News
People recovering from meningitis outbreak are challenged by another illness. As this issue of Medical Laboratory Observer goes to press, 32 people have died, and 428 have been sickened, by the outbreak of fungal meningitis linked to contaminated methylprednisolone acetate manufactured by the now shuttered New England Compounding Center. The Centers for Disease Control and Prevention (CDC) now is reporting that recovering patients are facing a new threat: they are returning to hospitals with epidural abscess, a potentially very serious complication. Epidural abscess is an infection near the spine where the tainted steroid was injected as treatment for back or neck pain. Its primary symptom is severe pain near the site of the injection. The abscesses are internal, and thus can be diagnosed only via an MRI. Some epidural abscesses can be drained via neurosurgery. Some cannot be surgically removed, however, because they wrap around nerves, and the only treatment option available to clinicians in those cases is combining antifungal drugs that may or may not be effective. Tom Chiller, MD, MPHTM, deputy chief of the CDC mycotic diseases branch, says that the number of people affected is still being evaluated. “We don’t have a good handle on how many [meningitis patients] are coming back. We are trying to assess how best to manage these patients.” A tragic story continues to unfold.
Cancer
NIH researchers identify novel genes that may drive aggressive form of uterine cancer. Researchers have identified several genes linked to one of the most lethal forms of uterine cancer, serous endometrial cancer. They have described how three of the genes are frequently altered in the disease, suggesting that the genes drive the development of tumors. The research team was led by researchers from the National Human Genome Research Institute (NHGRI). Its findings appear online in Nature Genetics.
To determine which genes are altered in serous endometrial cancer, senior author Daphne W. Bell, PhD, head of the Reproductive Cancer Genetics Section of NHGRI’s Cancer Genetics Branch, and her team undertook a comprehensive genomic study of tumors by sequencing their exomes, the critical 1% to 2% of the genome that codes for proteins. They began by examining serous tumor tissue and matched normal tissue from 13 patients. Pathologists processed the 26 tissue samples, which then underwent whole-exome sequencing at the NIH Intramural Sequencing Center.
The researchers then filtered through millions of data points to locate alterations. They looked for genes that were mutated in more than one of the tumors. They felt confident that alterations in nine genes could be driver genes in serous endometrial cancer. They discovered that three genes—CHD4, FBXW7, and SPSO—are altered at a statistically high frequency in serous endometrial cancer. This set of three genes is mutated in 40% of the serous endometrial cancer tumors and in 15% to 26% of the other endometrial cancer subtypes.
Probing further, the team looked for the same genes highlighted by their exome sequencing study within databases that organize genes according to their biological function. They found an enrichment of genes involved in chromatin remodeling, the process by which the contents of the cell nucleus, including DNA, are packaged and modified. CHD4 was one of the genes that formed the chromatin-remodeling cluster.
Infectious Disease
Antibiotic may aid treatment of extensively drug-resistant tuberculosis. When tested in patients hospitalized with extensively drug-resistant tuberculosis (XDR-TB) unresponsive to previous treatment, linezolid, an antibiotic used to treat severe bacterial infections, proved largely effective when added to the patients’ ongoing TB treatment regimen. Also, few patients developed resistance to the drug. These promising findings are from a study that appeared recently in the New England Journal of Medicine.
Researchers enrolled patients with chronic XDR-TB who had failed to respond to any treatment during the six months before. The patients were randomly assigned either to immediately begin 600 milligrams of linezolid once daily as part of their existing treatment regimen or to start the drug after a two-month delay. After no longer testing positive for the bacterium or after four months of therapy, whichever came first, participants were then randomly assigned for the next 18 months to continue taking either a daily 600-mg dose of linezolid or a daily 300-mg dose.
After four months, 79% of the patients in the immediate-start group and 35% in the delayed-start group no longer tested positive for TB. After six months of treatment with the drug, 87% no longer tested positive for the bacterium. Adverse effects associated with long-term linezolid use included bone marrow suppression and peripheral and optic neuropathy. Additional clinical trials are needed to identify the most effective dosage.
Nobel Prize
Regenerative medicine pioneers win Nobel Prize. The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to John B. Gurdon of the University of Cambridge and Shinya Yamanaka of Kyoto University for the discovery that mature cells can be reprogrammed to become pluripotent. The two, working decades apart, added significantly to scientists’ understanding of cellular differentiation and techniques for the generation of stem cells.
Gurdon discovered in 1962 that the specialization of cells is reversible. He replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog. In essence, Dr. Gurdon was the first to clone an animal.
Yamanaka discovered in 2006 how intact mature cells in mice could be reprogrammed to become immature stem cells. By introducing only a few genes, he could reprogram mature cells to become pluripotent stem cells.
