[Carrier frequency of alpha thalassemia mutations among newborns in northern Iran]

Background and Objective: Alpha Thalassemia is one of the most prevalent hemaglobinophaties worldwide. Alpha thalasseima patients may represent wide spectrum of symptoms ranging from asymptomatic to severe life threatening anemia. This study was done to assess the carrier frequency of alpha globin gene mutations among newborns in north of Iran

Methods: In this descriptive study, 412 cord blood samples of neonate from Amir Mazandari hospitali were randomly selected during 2012. Genomic DNA was extracted using phenol-chloroform method. Multiplex Gap- PCR and PCR-RFLP methods were applied in order to detect three common gene deletions, one triplication and one point mutation

Results: Total allelic frequency of investigated mutations was 0.0825. The -alpha3.7 deletion with allelic frequency of 0.0485 was the most prevalent mutation among 412 neonates. Allelic frequencies of -alpha4.2, alphaalphaalphaanti3.7 triplication and alpha-5nt mutations were 0.0206, 0.0109 and 0.0024; respectively and -Med double gene deletion was not detected

Conclusion: Most mutated cases had single gene deletion that is asymptomatic while -Med double gene deletion was not detected among the neonates. Therefore, there is low probability of a child birth with Hb H disorder in the region

Beta globin gene haplotypes associated with hemoglobin D-Punjab in northern Iran

Background and Objective: Hemoglobin D-Punjab is one of the variant of hemoglobin caused by a mutation on position 121 of beta globin gene which is frequent in India, PakistanandIran. Heterozygote form of this variant is mainly asymptomatic while in combination with hemoglobin S, severe form of anemia occure. This study was carried out to determine the beta globin gene haplotypes associated with hemoglobin D-Punjab in Northern Iran. Methods: This descriptive study was carried out on families of 18 individuals whom were carriers of hemoglobin D-Punjab in Sari in Northern Iran. Genomic DNA was extracted from peripheral blood samples using Phenol-chloroform st and ard protocol. In order to identify different haplotypes associated with hemoglobin D-Punjab, PCR-RFLP method and family linkage analysis were used. Results: In 17 subjects hemoglobin D-Punjab was linked to [+ - - - - + +] haplotype and in one case association with [- + + - + + +] haplotype was observed. Conclusion: The hemoglobin D-Punjab alleles have mainly unicentric origin and [- + + - + + +] rare haplotype may have different genetic origin or is created as a result of gene recombination

[Comparison of fluorescent spot test, decolorization test and quantitative enzyme assay in detection of G6PD enzyme deficiency]

Background and Objective: The national screening program for G6PD enzyme deficiency is not able to detect all affected neonates. This study was done to compare the fluorescent spot test [FST], decolorization test, and quantitative enzyme assay [QEA] for detecting G6PD enzyme deficiency in neonates

Methods: In this descriptive study, cord blood samples of 365 neonates were collected. Decolorization test, QEA and DNA test was done for each sample. All of the neonates were tested by FST as a part of national screening program on heel-prick blood sample collected on day 3-5 after birth. QEA was considered as the gold standard. According to QEA test results, neonates with <20% and 20-60% of mean normal enzyme activity were considered as total deficient and partial deficient, respectively

Results: Fluorescent spot test detected 13 male neonates with G6PD enzyme deficiency while decolorization test identified 18 male and 1 female neonates. Using QEA, 19 of male and 28 of female neonates with G6PD enzyme deficiency [26 cases with partial and 2 cases with total deficiency] were diagnosed. DNA analysis detected 34 female case as heterozygote and 14 male neonates as hemizygote for the disease

Conclusion: Fluorescent spot test do not have required sensitivity for screening of neonates with G6PD enzyme deficiency. QEA test is recommended to replace the fluorescent spot test in national screening program

[Prevalence of alloimmunization in major beta thalassemia in northern Iran [2010]]

Repeated blood transfusion is the major treatment for patients with major thalassemia. However due to antigen encounters, it may initiate body reactions, including alloantibodies against red blood cell antigens. This study was done to determine the Prevalence of alloimmunization in major beta thalassemia patients in northern Iran. This descriptive - analytic study was carried out on 218 thalassemic patients [100 males and 118 females] with average age of 22.5 +/- 7 years in northern Iran during 2010. Each sample was tested for the presence of Alloantibodies including C, Cw, Lea, E, Lua, Leb, K, Jkb, N, P1, D, Jka, M, S, Xga, e, Fya, s, c, Fyb, k, Kpa, Jsb, Lub and Coa. Eighty eight cases [40.4%; 95% CI: 33.9-46.9] were positive for the presence of alloantibodies. Alloantibodies against C, Cw, Lea red blood cell surface antigens were the most prevalent [40%]. No significant correlation was found between emergence of alloantibody with the age of initial, frequency and duration of blood transfusion. Alloimmunization is a common observation in thalassemic patients and should be prevented by transfusing compatible blood

Diagnostic value of fructosamine and glycosylated hemoglobin in estimating blood glucose level in diabetic patients with thalassemia major

Diabetes mellitus is one of complications that thalassemia major patients face with. Hence, blood glucose monitoring is of vital importance to these patients. Because of high level of fetal hemoglobin in these patients, the measurement of hemoglobin AI[c] is not reliable and should be displaced by fructosamine test. The current descriptive study was carried out on 33 beta-thalassemia major patients afflicted with diabetes mellitus [21 female and 12 male cases]. Blood glucose level, fructosamine, hemoglobin AI[C], serum ferritin and fetal hemoglobin were measured. Blood glucose levels are 204 +/- 103 mg/dL and 221 +/- 101 mg/dL [p=0.63]; fetal hemoglobin levels are 9% +/- 7% and 13% +/- 9% [p=0.22]; serum ferritin levels are 1744 +/- 1534 ng/mL and 3253 +/- 1773 ng/mL [p=0.96] in female and male patients, respectively. The level of fructosamine [42 +/- 124 mmol/L] and glycosylated hemoglobin [8.9% +/- 1.8%] are correlated significantly [r=0.69, p<0.01]. Both Hemoglobin A[1c] [r=0.75, p<0.01] and fructosamine [r=0.54, p<0/01] show a significant correlation with blood glucose level. In diabetic thalassemia major patients with frequent blood transfusion, the level of fructosamine and glycosylated hemoglobin are related significantly, therefore; they can be used alternatively

[ effect of hudroxyurea on extramedullary hematopoietic masses in patients with beta-thalassemia intermediate]

Since the need for transfusions in thalassemia intermediate [TI] patients is limited into some rare occasions they are almost always referred complaining of problems due to chronic anemia, bone marrow hyper-functioning [such as gall stones, osteoporosis] and also extramedullary hematopoiesis masses [EHM]. Different treatment modalities have been reported for managing the latter complication. We carried out this study to evaluating the effects of Hydroxyurea in reducing the size of such masses. The study was clinical trial comparing before and after characteristics of the patients referred to the Talassemia Research center from 2003 to 2006. Presentation of all was pain, weakness, paresthesia of legs and paraparesia/paraplegia. Diagnosis of EHM was confirmed by Spinal MRI [a 1.5 Tesla, Toshiba machine]. Hydroxiurea [Syrea, Medac, Germany] was administered 10-20 mg/kg/day. CBC, Urea, Creatinin were checked monthly. A Neurologist was observing the progression of patients. The second MRI was performed 3-6 months later. Another radiologist unaware of the sequence of imaging reported the changes of EHM during the period. Paired-t test and McNemar test were applied to compare the results. P< 0.05 was considered as statistically significant. Eight patients [7 males and 1 female] were enrolled in our study. Their age ranged from 26-44 years old. None had undergone transfusion, nor had they used pain killers. Neurologic symptoms were initiated from one week to a couple of months prior to their admission. They had administered Hydroxyurea in recommended dosage. The follow up takes 0.7 - 4.7 years. All subjects improved within 2 weeks, whereas none of them needed surgical procedures and radiotherapy. Both the MCV and NRBC changes were significant [P<0.02]. No considerable side-effects were noticed within the follow up period. HU is proved to be both effective and safe in treatment of EHM amongst patients with thalassemia intermediate who develop neurological symptoms. We suggest hydroxyurea as a "prophylactic agent" for several complications of TI

[Screening of developmental problem, day care centers, Sari, 2006]

There has not been enough attention towards the domains of development in pediatrics,so there are many deficiencies in monitoring the achievement of developmental milestones in our country. One of the important ways for the improvement of this problem is to use screening method. PEDS questionnaire is one of the screening tools for development. The aim of this study was to investigate about parents' evaluation of developmental status for their children. This was a cross-sectional descriptive study. The population included infants and children under the age of 6 in day care centers of Sari. Sampling method was clustering. The tool for data collection was PEDS questionnaire [Parents' Evaluation of Developmental Status] which consisted of 38 questions about demographic data and medical history of children as well as parents' concern about different developmental domains along with "Yes", "No" and "little" answers. The data were analysed using SPSS11 software. Chi square and Wilcoxon were used. P<0.05 was considered significant. Out of 829 questionnaires, 736 were returned [88.7%]. The Sample age was 4.23 +/- 1.32 gl. Fifty percent of participants were male. By average, in each developmental domains, 3.2% of parents had major concern and 9.5% had partial concern. The most common domains of concern were communication with others [6.4%], behavior [6.1%], speaking [4.3%], preschool and school education [3.1%], children's understanding [2.5%], the self care [2.1%], the use of fingers [1.4%], the use of legs and arms [1.1%]. Parents' concern had a significant relationship with parent's education, residence and history of illness in children [P<0.05]. Out of 23.4% of the infants and children who had later returned to the diagnosis center, 80% had behavioral disorder, 87.6% had speech disorder and 16.6% had hearing impairment. A considerable percentage of parents was concerned about developmental domains of their children, but follow up at referral centers was low. Parents' concern led to the diagnosis of an illness for a child in most cases

[Comparison between the results of academic staff self assessment and those made by the students, faculty of medicine, Mazandaran university of medical sciences, 2006]

Educational evaluation is a structured process for determination of quality and effectiveness and an educational program. Of the most common and studied methods used for evaluation of academic staff is evaluation by students, however, "self-assessment" of the academic staff has not been widely used and there are few studies about it. So the purpose of this study was to assess the correlation between the results of the academic staff "self assessment" and assessment by the students. This study was an analysis of correlation. Study population was clinical faculty members of Mazandaran University of Medical Sciences, recruited by simple sampling method. Tool of data collection was a questionnaire consisted of demographic and educational variables and questions about evaluation of theoretical and clinical teaching of member of staff. Validity and reliability of the questionnaire were approved. Each faculty member was assessed by students and themselves and correlation between them was analysed using SPSS 13. Totally 35 member of staff participated in self assessment, with a mean age of 43.7 +/- 7.46 years, 73% male. 95.6% of the staff and only 80.6% of the students have positive attitude toward assessment of the staff by students [p<0.001]. Not only there was a weak correlation between the results of staff "self assessment" and their assessment by students [r=0.020, r=0/125] but also there was a significant difference between them [p<0.001]. Difference between these measures was higher in minor teaching departments. There was a weak correlation between measures of members of staff "self assessment" and their assessment by students, so educational intervention, for improvement of competency for "self assessment" should be designed and implemented

Assessment of the effect of combination therapy with deferiprone and desferrioxamine on cardiac complications in major thalassemia

Cardiac complications in major thalassemia are the most debilitating problem among them. Iron chelating with desferrioxamine, may be difficult or inadequate. The aim of this research is to evaluate the effect of combination therapy with the two drugs "deferiprone and desferrioxamine" on cardiac complications in major thalassemia. In a clinical trial study [before and after], 47 [24 men and 23 women] patients with major thalassemia referred to Booali research center, 10 to 35 years old, all of whom were undertaken combination therapy with deferiprone and desferrioxamine, enrolled in this study. Echocardiography was performed for all patients before and after at least 6 months of combination therapy. Echocardiographic systolic and diastolic function indices including LVEF, EPSS, CI and E/A, EF slope and MPI, as well as presence of arrhythmia were obtained. The data were analyzed by paired T Test and Pearson correlation. There were significant changes in ferritin, systolic function and MPI, indicating statistically significant improvement. Ferritin decreased to 3306 +/- 1347ng/ml from 4489 +/- 1607ng/ml [p=0.000]. LVEF increased to 69.7 +/- 2.6% from 67.6 +/- 3.9% [p=0.04]. EPSS decreased to 2.9 +/- 1.3mm from 3.9 +/- 2.1mm [p=0.004]. Cardiac Index increased to 3.6 +/- 0.18 from 3.5 +/- 0.3 [p=0.02]. MPI decreased to 0.33 +/- 0.05 from 0.37 +/- 0.06 [p=0.03]. Arrhythmia and diastolic function were also slightly improved which were statistically nonsignificant. The results showed that combination therapy with the two drugs deferiprone and desferrioxamine led to decrease ferritin level and improve systolic function in patients with major thalassemia

Relationship between use of hydroxyurea and cholelithiasis in patients with major and intermediate beta-thalassemia

Cholelithiasis is a common problem among patients with homozygous major and intermediate beta-thalassemia due to chronic hemolysis, ineffective erythropoesis and other factors that causes variety of side effects. Hydroxyurea [HU] decreases hemolysis by increasing HbF production in homozygous beta-thalassemia patients. Up to now, there have not been evidences about relationship between use of Hydroxyurea and cholelithiasis in the patients. The aim of this study was to determine the relationship between use of HU and incidence of cholelithiasis in patients with major and intermediate beta-thalassemia referred to thalassemia research center of Mazandaran University of medical sciences at Boo-Ali Sina hospital of Sari, IRAN. This historical cohort study was performed in 2006. Study population was major and intermediate beta-thalassemia patients referred to Boo-Ali Sina Hospital of Sari, IRAN. The patients were divided to two groups: case and control groups. The case group [36 patients] was consisted of major or intermediate beta -thalassemia patients using hydroxyurea at least for one year, and the control group were: non-hydroxyurea user patients or beginning to use the drug less than 3 months. The groups were matched on order to age, gender and severity of the disease. Severity of the disease was determined according to grading, clinical and laboratory characteristics of the patients. Data about demographic information, severity of the disease and results of hepatobiliary ultrasound were recorded in a questionnaire. The data was analyzed using SPSS [11] software and t-test, Chi-square test and fisher exact test. Thirty-six [20 women [55.6%]] patients in case group and 36 [19 women [52.8%]] patients in control group were studied. The mean duration of use of hydroxyurea was 67.9 +/- 25.5 months with maximum 108 months [9 year]. The mean dosage of the drug was 14.9 +/- 5.9 mg/kg with maximum dosage 34 mg/kg. Thirteen [48.1%] patients in control group [12 cholelithiasis, 1 sludge] and 6 [19.4%] patients in case group [5 cholelithiasis, 1 sludge] had abnormal hepatobiliary sonography. The difference between two groups was significant statistically [P<0.02]. Among the different variables, a significant relationship was detected between gender of the patients and effect of HU on cholelithiasis. This study showed that the incidence of cholelithiasis in major and intermediate beta-thalassemia patients using hydroxyurea was less than non-hydroxyurea user patients did. As a result, it seems that there was a preventive effect of hydroxyurea in incidence of cholelithiasis in major and intermediate beta-thalassemia patients

Survey on relation between major thalassemia and desferiexamine with renal tubular damage

Thalassemia is a hereditary quantitative hemoglubinopathy which is common in mediteranian area including IRAN. Homos zygotic beta thalassemia patients suffer from severe anemia and complication of the disease in many organs. Studies have shown different results about renal complication and disease. Thus, in this study we investigated renal function of thalassemia Major [TM] patients in comparison with control group. This was a historical cohort Study. The population who TM patients was were admitted to Boalisina hospital, Sari, and control group were brothers and sisters of the patients who were matched in gender and age. Serum and urine markers of renal function were measured and demographic and therapeutic data were gathered from medical records. Analysis of the data was performed using SPSS 11 with statistical test [t, chi square]. The Total of 84 [42 patients and, 42 controls] patients were studied. The Mean age of the patients was 21.3 +/- 5.2 years. Dose of Deferral was 70 +/- 19 mg/kg. The results showed no significant statistical differences in levels of beta2 microglobulin, 24 urine protein, Excretion Fraction of Na and K between case and control group. There was significant differences in levels of serum BUN, creatinin, Potassium and urine potassium and creatinin between case and control group. Gender, level of Hb and serum Ferritin significantly affected the differences between two groups. In this study, evidences of renal tubular damage were not detected in TM patients. There was increase in levels of Bun, serum potassium, uric Acid, specially with severe anemia, high dose desferal and Iron over load