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Why women say yes to prenatal diagnosis.

Despite considerable concern of bioethicists, disabilities rights activists, feminists and others about the spread of prenatal diagnostic technologies, their routine acceptance in many parts of the world continues at a rapid pace. Yet, there is wide variation by country and region in rates of acceptance of prenatal diagnosis. We draw on John McKinlay's model of how a medical innovation becomes routinized to explore the circumstances that led to the widespread use of one prenatal diagnostic screen-the maternal serum alpha fetoprotein (MSAFP) test for the detection of neural tube defects and other developmental disabilities. As predicted by McKinlay's model, analysis of published data suggests that strong institutional or provider support is the best predictor of women's level of MSAFP test acceptance. Data collected at a health maintenance organization in California illuminate the processes through which medico-legal and institutional forces affect the use of MSAFP screening. By examining the language women use to talk about MSAFP screening, we show how providers also shape women's understandings of the meaning and purpose of MSAFP screening. These data ultimately shed light on how the very ethical issues which concern critics of prenatal diagnosis become obscured in the processes by which this screening test becomes accepted as routine.

Adult↗

FBL blood test as a predictive marker of breast cancer in high risk women.

The potential use of the ferritin bearing lymphocytes (FBL) blood test which enumerates oncofetal FBL as a biomarker for early breast cancer was explored. Analysis of the FBL positive test results carried out on high risk women who underwent biopsy in 1983-84 was found to be a significant predictor for early breast cancer (relative risk (RR) = 2.9, 95% confidence interval (CI) 1.4-5.8). A group of 635 women from the above study diagnosed in 1983-84 as having no evidence of breast cancer was further traced 8 years later with the aid of the National Cancer Registry. We identified 35 malignancies, including 19 cases of breast cancer. The RR of breast cancer for the FBL positive group was 2.51; 95% CI = 1.04-6.07 while for the other malignancies it was 0.93, 95% CI = 0.30-2.84. All the breast cancer cases in the FBL positive group were of the infiltrative duct carcinoma category and 71% were in early stage. In contrast, in the FBL negative group, 60% of the cases were infiltrative ductal carcinoma and most of them were at stage III. Positive FBL is associated with early manifestation of breast cancer and may be considered as a tool for the screening of breast cancer in high risk women.

Adolescent↗

Establishing biomarkers of oxidative stress: the measurement of hydrogen peroxide in human urine.

Hydrogen peroxide (H(2)O(2)) can be detected in freshly-voided human urine from healthy subjects and has been proposed as a "biomarker" of oxidative stress. This paper summarizes our studies to examine the extent to which urinary H(2)O(2) measurement fulfils the criteria for the "ideal biomarker". Levels of H(2)O(2), standardised for creatinine, varied widely between subjects. In most subjects, levels also varied considerably when measurements were made at different times and on different days. A reproducible increase in urinary H(2)O(2) was detected in all subjects examined after drinking coffee, a beverage rich in H(2)O(2). By contrast, green tea decreased urinary H(2)O(2) levels. We conclude that the H(2)O(2) in coffee is not excreted into urine. Instead, hydroxyhydroquinone from coffee is absorbed, excreted and oxidises in urine to produce H(2)O(2). No other confounders of urinary H(2)O(2) have been identified to date. Work is underway to compare H(2)O(2) levels with variations in other biomarkers of oxidative damage, to test the possibility that there are daily or other periodic variations in oxidative damage rates.

Adult↗

Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway activity in patients with chronic fatigue syndrome.

The elevated RNase L enzyme activity observed in some Chronic Fatigue Syndrome (CFS) patients may be linked to the low exercise tolerance and functional impairment that typify this disease. The purpose of this investigation was to determine if specific indicators of physical performance can predict abnormal RNase L activity in CFS patients. Seventy-three CFS patients performed a graded exercise test to voluntary exhaustion. Forty-six patients had elevated RNase L levels. This measure was employed as the dependent variable in a discriminant function analysis, with peak V02, exercise duration and Karnofsky Performance Scores (KPS) serving as the independent variables. All three variables entered the single significant function (p < 0.001). The elevated RNase L group had a lower peak V02 and duration than the normal group, but a higher KPS. The results suggest that both exercise testing and the RNase L biomarker have potential to aid in the diagnosis of CFS.

2',5'-Oligoadenylate Synthetase↗

Advances in periodontal disease markers.

A computer-assisted medline search was conducted to find the relevant articles concerning the periodontal disease markers in gingival crevicular fluid (GCF) and saliva published during the 10-year period from 1993 to July 2003. This review suggests that certain diagnostic uses of saliva and GCF show promise. Although both fluids have been used to evaluate the risk for an individual to develop periodontal disease and to monitor of the host response to periodontal therapy, GCF has the chance of being closely approximated to the periodontal tissues where periodontal disease begins. The enzymes contributed to extracellular matrix (ECM) molecules and non-ECM molecules degradation and markers for polymorphonuclear leukocytes (PMN) activity and influx into the gingival tissue seem to provide valuable information regarding the periodontal disease diagnosis and prognosis. There is also an increasing evidence implicating reactive oxygen species and nitric oxide pathway in the pathogenesis of periodontal diseases. Although promising results have been achieved with the assays evaluating the markers in assessment of periodontal disease status, up to now, none of these tests are used routinely. Further, one commercially available genetic test has been reported to have the potential to be used to predict the periodontal disease, but there are controversial reports on this genetic susceptibility test.

Biomarkers↗

Genotoxicity in native fish associated with agricultural runoff events.

The primary objective of the present study was to test whether agricultural chemical runoff was associated with in-stream genotoxicity in native fish. Using Sacramento sucker (Catostomus occidentalis), we combined field-caging experiments in an agriculturally dominated watershed with controlled laboratory exposures to field-collected water samples, and we coupled genotoxicity biomarker measurements in fish with bacterial mutagenicity analysis of water samples. We selected DNA strand breakage as a genotoxicity biomarker and Ames Salmonella mutagenicity tests as a second, supporting indicator of genotoxicity. Data from experiments conducted during rainfall runoff events following winter application of pesticides in 2000 and 2001 indicated that DNA strand breaks were significantly elevated in fish exposed to San Joaquin River (CA, USA) water (38.8, 28.4, and 53.6% DNA strand breakage in year 2000 field, year 2000 lab, and year 2001 field exposures, respectively) compared with a nearby reference site (15.4, 8.7, and 12.6% DNA strand breakage in year 2000 field, year 2000 lab, and year 2001 field exposures, respectively). Time-course measurements in field experiments supported a linkage between induction of DNA strand breakage and the timing of agricultural runoff. San Joaquin River water also caused significant reversion mutation in two Ames Salmonella tester strains. Salmonella mutagenicity corroborated in-stream effects, further strengthening a causal relationship between runoff events and genotoxicity. Potentially responsible agents are discussed in the context of timing of runoff events in the field, concordance between laboratory and field exposures, pesticide application patterns in the drainage, and analytical chemistry data.

Agriculture↗

[Evaluation of analytic test methods. Stomach-intestines status is the best diagnostic method in suspected vitamin B12 deficiency].

In the great majority of cases vitamin B12 deficiency is caused by chronic atrophic gastritis. This study has compared several different tests for the identification of patients for whom substitution therapy is needed or warranted. It is concluded that serum tests reflecting the state of the gastric body mucosa (serum pepsinogen A combined with serum gastrin or serum pepsinogen C) appear to be the logical first step in the workup of these patients in terms of high sensitivity and superior specificity as compared with other tests.

Biomarkers↗

Determination of biomarkers for intermediate end points in chemoprevention trials.

Renewed interest is being directed toward chemoprevention as a means of reducing cancer mortality. To overcome the inherent problems associated with using cancer development as a study end point, there has recently been a great surge of interest in defining the biomarkers associated with specific stages of the carcinogenic process as intermediate end points. We have detailed the evidence supporting the concept of field cancerization, a concept of general importance that is probably applicable to carcinogenesis and chemoprevention at many organ sites in humans, and presented results of tests of the potentially useful biomarkers proliferating cell nuclear antigen and blood group antigen. Because microassay techniques are more readily applicable to small biopsy samples, further expansion of these studies and exploration of panels of additional biomarkers are expected to generate exciting results in the field of chemoprevention.

ABO Blood-Group System↗

Prediction of breast cancer using volatile biomarkers in the breath.

We evaluated a breath test for volatile organic compounds (VOCs) as a predictor of breast cancer. Breath VOCs were assayed in 51 asymptomatic women with abnormal mammograms and biopsy-proven breast cancer, and 42 age-matched healthy women. A fuzzy logic model predicted breast cancer with accuracy superior to previously reported findings. Following random assignment to a training set (64) or a prediction set (29), a model was constructed in the training set employing five breath VOCs that predicted breast cancer in the prediction set with 93.8% sensitivity and 84.6% specificity. The same model predicted no breast cancer in 16/50 (32.0%) women with abnormal mammograms and no cancer on biopsy. A two-minute breath test could potentially provide a safe, accurate and painless screening test for breast cancer, but prospective validation studies are required.

Age Factors↗

[Coronary biomarkers and long-term clinical outcome in acute coronary syndrome without ST segment elevation].

BACKGROUND: The use of new biomarkers improved risk stratification for patients with acute coronary syndromes (ACS). AIM: To evaluate the relationship between multiple biomarkers and long-term clinical outcome in ACS without ST segment elevation. PATIENTS AND METHODS: Consecutive patients presenting with suspected ACS were studied. On admission to the emergency room, serum was obtained to determine highly sensitive C reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), lipoprotein (a) (LPa) and soluble P selectin (sPS). Clinical endpoints were mortality and a composite endpoint of major adverse cardiovascular events (MACE) including death, re-infarction, and angina. RESULTS: Seventy patients, aged 63+/-13 years, 54 males, were studied. Final diagnosis was unstable angina in 71% and non-ST-segment elevation myocardial infarction in 29%. MACE and mortality rate were 17% and 5.8%, respectively. We found higher plasma levels of hsCRP, ESR and Lp(a) in patients with MACE (p=0.032, p=0.015 and p=0.010, respectively). Plasma levels of hsCRP and ESR were also higher in patients who died during the follow up (p=0.002 y p=0.045, respectively). CONCLUSION: Plasma levels of inflammatory markers and atherosclerosis biomarkers are associated with a worse long-term clinical outcome in ACS without ST segment elevation. The inclusion of these biomarkers in the routine blood test on admission, could improve risk stratification of patients with ACS in the future.

Acute Disease↗

Screening for high-risk and elevated alcohol consumption in day and shift workers by use of the AUDIT and CDT.

BACKGROUND: Alcohol consumption levels and drinking patterns have been reported to vary between day and shift workers, although the results have been conflicting. Previous results indicate that questions about alcohol habits may be asked in the workplace. However, no studies have evaluated the Alcohol Use Disorders Identification Test (AUDIT) or the alcohol biomarker carbohydrate-deficient transferrin (CDT) in serum for this purpose. AIM: To investigate, in conjunction with routine health examinations, whether there is any difference between permanent day and shift workers in high-risk alcohol consumption, according to the AUDIT and CDT. Gamma-glutamyl transferase (GGT) in serum was included mainly as a comparison test. METHODS: The employees who attended for a regular health examination during the study period were offered voluntary alcohol screening with the AUDIT and CDT. RESULTS: Altogether, 990 employees (day, two-shift, and three-shift workers) participated in the study, 194 (20%) of whom screened positive with the AUDIT and/or CDT. There were no significant differences in the screening results between day and shift workers, whereas significantly fewer of the two-shift workers (odds ratio=0.5, 95% confidence interval=0.3-0.9) screened positive with CDT. CONCLUSIONS: The present findings on employees who attended for regular health examinations suggest that shift workers did not show a higher level of risky alcohol consumption than day workers, according to the results with the AUDIT, CDT and GGT. On the contrary, the two-shift workers appeared to drink significantly less.

Adult↗

The Internet Tracking Registry of Acute Coronary Syndromes (i*trACS): a multicenter registry of patients with suspicion of acute coronary syndromes reported using the standardized reporting guidelines for emergency department chest pain studies.

STUDY OBJECTIVE: Observational studies of well-described patient populations presenting to emergency departments (EDs) with suspicion of acute coronary syndrome are necessary to understand the relationships between patients' signs and symptoms, cardiac risk profile, test results, practice patterns, and outcomes. We describe the methods for data collection and the ED population enrolled in a multicenter registry of patients with chest pain. METHODS: Patients older than 18 years, presenting to one of 8 EDs in the United States or 1 ED in Singapore, and with possible acute coronary syndrome were enrolled in the Internet Tracking Registry of Acute Coronary Syndromes between June 1999 and August 2001. Prospective data, including presenting signs and symptoms, ECG findings, and the ED physician's initial impression of risk, were systematically collected. Medical record review or daily follow-up was used to obtain cardiac biomarker results, invasive and noninvasive testing, treatments, procedures, and inhospital outcomes. Thirty-day outcomes were determined by telephone follow-up and medical record review. RESULTS: The registry includes 15,608 patients, with 17,713 visits. Chest pain was the chief complaint in 71% of visits. The ECG was diagnostic of ischemia or infarction in 10.1% and positive cardiac biomarkers were observed in 10% of visits. Forty-three percent of patients were sent home directly from the ED. Of admitted patients, 5% died by 30 days, and 3% had documented coronary artery disease or had undergone percutaneous coronary intervention or coronary artery bypass grafting within 30 days. For patients discharged directly from the ED, 0.4% died or had a documented myocardial infarction within 30 days. Coronary artery bypass graft surgery, percutaneous coronary intervention, or a diagnosis of coronary artery disease was found in 0.5% of discharged patients. CONCLUSION: A unique description of undifferentiated ED chest pain patients with suspected acute coronary syndrome is provided. The data set can be used to generate and explore hypotheses to improve understanding of the complex relationships between presentation, treatment, testing, intervention and outcomes.

Biomarkers↗