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Biomedical subjects

A Lucas

Publications and source records attributed to A Lucas.

At least 91 records · Page 5Linked to original sources
PubMed2000

Clinical safety of iron-fortified formulas.

BACKGROUND: Iron-fortified formulas are recommended throughout infancy and are frequently used beyond, yet safety aspects have been inadequately studied. Iron could theoretically increase pro-oxidant stress, with potential adverse effects, including infection risk, and some clinicians suspect that iron-fortified formulas induce gastrointestinal disturbance. OBJECTIVE: A planned component of a large intervention trial has been to test the hypothesis that infants receiving iron-fortified formula do not have a higher incidence of infections (primary outcome) or gastrointestinal problems (secondary outcome) than infants on low iron-formulas or cow's milk. Methods. Children (n = 493) 9 months old receiving cow's milk were recruited in 3 UK centers and randomized to: 1) cow's milk as before, 2) formula containing.9 mg/L of iron, or 3) an otherwise identical formula but containing 12 mg/L of iron. Children were followed at 3 monthly intervals and the episodes of infections, diarrhea and constipation, and general morbidity to 18 months old were recorded. Hematologic indices of iron status were determined at 18 months old. RESULTS: Serum ferritin concentrations were increased in infants receiving iron-fortified formula but there were no intergroup differences in incidence of infection, gastrointestinal problems, or in general morbidity or weight gain. CONCLUSIONS: We were unable to identify adverse health effects in older infants and toddlers consuming a high iron-containing formula (12 mg/L) even when used in populations with a low incidence of iron deficiency.

Animals↗
PubMed2000

Optical detection of triggered atherosclerotic plaque disruption by fluorescence emission analysis.

Fluorescence emission analysis (FEA) has proven to be very sensitive for the detection of elastin, collagen and lipids, which are recognized as the major sources of autofluorescence in vascular tissues. FEA has also been reported to detect venous thromboemboli. In this paper we have tested the hypothesis that FEA can reproducibly detect in vivo and in vitro triggered plaque disruption and thrombosis in a rabbit model. Fluorescence emission (FE) spectra, recorded in vivo, detected Russell's viper venom (RVV)-induced transformation of atherosclerotic plaque. FE intensity at 410-490 nm 4 weeks after angioplasty was significantly lower (P < 0.0033 by analysis of variance) in RVV-treated rabbits when compared to control animals with stable plaque. FE spectral profile analyses also demonstrated a significant change in curve shape as demonstrated by polynomial regression analysis (R2 from 0.980 to 0.997). We have also demonstrated an excellent correlation between changes in FE intensity and the structural characteristics detected at different stages of "unstable atherosclerotic plaque" development using multiple regression analysis (R2 = 0.989). Thus, FEA applied in vivo is a sensitive and highly informative diagnostic technique for detection of triggered atherosclerotic plaque disruption and related structural changes, associated with plaque transformation, in a rabbit model.

Angioplasty, Balloon↗
PubMed2000

Quantification of carotid stenoses using 3D morphometer, CT angiography and conventional angiography.

BACKGROUND: The aim of this study is to compare the performances of 3D morphometer (M3D) regarding the quantification of extracranial carotid stenoses with selective 2D conventional angiography (reference technique) and spiral CT scan. METHODS: It is a prospective study, including 15 patients (mean age 75) presenting a symptomatic carotid lesion detected via duplex Doppler to be operated. Patients had to hold their breath for 20 seconds. Twenty-nine carotid bifurcations were studied by means of M3D and 2D conventional angiography (15 patients). Only 10 patients (19 bifurcations) underwent a CT scan. The measures were performed on a visual display unit by measuring the pixels as per the NASCET technique. Diameters (MIP technique) and surfaces (reformated axial slices) were measured. RESULTS: With MIP technique, a good correlation was found 20 times in 29 (69%) (overestimation: n=8/29) between M3D and angiography, but only in 9 of 19 cases (47%) between CT scan and angiography. Unlike with M3D, the slices re-oriented with CT scan gave better correlations: 15 times in 19 (79%). With the CT scan, the measures were impossible 8 times on MIP technique, and twice on reformated slices for calcified tight stenoses. Therefore, the quantification by means of spiral CT scan is easier by planimetry on slices. CONCLUSIONS: The reliability of these 3D explorations regarding quantification remains uncertain. The use of a morphometer, provided that technical adaptations are made, could replace selective sequences in multiple incidences that become accessible in the post-treatment period, with an acquisition field larger than the one of the CT scan.

Aged↗
PubMed1999

Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial.

BACKGROUND: We tested whether addition of n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) to infant-formula milk during the first 6 months promotes long-term cognitive and motor development, without adverse consequences. METHODS: We did a double-blind, randomised, controlled, efficacy and safety trial of formula with and without LCPUFAs, with an additional breastfed reference group, in four hospitals in two cities in the UK. The participants were 447 healthy full-term babies. 309 were fed formula (155 without LCPUFAs) and 138 were breastfed for at least 6 weeks. The main outcome measures were: Bayley Mental and Psychomotor Development Indices (MDI, PDI) at 18 months (primary efficacy outcome) and Knobloch, Passamanick, and Sherrards test at 9 months (secondary outcome). Principal safety outcomes were: infection, atopy, growth, and gastrointestinal tolerance. FINDINGS: Babies fed formula with and without LCPUFA did not differ in cognitive or motor development, growth, infection, atopy or tolerance. The mean (95% CI) MDI was 0.5 (-2.7 to 3.8) units and the PDI 0.6 (-1.8 to 3.0) units higher in the supplementation group. Formula-fed infants had similar developmental scores to the breastfed reference group after adjustment for higher social class and maternal education in the latter. INTERPRETATION: There was no evidence of a beneficial or adverse effect on cognitive and motor development or growth up to 18 months. Although no significant differences in safety outcomes were observed, we suggest such data should be collected in future LCPUFA trials. Our trial does not provide support for addition of LCPUFA to standard infant formula but we are now doing further follow-up of this cohort.

Animals↗
PubMed1999

Role of the C-terminal RDEL motif of the myxoma virus M-T4 protein in terms of apoptosis regulation and viral pathogenesis.

The purpose of this study was to investigate the significance of the C-terminal RDEL motif of the myxoma virus M-T4 protein in terms of apoptosis regulation and role in viral virulence. To accomplish this, a recombinant myxoma virus was created in which the C-terminal RDEL motif of M-T4 was deleted and a selectable marker (Ecogpt) was inserted immediately downstream. We hypothesized that removal of the RDEL motif from M-T4 would alter the subcellular localization of the protein and provide insight into its antiapoptotic role. Surprisingly, removal of the RDEL motif from M-T4 did not affect localization of the protein within the endoplasmic reticulum (ER), but it did reduce the stability of the mutant protein. Pulse-chase immunoprecipitation and endoglycosidase H analysis coupled with confocal fluorescent light microscopy demonstrated that the M-T4 RDEL(-) mutant protein is retained in the ER like wildtype M-T4 and suggests that the C-terminal RDEL motif is not the sole determinant for M-T4 localization to the ER. Infection of cultured rabbit lymphocytes with the M-T4 RDEL(-) mutant virus results in an intermediate apoptosis phenotype compared with the wildtype and M-T4 knockout mutant viruses. A novel myxomatosis phenotype was observed in European rabbits when infected with the recombinant M-T4 RDEL(-) mutant virus. Rabbits infected with the M-T4 RDEL(-) virus on day 9 postinfection exhibited an exacerbated edematous and inflammatory response at secondary sites of infections, particularly the ears. Our results indicate that the C-terminal RDEL motif may not be solely responsible for retention of M-T4 to the ER and that M-T4 may have a dual function in protecting infected lymphocytes from apoptosis and in modulating the inflammatory response to virus infection.

Amino Acid Motifs↗
PubMed1999

Role of the myxoma virus soluble CC-chemokine inhibitor glycoprotein, M-T1, during myxoma virus pathogenesis.

Myxoma virus is a poxvirus that causes a virulent systemic disease called myxomatosis in European rabbits. Like many poxviruses, myxoma virus encodes a variety of secreted proteins that subvert the antiviral activities of host cytokines. It was recently demonstrated that the myxoma virus M-T1 glycoprotein is a member of a large poxvirus family of secreted proteins that bind CC-chemokines and inhibit their chemoattractant activities in vitro. To determine the biological role of M-T1 in contributing to myxoma virus virulence, we constructed a recombinant M-T1-deletion mutant virus that was defective in M-T1 expression. Here, we demonstrate that M-T1 is expressed continuously during the course of myxoma virus infection as a highly stable 43-kDa glycoprotein and is dispensable for virus replication in vitro. Deletion of M-T1 had no significant effects on disease progression or in the overall mortality rate of infected European rabbits but heightened the localized cellular inflammation in primary tissue sites during the initial 2 to 3 days of infection. In the absence of M-T1 expression, deep dermal tissues surrounding the primary site of virus inoculation showed a dramatic increase in infiltrating leukocytes, particularly monocytes/macrophages, but these phagocytes remained relatively ineffective at clearing virus infection, likely due to the concerted properties of other secreted myxoma virus proteins. We conclude that M-T1 inhibits the chemotactic signals required for the influx of monocytes/macrophages during the acute-phase response of myxoma virus infection in vivo, as predicted by its ability to bind and inhibit CC-chemokines in vitro.

Animals↗
PubMed1999

Detection of transplant vasculopathy in a rat aortic allograft model by fluorescence spectroscopic optical analysis.

BACKGROUND AND OBJECTIVE: Transplant vasculopathy is a leading cause of late cardiac graft loss. We have examined laser-induced fluorescence (LIF) spectroscopy as an optical diagnostic tool for detection of intimal plaque development and inflammatory cellular invasion in a rat model of aortic allograft transplant. STUDY DESIGN/MATERIALS AND METHODS: Infrarenal aortic segments were transplanted from Lewis to Sprague Dawley rats. A range of vasculopathy development was produced by treatment with a viral anti-inflammatory protein. LIF spectra were recorded from the intima of aortic implants at 28 days. Fluorescence intensity was analyzed for correlation with vasculopathy development. RESULTS: Significant differences in LIF intensity at 400-450 nm (P < or = 0.05 by ANOVA) were detected. LIF emission was correlated with plaque growth (R2 = 0.980), vessel narrowing (R2 = 0.964), and cellular invasion (R2 = 0.971) by regression analysis. CONCLUSION: LIF optical analysis provides a nontraumatic diagnostic approach for detection of atherosclerosis prior to cardiac transplant or during development of vasculopathy after transplant.

Animals↗
PubMed1999

New black blood pulse sequence for studies of the heart.

The black blood concept is based on the signal void principle of the sequences in Spin Echo, SE or FSE, which are very useful for studying the mediastinum and heart. In this setting, new sequences are continuously introduced to eliminate the artifacts caused by breathing and heart movements. One such sequence is the Double-IR preparation Black Blood FSE. We report our experience in 97 patients, using this new pulse sequence to evaluate cardiac pathology, and establish comparisons with the conventional Spin Echo sequences. The study comprises mediastinal disease and aorta and heart explorations. We consider this new Double-IR preparation FSE sequence to be an excellent choice for evaluating chest, mediastinal and cardiac images. The sequence offers improved spatial resolution of both the vessels and other chest structures with respect to conventional Spin Echo imaging. With the exception of patients presenting severe heart problems, or in the presence of intense bradycardia, the required 16 cycles in apnea are well tolerated. The purpose of the present study is to present our initial results with this new pulse sequence as applied to cardiac pathology, in comparison with conventional Spin Echo imaging.

Aortic Diseases↗
PubMed1999

Double-blind, randomized trial of a synthetic triacylglycerol in formula-fed term infants: effects on stool biochemistry, stool characteristics, and bone mineralization.

BACKGROUND: The low sn-2 palmitate content of infant formulas results in formation of fatty acid calcium soaps in the stools and reduced calcium absorption. OBJECTIVE: Our objective was to test the hypotheses that increasing the proportion of sn-2 palmitate in formula for term infants would result in greater skeletal mineral deposition and reduced stool hardness. DESIGN: Healthy term neonates were randomly assigned to receive standard formula (n = 103) or formula containing 50% sn-2 palmitate (high-sn-2 formula; n = 100) for 12 wk. One hundred twenty breast-fed infants were also studied. The main outcome measures were 1) radial (single-photon absorptiometry) and whole-body (dual-energy X-ray absorptiometry) bone mineral content (WBBMC) at 12 wk and 2) stool frequency, volume, and consistency at 6 and 12 wk. Secondary outcome measures included stool fatty acid content. RESULTS: Infants receiving high-sn-2 formula had higher WBBMC (128.1 +/- 9.7 compared with 122.7 +/- 10.1 g, adjusted for size and sex), softer stools at 6 and 12 wk, and a lower proportion of stool soap fatty acids than did infants receiving the control formula. Breast-fed infants had adjusted WBBMC values (128.3 +/- 9.1 g) similar to those of infants fed high-sn-2 formula and significantly higher than those of infants fed the control formula. CONCLUSIONS: Changing the stereoisomeric structure of palmitate in infant formula resulted in higher WBBMC, reduced stool soap fatty acids, and softer stools more like those of breast-fed infants. The greater bone mass measured could be important if it persists beyond the trial period; this merits further investigation.

Absorptiometry, Photon↗
PubMed1999

Iron fortified follow on formula from 9 to 18 months improves iron status but not development or growth: a randomised trial.

AIMS: Iron deficiency anaemia is associated, in observational studies, with developmental disadvantage. This study tested the hypothesis that feeding iron supplemented formula from 9 to 18 months of age would improve developmental performance. SUBJECTS AND METHODS: 493 healthy children aged 9 months being fed pasteurised cows' milk were recruited from three UK centres. They were randomised to: cows' milk as before, formula containing 0.9 mg/litre iron, or formula containing 1.2 mg/litre iron, until 18 months of age. Bayley mental and psychomotor developmental indices were measured at 18 months, as were growth and haematological indices. RESULTS: Children fed iron fortified formula had higher plasma ferritin concentrations, but there were no significant intergroup differences in development or growth. CONCLUSIONS: There are no developmental or growth advantages in children given iron supplemented formula, but a benefit for a minority who were anaemic, or the possibility that a benefit may emerge at a later age, cannot be excluded.

Anemia, Iron-Deficiency↗
PubMed1999

Bone mineralization and turnover in preterm infants at 8-12 years of age: the effect of early diet.

Our previous studies raised two hypotheses: first that suboptimal early nutrition and second that human milk have enhancing effects on long-term bone mineralization. To test these hypotheses experimentally, we measured whole body and regional bone mineral content (BMC) and bone mineral density (BMD), using dual-energy X-ray absorptiometry and single-photon absorptiometry, and bone turnover at 8-12 years in 244 preterm children (128 boys) who participated in a prospective randomized study of diet during the neonatal period. Dietary randomizations studied were: banked human milk (BBM, n = 87) versus preterm formula (PTF, n = 96) as the sole diet or as a supplement to mother's expressed breast milk (EBM); PTF (n = 25) versus term formula (TF, n = 36) as sole diet. Ninety-five term children of the same age were also studied. First, preterm children were shorter and lighter than term children (height SD scores -0.49 (1.1) vs. +0.22 (0.9), weight SD scores -0.41 (1.2) vs. +0.38 (1.0)) and had significantly lower whole-body BMC than their peers; decrements were also evident at some regional sites. These differences disappeared after adjusting for bone area, body size, and pubertal status. Second, children previously randomized to BBM versus PTF or TF versus PTF showed no significant differences in anthropometry, BMC, BMD, or osteocalcin (OC). Third, there was no independent effect of the proportion of EBM on BMC, BMD, or OC and no interaction between randomized diet and the amount of EBM received. Fourth, plasma OC was significantly higher in preterm children than in term children (12.4 vs. 11.0 ng/ml, p < 0.005) and in preterm children who had received a low-nutrient (BBM/TF) as opposed to a high-nutrient diet (PTF) during the neonatal period (12. 9 vs. 11.9 ng/ml, p = 0.03). In conclusion, preterm children are shorter, lighter, and have lower bone mass than their peers at age 8-12 years. The lower BMC is, however, appropriate for the bone and body size achieved. Despite large differences in early mineral intake, early diet does not affect bone mass in preterm children, and fresh human milk has no specific effect. However, poor nutrition during the neonatal period may result in higher bone formation rates during childhood.

Biomarkers↗
PubMed1999

Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group.

OBJECTIVE: The aim of the present study was to assess the socio-economic impact at baseline and after one year of follow-up of clinical and health status characteristics and laboratory tests of adult-onset GH deficiency (AGHD), a well-known clinical entity, in a large group of Spanish hypopituitary patients with untreated AGHD. DESIGN AND METHODS: A total of 926 eligible patients with GHD (GH </= 5 ng/ml after stimulation) and at least one further pituitary hormone deficiency were retrospectively studied; 356 of these were followed for one year. Complete physical examination, IGF-I, lipid and routine biochemistry measurements and health-related quality of life (HRQoL) with the specific QoL-Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire were assessed at baseline and at 12 months in the prospective study. Health status and health-economic evaluation were measured by a specific questionnaire and a patient diary and compared with Spanish population study results. RESULTS: Clinical characteristics and laboratory tests of AGHD showed a higher incidence of cardiovascular risk factors and mortality compared with the general population (hypercholesterolaemia in 29% vs 18% and hypertension in 22.1% vs 14. 9%). QoL-AGHDA scores for patients were significantly worse (P<0.01) and direct health costs were higher than in the general population. CONCLUSIONS: Hypopituitary GHD adults had more cardiovascular risk factors, higher mortality, worse HRQoL and higher absolute health costs than the general population in Spain.

Adult↗
PubMed1999

Laser-induced fluorescence (LIF) recognition of the structural composition of porcine heart valves.

Reconstruction and replacement of heart valves with grafts fro pig tissue is a common procedure. However, bioprosthetic valves wear out in a shorter time span than mechanical valves. Bioprosthetic valve structure may contribute to degenerative changes that lead to valve failure. There is, at present, no method to examine the structure of a tissue valve prior to implant. Laser-induced fluorescence (LIF) of natural fluorophores is an elegant method developed for the detection of tumors, dermal lesions and atherosclerosis. We have studied LIF as a potential diagnostic technique for analysis of valvular tissue. Using excimer laser excitation, we examined natural fluorescence recorded from porcine aortic, mitral and pulmonary valves. All three valve outflow surface tissue layers are less fluorescent at 390-450 nm than the inflow layers. Immunohistochemical analysis of collagen I and elastin content in inflow and outflow surface layers of all three valves correlated well with LIF intensities and dI/d lambda values at selected wavelengths. In conclusion, the differences observed in emitted LIF from valve surface layers are found to correlate well with diversity in the structural protein content. The LIF spectroscopic measurements may provide an appropriate tool for examination of tissue valve structure prior to use for implantation.

Animals↗