Increased serum heat shock protein 27 antibody titers and prooxidant-antioxidant balance in patients with beta-thalassemia major.

OBJECTIVE: Determination of the serum heat shock protein 27 (Hsp27) antibody titers and prooxidant-antioxidant balance (PAB) in patients with thalassemia as markers of cell and oxidative stress, respectively. METHODS: Serum PAB and anti-Hsp27 antibody titers were measured in 140 patients with thalassemia major and 140 sex- and age-matched healthy volunteers. RESULTS: A significantly higher serum PAB value was observed in patients in comparison to controls. In the patient group, anti-Hsp27 antibody titers were significantly higher than for the control group (p < 0.001). We found a weak negative correlation between anti-Hsp27 antibody concentrations and the PAB (p = 0.03), but these values were not correlated with serum superoxide dismutase activity in the thalassemic patients. CONCLUSIONS: Increased levels of serum PAB and Hsp27 antibodies may be involved in the pathological consequences of ß-thalassemia major and may contribute to the development of endothelial injury.

Risk factors associated with life-threatening infections in children with febrile neutropenia: a data mining approach.

PURPOSE: To determine risk factors (RFs) and their relationship with life-threatening infection (LTI) in children with febrile neutropenia (FN). METHOD: In this cross-sectional study, from December 2008 to November 2009, all children with FN admitted to Dr Sheikh Pediatric Hospital were enrolled. For each patient, demographic, clinical, and laboratory data were recorded and they were followed up for occurrence of LTI. RESULTS: One hundred and twenty episodes of FN in 68 patients were analyzed. The most common underlying disease was acute lymphoblastic leukemia (53.3%), 9 (7.5%) died from an infection and 35 patients (29.1%) had a LTI. Five variables were identified as RFs for LTI, that is, body temperature ≥39°C (P=0.000), presence of mucositis (P=0.000), abnormal chest x-ray (P=0.001), platelet count <20,000/mm (P=0.000), and absolute neutrophil count <100/mm (P=0.001). Risk of LTI was increasing according to number of RFs presented at the beginning of admission (from 2.8% in patients without RF to 100% in patients with 5 RF). Data mining analysis showed relationship between RFs with platelet count as the most important variable in the high-risk group for LTI. CONCLUSIONS: Evaluation of important RFs and judging the severity of patients' condition by studying the importance and relationship between RF at the time of admission can be a useful method for screening LTI in children with FN.

Prevalence of ß-Thalassemia Mutations among Northeastern Iranian Population and their Impacts on Hematological Indices and Application of Prenatal Diagnosis, a Seven-Years Study.

BACKGROUND AND OBJECTIVE: ß-thalassemia results from a diverse range of mutations inside the hemoglobin subunit ß (HBB) gene. In a study of ß-thalassemia carriers and some of their at-risk fetuses in the Khorasan province of Iran, we aimed to recognize the most common mutations in the region. We also investigated a possible link between these mutations and some of the relevant hematological indices. METHODS: Amplification-refractory mutation system-PCR (ARMS-PCR) was used to detect the typical HBB mutations among 1593 individuals, suspected of having a mutated HBB allele from March/2011 to January/2018. Sanger sequencing of HBB had been performed, where ARMS-PCR was uninformative. In some cases, reverse dot blot was utilized. Analysis of variance was used to compare parametric variables. RESULTS: Among 1273 ß-thalassemia carriers, the prevalence of the mutations were reported as follows: IVS-I-5 (42.03%), IVS-II-1 (11.23%), codons 8/9 (4.79%), codon 44 (4.56%), codon 15 (3.53%), Los Angeles (2.91%), codon 5 (2.75%), IVS-I-110 (2.51%), -88 (2.20%) and other mutations were less than 2% of all of the reported mutations. 644 conceptions were subjected to prenatal diagnosis, using chorionic villus sampling. 118 cases were reported as normal. 352 cases were detected as carriers. 174 cases were diagnosed as affected. There was a significant difference in mean corpuscular volume and hemoglobin A2 levels between the nine most commonly reported mutation types (p<0.001). CONCLUSION: This study makes a reliable guide for ß-thalassemia diagnosis in the region. The possibility of a correlation between HBB mutations and hematological indices opens a gate of future investigations.

Evaluation of Bone Mineral Density in Children with Acute Lymphoblastic Leukemia (ALL) and Non-Hodgkin's Lymphoma (NHL): Chemotherapy with/without Radiotherapy.

BACKGROUND: Acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) are the most common malignancies in children and adolescents. Therapies such as corticosteroids, cytotoxic and radiotherapy will have harmful effect on bone mineral density (BMD) which can lead to increased possibility of osteoporosis and pathological fractures. SUBJECTS AND METHODS: This 3-year cross-sectional study was performed in 50 children with ALL (n=25) and NHL (n=25) at Dr. Sheikh Children's Hospital in Mashhad. Half the patients received chemotherapy alone (n=25), while the other half received chemotherapy plus radiotherapy (n=25). We assessed them in the remission phase by DEXA bone mineral densitometry at the lumbar spine and femoral neck (hip). The survey results were adjusted in accordance with age, height, sex and Body Mass Index. Results : The mean age was 3.93± 8.28 years. There was no significant difference in bone biomarkers (Ca, P, ALP, PTH) among ALL, NHL and also the two treatment groups. Children with ALL had lower density at the hip and lumbar spine (p-value<0.001 and p-value=0.018, respectively). Among the total of 50 patients, 3 patients had normal results for detected hip BMD (6%), while 14 (28%) had osteopenia and 33 had osteoporosis (66%). Only one patient had normal BMD among all the patients who received chemotherapy plus radiotherapy, whereas 2 patients had normal BMD with just chemotherapy treatment. Conclusion : Given that 94% of our patients had abnormal bone density, it seems to be crucial to pay more attention to the metabolic status and BMD in children with cancer.

Effect of zinc supplementation on serum antibody titers to heat shock protein 27 in patients with thalassemia major.

Objective This current study was conducted to determine the effect of zinc supplementation on antibody titers to heat shock protein 27 (anti-HSP27) in patients with beta-thalassemia major (ß-TM). Methods This was a double-blinded placebo-controlled clinical trial conducted at Dr Sheikh Hospital (Mashhad, Iran) from 2011 to 2012. Sixty-four patients (41 females and 23 males), aged between 8 and 18 years with transfusion-dependent ß-TM were randomly allocated to two age- and sex-matched groups. The zinc (case) group received 30 mg of daily zinc sulfate supplementation and the placebo (control) group received same shape and color placebo over 9 months period of the trial. Serum anti-HSP27 titers were measured at the third and ninth months of the trial, using an in-house enzyme-linked immune-absorbent assay. Result There was a significant difference in anti-HSP27 titers, between the groups after 9 months. The baseline value of anti-HSP27 was 0.44 ± 0.15 in zinc group and were significantly decreased to 0.40 ± 0.18 after 9 months on treatment, while the baseline value of anti-HSP27 were significantly increased from 0.43 ± 0.17 to 0.44 ± 0.18 in the placebo group (P = 0.01). Conclusion Serum anti-HSP27 titers were significantly reduced in patients with ß-TM treated with zinc supplements compared to a group treated with a placebo. It suggests that the potential antioxidant and anti-inflammatory effects of zinc supplements may account for a reduction in anti-HSP27 titers in patients with ß-TM.

Circumcision in males with bleeding disorders.

INTRODUCTION: Male circumcision practice is an invasive procedure that is using worldwide. It makes challenges to haemostatic system and its possible haemorrhagic side effects are more serious in bleeding individuals than normal subjects. In most cases, it can be complete controlled using infusion of appropriate amount of coagulation factors before and post circumcision. AIM: We aim to documentation type of coagulation therapy and post circumcision practice haemorrhagic presentation among 463 bleeder males of both common and rare bleeding disorders in north eastern part of country. METHODS: We retrospectively gathered information using evaluation medical records in 3 major hospitals during last 15 years and list of patients with bleeding disorders that obtained from haemophilia center. Also a call phone established for each bleeder person to complete data and updating of them. The survey took time from Sep 2009 - Mar 2011. The designed question form included data on doing circumcision or not, types of treatment before and post the procedure and occurrence of bleeding episodes after the surgery. RESULTS: Overall among 424 cases with various common and rare bleeding disorders who had circumcised, 239 cases (56.3%) had passed the procedure with bleeding experience (indication of undiagnosed cases who underwent circumcision or inadequacy of coagulation therapy), while 185 cases (43.7%) had passed it successfully and without noticeable bleeding experience. The types of coagulation therapy in each group have been cited. CONCLUSION: The circumcision practice in unequipped medical center for bleeder ones may make challenges for them and medical services. Also it needed supervision of expert haematologist for.

An investigation of the spectrum of common and rare inherited coagulation disorders in north-eastern Iran.

BACKGROUND: Health care officials and legislators need accurate data on prevalence and numbers of individuals with bleeding disorders in order to plan and allot their budgets; the manufacturers of coagulation factors also need these data to estimate the amount of factors required to prevent scarcity of these products. MATERIALS AND METHODS: We surveyed the prevalence of haemophilia A, haemophilia B, von Willebrand's disease and rare bleeding disorders in North-Eastern Iran. The survey was done in the period from September 2009 to March 2011. Information was collected from the medical records in three major hospitals and a haemophilia centre; the patients' updated data were obtained by telephone. RESULTS: Overall in the current survey 552 patients with inherited coagulation disorders were identified and their medical records obtained. Of these, 429 (77.5%) had common bleeding disorders (haemophilia A, haemophilia B, von Willebrand's disease), 85 (15.6%) had rare bleeding disorders (deficiency of coagulation factors V, VII, X, XIII, I, XI, combined factor V and VIII deficiency) and 38 (6.9%) had platelet disorders.The commonest bleeding disorders were haemophilia A (n=287, 51.9%), haemophilia B (n=92, 16.6%), von Willebrand's disease (n=50, 9%), factor V deficiency (n=21, 3.8%), factor VII deficiency (n=19, 3.4%), factor X deficiency (n=2, 0.36%), combined factor V and VIII deficiency (n=28, 5.8%), factor XIII deficiency (n=11, 1.99%), factor XI deficiency (n=2, 0.4%), afibrinogenaemia (n=2, 0.36%) and platelet disorders (n=38, 6.9%). DISCUSSION: There is notable population of individuals with bleeding disorders in North-Eastern Iran.