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Biomedical subjects

A F Fleming

Publications and source records attributed to A F Fleming.

At least 19 recordsLinked to original sources

The value of the intrinsic factor antibody test in diagnosing pernicious anaemia.

OBJECTIVE: Assessment of the usefulness of the intrinsic factor antibody (IF Ab) test in comparison to the Schilling test in diagnosing pernicious anaemia (PA) in patients with vitamin B12 deficiency. DESIGN: This study was designed to compare the If Ab test to the Schilling test using results obtained of patients presenting with megaloblastic anaemia and low serum vitamin B12 levels to a large referral hospital. SETTING: The Chris Hani Baragwanath Hospital, Soweto, Gauteng, South Africa. SUBJECTS: Results from 77 patients with megaloblastic anaemia, low serum vitamin B12 levels and with both Schilling and IF Ab test results available were included. MAIN OUTCOME MEASURES: The sensitivity and specificity of the IF Ab test was compared to the Schilling test with regard to making a diagnosis of PA in patients presenting with megaloblastic anaemia and low serum vitamin B12 levels. RESULTS: Relevant statistical analysis showed that in the correct clinical setting, a confident diagnosis of PA could be made without Schilling tests in patients with megaloblastic anaemia, vitamin B12 deficiency and positive IF Ab tests. In a small proportion of patients in whom the IF Ab is negative, Schilling tests still need to be performed. CONCLUSION: With the increased concern over rising medical costs and where limited facilities are available, the IF Ab, in the correct clinical setting, is a cost effective and reliable test for diagnosis of PA.

Anemia, Pernicious

Haemophilia in northern Nigeria.

Thirteen patients from 11 families were diagnosed as cases of haemophilia A or B during 1977 to 1984. The majority presented with post circumcisional bleeding. Cryoprecipitate and packed red cells were used in the management. Haemophilia and other inherited bleeding disorders are not as rare as otherwise assumed. This is the first report from Northern Nigeria.

Adolescent

Clinical features of HIV seropositive Zambian subjects.

Data was collected from 1595 anti-HIV positive patients out of which 90% of the patients were from the Copperbelt province, and the rest from five out of the eight other provinces of Zambia. One-hundred and one positive HIV patients were less than 2 years of age, 69 were aged 2 to 14 years and 1418 were aged above 15 years. The male to female ratio was about 1:1 at all ages, except that there was an excess of males below 5 years. Of the four most frequent symptoms or signs, loss of weight or malnutrition was regarded in about 50% of seropositive patients at all ages; generalized lymphadenopathy was seen in at least 35% of all age groups and most frequently at 2-14 (60%); chronic watery diarrhoea was most common at less than 2 years (44%) and least common in older children (17%); chronic chest infections had highest frequency in children 2-14 years (59%) and lowest in adults (32%). Intensive education of children before they are sexually active is the best hope for controlling the epidemic.

Adolescent

Glycophorin variants and Plasmodium falciparum: protective effect of the Dantu phenotype in vitro.

Experimental work was carried out to establish the growth characteristics of Plasmodium falciparum in an in vitro culture system using cells with the Dantu, Henshaw and S-s-U- blood-group variants. A flow cytometric technique, using the dye thiazole orange, was adapted for use on the Epics Profile II flow cytometer to count the parasites. This was performed at 24, 48 and 72 h. The ability of the parasites to grow in red cells of the Dantu and Henshaw phenotypes was also assayed by 3[H] hypoxanthine incorporation. Relative to control red cells, S-s-U- cells and Dantu cells were less suitable as host cells for P. falciparum in vitro. In contrast, cells expressing the Henshaw antigen were equally sensitive to P. falciparum infection as were normal controls. These data support the notion that glycophorins play an important role in P. falciparum infection. Further studies are required to evaluate the epidemiological significance of these results.

Animals

Residual risk of transmission of HIV through blood transfusion in South Africa.

Despite the ongoing review of donor recruitment criteria by local blood transfusion services and the development of highly sensitive and specific testing for the presence of antibodies to HIV in blood and blood products, there remains a residue of HIV in donated blood. This is because of donors who are in the 'window period' between acquisition of HIV and seroconversion, human errors and limits to the sensitivity and specificity of current tests. Data available from a national survey of HIV seroprevalence in South African blood donors allowed for the estimation of the number of units screened negative but likely to be infected with HIV. Assuming window periods of 4.8 and 14 weeks, a test sensitivity of 99.9%, a specificity of 98.5% and a human error rate of 0.1%, the likely rate of HIV-infected blood in the South African blood transfusion supply ranges from 1.1 to 3.9/100,000 units, with a likely estimate of 2.2/100,000 units. In the current South African blood transfusion setting, between 8.1 and 28.2 units of blood per annum will be HIV-positive with a likely estimate of 15.9 units. This corresponds to an odds ratio of between 1:90 909 and 1:25 641 units infected with HIV. These data are comparable with the risk in developed countries. The expected increase in the incidence and prevalence of HIV infection in all adult South African populations necessitates additional measures to ensure a blood supply which is as safe as possible. Some of these measures have already been taken by local blood transfusion services.

Blood Donors

Agriculture-related anaemias.

Man evolved as a hunter-gatherer, and the invention and spread of agriculture was followed by changes in diet, the environment and population densities which have resulted in globally high prevalences of anaemias due to nutritional deficiencies of iron, folate and (locally) vitamin B12, to infestations by hookworm and schistosomes, to malaria, and to the natural selection for the genes for sickle-cell diseases, beta-thalassaemias, alpha-thalassaemias, glucose-6-phosphate dehydrogenase deficiency, ovalocytosis and possibly (locally) elliptocytosis. The present explosion of population is driving an expansion of agriculture, especially the cultivation of rice, and this has led often to disastrous increases of transmission of malaria, schistosomiasis and other diseases, to widespread chemical pollution, and to degradation of the environment. Anaemia, as the commonest manifestation of human disease, is a frequent consequence. The urgent need for increased food production is matched by the urgent need for assessment and control of the health impact of agricultural development.

Adult

Leukaemias in Africa.

Until recently, cALL has been uncommon in sub-Saharan Africa, but there is now emerging a peak of incidence at the age 3 to 5 years in west and southern Africa. Prognosis for African patients with cALL is poor because of a multitude of clinical, biological and social factors. AML is seen at high frequency (probably indicating truly high incidence) in male children 5-14 years, of whom up to a quarter present with chloroma. It is predicted that the incidence of AML in adults may rise in the near future, related to cigarette smoking, occupational and environmental exposures to benzene and other pollutants, and the prescription of alkylating agents to young people with malignant disease. CML shows no particular epidemiological features, except for a high frequency in young adults and children, reflecting the age structure of the whole population. There are two forms of B-CLL: one is seen most commonly in women of low socioeconomic status towards the end of the their reproductive life, and is probably related to an initially polyclonal expansion of B-cells in response of recurrent malaria and other infections; the other is seen over the age of 45 years, with men being affected twice as commonly as women, as in the western world.

Acute Disease

CD10 antigen density in childhood common acute lymphoblastic leukaemia: comparisons of race and sex.

During the 25 month period from July 1989 until August 1991, 58 children with FAB defined acute lymphoblastic leukaemia (ALL) were referred for immunophenotypic analysis. Of these, 42 children with a common/pre-B phenotype (CD19/CD10-positive) were studied specifically to assess CD10 antigen density. A pattern of segregation was found between males and females and between black and white children. Black males, who are the worst prognostic group, had the lowest CD10 density, while white females, known to constitute the best prognostic group, had significantly higher CD10 antigen density than the other groups. Black females and white males occupied intermediate positions with respect to CD10 antigen density. A two way analysis of variance showed that although sex had contributed significantly to this variation (p = 0.0038), the contribution of race was marginal (p = 0.0530). It is hypothesized that low CD10 antigen density patterns in males and in Blacks could be causally related to poor prognosis.

Black People

Human retroviruses.

It was only in 1980 that the first human retrovirus, HTLV-1, was isolated. Since then, HTLV-2, HIV-1 and HIV-2 have been identified. All four viruses are transmitted with varying efficiency sexually, vertically from mother to infant, and through blood by transfusion or contamination. HTLV-1 is endemic in populations in south-west Japan, Taiwan, sub-Saharan Africa, the Caribbean, southern USA, central and south America, Australia, Papua New Guinea, Solomon Islands and western Asia. There is now epidemic spread amongst IVDUs in north and south America and southern Europe. HTLV-1 is the aetiological agent of adult T-cell leukaemia/lymphoma (ATL) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Other associations which may be causative are with polymyositis, infective dermatitis, gastrointestinal malignant lymphoma and chronic lymphatic leukaemia. ATL appears to be due to malignant transformation of HTLV-1 infected cells, and TSP/HAM to chronic activation of these cells. The epidemiology of HTLV-2 is being separated only recently from HTLV-1 through the application of PCR. It has a low level of endemicity in populations of central Africa, and central and south America. It is being spread epidemically amongst IVDUs in north America and southern Europe. Its association with any pathology in man remains uncertain. HIV-1 is epidemic and spreading rapidly throughout the world. In areas where homosexual contact was the predominant mode of transmission, heterosexual spread is becoming increasingly important. The areas where heterosexual contact is the predominant mode of transmission include the worst affected populations in the world, for example sub-Saharan Africa and some of the Caribbean. There have been recent and explosive increases of HIV-1 seroprevalence in IVDUs and female prostitutes in Asia, especially Thailand and India. Of the diverse pathology following infection, only the haematological consequences are reviewed in detail: these include anaemia, leucopenia, thrombocytopenia, disorders of coagulation and lymphomas. HIV-2, compared to HIV-1, is less infectious and causes less immunosuppression with more slowly progressive disease. It is prevalent in west Africa, but is spreading, albeit slowly, far beyond.

Acquired Immunodeficiency Syndrome

Genetic epidemiology of the beta s gene.

The beta s gene arose at least four times in Africa, with three of these mutations expanding through diverse ethnic groups, but limited to definite geographical areas: Atlantic west Africa for the Senegal haplotype linked beta s; central west Africa for the Benin haplotype; and equatorial, eastern and southern Africa for the Bantu haplotype. The fourth mutation (linked to the Cameroon haplotype) is restricted to a single ethnic group, the Eton of central Cameroon. The Benin haplotype linked beta s gene was spread by gene flow to the Mediterranean (north, south and east) and to the western portions of Saudi Arabia. An independent mutation linked to a fifth haplotype, Arab-India, is found among the tribals of India (independent from their geographical origin) and in the eastern oases of Saudi Arabia. It is also suspected of being associated with the beta s gene found in Afghanistan, Iran, Transcaucasia and central Asia. The selective force involved in the expansion of the gene was most likely P. falciparum malaria, and the time of the gene frequency increase was likely to have been during the expansion of agriculture about 4000 or more years ago in India and about 3000 years ago in Africa. The partial protection against severe and life-threatening malaria is through the limitation of P. falciparum parasitaemia. This is a complex process which involves at least two mechanisms: early intraerythrocyte parasite forms are in a suicidal position through increasing the tendency of HbAS cell to sickle and then be destroyed by the spleen; intraerythrocyte growth is inhibited during deep vascular schizogony. Although there is evidence that P. falciparum (and P. malariae) parasitaemias are limited in HbSS red cells, malaria is a major trigger to haemolytic and infarctive crises in sickle-cell disease, and a common cause of morbidity and mortality.

Africa