Szabo S.,HIV Community Program |
Moffett L.E.,HIV Community Program |
Cantwell- McNelis K.,HIV Community Program |
James C.W.,HIV Community Program |
Joseph A.,Molecular Diagnostics
Journal of the International Association of Physicians in AIDS Care | Year: 2010
Poor correlation has been reported between the Roche Cobas AmpliPrep/Cobas (TaqMan) HIV-1 TaqMan assay and the Roche Cobas Amplicor HIV-1 Monitor version 1.5 Amplicor assay. We report 8 patients who experienced unexplained detectable viremia, despite exemplary medication adherence, following a change in viral quantification assay from Amplicor to TaqMan in January 2008. All patients were found to have undetectable HIV RNA by branched DNA (bDNA) assay. © The Author(s) 2010.
Child N.,Auckland City Hospital |
Croxson M.C.,Auckland City Hospital |
Rahnama F.,Molecular Diagnostics |
Anderson N.E.,Auckland City Hospital
Journal of Clinical Neuroscience | Year: 2012
We conducted a retrospective audit of the outcomes of patients 15 years of age and older from the greater Auckland region who had a diagnosis of encephalitis over a five-year period. Patients were identified via a database search of all patients who had a cerebrospinal fluid (CSF) viral polymerase chain reaction (PCR) panel requested between 2005 and 2009. All CSF viral PCR were performed at one laboratory. This test was used as a default marker for patients who may have had encephalitis. There were 37 patients who met our definition of encephalitis during the study. Their ages ranged from 15 to 88 years (median 51 years), and 59% were female. There was an admission rate of 7.4 admissions per year or an annual incidence of approximately 0.5 cases per 100,000. An infective cause was found in 10 patients (27%): varicella zoster in five patients (14%), herpes simplex in four (11%) and enterovirus in one patient (3%). An autoimmune paraneoplastic encephalitis was felt most likely in three patients (8%); a paraneoplastic antibody screen was performed in two of these three but was negative in both. The cause of encephalitis was not identified in the other 24 patients (65%). There were five deaths (in-hospital mortality rate 14%). Encephalitis is an uncommon but important disease, because of the significant mortality. The cause of encephalitis remained undetermined in two-thirds of patients. © 2012 Elsevier Ltd. All rights reserved.
Bartley A.N.,Molecular Diagnostics |
Hamilton S.R.,University of Houston
Archives of Pathology and Laboratory Medicine | Year: 2015
Context.-Advances in molecular biomarkers of the gastrointestinal tract have contributed to a decline in the incidence of and mortality from diseases of the gastrointestinal tract. The discovery and clinical validation of new biomarkers are important to personalized cancer therapy, and numerous clinical trials are currently ongoing to help identify individualized therapy affecting these biomarkers and molecular mechanisms they represent. Distinct molecular pathways leading to cancers of the colorectum, esophagus, stomach, small bowel, and pancreas have been identified. Using biomarkers in these pathways to direct patient care, including selection of proper molecular testing for identification of actionable mutations and reporting the results of these biomarkers to guide clinicians and genetic counselors, is paramount. Objective.-To examine and review select clinically actionable biomarkers of the colon, esophagus, stomach, small bowel, and pancreas, including present and future biomarkers with relevant clinical trials. Data Sources.-Extensive literature review and practical and consultation experience of the authors. Conclusions.-Although numerous biomarkers have been identified and are currently guiding patient therapy, few have shown evidence of clinical utility in the management of patients with gastrointestinal cancers. Inconsistent results and discordant proposed algorithms for testing were identified throughout the literature; however, the potential for biomarkers to improve outcomes for patients with gastrointestinal cancer remains high. Continued advances through high-quality studies are needed. Copyright © 2015 College of American Pathologists.
Weihua Guan, assistant professor in electrical engineering, and his graduate student Gihoon Choi, show “AnyMDx: A Mobile Molecular Diagnostics Lab for Anyone, Anywhere, Anytime.” Credit: Penn State When a person contracts a disease, it takes time to diagnose the symptoms. Cell culturing, immunoassay and a nucleic-acid based diagnostic cycle all take several days, if not a week to determine the results. Not only do sick patients suffer during this time period, the wait can also lead to unnecessary disease spreading and perhaps avoidable antibiotic use. Weihua Guan has created a device that will deliver a diagnosis to the patient in 30 minutes. The assistant professor of electrical engineering in the School of Electrical Engineering and Computer Science, with the help of his graduate student, Gihoon Choi, has created "AnyMDx: A Mobile Molecular Diagnostics Lab for Anyone, Anywhere, Anytime" for rapid diagnosis. Their invention consists of three parts: a small footprint box which is the analyzer; a disposable disease-specific microfluidic compact disk that the doctor puts a patient's sample of blood, saliva, etc. in; and an optional smartphone app to interpret the results. "By leveraging our advanced microfluidic, microelectronic and optic technologies, we are now able to integrate all the steps in nucleic acid diagnosis, including sample preparation, amplification and results reading, in a 'sample-in-answer-our' fashion," said Guan. "Our device can handle a wide variety of samples: whole blood, saliva, swab, sputum, urine, stool and various pathogen types: parasites, bacteria and viruses. Our device requires no expertise to run the advanced molecular diagnosis and it delivers the results to the patient in under 30 minutes." Not only will AnyMDx be faster, Guan is working to make sure the device can be used in a harsh and resource-limiting environment. With help from funding from the College of Engineering's ENGineering for Innovation & Entrepreneurship (ENGINE) grant program, Guan and Choi are making sure the instrument is mobile, battery-powered and able to withstand any conditions, in any kind of environment. Collaborating with Liwang Cui in the College of Agricultural Sciences, their first objective is to get it deployed in the field by summer 2017 to Thailand and Myanmar to start diagnosing cases of malaria, where the disease is prevalent. Ultimately the goal is for hospitals, community clinics, doctors' offices and even pharmacies to have an AnyMDx readily available for diagnosis. Explore further: Researchers have developed a diagnostic device to make portable health care possible
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer. They also found evidence that this methylation signature may be present in many more types of cancer. The specific signature results from a chemical modification of DNA called methylation, which can control the expression of genes like a dimmer on a light switch. Higher amounts of DNA methylation (hypermethylation), like that found by the researchers in some tumor DNA, decreases a gene's activity. Based on this advance, the researchers hope to spur development of a blood test that can be used to diagnose a variety of cancers at early stages, when treatments can be most effective. The study appeared February 5, 2016, in The Journal of Molecular Diagnostics. "Finding a distinctive methylation-based signature is like looking for a spruce tree in a pine forest," said Laura Elnitski, Ph.D., a computational biologist in the Intramural Research Program at NIH's National Human Genome Research Institute (NHGRI). "It's a technical challenge to identify, but we found an elevated methylation signature around the gene known as ZNF154 that is unique to tumors." Dr. Elnitski is head of the Genomic Functional Analysis Section and senior investigator in the Translational and Functional Genomics Branch at NHGRI. In 2013, her research group discovered a methylation mark (or signature) around ZNF154 in 15 tumor types in 13 different organs and deemed it a possible universal cancer biomarker. Biomarkers are biological molecules that indicate the presence of disease. Dr. Elnitski's group identified the methylation mark using DNA taken from solid tumors. "No one in my group slept the night after that discovery," Dr. Elnitski said. "We were so excited when we found this candidate biomarker. It's the first of its kind to apply to so many types of cancer." In this new study, they developed a series of steps that uncovered telltale methylation marks in colon, lung, breast, stomach and endometrial cancers. They showed that all the tumor types and subtypes consistently produced the same methylation mark around ZNF154. "Finding the methylation signature was an incredibly arduous and valuable process," said NHGRI Scientific Director Dan Kastner, M.D., Ph.D. "These findings could be an important step in developing a test to identify early cancers through a blood test." The NIH Intramural Sequencing Center sequenced the tumor DNA that had been amplified using a technique called polymerase chain reaction (PCR). Dr. Elnitski and her group then analyzed the results, finding elevated levels of methylation at ZNF154 across the different tumor types. To verify the connection between increased methylation and cancer, Dr. Elnitski's group developed a computer program that looked at the methylation marks in the DNA of people with and without cancer. By feeding this information into the program, they were able to predict a threshold for detecting tumor DNA. Even when they reduced the amount of methylated molecules by 99 percent, the computer could still detect the cancer-related methylation marks in the mixture. Knowing that tumors often shed DNA into the bloodstream, they calculated the proportions of circulating tumor DNA that could be found in the blood. Dr. Elnitski will next begin screening blood samples from patients with bladder, breast, colon, pancreatic and prostate cancers to determine the accuracy of detection at low levels of circulating DNA. Tumor DNA in a person with cancer typically comprises between 1 and 10 percent of all DNA circulating in the bloodstream. The group noted that when 10 percent of the circulating DNA contains the tumor signature, their detection rate is quite good. Because the methylation could be detected at such low levels, it should be adequate to detect advanced cancer as well as some intermediate and early tumors, depending on the type. Dr. Elnitski's group will also collaborate with Christina Annunziata, M.D., Ph.D., an investigator in the Women's Malignancies Branch and head of the Translational Genomics Section at NIH's National Cancer Institute (NCI). They will test blood samples from women with ovarian cancer to validate the process over the course of treatment and to determine if this type of analysis leads to improved detection of a recurrence and, ultimately, improved outcomes. "Ovarian cancer is difficult to detect in its early stages, and there are no proven early detection methods," said Dr. Annunziata. "We need a reliable biomarker for detecting the disease when a cure is more likely. We are looking forward to testing Dr. Elnitski's novel approach using DNA methylation signatures." Current blood tests are specific to a known tumor type. In other words, clinicians must first find the tumor, remove a sample of it and determine its genome sequence. Once the tumor-specific mutations are known, they can be tracked for appearance in the blood. The potential of the new approach is that no prior knowledge of cancer is required, it would be less intrusive than other screening approaches like colonoscopies and mammograms and it could be used to follow individuals at high risk for cancer or to monitor the activity of a tumor during treatment. Once the blood test is developed, the scientific community must conduct studies to ensure that it does not indicate the presence of cancer when it is not there or miss cancer when it is there. Dr. Elnitski does not yet understand the connection between tumors and elevated DNA methylation. It may represent derailment of normal processes in the cell, or it may have something to do with the fact that tumors consume a lot of energy and circumvent the cellular processes that keep growth in check. Researchers also don't know exactly what the gene ZNF154 does. "We have laid the groundwork for developing a diagnostic test, which offers the hope of catching cancer earlier and dramatically improving the survival rate of people with many types of cancer," Dr. Elnitski said.