|
||||||||
|
RESEARCH BRIEFS
Virus-specific Immune Cell Shows High Impact with Low NumbersDespite its low frequency in the blood, a particular type of lymphocyte plays a crucial role in fighting a lethal neurodegenerative disease, according to new research in the November Journal of Virology.
This brain section from a person with PML shows the deteriorated white matter infected with JCV as the light-colored area on the upper right. (Image courtesy of Journal of Virology) Progressive multifocal leukoencephalopathy (PML) involves the destruction of myelin, leading to lesions in the white matter of the brain. Symptoms include difficulty in speaking or swallowing, paralysis, blindness, and dementia. The microbe that causes the disease, polyomavirus JC (JCV), is found in 85 percent of people. It usually is acquired by age 20 through oral ingestion, according to Igor Koralnik, director of the HIV/Neurology Center at Beth Israel Deaconess Medical Center and an HMS associate professor of neurology. The virus lies quiescent in a patient's kidneys until immunosuppression from cancer treatment, organ transplantation, or HIV allows it to express itself. Koralnik and his group previously demonstrated that HIV-positive patients who survived PML had JCV-specific cytotoxic T lymphocytes in their blood. To determine the frequency of these rare immune cells, the researchers developed their own highly sensitive assay by identifying the most common JCV epitope recognized by the lymphocytes, VP1p36, and using a lymphocyte-sorting technique to quantify the cells' frequency by flow cytometry. Koralnik found an approximate frequency of JCV-specific cytotoxic T lymphocytes ranging from 1/20,000 to 1/222,000 in peripheral blood mononuclear cells in HIV-positive patients with PML. The frequency of JCV-specific cytotoxic T lymphocytes is 10 times lower than that of other cytotoxic T lymphocytes against other DNA viruses, such as herpes simplex. Koralnik is currently investigating how such a low frequency of lymphocytes could allow healthy people to coexist with lethal JCV in their bodies. He also is using this knowledge for the development of novel immunotherapies for PML. There is no specific treatment for the disease. Before highly active antiretroviral therapy (HAART) for HIV, 10 percent of HIV patients with PML lived for more than one year. With the addition of HAART, 50 percent of these patients now survive beyond the one-year mark, adding urgency to the need for PML therapies. --Nicole Giese
Teaching Hospital Physicians Report Trouble Obtaining Specialty Services for the UninsuredTeaching hospitals are often key providers of health services to poor and uninsured patients, acting as a safety net maintaining access to health care for all. However, a recent survey of teaching hospital faculty by the Institute for Health Policy at Massachusetts General Hospital found that teaching physicians may have difficulty accessing specialty care for their uninsured patients. The study appears in the November/December issue of Health Affairs."Our research suggests that the safety net has more holes than previously thought," said lead author Joel Weissman, HMS associate professor of medicine at MGH. "Even patients who get initial access to care in teaching hospitals may have significant problems getting referred for specialty care and high-tech services or getting admitted for a nonemergency condition." The research team surveyed nearly 2,300 physicians at 121 U.S. academic health centers who had provided direct patient care during the previous year. About 25 percent reported problems with admitting an uninsured patient or having to limit that patient's care. Respondents were nine times as likely to report difficulty obtaining specialty care for their uninsured patients as they were for privately insured patients, especially with accessing nonemergency hospital admissions, high-tech services, and outpatient mental health and substance abuse services. For both admissions and specialty care, similar problems were reported for private and public institutions. Formal practice policies limiting care to uninsured patients were reported by 13 percent of responding faculty. Barriers to care of the uninsured included the limited number of such patients who were referred, inadequate reimbursement for services, and the understanding that even in the absence of formal policies, providing such care was discouraged by the practice or hospital. "One might ask what message it sends to residents in our teaching hospitals, when on the one hand, they are being taught that care is provided regardless of the patient's financial condition," Weissman said. "On the other hand, they see the problems their teachers have obtaining needed services for their uninsured patients." Weissman explains that efforts to provide services for the uninsured must go beyond primary care, which is the usual focus of existing safety net programs. He also notes that several currently available sources of reimbursement for care of the poor or uninsured, including Medicare and Medicaid subsidies and state uncompensated care pools, have traditionally been available only to hospitals and not to physician practice groups. He suggests that broadening the availability of such funds is a possible way to increase the availability of specialty services.
Study Challenges Proposed Changes to Clinical Definition of Mental IllnessTightening the mental health industry's clinical definitions of mental illness could complicate or halt the treatment of mildly ill patients, lead to greater mental illness severity, and add long-term costs to care and treatment, says an HMS study published in the November Archives of General Psychiatry.As the American Psychiatric Association prepares for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), there is strong debate on how the reference could be improved, including eliminating milder forms of diseases to prevent overtaxing the mental health care system. But according to Ronald Kessler, HMS professor of health care policy, tightening the DSM's definitions is not a trivial matter. "The reason this is important is that insurance coverage and research money will not go to those patients with diseases that are not in the DSM," he said. To find out how lack of treatment affects people with mild cases of mental illness, Kessler compared the participants' responses in the National Comorbidity Survey (NCS) to their responses in the follow-up study, NCS-2. In the early 1990s, the NCS assessed how many people had current DSM-defined disorders among a national sample of more than 8,000 people. More than 4,300 of these same people were re-interviewed for the NCS-2. Kessler looked specifically at people with milder cases of mental illness and found that those with mild cases are two times more likely to have severe mental illness 10 years later than those without a mental illness. Yet defining the boundary where mental health becomes mild mental illness is difficult. "Mental illness operates on a continuum, just as physical diseases do, and there's not a clear cut-off point for when treatment should not be available," Kessler said. Without a clear demarcation between mental health and illness, changing the DSM definitions could eliminate the advantage of treating mild illness. "If patients with mild mental illness get treated earlier, some of these people will not become severe who otherwise would," Kessler said. He concedes that it may not be cost-effective right now to treat many of the milder cases, but he compares mild cases of mental illness to borderline hypertension and massive heart attacks. "If untreated or unmonitored, hypertension can lead to a heart attack in the future, just as unmonitored, untreated mild mental illness can lead to severe mental problems," Kessler said. "Right now, we're waiting around for heart attacks in psychiatry." --Nicole Giese |
