Use of blood biomarkers to screen for obstructive sleep apnea.

Purpose: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased risk for cardiovascular disease, diabetes, and other chronic conditions. Unfortunately, up to 90% of individuals with OSA remain without a diagnosis or therapy. We assess the relationship between OSA and blood biomarkers, and test the hypothesis that combinations of markers provide a characteristic OSA signature with diagnostic screening value.

Comparison of Digital Rectal Examination and Serum Prostate Specific Antigen in the Early Detection of Prostate Cancer: Results of a Multicenter Clinical Trial of 6,630 Men.

To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 μg./l.

Blood biomarkers of endocrine, immune, inflammatory, and metabolic systems in obstructive sleep apnea.

Objective/background: Obstructive sleep apnea (OSA) is a common disorder, affecting over 100 million adults. Untreated OSA leads to serious health consequences and perturbations in endocrine, immune, inflammatory, and metabolic systems. Study objectives are to evaluate the association between OSA and biomarkers, and to test the hypothesis that a combination of markers may be useful in screening for OSA.

Absolute and relative changes (delta) in troponin I for early diagnosis of myocardial infarction: Results of a prospective multicenter trial.

Objectives: We investigated absolute and relative cardiac troponin I (TnI) delta changes, optimal sampling protocols, and decision thresholds for early diagnosis of myocardial infarction (MI). Serial cardiac biomarker values demonstrating a rise and/or fall define MI diagnosis; however the magnitude of change, timing, and diagnostic accuracy of absolute versus relative (percentage) deltas remains unsettled.

Methods: We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent symptoms of acute coronary syndrome at 14 medical centers.

Diagnostic performance of cardiac Troponin I for early rule-in and rule-out of acute myocardial infarction: Results of a prospective multicenter trial.

Objectives: To compare emergency department TnI serial sampling intervals, determine optimal diagnostic thresholds, and report representative diagnostic performance characteristics for early rule-in and rule-out of MI.

Methods: We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent ischemic symptoms suggestive of acute coronary syndromes at 14 medical centers. Diagnosis was adjudicated by an independent central committee.

Prospective evaluation of pregnancy-associated plasma protein-a and outcomes in patients with acute coronary syndromes.

Objectives: This study sought to investigate whether pregnancy-associated plasma protein-A (PAPP-A) is useful for risk assessment in non-ST-segment elevation acute coronary syndrome (NSTE-ACS).

Background: PAPP-A is a high molecular weight, zinc-binding metalloproteinase that is associated with vulnerable plaque and may be a predictor of cardiovascular disease and mortality.

Methods: We measured PAPP-A at baseline in 3,782 patients with non NSTE-ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) trial and followed for an average of 1 year.

Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation.

Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study.

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant recipients despite the introduction of posttransplantation viral monitoring and preemptive antiviral therapy. We evaluated the use of HLA class I tetramers in monitoring CMV-specific T-cell recovery to predict patients at risk for CMV-related complications. This prospective multicenter clinical trial obtained nearly 1400 tetramer/allele results in more than 800 biweekly blood samples from 83 patients monitored for 1 year after transplantation.

Analytical performance of a standardized single-platform MHC tetramer assay for the identification and enumeration of CMV-specific CD8+ T lymphocytes.

Major histocompatibility complex (MHC) multimers that identify antigen-specific T cells, coupled with flow cytometry, have made a major impact on immunological research. HLA Class I multimers detect T cells directed against viral, tumor, and transplantation antigens with exquisite sensitivity. This technique has become an important standard for the quantification of a T cell immune response.

Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging.

Objectives: Various methods have been proposed to increase the specificity of prostate-specific antigen (PSA), including age-specific PSA reference ranges, PSA density (PSAD), and percent free PSA (%fPSA). In this multicenter study, we compared these methods for their utility in cancer detection and their ability to predict pathologic stage after radical prostatectomy in patients with clinically localized, Stage T1c cancer.

Methods: Seven hundred seventy-three men (379 with prostate cancer, 394 with benign prostatic disease), 50 to 75 years old, from seven medical centers were enrolled in this prospective blinded study.

Percentage of free PSA in black versus white men for detection and staging of prostate cancer: a prospective multicenter clinical trial.

Objectives: In predominately white populations, measurement of the percentage of free prostate-specific antigen (%fPSA) has been shown to enhance the specificity of total PSA testing for prostate cancer while maintaining high sensitivity and to aid in prostate cancer staging. This study evaluated whether the %fPSA cutoff that maintained a 95% sensitivity in a white population yielded the same sensitivity and specificity in a black population and whether %fPSA was useful in predicting postoperative pathologic features in blacks.

Methods: We evaluated 647 white and 79 black men, prospectively enrolled at prostate cancer screening and surgical referral centers.

Prediction of post-radical prostatectomy pathological outcome for stage T1c prostate cancer with percent free prostate specific antigen: a prospective multicenter clinical trial.

Purpose: Prostate specific antigen (PSA) exists in bound (complexed) and unbound (free) forms in serum. The percentage of free PSA enhances the specificity of PSA testing for prostate cancer detection. We evaluated the use of percent free PSA preoperatively to predict pathological stage.

Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial.

Context: The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use.

Objective: To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied.

Design: Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif).

Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer.

Purpose: We reviewed the use of percent free prostate specific antigen (PSA) to enhance specificity of PSA testing and aid in the discrimination of benign and malignant prostate disease. We present proposed percent free PSA cut points and probability factors, and discuss factors that are believed to affect study outcomes and conclusions.

Materials And Methods: We reviewed the literature with respect to PSA and free PSA with particular emphasis on clinical use of percent free PSA and factors that may affect study outcomes.

Analytical performance of the Tandem-R free PSA immunoassay measuring free prostate-specific antigen.

The analytical performance of the Tandem-R free PSA assay available from Hybritech Inc. was evaluated. Comparison of recoveries of purified free (unbound) prostate-specific antigen (PSA) diluted in female serum in the Tandem-R free PSA assay and the Tandem-R (total) PSA assay demonstrated a link in calibration between the assays and an accurate determination of percent free PSA.

Analysis of percent free prostate-specific antigen (PSA) for prostate cancer detection: influence of total PSA, prostate volume, and age.

Objectives: To determine whether the use of the free-to-total PSA ratio (percent free PSA) could increase the specificity of PSA testing for prostate cancer detection in men with serum PSA concentrations between 4.0 and 10.0 ng/mL, and to assess the influence of total PSA, prostate volume, and age on percent free PSA.

Assessment of amyloid beta protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer's disease.

The principal constituent of amyloid plaques found in the brains of individuals with Alzheimer's disease (AD) is a 39-42-amino-acid protein, amyloid beta protein (A beta). This study examined whether the measurement of A beta levels in CSF has diagnostic value. There were 108 subjects enrolled in this prospective study: AD (n = 39), non-AD controls (dementing diseases/syndromes; n = 20), and other (n = 49).

A long-wavelength biolabeling reagent based on the oxonol fluorophore.

A red fluorescent dye of the oxonol class, bis-[1-(carboxymethyl)barbituric acid-(5)]-pentamethinoxonol, has been synthesized and, in the form of the succinimidyl active ester, has been applied to antibody labeling for application to flow cytometry and to imaging of tissue sections. The new dye, named CMOX (for carboxymethyloxonol), shows maximum excitation at 583 nm and emission at 611 nm, with a quantum yield of 0.2 in aqueous buffer and methanol.

Tau protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer's disease.

Neurofibrillary tangles and dystrophic neurites are characteristic pathological features found in the brains of Alzheimer's disease (AD) patients. A major constituent of these lesions is the cytoskeletal protein tau. This study examined whether the measurement of tau in cerebral spinal fluid (CSF) has value in the diagnosis of AD.

Selection of optimal prostate specific antigen cutoffs for early detection of prostate cancer: receiver operating characteristic curves.

A prospective clinical trial of prostate cancer screening was conducted at 6 university centers including 6,630 men 50 years old or older who underwent a serum prostate specific antigen (PSA) determination and digital rectal examination. Biopsies were performed if the PSA level was greater than 4.0 ng.

Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: receiver operating characteristic curves.

We present the results of a prospective multicenter clinical trial of nearly 5,000 men in which prostate specific antigen (PSA) density was compared to the serum PSA concentration alone for early detection of prostate cancer. All men were evaluated with PSA and digital rectal examination. If PSA was elevated (greater than 4 ng.

Accuracy of digital rectal examination and transrectal ultrasonography in localizing prostate cancer.

Not all prostate cancers are sonographically hypoechoic or palpable on digital rectal examination, and suspicious areas on transrectal prostatic ultrasonography or digital rectal examination often are not cancer. We present quadrant biopsy results from a multicenter prostate cancer screening study in which men were evaluated with prostate specific antigen (PSA) and digital rectal examination. If the PSA level was elevated (greater than 4.

Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men.

To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandem-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 micrograms/l or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 micrograms/l, 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests.