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Biomedical subjects

S M Filteau

Publications and source records attributed to S M Filteau.

At least 19 recordsLinked to original sources

Comparison of armspan, arm length and tibia length as predictors of actual height of disabled and nondisabled children in Dharavi, Mumbai, India.

OBJECTIVES: To investigate appropriate measurements to predict height in children with physical impairments to facilitate the accurate assessment of nutritional status in field studies. DESIGN: Case-control cross-sectional study. SETTING: Dharavi, a large slum in Mumbai, India. SUBJECTS: In total, 141 children with mixed disabilities and 162 nondisabled control children, aged 2-6 y. METHODS: Height/length, armspan, arm length and tibia length were measured to the nearest 0.1 cm using standard procedures. The relations between armspan, arm length and tibia length with height in controls were investigated using linear regression. RESULTS: Armspan (R(2)=0.93, P<0.001, n=158), arm length (R(2)=0.81, P<0.001, n=162) and tibia length (R(2)=0.72, P<0.001, n=161) were found to be strong predictors of height based on data from nondisabled control children. These measurements could be used to determine a more accurate height for children with physical impairments where the nature of the impairment may interfere with height measurements. CONCLUSIONS: Armspan, arm length and tibia length can be used to determine accurate height for children with physical impairments, for example, children with a nonambulatory status or those with kyphosis or scoliosis of the spine.

Anthropometry↗

Serum leptin in disabled and non-disabled children in an Indian slum population.

OBJECTIVE: To assess the concentration of serum leptin in a population of malnourished children and to compare the leptin levels of disabled and non-disabled children in this population. DESIGN: Case-control study. SUBJECTS: Eighty-one children, comprising 41 children with mixed disabilities and 40 non-disabled controls, were selected from 425 children involved in a case-control study assessing the nutritional status of children with disabilities in an Indian slum population. METHODS: Leptin was measured in the serum samples and was compared with anthropometry (weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ), weight-for-height Z-scores (WHZ), body mass index (BMI), mid-upper-arm circumference (MUAC), sub-scapular skinfold thickness and triceps skinfold thickness) and serum acute phase proteins. RESULTS: The children were very malnourished with WAZ=-2.07 (s.d. 1.15), HAZ=-2.15 (s.d. 1.85) and WHZ=-1.07 (s.d. 0.83). Leptin was extremely low in both the disabled (1.44 ng/ml; 95% confidence interval, CI, 1.23-1.69) and the non-disabled (1.19 ng/ml; 95% CI 1.04-1.35) children. There were no differences between the disabled and non-disabled groups as a whole but 15 children with neurological disabilities had significantly higher (P<0.05) serum leptin (1.65 ng/ml; 95% CI 1.29-2.06) than the non-disabled children. Girls (1.55 ng/ml; 95% CI 1.29-1.87) had significantly higher concentrations of leptin than boys (1.11 ng/ml; 95% CI 1.02-1.22; P=0.002). Leptin did not correlate with any biochemical or anthropometric measures. CONCLUSIONS: In this population, where malnutrition was common, serum leptin levels were very low and did not correlate with anthropometry. SPONSORSHIP: UK Department for International Development; Virgin Airways through the Great Ormond Street Hospital Trustees.

Acute-Phase Proteins↗

Feeding mode, intestinal permeability, and neopterin excretion: a longitudinal study in infants of HIV-infected South African women.

Exclusive breast feeding has been associated with a lower rate of mother-to-child HIV transmission than breast feeding plus other foods. To obtain further information on biologic outcomes of different feeding modes, we examined 272 infants of HIV-infected South African women at ages 1, 6, and 14 weeks. At each visit information about infant diet and morbidity was collected and infants underwent a lactulose/mannitol dual sugar intestinal permeability test. In a subset of infants, urinary neopterin excretion was measured as an indicator of immune system activation. Infants who had themselves become HIV-infected by 14 weeks had higher ( p <.01) intestinal permeability at 6 and 14 weeks and slightly (.05 < p <.1) higher neopterin excretion at all times than uninfected infants. At 1 week infants given no breast milk had higher ( p <.05) intestinal permeability than infants given breast milk exclusively or with other foods. Intestinal permeability in infants fed breast milk plus other foods was never increased relative to that of exclusively breastfed infants. Feeding mode had no effect on neopterin excretion. Thus, infant HIV infection induces changes in gut permeability and possibly immune system activation before clinical symptoms become apparent. The effects of feeding mode on infant intestinal permeability or urinary neopterin excretion do not explain a possible protective effect of exclusive breast feeding on mother-to-child transmission of HIV.

Adult↗

Variation in breastmilk HIV-1 viral load in left and right breasts during the first 3 months of lactation.

The mechanism and risk factors associated with mother-to-child transmission of HIV-1 through breastfeeding remain unclear; breastmilk viral load may be an important determinant of transmission. Analysis of breastmilk cell-free viral load in samples taken from each breast at 1, 6 and 14 weeks postpartum showed that HIV-1 is shed intermittently and load may differ considerably between breasts of an individual woman at any given time. Breastmilk HIV-1 load was undetectable in approximately one-third of samples.

Breast↗

The effect of antenatal vitamin A and beta-carotene supplementation on gut integrity of infants of HIV-infected South African women.

BACKGROUND: Vitamin A is important for protection against diarrhea, and supplements may benefit gut function of infants of HIV-infected mothers. METHODS: We studied 238 infants of HIV-infected South African women participating in a randomized, double-blind, placebo-controlled trial of vitamin A during pregnancy (1.5 mg retinyl palmitate and 30 mg beta-carotene daily) plus 60 mg retinyl palmitate at delivery. The placebo group received identical placebo capsules at the same times. When infants were 1, 6, and 14 weeks of age, lactulose/mannitol dual sugar intestinal permeability tests were performed. RESULTS: Maternal vitamin A supplementation did not significantly affect infant gut permeability in the group as a whole at any time. By multiple regression analysis, HIV infection of the infant by 14 weeks was significantly associated with increased gut permeability at both 6 and 14 weeks. After controlling for birth weight, gestational age, current weight, feeding mode and recent morbidity, there was a trend toward an interaction between vitamin A supplementation and HIV infection (P = 0.086) at 14 weeks. Vitamin A made no difference to gut permeability of uninfected infants (lactulose/mannitol ratio for vitamin A group: 0.11, 95% confidence interval [CI] 0.08, 0.15, n = 73 and for placebo group: 0.09, 95% CI 0.06, 0.12, n = 76), but largely prevented the increase in the ratio of HIV-infected infants (vitamin A group: 0.17, 95% CI 0.13, 0.23, n = 23; placebo group: 0.50, 95% CI 0.37, 0.68, n = 20). The effects on the lactulose/mannitol ratio were related to changes in lactulose, not mannitol, excretion. Vitamin A supplementation was associated with significantly lower lactulose excretion at 1 and 14 weeks, suggesting the major effect of vitamin A was on maintaining the integrity of gut tight junctions. CONCLUSIONS: Vitamin A supplementation of HIV-infected pregnant women may prevent the deterioration in gut integrity in the subgroup of their infants who themselves become infected. Improving vitamin A status of HIV-infected infants may decrease their gastrointestinal morbidity.

Adult↗

Subclinical mastitis as a risk factor for mother-infant HIV transmission.

Subclinical mastitis, as diagnosed by an elevated sodium/potassium ratio in milk accompanied by an increased milk concentration of the inflammatory cytokine, interleukin-8 (IL8), was found to be common among breast feeding women in Bangladesh and Tanzania. Subclinical mastitis results in leakage of plasma constituents into milk, active recruitment of leukocytes into milk, and possible infant gut damage from inflammatory cytokines. Therefore, we wished to investigate whether subclinical mastitis was related to known risk factors for postnatal mother-to-child HIV transmission, that is, high milk viral load or increased infant gut permeability. HIV-infected South African women were recruited at the antenatal clinic of McCord's Hospital, Durban. Risks and benefits of different feeding strategies were explained to them and, if they chose to breast feed, they were encouraged to do so exclusively. Women and infants returned to the clinic at 1, 6 and 14 weeks postpartum for an interview about infant health and current feeding pattern, a lactulose/mannitol test of infant gut permeability, and milk sample collection from each breast separately for analysis of Na/K ratio, IL8 concentration and viral load in the cell-free aqueous phase. Only preliminary cross-sectional analyses from an incomplete database are available at this point. Moderately (0.6-1.0) or greatly (>1.0) raised Na/K ratio was common and was often unilateral, although as a group right and left breasts did not differ. Considering both breasts together, normal, moderately raised or greatly raised Na/K was found, respectively, in 51%, 28%, 21% of milk samples at 1 week (n=190); 69%, 20%, 11% at 6 weeks (n=167); and 72%, 16%, 12% at 14 weeks (n=122). IL8 concentration significantly correlated with both Na/K and viral load at all times. Na/K correlated with viral load at 1 and 14, but not 6 weeks. At 1 and 14 weeks, geometric mean viral loads in samples with Na/K > 1.0 were approximately 4 times those in samples with Na/K < 0.6. At 1 week but not later times, exclusive breast feeding was associated with lower milk viral load than was mixed feeding. Gut permeability was unrelated to milk Na/K ratio or IL8 concentration and was not significantly increased by inclusion of other foods than breast milk in the infant's diet. The results suggest that subclinical mastitis among HIV-infected women may increase the risk of vertical transmission through breast feeding by increasing milk viral load. The importance of various causes of subclinical mastitis, which likely differ at 1 week from at later times and may include local infection or sterile inflammation, systemic infection, micronutrient deficiencies, or poor lactation practices, needs to be further clarified so that appropriate interventions can be implemented.

Africa South of the Sahara↗

Role of breast-feeding in managing malnutrition and infectious disease.

Breast-feeding policy tends to be an emotive issue. International agencies recommend exclusive breast-feeding for 4-6 months followed by continued partial breast-feeding into the second year of life in order to promote infant and child health and minimize the damage caused by the malnutrition-infection cycle. To what extent are these recommendations supported by the experimental evidence? Are they a simplification for emotional reasons or public health purposes? Breast-feeding is believed to benefit infants because breast milk contains the ideal mix of nutrients for infants, because it contains factors which promote development of the infant's gut and immune system and which prevent pathogen invasion, and because exclusive breast-feeding prevents intake of pathogens in food or water. However, some apparently contradictory evidence exists. First, in environments which are not highly contaminated breast-fed infants tend to growth falter relative to those fed formula. Second, in such environments partial breast-feeding is not associated with significantly increased gut damage relative to exclusive breast-feeding, suggesting that active promotion of gut development by breast-feeding is more important than simple avoidance of pathogens from other foods. Third, many immune factors in breast milk are probably present primarily to protect the mother, not the infant. Finally, breast milk itself may contain bacteria or viruses. This problem has come to the fore with the human immunodeficiency virus epidemic, since it is clear breast-feeding is an important mode of mother-to-child transmission. The present review will examine these challenges to the basis of the international infant feeding recommendations and will suggest that the science does actually support the policy.

Adult↗

Physiology, immunology, and disease transmission in human breast milk.

Breast feeding is an important mode of mother-to-child transmission of HIV. Interventions to decrease the number of infants becoming infected are particularly required for women in less developed countries where breast feeding is essential for infant survival. This review discusses the physiology and immunology of breast feeding and how maternal health interventions in the postpartum period may help decrease mother-to-child HIV transmission.

Breast Feeding↗

Vitamin A supplementation of South African children with severe diarrhea: optimum timing for improving biochemical and clinical recovery and subsequent vitamin A status.

BACKGROUND: Vitamin A has well-recognized benefits for prevention of diarrhea, but the impact of therapeutic doses given during diarrhea on biochemical and clinical outcomes is less clear. We investigated these potential therapeutic benefits within a study of the optimum time for vitamin A supplementation to promote vitamin A status. METHODS: Young children with severe diarrhea were randomized to receive 60 mg of retinol as retinyl palmitate during acute diarrhea or once symptoms had resolved, usually after 5 to 8 days. Either during acute diarrhea or after its resolution, children not receiving vitamin A were given identical placebo. On Days 0 and 3 we measured urinary neopterin, plasma retinol and acute phase proteins and intestinal permeability by the lactulose/mannitol test. Eight weeks after discharge children returned to hospital for a modified dose response test of vitamin A stores. RESULTS: Most children presented with watery diarrhea and grossly abnormal intestinal permeability and immune activation markers. At 8 weeks plasma retinol concentrations of children receiving vitamin A during acute diarrhea, compared with those receiving it in early convalescence [0.67 (95% confidence interval, 0.58 to 0.76) micromol/l vs. 0.68 (95% confidence interval, 0.59 to 0.79) micromol/l], and the proportion of children with deficient vitamin A stores (7 of 34 vs. 8 of 34) did not differ. Clinical features, lactulose/mannitol tests and urinary neopterin concentrations on Day 3 also did not differ significantly when vitamin A was given early or late. CONCLUSIONS: Even when it was given during severe diarrhea, a large dose of vitamin A improved vitamin A stores in a population in whom vitamin A deficiency is a public health problem. Vitamin A did not significantly improve early clinical or biochemical recovery from severe diarrhea.

Chi-Square Distribution↗

Use of the retinol-binding protein: transthyretin ratio for assessment of vitamin A status during the acute-phase response.

The ratio plasma retinol-binding protein (RBP):transthyretin (TTR) has been proposed as a means to improve the assessment of vitamin A status of individuals with concurrent infection or inflammation. We have measured RBP and TTR in stored sera from South African children who had accidentally ingested kerosene. Samples were collected from these children in hospital when suffering acute inflammation and respiratory distress, and from them and neighbourhood control children 3 months later. Vitamin A status was defined by modified relative dose response (MRDR) tests of liver retinol stores at 3 months and by serum retinol concentration both when children were ill and when they were well. Illness was defined as either being in hospital or, at follow-up, as having a raised plasma alpha 1-acid glycoprotein (AGP) level. The RBP:TTR value was significantly decreased by both illness and low liver retinol stores. When the effects on RBP:TTR of illness and vitamin A stores were considered together for the 3-month follow-up samples, only vitamin A status significantly decreased the value. We calculated sensitivity and specificity of the RBP:TTR ratio against established measures of vitamin A status using a cut-off value of 0.3 for RBP:TTR and standard cut-off values for MRDR (0.06) and plasma retinol (0.7 mumol/l). Compared with MRDR, RBP:TTR had sensitivities of 76% and 43% and specificities of 22% and 81% to detect vitamin A deficiency in hospitalized and well children respectively. Compared with plasma retinol, sensitivities were 88% and 44% and specificities were 55% and 64% in hospitalized and well children respectively. Only for the case of clinically well children with biochemical evidence of subclinical inflammation did sensitivity (62% and 100% against MRDR and plasma retinol respectively) and specificity (100% and 60% against MRDR and retinol) approach useful levels for an assessment tool. Overall, although a trend supporting the theory behind the use of the RBP:TTR for assessment of vitamin A status in infection was observed in the current study, the ratio did not provide adequate sensitivity and specificity to be a useful assessment tool.

Acute-Phase Reaction↗

The nutritional status of disabled children in Nigeria: a cross-sectional survey.

OBJECTIVE: To compare the nutritional status of disabled children in Nigeria with their non-disabled siblings and neighbours. A second aim was to investigate anthropometric techniques appropriate for disabled children in this situation. DESIGN: A cross-sectional survey. SETTING: Nasarawa and Plateau States and the Federal Capital Territory in Central Nigeria. SUBJECTS: 311 children under 10 years of age were studied: 112 with various disabilities, 87 siblings and 112 neighbours. METHODS: Selected anthropometric measurements, (height, weight, mid-upper arm circumference (MUAC), demispan and halfspan), and blood haemoglobin levels were assessed by trained personnel. All measurements of disabled subjects were compared to the non-disabled controls. RESULTS: The disabled subjects had mean height for age (ht/age) and weight for age (wt/age) significantly lower than the control group (P<0.05). These differences were due largely to the very low Z scores in children with neurological impairments, (ht/age= 3.07 (s.d.=1.6); wt/age= 2.0 (s.d.=1.2)). Measurement difficulties contributed to low height values in disabled children and halfspan was found to be a useful proxy for height in these children. MUAC results were higher for the children with disabilities due to polio than for controls. The mean haemoglobin levels were slightly but significantly higher (P<0.05) in the disabled and sibling groups compared to the neighbourhood group. CONCLUSION: Disabled children with neurological impairments and consequent feeding difficulties are nutritionally at risk, but others are no worse off than their non-disabled peers in this area. Halfspans may serve as a useful proxy indicator for estimating height in some children with physical impairments. SPONSORSHIP: The study was funded by a TEAR fund grant to JT for her MSc studies.

Anthropometry↗

Milk cytokines and subclinical breast inflammation in Tanzanian women: effects of dietary red palm oil or sunflower oil supplementation.

Previously, we have found that subclinical breast inflammation, as indicated by raised breastmilk concentrations of sodium and the inflammatory cytokine, interleukin-8 (IL-8), was highly prevalent in Bangladesh and associated with poor infant growth. In order to investigate further the prevalence of subclinical breast inflammation and to assess the impact of dietary intervention, we studied rural Tanzanian women taking part in a study of dietary sunflower or red palm oil supplementation during late pregnancy and lactation. We measured breastmilk concentrations of IL-8, the anti-inflammatory cytokine, transforming growth factor-beta2 (TGF-beta) and the ratio of sodium to potassium. We also estimated systemic inflammation by plasma concentrations of the acute phase proteins, alpha1-acid glycoprotein and C-reactive protein. There were highly significant intercorrelations among milk Na/K ratio and concentrations of IL-8 and TGF-beta, the last only after treatment with bile salts which also improved TGF-beta recovery in the enzyme-linked immunosorbent assay (ELISA). Plasma acute phase protein concentrations tended to correlate with milk Na/K ratio and IL-8, suggesting that subclinical breast inflammation was related to systemic inflammation. Dietary supplementation with vitamin E-rich sunflower oil but not provitamin A-containing red palm oil decreased milk Na/K, IL-8 and TGF-beta at 3 months postpartum; however, the effect was significant only for Na/K ratio. The results suggest that milk Na/K ratio, IL-8, and TGF-beta all measure the same phenomenon of subclinical breast inflammation but that Na/K ratio, having the lowest assay variability, is the most useful. Subclinical breast inflammation may result in part from systemic inflammation and may be improved by increased dietary intake of vitamin E-rich sunflower oil.

Acute-Phase Proteins↗

Acute phase proteins as markers of systemic illness in acute diarrhoea.

Fifty-seven Tanzanian children, 6-25 months, hospitalized with acute diarrhoea were grouped according to whether there was clinical evidence of systemic infection (SI) (n = 35) or not (n = 22). Serum acute phase proteins were measured in samples taken within 48 h of admission. Means for C-reactive protein (CRP) and serum amyloid A (SAA) were significantly higher in children with SI compared to those without (geometric means (95% CI); CRP, mg/l: 22.1 (13.6-35.5) vs. 7.4 (4.4-12.4); SAA, mg/l: 12.2 (6.8-22.1) vs. 4.9 (2.5-9.7)). Levels of alpha1-acid glycoprotein were similar in both groups (1.16 g/l (0.95-1.43) vs. 1.04 (0.83-1.29), respectively). CRP > or =30 mg/l had a positive predictive value of 95%, and specificity of 96% for correctly identifying SI, but a low sensitivity (51%) and negative predictive value (55%). Clinical outcome of diarrhoea was worse in children with SI: more needed intravenous fluids (23% vs. 5%), the duration of diarrhoea was longer (59.4 vs. 34.2 h) and mortality was higher (6% vs. 0%). APPs were not found to be useful markers of systemic illness in acute diarrhoea in this population.

Acute Disease↗

Breast milk immune factors in Bangladeshi women supplemented postpartum with retinol or beta-carotene.

BACKGROUND: Vitamin A supplementation of mothers postpartum may improve infant health, not only by increasing vitamin A delivery to the infant through breast milk but also by increasing delivery of milk immune factors. Our hypothesis was that postpartum supplementation with vitamin A increases milk concentrations of certain soluble immune factors. DESIGN: In a double-blind trial conducted in Matlab, Bangladesh, women at 1-3 wk postpartum were randomly assigned to receive until 9 mo postpartum 1) a single dose of 60 mg retinol as retinyl palmitate followed by daily placebos (n = 69), 2) daily doses of 7.6 mg beta-carotene (n = 72), or 3) daily placebos (n = 71). Milk samples collected at baseline and 3 mo postpartum were analyzed by enzyme-linked immunosorbent assay for secretory immunoglobulin A, lactoferrin, lysozyme, and interleukin 8; by HPLC for total retinol; and by atomic absorption spectroscopy for sodium and potassium. RESULTS: After mammary epithelial permeability (defined as an elevated Na:K) and baseline immune factor concentrations were controlled for, there were no significant treatment effects on immune factors at 3 mo. Increased mammary permeability was common (25% of women at baseline and 12% at 3 mo) and was associated with higher concentrations of milk immune factors. Low body vitamin A stores at baseline, as assessed by the modified-relative-dose-response test, were associated with a higher Na:K, but neither retinol nor beta-carotene supplementation affected the prevalence of increased mammary permeability. CONCLUSIONS: Postpartum vitamin A supplementation does not increase milk concentrations of immune factors. The causes of increased mammary epithelial permeability in this population require further study.

Bangladesh↗

Vitamin A status does not influence neopterin production during illness or health in South African children.

Excessive interferon-gamma (IFN-gamma) production appears to be a primary immunological lesion in vitamin A-deficient experimental animals but comparable data from humans is lacking. We investigated IFN-gamma production in South African children by measurement of urinary excretion of neopterin, a product of IFN-gamma-activated monocytes or macrophages. Preschool children were examined during an acute inflammatory illness resulting from accidental ingestion of kerosene and they and a neighbourhood control child were examined 3 months later when well. Vitamin A status was assessed by the modified relative dose response (MRDR) test at 3 months and serum retinol and acute phase proteins were measured at both time points. Urinary neopterin was measured for forty cases in hospital, forty-six cases after recovery, and forty-one controls. Significantly increased neopterin excretion was seen following kerosene ingestion and in association with raised serum acute phase protein concentrations. There was no relationship between neopterin excretion at either time point and vitamin A status as assessed by MRDR test. Urinary neopterin was negatively correlated with serum retinol but no significant relationship was observed when acute phase protein concentrations were included in a multiple regression, suggesting the correlation was secondary to illness-induced changes in serum retinol. The results indicate that, contrary to what is observed in rodents under experimental conditions, poor vitamin A status is not associated with altered regulation of IFN-gamma production in children.

Acute Disease↗