Archives of Iranian Medicine
Volume:19 Issue: 2, Feb 2016

Hypoglycemia is associated with adverse health outcomes and can result in vascular events in diabetic patients. The impact of hypoglycemia on cardiovascular outcomes in non-critically ill people with diabetes is not well-determined. So, we examined short-term cardiovascular outcomes of hypoglycemic events in people with type 2 diabetes treated with insulin during routine clinical care.
This study was conducted in Tehran, Iran from January 2012 to January 2013. One hundred and twenty non-critically ill people with type 2 diabetes on oral glucose lowering drugs were enrolled. Insulin therapy was initiated for uncontrolled diabetes. The patients were educated to perform self-monitoring of blood glucose on a daily basis. Furthermore, they were asked to record the results if they experienced any symptom indicative of hypoglycemia during the 24 weeks of the study. The occurrence of any major cardiovascular event including unstable angina, fatal or non-fatal myocardial infarction, fatal and non-fatal stroke, or death from cardiovascular cause was also evaluated based on the patients’ hospital records.
There were 210 hypoglycemic episodes and 31 major cardiovascular events. Forty four percent of patients with documented hypoglycemic episodes developed cardiovascular events compared to 15.6% of those who did not experience any hypoglycemia (P = 0.001). The odds ratio for occurrence of major cardiovascular events related to hypoglycemia was 7.41 (CI = 2.15–25.47) with a risk ratio of 2.66.
Hypoglycemia is a major risk factor for occurrence of the first major cardiovascular event in non-critically ill people with type 2 diabetes initiating insulin therapy.

TWINKLE (c10orf2) gene is responsible for autosomal dominant progressive external ophthalmoplegia (PEO). In rare cases, additional features such as muscle weakness, peripheral neuropathy, ataxia, cardiomyopathy, dysphagia, dysphonia, cataracts, depression, dementia, parkinsonism, and hearing loss have been reported in association with heterozygous mutations of the TWINKLE gene.
We have studied a large Iranian family with myopathy, dysphonia, dysphagia, and behavior change in addition to PEO in affected members.
We identified a missense mutation c.1121G > A in the c10orf2 gene in all affected members. Early death is a novel feature seen in affected members of this family that has not been reported to date.
The association of PEO, myopathy, dysphonia, dysphagia, behavior change and early death has not been previously reported in the literature or other patients with this mutation.

Probiotics, as live microbial food ingredients or functional foods, are often related to health promotion and diseases prevention. The growth of these beneficial probiotics was improved by non-digestible food ingredients that are defined as prebiotics. Inulin is one of the known prebiotics that improves the gastrointestinal health.
Aim: The aim of this study was to evaluate the functional properties of Lactobacillus paracasei TD3 (IBRC-M 10784) and the effects of inulin as prebiotic on these properties in vitro.
The tolerance of L. paracasei TD3 for low pH and pepsin (stomach condition), bile salt and trypsin conditions (small intestine conditions), antibiotics and pathogenic bacteria were evaluated by different methods.
Lactobacillus paracasei TD3 was obtained from TakGene Company. L. paracasei TD3 was resistant to acidic pH higher than 3.5 and was tolerant to pepsin condition lower than 0.723 µg/mL and to bile salts ≤ 0.4% w/v and tripsin condition equal to 72.32 u/g and lower. This strain was resistant to vancomycin, nalidixic acid, colistin and gentamicin while was sensitive to penicillin, streptomycin and tetracycline. L. paracasei TD3 showed antimicrobial activity against S. typhimurium, Sh. dysanteriae, Sh. flexneri and E. coli, respectively. Inulin promoted the growth of L. paracasei TD3 (log CFU) in different conditions and increased the antibacterial activity of L. paracasei TD3 against pathogenic bacteria without changing the tolerance of bacteria to pH and other conditions (P > 0.05).
L. paracasei TD3 (IBRC-M 10784) in combination with inulin can be considered a valuable strain for further investigations in human clinical studies.

Major thalassemic patients need lifelong transfusions. The consequence of these repeated transfusions is iron accumulation in different organs. The main aim of the present study was to investigate the correlation between heart, liver and pancreas hemosiderosis in thalassemic patients from Iran.
This cross-sectional study was conducted on 164 major thalassemia patients at Zafar Adult Thalassemia Center, a referral thalassemia center in Tehran, Iran, from May to November 2014. All patients were on regular blood transfusion at 2–4 week intervals to keep their hemoglobin at a level of 7–9 gr/dL before each transfusion. Demographic data were gathered from patients’ history. MRI T2* of liver, heart and pancreas were performed for all patients.
There was a moderate correlation between pancreatic T2* and cardiac T2* relaxation times (r = 0.42, P Poor correlation between liver and heart, as well as a weak to moderate correlation between pancreas and liver T2* relaxation times indicate that relying on liver MRI T2* to predict the exact condition of pancreas or heart iron overload might not be a reliable approach in thalassemia major patients. Our findings suggest the advantage of using pancreas and heart MRI T2* as a non-invasive method for estimation of iron overload instead of relying on liver MRI T2*.

Alzheimer and Parkinson diseases (AD and PD) are the two most important neurodegenerative disorders. This paper aims to determine the possible molecular linkage between these two common neurodegenerative diseases by a combination of computational investigations.
According to our aim, common sets of identified proteins from the KEGG database were further analyzed based on Gene Ontology (GO) annotation and sequence similarities by the agglomerative hierarchical clustering. Proteins possessing same characteristics were categorized based on biological features in distinct clusters using the R programming software. In addition to this, by the use of DAVID Program and PPI network analysis, more insight can be achieved.
The results of this study indicated that 23 proteins are common between these two diseases. Their ontology evaluations by application of clustering methods showed that proteins belonging to a specific cluster indicate discrete properties that are different from other clusters. Furthermore, PPI network analysis confirms that the proteins with similarity ontology and sequence are also in close relationship.
In conclusion, assessment of protein features supported the idea that mitochondria are the main malfunction compartment in AD and PD. Some of these common properties are apoptosis and mitochondria oxidation pathways that can be used for drug targeting. Moreover, examination of other neurodegenerative diseases can be helpful for comprehensive understanding of the origin of these diseases.

Although metabolic syndrome (MetS) is a major health problem worldwide, there is no universal agreement on its definition. One of the major disagreements is dealing with the issue of obesity in this definition. This study was conducted to determine a preferably better index of obesity which can be interrelated with other components of MetS in a single factor model of MetS.
DESIGN: Out of 6140 participants of a cohort study of subjects aged 10-90 years in northern Iran, the baseline data of 5616 participants aged 18-75 was considered. Confirmatory factor analysis was conducted using AMOS software to evaluate a single factor model of MetS in which blood pressure, triglyceride (TG), high density lipoprotein (HDL), fasting blood sugar (FBS) and obesity measures including waist circumference (WC), body mass index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) were used as indicators of metabolic syndrome. Four single factor models differing from each other by obesity indices were evaluated. The models were evaluated in all 5616 subjects and 4931 subjects without diabetes mellitus according to sex separately.
All single factor models had appropriate fit indices with CFI > 0.95, GFI > 0.95 and RMSEA While single factor validity of MetS was confirmed in almost all models, the best models were different according to sex and population of study.

We aim to evaluate the trend of national and sub-national (provincial) utilization pattern of antihypertensive medicines in the Iranian population in the past decade and evaluate whether there is any wealth-related inequality in utilization of these medicines among different provinces.
Either fixed effect or random effect linear panel data model was used to check the effect of wealth index on utilization of all antihypertensive medicines and each class, adjusting for other covariates including years of schooling, urbanization, mean age, and food type of provinces. The principal component analysis was applied to make summery measures for covariates using available national datasets.
The effect of wealth category on the utilization of all antihypertensive medicines among Iranian provinces was positive and significant (0.84; 95% CI: 0.09, 1.59). Accordingly as subgroup analysis, in BBs and CCBs classes, the effects of wealth category on utilization of medicines were positive and significant (0.36; 95% CI: 0.12, 0.60 and 0.27; 95% CI: 0.07, 0.40, respectively). However in ACEIs and Diuretics classes, the effects of wealth category were positive but not significant. In ARBs class, the effect of wealth on utilization was negative and not significant (-0.04; 95% CI: -0.27, 0.18).
According to this study, an inequality could be observed in Iran related to wealth category in utilization of total antihypertensive medicines between provinces.

Few studies have assessed the relationship between tooth loss and upper gastro-intestinal (GI) disorders including functional dyspepsia (FD) and gastro-esophageal reflux disease (GERD). This study aimed to investigate the relation between dental status and FD, its components and GERD among a large group of Isfahani adults.
In a cross-sectional study from April to May 2010, the dental status of 4109 Isfahani adults was evaluated using a self-administered questionnaire. Participants were categorized into three main groups: those with full dentition, individual who had lost 1–5 teeth and those who had lost >5 teeth. FD, its components and GERD were defined using Rome III criteria. Multivariable logistic regression was used to examine the relationship between dental status and gastrointestinal disorders.
After adjustment for potential confounders, we found no significant association between dental status, FD and GERD. However, individuals who had lost 1–5 teeth and >5 teeth had 34% and 109% greater odds for early satiation, respectively. In addition, individuals who had lost 1–5 teeth were 24% likely to have postprandial fullness and epigastric pain. Stratified analyses by gender also revealed a significant association between dental status and GERD as well as FD in females; such that those who had lost 1–5 teeth had 33% greater chance for GERD and those who had lost >5 teeth were 101% more likely to have FD compared with those with full dentition.
We found significant positive associations between tooth loss, GERD and FD in women, but not in men. We also found significant relations between tooth loss and components of FD, especially early satiety in the entire population.

Transplantation of mesenchymal stem cells (MSCs) in combination with pioglitazone, an agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), can reduce liver fibrosis in models of liver injury. In this study, we conducted a pilot study of intraportal infusion of autologous MSCs in combination with pioglitazone to assess safety, feasibility, and effectiveness in patients with compensated cirrhosis.
Two patients with compensated cirrhosis were enrolled in this study. Intraportal autologous bone marrow-derived MSCs were transplanted twice (6 months interval) to the patients. Meanwhile, 30 mg/day pioglitazone was prescribed for 12 months. Patients were assessed at baseline and months 1, 3, 6, and 12 post-infusion.
Procedural complications or any major adverse effects did not occur in this pilot study. The patient's clinical conditions remained stable with no evidence of deterioration during the course of the study. A transient improvement in the Model for End-Stage Liver Disease (MELD) score was observed at month 3 post-infusion in one patient, which eventually returned to baseline at month 12.
The combination of pioglitazone with MSCs is safe and feasible. The data justify further study of the combination therapy in cirrhotic patients.

Serum pepsinogen I and II are considered as indicators of changes in gastric morphology. Important publications from the last decades are reviewed with regard to the serum level of these biomarkers for the diagnosis of normal gastric mucosa, diffuse gastritis and its change to atrophic gastritis and intestinal metaplasia as well as gastric cancer. Due to the low sensitivity of serum biomarkers for diagnosis of gastric cancer, especially at its early stage and the poor prognosis of the tumor at the time of diagnosis, its prevention by eradication of H. pylori remains the mandatory strategy. On the other hand, the severity of regression and non-reversibility of precancerous lesions and intestinal metaplasia in gastric mucosa through eradication of H. pylori make it necessary to diagnose diffuse gastritis at its early stage. Increased serum pepsinogen II compared to normal serum pepsinogen I seems to indicate the presence of diffuse gastritis without precancerous lesions suitable for eradication of H. pylori infection, when it is serologically positive. A diagram illustrates the strategy of this therapeutic measure depending on the age of people and the level of serum biomarkers in areas with high gastric cancer prevalence.

Menopause is a critical phenomenon in women’s life. After cardiac diseases, menopause is the second major cause of living with a disability in 45–60 year old women. The majority of women will experience bothersome vasomotor symptoms (VMS). Menopausal hormone therapy (MHT) is the most effective treatment for these symptoms. The objective of this review is to focus on hormone therapy for relieving postmenopausal vasomotor symptoms.
For this systematic review, we primarily explored 125 papers published about hormone therapy for VMS from 2001 to 2015 by searching with combinations of the keywords in various databases. Among those, 59 papers met the initial search criteria and among them, 9 papers were potentially retrievable and reviewed. All included studies used estrogen formulations in the management of VMS.
Nine studies met all inclusion criteria. All studies assessed the effects of hormone replacement therapy on VSM. The results showed that low-dose oral and transdermal estrogen in all dose ranges were more likely than placebo to decrease the frequency of VMS. Indeed, the nanostructured formulation was safe and effective in relieving the symptoms of menopause. The mean daily decrease in the number of hot flashes from baseline was found in the studies.
MHT has a complex pattern. Understanding the natural history of VMS, and the risks and benefits of both hormonal therapies, helps to individualize management plans. Low-dose estrogen-based therapies can be the most effective regimens to relieve VMS. These medications can be used by different administration routes and formulations.

Leiomyoma is a benign smooth muscle tumor. Intra-venous extensions of these tumors occur due to tumor growth within uterine vein or lymphatic vessels. In rare cases, intracaval and intracardiac extension can also be seen. Clinical suspicion of this disease should become certain by use of imaging techniques. While the treatment is complete resection of the tumor, one or two-stage surgery can be planned for patient depending on tumor extension and patient’s condition. In this report, a 52-year-old woman with a rare presentation of uterine leiomyoma will be discussed. While the tumor was extended toward right atrium, the patient had nonspecific symptoms. By use of two-stage surgery, separated laparotomy and cardiopulmonary bypass, the tumor was completely removed.

Cytologic findings of pulmonary carcinoid have been well described. We report new cytological findings in a case of carcinoid tumor. The patient is a 36-year-old man presenting with hemoptysis of about six months in duration. Chest CT scans showed a well-defined round polypoid lesion measuring 1 × 1 cm within the right upper lobe of the bronchus with hyperinflation of the right upper lobe. Trans-bronchial fine needle aspiration and biopsy were done. Cytologic smears showed isolated and loose clusters of uniform round to spindle shape cells with round centrally located nuclei, fine granular (salt and pepper) chromatin and pale cytoplasm. Intranuclear pseudo-inclusions and grooves were seen in some tumor cells. No mitotic figures or necrosis were evident. A cytological diagnosis of carcinoid tumor was made and histopathologic examination and subsequent immunohistochemical study confirmed the diagnosis. Carcinoid tumor may be reliably diagnosed on fine needle aspiration cytology smears. Intranuclear pseudo-inclusions and grooves may be evident in tumor cells.

The history of leishmaniasis dates back to the distant past; however, its etiologic agent was unidentified until the mid-19th century. Here is an overview of some historical aspects of leishmaniasis in Iran mainly focused on the cutaneous form, from the mid-19th century onwards. In addition, short biographies of several contemporary researchers and experts of leishmaniasis and their achievements in the past decades are presented.