Biomedical subjects

Terrence Forrester

Publications and source records attributed to Terrence Forrester.

At least 19 recordsLinked to original sources

PubMed2007

The vascular effects of metabolic impairment clusters in subjects of different ethnicities.

BACKGROUND: Although metabolic syndrome affects vascular function, the impact of individual impairments and their clustering is unclear. OBJECTIVE: To assess the vascular impact of metabolic impairments before they reach treatment thresholds in different ethnic groups. METHODS: Metabolic variables, inflammatory markers, endothelium dependent vasodilatation (EDV) and carotid intima media thickness (CIMT) were measured in population samples of 82 Caucasians and 78 matched Afro-Caribbeans with no vascular disease. Insulin resistance was assessed using homeostasis model assessment (HOMA-IR). EDV was measured as the change in the height of the inflection point of the digital volume pulse following intravenous infusion of 5 mcg/min of albuterol (DeltaRIDeltaLB). Regression models were used to investigate the independent effects of metabolic impairment clusters and their interaction with ethnicity on EDV and CIMT. RESULTS: HOMA-IR (2.4-3.8, p < 0.0001), IL-6 levels (1.1-2.8 pg/mL, p = 0.02) and CIMT (0.71-0.83 mm, p = 0.009) increased whereas in DeltaRIBASELINE (77.6-72.9 percentage points, p < 0.0001) and DeltaRIDeltaLB (15.5-7.1 percentage points, p < 0.0001) decreased with the number of metabolic impairments present. DeltaRIDeltaLB decreased by 1.6 (95% CI 0.2-3.7) percentage points and CIMT increased by 0.06 (95% CI 0.02-0.10) mm for each metabolic impairment present after adjusting for age, gender, ethnicity and HOMA-IR. There were significant interactions between Afro-Caribbean ethnicity and metabolic impairments for IL-6 (p = 0.037) and DeltaRIDeltaLB (p = 0.002). CONCLUSIONS: Clustering of metabolic impairments is associated with inflammatory activation, impaired EDV and increased CIMT even before reaching treatment thresholds for individual impairments. This effect was more marked in Afro-Caribbean subjects.

Adult↗

PubMed2006

Asymptomatic bacteriuria in sickle cell disease: a cross-sectional study.

BACKGROUND: It is known that there is significant morbidity associated with urinary tract infection and with renal dysfunction in sickle cell disease (SCD). However, it is not known if there are potential adverse outcomes associated with asymptomatic bacteriuria (ASB) infections in sickle cell disease if left untreated. This study was undertaken to determine the prevalence of ASB, in a cohort of patients with SCD. METHODS: This is a cross-sectional study of patients in the Jamaican Sickle Cell Cohort. Aseptically collected mid-stream urine (MSU) samples were obtained from 266 patients for urinalysis, culture and sensitivity analysis. Proteinuria was measured by urine dipsticks. Individuals with abnormal urine culture results had repeat urine culture. Serum creatinine was measured and steady state haematology and uric acid concentrations were obtained from clinical records. This was completed at a primary care health clinic dedicated to sickle cell diseases in Kingston, Jamaica. There were 133 males and 133 females in the sample studied. The mean age (mean +/- sd) of participants was 26.6 +/- 2.5 years. The main outcome measures were the culture of > or = 10(5) colony forming units of a urinary tract pathogen per milliliter of urine from a MSU specimen on a single occasion (probable ASB) or on consecutive occasions (confirmed ASB). RESULTS: Of the 266 urines collected, 234 were sterile and 29 had significant bacteriuria yielding a prevalence of probable ASB of 10.9% (29/266). Fourteen patients had confirmed ASB (prevalence 5.3%) of which 13 had pyuria. Controlling for genotype, females were 14.7 times more likely to have confirmed ASB compared to males (95% CI 1.8 to 121.0). The number of recorded visits for symptomatic UTI was increased by a factor of 2.5 (95% CI 1.4 to 4.5, p < 0.005) but serum creatinine, uric acid and haematology values were not different in patients with confirmed ASB compared with those with sterile urine. There was no association with history of gram negative sepsis. CONCLUSION: ASB is a significant problem in individuals with SCD and may be the source of pathogens in UTI. However, further research is needed to determine the clinical significance of ASB in SCD.

Adult↗

PubMed2006

The role of inheritance and environment in predisposition to vascular disease in people of African descent.

OBJECTIVES: This study sought to compare vascular reactivity and carotid intima media thickness (CIMT) between Afro-Caribbean people in the United Kingdom (UK) and the West Indies and Afro-Caribbean and Caucasian people in the UK. BACKGROUND: Attenuated vascular reactivity and increased CIMT in black patients is seen as evidence for predisposition to vascular disease, but no comparisons exist between Afro-Caribbean people in different settings, which can provide insight into non-inherited determinants of increased ethnic susceptibility. METHODS: A representative community sample of 81 healthy Afro-Caribbean people and 101 Caucasian people in the UK was compared with 197 matched Afro-Caribbean people in Jamaica. Small vessel reactivity was assessed by measuring the absolute change from baseline in the reflection index (RI) of the digital volume pulse during intravenous infusion of albuterol (5 microg/min, DeltaRI(ALB)) and glyceryl trinitrate (5 microg/min, DeltaRI(GTN)). The CIMT was measured ultrasonographically in the distal 1 cm of the common carotid artery. RESULTS: Mean DeltaRI(ALB) was 4.2 percentage points (95% confidence interval [CI], 2.3 to 6.1, p < 0.001) lower in UK Afro-Caribbean people compared with Jamaican Afro-Caribbean people and 2.6 percentage points (95% CI, 0.4 to 4.7, p = 0.02) lower compared with Caucasian people, after adjusting for vascular risk profile. Adjusted mean CIMT of UK Afro-Caribbean people was 0.13 mm (95% CI, 0.08 to 0.17, p < 0.001) greater compared with Jamaican Afro-Caribbean people and 0.05 mm (95% CI, 0.01 to 0.10, p = 0.02) greater compared with Caucasian people. CONCLUSIONS: Healthy UK Afro-Caribbean people have greater and Jamaican Afro-Caribbean people have less impairment of vascular reactivity and intima media thickness compared with UK Caucasian people, suggesting that potentially modifiable environmental interactions may contribute to excess vascular disease in Afro-Caribbean people.

Black People↗

PubMed2006

In vivo rates of erythrocyte glutathione synthesis in adults with sickle cell disease.

Despite reports of lower GSH concentration in sickle cell disease (SCD), the in vivo kinetic mechanism(s) responsible for GSH deficiency is unknown. To determine whether suppressed synthesis was responsible for the lower erythrocyte GSH concentration, we used a primed intermittent infusion of [(2)H(2)]glycine to measure erythrocyte GSH synthesis in vivo in 23 individuals with homozygous beta(s) SCD and 8 healthy controls. Erythrocyte cysteine concentration, the rate-limiting precursor for GSH synthesis, plasma markers of oxidant damage, and dietary intakes of energy and protein were also measured. Compared with values of controls, SCD subjects had significantly lower erythrocyte GSH (P < 0.04) and cysteine concentrations (P < 0.004) but significantly faster fractional rates of GSH synthesis (P < 0.02). The absolute rates of GSH synthesis in SCD subjects compared with control subjects was greater by approximately 57% (P = 0.062). However, the concentrations of markers of oxidative damage, plasma derivatives of reactive oxygen metabolites, plasma nitrotyrosine, urinary isoprostane-to-creatinine ratio, and GSH-to-GSSG ratio, as well as dietary intakes of energy, protein, and GSH precursor amino acids, were not different between SCD subjects and controls. The findings of this study suggest that the lower erythrocyte GSH of SCD patients is not due to suppressed synthesis or impaired regeneration but rather to increased consumption. In addition, the lower erythrocyte cysteine concentration plus the faster rate of GSH synthesis strongly suggest that the endogenous cysteine supply is not sufficient to meet all anabolic demands; hence, cysteine may be a conditionally essential amino acid in individuals with SCD.

Adult↗

PubMed2006

Glutathione S-transferase polymorphisms may be associated with risk of oedematous severe childhood malnutrition.

It has been estimated that more than 50 % of deaths before the age of 5 years have undernutrition as an underlying cause. Severe childhood malnutrition, an extreme form of undernutrition, occurs as oedematous and non-oedematous syndromes. The reasons why only some children develop oedematous severe childhood malnutrition (OSCM) have remained elusive, but the heterogeneity of clinical appearances among children from relatively homogeneous backgrounds suggests that interindividual variation in susceptibility to OSCM may exist. We investigated variants of four glutathione S-transferase (GST) genes in a retrospective study among subjects (n 136) previously admitted to the Tropical Metabolism Research Unit, Jamaica, for the treatment of either OSCM (cases) or non-oedematous severe childhood malnutrition (controls). We found that GSTP1 Val(105) homozygotes were significantly more common among the cases (odds ratio (OR) 3.5; 95 % CI 1.1, 10.8). We also found an association of borderline significance between non-deletion GSTT1 genotypes (i.e. +/+ or +/0) and OSCM (OR 2.4; 95 % CI 1.0, 5.9). There was no significant association between OSCM and any of the other GST variants. These preliminary findings suggest that genetic variation within the GST superfamily may contribute to the risk of OSCM. Additional, larger data sets and studies of variants in other candidate genes are required in order to properly assess the true contribution, if any, of genetic variation to risk of OSCM. Such studies may improve our understanding of the causes of clinical heterogeneity in malnutrition.

Anthropometry↗

PubMed2006

Geographical variation in relationships between parental body size and offspring phenotype at birth.

BACKGROUND: Size and body proportions at birth are partly determined by maternal body composition, but most studies of mother-baby relationships have only considered the effects of maternal height and weight on offspring birth weight, and few have examined the size of effects. Paternal size and body composition also play a role, primarily through the fetal genome, although few studies have investigated relationships with neonatal phenotype. METHODS: Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria and Jamaica were used to investigate the effects of maternal measures (derived at 30 weeks' gestation, n=16,418), and also paternal size (n=3,733) on neonatal phenotype, for singleton, live-born, term births. RESULTS: After accounting for variation in maternal size and shape across populations, differences in neonatal phenotype were markedly reduced. Mother-baby relationships were similar across populations, although some were stronger in developing countries. Maternal height was generally the strongest predictor of neonatal length, maternal head circumference of neonatal head and maternal skinfold thickness of neonatal skinfolds. Relationships with maternal arm muscle area were generally weak. Effects of paternal height and body mass index were weaker than the equivalent maternal measurements in most studies. CONCLUSIONS: Differences in maternal body composition account for a large part of the geographical variation in neonatal phenotype. The size of the effects of all maternal measures on neonatal phenotype suggests that nutrition at every stage of the mother's life cycle may influence fetal growth. Further research is needed into father-baby relationships and the genetic mechanisms that influence fetal growth.

Adult↗

PubMed2006

Geographical variation in neonatal phenotype.

BACKGROUND: Recent studies have shown associations between size and body proportions at birth and health outcomes throughout the life cycle, but there are few data on how neonatal phenotype varies in different populations around the world. METHODS: Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria, and Jamaica (n=22,067) were used to characterize geographical differences in phenotype in singleton, live-born newborns. Measurements included birth weight, placental weight, length, head, chest, abdominal and arm circumferences, and skinfolds. RESULTS: Neonates in Europe were the largest, followed by Jamaica, East Asia (China), then Africa and South Asia. Birth weight varied widely (mean values 2,730-3,570 g), but in contrast, head circumference was similar in all except China (markedly smaller). The main difference in body proportions between populations was the head to length ratio, with small heads relative to length in China and large heads relative to length in South Asia and Africa. CONCLUSIONS: These marked geographical differences in neonatal phenotype need to be considered when investigating determinants of fetal growth, and optimal phenotype for short-term and long-term outcomes.

Anthropometry↗

PubMed2006

Lipid kinetic differences between children with kwashiorkor and those with marasmus.

BACKGROUND: It has been hypothesized that one factor associated with poor prognosis in kwashiorkor, but not in marasmus, is impaired lipid catabolism, which limits the supply of energy that is essential for survival when dietary intake is inadequate. However, this hypothesis has not been tested. OBJECTIVE: The objective was to measure lipid kinetics in malnourished children with kwashiorkor or marasmus. DESIGN: Glycerol concentration and flux (index of total lipolysis), palmitate concentration and flux (index of net lipolysis), and palmitate oxidation rate (index of fatty acid oxidation) were measured in 8 children (n = 5 boys and 3 girls) with kwashiorkor and 7 (n = 4 boys and 3 girls) with marasmus, aged 4-20 mo, in the postabsorptive state. The measurements were made approximately 3 d after admission, when the children were malnourished, and after the children attained normal weight-for-length, ie, at recovery. RESULTS: The glycerol concentration was higher in the malnourished stage than at recovery for the marasmus and kwashiorkor groups combined. Glycerol flux tended to be lower (P = 0.067) and palmitate flux significantly lower (P < 0.05) in the kwashiorkor group than in the marasmus group. Palmitate oxidation was significantly lower in the malnourished stage than at recovery in the kwashiorkor group but not in the marasmus group. In the malnourished stage, palmitate oxidation was slower in the kwashiorkor group than in the marasmus group, but no significant differences between groups were observed at recovery. CONCLUSIONS: Children with kwashiorkor break down fat and oxidize fatty acids less efficiently than do children with marasmus; this factor may explain the better survival rate in marasmus.

Female↗

PubMed2006

Glycine production in severe childhood undernutrition.

BACKGROUND: Although nutritionally dispensable amino acids are not essential in the diet, from a biochemical standpoint, dispensable amino acids such as glycine are essential for life. This is especially true under unique circumstances, such as when the availability of labile nitrogen for dispensable amino acid synthesis is reduced, as in severe childhood undernutrition. OBJECTIVE: We aimed to measure glycine production in children with edematous and nonedematous severe childhood undernutrition. DESIGN: Glycine flux and splanchnic glycine extraction were measured in 2 groups of children with edematous (n = 8) and nonedematous (n = 9) severe childhood undernutrition when they were infected and malnourished (clinical phase 1), when they were still severely malnourished but no longer infected (clinical phase 2), and when they were recovered (clinical phase 3). RESULTS: Total and endogenous glycine flux and splanchnic glycine uptake did not differ significantly between the edematous and nonedematous groups during any clinical phase. In both groups of subjects, none of the glycine kinetic parameters changed significantly from clinical phase 1 through phases 2 and 3. Compared with the value at clinical phase 3, plasma glycine concentrations were not significantly lower during clinical phase 1 or 2 in either group. CONCLUSIONS: These findings suggest that children with severe childhood undernutrition can increase their de novo glycine synthesis to compensate for the reduced contribution from chronic food deprivation. The maintenance of the plasma glycine concentration suggests that the rate of glycine production was sufficient to satisfy metabolic demands in these children when they were acutely undernourished and infected.

Amino Acids↗

PubMed2006

Sulfur amino acid metabolism in children with severe childhood undernutrition: cysteine kinetics.

BACKGROUND: Children with edematous but not nonedematous severe childhood undernutrition (SCU) have lower plasma and erythrocyte-free concentrations of cysteine, the rate-limiting precursor of glutathione synthesis. We propose that these lower cysteine concentrations are due to reduced production secondary to slower de novo synthesis plus decreased release from protein breakdown. OBJECTIVE: We aimed to measure cysteine production, de novo synthesis, and the rate of cysteine release from protein breakdown in children with SCU. DESIGN: Cysteine flux, de novo synthesis, and release from protein breakdown were measured in 2 groups of children with edematous (n = 11) and nonedematous (n = 11) SCU when they were infected and malnourished (clinical phase 1), when they were still severely malnourished but no longer infected (clinical phase 2), and when they had recovered (clinical phase 3). RESULTS: In clinical phase 1, cysteine production and its release from protein breakdown were slower in both groups of children than were the values in the recovered state. These kinetic variables were significantly slower, however, in the children with edematous SCU than in those with nonedematous SCU. De novo cysteine synthesis in clinical phase 1 was faster than the rate at recovery in the edematous SCU group, and there were no significant differences between the groups at any clinical phase. CONCLUSION: These findings suggest that cysteine production is reduced in all children with SCU because of a decreased contribution from protein breakdown and not from decreased de novo synthesis. The magnitude of this reduction, however, is much greater in children with edematous SCU than in those with nonedematous SCU.

Amino Acids, Sulfur↗

PubMed2006

Sulfur amino acid metabolism in children with severe childhood undernutrition: methionine kinetics.

BACKGROUND: Children with edematous but not nonedematous severe childhood undernutrition (SCU) have lower plasma and erythrocyte-free concentrations of cysteine and methionine, which suggests a decreased availability of methionine for cysteine synthesis. We propose that methionine production and metabolism will be slower in children with edematous SCU than in those with nonedematous SCU. OBJECTIVE: We aimed to measure methionine flux, its transmethylation and its transsulfuration, and homocysteine remethylation in children with SCU. DESIGN: Methionine kinetics were measured in 2 groups of children with edematous (n = 11) and nonedematous (n = 11) SCU when they were infected and malnourished (clinical phase 1), when they were still severely malnourished but no longer infected (clinical phase 2), and when they had recovered (clinical phase 3). RESULTS: At clinical phase 1, children with edematous SCU had rates of total methionine flux, flux from protein breakdown, and flux to protein synthesis that were slower than the rates of the nonedematous group. There were no significant differences in homocysteine remethylation or methionine transsulfuration and transmethylation between the groups at clinical phase 1. CONCLUSION: These findings suggest that, in the acutely malnourished and infected state, children with edematous SCU have slower methionine production than do children with nonedematous SCU because of a slower rate of release from protein breakdown. This slower methionine production is not, however, associated with slower rates of methionine transsulfuration and transmethylation or homocysteine remethylation.

Amino Acids, Sulfur↗

PubMed2006

Polymorphisms in genes involved in folate metabolism as risk factors for oedematous severe childhood malnutrition: a hypothesis-generating study.

BACKGROUND: Severe childhood malnutrition (SCM) occurs as both oedematous and non-oedematous syndromes. The reasons why some children develop oedematous SCM (OSCM) have remained elusive but differences in clinical presentation among malnourished children from similar backgrounds suggests that there might be inter-individual variation in susceptibility to OSCM. AIM: To estimate the strength of the association between variants of three genes involved in folate/methyl group metabolism [methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and cystathionine beta-synthase (CBS)] and risk of OSCM. METHODS: Patients previously admitted to the Tropical Metabolism Research Unit (TMRU) for treatment of either OSCM (cases, n = 74) or non-oedematous SCM (NOSCM, controls, n = 50) were recruited. Genotypes at four sites within the three genes (MTHFR C677T, MTHFR A1298C, MTR A2756G and CBS 844ins68) were determined using PCR-based assays. RESULTS: The MTHFR 677T [odds ratio (OR) 0.63, 95% CI 0.2-1.7] and MTR 2756G (OR 0.74, 95% CI 0.4-1.4) alleles were associated with moderate reduction in risk of OSCM whereas the CBS 844ins68 allele (OR 1.4, 0.7-2.4) was associated with an increased risk. None of these risks was significant at the 5% level. CONCLUSIONS: Genetic variation within folate/methyl group metabolic pathways might have a small but potentially important influence on risk of OSCM. Additional, larger data-sets will be required to test the specific hypotheses (about the putative effect size and direction of association) generated in this preliminary study. Such observations have the potential to improve our understanding of the pathogenesis of clinical heterogeneity in severe malnutrition.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2005

Ethnic differences in arterial responses and inflammatory markers in Afro-Caribbean and Caucasian subjects.

OBJECTIVE: Small vessel disease is more common in Afro-Caribbeans than Caucasians. We investigated underlying differences in metabolic, inflammatory, and vascular responses that may predispose Afro-Caribbeans to small vessel pathology. METHODS AND RESULTS: Seventy-eight Afro-Caribbeans aged 35-75 years, with no vascular disease or medications, were compared with 82 matched Caucasians for metabolic variables, fasting insulin, interleukin 6, tumor necrosis factor (TNF) alpha, and cytoplasmic repressor protein levels. Carotid intima media thickness (CIMT) was measured ultrasonographically. Small vessel function was assessed by measuring the absolute change from baseline in the reflectance index (RI) of the digital volume pulse during IV infusion of albuterol (5 microg/min, DeltaRIALB) and glyceryl tri nitrate (5 microg/min, DeltaRIGTN). Large artery elasticity was measured as the stiffness index (SI) and derived from the time to pulse wave reflection adjusted for subject height. Afro-Caribbeans had significantly higher diastolic blood pressure (80.3 versus 77.6 mm Hg; P=0.033), fasting insulin (14.0 versus 10.6 microU/mL; P=0.026), TNF-alpha (6.7 versus 4.3; pg/mL; P=0.001), and interleukin 6 (2.3 versus 1.5 pg/mL; P=0.036) levels compared with Caucasians. CIMT was greater (0.81+/-0.20 versus 0.75+/-0.18 mm; P=0.02) and small vessel reactivity attenuated (mean DeltaRIALB 6.8+/-8.0% versus 12.3+/-8.%; P<0.0001) in Afro-Caribbeans, but their large artery elasticity (mean index of large artery stiffness 9.9 versus 9.7 m/s; P=0.48) was comparable with Caucasians. CIMT was independently associated with an index of large artery stiffness (beta=0.03; P=0.002) in Caucasians but not in Afro-Caribbeans. There were independent relationships among Afro-Caribbean ethnicity, TNF-alpha, and insulin levels. CONCLUSIONS: Selective impairment of small artery function may contribute to excess small vessel disease in Afro-Caribbeans.

Adult↗

PubMed2005

An international comparative study of blood pressure in populations of European vs. African descent.

BACKGROUND: The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue. METHODS: Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants). RESULTS: The range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks. CONCLUSIONS: These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated.

Black or African American↗

PubMed2005

Relation between liver fat content and the rate of VLDL apolipoprotein B-100 synthesis in children with protein-energy malnutrition.

BACKGROUND: Fatty infiltration of the liver is associated with an increased morbidity and mortality in children with severe protein-energy malnutrition (PEM), but its pathogenesis remains unclear. Although impaired synthesis of VLDL apolipoprotein B-100 (VLDL-apo B-100) is generally accepted as the pathogenetic mechanism, the rate of it synthesis has not been measured in children with PEM. OBJECTIVE: The objective of the study was to ascertain the relation between the degree of hepatic steatosis and the rate of VLDL-apo B-100 synthesis in children with PEM. DESIGN: The fractional and absolute rates of VLDL-apo B-100 synthesis were measured with a prime-constant intravenous infusion of [2H3]leucine in 13 severely malnourished children (8 boys and 5 girls) aged 7-18 mo. Hepatic fat content was estimated by computerized tomography scanning by using the ratio of liver to spleen (L:S) attenuation. The ratio is inversely related to hepatic fat content such that the lower the L:S, the greater the amount of fat in the liver. RESULTS: There were significant inverse relations between L:S attenuation and VLDL-apo B-100 concentration (P < 0.02), the absolute rate of VLDL-apo B-100 synthesis (P < 0.02), and plasma triacylglycerol (P < 0.02) and serum cholesterol (P < 0.05) concentrations. CONCLUSIONS: These results suggest that children with PEM synthesize VLDL-apo B-100 at a faster rate as the degree of hepatic fat infiltration increases. Thus, fatty infiltration of the liver in PEM is not due to a reduction in the synthesis of VLDL-apo B-100.

Apolipoprotein B-100↗

PubMed2005

Protein kinetic differences between children with edematous and nonedematous severe childhood undernutrition in the fed and postabsorptive states.

BACKGROUND: Pathogenic factors that cause a child to develop the edematous instead of the nonedematous form of severe childhood undernutrition (SCU) during food deprivation are not clear. It was hypothesized that, in edematous but not nonedematous SCU, impaired protein breakdown leading to inadequate amino acids for maintenance of important organ systems was a factor. OBJECTIVE: We measured protein kinetics in children with edematous and nonedematous SCU. DESIGN: Endogenous leucine flux, an index of whole-body protein breakdown rate, was determined in 4 groups of children with edematous or nonedematous SCU in the malnourished and recovered states. Two groups were studied in the postabsorptive state, and 2 groups were studied in the fed state. RESULTS: In the postabsorptive state, leucine flux was slower (P < 0.01) in the edematous group than in the nonedematous group in the malnourished state, but in the recovered state, it was faster (P < 0.05) in the children who previously had edematous SCU. When compared with the malnourished state value, leucine flux at recovery doubled in the group that previously had edematous SCU, but it did not change in the other group. In the fed state, leucine flux was slower (P < 0.01) in the edematous group than in the nonedematous group in the malnourished state but not in the recovered state. In the recovered state, enteral leucine extraction by splanchnic tissues trended higher in the group that previously had edematous SCU than in the nonedematous group. CONCLUSION: These findings indicate different protein breakdown responses to food deprivation between children with edematous and nonedematous SCU and inherent differences in protein metabolism when they have recovered.

Adolescent↗

PubMed2004

UGT1A1 variation and gallstone formation in sickle cell disease.

Pigment gallstones are a common clinical complication of sickle cell (SS) disease. Genetic variation in the promoter of uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) underlies Gilbert syndrome, a chronic form of unconjugated hyperbilirubinemia, and appears to be a risk factor for gallstone formation. We investigated the association between UGT1A1 (TA)(n) genotype, hyperbilirubinemia, and gallstones in a sample of Jamaicans with SS disease. Subjects were from the Jamaican Sickle Cell Cohort Study (cohort sample, n = 209) and the Sickle Cell Clinic at the University of the West Indies, Kingston, Jamaica (clinic sample, n = 357). The UGT1A1 (TA)(n) promoter region was sequenced in 541 SS disease subjects and 111 healthy controls (control sample). Indirect bilirubin levels for (TA)(7)/(TA)(7) and (TA)(7)/(TA)(8) genotypes were elevated compared with (TA)(6)/(TA)(6) (clinic sample, P < 10(-5); cohort sample, P < 10(-3)). The (TA)(7)/(TA)(7) genotype was also associated with symptomatic presentation and gallstones in the clinic sample (odds ratio [OR] = 11.3; P = 7.0 x 10(-4)) but not in the younger cohort sample. These unexpected findings indicate that the temporal evolution of symptomatic gallstones may involve factors other than the bilirubin level. Although further studies of the pathogenesis of gallstones in SS disease are required, the (TA)(7)/(TA)(7) genotype may be a risk factor for symptomatic gallstones in older people with SS disease.

Adolescent↗

PubMed2004

Report on the 2nd World Congress on Fetal Origins of Adult Disease, Brighton, U.K., June 7-10, 2003.

In 1989, reports suggested that the fetal environment, as reflected in birth size, was related to the risk of noncommunicable diseases in adult life. This association was first described for coronary heart disease but rapidly extended to include type 2 diabetes, osteoporosis, and metabolic and endocrine homeostasis. This led to the development of the fetal origins of adult disease paradigm, which resulted in a refocusing of research effort over the next 10 y to consider the lifelong consequences of perinatal influences on chronic diseases. Previously, perinatal influences had largely been seen in terms of teratogenic effects or acute birth injury rather than whether trajectories and responses made during early development had lifelong consequences. Indeed, in developmental biology, it is widely recognized that adaptive plastic responses during early development often have consequences for function in later adulthood. Although the relative importance of this newly recognized set of phenomena to the burden of human disease has been controversial, the research precipitated by those early observations has confirmed their robustness and started to provide a mechanistic basis to this biology. Two world congresses have been held to review progress in this research. Both have been characterized by a unique multidisciplinary attendance ranging from molecular, experimental, and developmental biologists to epidemiologists and health economists.

Adult↗