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A F Fleming

Publications and source records attributed to A F Fleming.

At least 19 recordsLinked to original sources

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

Opportunistic infections in AIDS in developed and developing countries.

The acquired immune deficiency syndrome (AIDS) is fundamentally the same disease in all parts of the world, but the prevalence of microorganisms in an environment governs the patterns of disease arising from reactivated latent infections, invading pathogens and opportunistic infections. AIDS in Africa has certain characteristic presentations. Enteropathic AIDS is most common: Cryptosporidium and Isospora belli are identified in up to 60% of patients, but it is uncertain whether they are the causes of diarrhoea. Pneumocystis carinii pneumonia is rare. Tuberculosis, both pulmonary and extrapulmonary, is the supreme complicating infection. Herpes zoster is frequently the first clinical presentation, and has a 95% positive predictive value for HIV positivity. Measles may be more frequent in infants born to HIV-infected mothers, and appears to be worse in HIV-infected children. There is accelerated progress of both diseases in patients infected by HIV and Mycobacterium leprae. Salmonellosis is frequent. There is no direct interaction between malaria and HIV, but, by being a potent cause of anaemia, malaria enhances transmission of HIV to children through blood transfusion. HIV-positive subjects are liable to new or reactivated visceral leishmaniasis with dissemination to unusual sites. Cerebral toxoplasmosis is common. There are no apparent interactions between HIV and helminths, although there is one report of hyperinfection with Strongyloides stercoralis. Cryptococcal meningitis has high frequency. Infections with Histoplasma encapsulatum are common in tropical America, but there has been no increase of frequency of H. duboisii in Africa since the advent of AIDS.

Acquired Immunodeficiency Syndrome

AIDS in Africa.

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AIDS Serodiagnosis

Proguanil.

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Alopecia

The presentation, management and prevention of crisis in sickle cell disease in Africa.

About 120,000 infants are born each year with sickle cell disease (SCD) in Africa. The majority have Hb SS, but Hb SC and Hb S/beta+ thalassaemia are common in west Africa. The development of Plasmodium falciparum and P. malariae is partially inhibited in the Hb SS red cells, but malaria precipitates both haemolytic and infarctive crises, and is the commonest and most important cause of morbidity and mortality. The pneumococcus is likely to be the second major infectious cause of sickness and death. In one rural community, there were less than 2% of the expected number of subjects with SCD surviving beyond 5 years of age. Genetic factors improving prognosis include (1) the Senegal beta chain haplotype, which is linked to a high level of Hb F, and (2) alpha+ thalassaemia. Of environmental factors improving prognosis, the family is of first importance. The commonest age of presentation is 1-3 years. Children present with anaemic crises (malaria, splenic sequestration, folate deficiency, and possibly aplastic), infarctive crises (hand-foot syndrome, bone-pain, pulmonary and abdominal) or acute infections (malaria, pneumonia, septicaemia, meningitis, osteomyelitis). Tragically, many patients in central Africa have been infected by the human immunodeficiency virus (HIV) through blood transfusions; they present with generalised lymphadenopathy and other features of the acquired immunodeficiency syndrome (AIDS). The principles of management are (1) to ensure freedom from malaria, (2) to continue folic acid supplements, (3) to give blood transfusions only when anaemia endangers life, (4) to control pain, (5) to restore hydration, and (6) to prescribe broad spectrum antibiotics in large dosage and without delay, but only when there are definite indications, such as fever (greater than 39 degrees C), acute pulmonary disease, meningitis, and acute osteomyelitis. The advent of HIV and AIDS makes the control of SCD of even greater importance. Principles of control are (1) early diagnosis through appropriate laboratory techniques and selective screening, (2) education of parents, patients, health professionals and public, and (3) the maintenance of health at sickle cell clinics; measures must include antimalarial prophylaxis. SCD programmes should be integrated with primary health care and AIDS control programmes.

Africa

The aetiology of severe anaemia in pregnancy in Ndola, Zambia.

The aetiology of severe anaemia (haemoglobin less than 7.0 g dl-1) has been studied in 37 pregnant Zambians. Aetiology was usually multiple; 31 (84%) had Plasmodium falciparum malaria, 23 (62%) were folate deficient, 13 (35%) were iron deficient, one had sickle-cell anaemia and one had the acquired immunodeficiency syndrome (AIDS). Folate deficiency was most often secondary to malarial haemolysis: iron deficiency was nutritional, but hookworm was contributory in about one-third of patients. The anaemia of malaria and folate deficiency was both more common and more severe than anaemia due to iron deficiency; it was seen in younger women although primigravidae were not over-represented, it occurred earlier in pregnancy, and was associated with low birthweight. AIDS must now be included in the differential diagnosis of anaemia in pregnancy. Vigorous antimalarial treatment and prophylaxis are essential in the management and prevention of anaemia in pregnancy. Total dose iron infusion is indicated only when severe iron deficiency anaemia has been proven, and must be accompanied by antimalarial therapy and folic acid supplements. Because of the risk of transmission of human immunodeficiency virus, it is more important than ever to prevent anaemia and malaria in pregnancy, and to give blood transfusion only as a life-saving treatment.

Acquired Immunodeficiency Syndrome

Alpha thalassaemia in Zambian newborn.

The umbilical cord blood from 109 consecutive Zambian neonates (excluding those found to be anti-HIV positive) were analysed for haemoglobin (Hb) Bart's and for alpha thalassaemia by restriction endonuclease analysis. This showed that 52.3% had the genotype alpha alpha/alpha alpha, 38.5% had -alpha 3.7/alpha alpha, 7.3% had -alpha 3.7/-alpha 3.7 and 1.8% had alpha alpha alpha/alpha alpha. The alpha thalassaemia gene (-alpha) frequency was 0.27. There were no apparent differences in gene frequency between six major Zambian ethnic groups. Detection of Hb Bart's identified all alpha-thalassaemia homozygotes (-alpha/-alpha), but fewer than 10% of heterozygotes (-alpha/alpha alpha). alpha-thalassaemia was associated with slight but significant anaemia and microcytosis.

Female

Blood dyscrasia in unofficial vendors of petrol and heavy oil and motor mechanics in Nigeria.

The risk of blood dyscrasia has been measured in Nigerians exposed to benzene in petrol through inhalation and ingestion while employed selling petrol syphoned from oil-drums at the roadside. Significant degrees of anaemia, hypochromia, neutropenia and thrombocytopenia were found in male vendors of heavy oil for motor scooters (n = 20), vendors of petrol and heavy oil (n = 52) and vendors of petrol alone (n = 46) compared to adolescent (n = 49) and adult (n = 80) male controls. Motor mechanics (n = 57) working at small repair workshops were also at risk of anaemia through exposure to petroleum products. Petrol pump attendants (n = 38) at modern filling stations did not appear to have any such occupational hazard. The practices of unofficial roadside vendors of petrol and heavy oil, and to a less extent motor mechanics, in the developing world are dangerous to health, being associated with blood dyscrasia and probably with increased incidence of aplastic anaemia and leukaemia. Education of the public and legislation are required to stop these practices.

Adolescent

Twenty-five Zambians with leukaemias.

Twenty-five Zambians with leukaemias were diagnosed in three years in Ndola. Acute leukaemias were certainly under-diagnosed in children. The commonest leukaemia was chronic lymphatic leukaemia (CLL), seen in 6 males and 7 females: 3 females and 2 males were aged less than 45 years. The age and sex distribution of the leukaemias in Zambia appears to resemble those of other sub-Saharan tropical African countries. It is postulated that a retrovirus could be associated aetiologically with CLL in young adults.

Female

Haematological status of blood-donors with sickle cell trait and alpha thalassaemia in northern Nigeria.

Northern Nigeria is an endemic area for sickle haemoglobin (HbS), and it is common practice in many hospitals to accept blood for transfusion from donors with sickle cell trait (HbAS). In 212 healthy HbAS blood donors, the proportion of HbS was found to range between 24-47%. The HbS levels less than 38% were presumably due to the interaction of sickle-cell gene with the alpha + thalassaemia gene. Low HbS levels and presumed alpha + thalassaemia were associated with significant microcytosis and relatively low Hb A2 and Hb F, but differences were minimal. Carriers of sickle cell trait, with or without alpha + thalassaemia, appear to be acceptable as blood donors. Beta thalassaemia was not detected amongst 710 blood-donors.

Adolescent