Biomedical subjects
Publications and source records attributed to E P Mansvelt.
Factor V Leiden mutation is a risk factor for the development of thrombo-embolic episodes in pregnancy. A case is presented of a pregnant woman with repeated episodes of venous thrombosis with a complicated clinical course.
High FVIII:C levels have previously been shown to be an independent risk factor for thrombosis with 4.8 times higher potential risk of thrombosis in individuals with FVIII:C levels greater than 1.5 u/ml. Recently, we found that raised FVIII:C levels are largely attributable to elevated FVIII:Ag levels. The determinants of FVIII:Ag levels are unclear and might be partly genetic. The promoter of the F8 gene has recently been characterised we therefore investigated the promoter and the 3' terminus of the F8 gene for possible polymorphisms associated with raised FVIII:Ag levels in 62 selected individuals with a thrombotic tendency. We confirm previous reports that raised FVIII:C levels are largely attributable to an elevation in FVIII:Ag and this is also associated with elevation of vWF; non-O blood group: relatively short APTT and relatively low APC ratio. We screened 1140 bp of the proximal promoter including the protein binding sites identified by DNase I footprint analysis by SSCP, however no polymorphisms were identified. Direct DNA sequence analysis of the region -542 to +165 failed to identify any sequence polymorphisms. The recently described polymorphism in the polyadenylation cleavage site in the prothrombin gene associated with increased prothrombin activity prompted us to screen the region surrounding the 3' terminus of the F8 gene for polymorphisms but we found none.
Plasma retinol and indices of iron status were measured in 148 school children (6-12 years) receiving a soup fortified with iron and vitamin C for a period of 15 weeks. The most significant change in serum iron (P = 0.0005) and transferrin saturation (P = 0.0002) was seen in subjects with plasma retinol > or = 40 micrograms/dl, while subjects with plasma retinol < 20 micrograms/dl showed no response. Serum ferritin improved most in the retinol categories < 40 micrograms/dl, suggesting that the absorption of iron was not impaired by marginal vitamin A status, but that it was rather the mobilisation of iron from stores that was affected. Changes in vitamin A status correlated positively and significantly with changes in serum iron (r = 0.37; P = 0.0001) transferrin saturation (r = 0.27; P = 0.004) and haemoglobin (r = 0.21; P = 0.03), but negatively with serum ferritin (r = -0.28; P = 0.003). The presence of marginal vitamin A deficiency in a community may limit the effectiveness of an iron intervention programme and vitamin A status should therefore also be considered when such programmes are planned.
An intervention study was designed to evaluate the fatty acid (FA) status of children aged 6-11 years before and after iron fortification. Iron-deficient (ID) and matched controls without ID (n = 30) were selected. All children received soup (160 ml) fortified with 20 mg iron and 100 mg vitamin C for 15 weeks on school days. Measurements before and after intervention included dietary intake, haematological and iron status and FA composition of plasma and erythrocyte membranes (EMBs). The prevalence of low plasma ferritin concentration and transferrin saturation decreased in the ID children by 40% and 56%, respectively, with intervention. Plasma FAs reflected dietary FA intake. In comparison with controls, the ID group presented with increased percentage total saturated FAs (SFAs; p = 0.0002) in their EMB phosphatidylcholine (PC) and reduced percentage total polyunsaturated FAs (PUFAs; p = 0.0037) before intervention. Lower total n-3 FAs (p = 0.0070), including eicosapentenoic acid (EPA; p = 0.0034), docosapentenoic acid (DPA; p = 0.0048) and docosahexenoic acid (DHA; p = 0.0058), were observed in the ID group. The EMB phosphatidylethanol-amine (PEA) of the ID children presented with lower percentages of alpha-linolenic acid (ALA; p = 0.0001), EPA (p = 0.0051) and DHA (p = 0.0084) compared to controls before intervention. Iron intervention was associated with an increase (p < 0.05) in the percentage of n-3 FAs in the EMB-PC and EMB-PEA of the ID group to percentages comparable to that in the control group. It appears that iron status can influence FA metabolism of specific n-3 FAs in the EMBs of young children.
An intervention study was designed to evaluate the fatty acid (FA) status of children aged 6-11 years before and after iron fortification. Iron deficient (ID) and matched controls without ID (n = 30) were selected. All children received soup (160 mL) fortified with 20 mg iron and 100 mg vitamin C for 15 weeks on school days. Measurements before and after intervention included dietary intake, haematological and iron status and FA composition of plasma and erythrocyte membranes (EMBs). The prevalence of low plasma ferritin concentration and transferrin saturation decreased in the ID children by 40% and 56%, respectively, with intervention. Plasma FAs reflected dietary FA intake. In comparison with controls, the ID group presented with increased percentage total saturated FAs (SFAs; p = 0.0002) in their EMB phosphatidylcholine (PC) and reduced percentage total polyunsaturated FAs (PUFAs; p = 0.0037) before intervention. Lower total n-3 FAs (p = 0.0070) including eicosapentaenoic acid (EPA; p = 0.0034), docosapentaenoic acid (DPA; p = 0.0048) and docosahexaenoic acid (DHA; p = 0.0058) were observed in the ID group. The EMB phosphatidylethanolamine (PEA) of the ID children presented with lower percentages of alpha-linolenic acid (ALA; p = 0.0001), EPA (p = 0.0051) and DHA (p = 0.0084) compared to controls before intervention. Iron intervention was associated with an increase (p < 0,05) in the percentage of n-3 FAs in the EMB-PC and -PEA of the ID group to percentages comparable to that in the control group. It appears that iron status can influence FA metabolism of specific n-3 FAs in the EMBs of young children.
The peripheral blood and bone marrow findings in 25 patients found to have tuberculous granulomata on bone marrow examination were examined to determine whether specific haematological findings are associated with tuberculous infiltration of the bone marrow. All the patients had one abnormality or more on their full blood count. The presence of a peripheral lymphopaenia was the single factor common to all 25 patients studied. The peripheral lymphopaenia was only associated with bone marrow lymphopaenia in 14% of patients. Other findings of note were an association of peripheral monocytopaenia and absence of giant cells in the granulomata, and decreased iron stores in almost a third of the total number of patients. The relevance of the lymphopaenia, monocytopaenia and decreased iron stores are discussed and we propose that the absence of a peripheral lymphopaenia makes it very unlikely that there will be tuberculous localization in the bone marrow.
We report a case of acute monoblastic leukaemia in which the expression of the CD4 antigen occurred in the absence of myeloid and monocytic lineage specific markers. Unexpected marker profiles have biological and diagnostic implications and we also suggest that the inappropriate expression of the CD4 antigen may be implicated in the poor prognosis of this case.
Multiple sclerosis (MS) is believed to be an autoimmune process occurring in genetically susceptible individuals after an appropriate environmental exposure. We have exploited the homogeneous Afrikaner population of European ancestry to investigate the likelihood that iron dysregulation, in association with infectious and/or autoimmune disease susceptibility, may underlie the MS phenotype in a subgroup of patients. The functional Z-DNA forming repeat polymorphism of the natural resistance-associated macrophage protein-1 (NRAMP1) gene was analyzed in 104 patients diagnosed with MS and 522 Caucasian controls. A family-based control group consisting of 32 parental alleles not transmitted to MS offspring was additionally studied to exclude the likelihood of population substructures. Statistically significant differences in allelic distribution were observed between the patient and control samples drawn from the same population (P < 0.01). Evidence is furthermore provided that alleles considered to be detrimental in relation to autoimmune disease susceptibility may be maintained in the population as a consequence of improved survival to reproductive age following infectious disease challenge. Although it remains to be determined whether the disease phenotype in MS patients with allele 5 of the NRAMP1 promoter polymorphism is directly related to dysregulation of iron or modified susceptibility to viral infection and/or autoimmunity, a combination of these processes most likely underlies the disease phenotype in these patients. In view of the emerging role of polymorphic variants in complex diseases and minimizing of possible confounding factors in this association study, we conclude that allelic variation in the NRAMP1 promoter may contribute significantly to MS susceptibility in the South African Caucasian population.
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The product of the percentage blasts on the bone marrow aspirate (BMA) and the biopsy cellularity has been termed the "absolute blast index aspirate" (ABI-aspirate) and is used to measure disease response on day 7 of induction therapy. The authors compared the event-free survival (EFS) in high-risk and standard-risk patients as identified by the ABI-aspirate and the BMA percentage blasts on day 14 of induction therapy. Both indices identified high-risk cases. EFS of patients categorized as high-risk by these 2 methods and the high-risk criteria used by the authors' service (WCC of > 20 x 10(9)/L, age < 2 and > 8 years and a peripheral blood blast count of > 1.0 x 10(9)/L on day 8 of induction) did not differ. There was concordance between patients identified as high risk by all 3 methods. The results confirmed the prognostic value of the ABI-aspirate and the BMA percentage blasts on day 14 of induction therapy, but these methods were not superior to the high-risk criteria currently in use.