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Biomedical subjects

R G Hendrickse

Publications and source records attributed to R G Hendrickse.

At least 19 recordsLinked to original sources

Depression of the Ca(2+)-ATPase activity of the rat liver endoplasmic reticulum by the liver tumour promoters, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane and phenobarbital.

The effects of a short-term in vivo administration of two liver tumour promoters (phenobarbital and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane on rat liver endoplasmic reticulum Ca(2+)-ATPase were investigated. The specific activity values of this membrane-bound enzyme significantly decreased (P less than 0.01) by 51% for phenobarbital-treated rats and by 48% for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane-treated rats compared with control animals. The depression of liver endoplasmic reticulum Ca(2+)-ATPase appears to be a manifestation of the toxicological effect of tumour promoters.

Animals

Clinical implications of food contaminated by aflatoxins.

Aflatoxins have been incriminated, mainly on circumstantial evidence, in hepatocellular carcinoma, acute hepatic failure and Reye's syndrome, but other possible effects of continuous or intermittent dietary exposure to aflatoxins, which occurs widely in the tropics, have received little study. Over the past 10 years evidence has steadily accumulated that incriminates aflatoxins in the aetiology of kwashiorkor, a widespread and serious disorder of children in the tropics, previously believed to be caused by protein deficiency. Investigation of human breast milk, undertaken initially to elucidate the pathogenesis of kwashiorkor in breastfed infants, has revealed widespread and serious exposure to aflatoxins from this source. Extension of these studies to pregnant women, in turn, revealed widespread and serious prenatal aflatoxin exposure. In laboratory and farm animals, such exposure has serious implications for immune and hepatic functions, and is detrimental to growth and development. Recent analysis of heroin samples show that heroin addicts may also be exposed to these toxins. These findings show that human exposure to aflatoxins may begin prenatally, persist during breastfeeding, and continue into adult life. It is postulated that aflatoxins (i) play a role in the aetiology of kwashiorkor, (ii) increase neonatal susceptibility to infection and jaundice, (iii) increase childhood susceptibility to infections and malignant disease, (iv) compromise immune responses to prophylactic immunisations and (v) may play a role in the pathogenesis of diseases in heroin addicts. There are indications also that acute, fatal aflatoxin poisoning which masquerades as 'hepatitis' may occur more frequently than is currently appreciated.

Acute Disease

Aflatoxin excretion in children with kwashiorkor or marasmic kwashiorkor--a clinical investigation.

A group of five children with kwashiorkor, seven with marasmic kwashiorkor and one underweight child were given an aflatoxin-free diet consisting of maize meal and milk powder. Blood specimens were collected on admission; on day 4 and 10, 24 hour urine and stool samples were collected for the first ten days. Serum, urine and stool samples were analysed for aflatoxins using high performance liquid chromatography with fluorescent detection, after various extraction and clean-up procedures. The children with kwashiorkor and marasmic kwashiorkor excreted aflatoxins in stools for up to 9 and 6 days after admission respectively. No aflatoxins were detected in the stools or urine of the underweight child. In kwashiorkor, urinary excretion ceased after 2 days, while in marasmic kwashiorkor urinary excretion persisted for 4 days. In stools, B1 was the type of aflatoxin detected most frequently in kwashiorkor and least frequently in marasmic kwashiorkor. Aflatoxin M2 was frequently detected in the stools of both groups of children. Estimates of the total amount of aflatoxin excreted by kwashiorkor and marasmic kwashiorkor indicate that these children were harbouring up to 4 micrograms/kg body weight at the time of admission. These findings establish that aflatoxins accumulate in body fluids and tissues in kwashiorkor and marasmic kwashiorkor which is only slowly eliminated.

Aflatoxin B1

Iron-deficiency anaemia and its response to oral iron: report of a study in rural Gambian children treated at home by their mothers.

Haematological and iron parameters, measured in 907 children aged from 6 months to 5 years in rural Gambia at the start of the rainy season, differed from those in American reference populations as follows: mean haemoglobin levels were much lower at ages 1 and 2 years and mean levels of mean corpuscular volume (MCV) were lower at all ages (at age 1 year mean haemoglobin was 11.2 g/dl and mean MCV 68.2 fl); in a sample of 249 children randomly selected from the whole study population, mean serum iron levels were similar but mean transferrin saturation and mean serum ferritin levels were lower, especially at ages 1-3 years (at age 1 year mean serum iron was 11.1 mumol/l, mean transferrin saturation 16.9%, and geometric mean serum ferritin 8.8 ng/ml. A total of 213 children (23%) whose haemoglobin and mean corpuscular volume were both less than the 3rd percentile of the reference population received oral iron or placebo from their mothers during the rainy season when malaria transmission is maximal. Mean levels of haemoglobin, mean corpuscular volume, serum iron, transferrin saturation and serum ferritin rose in the iron-treated group and fell in the placebo group at all ages, except under 1 year for serum ferritin, to produce significant differences between the groups by the end of the study. Total iron-binding capacity showed no significant changes during the study. We concluded that oral iron given by the mother during the rainy season can be used to treat iron-deficiency anaemia in Gambian children who would otherwise become more anaemic.

Administration, Oral

The effects on malaria of treatment of iron-deficiency anaemia with oral iron in Gambian children.

In order to determine whether giving iron to iron-deficient children increases their susceptibility to malaria, 213 Gambian children aged between 6 months and 5 years with iron-deficiency anaemia were randomized to receive either oral iron or placebo during the rainy season when malaria transmission is maximal. Haematological and iron measurements improved significantly in the group given iron. Regular morbidity surveys showed that fever associated with parasitaemia occurred more frequently in the iron-treated group than in the placebo group. This difference was not significant for all parasitaemias grouped together, but became significant and progressively larger for parasitaemias of ten or more positive fields per 100 high power fields (P less than 0.025), and for parasitaemias of 50 or more positive fields per 100 high power fields (P less than 0.01). Three children in the iron-treated group but none in the placebo group had more than one episode of fever and parasitaemia. Splenomegaly rates rose appreciably during the study in both groups, but in children at age 2 years the splenomegaly rate at the end of the study was significantly greater in the iron-treated group. We concluded that there is a significantly increased risk of fever associated with severe malarial parasitaemia for children with iron-deficiency anaemia given iron during the season of maximal malaria transmission in this part of The Gambia.

Administration, Oral

Foetal and neonatal exposure to aflatoxins.

Studies on 125 primigravidae in rural Kenya revealed aflatoxins in the blood of 54 prenatally. At delivery re-examination of 34 showed aflatoxins in 12 previously negative. The overall detection rate was 53%. Blood from additional 59 women collected at delivery showed aflatoxins in 53%. Aflatoxins were detected in 37% of 101 cord bloods. There was no relationship between aflatoxins in maternal and cord bloods. The frequency of detection was significantly higher in maternal and cord bloods during the 'wet' than 'dry' months. The mean birth weights of females born to aflatoxin positive mothers was significantly lower (255 g) than those born to aflatoxin free mothers. Two stillbirths were recorded, in both cases maternal and cord blood showed aflatoxins. These findings and the adverse effects of prenatal aflatoxin exposure recorded in animal experiments indicate the need for further study of the effects of aflatoxins on the human foetus and newborn.

Aflatoxins

Protein-energy malnutrition in northern Sudan: prevalence, socio-economic factors and family background.

The socio-economic and family background and the nutrition of 145 children with kwashiorkor admitted to hospital in Khartoum over a 2-year period were compared with 113 marasmic kwashiorkor, 158 marasmic, and 186 nutritionally normal controls of similar age. Peak admissions for kwashiorkor were in the wet and post-wet season and the mean (SD) age was 1.6 (0.6) months. Mothers of malnourished children were more likely to be pregnant, and had poorer housing, sanitation and water supply, a lower income and food expenditure and less education than controls. Mothers of controls breastfed their children longer, introduced mixed feeding earlier, offered a wider variety of foods, and were more likely to have had their infants immunized. Neither family instability nor cultural practices which result in separation of children from their mothers appear to have an important role in protein-energy malnutrition in the Sudan. Families of kwashiorkor children had a higher food expenditure and better maternal education than marasmic children. There was no significant difference between the two groups in duration of breastfeeding or in the age of introduction of mixed diet. However, kwashiorkor children appeared to be offered more meat. Differences in food availability could account for the relative retardation of growth and lack of subcutaneous fat in marasmus compared to kwashiorkor.

Breast Feeding

Climatic conditions and kwashiorkor in Mumias: a retrospective analysis over a 5-year period.

Hospital records from a rural hospital in Kenya were retrospectively analysed for the total monthly admissions for kwashiorkor and all other forms of malnutrition over a 5-year period. These figures were related to the climatic conditions that prevailed during the year as derived from the records of a meteorological station in the area. The peak prevalence for kwashiorkor coincided each year with the season during which relative humidity was highest. The prevalence of kwashiorkor is discussed in relation to variable aflatoxin formation, which is influenced by seasonal changes in weather conditions.

Child

Detection of cow's milk protein intolerance by an enzyme-linked immunosorbent assay.

Circulating IgG antibodies to cow's milk proteins have been quantified in 182 children using an enzyme-linked immunosorbent assay (ELISA). Antibody levels in children with cow's milk protein intolerance (CMPI) were compared with those in control groups comprising other diarrhoeal diseases, atopic children, and a "normal" sample including children with toddler diarrhoea. Mean IgG antibody levels in children with CMPI were significantly higher than in any of the control groups. There were clear differences in peak antibody levels between CMPI and all other groups for each of the protein fractions tested. There was some overlap in titres between CMPI and other enteropathies but the assay gave 88% sensitivity and specificity for the diagnosis of CMPI overall and was 100% specific against the combination of non-enteropathic controls in this study. These findings indicate that the assay could be applied as an outpatient screening test for CMPI and would be particularly useful in differentiating "toddler" diarrhoea from CMPI.

Adolescent

Protein-energy malnutrition in northern Sudan: clinical studies.

The medical history, clinical features and investigations of 145 children with kwashiorkor were compared with 113 marasmic kwashiorkor, 158 marasmic children and 186 nutritionally normal controls of similar age admitted to hospital in Khartoum. Factors in the group with protein-energy malnutrition (PEM) which could relate to aetiology include: a history of prolonged illness and anorexia, frequent and prolonged episodes of diarrhoea and recent measles. The delay in achievement of developmental milestones in PEM children probably reflects the frequent and chronic illnesses in this group. An episode of previous oedema was reported in 22 per cent of marasmic kwashiorkor, 12 per cent of kwashiorkor and 12 per cent of marasmic children. Though hair and mucosal changes and enlarged liver were more common in the marasmic kwashiorkor and kwashiorkor groups, they were also common in marasmic children. There was no significant difference in behaviour (apathy, irritability, anorexia) between kwashiorkor and marasmic children. The classical skin changes of kwashiorkor were only seen in the oedematous children. The mortality was 19 per cent in kwashiorkor, 35 per cent in marasmic kwashiorkor, and 14.5 per cent in the marasmic group. The major differences between marasmus and kwashiorkor children were that the kwashiorkor children were reported larger at birth, achieved more normal developmental milestones, were taller and had larger head circumference than the marasmic children. The implications of these findings in relation to aetiology are discussed.

Anthropometry

Loperamide in acute diarrhoea in childhood: results of a double blind, placebo controlled clinical trial.

Fifty-three young children with acute diarrhoea were included in a hospital-based, double-blind trial of loperamide at two dose levels (0.4 and 0.8 mg/kg/day), given with standard oral rehydration therapy versus placebo plus oral rehydration therapy. The differences in the overall recovery rate were significant (P less than 0.05), the fastest being in the group given 0.8 mg/kg and slowest in the placebo group. Comparison between weights on admission and weights by day 3 showed that more children in the loperamide groups gained weight than in the placebo group (P less than 0.05). No serious side effects of loperamide were observed. The drug was withdrawn in one child because of excessive lethargy and sleep. The results indicate that loperamide in the doses employed is safe and may be a useful adjunct to oral rehydration in certain children.

Child, Preschool