H63D mutation of the hemochromatosis gene and serum ferritin levels in Thai thalassemia carriers

We determined the prevalence of the H63D and the IVS5#1G-A HFE mutations in 370 (169 males and 201 females) Thai thalassemia carriers and 201 normal subjects. While no IVS5#1G-A mutation was found, the H63D heterozygosity was identified in 5.5% (11/201) of normal subjects and 7.3% (27/370) of thalassemia carriers. Within the thalassemic group, the medians (ranges) of serum ferritin were 217.5 ng/ml (20.1-424.3) and 169.8 ng/ml (3.9-3,536.0) in male subjects and 30.4 ng/ml (11.9-130.7) and 49.3 ng/ml (0.6-931.0) in female subjects with (HD) and without (HH) H63D mutation, respectively. The proportions of subjects with elevated ferritin were found to be 37.5% (6/16) for HD and 14.0% (18/129) for HH in male and 0% (0/11) for HD and 3.0% (5/164) for HH in female subjects, respectively. Statistical analysis of all the data revealed no significant difference. Among 14 Hb E/beta-thalassemia patients, no difference in hematological data as well as serum ferritin levels was observed between those with (HD) and without (HH) H63D mutation. Therefore, the H63D heterozygosity has no significant effect on the serum ferritin level and screening for this HFE mutation in thalassemic patients is not recommended.     

Pulmonary Arterial Hypertension in Previously Splenectomized Patients with β-Thalassemic Disorders

Our aim was to study the cause and describe the clinical features of pulmonary arterial hypertension (PHT) in splenectomized beta-thalassemia (beta-Thal) patients. Ten splenectomized beta-Thal patients with systolic pulmonary artery (PA) pressure >30 mm Hg were evaluated by echocardiography, right-heart catheterization, and pulmonary angiography. Five of these patients later underwent hemodynamic studies. Echocardiography and pulmonary angiography on the 10 patients showed normal values of left ventricular systolic function and no findings of acute or chronic pulmonary embolism. Hemodynamic evaluation showed very high PA pressures associated with markedly increased pulmonary vascular resistance indices (PVRIs). Hematological evaluation of the 10 patients showed marked anemia, markedly increased numbers of nucleated red blood cells (nRBCs), and serum ferritin. Mean platelet count, plasma beta2 thromboglobulin, and thrombin-antithrombin III complex levels were significantly increased. It was concluded that PHT can be found in splenectomized beta-Thal patients. Features associated with PHT were female sex, hemoglobin E/beta-Thal, status many years postsplenectomy, marked anemia, markedly increased nRBC count, thrombocytosis, and very high serum ferritin levels. PHT was not due to pulmonary emboli. Our findings suggested that severe PHT was due to increased PVRI from thrombotic pulmonary arteriopathy, likely from chronic low-grade hypercoagulability and platelet activation after splenectomy.     

Oxidative stress,insulin resistance,dyslipidemia and type 2 diabetes mellitus

Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus(T2DM) and this appears to underlie the development of cardiovascular disease,T2 DM and diabetic complications.Increased oxidative stress appears to be a deleterious factor leading toinsulin resistance,dyslipidemia,β-cell dysfunction,impaired glucose tolerance and ultimately leading to T2 DM.Chronic oxidative stress,hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant,have high oxidative energy requirements,decrease the gene expression of key β-cell genes and induce cell death.If β-cell functioning is impaired,it results in an under production of insulin,impairs glucose stimulated insulin secretion,fasting hyperglycemia and eventually the development of T2 DM.     

Evaluation of health education in the Multi-professional Intervention and Training for Ongoing Volunteer-based Community Health Programme in the north-east of Thailand

This was a survey research conducted in Northestern Thailand during 2009-2010 and designed to evaluate the success of a health education program by comparing levels of health knowledge in the community before and after the launching of a Multi-professional Intervention and Training for Ongoing Volunteer-based Community Health Programme. The survey questionnaire included items about demographic characteristics and health knowledge. The participants were 1,015 members of various communities, who were randomly selected to be included in the survey before launching the intervention, and 1,030 members of the same communities randomly selected to be included in the survey after the intervention was completed. The demographic characteristics of both groups were similar. Overall knowledge and knowledge of all the diseases, except lung and cervical cancer, were significantly higher after the intervention. In conclusion, a Volunteer-based Community Health Programme has advantages for areas where the numbers of health personnel are limited. The use of trained community health volunteers may be one of the best sustainable alternative means for the transfer of health knowledge.     

Risk Factors for Colon Cancer in Northeastern Thailand: Interaction of MTHFR Codon 677 and 1298 Genotypes with Environmental Factors

Background

Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), such as MTHFR C677T and A1298C, are associated with several cancers. This study aimed to evaluate the effects of MTHFR polymorphisms on colon cancer risk and possible interactions with environmental factors in a population from northeastern Thailand.

Methods

This hospital-based case–control study was conducted during 2002–2006; 130 colon cancer cases and 130 age- and sex-matched controls were enrolled. Information was collected and blood samples were obtained for assay of MTHFR C677T and A1298C polymorphisms by polymerase chain reaction with restriction fragment length polymorphism techniques. Associations between variables of interest and colon cancer were assessed using conditional logistic regression.

Results

Increased risk of colon cancer was associated with alcohol consumption and bowel habits. Alcohol drinkers who consumed ≤0.50 or >0.50 units of alcohol per day had elevated risks (OR_adj = 3.5; 95% CI: 1.19–10.25 and OR_adj = 1.71; 95% CI: 0.74–3.96, respectively). The risk was also higher in subjects with frequent constipation (11.69; 2.18–62.79) and occasional constipation (3.43; 1.72–6.82). An interaction was observed between the MTHFR C677T polymorphism and freshwater fish consumption on colon cancer risk (P value for interaction = 0.031). Interactions were observed between the MTHFR A1298C polymorphism and bowel habits, family history of cancer, alcohol consumption, and beef consumption on colon cancer risk (P-value for interaction = 0.0005, 0.007, 0.067, 0.003, respectively).

Conclusions

In a Thai population, colon cancer risk was associated with alcohol and beef consumption, bowel habits, and family history of cancer. Interactions between MTHFR polymorphisms and environmental factors were also observed.Key words: colon cancer, MTHFR, polymorphism, environmental factors, Thailand     

Risk factors for colorectal cancer in northeast Thailand: lifestyle related.

Background: The incidence of colorectal cancer is variable around the world. Hiroshima, Japan had the highest incidence in men in 1997 with an age-standardized rate of 86.7 per 100,000 and New Zealand had the highest, at 40.6 per 100,000, in women. The incidence of colorectal cancer in Thailand is rather low and the latest figures for Northeast of Thailand are 7.1 per 100,000 for men and 4.7 for women. The reasons for these differences between countries are possibly due to variation in dietary habits, alcohol drinking or other cofactors. Methods: A case-control study was conducted in Khon Kaen, Northeast Thailand during 2002-2006 to study risk factors for colorectal cancer in a low risk area. Totals of 253 colorectal cancer cases (males 135, females 118) and 253 age- and sex-matched controls were recruited. Information on dietary habits, alcohol drinking, smoking and other information were collected by a structured questionnaire. Blood samples were collected for further study. Both univariate and multivariate analyses were carried out. Results: In the final model of multivariate analysis, the significant risk factors for colorectal cancer were a family history of cancer (OR=1.9 95%CI=1.2-2.9) and meat consumption (OR=1.0 95%CI=1.0007-1.0026). For BMI, subjects with higher BMI unexpectedly had a lower risk of colorectal cancer (OR=0.5 95%CI=0.3-0.8). Conclusion: Our study confirmed risk factors for colorectal cancer i.e. meat consumption and cancer in the family (genetic problem). However, the results for BMI are the reverse of expected, underlining one limitation of hospital-based case-control studies, in which cases are ill and admitted to the hospital at late stage.     

Development of severe anemia during fever episodes in patients with hemoglobin E trait and hemoglobin H disease combinations

Globin chain imbalance and tissue hypoxia are important determinants of the clinical severity of thalassemias. Phenotypic expression may be further modified by interactions between alpha- and beta-thalassemia defects. We retrospectively and prospectively studied the clinical and hematologic features in children and adults with hemoglobin (Hb) E trait/Hb H disease (SEA/Paksé) (seven cases) and Hb E trait/Hb H disease (SEA/Constant Spring) (29 cases) and found that they had similar presentations. The severity of these two intermediate thalassemic manifestations ranged from very mild to severe. Severe anemia developed in accordance with very high fever, whereupon the range of Hb and hematocrit (Hct) levels declined to 5.2-5.8 g/dL and 13%-19%, respectively. In one case, during a hemoconcentrated state as occurs in dengue hemorrhagic fever, the Hb and Hct were 10 g/dL and 31%; the latter rose to 35% after fluid therapy. In some patients, the range of Hb and Hct levels was constantly low (4.3-5.8 g/dL and 15%-19%, respectively). (If dengue hemorrhagic fever is misdiagnosed, a fatal outcome may occur for thalassemic patients.) After a hemodiluted condition as in acute post-streptococcal glomerulonephritis, the respective Hb and Hct were 5.4 g/dL and 19%. These observations suggest that the instability of Hb E, especially during fever, may play an important role in the clinical manifestations of Hb E trait/Hb H disease with Hb Paksé and with Hb Constant Spring.     

Recombinant activated factor VII combined with local measures in preventing bleeding from invasive dental procedures in patients with Glanzmann thrombasthenia.

Recombinant activated factor VII (rFVIIa), combined with local measures of fibrin glue and a celluloid splint, preventing bleeding from four invasive dental procedures is reported. A single dose of 180-200 micro g/kg was successfully used in three surgical removals of impacted teeth. Four doses of rFVIIa were required in another full mouth treatment of extraction, pulpotomy, filling and the stainless steel crowning of 13 teeth. The repeated dose of rFVIIa was given whenever the bleeding complication was visualized. It is cost-effective for preventing external bleeding. Additionally, an oral rinsing solution of tranexamic acid (25 mg/kg) was given three times a day for 7 days. In conclusion, rFVIIa has been shown to be an effective alternative to platelet concentrate in patients with Glanzmann thrombasthenia.     

Effect of Amino Acid Polymorphisms of House Dust Mite Der p 2 Variants on Allergic Sensitization

Purpose

The sequence variations of the Der p 2 allergen of Dermatophagoides pteronyssinus diverge along 2 pathways with particular amino acid substitutions at positions 40,47,111, and 114. The environmental prevalence and IgE binding to Der p 2 variants differ among regions. To compare IgE binding to Der p 2 variants between sera from Bangkok, Thailand and Perth, Western Australia with different variants and to determine the variant-specificity of antibodies induced by vaccination with recombinant variants.

Methods

The structures of recombinant variants produced in yeast were compared by circular dichroism and 1-anilinonaphthalene 8-sulfonic acid staining of their lipid-binding cavity. Sera from subjects in Bangkok and Perth where different variants are found were compared by the affinity (IC₅₀) of IgE cross-reactivity to different variants and by direct IgE binding. Mice were immunized with the variants Der p 2.0101 and Der p 2.0110, and their IgG binding to Der p 2.0103, 2.0104, and 2.0109 was measured.

Results

The secondary structures of the recombinant variants resembled the natural allergen but with differences in ANS binding. The IC₅₀ of Der p 2.0101 required 7-fold higher concentrations to inhibit IgE binding to the high-IgE-binding Der p 2.0104 than for homologous inhibition in sera from Bangkok where it is absent, while in sera from Perth that have both variants the IC₅₀ was the same and low. Reciprocal results were obtained for Der p 2.0110 not found in Perth. Direct binding revealed that Der p 2.0104 was best for detecting IgE in both regions, followed by Der p 2.0101 with binding to other variants showing larger differences. Mouse anti-Der p 2.0101 antibodies had a high affinity of cross-reactivity but bound poorly to other variants.

Conclusions

The affinity of IgE antibody cross-reactivity, the direct IgE binding, and the specificities of antibodies induced by vaccination show that measures of allergic sensitization and therapeutic strategies could be optimized with knowledge of Der p 2 variants.