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Biomedical subjects

Peter Benn

Publications and source records attributed to Peter Benn.

12 recordsLinked to original sources
PubMed2006

Three-stage contingent screening for Down syndrome.

OBJECTIVE: To demonstrate the potential value of three-stage sequential screening for Down syndrome. METHODS: Protocols were considered in which maternal serum pregnancy associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (hCG) measurements were taken on all women in the first trimester. Those women with very low Down syndrome risks were screened negative at that stage and nuchal translucency (NT) was measured on the remainder and the risk reassessed. Those with very low risk were then screened negative and those with very high risk were offered early diagnostic testing. Those with intermediate risks received second-trimester maternal serum alpha-fetoprotein, free beta-hCG, unconjugated estriol and inhibin-A. Risk was then reassessed and those with high risk were offered diagnosis. Detection rates and false-positive rates were estimated by multivariate Gaussian modelling using Monte-Carlo simulation. RESULTS: The modelling suggests that, with full adherence to a three-stage policy, overall detection rates of nearly 90% and false-positive rates below 2.0% can be achieved. Approximately two-thirds of pregnancies are screened on the basis of first-trimester biochemistry alone, five out of six women complete their screening in the first trimester, and the first-trimester detection rate is over 60%. CONCLUSION: Three-stage contingent sequential screening is potentially highly effective for Down syndrome screening. The acceptability of this protocol and its performance in practice, should be tested in prospective studies.

Algorithms↗
PubMed2005

Early growth response gene 1 (EGR1) is deleted in estrogen receptor-negative human breast carcinoma.

BACKGROUND: Patients with estrogen receptor (ER)-positive and ER-negative breast carcinomas differ in terms of disease progression, treatment regimens, and prognosis. The mechanism underlying the biologic differences of the two groups is understood poorly. Array comparative genome hybridization (CGH) on breast carcinoma subtypes demonstrated a consistent association between loss in regions of chromosome 5q and ER-negative tumors. It was shown previously that early growth response gene 1 (EGR1) on 5q acts like a tumor-suppressor gene, with its expression repressed in breast carcinomas. METHODS: To test the hypothesis that EGR1 is deleted differentially in ER-negative versus ER-positive breast carcinomas, fluorescence in situ hybridization was employed in this study to determine the EGR1 deletion status in 50 breast carcinoma specimens. Deletion status was measured by the signal ratio of EGR1/chromosome 5. Linear regression was used to assess the results. RESULTS: The mean EGR1/chromosome 5 ratio for the ER-negative group was significantly lower compared with the same ratio for the ER-positive group (P < 0.001). Although grade alone was not significant for predicting the ratio, the interaction between ER status and grade was significant (P < 0.01): For ER-negative specimens, the higher the grade, the lower the EGR1/chromosome 5 ratio. CONCLUSIONS: The EGR1 gene appeared to be deleted in ER-negative human breast carcinomas. Egr-1 may contribute to the pathogenesis of ER-negative breast carcinomas versus ER-positive breast carcinomas.

Breast Neoplasms↗
PubMed2005

Practical strategies in contingent sequential screening for Down syndrome.

OBJECTIVE: To design and assess the performance of protocols for contingent sequential Down syndrome screening that can be implemented in practice. METHODS: Protocols were designed in which all women received first-trimester measurement of nuchal translucency (NT) together with maternal serum pregnancy-associated plasma protein-A (PAPP-A) and either free beta- or total human chorionic gonadotrophin (hCG). Those women with borderline Down syndrome risks received follow-up second-trimester maternal serum involving double, triple, or quadruple serum screening markers: alpha-fetoprotein, free beta-hCG or total hCG, unconjugated estriol and inhibin-A. Specific ranges of risks were used to define the borderline group. Separate protocols were developed for the United Kingdom and the United States to reflect differences in commonly used tests, cut-offs, and the gestational age at testing. Detection rates and false-positive rates were estimated by multivariate Gaussian modelling with Monte Carlo simulation. RESULTS: Proposed protocols based on first-trimester NT, PAPP-A and free beta-hCG or total hCG, followed by selective use of second-trimester quadruple markers can result in a 91% detection rate and 2.1% false-positive rate for the United Kingdom and a detection rate of 89% and false-positive rate of 3.1% for the United States. For both countries, over 60% of affected pregnancies would be detected in the first trimester and less than 20% of women would require a second-trimester Down syndrome risk assessment. Use of alternative cut-offs to define those with borderline risks or different combinations of second-trimester markers also yielded high detection rates and low false-positive rates. CONCLUSION: With appropriate patient counselling, it should be possible to provide highly effective Down syndrome screening using contingent sequential protocols.

Biomarkers↗
PubMed2005

Sequential Down syndrome screening: the importance of first and second trimester test correlations when calculating risk.

Down syndrome screening can be particularly effective when both first and second trimester tests are performed. However, the counseling of women who have received sequential first and second trimester screening can be problematic. We evaluated an approximation where the post-test risk from the first trimester screening is used as the new a priori risk for the second trimester screening. The approximation disregards between-trimester test correlations. The Down syndrome detection rate based on the approximation (90.2%) would be close to that obtained when all correlations were considered (90.8%) but the false positive rate would be 26% higher (3.9% versus 3.1%, respectively). For any particular woman, the use of the approximation could result in highly inaccurate risks. We conclude that the correlations that exist between first and second trimester screening tests preclude the use of second trimester risks derived from the direct product of separate first and second trimester screening. Counseling issues in the delivery of sequential screening are discussed.

Down Syndrome↗
PubMed2005

Down syndrome screening in the first and/or second trimester: model predicted performance using meta-analysis parameters.

OBJECTIVE: To predict the screening performance for 17 policies currently in use or being considered for the near future. METHODS: Multivariate Gaussian modeling using parameters derived from published meta-analyses and new meta-analyses for gestation-specific nuchal translucency and between trimester correlations. RESULTS: For a 1% to 5% false-positive rate, first trimester screening achieved detection rates up to 16% to 25% higher than the best second trimester combination. Screening in both trimesters sequentially could yield an even greater increase in detection of 24% to 35%. The most efficient sequential policy was contingent screening, which has a high detection rate with only 15% of women needing second trimester tests. CONCLUSION: Modeling with meta-analysis derived parameters provides a reliable guide for policy and favors a contingent screening policy. The widespread practice of calculating first and second trimester risks separately should be abandoned.

Chorionic Gonadotropin↗
PubMed2005

Variation of fetal nasal bone length in second-trimester fetuses according to race and ethnicity.

OBJECTIVE: The purpose of this study was to determine the influence of race and ethnicity on the expected nasal bone length (NBL) based on biparietal diameter (BPD) measured in second-trimester fetuses. METHODS: We searched our ultrasound, obstetric, and cytogenetic databases for all second-trimester fetuses with measured NBLs. Fetuses with Down syndrome were identified and excluded from the analysis. Linear regression curves were generated for NBL by BPD according to race and ethnicity. Categories used were African American, Hispanic, Asian, and white. Analysis of variance was used to compare mean variation of observed from expected NBL by BPD according to race and ethnicity. RESULTS: There were 717 fetuses with NBL-by-BPD pairs who were available for analysis in our population, including 139 African American, 58 Hispanic, 22 Asian, and 498 white fetuses. Nasal bone length was highly correlated with BPD for each race (P < .001). Mean variances of observed from expected NBL by BPD were statistically different according to race or ethnicity (P = .0092). CONCLUSIONS: Race and ethnicity significantly affect the mean regression line of expected NBL by BPD among fetuses in the second trimester. Genetic sonographic norms, therefore, appear to require race- and ethnicity-specific formulas for NBL.

Black or African American↗
PubMed2004

Contingent screening for Down syndrome is an efficient alternative to non-disclosure sequential screening.

OBJECTIVE: To present a first and second trimester Down syndrome screening strategy, whereby second-trimester marker determination is contingent on the first-trimester results. Unlike non-disclosure sequential screening ('the Integrated test'), which requires all women to have markers in both trimesters, this allows a large proportion of the women to complete screening in the first trimester. METHODS: Two first-trimester risk cut-offs defined three types of results: positive and referred for early diagnosis; negative with screening complete; and intermediate, needing second-trimester markers. Multivariate Gaussian modelling with Monte Carlo simulation was used to estimate the false-positive rate for a fixed 85% detection rate. The false-positive rate was evaluated for various early detection rates and early test completion rates. Model parameters were taken from the SURUSS trial. RESULTS: Completion of screening in the first trimester for 75% of women resulted in a 30% early detection rate and a 55% second trimester detected rate (net 85%) with a false-positive rate only 0.1% above that achievable by the Integrated test. The screen-positive rate was 0.1% in the first trimester and 4.7% for those continuing to be tested in the second trimester. If the early detection rate were to be increased to 45% or the early completion rate were to be increased to 80%, there would be a further 0.1% increase in the false-positive rate. CONCLUSION: Contingent screening can achieve results comparable with the Integrated test but with earlier completion of screening for most women. Both strategies need to be evaluated in large-scale prospective studies particularly in relation to psychological impact and practicability.

Biomarkers↗
PubMed2002

Prenatal genetic diagnosis of Down's syndrome.

Down's syndrome is a common cause of birth defects and mental retardation. Prenatal screening and diagnosis of Down's syndrome is important to any pregnant woman interested in the health of her fetus and is of particular concern to the growing number of advanced maternal age women who are at increased risk of an affected pregnancy. Prenatal screening tests, performed in the first and second trimester, are based on maternal age, serum tests and fetal ultrasound. Definitive diagnosis requires amniocentesis or chorionic villus sampling. Hopefully, these invasive tests can, one day, be replaced with safer methods of obtaining fetal cells. Molecular genetic techniques are augmenting traditional chromosome analysis, broadening the range of identifiable genetic disorders and allowing earlier results.

Amniocentesis↗