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Biomedical subjects

A H Wu

Publications and source records attributed to A H Wu.

At least 19 recordsLinked to original sources
PubMed1999

Breast cancer and oral contraceptive use in Asian-American women.

Breast cancer incidence has historically been 4-7 times higher in the United States than in Asia. A previous study by the authors in Asian-American women demonstrated a substantial increase in breast cancer risk in women who migrated from Asia to the United States, with the risk almost doubling during the first decade after migration. Increased use of oral contraceptives soon after migration to the United States could possibly explain this rapid rise in risk. In a population-based case-control study of Chinese, Filipino, and Japanese-American women, aged 20-55 years, who lived in San Francisco-Oakland, California; Los Angeles, California; and Oahu, Hawaii during 1983-1987, 597 cases (70% of those eligible) and 966 controls (75%) were interviewed. Controls were matched to cases on age, ethnicity, and area of residence. Oral contraceptive (OC) use increased with time since migration; 15.0% of Asian-born women who had been in the West <8 years, 33.4% of Asian-born women who had been in the West > or =8 years, and 49.6% of Asian women born in the West had ever used OCs. However, duration of OC use (adjusted for age, ethnicity, study area, years since migration, education, family history of breast cancer and age at first full-term birth) was not associated with increased risk of breast cancer. Moreover, neither OC use before age 25 years nor before first full-term birth was associated with increased risk. Results were unchanged when restricted to women under age 45 years or under age 40 years. After adjustment for duration of OC use, women who had been in the United States > or =8 years were still at almost twice the risk of breast cancer compared with women who had been in the United States 2-7 years. This study suggests that OC use cannot explain the elevated risk observed in Asian women who migrated to the United States > or =7 years ago.

Adult↗
PubMed1999

Release of cardiac troponin in acute coronary syndromes: ischemia or necrosis?

Analysis of cardiac troponin T and I have been shown to be effective in detecting minor myocardial injury in cardiac patients who present with acute coronary syndromes (ACS). Determination of minor myocardial injury is significant, as these patients have a higher short-term morbidity and mortality than other unstable angina patients with normal concentrations for these markers. In this report, two theories are given as to why cardiac troponin is superior to other markers such as CK-MB for risk stratification. The 'low cut-off concentration model' is based on the fact that troponin is not increased in patients with skeletal muscle disease or injury, resulting in low baseline concentrations of the cardiac isoforms in the absence of active cardiac disease. This enables the use of low decision limits. Troponin also has a higher myocardial tissue content relative to CK-MB, thereby also increasing its clinical sensitivity to irreversible injury. In the 'reversible ischemia model', cytoplasmic free troponin T and I leak across the membrane of myocytes as the result of reduced coronary blood flow. Jeopardized myocardial tissue can recover with acute recanalization. Support for this model comes from clinical observations and animal studies.

Biomarkers↗
PubMed1999

Meta-analysis: dietary fat intake, serum estrogen levels, and the risk of breast cancer.

BACKGROUND: There is compelling evidence that estrogens influence breast cancer risk. Since the mid-1980s, dietary fat intervention studies have been conducted to investigate the effect of fat intake on endogenous estrogen levels. To further our understanding of the possible relationship between dietary fat and breast cancer, we conducted a meta-analysis of dietary fat intervention studies that investigated serum estradiol levels, and we reviewed the nature of the evidence provided by prospective analytic studies of fat consumption and breast cancer risk. METHODS: A computerized search of the English language literature on estrogen/estradiol and dietary fat intervention studies published from January 1966 through June 1998 was conducted using the MEDLINE database. Pooled estimates were derived from the change in estradiol levels associated with fat reduction from 13 studies. Analyses were conducted separately for premenopausal and postmenopausal women and in both groups combined. RESULTS AND CONCLUSIONS: Statistically significant reductions in serum estradiol levels of -7.4% (95% confidence interval [CI] = -11.7% to -2.9%) among premenopausal women and -23.0% (95% CI = -27.7% to -18.1%) among postmenopausal women were observed, with an overall -13.4% (95% CI = -16.6% to -10.1%) reduction observed. The greatest reductions occurred in two studies in which dietary fat was reduced to 10%-12% of calories compared with 18%-25% of calories in the other studies. A statistically significant reduction in estradiol levels of -6.6% (95% CI = -10.3% to -2.7%) remained after exclusion of these two studies. Review of prospective analytic epidemiologic studies that allowed for dietary measurement error suggests that the possibility that reducing fat consumption below 20% of calories will reduce breast cancer risk cannot be excluded. IMPLICATIONS: Dietary fat reduction can result in a lowering of serum estradiol levels and such dietary modification may still offer an approach to breast cancer prevention.

Adult↗
PubMed1999

Sudden death in dilated cardiomyopathy.

The purpose of this review is to examine the potential contribution of arrhythmia to the occurrence of sudden death in dilated cardiomyopathy (DCM) and to discuss current treatment options. We performed a search of the MEDLINE database from 1985 to the present and the reference citations of selected articles pertaining to the prognostic significance, management, and pathophysiology of arrhythmias in DCM. A large proportion of patients with DCM die suddenly, most secondary to ventricular arrhythmia and a smaller proportion due to bradyarrhythmia. The presence and severity of ventricular ectopy may predict risk for sudden death, but the role of electrophysiologic study and signal-averaged electrocardiography in further risk stratifying patients remains uncertain. Abnormalities of the autonomic nervous system and renin-angiotensin-aldosterone axis appear to promote the occurrence of ventricular arrhythmias. Angiotensin-converting enzyme inhibitors improve overall mortality in congestive heart failure, and the use of direct angiotensin-receptor antagonists is currently being studied. In addition, beta-receptor antagonists appear to improve morbidity and may prove to improve mortality in heart failure as well. Other interventions still under investigation include amiodarone and the implantable cardioverter-defibrillator. The underlying pathophysiology of sudden death in DCM involves primarily ventricular tachyarrhythmia. Angiotensin-converting enzyme inhibitors remain a mainstay of improving overall mortality, while further study on the roles for newer drugs and devices is ongoing.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Reflex testing I: algorithm for lipid and lipoprotein measurement in coronary heart disease risk assessment.

We reviewed the current literature in order to construct a reflex testing algorithm that maximizes clinical utility and cost-effectiveness of lipid and lipoprotein testing. The algorithm was based on the 2nd Report of the National Cholesterol Education Program Adult Treatment Panel guidelines for use of total cholesterol (TC), triglycerides (TG), HDL-C, and LDL-C, and published reports describing the clinical use of apolipoprotein B and lipoprotein (a). The success of this algorithm was tested in a low-risk general and a high-risk hyperlipidemic patient population. Lipid data and non-lipid risk factors were obtained from a national database and from patients seen at two lipid clinics. A total of 16,968 individuals from the National Health and Nutrition Examination Survey III database comprised the low-risk group, and 239 patients examined in the Hartford Hospital and Washington University Lipid Clinics comprised the high-risk group. We found a solid scientific base to support the NCEP guidelines and reasonable support for limited testing of apoB and Lp(a). According to the algorithm, the direct LDL-C assay was deemed unnecessary in 98% and 91% of low- and high-risk subjects, respectively, if one assumes that the Friedewald equation is adequate with TG < or = 4.00 g/l. With a more conservative cutoff of TG < or = 2.50 g/l, the algorithm canceled 92% and 81% of direct LDL tests, respectively. The algorithm also limited TG to 20 and 64%, apoB to 6 and 20%, and Lp(a) to 15 and 56%, of low- and high-risk groups, respectively. Use of a comprehensive, reflex algorithm for coronary heart disease risk assessment will substantially reduce the utilization of laboratory services without diminishing the clinical value of these tests. The algorithm will prevent the overuse of certain expensive tests (direct LDL) while promoting the limited use of underutilized tests [apoB and Lp(a)].

Adult↗
PubMed1999

Quantitative determination of cholesterol in lipoprotein fractions by electrophoresis.

The Helena REP cholesterol profile system (Helena Laboratories, Beaumont, TX) separates VLDL, LDL, HDL and Lp(a) by agarose gel electrophoresis, and quantitates cholesterol by enzymatic staining and densitometry. We compared results by electrophoresis to combined ultracentrifugation/precipitation (beta-quantification, BQ) for VLDL, LDL, and HDL cholesterol and to immunonephelometry for Lp(a) mass (Behring Diagnostics, Westwood, MA) in serum from 64 patients with a variety of lipid disorders. There was good agreement between methods, with a mean bias of -0.19 (-7.3), 0.09 (3.5), and 0.09 (3.4) mmol/l (mg/dl) for VLDL, HDL, and LDL cholesterol for electrophoresis vs. BQ. These differences were significant for HDL and VLDL cholesterol (P < 0.001), but not for LDL cholesterol measurement (P > 0.05). There was also good correlation between methods with coefficients of 0.83, 0.92, 0.91, and 0.97 for VLDL, HDL, Lp(a), and LDL, respectively. Our data indicate that this method can accurately and precisely measure LDL cholesterol directly in fresh serum from patients with a wide range of triglyceride values. However, HDL cholesterol measurement did not meet NCEP guidelines for precision and accuracy. Also, the poor resolution of VLDL and LDL in some specimens is a concern.

Chemical Precipitation↗
PubMed1999

Use of biochemical markers in acute coronary syndromes. IFCC Scientific Division, Committee on Standardization of Markers of Cardiac Damage. International Federation of Clinical Chemistry.

This paper presents evidence and suggestions from the IFCC Committee on "Standardization of Markers of Cardiac Damage" (C-SMCD) on the use of biochemical markers for the triage diagnosis of acute coronary syndromes. There is general agreement that both 'early' and 'definitive' biochemical markers of myocardial damage are necessary and that these assays must be available with a turnaround time of 1 h or less. Currently, myoglobin is the marker that most effectively fits the role as an 'early' marker, whereas 'definitive' markers are cardiac troponins. Since the sensitivity of the initial electrocardiogram is only 50% for detecting myocardial infarction, the use of biochemical markers may significantly contribute to the early diagnosis and become relevant when the electrocardiogram is not diagnostic. In addition, new sensitive biochemical markers, particularly the cardiac troponins, are presently the best to detect the presence of minor myocardial cell damage. With regard to this, two decision limits are probably needed for the optimal use of troponins: a low abnormal value suggesting the presence of myocardial damage and a higher value suggesting the diagnosis of myocardial infarction according to traditionally used criteria. Properly designed studies should be performed to establish limits for each commercially available troponin assay. Finally, it is recognized that there is no need for the use of any biochemical marker when the clinical diagnosis is unequivocal, other than for diagnosing reinfarction, estimating the infarct size, and monitoring thrombolytic therapy.

Acute Disease↗
PubMed1999

Homocysteine screening of a female Hispanic population.

A total of 821 women of Hispanic descent aged 21-65 years, were screened for total and high density lipoprotein (HDL) cholesterol through outpatient clinics and public screening. Of this group, 78 were invited back for further testing because they had a total cholesterol/HDL cholesterol ratio exceeding 4.5 indicative of high risk for cardiovascular disease. Written consent and a fasting blood sample was obtained from these women, and tested for serum homocysteine. The concentrations for 77 of the 78 women (mean 8. 40+/-2.24, range 4.21-13.99 micromol/l) were within the pre-established normal range for women. One subject had an exceptionally high homocysteine concentration of 137 micromol/l. This subject subsequently developed a stroke and has been institutionalized since that time. Blood from the subject and immediate family members were tested for the 5'-10'-methylenetetrahydrofolate reductase (MTHFR) polymorphism. The subject and her children were both hyperhomocysteinemic and heterozygous for the mutation. One of the children also had a low vitamin B12 concentration in blood. Although the high homocysteine and cardiovascular risk in these subjects were likely due to a dietary deficiency of the vitamins, the MTHFR mutation may have also been a contributing factor. With the availability of rapid assays, screening blood for homocysteine in subjects deemed at high risk for cardiovascular disease may be justified.

Adult↗
PubMed1999

A comparison of cardiac troponin T and cardiac troponin I in patients with acute coronary syndromes.

The majority of studies have shown that the performance of assays for cTnT and cTnI is almost identical in detecting AMI in patients with coronary artery disease. Currently cTnT may have an advantage over cTnI because available laboratory and POC platforms are standardized to a single reference material. Nevertheless, the decision to use cTnT or cTnI a given laboratory will probably be made on the basis of cost and the availability of automated instrumentation within that institution, and not necessarily on assay performance. A laboratory is unlikely to purchase an instrument to perform a single test. Because cTnI will soon be available on all commercial immunoassay analyzers, it seems likely that cTnI will become the analyte of choice.

Acute Disease↗
PubMed1999

Adulteration of urine by "Urine Luck".

BACKGROUND: In vitro adulterants are used to invalidate assays for urine drugs of abuse. The present study examined the effect of pyridinium chlorochromate (PCC) found in the product "Urine Luck". METHODS: PCC was prepared and added to positive urine controls at concentrations of 0, 10, 50, and 100 g/L. The controls were assayed for methamphetamine, benzoylecgonine (BE), codeine and morphine, tetrahydrocannabinol (THC), and phencyclidine (PCP) with the Emit II (Syva) and Abuscreen Online (Roche) immunoassays, and by gas chromatography/mass spectrometry (GC/MS). Two tests were also developed to detect PCC in urine: a spot test to detect chromate ions using 10 g/L 1,5-diphenylcarbazide as the indicator, and a GC/MS assay for pyridine. We tested 150 samples submitted for routine urinalysis, compliance, and workplace drug testing for PCC, using these assays. RESULTS: Response rates decreased at 100 g/L PCC for all Emit II drug assays and for the Abuscreen morphine and THC assays. In contrast, the Abuscreen amphetamine assay produced apparently higher results, and no effect was seen on the results for BE or PCP. The PCC did not affect the GC/MS recovery of methamphetamine, BE, PCP, or their deuterated internal standards, but decreased GC/MS recovery of the opiates at both intermediate (50 g/L) and high (100 g/L) PCC concentrations and apparent concentrations of THC and THC-d3 at all PCC concentrations. Two of 50 samples submitted for workplace drug testing under chain-of-custody conditions were positive for PCC, whereas none of the remaining 100 specimens submitted for routine urinalysis or compliance drug testing were positive. CONCLUSIONS: PCC is an effective adulterant for urine drug testing of THC and opiates. Identification of PCC use can be accomplished with use of a spot test for the oxidant.

False Negative Reactions↗
PubMed1999

National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for the use of cardiac markers in coronary artery diseases.

The Sixth Conference on the "Standards of Laboratory Practice Series", sponsored by the National Academy of Clinical Biochemistry (NACB), was held on August 4-5, 1998, at the Annual Meeting of the American Association for Clinical Chemistry, in Chicago, IL. An expert committee was assembled to write recommendations on the use of cardiac markers in coronary artery diseases. The NACB Committee prepared a preliminary draft of the guidelines, made them available on the World Wide Web (www.nacb.org), and distributed them before the presentations. The recommendations were divided into four areas: the use of markers in the triage of patients with chest pain, acute coronary syndromes, clinical applications other than acute myocardial infarction and research, and assay platforms and markers of acute myocardial infarction. The recommendations were revised and subsequently re-presented in part at the "Biomarkers in Acute Cardiac Syndromes Conference", sponsored by the Jewish Hospital Heart and Lung Institute, Louisville KY, on October 16-17, 1998. This report lists each recommendation, its scientific justification, and a summary of discussions from conference participants and reviewers. Approximately 100 individuals responded to various versions of these recommendations via direct correspondences, telephone calls to Committee members, electronic mail correspondence to the Committee Chairman, or oral questions and comments raised during one of the two conference presentations. Some of the recommendations were changed to reflect the consensus opinion. In cases in which there was no consensus, the Committee included pertinent discussion without necessarily changing the original recommendations. At times, the Committee members felt that although a particular recommendation might not be the current standard of care today, they anticipate that it likely will be adopted in the near future.

Biomarkers↗
PubMed1999

Biochemical markers of cardiac damage: from traditional enzymes to cardiac-specific proteins. IFCC Subcommittee on Standardization of Cardiac Markers (S-SCM).

Measurement of cardiac markers in blood has been the mainstay for diagnosis of acute myocardial infarction for nearly 50 years. The field has evolved from measurement of enzyme activity to mass concentrations of proteins using automated non-isotopic immunoassays. With changing clinical practices, cardiac markers are now needed to detect the presence of minor myocardial infarction in patients with unstable angina. Outcome studies have shown that patients with increased troponin are at high short-term risk for death and AMI. Recent developments involve the use of cardiac markers to select the most appropriate therapy for patients with acute coronary syndromes. The success of new cardiac markers such as troponin is due to their high cardiac specificity and the existence of assays with low detection limits. Traditional enzymes such as CK and CK-MB are thought to be released only in situations of irreversible myocardial necrosis. In the case of cardiac troponin, clinical observations and animal studies suggest that cytosolic free troponin may be released in reversible ischemia in addition to irreversible cell damage. The IFCC S-SCM has recommended use of two cut-off concentrations for cardiac troponin to differentiate normal from minor myocardial injury and AMI. A low cut-off may detect reversible ischemic events in some cases.

Biomarkers↗
PubMed1999

Proposals from IFCC Committee on Standardization of Markers of Cardiac Damage (C-SMCD): recommendations on use of biochemical markers of cardiac damage in acute coronary syndromes.

This paper presents evidence and suggestions from the IFCC C-SMCD on the use of biochemical markers for the triage diagnosis of acute coronary syndromes. There is general agreement that both 'early' and 'definitive' biochemical markers are necessary and that these assays must be available with a turnaround time of 1 h or less. Currently, myoglobin is the marker that most effectively fits the role as an 'early' marker, whereas 'definitive' markers are cardiac troponins. Since the sensitivity of the initial electrocardiogram is only 50% for detecting myocardial infarction, the use of biochemical markers may significantly contribute to the early diagnosis. New sensitive biochemical markers, particularly the cardiac troponins, are presently the best criterion to detect the presence of small myocardial cell damage. Two decision limits are probably needed for the optimum use of troponins: a low abnormal value suggesting the presence of myocardial damage and a higher value suggesting the diagnosis of myocardial infarction. Additional studies should be performed to establish limits for each commercially available assay. Finally, it is recognized that there is no need for the use of any biochemical marker when the clinical diagnosis is unequivocal, other than for diagnosing reinfarction, estimating the infarct size, and monitoring thrombolytic therapy.

Acute Disease↗
PubMed1999

Proposals from the IFCC Committee on Standardization of Markers of Cardiac Damage (C-SMCD): strategies and concepts on standardization of cardiac marker assays.

The search for sensitive and specific biochemical markers of cardiac damage has resulted in development of methods for the measurement of cardiac markers such as myoglobin, CK-MB mass and the cardiac troponins (cardiac troponin I and cardiac troponin T). There have been new clinical applications of already known markers based on improved, reformulated methods which often depend on advanced technologies. These developments are connected with analytical and interpretative challenges for the laboratory manager and for the clinician. In this situation, it is essential that international professional societies develop comprehensive and carefully elaborated guidelines for the quality management and use of these measurements and their results. Several professional associations have formed committees working on different issues regarding the measurement of biochemical markers of cardiac damage. Recognizing the huge interest in this field and substantial diagnostic relevance of these markers, the IFCC has established the Committee on "Standardization of Markers of Cardiac Damage" (C-SMCD) in 1997 inviting the already operating American and European groups to designate some of their members into the new committee. The task of the IFCC C-SMCD is to coordinate the different activities of the national groups, with preparation of international documents and recommendations under the auspices of IFCC and to initiate various standardization activities. The establishment of consensus/reference methods as well as development of primary and secondary matrix reference materials for markers of cardiac damage are extremely important in order to achieve comparability of test results, thus leading to an effective patient care.

Biomarkers↗
PubMed1999

Applications of forensic identity testing in the clinical laboratory.

DNA analysis is becoming routine in the clinical laboratory for the diagnosis of human diseases using various tissue sources. Most clinical specimens are followed by tracking forms that include patient demographic data, accession number, and date and time of collection. As part of a thorough quality assurance program, proper documentation of test requisitions and tracking forms is mandatory. Despite these efforts, specimen mislabeling or other mix-ups can, and do, occur. We demonstrate the utility of the PM + DQA1 typing kit and STR analysis using the Visible Genetics automated DNA sequencing system in the proper identification of such clinical specimens as urine, blood, and paraffin-embedded tissues. In each case, sufficient DNA was extracted from these specimen types using a nonorganic extraction protocol for typing purposes. We conclude that DNA typing methods are feasible for distinguishing clinical laboratory specimens of questionable identity and compliment existing quality assurance techniques.

Blotting, Southern↗
PubMed1999

Minimal standards for the performance and interpretation of toxicology tests in legal proceedings.

There have been several high profile criminal and civil cases that have been litigated in recent years involving toxicologic analyses and interpretations of blood, urine, and other specimens for drugs of abuse. Disputes have erupted between prominent toxicologists and laboratory scientists as to the validity and interpretation of the data presented. The disputes centered around the fact that the procedures used in these cases had not been properly validated with analytical noise being misinterpreted as a positive result. As with any analyses, forensic tests must be conducted in a manner such that they meet the minimum standards accepted within the toxicology community. No conclusions as to presence or absence of drug, its concentration, or its physiologic effects can be made if there is a failure to meet these basic standards. Several cases are presented where these standard tenets may not have been followed.

Blood Stains↗
PubMed1999

Standardization of creatine kinase-MB (CK-MB) mass assays: the use of recombinant CK-MB as a reference material.

BACKGROUND: The AACC assembled a committee to identify and validate a standard creatine kinase MB isoenzyme (CK-MB) material to improve the comparability of CK-MB mass assays. METHODS: Three protocols were used. In protocol I, various CK-MB materials prepared in different matrices were screened as candidate standards. In protocol II, participating manufacturers calibrated their systems with concentrates of human heart CK-MB and then tested 20 patient samples to evaluate calibration bias. In protocol III, participating manufacturers calibrated their immunoassay systems using recombinant CK-MB2 (rCK-MB2) diluted into their respective sample diluents and measured 50 samples. RESULTS: Candidate materials showed high recovery in stripped human serum, but bias improved only from 59% to 38%. These data led to the use of human heart CK-MB diluted in each manufacturer's sample diluent. This strategy reduced bias from 31% to 15%. Because human heart CK-MB is difficult to provide, a lyophilized source of CK-MB2 was identified. rCK-MB2 was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, reversed-phase HPLC, intrinsic protein fluorescence, circular dichroism, agarose gel electrophoresis, immunoreactivity studies, high and low temperature stability, and reconstituted stability to be equivalent to human heart CK-MB. Calibration of immunoassay systems with rCK-MB2 added into each respective manufacturer's sample diluent showed a 13% between-manufacturer bias. CONCLUSION: Lyophilized rCK-MB2 was determined suitable for use as a reference material for CK-MB mass assays.

Calibration↗