Maternal grandmothers improve nutritional status and survival of children in rural Gambia.

Hypotheses for the evolution of human female life-history characteristics have often focused on the social nature of human societies, which allows women to share the burden of childcare and provisioning amongst other members of their kin group. We test the hypothesis that child health and survival probabilities will be improved by the presence of kin using a longitudinal database from rural Gambia. We find that the only kin to improve the nutritional status of children significantly (apart from mothers) are maternal grandmothers, and that this is reflected in higher survival probabilities for children with living maternal grandmothers. There is also evidence that the reproductive status of the maternal grandmother influences child nutrition, with young children being taller in the presence of non-reproductive grandmothers than grandmothers who are still reproductively active. Paternal grandmothers and male kin, including fathers, have negligible impacts on the nutritional status and survival of children.

Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa.

BACKGROUND: Research over the past decade has suggested that prenatal and early postnatal nutrition influence the risk of developing chronic degenerative diseases up to 60 years later. We now present evidence that risk of death from infectious diseases in young adulthood is similarly programmed by early life events. METHODS: In three rural Gambian villages, affected by a marked annual seasonality in diet and disease, we have kept detailed demographic, anthropometric and health records since 1949. Fate was known with certainty for 3,162 individuals (2,059 alive/1,103 dead, most dying in childhood). For this case-control analysis of antecedent predictors of premature mortality, all adult deaths (n = 61) were paired with two randomly selected controls matched for sex and year of birth. RESULTS: Mean age at death was 25 (SD: 8) years. Adult death was associated with a profound bias in month of birth with 49 cases born in the nutritionally-debilitating hungry season (Jul-Dec) versus 12 in the harvest season (Jan-Jun). Relative to harvest season the hazard ratio for early death in hungry-season births rose from 3.7 (for deaths >14.5 years, P = 0.000013) to 10.3 (for deaths >25 years, P = 0.00002). Anthropometric and haematological status at 18 months of age was identical in cases and controls, indicating an earlier origin to the defect. Most deaths for which cause was known had a definite or possible infectious aetiology; none were from degenerative diseases of affluence. CONCLUSIONS: Early life exposures, correlated with season of birth, strongly influence susceptibility to fatal infections in young adulthood. The evidence suggests that nutritionally-mediated intrauterine growth retardation may permanently impair the development of immune function.

PIP: This paper presents the influence of prenatal and early postnatal nutrition on the risk of developing chronic degenerative diseases during late adulthood. Investigation of the thrifty phenotype hypothesis using 1949 birth records in three rural Gambian villages illustrates the severity of seasonality in diet and disease patterns. A database of 3162 individuals--2059 survivors and 1103 fatalities--was examined. Using a case-control analysis of antecedent predictors of premature mortality, all deaths were paired with two randomly selected controls matched for sex and year. Results revealed that the mean age at death was 25 years, with 49 adult death cases occurring in the nutritionally debilitating hungry season compared to 12 cases occurring during the harvest season. In relation to the harvest season, the hazard ratio rose from 3.7 (for deaths at age 14.5 years; p = 0.000013) to 10.3 (for deaths at age 25 years; p = 0.00002). Both the anthropometric and hematological status at 18 months was similar in cases and controls, with most deaths caused by a definite or possible infectious etiology without evidence of degenerative disease cause. This study concludes that early life exposures correlated with season of birth significantly influence the susceptibility to fatal infections in young adulthood. This also suggests that nutritionally mediated intrauterine growth retardation could permanently impair the development of immune function.

Possible routes of spread of carcinoma of the maxillary sinus to the oral cavity.

Carcinomas arising in the maxillary sinus, occasionally present clinically in the oral cavity along the occlusal ridge of the upper alveolus. The mechanism of this spread has not been investigated but it may resemble invasion of the mandible by oral carcinomas, which tend to invade the soft tissues rather than eroding through bone. In Britain, such patients are usually edentulous. This project examines deficiencies in the bony walls of the maxillary sinus to determine possible routes of spread. Maxillae were obtained from one side of 17 dissecting room cadavers, aged 71-95 years; 15 were edentulous. The roof of the maxillary sinus was removed in all specimens. Five maxillae were each cut into six slices, 0.5 cm thick, in a vertical bucco-lingual plane. In all, soft tissues were removed by treatment in dilute bleach. Histological sections, cut in the horizontal plane, were prepared of a further three maxillae. Several possible routes were identified by which tumors could spread from the sinus to the oral cavity: 1) directly through foramina in its floor; 2) through numerous foramina in its floor to the marrow cavity of the alveolar process, which mostly contained fat amongst narrow bony trabeculae. (The marrow cavity, in turn, had numerous communications with the occlusal surface); 3) through foramina which carried branches of the superior alveolar nerves and vessels; 4) through deficiencies in the bony walls of the sinus at the neurovascular grooves and elsewhere.

Towards a vaccine against malaria.

In many countries malaria is rapidly regaining its status as one of mankind's most important diseases, affecting not only indigenous populations but also travellers to endemic areas. This has stimulated much research into the mechanisms by which immunity is acquired to plasmodial infections and into the feasibility of producing effective vaccines against these. Four possible vaccines are under study, each targeted at a different stage of the complete life cycle of the Plasmodium. A vaccine targeted against the sporozoite could totally protect humans against mosquito-borne infection, while a vaccine against asexual erythrocytic forms would limit the morbidity and mortality of malaria rather than totally preventing it. In contrast, vaccines directed against the sexual forms of the parasite would not induce protection against infection, but would produce a transmission-blocking action, preventing the parasite developing in the mosquito vector. The construction of such vaccines and the measurement of the immune responses they induce has demanded the deployment of sophisticated and recently developed techniques, especially in immunology and molecular biology. However, man's capacity to acquire effective immunity to malaria has long been recognised and attempts to induce it artificially by means of vaccines have been made since the beginning of this century.

Agglutination of Plasmodium falciparum-infected erythrocytes from east and west African isolates by human sera from distant geographic regions.

Plasmodium falciparum-infected erythrocytes (PfE) were collected from acutely infected children in The Gambia and Tanzania and cultured for more than 30 hr until the parasites were mature trophozoites. Sera collected from these countries, other African countries, Asia, and South America were used in the PfE microagglutination test to determine whether PfE from East and West Africa share surface antigens. From the patterns of agglutination reactivity, we identified extensive antigenic diversity in surface antigens, but obtained no evidence for greater differences between isolates from East or West Africa and those within one region. The majority of sera from immune adults from The Gambia, Tanzania, Sudan, Nigeria, or Ghana were pan-agglutinating, and agglutinated all PfE isolates from The Gambia and Tanzania. Some sera from immune adults of Irian Jaya also agglutinated each of the seven African isolates, while others agglutinated many but not all of the isolates, similar to sera from immune adults of Flores, Indonesia. In contrast, sera from nonimmune adults from Colombia agglutinated few of the African isolates. It was remarkable, however, that sera from nonimmune Colombians agglutinated any African isolates. Our results are consistent with the following conclusions: some PfE surface antigen(s) are very diverse; this diversity is a feature of the parasite worldwide; the repertoire of isolate-specific surface antigens, although large, includes antigens that are either identical or antigenically cross-reactive in geographically very distant parasite populations; and African adults have pan-agglutinating antibodies that may contribute to protective immunity. Such pan-agglutinating antibodies could reflect the accumulation of a large repertoire of isolate-specific antibodies. The contribution of antibody against any shared PfE surface antigen to the pan-agglutinating reactivities is unknown and awaits development of the appropriate reagents.

The use of dermis to reconstruct the musculo-aponeurotic element of the anterior abdominal wall.

The use, in two patients, of a free graft of dermis to reconstruct the musculo-aponeurotic element of the anterior abdominal wall is described, one with a defect of the left epigastric region following resection of a desmoid tumour, the other with a periumbilical defect of the entire thickness of the abdominal wall following resection of a fungating colonic carcinoma, the latter patient with an adjacent left iliac defunctioning colostomy. A latissimus dorsi myocutaneous free flap was used to provide overlying cover for the graft.

Recombinant polypeptides for serology of malaria.

We have evaluated 3 molecularly defined polypeptides encoded by encloned Plasmodium falciparum genes for their ability to serve as antigens for detecting antimalaria antibodies. The recombinant proteins correspond to (i) a conserved part of 190-200 kDa schizont merozoite surface component, (ii) the carboxy terminal part of the P. falciparum aldolase, and (iii) the 5.1 antigen. Antibodies were detected using enzyme-linked immunosorbent assays (ELISA) in a high percentage of sera from individuals from a malaria endemic area in The Gambia (up to 99% for some adult groups). These results were further improved, especially for detection of antimalaria antibodies in children, when a pool of all 3 polypeptides (ELISA MIXT) was used as antigen. This ELISA MIXT improves presently available assays for the detection of antimalaria antibodies directed against asexual blood stages in respect of standardization, sensitivity and specificity.

The E-flat hand.

The disability suffered by a professional pianist because of difficulty in carrying out certain of the finger movement sequences involved in playing in the key of E flat appeared to be caused by limitation of independent flexion movements between the index and long fingers of his right hand. The range of independent movement of the fingers was considerably increased, with relief of his disability, by dividing the intertendinous connection between the extensor tendons of the two fingers on the dorsum of the hand.

Steroid hormone receptors in human salivary gland tumours.

Major salivary gland tumours were studied for the presence of hormone receptors for oestrogen and progesterone. Of the eight salivary gland tumours exhibiting varied histology, none showed high affinity receptors for oestrogen or progesterone. Salivary tissue from four patients with non-neoplastic salivary gland disease was also studied and found not to contain high affinity receptor sites. The absence of hormone receptors in these glands suggests that such tumours are not dependent on endocrine function.

Thoughts on malaria in pregnancy with consideration of some factors which influence remedial strategies.

There is evidence that pregnancy enhances the clinical severity of malaria, especially of P. falciparum infections. In pregnant women with little or no prior experience of the disease, P. falciparum causes severe clinical illness, substantial malaria mortality, increased rates of abortion and stillbirth and low birthweight of offspring; moreover, in such women, the clinical consequences seen unmodified by maternal parity. However, in pregnant women resident in highly endemic areas who have acquired considerable immunity through prolonged prior contact with malaria, parity appears to influence susceptibility to an important degree. Women who are pregnant for the first time are most affected, showing increased prevalence and density of parasitaemia, increased frequency of clinical illness (but not mortality) and significantly increased frequency of delivery of low birthweight children. In contrast, in multigravid women these clinical features are much less obvious and rarely attain statistical significance. The differences in susceptibility to malaria of pregnant women associated with parity and previous immunological experience require that protective strategies must be planned with full knowledge of the local epidemiology of malaria and be specifically targeted to the women who require them. Furthermore, the effectiveness of each strategy requires careful monitoring to permit such modifications as may be required by change in the immune status of the resident population.