Archives of Iranian Medicine
Volume:19 Issue: 6, Jun 2016

Hemoglobin A1c (HbA1c) measurement devices are widely used to evaluate glycemic control in diabetic patients. The aim of this study was to investigate the comparability of various HbA1c instruments used in Iran.
In the present study, 154 fresh whole blood samples from diabetic patients, with different HbA1c levels (4.0%-10%) and no types of hemoglobinopathy were analyzed by six HbA1c assays including one high performance liquid chromatography (HPLC) method (D10 HbA1c), two immunoassay methods (COBAS INTEGRA 400 and Pars Azmoon kit), one Boronate affinity method (Nycocard Reader II), and two ion exchange methods (Biosystems and DS5). The two National Glycohemoglobin Standardization Programs (NGSP) certified system, D10 and COBAS INTEGRA 400 which are certified as secondary reference measurement procedures, were considered as reference methods. The CLSI document (EP9-A2) - Method comparison and Bias estimation using patient samples, approved guideline - was used to compare the performance of different HbA1c instruments.
The mean of HbA1c in all four types of assays was less than the reference methods (P-value It can be concluded that although HbA1c standardization programs have resulted in great improvements in the comparability of HbA1c assays, unacceptable errors still exist and further national and international projects are required for standardization of HbA1c measurement. In this situation, it is recommended to use the same laboratory for HbA1c measurement to monitor diabetic patients.

Genetic and expression anomaly of HER-2 have been frequently observed in different cancers. However, an overall association of HER-2 polymorphism (Ile655Val) with available cancer studies has not yet been explored. In the present study, a probable correlation of HER-2 Ile655Val polymorphism with 6 major types of cancers including breast, lung, gastric, ovarian, thyroid and uterine has been collectively assessed.
Extensive data mining was performed using online available medical research databanks including Pubmed, Ovid, Medline and Embase. Research articles were retrieved based on common keywords “HER-2, polymorphism, (SNP) and cancer (including breast, gastric, lung, ovarian, thyroid and uterine). A database was maintained and updated for case control studies of HER-2 genotype Ile655Val (rs1136201) information until February 2015. Based on selection criteria, a total of 41 studies containing 37,111 subjects (17845 patients, 19266 controls) were selected for thorough insight about HER-2.
A significant risk association of HER-2 Ile655Val polymorphism was observed in different types of cancer using various genetic models (co-dominant heterogeneous Ile/Val vs Ile/Ile; OR=1.1, 95% CI = 1.01–1.16, P = 0.01 and dominant; OR = 1.12, 95% CI = 1.03–1.20, P = 0.0003). Interestingly, a strong correlation of Ile655Val heterogeneity was seen in the stratified subgroup of different population including African-American (co-dominant homogenous Val/Val vs Ile/Ile; OR = 8.7, 95% CI = 2.5–30.4, P = 0.0001, dominant; OR = 1.3, 95% CI = 1.03–1.7, P = 0.003; recessive; OR = 8.3, 95% CI = 2.4–28, P = 0.0002), Caucasians (co-dominant heterogeneous Ile/Val vs Ile/Ile; OR = 1.1, 95% CI = 1.0 – 1.2, P = 0.03, dominant; OR = 1.12, 95% CI = 1.0–1.2, P = 0.01). However, in Asian ethnic group, Ile655Val polymorphism lacked a significant association with cancer. This may be attributed to limited studies explored so far.
In summary, the current study reveals a significant association between cancer susceptibility and the HER-2 Ile655Val polymorphism in all genetic models.

Vaccination has been one of the most successful and cost-effective public health interventions in the last century and has saved millions of lives. In 1984, the Expanded Program on Immunization (EPI) was launched in Iran as one of the main components of Primary Health Care (PHC).
We aimed to investigate the burden of four vaccine-preventable diseases from 1990 to 2010 in Iran.
GBD study 2010 includes death rates, Years of Life Lost (YLLs), Years Lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs). YLLs is calculated through multiplying the number of deaths in each age group by a reference life expectancy for the same age group, while YLDs can be obtained from the prevalence of a disease multiplied by the disability weight (DW) for the same disease. The sum of these two indices yields DALYs. In the present study, we tried to produce new graphs and explain more about Iran results. We also describe the GBD study limitations.
Regardless of gender differences, DALYs rates for measles at all ages were 86.1220 and 5.5703 per 100 000 in 1990 and 2010, respectively, indicating approximately 94% decrease in this disease. The maximum and minimum rates of deaths from whooping cough for males aged under 5 was 4.0674 and 0.2713 per 100 000 in 1990 and 2000, respectively, which shows 93% decline in whooping cough from in this period.
This study demonstrated that vaccination has had a positive impact on the control of communicable diseases. But the results of this study have some limitations similar to GBD study which may pave the way for decision makers about other public health interventions. Moreover, since measuring the impact of various diseases on health plays an important role in public health, it can be an important step toward prioritization in health.

Critical limb ischemia is a manifestation of peripheral arterial disease characterized by insufficient arterial blood flow for maintaining tissue viability in the lower extremities. Therapeutic angiogenesis is used for peripheral arterial disease patients who are not candidates for surgical revascularization or radiological intervention. There is accumulating evidence for the beneficial impact of autologous bone marrow mononuclear cell transplantation for treatment of critical limb ischemia in humans. This study aims to investigate the safety and efficacy of repeated bone marrow mononuclear cell injections in comparison with a single bone marrow mononuclear cell injection in critical limb ischemia patients.
Patients with critical limb ischemia (n = 22) were randomized (http://clinicaltrials.gov/ct2 show/NCT01480414) to receive either a single (n = 11) or four (n = 11) intramuscular injections of bone marrow mononuclear cells as a cell therapy product.
There were no reported adverse events during the 24-week follow-up period after cell delivery. Efficacy assessment indicated that after cell injections, there was significant improvement in Ankle-Brachial Index, Visual Analog Scale, pain-free walking distance, and Wagner stage as well as reduction in ulcer size. There was no significant difference between the two groups in terms of clinical parameters. However, by the 24th week the pain-free walking distance improved significantly in the group who received four injections of cells.
Favorable clinical outcomes strongly indicate the long-term benefit of bone marrow mononuclear cell transplantation, either as one or several injections, for retrieval from critical limb ischemia. Repeated cell injections have shown increased improvement of pain-free walking distance in patients. These findings warrant further exploration in later-phase clinical trials with repeated injections.

Obesity is a common health problem in the world and the purpose of this study was to identify the trend of overweight, obesity and stunting among children under five from 1998 to 2013 that was carried out in three stages in the villages of Golestan province in the northern Iran (south east of the Caspian Sea).
Three cross-sectional studies with sample sizes of 7575, including 2339, 2749 and 2487 cases were carried out in 1998, 2004 and 2013, respectively. Among 118 villages, 20 were chosen by random sampling and all of the under-five-children in these villages were assessed. For all subjects, a questionnaire was completed and anthropometric indices were measured. Z-score was used for body index classification with following categories: Z≤ 2SD=Normal or under-nutrition; >2SD Z ≤3SD = Overweight and Z>3SD = Obesity. P-value under 0.05 indicated significance.
In 1998, 2004 and 2013, the prevalence of overweight was 8.5% (95% CI; 7.3–9.6), 3.3% (95% CI; 2.7–4.0) and 5.2% (95% CI; 4.2–6.1), that of obesity was 4.6%(95% CI; 3.8–3.5), 1.2% (95% CI; 0.8–1.6) and 3.5% (95% CI; 2.8–4.3), and that of stunting was 32.8% (95% CI; 31.0–34.6), 13.4% (95% CI; 12.2–14.6) and 15.7% (95% CI;14.3–17.2), respectively. In boys, the mean of height was significantly different in all age groups while the mean of weight was significant only at ages 13–24, 37–48 and 49–60 months (P A heterogenic trend was seen in stunting, overweight and obesity. Although short stature was the main cause of obesity in 1998, extra weight was its major cause in 2013. Renewed increase of obesity among children under-five is considerable in the northern Iran.

Kindler syndrome (KS) is an autosomal recessive skin disease characterized by actual blistering, photosensitivity and a progressive poikiloderma. The disorder results from rare mutations in the KIND1 gene. This gene contains 15 exons and expresses two kindlin-1 isoforms.
The aim of this investigation was to analyze mutations in the exons 1 to 15 of KIND1 gene in an Iranian family clinically affected with Kindler syndrome.
The mutations analysis of 15 coding exons of KIND1 gene was performed with PCR-SSCP and direct sequencing in 14 subjects from one Iranian family clinically affected with Kindler syndrome.
We identified eight new nucleotide changes in KIND1 in this family. These changes were found in g.3892delA, g.3951T>C, g.3962T>G, g.4190G>T, g.7497G>A, g.11076T>C, g.11102C>T and g.13177C>T positions. Among them, the g.13177C>T mutation resulting in the formation of a premature stop codon (Q226X) was detected only in seven affected family individuals as homozygous but was not present in 100 unrelated healthy controls.
This study suggests that nonsense mutation may lead to incomplete and non-functional protein products and is pathogenic and has meaningful implications for the diagnosis of patients with Kindler syndrome.

Natural disasters are one of the most important adverse health events. The earthquake that happened in the city of Tabas in 1978 was ranked third in terms of number of deaths caused by natural disasters over the past 100 years in Iran. This study was aimed to evaluate the economic and human capital consequences of earthquake in Tabas district.
We used a two percent random sample of Iran Census Dataset from 2006 to run a difference-in-difference study. The difference-in-difference methodology was used to evaluate (1) the mean changes in variables including years of schooling and wealth; (2) the odds changes in primary school completion and literacy of people born (5 or 10 years) post-event versus (5 or 10 years) pre-event in Tabas compared with the same values for those born in the same period of time in the control districts.
Differential increase in years of schooling for being born 10 years after the earthquake versus in 10 years before earthquake in Tabas was one-third of a school year less than in the control districts. There were 89.5% and 65.4% decrease in odds that an individual is literate, and 0.26 and 0.104 average decrease in the SES index for those born in Tabas in periods of 5 and 10 years, respectively, compared with control districts.
Tabas earthquake had negative long-term effects on human capital and wealth. This study can help official authorities to promote educational and economic plans and to implement comprehensive reforms in earthquake-stricken areas.

Human Piwil2, a member of Piwi subfamily of Argonaute proteins, is primarily expressed in testis, where it regulates self-renewal of germ cells. However, its ectopic expression has been reported with several tumors, including breast cancer. The upregulation of piwil2 in various stages of breast cancer suggested its suitability as a novel tumor biomarker. Considering the vital role of microRNAs (miRNAs) in regulating the expression of most human genes, we hypothesized a concomitant downregulation of the bioinformatically-predicted piwil2-targetting microRNAs in breast cancer.
We employed different bioinformatic tools to predict piwil2-targeting miRNAs. Then, from the list of predicted miRNAs, we chose two less studied miRNAs (miR-1267 and miR-2276) for experimental validation. Using a real-time RT-PCR approach, we quantified the relative expression of the miRNAs in 31 pairs of formalin-fixed paraffin-embedded tumor/non-tumor tissue samples.
Our data revealed a noticeable but not statistically significant (P = 0.133) downregulation of miR-1267 in tumor samples, compared to non-tumor samples obtained from the same patients. Downregulation of miR-1267 was more significant in higher grades of malignancies (fold change = 2.39, P = 0.033) and also in lymph nodes containing high-grade tumor cells (fold change = 6.66, P = 0.02). Interestingly, a significant upregulation of miR-1267 was observed in tumors at high stages (stage 3a, 3b), compared to low stages (stage 2a, 2b) (fold change = 8.05, P = 0.048). Similar patterns of expression alteration were also observed for miR-2276.
Altogether, our findings suggest a probable tumor suppressor role for miR-1267 and miR-2276 in breast tumor initiation and progression, but a probable promoting role for them in invasion and metastasis.

This study was designed to evaluate platelet transfusion outcome via flow cytometric monocyte phagocytic assay (FMPA).
Fifteen patients with a history of multiple platelet transfusions and fifteen controls were enrolled in this study. CMFDA-labeled platelets were incubated with patient's sera and were finally incubated with monocytes in a tube and analyzed by flow cytometry. Monocytes that phagocytosed platelets were detected as a CMFDA-positive platelet population via monocyte gate. The FMPA results were compared with CCI results for the patients.
The FMPA result correlated with 1-hour (r = -0.885, P = 0.001) and 24-hour (r = -0.884, P = 0.001) CCI. There is a significant difference in means of FMPA results between the patients with immune platelet refractoriness (68.46 ± 10.4%), non-refractory group (37.73 ± 15.21%) and the control group (18.27 ± 2.86%).
Our data showed that FMPA has good results in evaluation of platelet transfusion outcome and may be useful as an indicator of platelet transfusion response.

Optimal use of blood and blood components requires theoretical and practical knowledge in transfusion medicine. While the importance of education in transfusion medicine has long been recognized, a vacancy is widely felt in this regard in Iran. In this study, the current status of transfusion medicine education in Iran is evaluated using a review of studies conducted in this field.
To access articles related to transfusion medicine education in Iran, an electronic search was performed in databases, including Magiran, SID, IranMedex, Google Scholar, PubMed, ScienceDirect, and Scopus and the related articles were evaluated.
Knowledge of transfusion medicine was not optimal in various medical groups and there was no effective theoretical and practical education and training for transfusion medicine in medical universities. Almost all the studies concluded that transfusion medicine curricula should be implemented for both undergraduate and postgraduate students, because of its great importance in clinical practice.
Educational program of transfusion medicine is a basic need of medical education for medical students, interns, residents, nursing, and midwifery students in Iran. Considering our status and capacities and by using educational programs in the world, curricula are suggested for different educational levels. Implementation of these training programs plays a vital role in improving patients’ safety and also reduces the high costs of treatment with blood products.

Differential diagnosis between Lewy body disease and Alzheimer´s disease might be difficult because of similarities of clinical symptoms in both neurodegenerative diseases. DatSCAN is a modern functional neuroimmaging method which differentiates between this similar diseases and helps in correct treatment strategy. We report our positive experience with DatSCAN in differentiating Lewy body disease from Alzheimer´s disease. This is a case report of a woman with Lewy body disease, initially diagnosed as Alzheimer´s disease. DatSCAN neuroimmaging method was used in differential diagnosis of dementia. Memory impairment, impaired activities of daily living, sleep and behavioral disturbances were present in our case. Donepezil was well tolerated, but haloperidol administration was followed by development of severe dystonia. DatSCAN showed deficient dopaminergic presynaptic transport in substantia nigra and striatum. This finding is typical for Lewy body disease not for Alzheimer´s disease. DatSCAN neuroimmaging is a suitable method for differentiating Lewy body disease from Alzheimer´s disease. Deficient dopaminergic presynaptic transport in substantia nigra and striatum is typical for Lewy body disease.