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Biomedical subjects

P Christian

Publications and source records attributed to P Christian.

At least 19 recordsLinked to original sources

Current research priorities in chronic fatigue syndrome/myalgic encephalomyelitis: disease mechanisms, a diagnostic test and specific treatments.

Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of at least 6 months duration, which is accompanied by various rheumatological, infectious and neuropsychiatric symptoms. A collaborative study group has been formed to deal with the current areas for development in CFS research--namely, to develop an understanding of the molecular pathogenesis of CFS, to develop a diagnostic test and to develop specific and curative treatments. Various groups have studied the gene expression in peripheral blood of patients with CFS, and from those studies that have been confirmed using polymerase chain reaction (PCR), clearly, the most predominant functional theme is that of immunity and defence. However, we do not yet know the precise gene signature and metabolic pathways involved. Currently, this is being dealt with using a microarray representing 47,000 human genes and variants, massive parallel signature sequencing and real-time PCR. It will be important to ensure that once a gene signature has been identified, it is specific to CFS and does not occur in other diseases and infections. A diagnostic test is being developed using surface-enhanced, laser-desorption and ionisation-time-of-flight mass spectrometry based on a pilot study in which putative biomarkers were identified. Finally, clinical trials are being planned; novel treatments that we believe are important to trial in patients with CFS are interferon-beta and one of the anti-tumour necrosis factor-alpha drugs.

Fatigue Syndrome, Chronic↗

Prevalence and risk factors of chlamydia and gonorrhea among rural Nepali women.

OBJECTIVES: The epidemiology of sexually transmitted infections (STI) in rural, developing world populations is poorly understood. We estimated the prevalence and risk factors of Neisseria gonorrhoeae and Chlamydia trachomatis in a female population in rural Nepal. METHODS: We conducted a cross sectional study in a sample of 1177 postpartum women participating in a micronutrient supplementation trial in Nepal. Urine samples were collected to test for the two infections using the ligase chain reaction (LCR). RESULTS: C trachomatis was detected in 1.0% (95% confidence intervals (CI): 0.4 to 1.5) and N gonorrhoeae in 2.3% (95% CI: 1.2 to 3.4) of women. None of the women tested positive for both. Self report of all three symptoms of lower abdominal pain, pain and burning on urination, and vaginal discharge was associated with the presence of gonorrhoea (odds ratio (OR): 12.1, 95% CI: 1.3 to 115.0). Neonatal eye discharge was associated with maternal gonococcal infection (OR = 5.2, 95% CI: 1.1 to 24.9). Incidence of low birth weight was not related to these maternal infections, but very preterm delivery (<32 weeks) was higher among women positive for gonorrhoea (OR = 4.7, 95% CI: 1.0 to 22.0). In a multivariable analysis, low body mass index (<18.5) and cattle ownership were associated with gonorrhoea (p <0.05), whereas woman's literacy was associated with chlamydia (p = 0.06). CONCLUSION: We found the rates of N gonorrhoeae and C trachomatis to be low among women in this rural population of Nepal.

Body Mass Index↗

Controlled degradation and macrophage responses of a fluoride-treated polycaprolactone.

We have developed a new bone replacement material based on polycaprolactone (PCL), which can act as a suitable matrix for monomer transfer molding of degradable composites. A boron trifluoride catalyst with glycerol additive was used to produce PCL with a degradation rate that can be altered by treatment with fluoride ions. The effect of cations on the degradation of the polymer and macrophage cell responses are discussed. We found that treatment with fluoride ions reduced the degradation rate. No significant difference between these three fluorides was observed although a general trend was seen where KF-treated PCL appeared to degrade slower than NaF-treated PCL which was slower than NH(4)F-treated PCL. Variation in solubilities of the salts was observed where the K(+) cation had the highest solubility and the Na(+) cation had the lowest solubility, which suggests that NaF was able to degrade the polymer more efficiently than the other fluorides. No significant macrophage activation was observed after culture on the polymer surfaces as determined by peroxide and IL-1 beta release, whereas some activation occurred after culture in degradation products.

Animals↗

Cigarette smoking during pregnancy in rural Nepal. Risk factors and effects of beta-carotene and vitamin A supplementation.

OBJECTIVE: We examined risk factors of smoking and the association between smoking and pregnancy-related and 6-month infant mortality in rural Nepal, where 30% women reported smoking during pregnancy. DESIGN: Cross-sectional analysis of risk factors associated with smoking status and health consequences of smoking, using prospective data collected as part of a randomized community trial to examine the effect of maternal vitamin A or beta-carotene supplementation on maternal mortality. SETTING: Rural, southeastern plains of Nepal. SUBJECTS AND METHODS: A total of 17 767 women contributed at least one pregnancy during 3.5 y of the study. Data on cigarette or bidi (rolled tobacco) smoking were collected using a 7-day recall, twice during pregnancy. Associations between smoking status and maternal diet, morbidity profile, household socioeconomic status and serum concentration of retinol, carotenoids and tocopherols were examined. Further, relative risk (RR) and 95% confidence intervals (CI) were calculated to estimate supplement effects on pregnancy-related mortality, stratified by smoking status during pregnancy. RESULTS: Smokers were more likely to be older, illiterate and poor compared to nonsmokers. Fruit and vegetable consumption among smokers and nonsmokers did not vary. However, smokers were more likely to consume meat/fish/eggs and less likely to consume milk than nonsmokers. They were also more likely to report symptoms of vaginal bleeding, edema, severe headache and convulsions during pregnancy relative to nonsmokers. Mortality per 100,000 pregnancies appeared to be higher among smokers than nonsmokers in the placebo group (915 vs 584, RR=1.57, 95% CI: 0.80-3.08). beta-Carotene supplementation reduced pregnancy-related mortality both among smokers (RR=0.31 95% CI: 0.11-0.89) and nonsmokers (RR=0.41, 95% CI: 0.19-0.89). Similar results obtained with vitamin A supplementation were not statistically significant. Infant mortality up to 6 months was approximately 30% higher among smokers compared to nonsmokers in the placebo group both before and after adjusting for confounding factors. Neither supplement given to women reduced infant mortality. CONCLUSIONS: Cigarette smoking during pregnancy is associated with an increased risk of maternal and infant mortality in rural Nepal. beta-Carotene and to some extent vitamin A may reduce the risk of pregnancy-related mortality, but not infant mortality, among both smokers and nonsmokers.

Adult↗

Long-term craniofacial osteoblast culture on a sodium phosphate and a calcium/sodium phosphate glass.

The aim of this study was to determine the characteristics of human craniofacial osteoblasts cultured on sodium phosphate glass and calcium-sodium phosphate glass in a long-term culture of up to 28 days. The characteristics studied were attachment, proliferation, alkaline phosphatase activity, collagen-1 production, and mineralization. A comparison of the degradation rate, measured by mass loss of the glasses, which are intended for use as a component of a novel degradable composite for craniofacial bone repair, was also performed. It was our hypothesis that the glass would be degradable with a change in degradation rate observed by calcium addition and support osteoblast proliferation and expression of the above characteristics. The inclusion of calcium into the reaction mixture significantly decreased the degradation rate, and it is suggested that the slower degradation is the result of pseudo crosslinking (ionic crosslinks rather than covalent bonding) of the polyphosphate chains by the calcium ions. Therefore, twice as many P-O bonds will need to be hydrolyzed for dissolution of the metal phosphate to occur, therefore greatly reducing the rate of hydrolysis. Osteoblasts were able to attach, spread, and proliferate in a manner comparable with the positive control, as shown by analysis of variance. Formation of a collagen-rich mineralized matrix was also observed. The results presented here suggest that a biocompatible soluble glass has been produced, which has potential to be included in a novel biodegradable craniofacial implant.

Calcium↗

Craniofacial osteoblast responses to polycaprolactone produced using a novel boron polymerisation technique and potassium fluoride post-treatment.

There is no ideal material for craniofacial bone repair at present. The aim of this study was to test the biocompatibility of polycaprolactone (PCL) synthesised by a novel method allowing control of molecular weight and degradation rate, with regard to it being used as matrix for a biodegradable composite for craniofacial bone repair. Human primary craniofacial cells were used, isolated from paediatric skull after surgery. Cell responses were analysed using various assays and antibody staining. Cells attached and spread on the PCL in a similar manner to the Thermanox controls as shown by phalloidin staining of F-actin. Cells maintained the osteoblast phenotype as demonstrated by alkaline phosphatase assay and antibody staining throughout the time points studied, up to 28 days. Cells proliferated on the PCL as shown by a DNA assay. Collagen-1 staining showed extensive production of a collagen-1 containing extracellular matrix, which was also shown to be mineralised by alizarin red staining. Short-term (up to 48 h) attachment studies and long-term (up to 28 days) expression of markers of the osteoblast phenotype have been demonstrated on the PCL. This new method of synthesising PCL shows biocompatibility characteristics that give it potential to be used for craniofacial bone repair.

Absorbable Implants↗

Synthesis, degradation, and in vitro cell responses of sodium phosphate glasses for craniofacial bone repair.

This report outlines the initial synthesis, degradation, and short-term biocompatibility of sodium phosphate glasses, for use in the drawing of fibers and manufacture of biodegradable composites. Biocompatibility studies were performed using a macrophage cell line and primary human craniofacial osteoblasts. Sodium hydrogen phosphate and sodium dihydrogen phosphate glass synthesized for less than 1 h, resulted in a higher degradation rate than glass synthesized for 3 h or more (0.015 mg cm(-2) h(-1)). Glasses with high and low ratios of hydrogen phosphate to dihydrogen phosphate had very similar degradation rates. A condensation route for the formation of the glass should give rise to varying degradation rates with varying ratios of starting materials. It is suggested that the degradation rate of the glass is independent of the concentrations of the initial reagents and that ring-opening polymerization, which reaches an equilibrium state, occurs. Biocompatibility studies suggest minimal macrophage activation (low levels of peroxide and interleukin-1beta release and rounded morphology) and high osteoblast biocompatibility. The ultimate aim of our studies is to produce a biocompatible soluble phosphate glass that can be drawn into fibers for incorporation into a polycaprolactone matrix for craniofacial bone repair. This report demonstrates the successful production of a soluble glass, which is biocompatible with regard to osteoblasts and macrophages. Recent data from our laboratory have demonstrated successful fiber drawing and production of a novel polycaprolactone.

Absorbable Implants↗

Evolutionary and taxonomic implications of conserved structural motifs between picornaviruses and insect picorna-like viruses.

A comparison of the recently determined structure of an insect picorna-like virus, Cricket paralysis virus (CrPV), with that of the mammalian picornaviruses shows that several structural features are highly conserved between these viruses. These conserved features include the topology of the coat proteins, the conformation of most loops, and the general arrangement of the internally located N-terminal arms of the coat proteins. The conformational conservation of the N-termini of the three major coat proteins between CrPV and the picornaviruses suggests a putative ancestral T = 3 virus. Comparisons of the genome structure and amino-acid sequence of the coat proteins of CrPV with a number of other insect picorna-like viruses show that most of them belong to a novel group, recently given the interim name Cricket paralysis-like viruses. Two other insect picorna-like viruses, Infectious flacherie virus (IFV) and Sacbrood virus (SBV), for which the genome sequences have recently been determined, have very different coat protein sequences and a genome organization more like the picornaviruses. However, the position of the small VP4 protein in the structural protein polyprotein as well as the mechanism for its cleavage from VP3 upon assembly strongly suggests an evolutionary link to the "Cricket paralysis-like viruses". We propose that the picornaviruses, Cricket paralysis-like viruses and IFV/SBV group are a natural assemblage. The ancestor for this assemblage had a structure based upon the CrPV/picornavirus paradigm and a genome encoding a single major coat protein; gene duplication and rearrangements have subsequently produced the viruses that we observe today. We also discuss the possible relatives of the proposed assemblage and the likely implications of future structural studies that may be carried out on the putative relatives.

Amino Acid Motifs↗

A comparison of techniques for detecting Invertebrate iridescent virus 6.

The aim of this study was to compare the sensitivity and precision of various methods for the detection and quantification of Invertebrate iridescent virus 6 (IIV-6) (Iridoviridae) isolated from a the stem-boring moth Chilo suppressalis, and to apply these techniques to the detection of covert infections in the wax moth, Galleria mellonella. The relationship between the virus concentration and absorbance at 260 nm was linear over the range of 1.6 x 10(9)-5.6 x 10(10) particles/ml. TCID(50) assays using 12 different cell lines indicated that two Drosophila lines, DL2 and DR1, had the highest susceptibility whereas cell lines from Aedes albopictus and Plutella xylostella were four orders of magnitude less sensitive. TCID(50) values for IIV-6 in Spodoptera frugiperda Sf9 cells gave the particle-infectivity ratios of 15-64 virus particles/IU. An insect bioassay involved injecting doses of 1-100 IIV-6 particles into the third instar G. mellonella larvae. The prevalence of patent infection was 20-26% at a dose of 1 particle per larva rising to 86-92% at 10 particles and 100% at doses of 50 or 100 particles. Of the insects that survived to adulthood, between 5.8 and 75% caused patent infections when injected into G. mellonella larvae, indicating that they were covertly infected. A PCR technique resulted in 95% detection at 1000 virus particles per insect. Of the insects that proved positive for covert infection by insect bioassay, 41% also proved positive by PCR analysis. It is concluded that the G. mellonella bioassay is highly reliable for detection of doses of 10 particles or more and for determining the relative activity of IIV-6 preparations at doses as low as 1 particle per insect. PCR had a slightly lower sensitivity followed by the insect cell culture assay.

Aedes↗

Zinc supplementation might potentiate the effect of vitamin A in restoring night vision in pregnant Nepalese women.

BACKGROUND: Zinc deficiency may result in abnormal dark adaptation or night blindness, a symptom primarily of vitamin A deficiency. During a placebo-controlled trial in Nepal, weekly vitamin A supplementation of women reduced but failed to eliminate the incidence of night blindness during pregnancy, suggesting a role for zinc. OBJECTIVE: The study examined the efficacy of daily zinc supplementation in restoring night vision of pregnant women who developed night blindness while routinely receiving either vitamin A, beta-carotene, or placebo in a field trial. DESIGN: Women (n = 202) who reported to be night blind during pregnancy were randomly assigned in a double-blind manner, stratified on vitamin A, beta-carotene, or placebo receipt, to receive 25 mg Zn or placebo daily for 3 wk. Thus, the 6 groups studied were as follows: beta-carotene + zinc, beta-carotene alone, vitamin A + zinc, vitamin A alone (vitamin A + placebo), zinc alone (zinc + placebo), and placebo (2 placebos: one for the vitamin A or beta-carotene study and one for the zinc study). Women underwent a clinic-based assessment that included pupillary threshold testing and phlebotomy before and after supplementation. Supplement use and daily history of night blindness were obtained at home twice every week. RESULTS: Zinc treatment increased serum zinc concentrations, but alone (zinc alone group), failed to restore night vision or to improve dark adaptation. However, women in the vitamin A + zinc group who had baseline serum zinc concentrations <9.9 micromol/L were 4 times more likely to have their night vision restored (95% CI: 1.1, 17.3) than were women in the placebo group and tended to have a small improvement in pupillary threshold scores (by 0.21 log candela/m2; P = 0.09). CONCLUSION: These data suggest that zinc potentiated the effect of vitamin A in restoring night vision among night-blind pregnant women with low initial serum zinc concentrations.

Adult↗

Twinning rates and survival of twins in rural Nepal.

BACKGROUND: Twin pregnancies are common but there are few data on rates of twinning or survival of liveborn twin infants in developing countries. METHODS: The rates of multiple births were calculated in a population-based cohort of married women of childbearing age who were enrolled in a randomized community trial to assess the impact of vitamin A or beta-carotene on maternal and infant health and survival. RESULTS: The rate of twinning was 16.1 per 1000 pregnancies (7.4 if only twin pregnancies resulting in two liveborn infants were used). The rate for triplets and quadruplets was 0.19 and 0.06 per 1000 pregnancies. Twinning rates were higher among women of higher parity, but were not associated with maternal age. Twinning rates among twins where at least one was live born (or increased in utero survival) were 30% (95% CI : -1%, 71%) and 44% (95% CI : 9%, 89%) higher among women receiving vitamin A and beta-carotene supplements than placebo, after adjusting for maternal age, gestational age, and parity. The perinatal mortality rate was 8.54 times higher for twins than singletons, 7.32 higher for neonatal mortality, and 5.84 higher for cumulative 24-week mortality. This difference was reduced but not erased by adjusting for gestational age. No difference in survival of liveborn twin infants was seen by supplement group. A higher mortality rate among male twins was largely explained by gestational age. CONCLUSIONS: Multiple births are relatively common occurrences in rural Nepal, and carry a much higher mortality risk for the infants than for singletons. Vitamin A or beta-carotene supplementation appeared to increase the rate of twinning, or improve the survival of twins in utero, but did not increase twin survival after birth.

Adult↗

Maternal night blindness increases risk of mortality in the first 6 months of life among infants in Nepal.

Night blindness occurs commonly among women during pregnancy in rural NEPAL: We examined the relationship between maternal night blindness and the risk of mortality occurring among infants in the first 6 mo of life. Stratified analysis by maternal night blindness status during pregnancy was done for 10,000 women participating in a randomized, placebo-controlled trial of vitamin A and beta-carotene supplementation. Mortality of infants of non-night blind women in all three supplementation groups was similar, and when combined, was 63/1000 live births. Relative to this, mortality was higher by 63% [95% confidence interval (CI): 9-138%) and 50% (95% CI: -3 to 133%) among infants of night blind women receiving placebo and beta-carotene, respectively, but only by 14% (95% CI: -33 to 93%) among those receiving vitamin A. Thus, 6-mo mortality was higher among infants of women who had night blindness during pregnancy. Maternal receipt of vitamin A reduced this risk.

Female↗

Expression and redistribution of cellular Bad, Bax, and Bcl-X(L) protein is associated with VCD-induced ovotoxicity in rats.

Previous studies have shown that 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in rats is likely caused by acceleration of the normal rate of atresia (apoptosis). VCD-induced ovotoxicity is specific for small preantral follicles and is associated with increased activity of caspase cascades. The present study was designed to investigate the alteration of expression and distribution of several Bcl-2 family member proteins induced by dosing of VCD in rat small ovarian follicles. Female F344 rats were given a single dose of VCD (80 mg/kg, i.p., 1 day; a time when ovotoxicity is not initiated), or dosed daily for 15 days (80 mg/kg, i.p., 15 days; a time when significant ovotoxicity is underway). Four hours following the final dose, livers and ovaries were collected. Ovarian small (25-100 microm) and large (100-250 microm) preantral follicles were isolated, and subcellular fractions (cytosolic and mitochondrial) were prepared. Compared with controls, levels of the proapoptotic protein, Bad, were greater in both cytosolic and mitochondrial fractions of small preantral follicles collected from 15-day VCD-treated rats (cytosol, 1.97 +/- 0.16; mitochondria, 2.20 +/- 0.24, VCD/control, P < 0.05). After 15 days of daily VCD dosing, total cellular antiapoptotic Bcl-x(L) protein levels were unaffected in small preantral follicles, but its distribution in mitochondrial and cytosolic components was altered (mitochondria, 0.635 +/- 0.08; cytosol, 1.39 +/- 0.14, VCD/control, P < 0.05). Likewise, VCD did not affect protein levels of proapoptotic Bax in small follicles on Day 15. However, consistent with a Bax-mediated mechanism of apoptosis, the relative ratio of Bax/Bcl-x(L) in the mitochondrial fraction of small preantral follicles was significantly increased by VCD dosing (1.62 +/- 0.21, VCD/control, P < 0.05). Immunofluorescence staining intensity evaluated by confocal microscopy visualized cytochrome c protein in the cytosolic compartment in granulosa cells of preantral follicles in various stages of development. Relative to controls, within the population of small preantral follicles, staining intensity was less (P < 0.05) and presumably more diffuse, specifically in stage 1 primary follicles from VCD-treated animals (15 days). VCD caused none of these effects in large preantral follicles or liver (not targeted by VCD). These data provide evidence that the apoptosis induced by VCD in ovarian small preantral follicles of rats is associated with increased expression of Bad protein, redistribution of Bcl-x(L) protein and cytochrome c from the mitochondria to the cytosolic compartment, and an increase in the Bax/Bcl-x(L) ratio in the mitochondria. These observations are consistent with the involvement of Bcl-2 gene family members in VCD-induced acceleration of atresia.

Animals↗

Night blindness during pregnancy and subsequent mortality among women in Nepal: effects of vitamin A and beta-carotene supplementation.

Night blindness due to vitamin A deficiency is common during pregnancy among women in Nepal. The authors assessed the risk of maternal death during and after a pregnancy with night blindness among women participating in a cluster-randomized, placebo-controlled vitamin A and beta-carotene supplementation trial in Nepal from July 1994 to September 1997. Subjects were 877 women with night blindness and 9,545 women without night blindness during pregnancy. Women were followed from the time they declared that they were pregnant through the end of the study, representing a median follow-up of 90 weeks (interquartile range: 64-121 weeks). Mortality of night-blind women in the placebo group was 3,601 per 100,000 pregnancies. In comparison, the relative risk of dying among nonnight-blind women in the placebo group was 0.26 (95% confidence interval (CI): 0.13, 0.55), and the relative risk among women with or without night blindness in the vitamin A/beta-carotene group was 0.32 (95% CI: 0.10, 0.91) and 0.18 (95% CI: 0.09, 0.36), respectively. Night-blind women were five times (95% CI: 2.20, 10.58) more likely to die from infections than were women who were not night blind. These findings show that night blindness during pregnancy is a risk factor of both short- and long-term mortality among women. Vitamin A/beta-carotene supplementation ameliorates this risk to a large extent.

Adolescent↗

Physical and biocompatibility properties of poly-epsilon-caprolactone produced using in situ polymerisation: a novel manufacturing technique for long-fibre composite materials.

Preliminary investigations into a novel process for the production of poly-epsilon-caprolactone (PCL) to be used as a matrix material in a bioabsorbable composite material are detailed. This material is primarily being developed as a bone substitute for use in maxillofacial reconstructive surgery, however, the technique described could be adapted to other areas where bioabsorbable composite materials may be used. The development of a totally bioabsorbable long-fibre composite material would allow a two-stage degradation to occur with the matrix material degrading first leaving a scaffold structure of degradable fibres which would be absorbed at a later stage. Caprolactone monomer was polymerised in situ within a tool cavity to produce a net shape moulding. Inclusion of a fibre preform within the tool cavity which was impregnated by the liquid monomer produces a long-fibre composite material. PCL with a range of molecular weights has been produced using this liquid moulding technique to assess the physical and biocompatibility properties compared to commercially available PCL. Osteoblast-like cells derived from human craniofacial bone (CFC) have been used to assess the in vitro biocompatibility of the PCL. The results show that high-quality PCL with a narrow molecular weight distribution and properties similar to commercially available PCL can be produced using this technique. Polymerisation of the monomer around a woven fibre preform made of a poly(lactic acid) (PLA)/poly(glycolic acid) (PGA) copolymer (vicryl mesh) produced a bioabsorbable long-fibre composite material. Further work is ongoing to develop this system towards a method for improving craniofacial bone reconstruction.

Biocompatible Materials↗

The role of vitamins in the prevention and control of anaemia.

OBJECTIVE: While iron deficiency is regarded as the major cause of nutritional anaemia, changes in vitamins A, B12, C and E, folic acid and riboflavin status have also been linked to its development and control. This paper provides a systematic review of vitamin supplementation trials relating to the control of nutritional anaemia. METHODS: A MEDLINE search was used to find reports of vitamin supplementation trials that reported changes in anaemia or iron status. RESULTS: Vitamin A can improve haematological indicators and enhance the efficacy of iron supplementation. Both folate and vitamin B12 can cure and prevent megaloblastic anaemia. Riboflavin enhances the haematological response to iron, and its deficiency may account for a significant proportion of anaemia in many populations. Vitamin C enhances the absorption of dietary iron, although population-based data showing its efficacy in reducing anaemia or iron deficiency are lacking. Vitamin E supplementation given to preterm infants has not reduced the severity of the anaemia of prematurity. Vitamin B6 effectively treats sideroblastic anaemia. Multivitamin supplementation may raise haemoglobin (Hb) concentration, but few studies have isolated the effect of multivitamins from iron on haematological status. CONCLUSIONS: In general, the public health impact of vitamin supplementation in controlling anaemia is not clear. Neither are the complex interactions involving multiple vitamins in haematopoiesis sufficiently understood to explain the observed variability in haematological responses to vitamins by age, population, vitamin mixture and dosages. Further research is needed to understand the roles of individual and combined vitamin deficiencies on anaemia to design appropriate micronutrient interventions to prevent anaemia.

Anemia↗

Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal.

BACKGROUND: The effect of vitamin A supplementation on the survival of infants aged <6 mo is unclear. Because most infant deaths occur in the first few month of life, maternal supplementation may improve infant survival. OBJECTIVES: The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants <6 mo of age. DESIGN: Married women of reproductive age in 270 wards of Sarlahi district, Nepal, were eligible to participate. Wards were randomly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate (vitamin A), 42 mg all-trans-beta-carotene, or placebo. Pregnancies were followed until miscarriage, stillbirth, maternal death, or live birth of one or more infants, who were followed through 24 wk of age. RESULTS: A total of 43559 women were enrolled; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial. The rate of fetal loss was 92.0/1000 pregnancies in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.06 (95% CI: 0.91, 1.25) and 1.03 (95% CI: 0.87, 1.19), respectively. The 24-wk mortality rate was 70.8/1000 live births in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.05 (95% CI: 0.87, 1.25) and 1.03 (95% CI: 0.86, 1.22), respectively. CONCLUSIONS: Small weekly doses of vitamin A or beta-carotene given to women before conception, during pregnancy, and through 24 wk postpartum did not improve fetal or early infant survival in Nepal.

Adult↗

Efficacy of a vitamin A-fortified wheat-flour bun on the vitamin A status of Filipino schoolchildren.

BACKGROUND: Wheat flour is a possible food vehicle for vitamin A fortification. OBJECTIVE: This study assessed the efficacy of consumption of a vitamin A-fortified wheat-flour bun (pandesal) on the vitamin A status of school-age children. DESIGN: This was a double-masked clinical trial conducted in 396 and 439 children aged 6-13 y attending 4 rural schools in the Philippines. The children were randomly assigned to a vitamin A-fortified (experimental) or nonfortified (control) group. A 60-g vitamin A-fortified pandesal (containing approximately 133 microg retinol equivalents) or a nonfortified pandesal was consumed by the children 5 d/wk for 30 wk. Vitamin A status, hemoglobin concentration, anthropometric status, morbidity, and dietary intake were assessed at baseline and 30 wk later. A modified relative dose response (MRDR) was assessed in a subsample of 20% of the children ( approximately 75/group) with the lowest initial serum retinol concentration at the 30-wk follow-up. RESULTS: Baseline serum retinol significantly modified the effect of the intervention. The fortified group, whose initial serum retinol concentrations were below the median, had a 0.07 +/- 0.03-micromol/L greater improvement in serum retinol at the 30-wk follow-up than did the control group (P: = 0.02). Improved vitamin A status was also evident in the MRDR subsample. End-of-study differences in the MRDR showed that vitamin A- fortified pandesal intake decreased the percentage of children with inadequate liver vitamin A stores by 50% (15.3% compared with 28.6%; P: = 0.05). CONCLUSIONS: Daily consumption of vitamin A-fortified pandesal significantly improved the vitamin A status of Filipino school-age children with marginal-to-low initial serum retinol concentrations.

Adolescent↗