A comparative study was done to determine the profile of vitamin B12 and folate status in Malaysians during two different periods. For the period of 1987/88, we analysed a total of 9,162 cases (inpatients) referred for vitamin B12 estimation and 10,290 cases for folate estimation. We found that 2.6% were vitamin B12 deficient and 31.2% were folate deficient. For the period of 1992/93, of the 9,962 cases assayed, 8.2% were found to be vitamin B12 deficient whereas 7.6% of the 10,355 cases referred were folate deficient. Vitamin B12 and folate were assayed either using microbiological or radioassays. These findings indicate that there appears to be a change in the status of both vitamin B12 and folate over the five year interval.
The finding of a prolonged bleeding time in a patient whose platelet count is normal suggests some abnormality in the function of the platelets. This situation may be due to an inherent platelet defect or to the deficiency of a plasma factor necessary for some aspect of platelet function. Defects of platelet function are also seen in a wide range of disease states and may be caused by many different classes of drugs. Simple methods are available to identify abnormalities in platelet numbers and/or function. Tests of platelet aggregation, using the aggregometer, are now widely used to investigate patients suspected of having platelet disorders. We observed in the last four years that thrombocythopenia is quite common amongst children and bleeding from platelet dysfunction, congenital or acquired, is not rare in Malaysia. This study was done to assess the prevalence of platelet abnormality in a section of the general 'healthy' population of school-going children and to study the possible causes of any abnormalities detected.
The common chromosome abnormalities that are encountered in the various types of leukemia are discussed here. Chromosome abnormalities in leukemia are non-random and certain chromosomal changes are now becoming recognised as being rather specific for certain leukemia types.
A study was conducted on a total of 100 women attending the Family Planning Clinic in Kuala Lumpur. 50 took combined low-dose estrogen and progesterone pills for a year or more and the other 50 used different methods of birth control. Platelet aggregation, ATP release, Thromboxane B2, and 6-keto-prostaglandin F1alpha estimations were made to evaluate the effect of oral contraceptives (OCs) on platelet function and prostanoid production. The results showed no significant differences in the parameters measured in the 2 groups investigated. These findings are comparable to those reported by other studies, suggesting relatively low risk, if any, of thrombosis in OC users.
The present findings suggest the possible involvement of an active mechanism for transport of iron to the fetus. In all the 19 subjects studied, the cord serum iron levels tended to be higher (129.2 ± 56.8 ug/100ml) than the maternal serum iron levels (74.0 ± 35.9 ug/100ml) at parturition even in maternal iron deficiency. The significant difference (P< 0.001) between cord serum iron levels and the maternal iron levels shows that an active transport mechanism working against a gradient in favour of the fetus exists. The availability of iron to the fetus appears to be dependent on maternal serum iron levels but not on maternal iron stores. This finding serves to stress the importance of iron supplements in pregnancy. A hypothetical model for iron transfer from maternal circulation to fetal circulation is described.
The spectrum of beta-thalassemia mutations in Malaysia has been determined in 45 beta-thalassemia chromosomes using dot blot hybridization of the polymerase chain reaction amplified DNA and direct DNA sequencing. Eleven different molecular defects, including those previously detected in Chinese, Asian Indians, and American blacks, and a novel frameshift mutation causing beta zero-thalassemia were detected. Since this novel mutation, a T deletion in codon 15 creates a new restriction site for EcoRII enzyme; the mutation could be detected by EcoRII digestion of the appropriate amplified fragment. The results of the present study provide additional information on the molecular heterogeneity of beta-thalassemia in this population. We also demonstrated the nonradioactive detection method of the beta-thalassemia mutation based upon the digoxigenin-labeled oligonucleotide probes.
Folate and vitamin B 12 status in pregnancy was studied in a group of 190 Malaysian mothers belonging to the three major ethnic origins. Cord blood was also analysed for the same vitamins. Ethnic variations with regard to deficiency in these two vitamins was determined. About 58.5 percent of the pregnant mothers suffered from lowered serum folate levels and 32.4 percent had lowered RBC folate levels. In contrast vitamin B 12 levels were within normal limits. Cord blood levels of these vitamins were significantly higher than. the corresponding levels in the maternal blood, suggesting the possible involvement of an active process in the transfer of folates and vitamin B 12 to the fetus.
Whole blood samples from patients with various forms of alpha- and beta- thalassaemia were incubated with 14C-Leucine to determine the relative rates of production of the alpha and beta chains by their reticulocytes. The labelled globin chains were fractionated by CM-Cellulose Chromatography in 8M Urea and the incorporated activity determined. The relative rates of synthesis of alpha and beta chains in some cases of alpha and beta- thalassaemia were established and the chain synthetic ratios were compared with similar ratios in normal individuals. The results show that it is possible to identify from the relative rates of in-vitro synthesis of the alpha and beta chains, the presence of the common thalassaemia slates in particular beta-thal trait, beta-thal homozygotes, Hb H disease and alpha0-thal trait. The presence of transfused blood does not affect the result. This study indicates that an abnormal alpha/beta chain synthesis ratio is useful in defining alpha and beta-thalassaemia variants.
Our previous study showed vitamin E deficiency in newborns (69.7%) and mothers at term (85.9%) when the ratio between serum vitamin E in mg/dl and total lipids in g/dl was used as an indicator of vitamin E status. This study was conducted to determine the human milk content of vitamin E. During the first 12 days of lactation milk vitamin E levels remained almost constant (day 1, 0.68 mg/dl; day 12, 0.65 mg/dl), milk total lipid levels increased daily (day 1, 1.11 g/dl; day 12, 3.60 g/dl), and the ratio between milk vitamin E and total lipids dropped steadily (day 1, 1.3; day 12, 0.2). In spite of this drop in vitamin E status, it is unlikely that vitamin E availability will be affected in neonates, because normal neonates absorb milk fats well and this ability increases with age.
Clinical studies were carried out on mild Indian sickle cell anaemia in Malaysia, and genetic and fertility studies were carried out on 101 families with and without sickle-cell haemoglobin (Hb S). The Indian sickle cell anaemia patients reached adulthood, and pregnancies and deliveries were uneventful without blood transfusion. There was no foetal wastage and the number of children produced was not significantly different from that in families without Hb S. 28 Indian patients hospitalized with Plasmodium falciparum malaria infection were also examined for their beta S genotype. P. falciparum malaria infection occurred much more frequently in individuals without Hb S than in Hb S carriers.
The Indian rubber estate workers in Negri Sembilan, Malaysia, who originated from Orissa in India were found to have a high frequency of Hb S (Joishy SK, Hassan K: Clin Res 28:280, 1980). Unlike the usually severe clinical picture of sickle cell anemia seen in African and American blacks, the clinical picture of the disease in this population was mild and many have reached old age. We studied the leukocyte DNA of 12 patients with sickle cell anemia, ranging in age from 4 to 61 years and 30 sickle cell trait carriers, ranging in age from 7 to 63 years, for the presence of alpha-globin gene deletions by gene mapping according to Southern (Southern EM: J Mol Biol 98:503, 1975), using alpha- and zeta-globin gene probes obtained by nick translation of the alpha- and zeta-globin genes cloned into plasmid. All 12 sickle cell anemia patients were found to have alpha-thalassemia2 (alpha-thal2), either in the homozygous or heterozygous condition. Of the Hb S trait carriers, six did not have alpha-thal2 or alpha-thal1 and 24 had alpha-thal2 (15 heterozygous, 9 homozygous). Seven of these Hb S trait carriers with alpha-thal2 had an additional gene abnormality. Five of them had a fast-moving Eco RI fragment 5.6 kb long that hybridized with zeta-specific probe but not with alpha-specific probe. An unusual DNA pattern of a different type was further found in the other two. Bgl II restriction analysis showed that the alpha-thal2 was mostly of the rightward deletion alpha-thal1 genotype. None of the sickle cell anemia patients and Hb S trait carriers had deletion type alpha-thal1. The sickle cell anemia patients had very high levels of Hb F and low levels of Hb A2. The Hb S trait carriers with alpha-thal2 had relatively low levels of Hb S.
PIP: Long term use of low doses of combination oral contraceptives appears to increase plasminogen level, thereby increasing fibrinolytic activity and reducing the risk of thromboembolism. Blood levels of plasminogen, tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI), were measured before and after stress (5 minutes of stair climbing) in a group of 30 women, 23-40 years old, who had taken 30 mcg of ethinyl estradiol with 150 mcg of desogestrel or levonorgestrel for at least 1 year. Similar measurements were taken from a control group of 30 women matched for age, height, and weight. Plasminogen and tPA levels in both groups increased significantly after exercise. The level of PAI did not change significantly with stress in either group. The level of plasminogen was significantly higher in the group taking contraceptives, whether before or after exercise, when compared to the control group. Levels of tPA and PAI, although slightly increased in the oral contraceptive group, were not significantly different between the two groups. The increase in plasminogen may be due to the estrogen component of the contraceptives. Stress seems to increase fibrinolytic response.
Cytogenetic investigations were carried out on 117 women with primary amenorrhea who had been referred to our Genetics Laboratory by clinicians throughout Malaysia, after exclusion of other causes of the disorder. Thirty-six cases (31%) showed numerical or structural abnormalities of the sex chromosomes. These can be broadly classified into 4 main types, namely, presence of a Y chromosome (14%), X-chromosome aneuploidies (8%), structural anomalies of the X-chromosome (7%) and lastly, presence of a marker chromosome (2%). Mosaics constituted 17% of the abnormalities observed, always in association with a 45,X cell line. There was no observable correlation between the phenotype of the patients and their respective abnormal karyotypes. The aetiological role of sex chromosomal abnormalities in these amenorrheic women is discussed.
Immunoperoxidase staining was compared with flowcytometry for the enumeration of lymphocyte subsets. The percentages obtained for peripheral blood lymphocytes using immunoperoxidase (CD3 = 76 CD4 = 27.9, B = 10.7 CD4/CD8 = 1.8) differed significantly from those obtained by flowcytometry (CD3 = 65.7 CD4 = 39.4, CD8 = 25.6, B = 16.7, HLA DR = 11.9 CD4/CD8 = 1.54) for certain subsets (CD3, CD4, B). There was no significant difference in lymphocyte subsets between children and adults using the same method. These differences are probably due to the different methods used to prepare lymphocytes for analysis. Other factors that should also be considered are the presence of CD4 antigen on monocytes and CD8 on natural killer cells.
A cytogenetic survey 01 124 children in lour special schools for the mentally handicapped was carried out to determine the contribution of chromosomal abnormalities to the aetiology of mental retardation in these children. All the children were karyotyped employing the G·banding technique 01 43 (34.7%) with an abnormal chromosome complement, 40 had Down's Syndrome, and 3 had other chromosomal abnormalities, namely a translocation 1;17, a mosaic male/trisomy 18 and a Klinefelter's syndrome. Polymorphic variants involving chromosomes 1, 9, and 14 were also observed. Two other children showed variants of the Y chromosome (one a small Y and the other a metacentric Y). The possible contribution by these abnormal variants to mental retardation is discussed. Details of the abnormal cytogenetic findings are reported.
An Indian family with all 3 sons having the fragile X syndrome is reported. The frequency of fragile X cells observed ranged from 4·16%. The phenotypically normal mother, although an obligate carrier, did not express any fragile X chromosomes in her Iymphocyte cultures. The range of mental retardation in affected
hemizygous males and heterozygous females as well as the significance of the fragile X chromosome in prenatal diagnosis are discussed.
The effects on serum lipids of diets prepared with palm olein, corn oil, and coconut oil supplying approximately 75% of the fat calories were compared in three matched groups of healthy volunteers (61 males, 22 females, aged 20-34 y). Group I received a coconut-palm-coconut dietary sequence; group II, coconut-corn-coconut; and group III, coconut oil during all three 5-wk dietary periods. Compared with entry-level values, coconut oil raised the serum total cholesterol concentration greater than 10% in all three groups. Subsequent feeding of palm olein or corn oil significantly reduced the total cholesterol (-19%, -36%), the LDL cholesterol (-20%, -42%%) and the HDL cholesterol (-20%, -26%) concentrations, respectively. Whereas the entry level of the ratio of LDL to HDL was not appreciably altered by coconut oil, this ratio was decreased 8% by palm olein and 25% by corn oil. Serum triglycerides were unaffected during the palm-olein period but were significantly reduced during the corn-oil period.