Keeping you up to date with recent developments in diagnostics . . .

Researchers seek to reduce time, cost of TB testing . . . Researchers in Switzerland hope to reduce the time and cost of diagnosing tuberculosis (TB) by measuring the heat bacteria produce as they grow. A team led by Olivier Braissant from Lausanne University is developing a method using microcalorimeters, which produce unique electrical signals based on the heat given off by different chemical, physical or biological processes. This could remove the need for scientists to grow samples of TB bacteria in a lab for examination, which can take up to 57 days — the microcalorimeter method takes less than two weeks. Other faster methods have been developed but the researchers say that these are expensive and require equipment and materials often not available in developing countries. This can include consumables such as fluorescent or radioactive probes, adding to the initial cost of equipment, which can be around $39,000 (£23,700). Simple calorimeters can be built for around $1,000 (£600). The researchers used a computer to amplify the microcalorimeter signal and produce a graphical footprint that is unique to each species of bacteria. Braissant's team has shown that this method works in a laboratory — results are published in the Journal of Applied Microbiology — and the team are now planning to test it in the field. 'Microcalorimeters have already been shipped to Tanzania and we hope to start a first validation of our approach in the field before the end of the year,' said Braissant. The method could also be used to test the effects of new types of antibiotic on the bacteria, as multiple samples from the same person can be tested for bacteria growth at the same time. One third of the world's population is infected with TB and in 2009 there were 1.7 million deaths from the disease. The highest number of these deaths was in Africa.

Biomarker may lead to important clue in ovarian cancer detection . . . Using a new approach to developing biomarkers for the very early detection of ovarian cancer, researchers at Rush University Medical Center (Chicago) have identified a molecule in the bloodstream of infertile women that could one day be used to screen for those at high risk for the disease — or even those with early-stage ovarian cancer. The molecule, an antibody that the human body manufactures, is an autoimmune response to mesothelin. This well-studied protein is found in abundance on the surface of ovarian cancer cells but present only in limited amounts in normal human tissue. The study is published in the online version issue of Cancer Epidemiology, Biomarkers & Prevention, published by the American Society for Cancer Research (Philadelphia). “The finding is extremely important because at present medical tests are unable to detect ovarian cancer in its early stages, which is why death rates from this disease are so high,“ said Judith Luborsky, PhD, professor of pharmacology, obstetrics and gynecology and preventive medicine at Rush and lead author of the study. “Our approach to discovering cancer biomarkers was unique in this study. Instead of investigating molecules specific to ovarian cancer alone, we asked what molecules women with a risk of ovarian cancer and those with ovarian cancer had in common,“ Luborsky said. The study enabled the researchers to explain the link between infertility and ovarian cancer that has been established in numerous epidemiological surveys. “More important, with the discovery of the mesothelin antibody, we now have what appears to be a biomarker that can potentially be used in screening tests to help us conquer ovarian cancer,“ Luborsky said. According to the American Cancer Society's (Atlanta) most recent estimates, there are expected to be about 21,900 new cases of ovarian cancer in the U.S. in 2011 and about 15,460 deaths from the disease. Ovarian cancer is the ninth most common cancer in women (not counting skin cancer) and ranks fifth as the cause of cancer death in women. The poor prognosis for women with ovarian cancer is due to the lack of both clinical symptoms when the cancer first develops and the absence of laboratory tests specific to the disease. In the study at Rush, researchers tested for mesothelin antibodies in the bloodstream of 109 women who were infertile, 28 women diagnosed with ovarian cancer, 24 women with benign ovarian tumors or cysts, and 152 healthy women. Infertility was due to endometriosis, ovulatory dysfunction or premature ovarian failure or was unexplained.

AnalizaDx develops prostate screening tool . . . A new prostate screening test developed by AnalizaDx (Cleveland), and studied by researchers at the Seidman Cancer Center at University Hospitals (UH; Cleveland) Case Medical Center along with colleagues at the Cleveland Clinic, the Veterans Administration Boston Healthcare and the National Cancer Institute, may prove to be a promising new tool in the diagnosis of prostate cancer. The study which will be published in the September issue of Urology found that this new screening test, the PSA/SIA assay, may be more sensitive in detecting prostate cancer than traditional screening methods. “This has the potential to be a major advance in the development of more accurate tests for prostate cancer diagnosis,“ says Mark Stovsky, MD, principal investigator and lead author of the study, urologist at UH Case Medical Center and Associate Professor of Urology at Case Western Reserve University School of Medicine. “Prostate cancer is the most common cancer in men but traditional screening is not very accurate. This test provides a new way to look at prostate cancer diagnosis utilizing a novel biological assay which differentiates PSA molecular structures arising from cancer versus non-cancerous glands.“ The accuracy of traditional prostate cancer screening (serum prostate-specific antigen or PSA) is limited by both relatively high false positive and false negative rates. Current diagnostic strategies that use total PSA to determine the need for biopsy demonstrate false positive rates of about 55%-75%. This finding can therefore lead to unneeded prostate biopsies and unnecessary worry in patients. Additionally, the serum PSA test carries, in some studies, false negative rates of up to 15 percent, meaning that some men with 'normal' PSA values actually have cancer. What is needed is a test that can more accurately predict the presence of prostate cancer on biopsy. Working with AnalizaDx, Stovsky and colleagues studied a urine-based test that works differently than most prostate screening methods by using a novel assay to separate PSA protein structures as being linked to either a 'cancer' or 'non-cancer' pathologic diagnosis based on ultrasound guided biopsy. Instead of attempting to find a single genetic biomarker which predicts the presence of cancer, the PSA/SIA assay is based on the assumption that there may be myriad different ultra-structural changes in the PSA protein which define the cancer phenotype. The authors theorize that the extremely high sensitivity of the test is the result of the ability of the PSA/SIA biological filter to categorize the myriad ultra-structural changes in the PSA protein as being made by either cancer versus non-cancer glands. The PSA/SIA assay was also found to have relatively high specificity (low false positive) results compared to the traditional serum PSA test.

New Microscopes can observe neurons activity . . . Like far away galaxies, powerful tools are required to bring the minute inner workings of neurons into focus. Borrowing a technique from materials science, a team of neurobiologists, psychiatrists, and advanced imaging specialists from Switzerland report in The Journal of Neuroscience how Digital Holographic Microscopy (DHM) can now be used to observe neuronal activity in real-time and in three dimensions - with up to 50 times greater resolution than ever before. The application has immense potential for testing out new drugs to fight neurodegenerative diseases such as Alzheimer's and Parkinson's. Neurons come in various shapes and are transparent. To observe them in a Petri dish, scientists use florescent dyes that change the chemical composition and can skew results. Additionally, this technique is time consuming, often damages the cells, and only allows researchers to examine a few neurons at a time. But these newly published results show how DHM can bypass the limitations of existing techniques. “DHM is a fundamentally novel application for studying neurons with a slew of advantages over traditional microscopes,“ said Pierre Magistretti of EPFL's Brain Mind Institute and a lead author of the paper. “It is non-invasive, allowing for extended observation of neural processes without the need for electrodes or dyes that damage cells.“ Senior team member Pierre Marquet adds, “DHM gives precious information not only about the shape of neurons, but also about their dynamics and activity, and the technique creates 3-D navigable images and increases the precision from 500 nanometers in traditional microscopes to a scale of 10 nanometers.“ A good way to understand how DHM works is to imagine a large rock in an ocean of perfectly regular waves. As the waves deform around the rock and come out the other side, they carry information about the rock's shape. This information can be extracted by comparing it to waves that did not smash up against the rock, and an image of the rock can be reconstructed. DHM does this with a laser beam by pointing a single wavelength at an object, collecting the distorted wave on the other side, and comparing it to a reference beam. A computer then numerically reconstructs a 3-D image of the object - in this case neurons - using an algorithm developed by the authors. In addition, the laser beam travels through the transparent cells and important information about their internal composition is obtained.

Compiled by Omar Ford, MDD
omar.ford@ahcmedia.com