Biomedical subjects
Publications and source records attributed to A Lucas.
Dietary taurine intake may explain the benefits of both breast milk and preterm formula to neurodevelopment. Low plasma neonatal taurine was associated with lower scores on the Bayley mental development index at 18 months and the WISC-R arithmetic subtest at 7 years. Currently it is not mandatory to add taurine to infant formulas.
Two groups of adolescents, one born preterm and one with a diagnosis of developmental amnesia, were compared with age-matched normal controls on measures of hippocampal volume and memory function. Relative to control values, the preterm group values showed a mean bilateral reduction in hippocampal volume of 8-9% (ranging to 23%), whereas the developmental amnesic group values showed a reduction of 40% (ranging from 27% to 56%). Despite equivalent IQ and immediate memory scores in the two study groups, there were marked differences between them on a wide variety of verbal and visual delayed memory tasks. Consistent with their diagnosis, the developmental amnesic group was impaired relative to both other groups on nearly all delayed memory measures. The preterm group, by contrast, was significantly impaired relative to the controls on only a few memory measures, i.e., route following and prospective memory. We suggest that early hippocampal pathology leads to the disabling memory impairments associated with developmental amnesia when the volume of this structure is reduced below normal by approximately 20-30% on each side. Whether this is a sufficient condition for the disorder or whether abnormality in other brain regions is also necessary remains to be determined.
BACKGROUND: The optimal age for the introduction of solid foods (weaning) in infants is poorly researched yet may have implications for both short and longer term health. Many parents do not comply with current guidelines. OBJECTIVE: To determine and compare the age at weaning in term appropriate size for gestational age (AGA), small for gestational age (SGA), and preterm infants, and factors associated with weaning age in these groups. DESIGN: Data from > 2000 infants from seven prospective randomised trails conducted between 1990 and 1997 were used to address the objectives. RESULTS: Most infants, term AGA, SGA, or preterm, received solids before 4 months of age. Only 2% of term infants were exclusively breast fed to 6 months of age. Formula fed infants received solids on average two weeks earlier than breast fed infants. Preterm infants were significantly more likely, and term SGA infants less likely, to receive solids at both 6 and 12 weeks after term than term AGA infants. Weight at 6 weeks of age was a stronger predictor of earlier weaning than either birth weight or weight gain from birth to 6 weeks in term infants. In preterm infants, formula feeding and maternal smoking were associated with earlier weaning. CONCLUSIONS: Infants born in the mid 1990s were weaned on average earlier than the 4 months recommended by the Department of Health. Earlier weaning was associated with less positive health behaviours. Further research is required to provide evidence based weaning guidelines, including specific advice for SGA and preterm infants, and to investigate longer term consequences of weaning practices.
UNLABELLED: Studies in animals have indicated that cholesterol metabolism is susceptible to manipulation by diet and growth in early life. In humans, low birthweight has been associated with increased risk of coronary heart disease. AIM: To establish whether plasma lipids and indicators of cholesterol absorption, synthesis and breakdown differ in children born preterm and at term. METHODS: Plasma total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triacylglycerols, apolipoprotein A1, apolipoprotein B, lathosterol (indicator of cholesterol synthesis), campesterol (indicator of cholesterol absorption), 7-alpha hydroxycholesterol (indicator of cholesterol breakdown) were measured in up to 407 children born preterm and 36 children born at term. RESULTS: Children born preterm had lower cholesterol synthesis (p = 0.002) and lower cholesterol breakdown (p < 0.001) than those born at term, but their plasma cholesterol concentration was not significantly different. After adjusting for current size, birthweight and gestational age were significantly related to plasma lathosterol and 7-alpha hydroxycholesterol. However, when both birthweight and gestational age were adjusted, only gestational age remained significant. There were no significant differences in plasma campesterol between the two groups. CONCLUSION: Being born preterm may have a long-term effect on cholesterol metabolism in children 8-12 y later. Those born prematurely had lower cholesterol synthesis and breakdown, but their plasma cholesterol concentration was similar at this age. These parameters need to be studied in older cohorts.
A new immunocapture technique has been applied to the diagnosis of ovine brucellosis under experimental conditions. The tests were made on a serum bank derived from both young and adult ewes vaccinated conjunctivally with the Rev 1 strain at a dose of 10(8) to 10(9) colony-forming units. Adult ewes were infected experimentally two-and-a-half years after they had been vaccinated and the results were compared with an unvaccinated control group. The condition of each animal in terms of infection with Brucella melitensis was determined by clinical and bacteriological investigations. The development of the immune response was compared by the rose bengal test, the complement fixation test, the Coombs' test and the immunocapture technique for 180 days after the vaccination and for 410 days after the experimental infection, that is, the two following gestations. The results suggest that the new technique is more specific in animals vaccinated conjunctivally, regardless of their age when they were vaccinated. After the experimental infection, significantly (P < 0.05) fewer of the vaccinated sheep which were free of clinical signs and were not excreting B melitensis reacted positively to the test.
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An endothelial nitric oxide synthase (eNOS) gene polymorphism (Glu298Asp) has been associated with cardiovascular disease. We investigated whether carriage of the polymorphism was associated with functional changes in the endothelium, and how genotype altered the harmful and beneficial impact of environmental influences on the endothelium. Endothelium-dependent, flow-mediated brachial artery dilatation (FMD) and endothelium-independent dilatation response to glyceryl trinitrate were measured using high-resolution ultrasound in 248 subjects (131 female, 117 male, aged 20 to 28) genotyped for the Glu298Asp polymorphism. Vascular function was compared between genotype groups and interactions with the proatherogenic risk factor, smoking, and the antiatherogenic influence of n-3 fatty acids (n-3FA) were investigated. Vascular function was not related to genotype in the group as a whole or within sexes. However, among males, smoking was associated with lower FMD in Asp298 carriers (nonsmokers 0.125+/-0.085 mm versus smokers 0.070+/-0.060 mm, P=0.006) but not in Glu298 homozygotes (nonsmokers 0.103+/-0.090 mm versus smokers 0.124+/-0.106, P=0.5). In the whole group, n-3FA levels were positively related to FMD in Asp298 carriers (reg coeff=0.023 mm/%, P=0.04, r=0.20) but not in Glu298 homozygotes (reg coeff=-0.019 mm/%, P=0.1). These differences between genotype groups were significant in interaction models. The Glu298Asp polymorphism is associated with differences in endothelial responses to both smoking and n-3 FA in healthy young subjects. These findings raise the possibility of genotype-specific prevention strategies in cardiovascular disease.
OBJECTIVE: To develop a disease-specific questionnaire suitable to measure health-related quality of life (HRQOL) in acromegaly (ACROQOL). DESIGN, PATIENTS AND MEASUREMENTS: For the development of the ACROQOL questionnaire different sources of information were used: First, a literature search was performed to identify relevant papers describing the impact of acromegaly in HRQOL. Second, 10 endocrinologists identified the main domains of impact on HRQOL in patients with acromegaly. Third, 10 in-depth, semistructured interviews were conducted in acromegalic patients to identify domains and items related to the self-perceived impact of acromegaly in patients' life. Qualitative analyses of the information were performed identifying domains and items to be included in the questionnaire. Those items considered ambiguous, complicated to read, double-barrelled, with jargon terms, too long, or negatively worded were excluded. Each remaining item was subsequently rated by the same panel of endocrinologists and experts in HRQOL evaluation, and assessed according to clarity of wording, frequency of occurrence and importance among patients with acromegaly. Analysis of internal consistency of the questionnaire was evaluated with a Cronbach's Alpha. A preliminary questionnaire was administered to 72 patients with acromegaly. Rasch analysis (dichotomous logistic response model) of the answers given by these patients allowed parameter estimates and model data fit indices to be computed and misfitting items deleted. Frequency of occurrence and degree of agreement with the statements were selected as response choices in a 5-point Likert type scale. RESULTS: The following domains related to HRQOL in acromegaly were identified: physical and psychological functions, social, daily activities, symptoms, cognition, general health perception, sleep, sexual function, pain, energy and body image. An initial set of 204 expressions were identified from the initial transcripts of the patient interviews. After elimination of ambiguous or unclear expressions, 142 items remained drafted in question form. From the quantitative analysis of the item rank position within each of the three areas of clarity, frequency and importance, the 38-item questionnaire was produced, with satisfactory internal consistency (Cronbach's Alpha 0.94). Rasch analysis produced a further reduction to the final 22-item questionnaire (Cronbach's Alpha 0.91) containing two scales that evaluate physical (eight questions) and psychological aspects related to appearance and personal relations (seven items each). The evaluation of the item parameters confirmed the construct validity of the new instrument. The substantial reliability of the questionnaire suggested the sample was well targeted by the questionnaire. The initial Spanish version was translated into English and presented to five English-speaking Australian patients with acromegaly to assess and correct for comprehension, clarity, cultural relevance and suitable wording. CONCLUSIONS: We present the ACROQOL questionnaire, developed and preliminarily validated to specifically assess HRQOL in patients with acromegaly.
BACKGROUND: Epidemiological studies have reported an inverse relationship between vitamin E status and coronary heart disease. This relationship has not, however, been confirmed by the majority of intervention studies, which have been carried out relatively late in the disease process. The protective effects of vitamin E may be more important earlier in life, before vascular changes have become established. This study investigated whether dietary vitamin E could prevent preclinical arterial changes in young adults relevant to the development of cardiovascular disease. MATERIALS AND METHODS: Measures of vascular function (arterial distensibility and endothelial-dependent and -independent vascular responses) were assessed by noninvasive high resolution ultrasound and related to plasma vitamin E and total antioxidant concentrations in 326 adults, aged 20-28 years. RESULTS: Neither vitamin E (alone or adjusted for lipids) nor total antioxidant status were significantly related to vascular endothelial function or arterial distensibility in either sex. There was no threshold level of vitamin E above which vascular function improved and neither vitamin E nor total antioxidant status interacted with any risk factor, such as smoking or increased low-density lipoprotein concentrations. CONCLUSIONS: Neither plasma vitamin E concentrations nor total antioxidant status achieved by dietary intake during young adulthood were related to vascular endothelial function or arterial distensibility.
OBJECTIVES: to investigate the relationship between calf vessel run-off assessed by hand-held Doppler, graft patency and patient survival following infra-inguinal graft surgery. DESIGN: prospective cohort study of 258 consecutive patients undergoing infra-inguinal bypass grafts in one centre between 1995-99. MATERIALS AND METHODS: ankle Doppler auditory waveform characteristics were documented for patients considered for infra-inguinal bypass grafting. Doppler signals from the anterior tibial, posterior tibial and dorsalis pedis arteries were scored triphasic/biphasic (2), monophasic (1) or absent (0). A total Doppler run off score (0-6) was calculated. Following surgery graft surveillance was undertaken using duplex ultrasound at 6, 12, 26 and 52 weeks. Graft and patient survival were analysed using Cox regression analysis. RESULTS: overall primary assisted graft patency at one year was 80%. With an increasing Doppler score from 0 to 6, primary assisted graft patency steadily rose from 50% to 100% (p = 0.0002), accompanied by a steady fall in patient mortality from 50% to 5% (p = 0.0003).
AIMS: Fish consumption is inversely associated with cardiovascular mortality, presumably because of n-3 fatty acids in fish. Whether the protection of n-3 fatty acids extends beyond clinical coronary disease to influence the early vascular biology of atherosclerosis remains unclear. This study determined whether circulating levels of n-3 fatty acids are associated with vascular endothelial function in early adulthood. METHODS AND RESULTS: Three hundred and twenty-six adults (157 males, 169 females, aged 20 to 28 years) had high-resolution ultrasound measurements of flow-mediated brachial artery dilatation (FMD) (endothelium-dependent) and arterial response to glyceryl trinitrate (endothelium-independent). Levels of the n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid in plasma and erythrocyte membranes of subjects were measured. n-3 Fatty acid levels were not related to vascular function in the whole group. In smokers, however, n-3 fatty acids were positively related to flow-mediated dilatation (plasma DHA vs. FMD: 0.045 mm. %(-1), 95% CI 0.011 to 0.079, P=0.01). Flow-mediated dilatation was also associated with n-3 fatty acid levels in subjects in the top third of the insulin, glucose and triglyceride distributions. CONCLUSION: In young smokers and those with higher fasting insulin, glucose or triglyceride concentrations (factors associated with endothelial dysfunction), n-3 fatty acid levels were positively associated with flow-mediated dilatation. This raises the possibility that physiological levels of circulating n-3 fatty acids may protect the endothelium from early adulthood.
In the present work, the compared effect of milk base and starter culture on acidification, texture, growth, and stability of probiotic bacteria in fermented milk processing, was studied. Two strains of probiotic bacteria were used, Lactobacillus acidophilus LA5 and L. rhamnosus LR35, with two starter cultures. One starter culture consisted only of Streptococcus thermophilus ST7 (single starter culture); the other was a yogurt mixed culture with S. thermophilus ST7 and L. bulgaricus LB12 (mixed starter culture). For the milk base preparation, four commercial dairy ingredients were tested (two milk protein concentrates and two casein hydrolysates). The resulting fermented milks were compared to those obtained with control milk (without enrichment) and milk added with skim milk powder. The performance of the two probiotic strains were opposite. L. acidophilus LA5 grew well on milk but showed a poor stability during storage. L. rhamnosus LR35 grew weakly on milk but was remarkably stable during storage. With the strains tested in this study, the use of the single starter culture and the addition of casein hydrolysate gave the best probiotic cell counts. The fermentation time was of about 11 h, and the probiotic level after five weeks of storage was greater than 106 cfu/ml for L. acidophilus LA5 and 10(7) cfu/ml for L. rhamnosus LR35. However, an optimization of the level of casein hydrolysate added to milk base has to be done, in order to improve texture and flavor when using this dairy ingredient.
OBJECTIVES: The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina. BACKGROUND: Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed. METHODS: Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker. RESULTS: Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05). CONCLUSIONS: Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.
Low birthweight may predispose to the development of atherosclerosis later in life. We have tested the hypothesis that low birthweight as a result of preterm birth is associated with reduced flow-mediated endothelial-dependent vasodilation (FMD), which is an early stage in the development of atherosclerosis. Mean FMD in adolescents born preterm who had a low birthweight did not differ from that for controls born at term (0.225 mm vs 0.220 mm, SD 0.1 for both means, p=0.78). Our findings indicate that low birthweight attributable to prematurity does not increase the risk of vascular disease later in life.
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OBJECTIVES: To test the hypothesis that duration of breast feeding is related to changes in vascular function relevant to the development of cardiovascular disease. DESIGN: Population based observational study. SETTING: Cambridge. PARTICIPANTS: 331 adults (171 women, 160 men) aged between 20 and 28 years, born in Cambridge Maternity Hospital. MAIN OUTCOME MEASURES: Distensibility of brachial artery, type and duration of infant feeding, current lipid profile, and other cardiovascular risk factors. RESULTS: The longer the period of breast feeding the less distensible the artery wall in early adult life, with no sex differences (regression coefficient = -3.93 micrometer/month, 95% confidence interval -7.29 to -0.57, P=0.02). However, in those breast fed for less than four months, arterial distensibility was not significantly reduced compared with an exclusively formula fed group. The vascular changes observed were not explained by alterations in plasma cholesterol concentration in adult life. CONCLUSIONS: Breast feeding in infancy is related to reduced arterial function 20 years later. These data should not alter current recommendations in favour of breast feeding, which has several benefits for infant health. Further work is needed, however, to explore the optimal duration of breast feeding in relation to cardiovascular outcomes.
BACKGROUND: Low birth weight is related to increased risk of coronary heart disease in adults and recently has been associated with vascular endothelial dysfunction in children. We investigated whether the relation between birth weight and endothelial function was still present in early adult life and whether there was an interaction with emerging risk factors. METHODS AND RESULTS: In 315 adults (165 women, 150 men, aged 20 to 28 years), high-resolution ultrasound was used to determine endothelium-dependent and -independent vascular responses of the brachial artery. Vascular measures were related to classic risk factors (smoking history, lipid profile, blood pressure, fasting insulin, exercise capacity, body mass index, and combined risk score) and birth weight. Low birth weight was associated with reduced flow-mediated dilation (coefficient=0.18 kg(-1), 95% CI 0.004 to 0.35, P:=0.04) but not with endothelium-independent dilation. The difference in flow-mediated dilation between the top and bottom fifths of birth weight was the same as between smokers and nonsmokers. Increasing levels of acquired risk factors overwhelmed the association, and there was a significant interaction of risk score with the birth weight-endothelial function relation (coefficient of interaction term [birth weightxrisk score] = -0.12, 95% CI -0.22 to -0.03, P:=0.01). CONCLUSIONS: Low birth weight is associated with endothelial dysfunction in young adults. This is most marked in individuals with lower risk factor profiles and may be relevant to the pathogenesis of atherosclerosis in later life.
BACKGROUND: Despite data relating body size in early life to later cardiovascular outcomes, the hypothesis that nutrition affects such outcomes has not been established. Breastfeeding has been associated with lower blood pressure in later life, but previous studies have not controlled for possible confounding factors by using a randomised design with prospective follow-up. We undertook such a study to test the hypothesis that early diet programmes blood pressure in later life in children randomly assigned different diets at birth. METHODS: Blood pressure was measured at age 13-16 years in 216 (23%) of a cohort of 926 children who were born prematurely and had participated at birth in two parallel randomised trials in five neonatal units in the UK. Dietary interventions were: donated banked breastmilk versus preterm formula and standard term formula versus preterm formula. FINDINGS: Children followed up at age 13-16 years were similar to those not followed up in terms of social class and anthropometry at birth. Mean arterial blood pressure at age 13-16 years was lower in the 66 children assigned banked breastmilk (alone or in addition to mother's milk) than in the 64 assigned preterm formula (mean 81.9 [SD 7.8] vs 86.1 [6.5] mm Hg; 95% CI for difference -6.6 to -1.6; p=0.001). In non-randomised analyses, the proportion of enteral intake as human milk in the neonatal period was inversely related to later mean arterial pressure (beta=-0.3 mm Hg per 10% increase [95% CI -0.5 to -0.1]; p=0.006). No differences were found in the term formula (n=44) versus preterm formula (n=42) comparison. INTERPRETATION: Breastmilk consumption was associated with lower later blood pressure in children born prematurely. Our data provide experimental evidence of programming of a cardiovascular risk factor by early diet and further support the long-term beneficial effects of breastmilk.