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Biomedical subjects

J E O'Brien

Publications and source records attributed to J E O'Brien.

71 records · Page 4Linked to original sources

Logistic regression generated probability estimates for trisomy 21 outcomes from serum alpha fetoprotein and beta human chorionic gonadotrophin: simplification with increased specificity.

Traditional Gaussian approaches to biochemical screening make calculations very cumbersome. We have sought to develop a logistic regression mathematical model for the calculation of risk for trisomy 21 in multiple marker screening that would be more "user friendly." Biochemical screening data from 15,444 patients with confirmed normal outcomes and 28 with trisomy 21 were analyzed by logistic regression analysis (LRA) to produce a direct mathematical approach to risk calculation that combines the improvements in sensitivity and specificity already demonstrated by us with extreme value cumulative function surface fittings, but which can be extended for other exploratory variables. LRA yields a 71.4% sensitivity with a 95% specificity which is comparable to our previously published discriminant aneuploidy detection (DADs) approach; both are an improvement over the commonly used Gaussian approach of risk assessment. In our study population, LRA performed as well as DADs; both performed better than the Gaussian method, and LRA is a simpler approach.

Aneuploidy↗

Maternal thyroid function does not alter maternal serum alpha-fetoprotein interpretation.

OBJECTIVE: Endocrine alterations of metabolism such as diabetes and obesity are known to affect maternal serum alpha-fetoprotein interpretation. Thyroid function has been questioned, e.g., because of binding globulins, but not adequately studied as to its impact upon maternal serum alpha-fetoprotein. The purpose of this study was to assess the possible effects of T4 and thyroid-stimulating hormone (TSH) on alpha-fetoprotein production, and to determine if thyroid function (hypothyroidism) alters maternal serum alpha-fetoprotein. METHODS: We evaluated maternal serum alpha-fetoprotein, T4, and TSH records of 25,551 patients, between 14 and 20 weeks' gestation, on whom both studies had been ordered by the patient's primary obstetrician to rule out maternal thyroid disease in pregnancy. Statistical analyses were performed by chi 2 and regression analysis. RESULTS: Patients were stratified according to thyroid function tests into two groups: hypothyroidism (T4 < 6.5 micrograms/dL and/or TSH > 5.0 micrograms/mL), and normal or hyperthyroidism (T4 > or = 6.5 micrograms/dL and/or TSH > or = 5.0 microU/mL). Maternal serum alpha-fetoprotein values were compared among groups for each gestational age. No significant variation or correlation of maternal serum alpha-fetoprotein and thyroid function was observed. CONCLUSIONS: Although other endocrine abnormalities are known to impact maternal serum alpha-fetoprotein values either through decreased production, decreased placental permeability, or plasma volume distribution alterations, maternal thyroid status does not interfere with proper interpretation of maternal serum alpha-fetoprotein.

Female↗

Simple preparation of the major urinary metabolites of flunitrazepam and nitrazepam.

An alarming increase in the misuse/abuse of nitrobenzodiazepine derivatives, especially flunitrazepam, prompted us to establish reliable analytical protocols for their routine detection. Whilst the parent drugs are readily available from a number of commercial sources, it was found difficult to obtain samples of the corresponding amino metabolites which were required as analytical standards. This lead us to develop the straightforward synthetic protocol described here, to convert the readily available parent drugs, namely flunitrazepam and nitrazepam, to their respective 7-amino derivatives. The method requires minimum laboratory facilities. It involves the reduction of the nitro functionality in the parent drug to an amino group using tin (II) chloride under mild conditions, using ultrasonication at room temperature. The method is simple and should give toxicology laboratories better access to these much needed compounds.

Anti-Anxiety Agents↗

Maternal weight differences do not explain ethnic differences in biochemical screening.

In previous work, we and others have shown that serum levels of alpha-fetoprotein, human chorionic gonadotropin, and estriol vary among the four commonly defined racial/ethnic groups seen in the United States: white, African-American, Asian, and Hispanic. We have suggested that better sensitivity and specificity could improve screening sensitivity and specificity. However, it has been argued that systematic weight differences among the groups could explain the variation. We evaluated the results from 208,257 patients having screening and found systematic weight differences. However, these differences were not as large as the racial/ethnic differences, showing that weight does not fully explain the discrepancy, and, therefore, four separate data bases give more accurate results.

Asian↗

Variability of adjustments to indices in determining patient risk in biochemical screening.

It has long been appreciated that the measurement of biochemical parameters for prenatal screening for neural tube defects, and later aneuploidy, is not as simple as measuring hemoglobin or hematocrit. Early in the game, it was recognized that there are gestational age curves, and that since alpha-fetoprotein (AFP), for example, is a fetal product, its distribution varies as a function of maternal plasma volume, and therefore the weight of the mother. A number of different adjustment factors have been used for AFP and other parameters for years, with varying degrees of consistency and reliability. Here we review a number of adjustments that have been used, and try to give priority to those that have been most effective. Furthermore, laboratories and programs need to be cognizant that with newer parameters being added, the specifics of requirements will vary on a case-by-case parameter basis, and optimal screening can only be achieved with the appropriate adjustments.

Biomarkers↗

Distribution of neural tube defects as a function of maternal weight: no apparent correlation.

OBJECTIVES: Maternal nutritional deficiency is an important predisposing factor to congenital neural tube defects (NTDs). It was hypothesized that obese women may have an increased risk for NTDs. The aim of the present study was to address this question in a large cohort. METHODS: A total of 72,915 consecutive cases of biochemical screening that had documented maternal weights and pregnancy outcomes were identified from the Quest Diagnostic Laboratories database. Patients were divided into five ranges of maternal weights, and the incidence of NTDs was calculated for each group. Based on the different definitions of maternal overweight, the data were also analyzed based on 2 groups only, obese and nonobese, using three cutoff points. RESULTS: Seventy-nine pregnancies were complicated by NTDs (incidence of 1.08 per 1,000 pregnancies). Differences between maternal weights ranges were not found to be statistically significant (chi2 = 5.997, p = 0.19, power = 0.99). Differences between obese and nonobese mothers were not found to be statistically significant for all three analyses as well. CONCLUSIONS: Our present results do not support an association between maternal obesity and NTDs.

Body Weight↗

Similarity of twins to singleton maternal serum alpha-fetoprotein ratio by race: no need to establish specific multifetal tables.

The purpose of this study was to assess the need for race-specific maternal serum alpha-fetoprotein (MSAFP) curves in twin gestations. MSAFP values were evaluated in 535 samples obtained from twin gestations. Results were grouped according to gestational age (from 15 to 20 weeks), as with our singletons. Separate median curves were determined for black and for white pregnancies. On average, the median serum alpha-fetoprotein (AFP) for twins was about twice (2.1 +/- 0.3) the median of singletons. MSAFP in blacks was commonly higher than in white pregnancies of comparable gestational age. Using a 4.5 multiple of the singleton median cutoff in twin white pregnancies, 3.9% of the results were defined as 'high', similar to the rate observed in singleton pregnancies. 'Low' results in twins were defined as AFP values lower than 1.0 multiples of the singleton median (in pregnancies of similar gestational age and race). About 7% of the serum samples for whites were defined as 'low' by this criteria. Data for blacks were comparable. Race-dependent median values should be used for MSAFP interpretation in twin as well as singleton pregnancies. 'High' and 'low' percentages are comparable to our large data bank of singleton pregnancies and seem to be adequate for interpretation of serum AFP in twins. Therefore, the race-specific singleton multiples are sufficient, obviating the need to build specific median curves for multifetal gestations.

Black People↗

Maternal serum alpha-fetoprotein screening: the need to use race/ethnic specific medians in Asians.

OBJECTIVES: We questioned whether race-specific databases for maternal serum alpha-fetoprotein (MSAFP) screening should be added to those already available for African-American and white patients. STUDY DESIGN: We analyzed 138,272 MSAFP samples. The geographic origin of the samples was New York metropolitan area. Patients were classified as white, African-American, Hispanic or Asian. The usual adjustments were made and groups compared. Statistical analysis included ANOVA and multiple comparison test. RESULTS: MSAFP values are highest (p < 0.05) for Asians, followed by African-Americans, Hispanics, and whites, although the difference between Hispanic and white was not significant. CONCLUSIONS: Four separate databases are definable if specimen quantity is sufficient. Race/ethnic specific databases are more likely to yield the most accurate detection of abnormal MSAFP values, and therefore, fetal anomalies.

Asian↗

Multiple marker screening in multifetal gestations: failure to predict adverse pregnancy outcomes.

The objective of the study was to assess whether the association known in singleton pregnancies of high maternal serum alpha-fetoprotein (AFP) or human chorionic gonadotropin (HCG) with adverse outcomes applies also to multifetal gestations. Maternal serum AFP and HCG were evaluated in 207 multifetal pregnancies. High values were defined as a maternal serum AFP of > 4.5 and a HCG of > 4.0 multiples of the median (MoM), with appropriate adjustments. Results were correlated with premature delivery, stillbirths, or pregnancy termination for fetal anomalies. There were 10 stillbirths, 7 terminations of pregnancy for fetal anomalies, and 66 premature deliveries in the study group. Maternal serum AFP was somewhat higher in abnormal pregnancies than in those with normal outcome (3.4 vs. 2.5 MoM, respectively, NS). A high AFP level was found in 6% of pregnancies with adverse outcomes and in 4% of uncomplicated gestations (NS). High HCG values, also observed in 5% of cases, were all associated with normal outcome. Multiple marker screening suggested an increased risk for aneuploidy in 9% of patients, all of whom were euploid on amniocentesis karyotypes. Maternal serum screening in multiple gestations is confounded by the differing contributions of fetuses, and abnormal results cannot reliably predict adverse pregnancy outcomes.

Adolescent↗

Congenital glaucoma and skeletal dysplasia.

We have observed congenital glaucoma in a patient with a skeletal dysplasia closely resembling Kniest syndrome. The clinical and radiographic features, along with the differential diagnosis of Kniest syndrome, are discussed. Review of the literature suggests a relationship between the pathophysiology of bone dysplasia and congenital glaucoma. Congenital glaucoma may be an additional ocular finding in Kniest syndrome.

Abnormalities, Multiple↗

Prevalence of back pain among radiation therapists.

Low back pain among radiation therapists appears to be positively associated with age, time working as a radiation therapist and a number of other factors including level of fitness and perceived stress levels. These are the authors' findings from a pilot survey they conducted of radiation therapists employed in eight radiation oncology departments.

Adult↗

Similarity of insulin-dependent diabetics' and non-insulin-dependent diabetics' levels of beta-hCG and unconjugated estriol with controls: no need to adjust as with alpha-fetoprotein.

OBJECTIVE: To determine if the same systematic alteration of serum values seen for alpha-fetoprotein (AFP) in diabetic patients is also seen for beta-hCG and unconjugated estriol (uE3). METHODS: Serum AFP, beta-hCG, and uE3 results were obtained in 18,639 patients for whom complete follow-up information was obtained. Patients were divided into euglycemic (n = 18,088), insulin-requiring diabetics (n = 104), and non-insulin-requiring diabetics (n = 437), as well as by race. RESULTS: The 20% adjustment used for AFP appropriately corrects serum values. No such systematic variation is seen for either beta-hCG or uE3 by glycemic status or race. CONCLUSION: No adjustment for beta-hCG or uE3 is necessary for diabetes for biochemical screening programs.

Black or African American↗