Association of HLA class II allele and haplotype frequencies with chronic myelogenous leukemia and age-at-onset of the disease.

Chronic myelogenous leukemia (CML) is characterized by the presence of Philadelphia chromosome resulting from bcr/abl translocation. To clarify the association between HLA class II allele and haplotype frequencies in CML, 50 patients referred to Hematology Oncology and Bone Marrow Transplantation (BMT) center, Shariaty Hospital, Tehran, Iran, were randomly selected and compared with a group of 80 unrelated healthy blood donor subjects. HLA class II alleles were determined by PCR-SSP method. The results showed that the frequencies of DQB1*03011 (P=0.01) and DQA1*0505 (P=0.05) were higher, while that of DQB1*03032 (P=0.04) was lower in patients than in the controls. Regarding age-at-onset, the frequency of HLA-DRB1*07 (P=0.03) and -DQA1*0201 (P=0.03) alleles were higher in patients younger than 35 years. The most frequent haplotypes in our CML patients were HLA-DRB1*11/-DQB1*03011/-DQA1*0505 (P=0.01) and HLA-DRB1*04/-DQB1*0302/-DQA1*03011 (P=0.02). In conclusion, it is suggested that positive and negative association in certain HLA alleles and haplotypes exist in Iranian patients with CML.

Tricyclic antidepressants intoxication in Tehran, Iran: epidemiology and associated factors.

BACKGROUND: Tricyclic antidepressant (TCA) intoxication contributes a large number of drug toxicities with serious complications. There are a few studies about factors associated with TCA intoxication. This study therefore aimed to identify determinants of this type of intoxication. METHODS: A cross-sectional study was carried out at Loghman-Hakim Poison Hospital during a 6-month period. All poisoned patients aged >12 years presented to this hospital during the mentioned period were evaluated. Then, TCA-poisoned patients were compared with other drug intoxications as the control group to determine factors associated with TCA intoxications. RESULTS: There were 9809 admissions, of which 1583 (16.1%) patients including 601 (38%) males were intoxicated with TCAs. Mean age of the subjects was 26.5 + 10 years. Most of the TCA intoxications (74.4%) were intentional (p = 0.01). Amitriptyline was the most frequent agent followed by Nortriptyline. There was no significant difference between TCA and non-TCA intoxications regarding the mortality (1.3% in TCA vs. 1.1% in others, p = 0.45). Logistic regression analysis revealed that sex, addiction status, and history of psychological problems have association with TCA intoxication. CONCLUSIONS: The results of this study are helpful in identifying individuals who are prone to TCA intoxication and may be useful in implementation of preventive strategies.

Evaluation of the effects of ischemic preconditioning with a short reperfusion phase on patients undergoing a coronary artery bypass graft.

PURPOSE: This study was conducted to evaluate the effects of ischemic preconditioning (IP) with a short period of reperfusion (2 min) during brief ischemic preconditioning (6 min) on patients undergoing coronary artery bypass grafting (CABG). METHODS: In a randomized controlled trial, 40 patients undergoing on-pump CABG with cold blood cardioplegia were allocated into two groups, one IP and one control. IP was induced by 2 cycles of ascending aorta clamping (2 min for each) followed by two reperfusion phases (1 min for each). Left ventricular ejection fraction (LVEF) was measured before and after surgery. Creatine phosphokinase (CK) and CK-MB were measured 12 hrs before surgery, immediately after aortic clamping, and 24 hrs after CABG. Postoperative myocardial infarction (MI), ventricular arrhythmia, duration of inotropic support, and hemodynamic parameters were also noted. RESULTS: More patients in the control group needed inotropic support (65% vs. 40%, P<0.05). Moreover, duration of inotropic support was longer in the control group (9 ± 1.2 vs. 3.8 ± 1.4 hrs, P<0.05). There were no significant differences between two groups regarding development of ventricular arrhythmia, MI, values of CK, CK-MB, and postoperative LVEF. No patient needed an intra-aortic balloon pump, and no deaths occurred. CONCLUSION: A short period of reperfusion phase declined post-CABG inotrope requirements; however, it did not reduce the cardiac enzymes. Our results suggested that reperfusion should be longer than 2 min to be capable of reducing cardiac enzymes.

Effect of milrinone on short-term outcome of patients with myocardial dysfunction undergoing coronary artery bypass graft: A randomized controlled trial.

BACKGROUND: Myocardial dysfunction needing inotropic support is a typical complication after on-pump cardiac surgery. In this study, we evaluate the effect of milrinone on patients with ventricular dysfunction undergoing coronary artery bypass graft (CABG). METHODS: Seventy patients with impaired left ventricular function [left ventricular ejection fraction (LVEF) < 35%] undergoing on-pump CABG were enrolled. Patients were randomized to receive either an intraoperative bolus of milrinone (50 microg/kg) or saline as placebo followed by a 24-hour infusion of each agent (0.5 microg/kg/min). Hemodynamic parameters and transthoracic echocardiographic measurement of systolic and diastolic functions were the variables evaluated. RESULTS: Serum levels of creatine phosphokinase (CPK), the MB isoenzyme of creatine kinase (CK-MB), occurrence of myocardial ischemia or infarction, and mean duration of using inotropic agents were significantly lower in the milrinone group (p < 0.05). There were no significant differences between the two groups regarding the development of ventricular arrhythmia, duration of cardiopulmonary bypass, intra-aortic balloon pump and inotropic support requirement, duration of mechanical ventilation, duration of intensive care unit stay and mortality rate. Although mean pre-operative LVEF was significantly lower in the milrinone group, there was no significant difference between post-operative LVEFs. CONCLUSIONS: We suggest that perioperative administration of milrinone in patients undergoing on-pump CABG, especially those with low LVEF, is beneficial.

Cytokine single nucleotide polymorphisms in Iranian populations.

Cytokines are important immunomodulatory molecules involved in immune responses against microorganisms; they also have an important role in the setting of immune system disorders. Cytokine single nucleotide polymorphisms have been extensively studied in different, normal populations as well as in association with disease. Cytokine gene polymorphisms are potentially important as genetic predictors of disease susceptibility, clinical outcome, and as a tool for anthropological studies. In this study, samples have been collected from 455 healthy individuals located in different regions of Iran (Tehran, Yazd, Sistan and Balochistan). Allele and genotype frequencies of cytokine SNP, including: IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-4RA, IL-6, IL-10, IL-12, TNF-alpha, TGF-beta and IFN-gamma were investigated, using the PCR-SSP method. Allele frequencies in Tehran and Yazd populations were similar, except for TGF-beta. Allele frequencies in Sistani & Baloch populations were similar at all positions, except for IL-1beta at position of -511 and IFN-gamma genes at position UTR5644; there were some differences in allele frequencies comparing these populations with the Yazd population, including: IL-4, IL-6, IL-10, TGF-beta and TNF-alpha. Although some significant differences were observed for some cytokines, it seems that the cytokine gene polymorphism profile of the Iranian population is similar to that of Caucasians, particularly the Italian population.

Association of HLA class II alleles with childhood asthma and Total IgE levels.

Asthma is a complex and multifactorial disorder. Several studies have reported association between different HLA- DQB1 and HLA- DRB1 alleles and allergic asthma. The aim of the present study was to investigate the association of HLA-class II alleles and haplotypes, with total serum IgE and the results of the skin prick test in Iranian children with allergic asthma. A total of 112 patients with allergic asthma symptoms (75 males and 37 females) were selected randomly from the pediatric hospital. In some patients total serum IgE and prick test were determined. Data of this study shows that HLA-DRB1*12 significantly increased in asthmatic patients (4.5% vs. 0%, P-value=0.04). HLA-DQB1*0603 and 0604 alleles were significantly higher in asthmatics than those in normal controls (10% vs. 0%, P-value= 0.0001; and 9.3% vs. 3.7%, P-value= 0.04, respectively). The statistical significance was relinquished after p value correction for all alleles except for HLA-DQB1*0602 (Pc=0.03) and HLA-DQB1*0603 (Pc=0.0015). Conversely, HLA-DQB1*0501 and 0602 were decreased in asthmatics compared to normal controls (7.5% vs. 13.5%, P-value= 0.05; and 4% vs. 12.5%, P-value= 0.002, respectively). The mean of total IgE in patients was 483 IU, and it was significantly high about 1140 IU in asthmatic patients with positive skin prick test to house dust. The most frequent alleles in asthmatic patients with the total IgE>200 IU/mL were HLA-DRB1*11and 1401, HLA-DQA1*0505, HLA-DQB1*0301 and in patients with total IgE<200 IU/mL were HLA-DRB1*0301, 07 and 1301, HLADQA1*0201 and 0301, HLA-DQB1*0201. These data suggests that HLA-DRB1, DQA1 & DQB1 alleles and haplotypes might be implicated in susceptibility to allergy and asthma and serum IgE production. As asthma and atopy are multifactorial disorders, probably HLA genes are involved in the regulation of immune specific responses to common allergen.

HLA class II allele and haplotype frequencies in Iranian patients with leukemia.

Previous studies demonstrated significant differences in a number of HLA allele frequencies in leukemia patients and normal subjects. In this study, we have analyzed HLA class II alleles and haplotypes in 110 leukemia patients (60 acute myelogenous leukemia "AML", 50 chronic myelogenous leukemia"CML") and 180 unrelated normal subjects. Blood samples were collected from all of the patients and control subjects. DNA was extracted by salting out method and HLA typing was performed using PCR-SSP method. Significant positive association with AML was obtained for HLA-DRB1*11allele (35% vs. 24.7%, P=0.033). Two alleles including HLA-DRB4 and -DQB1*0303 were significantly less frequent in AML patients than in controls. HLA-DQB1*0303 allele was never observed in CML patients compared with allele frequency in controls (4.2%). According to haplotype analysis, HLA-DRB1*0101/DQA1*0104/-DQB1*0501 frequencies were significantly higher and -DRB1*16/-DQA1*01021/-DQB1*0501 frequencies were significantly lower in CML patients than in controls. In conclusion it is suggested that HLA-DRB1*16 allele and HLA-DRB1*15/-DQA1*0103/-DQB1*06011 and -DRB1*16/-DQA1*01021/-DQB1*0501 haplotypes predispose individuals to AML and HLA-DRB4 allele predispose to CML. Future studies are needed to confirm these results and establish the role of these associations in AML and CML.

HLA class II allele and haplotype frequencies in iranian patients with acute myelogenous leukemia and control group.

Previous studies have demonstrated some significant differences in HLA allele frequencies in leukemic patients and normal subjects. We have analyzed HLA class II alleles and haplotypes in 60 Iranian patients with acute myelogenous leukemia (AML) and 180 unrelated normal subjects. Blood samples were collected after obtaining informed consents. From the patients and control DNA extraction and HLA typing were performed using PCR-SSP method. Significant positive association with the disease was found for HLA-DRB1*11 allele (35% vs. 24.7%, p=0.033). Two alleles including HLA-DRB4 and -DQB1*0303 were found to be significantly decreased in patients compared to controls. Regarding haplotype analysis, no significant association was found between case and control groups. It is suggested that HLA-DRB1*11 allele plays as a presumptive predisposing factor while the HLA-DRB4 and -DQB1*0303 alleles are suggested as protective genetic factors against acute myelogenous leukemia. Larger studies are needed to confirm and establish the role of these associations with acute myelogenous leukemia.