancreatic cancer or death. The results also revealed that high liquor consumption was associated with higher risk of pancreatic cancer. Nevertheless, the follow-up durations in most of these studies were shorter than that to lead to pancreatic cancer. Conclusion: Long-term heavy alcohol drinking can increase the morbidity or mortality of pancreatic cancer. Regarding that several genetic and environmental variations involve in the pathogenesis of this cancer, simultaneous control of these differences should be addressed to determine the net effect of alcohol drinking on pancreatic cancer.

---

---