By Melanie Fridl Ross
GAINESVILLE, Fla. - In the month after the Sept. 11, 2001, attack on the World Trade Center, millions grappled with the emotional heartache of a national tragedy. Scientists now have discovered new evidence of physical consequences for the heart as well among patients living hundreds of miles from Ground Zero who rely on a pacemaker-like device that corrects dangerously rapid arrhythmias with electric shock.
University of Florida researchers found that patients who saw a doctor for routine monitoring of the device, known as an implantable cardioverter defibrillator, or ICD, had a nearly three-fold increase in the number of shocks they received in the four weeks after Sept. 11. The scientists will present their findings today (3/8) at the annual scientific meeting of the American College of Cardiology in New Orleans.
An estimated 400,000 people die from unstable heart rhythms each year. Experts say an additional 80,000 receive an ICD, which works by constantly monitoring the heartbeat, halting dangerously rapid rhythms by delivering a small electrical jolt to the heart. It also can correct abnormally slow heart rhythms by pacing the heartbeat with electrical pulses.
UF experts collaborated with researchers at St. Luke's-Roosevelt Hospital in New York, who previously noted an increase in the incidence of arrhythmias and the frequency of ICD shocks among patients living in the metropolitan area in the month after the attack. The current study was the first to show a similar effect in patients living at a distance. The findings prompt speculation that terrorism, major life stress and mass disasters might trigger adverse effects among heart patients nationwide, even if they live in an area not directly touched by these events.
"This is the first time after a tragedy has occurred in our country that anybody has looked to see whether it affects patients all across the country," said Omer Shedd, M.D., a postdoctoral fellow in cardiovascular medicine at UF's College of Medicine. "Because the World Trade Center attacks were so heavily publicized - virtually everybody in the country was exposed to that tragedy - we thought we may find an increase in morbidity and possibly mortality in our area. The implications are that the event had a much more widespread effect than previously recognized."
Physicians increasingly acknowledge that emotional stress is a powerful stimulus for cardiovascular events. Previous research has directly linked cardiovascular and psychological reactions in people experiencing sudden and severe life stress, such as the aftermath of a natural disaster or the terror of war. The number of heart attacks and sudden deaths, for example, increased among Israelis after the Scud missile attacks on Israel during the Gulf War. Similar effects have been noted among Californians after major earthquakes. The threat of terrorism has raised additional concern, researchers say.
"There are some data to suggest that a lot of arrhythmias are anxiety-driven," Shedd said. "When people become anxious, the levels of certain hormones in the body increase, and that can trigger rhythm problems and heart problems."
If doctors could better characterize or identify patients prone to experiencing high levels of anxiety, whether it's related to a national event or an event at home such as the loss of a family member, then perhaps they could help prevent arrhythmias and other cardiovascular complications, Shedd said.
For the current study, UF scientists reviewed the medical records of 132 Floridians, mostly men, who were seen for routine checkups at UF or at Gainesville's Malcom Randall Veterans Affairs Medical Center, both in the month before and the month after the Sept.11 attack. The average age of those enrolled in the study was about 63. The frequency of heart arrhythmias requiring ICD treatment increased by more than 68 percent among the study participants shortly after the attack. Patients with arrhythmias in the month before also experienced twice as many in the month afterward.
In all, 11 percent of study participants had abnormal heart rhythms in the month afterward, compared with 3.5 percent in the month before. Because the research was a retrospective study, however, scientists do not know whether the patients were personally touched by the tragedy, through knowing friends or relatives living in the New York metropolitan area.
"These data provide real-world evidence that stress affects both the mind and the heart," said UF psychologist Sam Sears Jr., Ph.D., of the College of Public Health and Health Professions "Even witnessing a national tragedy has a similar effect as experiencing a tragedy. It doesn't have to be a death in your family for it to affect the heart. Fortunately, the ICD protects patients under these unusually stressful circumstances. What's interesting about this study was that the effect occurred because they were Americans. It suggests we've internalized our identity and (the victims') identity as Americans."
The key is to get at-risk patients the psychological help they might need to cope with stressful events, and to let them know that if they do experience an increase in arrhythmias caused by stress they are likely to subside with time, said Anne B. Curtis, M.D., a professor of cardiovascular medicine at UF's College of Medicine.
"When tragedies like this happen we've got to anticipate that patients may have more events," Curtis said. "And if they do, we need to reassure patients that it may simply be related to the stress of the situation, more so than to the notion that the underlying arrhythmia may have changed in a substantial way."
In coming months, researchers will continue to assess the effects of patient anxiety, depression and other psychological problems on arrhythmias, and on the incidence and frequency of shocks in patients with ICDs.
"One of the things we'd like to do is find better ways to identify those patients before these kinds of events happen," Shedd said. "We also want to learn the best way to treat patients like this. Do they need long-term medications for anxiety or depression, or are we better off giving them a so-called 'pill-in-the-pocket,' which they can use at a time when they are experiencing a lot of anxiety? We don't know if that would work or not. Those are some areas we'd like to look into."
Sandra B. Dunbar, R.N., D.S.N., a professor of nursing and medicine at Emory University who is testing an education-based stress reduction intervention in ICD patients, called the UF study important, saying, "It emphasizes the importance of the lifesaving technology, as many of these patients would have died without their ICDs. And it clearly supports the need to better prepare cardiac patients for dealing with stress and anxiety to prevent arrhythmias. Future studies that incorporate nondrug approaches, such as teaching coping techniques, would be important."
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UF scientists find immune system cells fight cancer's return, predict
outcome soon after stem cell transplant
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By Melanie Fridl Ross
GAINESVILLE, Fla.- By measuring levels of cells crucial to marshaling the forces of the immune system, University of Florida researchers have been able to predict with greater accuracy the likelihood cancer patients who have received a blood stem cell transplant will go into remission or suffer a relapse and die.
Known as dendritic cells, these captains of the immune system normally initiate the body's response to infection or disease, ordering a veritable molecular military of soldier-like cells to the front lines. Remarkably, when dendritic cells are produced in large enough numbers after blood stem cell transplantation, they appear to single-handedly launch the body's fight against the return of blood-borne cancers, without attacking a patient's healthy tissues.
Until recently, doctors largely presumed that successfully battling leukemia and related cancers would require the use of powerful drugs or infusions of cells altered to trigger recognition of malignant cells, enabling the immune system to better target them. The new findings, reported in the journal Blood, raise the hope of someday using patients' own naturally occurring dendritic cells to attack their cancer.
"This is the first study to demonstrate that dendritic cells by themselves can fight off cancer," said the study's lead author, Vijay Reddy, M.D., Ph.D., an assistant professor of hematology and oncology at UF's College of Medicine. "It's the first study in any cancer patient to show that if you don't have enough dendritic cells the cancer comes back. And it's the first study in the bone marrow transplant arena that shows that large numbers of dendritic cells are important to having a good immune system after transplant to avoid death after transplant.
"Essentially, if you have dendritic cells in your blood it's good for you; if you don't have them it's bad," said Reddy, who also is affiliated with the UF Shands Cancer Center.
Each year, an estimated 30,000 patients undergo a bone marrow or peripheral blood stem cell transplant for a diagnosis of leukemia or another blood disease. Both types of transplantation aim to restore patients' blood stem cell counts after their own stem cells have been wiped out by high-dose chemotherapy or radiation therapy used to treat cancer. After they are infused into the bloodstream, stem cells take up residence in the bone marrow, where they give rise to the immune system's infection-fighting white blood cells, red blood cells or
platelets.
An increasing number of researchers have become interested in dendritic cells, evaluating their use in the development of cancer vaccines and assessing their effectiveness in priming the immune system to fight prostate, breast and other cancers. But the UF study was the first to discover that in and of themselves they are highly predictive of outcome, and thus presumably powerful in their own right.
"Up to now, to gauge prognosis the most important things we've been looking at are how well the donor and recipient are matched, the kind of disease they're receiving the transplant for and how well the treatments given before the transplant have led to cancer control," said study co-author John Wingard, M.D., a professor of medicine at UF's College of Medicine and director of the Bone Marrow Transplant Program at Shands at UF medical center.
In the study, UF physicians took blood samples from 50 patients within two to four weeks after they received a bone marrow or peripheral blood stem cell transplant from a donor. Most were being treated for leukemia, lymphoma or multiple myeloma. Patients with a low dendritic cell count were nearly 12 times more prone to cancer relapse in the study period, which lasted on average nearly a year and a half. They also were more than three times as likely to develop graft-versus-host disease and ultimately were nearly four times more likely to die.
Researchers are still puzzled why some patients boasted high levels of dendritic cells, whereas others had low levels. They evaluated how many cells of various types - including dendritic - were in the donor graft, but found no correlation with the number of dendritic cells produced after transplantation. Learning more about the phenomenon will help them discover ways to optimize dendritic cell counts after transplantation.
"If we measured the levels of dendritic cells in the person's blood at the time of engraftment and discovered they were low, then perhaps we could boost with additional cells from the donor," Wingard said. "That could have enormous therapeutic importance."
Interestingly, patients who had large numbers of dendritic cells also were less likely to suffer a deadly complication of transplantation, graft-versus-host disease, in which transplanted cells - the graft - don't discern between healthy tissues and cancer and attack both.
"Essentially, when the immune cells from the donor in the transplant graft get into the patient, these cells look at the patient and say 'Hey, this is not my body. I'm Joe Smith but this is Joe someone else,'" Reddy said. "The cells can literally attack the body, causing graft-versus-host disease. The same cells, however, also look at the cancer and say, 'Hey, this doesn't belong here.' They can fight the cancer, therefore causing graft-versus-leukemia, which is a beneficial effect. So what we need to do is identify these cells that can have the graft-versus-leukemia and not have this negative effect of fighting the rest of the body, because we want the cells to live in harmony in the patient except for fighting off the leukemia. This is our biggest problem as well as the most exciting area of research."
Edmund Waller, M.D., Ph.D., director of the Bone Marrow Stem Cell Transplant Center at Emory University, said the UF findings represent "important observations regarding the role of dendritic cells in transplant outcomes."
"These studies will lead to a better understanding of how relapse is controlled by allogeneic (from a genetically matched or similar donor) transplantation," Waller said. "The increasing evidence that dendritic cell subsets are critical in the regulation of immune responses suggests novel approaches to improve allogeneic transplantation."
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