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Biomedical subjects

J N Macri

Publications and source records attributed to J N Macri.

At least 37 records · Page 2Linked to original sources
PubMed1993

First-trimester free beta (hCG) screening for Down syndrome.

Maternal serum free beta (hCG) levels are elevated (median 2.20 MOM) in the first trimester of pregnancy in 38 Down syndrome cases as compared with appropriate controls. This observation may form the basis for its use as a marker in screening for Down syndrome in the first trimester. Altered levels of the free beta analyte are observed in pregnancy conditions or complications other than Down syndrome.

Biomarkers↗
PubMed1993

First-trimester biochemical screening for fetal chromosome abnormalities and neural tube defects.

Alpha-fetoprotein (AFP), unconjugated oestriol (UE3), intact human chorionic gonadotrophin (intHCG), and the free beta subunit of chorionic gonadotrophin (F beta HCG) were investigated in a series of 21 chromosomally abnormal and 14 open neural tube defect pregnancies ascertained from a series of 14,000 prospectively collected maternal serum samples at 6-14 weeks' gestation. In 16 cases of Down's syndrome, significant reductions were found for AFP (0.65 multiples of the normal median) and UE3 (0.67 MOM). IntHCG levels were unaltered (0.97 MOM) but a significant increase was found for F beta HCG (1.96 MOM). Significant correlations were found for AFP and UE3 in the controls and for intHCG and F beta HCG in both the control and the Down's syndrome pregnancies. In a group of five trisomy 18 pregnancies, median MOMs were for AFP 0.71, for UE3 0.34, for intHCG 0.27, and for F beta HCG 0.15. None of 13 pregnancies with open neural tube defects at 8-13 weeks gestation had elevated maternal serum AFP levels, whereas matched second-trimester samples from the same pregnancies at 16-18 weeks gestation all had significantly elevated AFP levels. Thus, biochemical screening for chromosome abnormalities may be practicable in the first trimester using free beta human chorionic gonadotrophin in combination with AFP and maternal age. However, a separate screening protocol using AFP at 15-18 weeks gestation would still be required for effective detection of neural tube defects.

Biomarkers↗
PubMed1993

Free beta-chorionic gonadotropin: a cross-reactivity study of two immunometric assays used in prenatal maternal serum screening for Down's syndrome.

We have evaluated the cross-reactivity characteristics of two distinct immunometric assays for the measurement of free beta-human chorionic gonadotropin (free beta). These maternal serum assays have been used in the initial studies which evaluated free beta as a marker in the prenatal detection of Down's syndrome. It has been suggested that free beta assays are subject to substantial potential for cross-reactivity. To confirm that free beta was the analyte responsible for enhanced detection efficiency both non-competitive and competitive cross-reactivity evaluations were undertaken. These studies demonstrated acceptably small cross-reactivity to other glycoprotein hormones or their beta components. We conclude that properly designed free beta assays will provide specific analyte measurement and improved detection efficiency in Down's syndrome screening.

Antibodies, Monoclonal↗
PubMed1993

Dual analyte immunoassay in neural tube defect and Down's syndrome screening: results of a multicentre clinical trial.

We report a multicentre clinical field trial of a novel dual analyte enzyme immunoassay method for the simultaneous measurement of alpha-fetoprotein (AFP) and free beta-human choriogonadotropin (hCG) in the same microtitre well. The assay was shown to have good technical performance in the hands of all trial centres, with between assay coefficients of variation better than 10% for both analyte across the whole of the assay ranges. The method compared well with single analyte measuring procedures and produced acceptable performance as judged by external quality assurance criteria. Recovery of added analyte and analyte dilution curves also showed acceptable performance. In clinical evaluation of a large set of neural tube defect cases, good clinical discrimination from unaffected cases was observed using AFP. With over 150 Down's syndrome cases, the combination of AFP and free beta hCG confirmed the high detection rates achievable using this marker combination, with detection rates in excess of 70% in early gestation. We conclude that the combination of clinically superior markers coupled with technologically innovative assay design will lead to more efficient Down's screening programmes.

Adolescent↗
PubMed1993

Stability of intact chorionic gonadotropin (hCG) in serum, liquid whole blood, and dried whole-blood filter-paper spots: impact on screening for Down syndrome by measurement of free beta-hCG subunit.

The use of multiple maternal serum biochemical markers in screening for Down syndrome is gaining worldwide acceptance. We sought to study the impact of the potential instability of intact human chorionic gonadotropin (hCG) on free beta-hCG subunit, a marker that has recently been used successfully in such screening. We found that, in practice, any changes in free beta-hCG due to the instability of intact hCG do not inhibit the effectiveness of free beta-hCG as a marker for Down syndrome. This was proven by controlled laboratory experiments at various stress temperatures, freeze-thaw studies, and analysis of a large set of screening data with particular reference to time in transit for individual samples. Data from controlled dissociation studies demonstrate that any apparent increase in free beta-hCG due to the instability of intact hCG cannot be attributed simply to the dissociation of intact hCG. Finally, for large-scale mass population screening in areas of the world where transport delays, safety concerns, and high temperatures preclude the shipment of liquid whole blood, dried whole-blood spots in filter paper provide a suitable delivery system with many advantages.

Blood Specimen Collection↗
PubMed1992

Dual Analyte immunoassay--a new approach to neural tube defect and Down's syndrome screening.

A microtiter plate based Dual Analyte enzyme-immunoassay method for the simultaneous measurement of alpha-fetoprotein (AFP) and Free-beta human chorionic gonadotrophin (hCG) was evaluated. This rapid assay, which has application in both Neural Tube Defect screening and Down's screening, shows good precision with between assay coefficients of variation between 5 and 7.5% for AFP and 3.7 to 5.8% for Free-beta(hCG). Correlation with single analyte procedures is good, with correlation coefficients being greater than 0.91 in both cases. Clinical discrimination in detecting both types of abnormalities is not compromised by this new simultaneous Dual Analyte assay. We conclude that the Dual Analyte approach, which combines analytes achieving the highest known detection efficiency, will bring about improvements in the efficiency of screening, reduce costs and improve report turnaround, all leading to better quality of patient care.

Chorionic Gonadotropin↗
PubMed1990

Maternal serum Down syndrome screening: free beta-protein is a more effective marker than human chorionic gonadotropin.

The use of quantitative human chorionic gonadotropin measurement in obstetrics has a long and successful history. Prior studies on the utility of human chorionic gonadotropin in Down syndrome screening have utilized assays that measure the intact human chorionic gonadotropin molecule. This study targeted a distinct marker, the human chorionic gonadotropin free beta-protein, which is present in second-trimester maternal serum at much lower concentrations than is intact human chorionic gonadotropin. Our study of 29 cases of trisomy 21 and 450 control samples shows 80% detection efficiency with maternal serum alpha-fetoprotein, the free beta-protein, and maternal age in pregnancies under 17 weeks' gestation. We conclude that the combination of maternal serum alpha-fetoprotein and the human chorionic gonadotropin free beta-protein will be useful in the prenatal detection of trisomy 21.

Antibodies, Monoclonal↗
PubMed1990

Maternal serum Down syndrome screening: unconjugated estriol is not useful.

Study of 41 known Down syndrome cases and 441 matched controls did not confirm earlier reports that low unconjugated estriol levels can be used to detect fetal Down syndrome. Hence the obstetric community should exercise caution in using unconjugated estriol levels as a marker in prenatal Down syndrome screening.

Down Syndrome↗
PubMed1990

Maternal serum alpha-fetoprotein (MSAFP) patient-specific risk reporting: its use and misuse.

Fundamental to maternal serum alpha-fetoprotein screening is the clinical utility of the laboratory report. It follows that the scientific form of expression in that report is vital. Professional societies concur that patient-specific risk reporting is the preferred form. However, some intermediate steps being taken to calculate patient-specific risks are invalid because of the erroneous assumption that multiples of the median (MoMs) represent an interlaboratory common currency. The numerous methods by which MoMs may be calculated belie the foregoing assumption.

Algorithms↗
PubMed1987

Maternal serum alpha-fetoprotein screening. II. Pitfalls in low-volume decentralized laboratory performance.

Assays of maternal serum alpha-fetoprotein are subject to the phenomenon of assay drift, which may be defined as incorrect increase or decrease of alpha-fetoprotein values from their true values. Low maternal serum alpha-fetoprotein weekly volume (for example, fewer than 500 specimens per week) will result in a greater than 47% probability that 10% assay drift will not be recognized. Further, laboratory reports to clinicians may lead to either misdirecting 43% more pregnant women (with positive drift) into further (possibly invasive) diagnostic procedures or the offer of further diagnostic services to 32% fewer gravidas at increased risk (with negative drift) than should be so managed. We address the problem outlined above and present the reasons for establishment of regional maternal serum alpha-fetoprotein screening programs operating at sufficient volume to permit the identification and control of assay drift.

Clinical Laboratory Techniques↗
PubMed1987

Maternal serum alpha-fetoprotein screening. III. Pitfalls in evaluating black gravid women.

Maternal serum alpha-fetoprotein levels are higher in black women. Misinterpretation of maternal serum alpha-fetoprotein screening results can subject black gravid women to unnecessary invasive diagnostic procedures and their calculable risks. Screening errors for black women can result from the use of normative data bases established with maternal serum samples drawn from other racial groups or the use of such data bases in conjunction with a published correction factor. Because the incidence of open neural tube defects is lower for blacks than for others, excessive false positive results for blacks (estimated to be 8817 to 28,215 cases annually) would be a pernicious misapplication of maternal serum alpha-fetoprotein screening. We address the problem outlined above and recommend independently developed, valid, normative data bases.

Black People↗
PubMed1986

Critical issues in prenatal maternal serum alpha-fetoprotein screening for genetic anomalies.

Prenatal screening, in this Clinical Opinion article, is defined as a population-based search for subgroups of pregnancy that by virtue of their maternal serum alpha-fetoprotein levels may be at increased risk for genetic anomalies. The identification of subgroups at risk for neural tube defects, ventral wall defects, and chromosomal trisomies presents clinicians with unprecedented information and issues, including the biomedical basis for prenatal screening, the distinction between screening and diagnosis, and the decision-making function of the patient. The interest and, perhaps, ambivalence of the clinical community to prenatal screening are understandable. Obstetricians ordering prenatal screens are challenged by medical data associated with epidemiology, pathology, and genetics, including: prevalence of disease, interpretive biochemical reporting, and the assessment and communication of patient-specific risks. Obstetricians ordering screens will be called on to provide information generally used by other specialists at other stages of care. What information, how it is biomedically determined, its form for communication to patients, and pitfalls in the process are discussed.

Body Weight↗