Clinical Chemistry Podcast

In well-resourced countries with a low incidence of tuberculosis, a major focus of TB control efforts is the detection and treatment of latent TB infection to prevent reactivation to active TB disease. This approach is particularly relevant for healthcare workers. Interferon Gamma Release Assays are used to detect the release of interferon from T cells stimulated by tuberculosis specific antigens. However, these tests differ in cost and complexity than the conventional tuberculin skin test.

Recent studies have demonstrated that a variety of cells release exosomes or microvesicles into nearby biological fluids such as blood and saliva. During the exocytic process various proteins' messenger RNA and micro RNA are included in these exosomes.

Tacrolimus or FK506 is a macrocyclic lactone that is commonly used along with other immunosuppressant drugs to reduce graft rejection in organ transplantation by suppressing the immune system. Because of its narrow therapeutic window, it is critical to accurately monitor blood concentrations of this drug for optimal efficacy.

Platelet function testing has traditionally been used to diagnose inherited qualitative and quantitative defects in platelet function, such as Von Willebrand disease, but with the increased use of anti-platelet agents to prevent arterial thrombosis and the interest in identifying patients at risk for thrombosis despite anti-platelet therapy, the use of platelet function testing to monitory response to anti-platelet therapy, for example, aspirin, has become a hot topic.

Over the past several years, investigations have shown that many clinical studies remain unpublished and even among published studies the results are often presented selectively.

Pregnancy tests such as the ones used to test urine in hospitals have been shown to give false-negative results in certain patients.

In the February 2014 issue of Clinical Chemistry, the influence of PCR reagents on DNA polymerase extension rates were studied by examining nucleotide incorporation with DNA dyes. We are joined by one of the authors of that study, Dr. Carl Wittwer. He is Professor of Pathology at the University of Utah Health Sciences Center and is also affiliated with ARUP Laboratories, BioFire Diagnostics, and is an Associate Editor of Clinical Chemistry.

Type 1 diabetes is a chronic progressive autoimmune disorder with complex, polygenic susceptibility. Environmental factors which are poorly defined also contribute to the pathogenesis. This disease is characterized by lymphocyte infiltration into the islets of Langerhans in the pancreas, leading to inflammation and selective destruction of the insulin-producing beta cells resulting in hyperglycemia.

The latest incarnation of polymerase chain reaction, Digital PCR, takes three decades of development in enzyme chemistry and assay design and applies them with formidable precision and sensitivity.

Hemoglobin A1C is one of the analytes most commonly measured in clinical laboratories in patients with diabetes mellitus. Physicians use Hemoglobin A1C to monitor long-term glycemic control, adjust therapy, and predict complications of diabetes. It was recently added as a criterion for diagnosis of diabetes.

Although standardization of barcodes and label formats has lowered the number of mislabeled specimens in clinical laboratories, it remains a potential source of pre-analytical error. Published error rates of mislabeled specimens range up to as high as just over 1 percent.

Gestational diabetes mellitus is often defined as any degree of glucose intolerance during pregnancy. Fetal complications and adverse outcomes for both the fetus and the mother are important concerns in gestational diabetes.

Acute kidney injury is an important health problem. Patients who develop acute kidney injury have increased in-hospital mortality, and if they do survive, they still suffer long-term increased morbidity and mortality. For that reason there has been great interest in the development of biomarkers that could identify kidney injury in its earliest stages, at a time when interventions might be more successful.

Acute kidney injury is an important health problem. Patients who develop acute kidney injury have increased in-hospital mortality, and if they do survive, they still suffer long-term increased morbidity and mortality. For that reason there has been great interest in the development of biomarkers that could identify kidney injury in its earliest stages, at a time when interventions might be more successful.

The discovery phase of proteomics is essential for the identification of suitable markers for exploration and validation of promising new clinical tests. But can researchers be certain if what they believe they are measuring is in fact what they are actually measuring?

The January 2014 issue of Clinical Chemistry is devoted to the area of women's health. It includes a multi-center report on the application of measuring the circulating products of the proteolytic enzyme carboxypeptidase-N for the early detection of breast cancer. Accompanying that paper was an editorial by Eleftherios Diamandis on the tumor microenvironment and if released peptides could form the basis for early diagnosis breast cancer tests.

Until recently, much of the research in medical literature used primarily male populations. Slowly we've come to appreciate the importance of studying female populations due to the differences in normal physiology as well as disease pathology between men and women.

The development of in vitro fertilization in the 1970s has revolutionized the treatment of infertility. The ability to culture embryos has allowed for the development of the preimplantation genetic diagnosis. This involves removing a cell from the developing embryos for genetic testing before choosing one to implant. Just like prenatal diagnosis, it is used to screen for various genetic diseases before birth. For women of advanced maternal age or couples with known genetic mutations, the ability to screen of embryos free of certain genetic mutations is reassuring.

Women who present with acute coronary events are less frequently to be properly diagnosed and often have worse outcomes than men. Part of the problem may be that women are less apt to manifest increased biomarkers or often receive less aggressive guideline-mandated care. Women also have lower reference values for biomarkers of cardiac injury that are rarely taken into account.

Gestational diabetes mellitus is becoming more common as the epidemic of obesity and type 2 diabetes continues. Newly proposed diagnostic criteria will, if adopted universally, further increase the prevalence of this condition.

In making the diagnosis of diabetes, there are several advantages using determinations of hemoglobin A1c rather than glucose measurements. These include the pre-analytics stability of hemoglobin A1c in the sample, a low within-subject biological variation, as well as being free from the dietary restrictions associated with measuring glucose.

Cell free DNA from transplanted organs in the circulation of transplant recipients is a potential biomarker of rejection. But most of these methods entail high costs, long turnaround times and the need for donor DNA.

Multiplex digital PCR can be used for the sensitive detection of circulating tumor DNA with performance unachievable by other current molecular detection approaches.

The elevation in the concentrations of prostate-specific antigen, or PSA, in blood after prostatectomy is the only available marker from monitoring relapse after surgery. This increase in PSA is sometimes called biochemical failure or biochemical relapse. PSA monitoring, however, cannot predict relapse at the time of surgery.

New diagnostics technologies such as microarrays, next generation, or massively parallel sequencing, are generating an unprecedented amount of data. This requires a sophisticated knowledge of bioinformatics for proper storage, analysis, and mining of these very large data sets.

The application of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry or MALDI-TOF MS, to microbial identification is revolutionizing clinical microbiology, providing rapid identification with minimal sample preparation and potential cost savings.

And our guest today is Dr. Nader Rifai, Editor-in-Chief of Clinical Chemistry and Chair of the Clinical Chemistry Trainee Council, to announce the launch of a new program from AACC's Clinical Chemistry Trainee Council, the Question Bank. And Dr. Rifai, why was the Question Bank created?

The discovery phase of proteomics is critical in the identification of suitable markers for exploration and validation of promising new clinical tests. But can laboratories be certain if what they believe they are measuring is, in fact, what they actually measuring?

The analysis of circulating cell-free tumor DNA has considerable potential for the detention and monitoring of cancers. Substantial effort has been made to identify cancer associated genetic changes that might be suitable for use as new tumor markers. However, only a few of these genetic markers have been translated into clinical use.

The clinical microbiology laboratory is sometimes considered low-tech, particularly when compared to the high degree of automation found in the clinical chemistry laboratory. However, systems are emerging for the clinical microbiology laboratory with the potential to automate almost all areas of testing, including inoculation of primary culture plates, detection of growth on culture media, susceptibility testing, and extraction and detection of nucleic acids from clinical specimens.

The clinical microbiology laboratory is sometimes considered low-tech, particularly when compared to the high degree of automation found in the clinical chemistry laboratory. However, systems are emerging for the clinical microbiology laboratory with the potential to automate almost all areas of testing, including inoculation of primary culture plates, detection of growth on culture media, susceptibility testing, and extraction and detection of nucleic acids from clinical specimens.

For many taking a home pregnancy test can be upsetting, particularly if there is not complete confidence in the result. The November 2013 print issue of Clinical Chemistry published a paper from a group led by Dr. Ann Gronowski that reported false-negative results in point-of-care and over-the-counter qualitative hCG devices.

Maintaining long-term stability of analytical procedures is an important responsibility for clinical laboratories. This process typically includes a comparison of current and new reagent lots through paired measurements of patient or control samples, with defined criteria for acceptance and rejection of the new lot.

Pregnant women identified as high risk based on the prenatal screen can then undergo invasive procedures such as amniocentesis to confirm the diagnosis. Unfortunately, a large number of women with unaffected pregnancies undergo invasive procedures, putting the fetus at unnecessary risk for miscarriage.

Maintaining long-term stability of analytical procedures is an important undertaking for clinical laboratories. This process typically includes comparison of current and new reagent lots through paired measurement of patient and control samples, with defined criteria for acceptance and rejection of the new lot.

Personalized medicine implies that an individual's unique genetic makeup provides key information to guide prevention, diagnosis, and treatment of disease. It's highly probable that no one besides yourself has ever been born or ever will be again with your precise DNA sequence, unless you are an identical twin and even then maybe not.

The US Food and Drug Administration has long maintained its right to regulate LDTs; however until recently they've chosen to exercise discretion and have left this to the individual laboratories and other regulatory agencies. This is now in a state of change, and the FDA has stated that it would issue guidance on its oversight of Laboratory Developed Tests.

The US Food and Drug Administration has long maintained its right to regulate LDTs; however until recently they've chosen to exercise discretion and have left this to the individual laboratories and other regulatory agencies. This is now in a state of change, and the FDA has stated that it would issue guidance on its oversight of Laboratory Developed Tests.

The US Food and Drug Administration has long maintained its right to regulate LDTs; however until recently they've chosen to exercise discretion and have left this to the individual laboratories and other regulatory agencies. This is now in a state of change, and the FDA has stated that it would issue guidance on its oversight of Laboratory Developed Tests.

Prenatal development involves a series of highly-organized genetic and epigenetic events. Abnormalities in the epigenetic control of developmental processes have been implicated in infertility, spontaneous abortion, intra-uterine growth abnormalities, and numerous post-natal consequences.

Human growth hormone is an important peptide hormone that stimulates growth, cell reproduction, and cell regeneration. Measuring growth hormone in the blood is an important clinical assay, but may be problematic due to heterogeneity of the hormone that may arise from alternative splicing, different post-translational or modifications, oligomerization, formation of complexes, and proteolytic processing. Although standards for growth hormone are available, data from external quality assessment programs show large differences exist between measurement results obtained with different assays.