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Thomas B Ledue

Publications and source records attributed to Thomas B Ledue.

11 recordsLinked to original sources
PubMed2006

Reference distributions for apolipoproteins AI and B and the apolipoprotein B/AI ratios: a practical and clinically relevant approach in a large cohort.

The two serum apolipoproteins in the highest concentrations, apolipoprotein (apo) AI and apolipoprotein B, and the apolipoprotein B/AI ratio are measured to assess clinical risk for atherosclerotic heart and peripheral vascular diseases. The study is based on a cohort of over 37,000 Caucasian individuals from northern New England measured in one laboratory by immunonephelometry using standardized reference materials. All samples received for protein analyses were accepted provided adequate identifying information was available. Laboratory and demographic information was entered into a single database for subsequent study. Our results show that for males without evidence of inflammation, values of apo AI change little through life. For females, however, values gradually increase until about 60 years of age then fall somewhat thereafter. Among adults, females have higher apo AI values on average, than males. Apo B values change significantly through life, increasing after the end of the second decade to a peak during the sixth decade, then falling thereafter. In the past, concern has been expressed that apo AI is an acute phase reactant (APR), thus complicating cardiovascular risk assessment. The effects of an APR (C-reactive protein >or=10 mg/L) on apo AI, but not on apo B, are measurable for both sexes, most noticeably beyond the age of 60 years in males and females. When values were expressed as age- and gender-specific multiples of the median (MoMs), the resulting distributions fit a log-Gaussian distribution well over a broad range. The size of the relatively homogenous cohort, by a standardized approach, provides a firm basis for comparison to preexisting reference intervals and for establishing a clinically useful and current reference interval for the three main apolipoprotein values.

Age Distribution↗
PubMed2006

Reference distributions for apolipoproteins AI and B and B/AI ratios: comparison of a large cohort to the world's literature.

Limiting the clinical utility of apolipoproteins AI (apo AI) and B (apo B) and the apo B/AI ratios until the last decade has been the lack of satisfactory methods for quantifying serum levels and credible reference materials. Great technological strides have been made in the last few years. The remaining barrier to more relevant and cost-effective use of serum protein data for diagnosis and prognosis has been the availability of widely recognized reliable reference intervals from birth to old age for both males and females. A total of 82 publications reporting reference intervals have been identified that meet most of the same inclusion criteria used in our prior six studies. These have been analyzed statistically and compared to similar studies, i.e., sufficient number, listed subject criteria, method, and reference material, in general terms. Published smaller studies with constrained age ranges, agree on average with our large series of life-long reference intervals that range from less than one year to over 80 years. This study was performed to assess the degree of agreement between smaller reference interval studies to our large population analysis. This meta-analysis provides support and reassurance that many of the smaller reference intervals published previously fall within reasonable limits of out large population.

Age Distribution↗
PubMed2006

Serologic associations of anti-cytoplasmic antibodies identified during anti-nuclear antibody testing.

BACKGROUND: There are currently no guidelines concerning additional laboratory testing for specific autoantibodies among anti-nuclear antibody-negative sera with an anti-cytoplasmic staining pattern identified by indirect immunofluorescence assay. Moreover, few data are available that address this laboratory situation. METHODS: We performed specific autoantibody assays in 200 sera with an anti-nuclear antibody titer < or =1:32 and a cytoplasmic titer (undefined staining pattern) of > or =1:64, identified sequentially in the course of routine anti-nuclear antibody testing. RESULTS: A total of 85 sera (42.5%) were positive in one (n=57) or more (n=28) of the specific autoantibody tests performed. Autoantibodies identified were antimitochondrial (15%), antimicrosomal (13%), anti-neutrophil cytoplasmic (10%), anti-smooth muscle (6%), anti-parietal cell (4%), and extractable nuclear antigen (8.5%, including histones, SSA, SSB, Sm, Jo-1 or Scl-70). A positive result in one or more of these assays was more frequent at anti-cytoplasmic titers > or =1:1024 (77.8%) than at titers of 1:64-1:128 (7%) (chi2=25.3, p<0.001). CONCLUSIONS: The present data demonstrate that undefined anti-cytoplasmic staining in anti-nuclear antibody-negative sera is associated with, although not necessarily caused by, a high frequency and wide range of specific autoantibodies. Further work is needed before specific recommendations can be made concerning follow-up in subjects with this laboratory finding.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2004

Reference distributions for complement proteins C3 and C4: a practical, simple and clinically relevant approach in a large cohort.

The two serum proteins of the complement cascade in the highest concentrations, C3 and C4, respond to various conditions in much the same manner as do other positive acute-phase proteins. A major difference is that they are relatively sluggish in response to cytokine drive, requiring several days rather than hours to be detectably elevated by serial measurements. As with other acute-phase proteins, there are many processes that up- or down-regulate synthesis, including infection or inflammation, hepatic failure, and immune-complex formation. Clinicians may find it difficult to distinguish among these processes, because they often occur simultaneously. The situation is further complicated by genetic polymorphism, with rare instances of markedly reduced synthesis and circulating levels, and consequent vulnerability to infection. C3 and C4 are measured for clinical purposes to help define certain rheumatic and immunologically mediated renal diseases. Interpreting the measured blood levels of these two components requires one to consider the intensity of the inflammatory drive, the timing of the suspected clinical process, the production of complement-consuming immune complexes, and the possible existence of benign circumstances. In this fifth article in a series, reference ranges for serum levels of two complement proteins (C3 and C4) are examined. The study is based on a cohort of over 55,000 Caucasian individuals from northern New England, who were tested in our laboratory in 1994-1999. Measurements were standardized against certified reference material (CRM) 470/reference preparation for proteins in human serum (RPPHS), and analyzed using a previously described statistical approach. Individuals with unequivocal laboratory evidence of inflammation (C-reactive protein of 10 mg/L or higher) were excluded. Our results show that the levels of C3 and C4 change little during life and between the sexes, except that they increase slightly and then fall after age 20 in males and at about age 45 in females. When values were expressed as multiples of the age- and gender-specific median levels, the resulting distributions fitted a log-Gaussian distribution well over a broad range. When patient data are normalized in this manner, the distribution parameters can be used to assign a centile corresponding to an individual's measurement, thus simplifying interpretation.

Acute-Phase Proteins↗
PubMed2004

Reference distributions for alpha2-macroglobulin: a practical, simple and clinically relevant approach in a large cohort.

In this 11th article in a series, reference values of serum levels alpha(2)-macroglobulin alpha(2)M) are examined. The study is based on a cohort of 40,420 Caucasian individuals from northern New England that were tested in our laboratory between 1994 and 2000. Measurements were standardized against Certified Reference Material (CRM 470)/Reference Preparation for Proteins in Human Serum (RPPHS) and the results analyzed using a previously described statistical approach. Individuals with unequivocal laboratory evidence of inflammation (C-reactive protein >10 mg/L) were excluded in one leg of the study and included in the other, confirming that alpha(2)M does not respond to acute phase drive in man. Nephrotic syndrome, diabetes mellitus, and chronic liver disease have significant effect on levels of alpha(2)M. Dramatic changes occur during life with males higher from birth to age 12, females thereafter have higher values until the ninth decade. When values were expressed as multiples of the age- and gender-specific median levels, the resulting distributions fitted a log-Gaussian distribution well over a broad range. When patient data are normalized in this manner, the distribution parameters can be used to assign a centile corresponding to an individual's measurement thus simplifying interpretation.

Adolescent↗
PubMed2003

Preanalytic and analytic sources of variations in C-reactive protein measurement: implications for cardiovascular disease risk assessment.

BACKGROUND: C-reactive protein (CRP) is a widely recognized indicator of inflammation and is known to play an important role in atherogenesis. Recent prospective studies have demonstrated that increased CRP concentrations within the reference interval are a strong predictor of myocardial infarction, stroke, sudden cardiac death, and peripheral vascular disease in apparently healthy adults. On the basis of available evidence, the American Heart Association and the CDC have issued guidelines for the utility of CRP in the primary prevention of coronary heart disease and in patients with stable coronary disease or acute coronary syndromes. Nevertheless, there remains considerable work to optimize the utility of this marker for risk assessment. ISSUES: Most traditional CRP tests designed to monitor acute and chronic inflammation have inadequate sensitivity for risk stratification of coronary disease. Thus, manufacturers have had to develop tests with higher sensitivity. Because an individual's CRP concentration will be interpreted according to fixed cut-points, issues related to the preanalytic and analytic components of CRP measurement must be considered and standardized where possible to avoid potential misclassification of cardiovascular risk. CONCLUSIONS: Efforts to define performance criteria for high-sensitivity CRP applications coupled with growing awareness of the physiologic aspects of CRP most likely will lead to refinements in standardization, improved performance in quality-assessment schemes, and enhanced risk prediction.

Animals↗
PubMed2003

Commutability of the CRM 470 C-reactive protein value in the Dade Behring N High Sensitivity CRP assay.

Certified Reference Material 470 (CRM 470) demonstrates commutability with both the manufacturer's calibrator and with dilutions of serum pools in the Dade Behring N High Sensitivity assay for C-reactive protein (CRP). Both regression and back calibration show similar nonlinearity for all materials, largely due to the method of calibration curve fitting used in this assay. Significant differences in values among the currently available commercial assays can be largely overcome by using appropriate calibration curve fitting and the recommended value transfer protocol, which includes a minimum of two assay runs on each of at least 3 separate days, with weight correction of all reconstitutions and dilutions. An initial weight-corrected dilution should be made each day because of the relatively high level of CRP in CRM 470. In our opinion, the degree of nonlinearity, imprecision, and differences in values in currently available assays renders the use of fixed clinical decision cut-points questionable for high-sensitivity CRP. An alternative approach is suggested.

C-Reactive Protein↗
PubMed2002

Reference distributions for serum iron and transferrin saturation: a comparison of a large cohort to the world's literature.

The appropriate clinical use of serum iron and transferrin saturation (TSAT) requires satisfactory reference intervals from birth to old age, and for males and females. This study identified 54 publications from 1974 to 2001 that met the criteria used in three prior meta-analyses, and these were analyzed statistically. A summary of our review is presented along with our reference population data on these measurements. This analysis places previous publications in perspective and suggests possible reasons for the observed differences. Previous studies of the individual analytes, serum iron, transferrin, and TSAT values agree with the reference ranges presented in this study, although the entire experience over time and between sexes has not been available before. Our 95% reference ranges are somewhat broader than those of the smaller studies, but they agree well with those of the larger ones.

Adolescent↗
PubMed2002

Reference distributions for serum iron and transferrin saturation: a practical, simple, and clinically relevant approach in a large cohort.

The principal considerations driving iron status evaluation are clinical concern for anemia and the possibility of iron-storage disease. Most often, the circulating levels of transferrin (or total iron binding capacity) and serum iron are measured and the percentage of transferrin saturation (TSAT) is then computed. Optimally, reference ranges for these analytes should exclude the effects of the acute phase response, nutritional status, estrogen effect, specific genetic disorders, liver disease, and blood transfusion. The current study reports reference ranges for serum iron and TSAT within a cohort of over 55,000 Caucasians from northern New England, tested in our laboratory between 1994 and 1999. Measurements were standardized against serum reference material (SRM) 937 (for iron) and certified reference material (CRM) 470 (also called reference preparation for proteins in human serum (RPPHS)) (for transferrin), and analyzed using a previously published approach. Individual cases with evidence of inflammation (C-reactive protein > or =10 mg/L), or iron overload (TSAT >80% for males and >70% for females) or serum iron values <5 micro mol/L, were removed. Among the referent individuals, iron and TSAT levels rose slightly until the teen years, at which time levels in males increased while those in females remained essentially constant. Between 20 and 70 years of age, males had 10-15% higher iron levels and 15-20% higher TSAT levels than females. When values were expressed as multiples of the age- and gender-specific median levels, the serum iron and TSAT observations fit log-Gaussian distributions reasonably well from the 20th to 99th centile, and the 10th to the 99th centile, respectively. After normalization, the Gaussian parameters can be used to assign a corresponding centile to an individual's measurement, simplifying interpretation. These data provide new and more detailed reference ranges for serum iron and TSAT.

Acute-Phase Proteins↗
PubMed2002

Development of immunoturbidimetric assays for fourteen human serum proteins on the Hitachi 912.

Many laboratories rely on dedicated nephelometers or turbidimeters and commercial reagent kits for the evaluation of serum proteins. However, with growing emphasis on cost containment, laboratories are forced to seek additional operational efficiencies by capitalizing on the use of existing analyzers whenever possible. In the present paper we describe the development of immunoturbidimetric assays for routine analysis of 14 human serum proteins (alpha1-antitrypsin, alpha2-macroglobulin, albumin, apolipoproteins Al and B, complement components 3 and 4, haptoglobin, immunoglobulins A, G, and M, orosomucoid, prealbumin, and transferrin) on the Hitachi 912, a general chemistry analyzer. With this system, we obtained excellent precision at levels corresponding to low, normal, and high physiologic concentrations of each protein (within-run imprecision CVs < or = 3.4%, total imprecision CVs < or = 4.1%). Linearity for each method was within 5% of the expected value throughout the calibration range, and method comparisons with either the Roche turbidimetric or Dade Behring nephelometric assays were in good agreement (r >0.97). We observed no significant interference from bilirubin (up to 718 micromol/l), hemoglobin (up to 8 g/l), triglyceride (up to 14.7 mmol/l) or rheumatoid factor (up to 4,140 IU/ml). Calibration for the 14 protein assays was stable for at least 7 days and onboard refrigerated reagents were stable for at least 3 months. The instrument's automated sample re-run feature minimized sample handling and helped to conserve specimens. In conclusion, the newly developed assays on the Hitachi 912 offer high throughput (>250 tests per hour) without the associated cost of a dedicated instrument for protein assays.

Blood Proteins↗