Human genomics: implications for health.

Human genome research which tries to map and sequence all the 3 billion nucleotides in the entire DNA is progressing rapidly. Completion of the human genome sequencing is expected before the year 2005. Human genes, totalling 50,000-100,000, will be identified, allowing the complete set of proteins--'the proteome' to be known. This together with genomic research in other species will lead to complete understanding of life at the molecular level and also its evolutionary history of 3,500 million years. Genomics will bring about a revolution in biology and health, because it is equivalent to having a 'Biological Periodic Table' which is a foundation for understanding life, health, disease and for deriving of new tools for diagnosis, treatment, prognosis and prevention. Human genomics will give rise to Predictive--Preventive Medicine and Precision Medicine. It will have profound social implications. Preparation for the future is needed for societies to cope with and make proper use of the tremendous changes to be brought about by genomics.

The molecular basis of alpha-thalassemia in Thailand.

Alpha thalassemia is the most common single gene mutation worldwide. In Thailand there exists 15-30% alpha-thalassemia carriers distributed throughout the country. DNA analysis by Southern blot hybridization reveals that the two major alpha-thalassemia alleles, alpha-thalassemia 1 and alpha-thalassemia 2 have different extents of alpha-globin gene deletion. In alpha-thalassemia 1, approximately 20 kb of DNA including the two linked alpha 1-and alpha 2-genes are removed and only the alpha-globin gene is intact. Total deletion of the alpha-globin gene cluster is rarely observed. In contrast, only one alpha-globin gene is deleted in alpha-thalassemia 2 of which two types have been detected, one involving a deletion of 4.2 kb of DNA (leftward type, -alpha 4.2) and another of 3.7 kb (rightward type, -alpha 3.7); the latter being more common than the former in Thailand. Compound heterozygosity for alpha-thalassemia 1 and alpha-thalassemia 2 results in HbH disease while homozygosity for alpha-thalassemia 1 leads to Hb Bart's hydrops fetalis, the most severe form of thalassemic disease. Three alpha-thalassemic hemoglobinopathies have been detected in Thailand, two of which produce a remarkable reduction in gene product. Upon interacting with alpha-thalassemia 1 gene they can lead to HbH disease. The most common in this group is Hb Constant Spring which arises from mutation of the termination codon in the alpha 2-gene resulting in an elongation of the alpha-globin chain.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis of hypoxemia.

Thrombocytosis and morphological changes in shape and size of circulating platelets are commonly found in splenectomized thalassemia patients. Functional abnormalities of the platelets are evidently related to their fragile nature. Spontaneous aggregation of platelets can easily occur following application of mild pressure either from a stirring magnetic bar or due to centrifugal force. Platelets are hyper-reactive to chemical stimulation and the release of platelet granule contents (eg ATP) together with other membranous lipid metabolites, thromboxane A2 and malondialdehyde is markedly enhanced. The lipid soluble antioxidant, vitamin E is depleted from various blood compartments. The findings suggest that circulating platelets in splenectomized thalassemia are continuously attacked by yet to be identified blood borne factor(s) and the defective platelets could play a pivotal role in the pathogenesis of hypoxemia.

Hypoxemia in thalassemia.

Data are reviewed describing hypoxemia, a newly identified feature in thalassemia. Evidence indicates platelet aggregation in the pulmonary circulation as being a key factor leading to hypoxemia and cor-pulmonale with right heart failure.

Clinical assessment of the efficacy and tolerance of zingiber cassumunar roxb in bronchial asthma.

An open study was carried out on 22 individuals with a moderate degree of assess the prophylactic efficacy and tolerance of Zingiber cassumunar Roxb. The group consisted of 8 men and 16 women, aged 19-64 years (mean age 44.1 years). After six weeks of basal assessment, all subjects received oral Zingiber cassumunar Roxb, at a dosage of 500 mg. per day for body weight of 50 kg. or under, 750 mg. per day for body weight between 50-55 kg. and 1,000 mg. if over 55 kg. The drug was given orally twice daily for 16 weeks. Examination of the patients was made before starting the treatment and after on the 2nd, 4th, 6th, 10th, 14th, 18th, 22nd week, respectively. Monitoring of the following parameters was performed: patient’s symptoms, ventilatory function, and consumption of antiasthmatic drugs. Zingiber cassumunar Roxb, was found to provide a significant protection against asthmatic attacks in 19 out of 22 cases (86.4%). Statistically significant reduction in asthmatic symptoms as well as the reduction in the use of bronchodilators and steroids were noted between 1-3 and 2-4 months after treatment respectively. Statistically significant improvement in peak expiratory flow rate and FEV1 were also noted in the second month of treatment. Slightly increased frequency in bowel movement was noted in 5 patients and one patient complained of mild headache.

Cardiac pathology in 47 patients with beta thalassaemia/haemoglobin E.

Autopsy protocols and heart slides of 47 patients with beta thalassaemia/haemoglobin E disease were reviewed. All but 1 patient had cardiac hypertrophy, accompanied by dilatation in 17; 5 of 9 patients (56%) with right ventricular and 11 of 22 patients (50%) with biventricular hypertrophy had chronic pulmonary thromboembolism. Cardiac iron deposition while present in 15 patients (32%) was very slight, in contrast to the amount of iron in their liver and pancreas. Four patients had fibrinous pericarditis, 2 with rheumatic heart disease. Twelve patients had chronic pericardial changes, 7 with adhesive pericarditis. The effects of cardiac pathology on the morbidity and mortality of patients with beta thalassaemia/haemoglobin E disease were discussed.

Heterogeneity of beta thalassaemia in Thailand.

Beta thalassaemia in Thailand is heterogeneous. Clinical, genetical, haematological and globin chain biosynthetic studies were performed in seven beta-thalassaemia families. The results showed different gene combinations. These were alpha-thalassaemia/homozygous beta 0-thalassaemia, questionable double heterozygosity between a beta-thalassaemia and a silent beta-thalassaemia genes with low Hb F of unexplained cause, silent beta-thalassaemia/beta+ - or beta 0-thalassaemia, high Hb A2 high Hb F-beta-thalassaemia - a new mutant, mild beta+-thalassaemia/Hb E, and beta 0-thalassaemia/heterocellular HPFH or delta beta-thalassaemia associated with alpha-thalassaemia. Most of variability of clinical and haematological findings in these families is due to heterogeneity of the beta-thalassaemia and related genes.

Increased circulating platelet aggregates in thalassaemia.

Examination for circulating platelet aggregates according to Wu and Hoak revealed increased circulating platelet aggregates in 71% of splenectomized and 35% of nonsplenectomized patients with beta (0)-thalassaemia/Hb E disease. This may be causally related to the newly observed high incidences of pulmonary artery thrombosis and hypoxaemia in splenectomized thalassaemic patients. It is recommended that anti-platelet aggregation drugs such as aspirin and/or dipyridamole are given to thalassaemic patients after splenectomy.

Hypoxaemia and the effect of aspirin in thalassaemia.

Blood gas analysis of arterial blood was performed in 34 patients with beta o-thalassaemia/haemoglobin E disease and homozygous beta o-thalassaemia. Among the 22 splenectomised patients 19 had PaO2 lower than the normal expected value, and 18 of these had PaO2 lower than 80 mmHg. Of the 12 non-splenectomised patients 5 had PaO2 lower than the expected normal value but only in one case it was lower than 80 mmHg. After aspirin or Persantin administration there was a definite rise in the PaO2 in 10 out of 12 patients. The hypoxaemia is believed to occur from increased platelet aggregation leading to pulmonary artery occlusion. The rise of the arterial PaO2 after aspirin administration indicates that the observed hypoxaemia is due to reversible platelet aggregation in the majority of cases.

Pulmonary artery obstruction in thalassaemia.

A new feature has been encountered in review of a large species of autopsy materials of beta-thalassaemia/Hb E disease. Among 43 patients pulmonary arterial obstructive lesions were found in 19 (44%), of which 17 were splenectomised cases. The pulmonary arterial thromboembolism may have been due to circulating platelet aggregates. This newly discovered pathology may be an additional factor contributing toward dyspnoea and heart failure in thalassaemia besides anaemia and cardiac iron deposition. If it is proven that this pulmonary arterial thromboembolism is indeed due to circulating platelet aggregates, preventive measure by administration of drugs reducing platelet aggregation such as aspirin and Persantin may be indicated, especially after splenectomy.

G-6-PD variants in Chinese in Thailand.

Partial purified erythrocyte G-6-PD from 25 G-6-PD deficient southern Chinese male residents in Thailand was characterized. Five G-6-PD variants were found : G-6-PDs Canton (8), Dhon (or Taipei-Hakka) (8), Mahidol (or B (-) Chinese) (6), Haad Yai (1), and Hong Kong (1). One person whose enzyme was not fully characterized might have G-6-PD Haad Yai or a new variant.