Biomedical subjects
Publications and source records attributed to W H Lamb.
A girl with failure to thrive and a haemoglobin of 140 g/l at 1.3 years died from a brain haemorrhage 2.5 years later. Renal artery stenosis had caused severe, chronic hypertension and increased erythropoietin secretion (haemoglobin 182 g/l). Blood pressure should be measured in all unwell children, including those failing to thrive.
A patient with sideroblastic anaemia, development delay, and trichothiodystrophy is presented. Trichothiodystrophy is a feature of several autosomal recessive diseases. Photosensitivity, failure to thrive, and developmental delay are commonly observed in affected cases. X linked inheritance accounts for the bulk of cases with sideroblastic anaemia. This case highlights the importance of routine hair microscopy in cases of atypical ectodermal dysplasia.
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Data from the 1984-1985 epidemic of measles in Keneba, a Gambian village, have been reanalysed in order to test the effect of same sex vs. opposite sex transmission of measles on the severity of infection. A person infected by someone of the opposite sex was more likely to have severe infection with pulmonary complications than a person infected by someone of the same sex [RR (relative risk) = 2.8, 95% confidence interval (CI): 0.9-9.7]. A secondary case infected by someone of the opposite sex was significantly more likely to have a more severe illness relative to the primary case than a patient infected by someone of the same sex (P = 0.026, Fisher's exact test). There were slightly more female than male primary cases while male secondary cases had a higher risk than female cases of being infected by someone of the opposite sex (RR = 2.6, 95% CI: 0.9-6.9).
An infant of 31 weeks' gestation presented with refractory neonatal hypoglycaemia secondary to islet cell dysregulation. Treatment was started with somatostatin analogue and his glycaemic control improved initially. Tolerance developed, however, in that the dose required to maintain control increased by a factor of 40. The infant subsequently underwent pancreatectomy. It is safe to use somatostatin analogue in a preterm infant, but tolerance to the drug rapidly develops.
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Two babies are described with oesophageal atresia, a tracheo-oesophageal fistula and severe subglottic tracheal stenosis. A third baby, who did not survive, had a tracheal agenesis associated with bronchi arising from the oesophagus. A review of the types of tracheal stenosis and agenesis associated with various forms of tracheo-oesophageal fistula is included.
The effect of a combined supplement of iron, thiamine, riboflavin and vitamin C on malarial incidence in 5 to 14-year-old children was tested in a malnourished rural community in a region of The Gambia noted for high prevalence of malaria during the rainy season. 190 children, divided into 2 matched groups, received either the supplement or a matching placebo for 3 months. No significant difference in malarial incidence was observed between the 2 groups, despite a major improvement in biochemical indices of nutrient status in the supplemented group, especially for riboflavin and vitamin C. Severity of episodes was also similar between groups, but in subjects who developed parasitaemias there was a trend towards higher parasite counts in those receiving the active supplement. Nutritional interventions in malarious areas may have adverse effects on malaria, and the increase in parasitaemia was compatible with the hypothesis that a small but significant reduction in defences had occurred. However, the absence of increases in the incidence of proven malaria cases and their severity must also be taken into account, in order to make a balanced assessment of the possible increase in risk. Further investigations are needed to measure the risk in benefit rates, and to consider the effects of individual nutrients in isolation.
Three trials of intradermal hepatitis B virus (HBV) vaccines were made in Gambian children. In the first trial HBV vaccine (1 microgram) was given to neonates in the same syringe with BCG followed by two further does of 1.0 microgram of intradermal HBV vaccine. The trial was a failure, for 19 of 32 subjects had an HBV surface antibody response of less than 10 m.i.u./ml. In the second trial in young children two different regimes were used: two doses of 2 micrograms HBV vaccine were given intradermally after a 20 micrograms intramuscular dose or three doses of 2 micrograms were given intradermally. In both cases geometric mean antibody responses were significantly lower than in the control group who were given 20 micrograms HBV intramuscularly followed by two 10 micrograms doses intramuscularly. Vaccine failures, defined as the presence of HBV surface antigen or core antibody or absence of surface antibody, were also significantly higher in the intradermal groups. In the third trial 4 micrograms of vaccine were given intradermally to 20 young children with a multiple orifice head fired by a jet gun: all had a good HBV surface antibody response of greater than 100 m.i.u./ml of serum.
Birthweight data from 197 rural Gambian women who received an energy-dense prenatal dietary supplement over a 4-y period (net intake = 430 kcal/d) was compared with data from 182 women from 4 baseline years. Preintervention birthweights averaged 2944 +/- 43 (SEM) g when women were in positive energy balance during the dry harvest season (pregnancy weight gain greater than 1200 g/mo). Birthweights decreased to 2808 +/- 41 g (p less than 0.01) in the wet season when food shortages and agricultural work caused negative energy balance (weight gain less than 500 g/mo). There were no detectable secular trends in the baseline data. Supplementation was ineffective during the dry season but highly effective during the wet season: +225 +/- 56 g, p less than 0.001 (unadjusted) or +200 +/- 53 g, p less than 0.001 (adjusted for sex, season, and parity) by between-child multiple regression analysis; +231 +/- 65 g, p less than 0.001 by within-mother analysis. The proportion of low-birthweight babies (less than 2501 g) decreased from 23.7-7.5%, p less than 0.002. The observed threshold effect emphasizes the importance of selective targeting of interventions to truly at-risk groups.
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Mastitis was found to be a sizeable clinical problem in a group of lactating Gambian mothers. The mean monthly incidence was 2.6% and repeated episodes of mastitis were common. The role of milk antimicrobial factors in the local defence of the breast against mastitis was investigated by analysis of IgA, IgG, IgM, C3, C4, lactoferrin and lysozyme in the breast milk of 10 mastitis patients. Acute inflammation of the breast was accompanied by the rapid appearance of high concentrations of serum-derived immunoproteins in mastitic milk. Changes in the milk levels of lactose, sodium and transferrin indicated that this was due to a temporary opening of the paracellular pathway. Concentrations of secretory immunoproteins (IgA, lactoferrin and lysozyme) exhibited a delayed response, being elevated one week after the attack of mastitis. The normal milk of mastitis sufferers was significantly deficient in IgA, C3 and lactoferrin when compared with other lactating women suggesting that the former were predisposed to mastitis.
We have investigated infant-caregiver interactions in an isolated African subsistence farming community where women perform arduous agricultural tasks in addition to their normal domestic duties which include child care. 49 babies aged 3-18 months were studied on one or two occasions. Detailed observations were made of the level of care and of positive and negative stimulation offered to the child. Children were left in the charge of young nursemaids for up to 40% of the day while the mothers tended the crops. Despite this the total amount of positive and negative stimulation and care were similar whether or not the mother was engaged in fieldwork on the day of study. Grandmothers and fathers were both relatively unimportant caregivers. Total positive stimulation did not increase with age; on the contrary, young babies (3-9 months of age) were offered more positive stimulation and less negative stimulation than older ones (12-18 months). A positive correlation was found between total positive stimulation and developmental quotient (assessed by the Griffiths test). Similar amounts of care were given at all ages and there was no difference in the treatment of the two sexes.
Eighty-one pregnant or lactating women living in a village in The Gambia were allocated to treatment groups to receive a daily placebo, riboflavin, ferrous sulphate or ferrous sulphate plus riboflavin. At the beginning of the study and at 3 and 6 weeks thereafter women were examined clinically and blood samples collected for haematological and biochemical measurements. Pregnant women showed a wide range of response to supplement but among the lactating women an interesting pattern emerged: whereas the haematological status of the placebo group declined over 6 weeks, in the group receiving iron supplements this deterioration was reduced although not significantly. Riboflavin given in addition to iron resulted in a significant increase in circulating plasma iron and in iron stores, relative to the placebo.
Forty boys and girls between 11 and 14.5 years with evidence of subclinical vitamin deficiencies were allocated to two groups to receive, twice weekly, either a placebo or a multivitamin and iron supplement. Prior to supplementation and on two subsequent occasions about 5 weeks apart, the children performed an exercise regimen on a treadmill during which expired air was collected and heart rate monitored. The supplement resulted in marked improvements in riboflavin and vitamin C status and checked the decline in iron stores seen in the unsupplemented children. During the study the running performance of unsupplemented children deteriorated, and markedly so in a subgroup with initially poor nutrient status. The vitamin and iron supplement prevented this deterioration so as to produce a significant reduction in the energy cost of treadmill running in the more malnourished subgroup, relative to the changes seen in children receiving no supplement.
As an adjunct to the general nutrition research programme, the MRC Dunn Nutrition Unit has provided for the past 10 years a continuous medical service to three adjacent rural Gambian villages. There have been substantial reductions in annual childhood mortality rates. Perinatal mortality fell from 109.6 to 45.5 per 1000 births, infant mortality from 148.5 to 24.5 per 1000 live births, and mortality in children aged 1-4 years from 109.1 to 13.3 per 1000. There have been no pregnancy-related maternal deaths in the community for 8 years; 16 could have been expected given current estimates of maternal mortality elsewhere in rural Gambia. Of all the health and nutritional interventions introduced the single most important factor has apparently been the on-the-spot, 24 h availability of a physician or qualified midwife.
Five different vaccination schedules were used to immunise Gambian infants aged 4-6 months against measles with the attenuated Edmonston-Zagreb strain of virus, which has a history of passage in human diploid cells. Vaccine aerosol given either by mask in a dose of 3500 or 7000 plaque-forming units (PFU) or from a plastic bag at a dose of 7000 PFU raised haemagglutinin-inhibiting or plaque-inhibiting measles antibody 16-24 weeks after vaccination to a titre of 1 in 8 or greater in all but 3 of the 51 children so vaccinated. All 21 infants given 11 400 PFU of vaccine intradermally in two divided doses and the 21 given 39 000 PFU of the virus subcutaneously also had satisfactory levels of measles antibody 16 weeks after vaccination. None of the vaccinated children had clinical evidence of measles in the 12 to 17 months after vaccination. The Edmonston-Zagreb vaccine, given subcutaneously or by other routes at 4-6 months, may be useful in preventing measles in infants in African cities, where 15-30% of children have measles before they are 9 months old, which is the recommended age for immunisation with the chick-cell-adapted strains of measles virus.