Polybrominated diphenyl ethers and perfluorinated alkyl substances in blood serum of New Zealand adults, 2011-2013.

A national survey was conducted in 2011-2013 to assess serum concentrations of brominated flame retardants (BFRs) and perfluorinated alkyl substances (PFASs) in adult New Zealanders. Participants were randomly selected from the 2010 Electoral Roll within 64 demographic strata according to 4 age groups, 4 geographic regions, 2 ethnic groups (Maori/non-Maori) and sex. Eligible participants (n = 734; response rate of contacted individuals = 37%) donated up to 30 mL of blood, after which serum was pooled (49 pools for BFRs, 63 pools for PFASs) according to demographic strata. BFRs were analysed by GC-HRMS and PFASs by LC-MS/MS. Associations between serum BFRs and PFASs and demographic variables (age, region, ethnicity, sex) were assessed using regression analysis. The weighted geometric mean (GM) serum concentrations of BDE47, BDE99, BDE100, and BDE153 were 2.0, 0.66, 0.43, and 1.2 ng/g lipid, respectively. The weighted geometric mean (GM) serum concentrations of PFOS, PFOA, PFHxS, and PFNA were 3.4, 2.4, 1.0, and 0.66 ng/mL, respectively. The majority of BFRs showed higher serum concentrations in younger age groups. Conversely, the four PFASs showed higher serum concentrations in older age groups. Concentrations of BFRs and PFASs were generally lower in females compared to males. In New Zealand, both age and sex are important determinants of BFR and PFAS serum concentrations.

Chlorinated persistent organic pollutants in serum of New Zealand adults, 2011-2013.

A national survey was conducted in 2011-2013 to assess serum concentrations of persistent organic pollutants (POPs) in adult New Zealanders. Participants were randomly selected from the 2010 Electoral Roll within 64 demographic strata according to 4 age groups, 4 regions, 2 ethnic groups (Maori/non-Maori) and gender. Eligible subjects (n=734) donated up to 30ml of blood, after which serum was pooled (n=49) according to demographic strata prior to analysis by GC-HRMS. Associations between demographic variables (age, region, ethnicity, gender) and serum POPs were assessed using linear regression. The weighted geometric mean (GM) of PCDD/Fs was 5.3pg/g lipid toxic equivalents using the WHO 2005 toxic equivalence factors (TEQ05), which increased by age (3.2, 4.4, 4.8, and 8.1pg/g lipid for the 19-24, 25-34, 35-49, and 50-64year age groups, respectively). The weighted GM of dioxin-like PCBs was 1.4pg TEQ05/g lipid which also increased by age (0.82, 0.86, 1.4, and 2.3pg/g lipid for the same age groups, respectively). Of the detected OCPs, the highest concentration was observed for p,p'-DDE (weighted GM, 220ng/g lipid) followed by hexachlorobenzene (HCB; 7.3ng/g lipid), beta-HCH (7.0ng/g lipid), and dieldrin (4.7ng/g lipid). For most Cl-POPs, concentrations were lowest in the youngest age group, and were similar for men and women and Maori and non-Maori. Serum Cl-POPs were, on average, 50% lower than those measured 15years earlier in 1997. This survey provides evidence of declining serum concentrations of chlorinated POPs in the New Zealand adult population. Age was the most important determinant of POPs concentrations. Body burdens of PCDD/Fs and PCBs in New Zealand are relatively low by international comparison, while for OCPs they are similar or lower compared to those reported for other developed countries.

The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery.

INTRODUCTION: The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for 'drug' delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the 'PEG dilemma', balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem. Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking. Expert opinion: The possibility of using attenuated toxins as antisense and siRNA delivery systems has been demonstrated in vitro. Systems based upon attenuated anthrax toxin have been shown to have high activity (equivalent to nucleofection) and low toxicity whilst not requiring cationic 'helpers' or condensing agents, divorcing these systems from the problems associated with the PEG dilemma. It remains to be seen whether these systems can operate safely, efficiently and reproducibly, in vivo or in the clinic.

Population pharmacokinetics of acyclovir in children and young people with malignancy after administration of intravenous acyclovir or oral valacyclovir.

Acyclovir is effective in the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. The aim of this study was to characterize the population pharmacokinetics of acyclovir observed following treatment with intravenous acyclovir and oral valacyclovir (valaciclovir) in young people with malignancy. Plasma acyclovir concentration-time data were collected from 43 patients (age range, 9 months to 20 years) who had been given multiple doses of acyclovir (5 mg/kg of body weight) and/or valacyclovir (10 mg/kg). Nonlinear mixed-effect modeling was employed to analyze acyclovir population pharmacokinetics and identify influential covariates. Simulations (n = 1,000) were conducted to explore the ability of the current doses to maintain acyclovir concentrations above the recommended 50% inhibitory concentration for HSV or VZV (0.56 mg/liter or 1.125 mg/liter, respectively) for more than 12 h. A one-compartment pharmacokinetic model with first-order elimination best described the acyclovir concentration-time data. The population mean estimates for clearance (CL), volume of distribution (V), absorption rate (k(a)), and bioavailability (F) were 3.55 liters/h, 7.36 liters, 0.63 h(-1), and 0.60, respectively. Inclusion of body weight and estimated creatinine CL (CL(CR)) in the final model reduced the interindividual variabilities in CL and V from 61% to 24% and from 75% to 36%, respectively. Simulations revealed that with the use of the current doses, maximal efficacy can be achieved in over 45% of patients weighing 25 to 50 kg and with CL(CR) levels of 2.0 to 4.0 liters/h/m(2), but only in a much smaller proportion of patients, with low weights (10 kg) and high CL(CR)s (5.5 liters/h/m(2)), suggesting that higher doses are required for this subgroup. This validated population pharmacokinetic model for acyclovir may be used to develop dosing guidelines for safe and effective antiviral therapy in young people with malignancy.

A fatal case of Lassa fever in London, January 2009.

In January 2009, the eleventh [corrected] case of Lassa fever imported to the United Kingdom was diagnosed in London. Risk assessment of 328 healthcare contacts with potential direct exposure to Lassa virus - through contact with the case or exposure to bodily fluids - was undertaken. No contacts were assessed to be at high risk of infection and no secondary clinical cases identified.

Novel mutations in abetalipoproteinaemia and homozygous familial hypobetalipoproteinaemia.

Abetalipoproteinaemia (ABL) and homozygous familial hypobetalipoproteinaemia (FHBL) are rare inherited disorders associated with low or undetectable levels of apolipoprotein B (apoB)-containing lipoproteins. Patients present with the symptoms and sequelae of fat malabsorption, including fat-soluble vitamin deficiencies. We describe two novel mutations: one an APOB gene mutation causing FHBL and the other a microsomal triglyceride transfer protein (MTP) gene mutation causing ABL. Two siblings of consanguineous parents were homozygous for an apoB mutation 4339delT causing an apoB-30.9 truncation. In another family, a boy born to consanguineous parents was homozygous for a 319 bp in-frame deletion of MTP exon 15 (c.2076-39_2303 + 52del319). All three children presented with malabsorption and liver dysfunction and had similar very low serum lipid, apoB, and fat-soluble vitamin levels. The FHBL parents had low serum lipid and apoB profiles distinguishing the disorder from the normal levels in ABL parents. Future patients presenting with FHBL or ABL should be genotyped to provide further insight into the varying clinical severity related to molecular heterogenicity in these two conditions.

The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis.

Beta-alanine in blood-plasma when administered as A) histidine dipeptides (equivalent to 40 mg . kg(-1) bwt of beta-alanine) in chicken broth, or B) 10, C) 20 and D) 40 mg . kg(-1) bwt beta-alanine (CarnoSyn, NAI, USA), peaked at 428 +/- SE 66, 47 +/- 13, 374 +/- 68 and 833 +/- 43 microM. Concentrations regained baseline at 2 h. Carnosine was not detected in plasma with A) although traces of this and anserine were found in urine. Loss of beta-alanine in urine with B) to D) was <5%. Plasma taurine was increased by beta-alanine ingestion but this did not result in any increased loss via urine. Pharmacodynamics were further investigated with 3 x B) per day given for 15 d. Dietary supplementation with I) 3.2 and II) 6.4 g . d(-1) beta-alanine (as multiple doses of 400 or 800 mg) or III) L-carnosine (isomolar to II) for 4 w resulted in significant increases in muscle carnosine estimated at 42.1, 64.2 and 65.8%.

Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants.

BACKGROUND: There are no published reference intervals for concentrations of alpha-fetoprotein (AFP) in the cerebrospinal fluid (CSF) of normal infants. The presence of abnormal concentrations of AFP in plasma or CSF may indicate the presence of a teratoma or a germ cell tumour with yolk sac elements. We measured CSF AFP in infants who did not have malignancy in order to determine its reference intervals. METHODS: AFP was measured in the CSF and/or plasma in 128 infants. Of these, 91 infants had CSF AFP measurements, 94 infants had plasma AFP measurements and in 60 infants AFP concentrations were determined in paired CSF and plasma samples. The patients ranged in age from 1 to 110 days. Both CSF and plasma AFP concentrations were measured by a microparticle enzyme immunoassay using an AxSYM analyser. RESULTS: Using ages corrected for prematurity, the median CSF AFP concentration for babies -69 to 31 days old was 61 kIU/L (5th-95th centile: 2-889 kIU/L), while the median CSF AFP concentration for infants 32 to 110 days was 1.2 kIU/L (5th-95th centile: 0.1-12.5 kIU/L). By age 6 weeks, the concentrations were close to those found in adult plasma and all CSF AFP concentrations from infants with a corrected age over 2 months were <3 kIU/L. CONCLUSION: We have defined reference intervals for CSF AFP concentrations in infants. These results may assist in the diagnosis of CNS tumours, particularly congenital CNS tumours containing yolk sac elements.

Demographic profile of the elderly population in Dublin accident and emergency hospital catchment areas.

The Dublin metropolitan area is now divided into a number of clearly defined accident and emergency (A & E) catchment areas since the closing of the smaller inner city hospitals and the opening of newer hospitals on the periphery of the city. We examined the demographic profile of the elderly population in Dublin city and county served by each of the new catchment areas. Whilst the elderly population make up 9.9% (105,188) of the Dublin population (1996 census) they make up over 20% of the A & E attendances and up to over 40% of the A & E admissions in major Dublin hospitals. There is a wide variation in the percentage elderly population in each hospital catchment area with inner more settled city areas having a much higher percentage elderly population over those hospital catchment areas that serve newer housing areas. We also looked at the level of deprivation. Combining the two most deprived levels St James's Hospital had the largest absolute number and the highest percentage of deprived elderly 12,736 (51.1%) followed by the Mater 6,919 (32.9%), Beaumont 5371 (31.5%), James Connolly 2,983 (38.1%), Tallaght 2012 (22.3%) and St Vincent's Hospital 1987 (7.7%). Hospitals with high numbers of elderly and serving deprived catchment areas face particular resource problems in meeting the needs of the population that they serve. A significant increase in the provision of publicly funded community facilities and long stay accommodation is required to meet the needs of the large number of deprived elderly in the inner city area. Failure to respond to these demographic challenges will have a profound effect on the ability of hospital emergency services to meet the increasing pressures posed by the high volume of acutely sick economically deprived elderly presenting to hospital accident and emergency departments.

Abdominal fat and birth size in healthy prepubertal children.

BACKGROUND: Studies examining the foetal origins hypothesis suggest that small birth size may be a marker of foetal adaptations that programme future propensity to adult disease. We explore the hypothesis that birth size may relate to fat distribution in childhood and that fat distribution may be a link between birth size and adult disease. OBJECTIVE: To investigate the relationship between birth size and abdominal fat, blood pressure, lipids, insulin and insulin:glucose ratio in prepubertal children. DESIGN: Cross-sectional study, based on a birth cohort of consecutive full-term births. SUBJECTS: Two hundred and fifty-five (137 females) healthy, 7- and 8-y-old children. MEASUREMENTS: Body composition and abdominal fat was measured by dual energy X-ray absorptiometry. Lipid, glucose and insulin profiles were measured after an overnight fast and an automated BP monitor was used for blood pressure measurements. RESULTS: There was a negative association between abdominal fat and birth weight s.d. score across a range of normal birth weights (beta=-0.18; 95% CI=-0.31 to -0.04, P=0.009) and a positive association with weight s.d. score at 7/8 y (beta=0.35; 95% CI=0.24 to 0.46, P<0.001). Children who were born with the lowest weight s.d. score and had the greatest weight s.d. score at 7/8 y had significantly more (P<0.001) abdominal fat, as a percentage of total fat (6.53+/-1.3%) than those who had the highest birth weight s.d. score and the lowest weight s.d. score at 7/8 y (4.14+/-0.5%). Similar results were seen if head circumference, but not ponderal index, was used as an indicator of birth size. Increased abdominal fat was associated with higher total cholesterol:HDL cholesterol, higher triglyceride concentration and increased diastolic blood pressure. CONCLUSIONS: Birth weight independently predicted abdominal fat. Children with the highest amount of abdominal fat were those who tended to be born lighter and gained weight centiles. Increased abdominal fat was associated with precursor risk factors for ischaemic heart disease.

Pathogenesis and recovery of tetraplegia after electrical injury.

The site of neurological damage causing paralysis after electrical trauma remains to be clarified. A patient is described who developed a flaccid tetraplegia after a high voltage electrical injury. The findings on initial examination and neurophysiological investigation showed a very severe generalised sensory-motor polyneuropathy. His subsequent follow up over 60 months showed a remarkable degree of reinnervation and the unmasking of a myelopathy. The degree of reinnervation noted suggests an axonopathy that left the other elements of the peripheral nerves relatively spared. These findings provide the most convincing evidence to date that a generalised polyneuropathy can follow electrical injury and that it results from non-thermal mechanisms such as electroporation.

Transient hyperphosphatasaemia: an important condition to recognize.

OBJECTIVE: To investigate the prevalence and aetiology of transient hyperphosphatasaemia (TH) of infancy and childhood in a tertiary referral paediatric hospital. METHODOLOGY: Retrospective review of the medical records of patients with measured plasma alkaline phosphatase (ALP) activity of over 1000 U/L. RESULTS: Over a period of 1 year, 68 children with plasma ALP activity of over 1000 U/L were identified. The main aetiologies were liver disease (34 cases), TH (21 cases) and bone disease (11 cases). The mean age of children with TH was 1 year and 5 months and there was a male predominance (3:1). The children with liver and bone disease were older (mean ages of 6 years, 6 months and 5 years, 1 month, respectively) and there was no gender difference. The mean plasma ALP activity for the children with TH was 3395 U/L, and in those patients in whom ALP activity was measured sequentially, mean ALP returned to within normal limits after an average of 70 days. There was a seasonal predominance of TH cases, with a significant number presenting during the winter, suggesting a viral aetiology. The most common clinical presentation of children with TH was gastroenteritis (8/21). CONCLUSION: Cases of TH can be clearly identified by considering the age of the patient and by excluding other known causes of markedly elevated ALP, in particular liver or bone disease. Using these exclusion criteria, the prevalence of TH was found to be high. Early recognition of this benign condition may prevent misdiagnosis and further unnecessary investigations.

Sequential changes in in vivo muscle and liver protein synthesis and plasma and tissue glutamine levels in sepsis in the rat.

We have investigated sequential changes in skeletal muscle and hepatic protein synthesis following sepsis, and their relationship to changes in circulating and tissue glutamine concentrations. Male Wistar rats underwent caecal ligation and puncture (CLP) or sham operation, with starvation, and were killed 24, 72 or 96 h later. A group of non-operated animals were killed at the time of surgery. Protein synthesis was determined using a flooding dose of L-[4-(3)H] phenylalanine, and glutamine concentrations were measured by an enzymic fluorimetric assay. Protein synthesis in gastrocnemius muscle fell in all groups. Gastrocnemius total protein content was reduced after CLP and at 72 and 96 h after sham operation. After CLP, protein synthesis was lower at 24 h, and total protein content was lower at 72 and 96 h, than in sham-operated animals. CLP was associated with increased liver protein synthesis at all time points, whereas there was no change after sham operation. Liver protein content did not change after CLP, but was lower at 72 and 96 h after sham operation than in non-operated animals. Plasma glutamine concentrations were reduced at 24 h after sham operation, and at 72 and 96 h after CLP. Muscle glutamine concentrations were reduced in all groups, with the decrease being greater following CLP than after sham operation. In the liver, glutamine concentrations were unchanged after CLP, but increased after sham operation. In rats with sepsis, decreases in muscle protein synthesis and content are associated with markedly reduced muscle glutamine concentrations. Plasma glutamine concentrations are initially maintained, but fall later. In liver, protein synthesis is increased, while glutamine concentrations are preserved. These results support a peripheral-to-splanchnic glutamine flux in sepsis.

MFO induction in fish by filtrates from chlorine dioxide bleaching of wood pulp.

Spent bleaching liquors from pulp bleached with chlorine dioxide were assessed for their potency to induce hepatic mixed function oxygenase enzymes (MFO) in rainbow trout, as indicated by activity of ethoxyresorufin-o-deethyase (EROD). Filtrates were collected from two kraft mills in Central Canada to assess the potency of filtrates from hardwood and softwood bleaching. All mill-scale bleaching filtrates induced MFO activity, and filtrates from softwood pulp bleaching appeared more potent than filtrates from hardwood bleaching. Filtrates from the final bleaching stage were most potent, and filtrates from the first stage were the least potent. In laboratory bench-scale bleaching experiments, pulp from softwood and hardwood kraft mills in Eastern Canada was bleached via an industry-standard 5-stage chlorine dioxide bleaching sequence. The filtrates were collected and used in fish bioassays to assess EROD-inducing potency. Potency of bench-scale filtrates varied depending on wood furnish (i.e. softwood vs. hardwood) and the bleaching stage, with all bench-scale filtrates being much weaker EROD inducers than mill-scale filtrates. Recycled paper mill washwater is a possible source of compounds causing increased potency of the mill-scale filtrates.

Newborn screening for congenital hypothyroidism, Victoria, Australia, 1977-1997. Part 1: The screening programme, demography, baseline perinatal data and diagnostic classification.

Clinical, demographic and laboratory data from infants with congenital hypothyroidism (CH) born in the Australian state of Victoria from the commencement of neonatal screening in mid-1977 until December 1988 are reported. These provide a baseline for a 12-year prospective longitudinal study on physical and neuro-psychological outcome until mid-1997, the subject of a second paper. Infants with CH were detected using a primary TT4 screening test. Demographic data were collected prospectively using a clinical assessment protocol. Nearly all affected infants underwent 99mTc pertechnetate scanning at the initial assessment to determine the underlying aetiology of their hypothyroidism. 704,723 infants were screened and 199 with permanent primary hypothyroidism (one in 3,541) were identified. The most common aetiologies were thyroid ectopia (46%), thyroid aplasia (33%), and 'dyshormonogenesis' (11%). The clinical abnormalities classically described in CH were more evident in infants with aplasia, and the striking female preponderance in infants with thyroid dysplasia (syn. dysgenesis) was confirmed. Other features included increased frequencies of 'dyshormonogenesis' in infants of parents of Middle-Eastern origin and of labour induction in infants with dysplasia. A closed posterior fontanelle was not found in any infant with thyroid aplasia.

Newborn screening for congenital hypothyroidism, Victoria, Australia, 1977-1997. Part 2: Treatment, progress and outcome.

A controlled longitudinal prospective study is reported of physical and neuropsychological progress up to 12 years in 152 children with congenital hypothyroidism (CH), detected by newborn screening in the Australian state of Victoria and born between the onset of screening in mid-1977 and December 1988. Linear growth of the CH children was normal. Throughout they were slightly heavier and the median head circumference was slightly larger compared with reference data. Those with thyroid aplasia required a marginally larger dose of thyroxine to achieve euthyroidism. Assessment of cognitive outcome in the children with permanent primary CH revealed the mean scores at 2, 5 and 8 years to be from 8.5 (p<0.001) to 10.2 (p<0.001) points lower than in a group of 60 euthyroid controls. However, there was large overlap and, of the affected children, only 10.1% at 2 years, 3.9% at 5 years and 6.8% at 8 years fell more than 2 SD below the means of the euthyroid controls. On univariate analysis, variables shown to have significant correlation with cognitive outcome at 8 years in the CH children were newborn activity, baseline TT4 and FTI, initial T4 dosage, socio-economic classification, maternal age, maternal education and presence of a serious accompanying disorder. On multiple regression analysis, significant variables were baseline bone age, maternal age and education, and presence of a serious accompanying disorder. No single thyroidal or extra-thyroidal variable could be identified to account for the discrepancy between the children with CH and the controls.

Flow cytometric evaluation of defects of the mitochondrial respiratory chain.

Cultured human skin fibroblasts from 12 patients with a variety of mitochondrial respiratory chain defects were examined for their capacity to oxidize dihydrorhodamine-123 to the fluorescent molecule rhodamine-123 using a flow cytometer. We found that cells from patients with functional defects in respiratory chain enzymes were less able to oxidize dihydrorhodamine-123 than those of healthy controls. Ten of the cell strains had reduced activity in at least one of the respiratory chain complexes and also showed significantly reduced fluorescence when compared to the mean of eight normal control cell strains. One patient had mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (with the A3243G mutation) and reduced respiratory chain activities in muscle and liver. Molecular analysis did not show the mutation in cultured skin fibroblasts, and had correspondingly normal fluorescence. The 12th cell strain showed reduced fluorescence but did not reach statistical significance. This strategy could be of use in helping direct further investigations in patients, and in studying the biochemical pathogenesis of mitochondrial DNA mutations in cybrid studies.

Reversible tetraplegia due to polyneuropathy in a diabetic patient with hyperosmolar non-ketotic coma.

Critical illness polyneuromypathy has not previously been reported as a complication of diabetic coma. We describe a patient with hyperosmolar non-ketotic coma (HONK) complicating gram-negative sepsis in whom persistent coma and profound tetraplegia caused considerable concern. Although, initially, it was feared that the patient had suffered a central neurological complication such as stroke or cerebral oedema, a diagnosis of critical illness motor syndrome (CIMS) was subsequently confirmed neurophysiologically. Profound limb weakness associated with HONK is not necessarily due to a catastrophic cerebral event, rather it may be a result of CIMS, which has an excellent prognosis for full neurological recovery.

Initial characterization of the GH-IGF axis and nutritional status of the Ati Negritos of the Philippines.

BACKGROUND AND OBJECTIVE: The Ati Negritos are a Pygmy-like aboriginal population from the Philippines with physical characteristics of short stature, dark skin and woolly, kinked hair. Their final height, components of their GH-IGF axis and various nutritional markers are described. SUBJECTS, DESIGN AND MEASUREMENTS: Auxological data and sera for the components of the GH-IGF axis and nutritional parameters were collected from 9 adult Ati Negritos in their native environment and 10 Filipinos in Sydney. RESULTS: The height SDS (- 3.66 +/- 1.1 vs. - 1.01 +/- 1.2), weight SDS (- 2.30 +/- 1.6 vs. 0.10 +/- 0.7), and BMI SDS (- 1.4 +/- 1.8 vs. - 0.2 +/- 0.5) between the two groups were significantly different (P < 0.01). The mean height of the 6 male Ati Negritos was 149 +/- 7 and 144 +/- 3 cm for the females and are comparable with the African Pygmies and the Mountain Ok people of Papua New Guinea. The Ati Negritos showed lower growth hormone binding protein (GHBP), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), acid labile subunit (ALS), zinc, albumin, ferritin, iron, iron saturation and much higher insulin-like growth factor binding protein 2 (IGFBP-2) and plasma transferrin concentrations. No differences were noted in random growth hormone (GH), plasma insulin-like growth factor II (IGF-II), nor in their plasma concentrations of prealbumin, thyroid stimulating hormone (TSH) and free thyroxine (T4). CONCLUSION: Perturbations of both the GH-IGF-I axis and nutritional markers exist in the Ati Negritos. These findings may be determinants of their stature; however, the aetiology of these changes remains to be fully elucidated.