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L M Neveux

Publications and source records attributed to L M Neveux.

30 records · Page 2Linked to original sources
PubMed1996

Refinements in managing maternal weight adjustment for interpreting prenatal screening results.

This study examines the relationship between maternal weight and serum levels of alpha-fetoprotein, unconjugated oestriol, and human chorionic gonadotropin in a population of 47,585 women being provided with prenatal screening for Down's syndrome and open neural tube defects. The study population contains sufficient numbers of women at the extremes of weight to allow the determination that a reciprocal-linear equation more accurately describes the weight relationship for two of the three analytes than the currently used log-linear equations. The reciprocal-linear equations, while more appropriate, provide only a minimal advantage over the log-linear equations. A more important finding is that published weight equations may not be optimal for some screening programmes, due to differences in the mean weight of the populations being tested. Screening programmes are encouraged to calculate their own weight correction formulae, based on data from their own population, and to monitor the mean maternal weight to detect when modifications in the weight correction formulae might be indicated.

Body Weight↗
PubMed1996

Can reliable Down's syndrome detection rates be determined from prenatal screening intervention trials?

OBJECTIVES - To develop a standardised approach for analysing Down's syndrome screening performance in clinical practice and to apply it to published intervention trials in order to estimate detection and false positive rates more accurately. METHODS - Peer reviewed intervention trials, grouped by specific combination of analytes, were reanalysed. Revised detection rates were calculated for each study, taking into account both the high spontaneous loss during the last half of pregnancy and the possible under ascertainment of Down's syndrome live births not detected by screening. Collective screening performance was estimated, when possible, using a published methodology based on fitting receiver-operator characteristic curves. RESULTS - Sixteen trials were analysed; 11 using three, and five using two, analytes. Collective screening performance for the triple analyte trials was Down's syndrome detection rates of 57, 64, and 69% at amniocentesis referral rates of 3, 5, and 7% respectively. Four of the five studies involving two analytes performed less well, individually, when compared with the overall performance of the three analyte studies. It was not possible to estimate collective performance for the two analyte studies because there were too few. CONCLUSIONS - Accurate Down's syndrome detection rates are difficult to obtain in intervention trials owing to two potential biases, both of which tend to produce overestimates of the true rates. These sources of bias need to be taken into account when analysing and reporting Down's syndrome intervention trials. The methodology presented here offers the opportunity to achieve a more reliable, standardised estimate of both individual and collective intervention trial screening performance.

Adult↗
PubMed1995

Anti-oxidized LDL antibodies and antiphospholipid antibodies in healthy subjects: relationship with lipoprotein- and oxidation-related analytes.

IgG autoantibodies against malondialdehyde-modified LDL (alpha oxLDL), antiphospholipid antibodies (APA) and oxidation- and lipoprotein-related analytes were assayed in sera from healthy subjects (51 males, 115 females, aged 22-63 years). alpha OxLDL levels were associated (P < 0.03) with IgG alpha cardiolipin (r = 0.18), IgM alpha cardiolipin (r = 0.17) and IgM alpha phosphatidyl-serine (r = 0.16) but not with age, cholesterol, triglyceride, apolipoproteins B and AI, lipoprotein(a), lipid peroxides, ceruloplasmin, copper, ferritin, transferrin or iron. APA levels were inversely associated with levels of both oxidation- and lipoprotein-related analytes. Ferritin (3.5%) and alpha oxLDL (1.4%) contributed independently to variation in IgG alpha cardiolipin levels, and apo B (2%) to variation in IgM alpha cardiolipin levels. These associations are small, indicating that there are no major biological associations between the measured variables. The lack of association between alpha oxLDL and lipoprotein- or oxidation-related analytes suggests that the relevant antigen is not in serum.

Adult↗
PubMed1995

Oxidation-related analytes and lipid and lipoprotein concentrations in healthy subjects.

The relations between oxidation-related analytes and lipoprotein risk factors for coronary heart disease are poorly understood. To address this issue, ceruloplasmin, copper, iron, ferritin, cotinine, lipid peroxides, cholesterol, triglyceride, apoB, apoA-I, and lipoprotein(a) levels were measured in sera from apparently healthy subjects (51 men and 115 women). Pairwise comparisons revealed strong positive associations (P < .001) of copper and ceruloplasmin with lipid peroxides, total cholesterol, triglycerides and apoB, of transferrin with apoA-I and cholesterol, and of ferritin with triglycerides. Serum levels of oxidation-related analytes did not differ between smokers and nonsmokers. In multivariate analysis, serum copper was the major independent determinant of serum lipid peroxide level, accounting for 15% of the variability in concentration (ferritin accounted for 1.6%). Copper and ceruloplasmin accounted for 20.5% of the variation in triglyceride levels; triglycerides and apoB accounted for 12% of the variability in ferritin levels; apoB and apoA-I accounted for 9% of the variability in transferrin levels. The data suggest that serum copper contributes to lipid peroxidation in vivo. There are significant associations between lipoprotein and transition metal-related analytes, and further work is needed to elucidate the physiological basis for these relations.

Adult↗
PubMed1994

Replacing creatinine measurements with specific gravity values to adjust urine cotinine concentrations.

Creatinine and specific gravity (relative density) measurements both allow differences in urine concentration to be taken into account in determining urine cotinine concentrations. In this study we demonstrate that the variance of urine cotinine measurements is reduced comparably when either creatinine or specific gravity measurements are used for correction. This reduction in variability improves the correlation between urine cotinine measurements and clinical endpoints. In this study, the clinical endpoints were pulmonary function in a population of nonsmoking children with asthma, 42% of whom were reported to have been exposed to environmental tobacco smoke. When corrected by either creatinine measurements or specific gravity values, the urine cotinine measurements performed as well or better than reported exposure (and comparably with each other) in assessments of lung function. A dose-response relationship was also more consistently apparent. Specific gravity values can be used reliably in place of creatinine values to adjust urine cotinine measurements for both research and clinical purposes.

Asthma↗
PubMed1993

The relationship between serum levels of lipoprotein(a) and proteins associated with the acute phase response.

The association of serum lipoprotein(a) (Lp(a)) with inflammation was investigated in a primarily rheumatologic study group (n = 570; 202 males and 368 females) by studying the relationship between serum levels of Lp(a) and a panel of acute phase proteins (C-reactive protein (CRP), alpha 1-antitrypsin (AAT), alpha 1-acid glycoprotein (AGP), haptoglobin (HPT), complement components 3 and 4 (C3, C4), prealbumin (PAL), albumin (ALB) and transferrin (TRF)). Lp(a) data were adjusted for age and sex, but not clinical condition as no significant differences in Lp(a) levels were observed, using analysis of variance, among the 15 diagnostic categories in the study group. Univariate analyses revealed significant positive associations between Lp(a) levels and levels of C4, AGP, C3 and HPT. Multivariate analysis revealed that C4 and AGP (in descending order of significance) were significant independent predictors of Lp(a) concentration, together accounting for 2.9% of the variability in Lp(a) concentration in the present study group. The data indicate that confounding effects of an acute phase response should be considered in epidemiologic studies, if a high prevalence of inflammation is suspected.

Acute-Phase Proteins↗
PubMed1993

Association between exposure to environmental tobacco smoke and exacerbations of asthma in children.

BACKGROUND: Exposure to environmental tobacco smoke, as reported by parents, has been linked to diminished pulmonary function and more frequent exacerbations of asthma in children with the disease. Further insight into this association might be gained by using urine cotinine levels to measure actual exposure. METHODS: We measured urine cotinine levels in 199 children with asthma; 145 also underwent pulmonary-function studies. A parent answered questions about each child's exposure to environmental tobacco smoke. Acute exacerbations of asthma during the preceding year were documented through blinded review of medical records. Possible confounding factors were accounted for by the use of multivariate analysis and by comparisons of serum theophylline levels in exposed and unexposed children. RESULTS: The median urine cotinine levels were 5.6 ng per milliliter in the 116 children reported not to have been exposed to tobacco smoke, 13.1 ng per milliliter in the 53 children exposed to cigarette smoking by the mother or other persons, and 55.8 ng per milliliter in the 30 children exposed to cigarette smoking by the mother and other persons. Acute exacerbations of asthma increased with exposure, whether such exposure was reported by a parent or identified on the basis of the cotinine level; the relative risks for the highest as compared with the lowest exposure category were 1.8 (95 percent confidence interval, 1.4 to 2.2) for reported exposure and 1.7 (95 percent confidence interval, 1.4 to 2.1) for exposure indicated by cotinine levels. The forced expiratory volume in one second (FEV1), the forced expiratory flow between 25 and 75 percent of vital capacity, and the ratio of FEV1 to forced vital capacity also decreased with increases in both measures of exposure. CONCLUSIONS: Measurement of urine cotinine levels provides further evidence of an association between exposure to environmental tobacco smoke and pulmonary morbidity in children with asthma. These data emphasize the need for systematic, persistent efforts to stop the exposure of children with asthma to environmental tobacco smoke.

Adolescent↗
PubMed1993

The molecular weights of twelve apolipoprotein(a) variants, determined using haptoglobin 2-2 polymer molecular weight standards.

Apolipoprotein(a) [apo(a)] variants were characterized in 398 sera by immunoblotting: (a) by molecular weight, using a haptoglobin 2-2 polymeric series as standards, and (b) by nomenclature, using serum pools containing previously characterized apo(a) variants as standards. The haptoglobin 2-2 standard curve (172-859 kDa) alleviates the necessity of obtaining molecular weights by extrapolation. Among the 398 sera, 40.2% had double apo(a) bands (54 phenotypes), 58.0% had a single apo(a) band and 1.8% were null (no bands observed). An inverse, though non-monotonic, relationship was observed between apolipoprotein(a) molecular weight and serum lipoprotein(a) [Lp(a)] concentration. Due to the large size of apo(a) and the relatively small increment between variants (15-16 kDa), molecular weight could not be used alone to characterize variants. Even with a CV of 3-4%, there was an overlap between variant molecular weight estimates. However, in combination with the identification of variants by comparison with standards, the haptoglobin 2-2 standard curve could be used to obtain mean molecular weight estimates for each variant. 12 distinct variants were identified among the sera, with apparent mean molecular weights of 314, 388, 410, 433, 454, 466, 503, 519, 528, 543, 553 and 572 kDa, respectively. These molecular weight estimates are consistent with the theoretical molecular weight range for apo(a) variants, calculated from sequence and carbohydrate analysis, of 238-643 kDa.

Apolipoproteins A↗
PubMed1992

Effect of sample storage on the assay of lipoprotein(a) by commercially available radial immunodiffusion and enzyme-linked immunosorbent assay kits.

Lipoprotein(a) [Lp(a)] was measured by both a radial immunodiffusion (RID) kit from Immuno AG (Zurich, Switzerland) and a Tint Elize enzyme-linked immunosorbent assay (ELISA) kit from CytRx Biopool Ltd. (Umeå, Sweden) in serum samples that had been stored at -20 and -70 degrees C for six months. Storage temperature had no significant effect on the Lp(a) concentrations obtained by either method. After six months, mean Lp(a) degradation was 46% (95% confidence interval, 34-58%) with the RID kit; the ELISA data could not be compared between time points. In fresh sera, Lp(a) concentrations obtained by RID were 41% higher than by ELISA (because of differences in assay calibration materials), but in paired measurements of a set of 215 samples stored at -40 degrees C for an average of 10 years, Lp(a) concentrations were 62% lower by RID. This suggests that RID is more sensitive to the effects of long-term storage than is ELISA.

Drug Stability↗
PubMed1991

An improved method for determining high molecular weights by protein immunoblotting: application to apolipoprotein(a) phenotyping.

The determination of very high molecular weights (greater than 500 kd) by protein immunoblotting is limited by a lack of commercially available molecular weight standards in that range. We have therefore investigated the use of the human haptoglobin 2-2 phenotype polymeric series as a high molecular weight standard curve. Using pre-electrophoresed 3-12% SDS polyacrylamide gradient gels, non-dissociated haptoglobin 2-2 serum was separated, transferred and probed with anti-human haptoglobin. We were able to visualize up to 13 bands, with a theoretical molecular weight range of 171.9-859.5 kd, in non-dissociated haptoglobin 2-2 serum. Molecular weights up to 584 kd were confirmed by comparison with available standards. The method was then applied to the determination of apolipoprotein(a) [apo(a)] phenotype molecular weights. Precision of the method was excellent, with intra-run CVs of less than 2.9% and inter-run CVs of less than 3.2% for apo(a) molecular weight. This method of molecular weight calibration is applicable to the characterization of any high molecular weight protein that can be successfully electrophoresed, transferred and visualized.

Apolipoproteins A↗
PubMedDate not supplied

Second-trimester levels of maternal serum human chorionic gonadotropin and inhibin a as predictors of preeclampsia in the third trimester of pregnancy.

OBJECTIVE: To determine whether second-trimester maternal serum levels of inhibin A, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and alpha-fetoprotein (AFP) are predictive of the later onset of preeclampsia in pregnancy. METHODS: Retrospective evaluation of serum analyte levels in 60 women with preeclampsia compared with 300 controls. Levels of each analyte were compared in women with preeclampsia and controls using matched rank analysis. Analytes that were significantly different between groups were examined with univariate and bivariate Gaussian distribution analysis. RESULTS: Second-trimester inhibin A (1.36 multiples of the median [MoM]) and hCG (1.40 MoM) levels were significantly but modestly elevated in women who later developed preeclampsia. A combination test of maternal age plus inhibin A and hCG predicted 23% of cases of preeclampsia with 95% specificity. There was a statistically significant trend for inhibin A, but not hCG, levels to be higher when the onset of preeclampsia occurred within a shorter (<17 weeks) interval after collection of the second-trimester screening sample. CONCLUSIONS: Second-trimester serum levels of inhibin A and hCG are modest predictors of the later onset of preeclampsia. Inhibin A may be a better predictor of early-onset preeclampsia, which is associated with a higher maternal and perinatal morbidity and mortality, than preeclampsia at or near term.

Adult↗