"The levels we found were as high or higher than those we see in people with long-standing infection," said Dr. Christopher D. Pilcher, assistant professor of medicine at the University of North Carolina at Chapel Hill. "But our patients had all been infected within the previous three months. Their body fluids had high concentrations of virus even within two to three weeks of the beginning of symptoms."

Flu-like symptoms are often the first signs of the deadly infection during the first weeks after first contracting HIV, the period scientists call "primary HIV infection." These symptoms are far less debilitating than those patients with full-blown AIDS experience and can include fever, muscle aches, rash, swollen glands and, sometimes, sore throat, Pilcher said. Those symptoms sent the 17 patients to the doctor for treatment in the first place.

A second key finding was that virus levels, which scientists call "viral load," dropped rapidly in all fluids analyzed after doctors began treating patients with the latest drugs, he said. Earlier, the UNC team and other researchers proved the drugs worked during chronic infections, but their effect on primary infection was unknown.

"Together, these findings suggest that combination anti-retroviral therapy -- the HIV 'cocktail' therapy -- is a potential avenue for public health intervention," Pilcher said. "In other words, such treatment could become a public health strategy to reduce shedding of virus from semen and vaginal fluid especially and possibly reduce the number of people contracting the virus to begin with."

Such a strategy might help curtail the epidemic by augmenting current prevention efforts involving education, treatment of other sexually transmitted diseases, condom distribution and tracing sexual partners, the physician said. However, one hurdle to diagnosing very early infections is that routine antibody tests to HIV are likely to be negative during this period. It's necessary to use other, more sophisticated tests such as polymerase chain reaction to directly detect the presence of the virus during primary HIV infection. Those more revealing tests were used to screen patients for the new study.

A report on the research appears in the current issue of the journal AIDS.

Co-authors of the report at UNC are Dr. Diane C. Shugars, Dr. Susan A. Fiscus, Dr. Kevin R. Robertson, Dr. Joseph Eron, Prema Menezes of the UNC schools of medicine and dentistry. Other authors are Dr. Charles C. Hicks and Julieta Giner of Duke University, Dr. Jeffrey L. Lennox and Beth Dean of Emory University and Dr. Clyde E. Hart of the Centers for Disease Control and Prevention.

For the past several years, medical scientists have focused heavily on early infection with HIV because it offers a window into the nature of the virus' attack on the body, Pilcher said. "We have wanted to know how quickly the virus gets into various body fluids, how widely it attacks different organs and what that says about ways the virus enters the body," Pilcher said. "In addition, there's also been the suspicion that primary HIV infection is a time of important infectiousness."

Therefore, a second goal has been to learn whether virus is shed specifically into genital and oral fluids during early infections because those fluids are the primary vehicles of sexual transmission of HIV, he said. The new findings, which involved 17 patient volunteers, show that conclusively. "Our results are not surprising since they are basically what those of us who study primary infection would have expected, but they've not been demonstrated before," Pilcher said. "This is fundamental information that has been very difficult to get in the past because it's extremely difficult to make this early diagnosis. You have to be suspicious enough to test for it and not just believe that a person has mononucleosus or the flu."

Another reason these studies are difficult, he said, is that researchers rarely have reason to ask patients suffering flu-like symptoms to donate semen, spinal fluids and other fluids.

A fairly large group of AIDS researchers now believe primary infection with HIV might drive the AIDS epidemic, the physician said. Primary infection might be a time of heightened infectiousness or even the peak of infectiousness.

"The Centers for Disease Control and Prevention and other public health agencies have not emphasized efforts to diagnose primary infection as part of prevention in the past," he said. "If primary infection is driving the epidemic, we'll need to pay a lot more -- and earlier -- attention to it. Our study provides the strongest direct evidence yet that patients are infectious during primary HIV infection, and that may be another reason to reconsider public health efforts to identify people early."

Lead author Dr. Arie Belldegrun, chief of urologic oncology at the center, said his early-phase study suggests that intra-tumoral immunotherapy, in combination with surgery to remove the prostate, represents a new option for treating men with cancer that has spread beyond the boundaries of the prostate.

Historically, prostate cancer was believed to be resistant to immunotherapy. Belldegrun said his study proves otherwise. “Based on our earlier studies in the laboratory, which were published in the journal Cancer, we suspected that this approach might work in humans,” he said. “We did not know, however, that gene therapy and immunotherapy could be options for patients with locally advanced prostate cancer, a high-risk group to whom we have little to offer right now.”

The study outlined in the article involves injecting gene-based immunotherapy — using an ultrasound guidance system — directly into the diseased prostate prior to surgery or after the failure of radiation therapy. The treatment proved to be safe and, because the therapy was injected into the prostate and not delivered systemically, as chemotherapy is, it resulted in few side effects, Belldegrun said. And in more than half of the patients, the therapy resulted in reduced PSA levels, a blood marker that signals the presence of prostate cancer.

“This is the first clinical study of its kind aimed at exploring the role of immunotherapy and gene therapy in prostate cancer patients,” Belldegrun said. “We’re encouraged by the significant reductions of PSA levels and by the clinical outcome in this high-risk group of patients.”

In this study, 24 patients with locally advanced prostate cancer were treated with gene-based immunotherapy. A gene that expresses interleukin 2 (IL-2) was injected directly into the prostate. A hormone-like substance, IL-2 stimulates the immune system to attract so-called “killer cells,” or lymphocytes, which researchers hope will seek out and destroy cancer cells, Belldegrun said. The study proved for the first time that IL-2 is active against prostate cancer.

Belldegrun and his team of researchers use gene therapy to deliver the IL-2 to the prostate, a novel approach in prostate cancer. The IL-2 is a passenger of sorts, riding in the gene therapy vehicle, Belldegrun said. The injection itself is done on an outpatient basis, so no hospital stays are necessary. The use of ultrasound for guidance allows researchers to deliver therapy with great accuracy.

“We proved this is a feasible approach for patients with locally advanced prostate cancer,” said Dr. Robert Figlin, an oncologist at UCLA’s Jonsson Cancer Center, co-author of the study and a professor of medicine and urology at the UCLA School of Medicine. “Because of its location, we were able to inject into the prostate these genes that stimulate the immune system to fight cancer.

We anticipate that, in the near future, newer and more powerful agents will be delivered directly to the prostate via gene therapy — perhaps eliminating the need to remove the prostate. This is an important new concept and a proof of principal that the technology can work.”

Because of the success in this early study, five centers nationwide, including UCLA’s Jonsson Cancer Center, are now testing this treatment method in much larger phase II studies, Belldegrun said.

“We are encouraged by these early results and consider them valuable, especially in light of the apparent safety and lack of toxicity seen with this treatment,” the Human Gene Therapy article states. “These results provide the foundation for the principle of locally administered gene therapeutic modalities in the treatment of prostate cancer.”

If prostate cancer is discovered early enough, surgery is often all that’s needed to eliminate the cancer. But when patients are diagnosed after the cancer has spread beyond the prostate, options are limited and survival rates decrease, Belldegrun said.

The difficulty is that early-stage prostate cancer often results in few symptoms, so patients may not know they have the disease until after it has spread. In advanced prostate cancer, symptoms can include trouble having or keeping an erection, blood in the urine, swollen lymph nodes in the groin area and pain in the pelvic area.

Other than skin cancer, prostate cancer is the most common type of cancer found in American men, according to the American Cancer Society. About 198,000 new cases of prostate cancer will be diagnosed in the United States this year. About 31,500 men will die.

Dr. Scott Grundy, director of the Center for Human Nutrition at UT Southwestern Medical Center at Dallas, chaired the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), the executive summary of which is published in today’s Journal of the American Medical Association. Grundy also chaired the NCEP Adult Treatment Panel II, which issued the last cholesterol guidelines in 1993.

"The new guidelines are expected to substantially increase the number of Americans being treated for high cholesterol," said Dr. Claude Lenfant, director of the NHLBI. "If these guidelines are followed, about 65 million adults will be on dietary treatment and about 36 million will be prescribed a cholesterol-lowering drug."

The report includes several important new features:

* A major focus on identifying people who have multiple risk factors for coronary heart disease.

* More aggressive cholesterol-lowering treatment for people at high risk.

* Modifications of low HDL (high-density lipoprotein) and triglyceride classification to better identify people at risk for heart disease.

* New dietary and lifestyle recommendations to enhance both LDL lowering and other risk factors.

* Identification of the metabolic syndrome as an enhancer of risk beyond elevated LDL cholesterol.

The report reaffirms that elevated LDL is a major cause of coronary heart disease and LDL-lowering therapy significantly reduces that risk.

Coronary heart disease (CHD) is the No. 1 killer of Americans, claiming about 500,000 lives yearly. Studies have consistently shown that by lowering LDL levels, risk for coronary heart disease is reduced by as much as 40 percent. Those at highest risk for heart attack include those with heart disease; however, other conditions confer as high a risk for heart attack as having heart disease itself. These conditions include the presence of atherosclerosis in other arteries, diabetes and multiple risk factors. These risk factors include cigarette smoking, hypertension, low HDL, family history, or age (men over 45 or women over 55).

For this reason, the panel recommends that adults 20 and over have their total cholesterol, LDL, HDL and triglyceride levels evaluated once every five years.

Low HDL is now defined as less than 40 milligrams per deciliter; the 1993 report defined low HDL as less than 35 mg/dL. Studies have shown a significant link between low HDL levels and an increased risk of heart disease. A higher HDL level, above 60 mg/dL, is considered a "negative" risk factor and is protective against heart disease.

"The aggressive management and treatment of high blood cholesterol leads to significant improvement," said Grundy.

"ATP III maintains attention on intensive treatment of patients with CHD. But it also adds a new feature. The new focus is on prevention of coronary heart disease in persons with multiple risk factors. Many of these persons are at high risk and deserve more intensive intervention than recommended in ATP II," Grundy said.

In some individuals a change in lifestyle and eating patterns can have a powerful effect on lowering LDL, Grundy said. Today’s report recommends "therapeutic lifestyle changes" (TLC), which have four components: * The TLC diet, which replaces the Step I and Step II diets, reduces intake of saturated fats to less than 7 percent of total calories and dietary cholesterol intake to less than 200 mg per day. * Reducing saturated fats and cholesterol will lower LDL. LDL lowering can be enhanced by consuming 2 grams of either plant stanols or sterols, which are found in certain margarines and salad dressings, and/or 10 to 25 grams of soluble fiber each day. Fruits, oats, barley and legumes contain high concentrations of soluble fiber. "It is possible to double LDL lowering by these latter recommendations." Grundy said. "These new approaches to dietary treatment of LDL represent a major new feature of ATP III."

* Weight reduction. The report defines abdominal obesity as a waist circumference of more than 40 inches in men and more than 35 inches in women. "Overweight and obesity are recognized as major, underlying risk factors for coronary heart disease…weight reduction will enhance LDL lowering and will reduce other risk factors as well," the panel said.

* Increased physical activity, which improves HDL.

A new area of emphasis for the ATP III is the metabolic syndrome, which occurs in one-fourth of Americans. It consists of a constellation of risk factors that include overweight and obesity, high triglycerides (200 mg/dL or greater), low HDL, high blood pressure, high blood glucose and a tendency to form blood clots. The panel identifies these people as candidates for intensified therapeutic lifestyle changes.

"The metabolic syndrome has emerged as being as strong a contributor to early heart disease as cigarette smoking," Grundy said. "In addition, the insulin resistance that goes along with the syndrome is one of the underlying causes of Type II diabetes (non-insulin dependent diabetes mellitus). It’s thus very important to recognize the syndrome and treat it with lifestyle changes."

The ATP III also advises against use of hormone-replacement therapy as an alternative to cholesterol-lowering drugs. Clinical trials have failed to show that the use of estrogen reduces a woman’s risk for heart disease, Grundy said.

The first Adult Treatment Panel report, published in 1988, focused on the prevention of CHD, before any signs of clinical disease. The report identified LDL cholesterol as the primary target of therapy and emphasized clinical management of patients with higher levels of LDL. In the second report, published in 1993, the panel reaffirmed the importance of treating high LDL cholesterol to prevent the development of CHD. It also outlined an intensive plan to manage LDL cholesterol in people who already have heart disease.

"In a perfect world, everyone would have low cholesterol," said panel member Dr. Margo Denke, associate professor of internal medicine at UT Southwestern, an investigator in the Center for Human Nutrition.

"In this third panel, we tried to more carefully define who is most at risk of coronary heart disease," Denke said.

"Reaching the next level of leukemia treatment will require many new approaches that draw upon our expanding knowledge about how healthy cells differentiate during normal growth and development," said Beverly Lange, M.D., director of experimental therapeutics within the Division of Oncology at The Children’s Hospital of Philadelphia, who is an expert in these new attack strategies.

Unlike conventional cancer drugs, the newer drugs are based on detailed knowledge of cellular mechanisms that can be used to manipulate cancer cells in a way that is gentler to surrounding healthy cells.

Oncologists at Children’s Hospital are investigating a number of novel, even unlikely, drugs as highly specific, less toxic weapons against childhood leukemia. For example:

-- A form of vitamin A is being used to reprogram a cancer cell into becoming a harmless, normal white blood cell.

-- Borrowing from its use in traditional Chinese medicine, carefully controlled doses of arsenic can trigger cancer cells to commit suicide by mimicking the normal developmental process of "apoptosis," or programmed cell death.

-- A new type of leukemia drug, the bioengineered compound Glivec, can block the genetic signals that direct cancer cells to grow, while leaving normal cells largely unharmed.

-- The naturally occurring protein interleukin-2 may kick-start the body’s immune system to better fight leukemia.

Taming cancer cells

Some experimental new treatments rely on methods that neutralize or disrupt cancer cells rather than killing them outright in a frontal attack. "Most conventional cancer drugs rely on lysis, in which a direct attack by the drug causes the cancer cell to burst and die," Dr. Lange explained. But cells may also die through indirect methods that target cancer cells while sparing normal cells.

One such method is terminal differentiation, in which a cell enters a mature stage, with a limited lifespan. For example, all-trans-retinoic acid, a form of vitamin A, is used in this way against the diseased blood cells found in acute promyelocytic leukemia (APML). Rather than directly killing the cancer cell, all-trans-retinoic acid forces the cell to differentiate into a mature white blood cell by reprogramming its genetic mechanisms. It redirects the cancer cell into behaving like a normal blood cell rather than an immortal, constantly dividing cancer cell. "At the same time it dooms the cell, because mature white blood cells live for only 12 hours," said Dr. Lange.

Arsenic and cell suicide

When all-trans-retinoic acid does not work against APML, low doses of arsenic may be helpful, using a different cellular mechanism. By targeting a receptor on the surface of the cancer cell, arsenic triggers the process of "apoptosis," or programmed cell death.

This suicide apparatus resides in all cells as a set of proteins that remain dormant until set in motion by molecular signals specific to each type of cell. In early embryonic development, apoptosis sculpts tissues by eliminating unneeded cells. Throughout life, it serves to destroy diseased or nonproductive cells. However, cancer cells may fail to respond to apoptosis signals and become immortal and deadly.

Arsenic can reset the genetic machinery, permitting apoptosis to seal the fate of cancer cells. At the same time, the low dose of arsenic spares healthy cells. Both arsenic and all-trans-retinoic acid are derived from compounds used in traditional Chinese medicines. "Although APML is a relatively rare disease," said Dr. Lange, "these treatments may be useful in other cancers as well."

Blocking cancer signals

News reports over the past year have heralded highly encouraging results from clinical trials of Glivec (STI-571) for adults with chronic myeloid leukemia (CML). Glivec represents a new class of drugs called signal transduction inhibitors that block the signaling pathways that cause cancer cells to grow. It is bioengineered to zero in on a cell receptor present in leukemia cells that carry a genetic defect called the Philadelphia chromosome.

This targeted approach causes minimal side effects to healthy tissue. While CML is rare in children, the same genetic defect found in CML, the Philadelphia chromosome, occurs in an aggressive form of childhood acute lymphoblastic leukemia (ALL).

Directed by Dr. Lange, Children’s Hospital is testing Glivec against that treatment-resistant form of ALL. Through its participation in the Children’s Oncology Group, a collaborative national organization that pools data and expertise from many cooperating cancer centers, Children’s Hospital is currently conducting pediatric trials of the drug. Because studies have suggested Glivec may have wider applications against other types of cancer, Children’s Hospital will test it later this year in children with highly malignant brain tumors.

Boosting immune effects

Also under the umbrella of the Children’s Oncology Group, Dr. Lange is leading tests of interleukin-2 (IL-2), a compound that occurs naturally in the body. IL-2 is an immune system protein that plays an important role in an immune response that occurs after a bone marrow transplant. In the "graft vs. leukemia effect," IL-2 stimulates the body’s natural killer cells to attack leukemia cells and drive the disease into remission.

"This finding should lead to a change in diagnostic testing and treatment," said Dr. Jeffrey A. Towbin, a professor of pediatric cardiology at Baylor. "It could also improve long-term survival."

The discovery, reported in the New England Journal of Medicine, shows why many children suffer heart transplant failure months and even years after surgery, including cardiac rejection and the development of transplant coronary artery disease. The study indicates that frequent biopsies are the best method to identify the virus.

The research team, led by Towbin and Dr. Neil E. Bowles, an assistant professor of pediatric cardiology at Baylor, has been studying for the past decade the reasons for heart transplant failure in children. "It's been the bane of all transplant doctors -- the development of coronary artery disease in transplant patients leads to either sudden death or the need for retransplantation," said Towbin, also associate chief of pediatric cardiology at Texas Children's Hospital and director of the Heart Failure and Transplant Service and Cardiac Research. "Nobody has understood why this happens, but now we know there's a viral connection."

The team studied 553 biopsies from 149 transplant recipients, ages newborn to 18 years old, over a five-year period. The biopsies were evaluated for common viral infections by using a polymerase chain reaction, or PCR, test. All of the biopsies were sent from Loma Linda University Children's Hospital in California.

Results showed that 85 percent of the patients who at some point after transplant tested PCR-positive suffered an adverse event within three months of that result.

"The infection isn't there at transplant, it wasn't there along the way and suddenly it's there," Towbin said. "It's likely to be due to an upper respiratory illness."

In the majority of cases, the infection was late onset, appearing more than two years after transplant, Bowles said. The infections or evidence of rejection did not show up on non-invasive tests.

The findings indicate that the current therapy for transplant rejection should be changed, Towbin said. Now, when the heart shows signs of rejection, indicated by inflammation within the heart, the therapy is anti-inflammatory medications, such as steroids and increased immunosuppresent drugs. After the therapy reduces the inflammation, the patient is sent home with a clean bill of health, he said.

"But, nothing has been done about the virus. It's still sitting there as a low-level illness that over time creates the problem," Towbin said.

Towbin and Bowles said the discovery suggests that all heart transplant patients should be biopsied routinely with PCR evaluation performed each time. They believe these results could lead to new therapies and preventative measures, such as an anti-viral vaccine for use prior to transplant.

"This study suggests that breast-feeding may prevent obesity later in life," says lead author Matthew Gillman, MD, associate professor at Harvard Medical School and Harvard Pilgrim Health Care. "Our study, along with others, supports the recommendation of the American Academy of Pediatrics to breast-feed infants for the first year."

Obesity has risen dramatically among children and adults. Overweight teens tend to have higher blood pressure and cholesterol, lower self esteem, and on average fare less well in school and earn less as young adults. They also are much more likely to grow into obese adults who face serious health consequences, such as heart disease, diabetes and arthritis.

"Once present, obesity is hard to treat," Gillman says. "For these reasons, prevention is paramount."

Gillman and his colleagues analyzed questionnaires filled out by 8,186 girls and 7,155 boys ages 9 to 14 in the Growing Up Today Study. About 5 percent of the girls and 9 percent of the boys were overweight, defined as having a body mass index (weight divided by height squared) greater than 95 percent of children of the same age and sex. That’s slightly lower than found in the general U.S. population.

When the researchers questioned the mothers – all part of the Nurses’ Health Study II – they found that 62 percent of the children were only or mostly fed breast milk for the first six months of life, while 31 percent were only or mostly fed infant formula. Just less than one-half were breast-fed for at least seven months, and about one-third were breast-fed for three months or less. Nationally, less than 30 percent of infants are breast-fed for at least 6 months.

Among the mostly breast fed, about 4 percent of the girls and 7 percent of the boys were overweight compared to the 6 percent of the girls and 11 percent of the boys fed mostly infant formula. Among those who were breast fed for seven months or more, about 4 percent of the girls and 7 percent of the boys were overweight compared to about 6 percent of girls and 12 percent of boys who drank breast milk for three months or less.

The researchers statistically adjusted the results for age, gender, sexual maturity, total calorie intake, physical activity, time watching television, mothers body mass index, and other social, economic and lifestyle factors known to influence weight. In this study, breast-feeding includes women who fed infants breast milk extracted from breast pumps.

The adjusted figures show that infants who were breast-fed more than formula fed or who were breast-fed for longer periods had approximately 20 percent lower risk of being overweight in the preteen and teen years.

The results make biological sense, Gillman says. Breast-feeding could protect against later obesity by providing infants more control over when and how much they consume—when they’re full instead of when a bottle is empty, for example—which could shape future eating behavior. Also, breast milk itself might provide early "metabolic programming," leading to less fat accumulation, for example. Gillman would like to see further studies among more representative samples of the U.S. population.

"Breast milk is already acknowledged as the best food for infants," says William Dietz, division of nutrition and physical activity, Centers of Disease Control and Prevention, in an accompanying editorial. "The increased initiation and duration of breastfeeding may also provide a low-cost, readily available strategy to help prevent childhood and adolescent obesity."

Women who walk regularly are less likely to experience the memory loss and other declines in mental function that can come with aging, according to study author and neurologist Kristine Yaffe, MD, of the University of California, San Francisco.

"This is an important intervention that all of us can do and it could have huge implications in preventing cognitive decline," Yaffe said.

For the study, researchers tested the cognitive abilities of 5,925 women who were 65 and older once and then again six to eight years later. The women who walked the least were most likely to develop cognitive decline -- 24 percent of them had significant declines in their test scores, compared to 17 percent of the most active group. The least active women walked an average of about a half mile per week, while the most active group walked an average of nearly 18 miles per week. Walking included exercise and walking as a part of daily activities.

"But we also found that for every extra mile walked per week there was a 13 percent less chance of cognitive decline," Yaffe said. "So you don't need to be running marathons. The exciting thing is there was a 'dose' relationship which showed that even a little is good but more is better."

Physical activity was measured by the number of blocks walked per week and also by the number of calories used in walking, recreation and stair-climbing.

"The results were almost identical when we measured the total number of calories used," Yaffe said. "Examples of moderate activities that would reduce risk of decline would be playing tennis twice a week or walking a mile per day or playing golf once a week."

Ronald J. Tusa, M.D., Ph.D., professor of Neurology, Emory University School of Medicine, and director of Emory’s Dizziness and Balance Center and Susan J. Herdman, P.T., Ph.D., Emory University School of Medicine, will report at the American Academy of Neurology meeting, in Philadelphia, successful diagnostic procedures and treatment options for BPPV.

BPPV is caused by misplaced calcium carbonate crystals (otoconia) in the semicircular canals (SCC) in the inner ear that have broken free and are found in the fluid of the inner ear. When the head is moved in certain positions, it causes brief periods of vertigo.

"Patients with BPPV usually complain of vertigo in the morning when they get up or turn over in bed," according to Dr. Tusa. "It can also occur when the patient lies down in bed or tilts the head backwards, maybe while taking a shower or sitting in a dentist chair." Patients also complain of poor balance and trouble walking that may last for several hours following an episode of positional vertigo.

BPPV can affect three areas of the SCC, the posterior, the anterior and the horizontal SCCs. The most common is the posterior SCC.

Drs. Tusa and Herdman have studied several ways to diagnose and treat patients with BPPV. "A common test used to confirm the diagnosis of BPPV is the Dix-Hallpike test," says Dr. Herdman. "It involves turning the head to a certain degree while the patient is sitting, then quickly lying the patient back so the head is hanging off the examination table. If the patient has BPPV, the patient should feel a sense of dizziness." Patients can also be tested for BPPV using a sidelying test and a test of balance.

According to Drs. Tusa and Herdman, there are three basic bedside treatments for BPPV, all of which take less than five minutes to administer. They are canalith repositioning treatment (CRT), Liberatory treatment and Brandt-Daroff (BD) treatment.

CRT is used on patients with severe canalithiasis (free-floating otoconia). It is effective in 85-95% of patients with one treatment. Liberatory treatment is effective in dislodging otoconia attached to the cupula (the cover of the semicircular canals). This procedure has a success rate of 53% after one treatment and 76-90% after two treatments. However, this treatment is difficult to perform on elderly patients because of the quickness of the procedure. The BD treatment is a series of repetitive exercises that works by dispersing free-floating otoconia and possibly by dislodging any otoconia attached to the cupula. This is the best treatment for mild canalithiasis, when the patient still has symptoms but no signs of BPPV after a single treatment. BD treatment can also be used in patients with severe BPPV, but it is not the first choice since it causes vertigo and takes up to two weeks for success.

In all of the treatments, patients come to the Dizziness and Balance Center and undergo evaluation, testing and treatment by Drs. Tusa and Herdman. Then, in many cases, the patients learn how to administer the treatment themselves and can perform them at home. There are still more ways to treat other forms of BPPV in the anterior and horizontal SCCs. "Treatment varies according to the SCC involved, whether the otoconia is free-floating or attached to the cupula and the severity of the vertigo," says Dr. Tusa. "We hope our research will be of assistance to a number of people who haven’t been able to find relief from their vertigo elsewhere."

Emory’s Dizziness and Balance Center uses a multidisciplinary approach for diagnosis and treatment. It features physicians and therapists trained in neurology, ophthalmology, otolaryngology, psychiatry and physical therapy. Specialized equipment, including a rotary chair to measure eye movements during head rotation and a dynamic platform posturography to test balance, help provide key information to aid in proper diagnosis.

Dr. Tusa, who holds joint appointments in the Emory Departments of Neurology, Ophthalmology and Otolaryngology, is the founder and former director of the University’s of Miami’s Dizziness and Eye Movement Center. Before that, he spent 13 years at Johns Hopkins University, where he began his research in vision and eye movement. He is the author of two books and numerous chapters and articles for professional journals concerning disorders of the eyes and ears.

"The key to parathyroid hormone’s fracture-thwarting powers is that it stimulates bone formation dramatically—it doubles the normal rate," says Robert Neer, MD, director of the Osteoporosis Center at MGH. Currently available osteoporosis treatments slow bone resorption and bone loss. In contrast to these anti-resorption drugs, parathyroid hormone promotes bone formation. The study showed that after 21 months, the women taking parathyroid hormone had up to 13 percent more bone in their spine than those taking placebo. The average increase in bone for women taking currently available drugs is 9 percent or less, after two to three years of treatment.

The effect can be illustrated by a half-filled glass of water with a hole in the bottom. Current drugs concentrate on slowing the leak, but parathyroid hormone acts by replenishing the water at a greater rate than is lost through the leak.

Neer was principal investigator in the international clinical trial sponsored by Eli Lilly and Company. Working with 99 investigators in 17 countries, the team enrolled 1,637 postmenopausal women with osteoporosis. None of the women were taking other prescription drugs for osteoporosis, and each was placed on one of three regimens: placebo, 20 or 40 micrograms of parathyroid hormone injected subcutaneously each day.

"Parathyroid hormone reduces the percentage of women with osteoporosis who develop a new vertebral fracture by 65 and 69 percent. No other drug has reduced it more than 40 to 50 percent," says Neer. The hormone lowered a woman's risk of developing multiple spinal fractures even more strikingly-by 77 and 86 percent, and it also reduced the risk of nonspine fractures by 35 and 40 percent.

Volunteers were treated for a mean of 18 months. The trial was terminated when a Lilly study in rats revealed that high-doses of parathyroid hormone given for two years caused massive bone overgrowth and bone cancer in the animals. The investigators subsequently undertook extensive reviews and wide consultations, Neer says, and concluded that these high dose toxicology studies do not predict the effects of parathyroid hormone in humans. Humans who have overactive parathyroid glands and, as a result, chronically produce high amounts of parathyroid hormone have not been found to have an increased risk of bone cancer. None of the women in this study or previous studies with parathyroid hormone developed bone cancer. Lilly has resumed studies on the hormone and has requested U.S. Food and Drug Administration (FDA) approval to market it as a treatment for osteoporosis.

Treatment may eventually extend to other people with osteoporosis. "Because parathyroid hormone acts at a very fundamental level to stimulate new bone formation, it has worked on all forms of osteoporosis tested to date, including osteoporosis in men and osteoporosis induced by cortisone-like drugs," Neer says. "And it prevents estrogen-deficiency bone loss in women with normal bones."

While parathyroid hormone reduces osteoporosis-related fractures, it will not, by itself, provide a cure for most patients, says Neer. "To cure osteoporosis, the most logical approach would be to increase bone formation and simultaneously suppress bone destruction. And that will require administering two drugs," Neer says. With the half-filled glass analogy, that would mean replenishing the water in addition to plugging the leak. Neer and others are currently investigating this type of approach with funding from the National Institutes of Health.

The need for an effective fracture-reducing drug has never been greater. In the United States today, 10 million individuals already have osteoporosis. Between $9 billion and $10 billion are spent annually to treat osteoporosis-related fractures. And the numbers will go up as the population ages, says Neer.

The current NEJM study is a continuation of more than 70 years of parathyroid research at MGH and elsewhere. In the 1920s, MGH researchers discovered that parathyroid hormone not only regulated calcium levels in the blood, but also increased bone density in animals. By the 1970’s, MGH researchers were the first to determine the chemical structure of human parathyroid hormone, which then enabled them to synthesize it for the first time. In a series of clinical studies reported in the 1980’s, Neer and his colleagues first showed that daily doses of the hormone significantly increased bone density in women and men.

The long-range Swedish study of persons 75-years-old and older found that more than half (46 out of 78) of those diagnosed with dementia had both low levels of vitamin B12 or folate and Alzheimer's type dementia.

Study authors theorized that vitamin B12 or folate deficiencies affect Alzheimer's disease by influencing neurotransmitters or the levels of the amino acid homocysteine in the body. Either vitamin B12 or folate deficiency can increase homocysteine levels. Homocysteine has a neurotoxic effect that could lead to cell death or neurological conditions such as Alzheimer's disease.

"In our study, we found that low levels of either of these two vitamins were related to an increased Alzheimer's disease risk," said study co-author Hui-Xin Wang. "Monitoring B12 and folate levels is important in order to avoid unfavorable conditions, even for those elderly people who are quite healthy in terms of cognition."

For more than thirty years, researchers have observed low vitamin B12 and folate levels in elderly people, according to Wang. It had also been previously theorized that this vitamin deficiency might be tied to neurological or psychiatric disorders. This study breaks new ground by connecting these deficiencies with Alzheimer's disease.

Vitamins B12 and folate (a form of water-soluble vitamin B) are found in common foods. Vitamin B12 is naturally found in animal foods including fish, milk and milk products, eggs, meat, and poultry. Leafy greens such as spinach and turnip greens, dry beans and peas, fortified cereals and grain products, and some fruits and vegetables are rich food sources of folate.

Study data were pulled from a population-based longitudinal study in Sweden called the Kungsholmen Project. A random sample of 370 non-demented persons, age 75 and older, and not treated with B12 or folate dietary supplements, was followed for three years to detect cases of Alzheimer's disease. Within the timeframe of the study, 78 people developed some form of dementia.

The American Academy of Neurology, an association of more than 17,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research.

"It’s very exciting to be able to repair hearts in a much less invasive way than in the past," Dr. Block says.

Constructed of a biocompatible metal alloy known as MP35n and covered with a polyester fabric, CardioSEAL® is a small umbrella shaped object with four independent arms that radiate outwards from a connection in the center. Spring coils along the arms allow the device to be collapsed as it is carried on a catheter to the heart, guided through the femoral vein by an Emory cardiologist using echocardiographic imaging.

When the device reaches the site of the cardiac hole, the springs allow it to be opened and the slight tension the springs create holds it in place. In less than a month, tissue grows into the fabric and the implant becomes, literally, a part of the heart.

CardioSEAL® is FDA approved to close three kinds of cardiac holes -- Patent Foramen Ovales (PFOs), Ventricular Septal Defects (VSDs) and Fenestrated Fontans (FF s). PFOs are holes in the heart needed before birth to transfer oxygenated blood from the umbilical cord to the unborn child; if a PFO remains open after birth, it creates a pathway for blood clots. VSDs are abnormal openings between the heart’s chambers that can lead to heart failure. An FF defect results from the Fontan procedure which corrects congenital cardiac defects in people born with three chambered hearts but creates a fenestration, or window-like hole, that eventually must be closed.

The CardioSEAL® procedure takes place in the Emory University Hospital cardiac catheterization lab with patients placed under either or general or local anesthesia. Most can go home the next morning. The risks associated with the procedure are, for the most part, similar to those associated with other heart catheterization procedures, according to Dr. Block.

Scientists at the University of Pennsylvania School of Medicine and the Department of Veterans Affairs Medical Center in Philadelphia believe the results of a recent study show that the medication propranolol may provide a bridge for cocaine-dependent patients struggling to get past the first critical weeks of recovery and stay in treatment.

The results of the propranolol study is published in "Drug and Alcohol Dependence," a peer-reviewed journal.

“The drop out rate in cocaine treatment programs is very high,” said Penn’s Kyle Kampman, M.D., the study’s lead researcher. “We found that when patients who experienced severe withdrawal symptoms were given propranolol, they tended to stay in treatment longer and use less cocaine.”

Propranolol works to block the anxiety-producing effects of adrenaline. Those suffering severe withdrawal symptoms are often more sensitive to adrenaline, which can heighten anxiety in stressful situations and undermine treatment, Kampman said.

The findings emerged in an eight-week, double blind, placebo-controlled trial in which propranolol was administered to 108 people addicted to cocaine. Participants in the study, conducted in the fall of 1999, received counseling twice weekly along with regular doses of propranolol or a placebo. Scientists concluded that subjects with more severe cocaine withdrawal symptoms responded better to propranolol in comparison to those given the placebo.

“The patients who come in with severe withdrawal symptoms generally are heavier users and are tougher to treat,” said Kampman. “We know from previous studies that they are more likely to drop out of treatment programs and are unable to detoxify. Propranolol may be one way to keep them in treatment longer.”

The propranolol investigation was funded through a grant from the National Institute on Drug Abuse (NIDA).

The study echoes an earlier investigation led by Kampman into amantadine, a medication used to treat Parkinson’s disease. In that study, researchers found that the medication may reduce cocaine cravings in patients experiencing significant withdrawal symptoms.

In the amantadine study, conducted in 1994, 61 cocaine dependent outpatients participated in a four-week, double blind, placebo controlled study in which participants received 100 mg of the medication three times daily. Results indicated that the craving for cocaine in those patients who suffered the most intense withdrawal symptoms diminished when amantadine was administered.

Amantadine is thought to raise dopamine levels in the brain, reducing the craving for cocaine. The results of the investigation into amantadine were reported in the American Journal of Psychiatry in December 2000. The study was peer-reviewed and supported through a NIDA grant.

"This study has tremendous implications," said Robert H. DuRant, professor and vice chair of pediatrics at Wake Forest and an author of the study. "It shows that exposure to this type of violence on television during this crucial period of time when a teen's cognitive, social and physical development is still being cemented, probably affects adolescents in a negative way."

Adolescents who watch wrestling on TV are exposed to a high frequency of violence between men and women, alcohol use and hearing women referred to in derogatory terms such as "bitch," according to the study. In addition, the scenarios played out in the TV dramas often present violence as a solution to a problem.

"The level of vulgar language, verbal abuse and physical abuse modeled, with unrealistic outcomes, is astonishing," DuRant said. "For example, during one wrestling match a man dangled a woman upside down and then dropped her on her head, knocking her unconscious. In reality, I know this act would have broken her neck and probably would have killed her. In addition, the announcer of the program, speculating on what the wrestler was going to do with the woman, stated that she 'deserved it' because she had cheated on this wrestler earlier. This teaches an adolescent that it is OK to use violence to resolve conflicts and that women deserve abusive treatment."

This study is in agreement with multiple previous studies by DuRant that have found that exposure to violence is the strongest correlate with the use of violence and weapon carrying among adolescents. In this study, researchers asked a random sample of 2,228 North Carolina high school students, how many times they had watched wrestling on TV in the past two weeks. Among males, 35.1 percent had watched wrestling and 24.6 percent had watched it 6 or more times during the previous two weeks. Among females, 35.1 percent had watched wrestling and 9.1 percent had watched it 6 or more times.

Watching wrestling by males was associated with having started a fight with a date, been a date fight victim, gun carrying, other weapon carrying, fighting, spit tobacco use, non-prescription Ritalin use and driving after drinking. Alcohol or drug use during the last fight by the date or by the student was associated with watching wrestling more frequently, according to the study.

Of significance is that the relationships between watching wrestling and health risk behaviors were stronger among females than among males, DuRant said.

Watching wrestling by females was associated with having started a date fight, been a date fight victim, gun carrying, carrying a gun at school, other weapon carrying at school, fighting, fighting at school, being injured in a fight, alcohol use, alcohol use at school, marijuana use, Ritalin use and riding with a drinking driver. Also, alcohol or drug use by the female student or her date was associated with viewing wrestling more frequently.

"The bottom line is that we are affected by what we expose ourselves to," DuRant said. "This study shows that the incidence of date fighting and other violence increases when the exposure to violence increases. Now, wrestling doesn't in itself cause violence, but when combined with overall socialization, violence on television can affect what is perceived as socially acceptable behavior." Of the 2,228 students who participated in the study, 51.4 percent were female and 38.3 percent were of minority ethnicity.

The study led by a pediatrician and medical geneticist at the University of North Carolina at Chapel Hill, found such disorders accounting for more than two-thirds of all children admitted to a large full-service pediatric hospital over a one-year period.

Moreover, regardless of reason for admission, children whose underlying disorder had a strong genetic basis tended to be hospitalized longer, charges for their care accounting for 80% of total costs.

The new findings and their potential implications were presented at the 2001 Pediatric Academic Societies and American Academy of Pediatrics joint meeting in Baltimore, Maryland.

"We consider this study a first step in quantifying the enormous impact of genetic factors on inpatient pediatrics and the health care system," said Shawn E. McCandless, MD, assistant professor of Pediatrics in the Division of Biochemical Genetics and Metabolism at UNC-CH School of Medicine.

"This clearly emphasizes that we the need to train a medical workforce that understands genetic issues, that's able to utilize new genetic information to deliver better patient care and that is able to accurately and appropriately inform patients of the genetic aspects of their disorders."

The medical geneticist notes that a survey of pediatric inpatient admissions in 1973 found a possible genetic basis in just over half, and a clear-cut genetic basis in only 4.5%. "We sought to update this important study in light of current hospitalization practices and new knowledge about genetics," McCandless explained.

The new study surveyed a computerized database of 5747 consecutive admissions, representing 4224 individuals, some with multiple admissions. All had been admitted in 1996 to Rainbow Babies and Children's Hospital in Cleveland, Ohio. McCandless, then a postdoctoral fellow at Case Western Reserve University, conducted his research with Jeanne W. Brunger, MA, now at North Shore University Hospital, Manhasset, NY, and pediatrician Suzanne B. Cassidy, MD, currently at the University of California Irvine.

The researchers included all patients aged 18 years and under, newborns excluded. Patients were divided into one of four groups based on the presence and cause of an underlying chronic medical condition.

I - underlying condition with a clear genetic cause (cystic fibrosis, sickle cell disease, chromosomal rearrangements); II - underlying condition with strong genetic predisposition (asthma, juvenile diabetes, childhood cancers); III - underlying condition with no recognized genetic component (disability due to near drowning, head injury); IV - no underlying condition.

"We found that 35% fell into category I, 36.5% into category II, and slightly less than a third fell into the last two categories, 1.3% and 27.2%, respectively," McCandless said. "So 71.5% of patients admitted to hospital had an underlying disorder with a significant genetic component."

When the study team looked at the charges for care, they found total charges of over $62 million, of which disorders with a genetic basis (groups I and II) accounted for $50 million. And of that $50 million, 63% (more than $31 million) was charged to patients in group I.

In addition, length of hospital stay for children of group I was 40% longer than that for children in group IV. "And there is some evidence that the severity of illness was greater for children with genetic diseases than those having no genetic disorder," McCandless added.

The Carolina researcher points out that "in most instances" the underlying disorder was the primary cause for the admission or was the reason for it.

"We saw very few children who were admitted with simple problems like broken arms or pneumonia. Most individuals that were admitted with simple problems required hospitalization because of an underlying disability that complicated the care," McCandless said.

"There were patients with respiratory illness who, absent an underlying genetic disease, would not have been admitted to the hospital. But because of their underlying asthma or their underlying chest deformity from their genetic disorder, they were not able to cope with the infection as well as children without the underlying disorder."

McCandless noted that the scope of future studies needs broadening.

"A study like this really is the first step. While each individual genetic disease is uncommon, as a group they are not rare. This study demonstrates that genetically determined disorders are a factor in most admissions to a children's hospital. The next step is to broaden the outlook and study larger pediatric populations and to extend this research to adult inpatient and outpatient units.

Death from anthrax is due to the toxin produced by the bacteria. In its airborne form, just a teaspoonful of anthrax could wipe out hundreds of people. Though rarely a natural threat to humans, anthrax is especially dangerous as a potential weapon in terrorism and biological warfare.

Though a vaccine exists, most people have no vaccine-induced immunity to anthrax because the rarity of infection makes a mass vaccination program impractical. Yet current therapies demand that any unvaccinated person exposed to the bug receive antibiotic therapy before symptoms occur. Otherwise, the victim with systemic anthrax dies rapidly. The discovery by R. John Collier and colleagues may offer a better way to fight back before or after infection.

The researchers tested whether they could prevent infection using forms of the anthrax bacterium with a mutation in a toxin subunit dubbed "protective antigen." When protective-antigen mutants were injected together with a normally lethal mix of toxin, rats did not develop any symptoms of poisoning. The protective-antigen variants "totally protected the animals, whereas the control animals became moribund within 90 minutes," says Collier, the Maude and Lillian Presley Professor of Microbiology and Molecular Genetics at the Medical School. "We’re most encouraged about the experiments in rats. The results are remarkable."

The protective-antigen mutants are good candidates for an anthrax therapy because the normal form of protective antigen in and of itself is already known to be safe in humans: it is the major component of the current anthrax vaccine, the use that gave the subunit its name.

The mutant protective-antigen molecules can elicit an immune response in rats equivalent to that produced by normal protective antigen. In the future, mutant protective antigen may fill the bill as both an anthrax vaccine and treatment, negating the need for two separate pharmaceuticals.

The anthrax bacterium normally secretes three toxin components into the bloodstream: protective antigen, lethal factor, and edema factor. These assemble into the toxin on the outside surface of human cell membranes. In order for symptoms to develop, lethal factor and edema factor must move to the cell interior.

Normally, seven protective-antigen molecules form a doughnut-shaped channel that enables lethal factor and edema factor to cross the usually impenetrable cell membrane and enter the cytoplasm. There, they disrupt normal cell function. The protective-antigen mutants identified by Collier and colleagues most likely act by blocking the formation of a normal protective-antigen channel.

The presence of just one mutant protective-antigen molecule in an otherwise normal channel may be potent enough to disrupt the entire channel. A mutant protective antigen, therefore, can block the toxic effects of anthrax even when it is outnumbered by normal protective antigen molecules. The three most potent protective-antigen variants that Collier identified fully prevented development of symptoms when present in a one-to-four ratio with normal protective antigen.

To wield their tools of destruction, certain other disease-causing bacteria, such as Staphylococcus, also require the formation of doughnut-like structures similar to the protective-antigen channel. Therefore, "it may be possible to generalize this approach to other diseases" Collier says.

One challenge to developing this approach as a therapy is devising a strategy to determine efficacy in humans. The researchers are now determining whether more potent protective-antigen mutants can be made. Future efficacy studies using a mouse model of anthrax infection will be performed at U.S. Army laboratories in Maryland.

Activated Protein C, or APC, helps snuff out a crucial step in the chain of events that can lead to the death of neurons. While brain damage from stroke initially begins with a lack of blood flow to the brain, the damage is increased by a cascade of reactions, including overzealous attempts by the body’s own immune system to “fix” the damage. White blood cells are recruited to the stroke site by chemical messengers and try to clean up the damage – but the response often magnifies the injury and can cause a patient’s condition to worsen. It’s a bit like an over-enthusiastic security guard inadvertently roughing up legitimate guests during an effort at crowd control.

In a study in the journal Circulation, scientists report on work in mice which shows that APC can stem the flood of harmful white blood cells into the brain, one key to reducing the effects of stroke. Strokes are the leading cause of long-term disability in the United States, where there are about 4 million stroke survivors.

“The damage from a stroke doesn’t happen just because the brain is deprived of oxygen and other nutrients; it’s partly a result of the body’s response,” says lead author Berislav Zlokovic, M.D., Ph.D., of the University of Rochester Medical Center. “The influx of white blood cells into the brain causes tremendous damage. The role of inflammation in inflicting damage to the brain is only recently becoming appreciated.”

Zlokovic did the work in collaboration with John Griffin and Jose Fernandez of Scripps Research Institute in La Jolla, Calif., and Masayoshi Shibata, S. Ram Kumar, Arun Amar, and Florence Hofman of the University of Southern California.

For more than a decade Griffin and Zlokovic have studied APC together and have discovered how the compound helps prevent blood clots. Some researchers believe that people who have low levels of APC, a natural compound made by the body that helps prevent blood clots, are more likely to suffer a stroke. Eli Lilly is developing a genetically engineered version of APC for use against sepsis, an often-fatal blood disorder; a study published March 8 in the New England Journal of Medicine showed that APC reduced by 20 percent the rate of death in sepsis patients.

In research sponsored by the National Heart, Lung, and Blood Institute, Zlokovic’s team found that in mice that had strokes, animals that were given APC were much more likely to survive than their counterparts that did not receive APC. The animals showed a number of benefits: their brains had more blood flow and less swelling, their blood was less likely to clot, a smaller portion of the brain was affected by the stroke, and their brains contained only negligible levels of white blood cells known as neutrophils. It’s this last feature that grabbed the team’s attention.

Normally the brain is off limits to extra white blood cells, because the blood/brain barrier keeps toxins and other damaging materials out. Though the cells circulate in the blood that flows through the brain, the blood vessels fail to put out adhesion molecules – the brain’s version of a welcome mat – for the cells to latch onto. Without the adhesion molecules, known as ICAM-1 molecules, white blood cells flow right by.

“These white blood cells normally roll along inside the blood vessel, temporarily attaching and then detaching from the vessel walls and moving along with the blood flow,” Griffin says. “But if there’s damage or inflammation, the white blood cells stick tightly to the wall instead of rolling along. Then if the cells receive certain signals, they start slinking through the vessel wall and into the surrounding tissue.”

Those signals come in the form of the adhesion molecules, which act like tiny docking ports. In times of brain damage or stress the molecules suddenly become available, oftentimes within just 15 or 30 minutes of a stroke. These enable white blood cells like neutrophils to gain a foothold in a blood vessel and then migrate into brain tissue

The scientists found that APC suppresses the ICAM-1 adhesion molecules, preventing white blood cells from entering the brain. In the study in Circulation, APC-treated mice had 90 percent fewer white blood cells than their counterparts in the brain tissue surrounding the initial site of stroke.

“Once white blood cells are able to adhere to blood vessel walls, they have an open path to the brain. White blood cells neutralize pathogens, but in the process, they often damage healthy tissue as well. We’re trying to restrict this reaction,” says Zlokovic, chief of the Division of Neurovascular Biology at the University of Rochester’s Center for Aging and Developmental Biology. “APC helps to keep white blood cells under control.”

The APC project is part of a wider research effort by Zlokovic, a neurosurgeon who specializes in studying the role of blood vessels in neurodegenerative disorders like Alzheimer’s disease and stroke. Last year he showed that blood circulation in the brain plays a key role in the prevention of beta amyloid plaques that speckle the brains of Alzheimer’s patients. He and Griffin are continuing their studies to see whether APC might someday become a stroke treatment.

“From the time that blood flow stops to the time that brain cells die, there is a series of complex reactions. Understanding those reactions, which involve inflammation, apoptosis, and other processes, is a very hot topic in research,” says Griffin, professor of molecular and experimental medicine at Scripps Research Institute.

The work points toward a method to short-circuit epileptic seizures and convulsions before they strike, through the use of implantable brain devices and medications, according to Brian Litt, MD, author of the study. It appears April 26 in the journal Neuron.

"This study is part of a large collaborative effort to control symptoms of a condition that dominates the lives of otherwise healthy individuals by its dramatic unpredictability," Litt said. “The potential to use our findings to help people with poorly controlled seizures world-wide is enormous.”

About 50 million people throughout the world suffer from epilepsy. Almost 25 percent have seizures that are not controlled by any available therapy.

Although epilepsy is the most common neurologic disease after stroke, its cause cannot be identified in a large percentage of cases. Recently, scientists looking for changes in the brain that predict seizures have had some success using mathematically-based chaos theory. But those studies have generally been limited in scope -- they concentrate on a period of minutes prior to seizures -- and are further limited by the difficulty of applying an abstract theory to what actually happens inside the brain.

Litt and his colleagues, on the other hand, relied on the traditional method of measuring brain activity through EEG (electroencephalograpy) readings for five epilepsy patients who were being evaluated for surgery and had therefore stopped taking anti-seizure medication. The EEG readings tracked the patients for periods ranging from four to 14 days.

Using electrodes implanted in both sides of the brain, the scientists examined "a continuous stream of data for reproducible patterns associated with seizures, and found a chain of events that predicted that seizures were going to occur," Litt said.

The researchers discovered cycles of abnormal brain activity -- epileptic discharges -- lasting 15 to 30 minutes. The discharges became more frequent over a period of hours as they led to brief, asymptomatic seizures at specific points in the brain.

Those smaller seizures triggered a steady increase in activity that spread across the brain and culminated in clinical seizures. Litt likened this cascade of events to a match striking over and over, lighting and re-lighting a fuse in the affected part of the brain. The fuse goes out and re-ignites more and more frequently, until finally it ignites the energy that leads to clinical seizures. In some of the study patients, the process lasted up to seven hours.

"This information provides a real opportunity to stop abnormal activity in epileptic brain regions before seizures develop," Litt said. Although substantial work remains before the study findings can be put to clinical use, he believes scientists may eventually be able to implant devices in the brain that will abort seizures by reacting to, and diffusing, the cycle of increasing abnormal brain activity.

Litt collaborated in the study with Rosanna Esteller; Javier Echauz, PhD; Maryann D'Alessandro; Rachel Shor; and George Vachtsevanos, PhD, all of the Georgia Institute of Technology, along with Thomas Henry, MD; Page Pennell, MD; Roy Bakay, MD, and Charles Epstein, MD, of Emory University. Marc Dichter, MD, PhD, of Penn also collaborated in the study.

The investigators examined and compared archived neonatal blood samples from children, born in four northern California counties from 1983 to 1985, who later developed autism, mental retardation, cerebral palsy, or developed normally. The investigators measured concentrations of several neural growth factors and found that the growth factors were significantly elevated in the neonatal blood of children who later developed autism or mental retardation, but not in the blood from children who developed cerebral palsy or blood from the normal controls.

“Finding that major regulators of brain development were different in children with autism from normal controls in the first days of life opens an exciting new avenue of research,” says Karin B. Nelson, M.D., Senior Investigator in the Neuroepidemiology Branch of the NINDS. “We think this work will be a step to better understanding the biologic basis of autism and hope it will lead to better ways to treat and perhaps prevent autism.”

“We have these promising new results because the California Department of Health Services had the foresight many years ago to save specimens from the newborn screening program,” added study co-author, Judith K. Grether, Ph.D., of the California Department of Health Services. “This archive of newborn blood specimens is an incredible treasure, providing a tremendously valuable resource for scientific study of a wide range of developmental disabilities and birth defects.”

Neural growth factors are important to the formation of the central nervous system during embryonic development. Previous research shows that many of these growth factors play a vital role in the production of new brain cells and the organization of those cells into distinct networks. The investigators hypothesize that an abnormal abundance of these proteins may disrupt the normal process of cell migration, differentiation, and programmed death during early nervous system development. Animal studies have shown that an early shortage of one of these proteins leads to microcephaly and other developmental problems.

The investigators speculate that a breakdown in the regulation of factors that influence early brain development is important in autism and mental retardation. Since these disorders cannot be clinically diagnosed until later in childhood, the identification of molecular markers could be helpful in the early diagnosis of the disorders and in the design of future clinical studies to test therapies. The researchers plan to continue their work to further elucidate the biological and genetic mechanisms that underlie the development of autism and other developmental disorders.

Autism is a pervasive developmental disorder that affects approximately 10 to 20 people in every 10,000 and affects males about four times more frequently than females. Symptoms of autism may surface in children around the age of 2. People with classical autism show three types of symptoms: impaired social interaction, problems with verbal and nonverbal communication, and unusual or severely limited activities and interests. People with autism may also show abnormal responses to sensory stimuli, such as touch, sounds, and sights. Twin studies suggest that autism has a strong genetic component.

Mental retardation is a term that is applied to people who show significantly delayed or impaired mental, intellectual, and social development. People with mental retardation generally score below 70 points on an intelligence quotient (IQ) test and have trouble adapting to complex social situations.

Cerebral palsy is a term used to describe a group of chronic disorders caused by faulty early development of or damage to motor areas in the brain. Symptoms of cerebral palsy include difficulties with control of limb movement. Some people with cerebral palsy may also have mental impairment.

(1) Nelson, K. B.; Grether, J. K.; Croen, L. A.; Dambrosia, J. M.; Dickens, B. F.; Jelliffe, L. L.; Hansen, R. L.; Phillips, T. M. “Neuropeptides and Neurotrophins in Neonatal Blood of Children with Autism or Mental Retardation.” Annals of Neurology, May 2001, Vol. 49(5), 597-606.

Weary and her colleagues asked 194 college students to watch videotapes of an 11-year-old boy performing moderately difficult tasks from an intelligence test. The task involved arranging pieces of a puzzle. The subjects were then asked to rate the boy's performance on the task and his overall intelligence.

Subjects in the study were also given a test to measure their overall tendencies towards pessimism or optimism.

The results showed that pessimists judged the boy as less intelligent than did optimists under one condition: if they were asked to memorize an eight-digit number before watching the videotape - a number they would have to recall after the viewing.

However, pessimists and optimists gave the boy similar intelligence ratings if they were not given any number to memorize.

Weary said that when pessimists were asked to memorize the number, their minds were busy when watching the videotape. The result is that their natural tendencies toward pessimism unconsciously altered their perceptions of how well the boy performed on the intelligence test. This, in turn, affected how they rated the boy's intelligence.

However, those who didn't have to memorize the number could focus solely on watching the boy's performance and compensate for their natural negativity.

"Our results suggest pessimists know they are more negative than others and try to eliminate that bias if they have the mental resources," Weary said. "When they watch the videotape, they expect a bad performance. When that doesn't happen, they are surprised - and that causes them to adjust their judgment to be more fair."

This finding contradicts some theories that suggest people don't alter their initial impressions of a person's behavior.

"We believe people can actually correct for their own biases," she said. "People can reconsider what they observed and recode it in their memory. Pessimists may begin watching the videotape with the expectation that the boy is not going to do well. But if they have the metal resources, they can change that initial impression and decide the boy did well on the test."

Weary said the results have many real-world applications. "If you work in a high-stress, fast-paced office, it may be difficult to get a fair evaluation if your supervisor tends to be pessimistic and depressed," she said.

Even if your supervisor is not a pessimist, Weary added, you still might be at risk for an overly harsh evaluation. One not-so-favorable piece of information about your work could become the basis for a negative evaluation if your supervisor doesn't have time to think about other aspects of your job performance.

"In such a setting, a supervisor may have a hard time correcting his or her unconscious negativity when evaluating employees' performances," she said. "The social and economic costs for employees of such judgments may well be very real and very significant."

The best advice is to make sure your supervisor is not distracted or hurried when he or she is evaluating your work, she said.

Commonly referred to as the silent killer, uncontrolled hypertension prematurely ages arteries and can lead to stroke, heart attack and kidney failure. Only 27 percent of the nearly 50 million Americans who have hypertension keep it under control (blood pressure less than 140/90). The blood pressure control rate at the latest follow-up in the Mayo Clinic study was 75 percent.

The study examined the use of rapid medication dosage adjustments at Mayo Clinic’s Short-term Hypertension Care Clinic, a nurse-managed, physician-supervised treatment clinic. Each year over 7,500 patients are referred to trained nurses with specialized expertise at the clinic after physician evaluation. Most are seen two-to-three times a day by a nurse over three-to-four days before they return home to their doctor’s care. The study used semiautomatic home blood pressure measurements of 60 of those patients over 12 months of follow-up to see whether the favorable results achieved at the clinic continued over the long term.

"Many patients travel to Mayo Clinic from a great distance to be treated for other medical conditions, and in the course of their examination hypertension is discovered so they are referred to us," says Vincent Canzanello, M.D., a Mayo Clinic hypertension specialist and author of the study.

"This short-term clinic was developed in the 1980s to help get patients’ hypertension under control within a week, since we knew it would be impractical for them to return for medication adjustments over a period of months."

Conventional hypertension treatment typically involves monthly blood pressure checks followed by medication adjustments. The Mayo Clinic approach involves an initial consultation with a physician, who prepares the drug treatment plan and reviews it with the nurse who implements it. Patients then see the nurse several times over three or four days, and the nurse adjusts drug dosages as needed to bring blood pressure under control.

In the first study, researchers found that the threat of lay-offs can put workers at risk for workplace injuries and accidents. In this study of 237 food-processing plant employees, employees who feared they might be laid off showed decreased safety motivation and compliance, which are related to higher levels of workplace injuries and accidents.

Psychologist Tahira M. Probst, Ph.D., and Ty L. Brubaker, B.S., of Washington State University Vancouver, surveyed workers at two plants of a large U.S. food processing company which had recently undergone major organizational changes affecting the job security of the company's employees. In the first plant, an entire shift of workers was laid off in preparation for what was rumored to be the eventual shut down of the entire plant. At the other plant, the swing shift was being eliminated in favor of a night shift. Those employees who could not work the night shift, like single-parent employees with no day-care alternatives, were expected to lose their jobs. Employees at both plants were asked to take part in the study at two time periods, immediately after the shift changes were announced, and six months following the organizational restructuring.

The researchers found that those employees who were worried about losing their jobs showed less safety motivation and compliance on the job, which in turn were related to higher levels of workplace injuries and accidents. For the plant workers, that meant an increase in wrist, hand and arm injuries, the most common type of injury associated with food processing plants.

It is possible, the authors explained, that employees who have to juggle competing job demands of production, quality and safety may feel pressured to cut safety corners to keep their production numbers up, especially if they fear losing their job and are not actively rewarded for safe behavior.

"These results suggest that organizations not only need to consider the effects that employee job insecurity has on the job satisfaction, health and turnover intentions of employees, but also need to consider the possibility that job insecurity can have potentially dangerous implications for employee safety attitudes and behaviors," said the authors.

In the second study, 2,048 workers from across the country were questioned about the impact of their job on their physical and mental health. Researchers Susan L. Ettner, Ph.D., of the University of California, Los Angeles and Joseph G. Grzywacz, Ph.D., of the University of Northern Iowa found that serious on-going work stress and job pressure or working long hours and more shift work resulted in more negative reported effects of work on physical and mental health.

Specifically, those who worked nights or more than 45 hours per week (compared with 35 - 45 hours per week) were more likely to report that their job undermines their health. Individual personality characteristics also were related to workers' perceptions of how their jobs affect their health. Those workers with higher levels of neuroticism (emotionally unstable traits such as anxiousness, nervousness and sadness) and a lower level of extraversion were more likely to believe their job had a negative affect on their health.

In the two-part study, Japanese researchers also found that oxidized LDL was higher in the plaques of individuals with unstable angina than those with stable angina. Oxidized LDL (ox-LDL) is a form of LDL that has combined with oxygen. It is considered more dangerous than LDL because it promotes clogging of blood vessels. Stable angina is chest pain that occurs during exertion. People with unstable angina experience chest pain even while at rest.

"It is accepted that inflammation within the plaque plays a key role in destabilizing the lesions, which leads to coronary events such as heart attacks. Our findings not only support this concept, but suggest a pivotal role of oxidized LDL in this process." says study author Makiko Ueda, M.D., professor of pathology, Osaka City University Medical School in Japan.

The first part of the study included 135 patients who had various signs and symptoms of heart attack or angina. There were 45 patients with heart attack, 45 patients with unstable angina, 45 patients with stable angina, and a control group. The patients with heart attack were studied within 24 hours of the onset of chest pain. Blood samples were taken from all patients when they were admitted to the hospital.

Researchers found that average levels of ox-LDL in patients who had a heart attack were 1.95 nanograms (ng) per 5 micrograms of LDL protein, compared to 1.19 ng/5 micrograms LDL for those with unstable angina, 0.89 ng/5 micrograms LDL for stable angina and 0.58 ng/5 micrograms LDL for controls. The more serious the condition, the higher the oxidized LDL. The researchers say this observation strongly suggests that the amount of oxidized LDL in circulating plasma could serve as a marker for cardiovascular events.

Levels of ox-LDL were measured using a "sandwich ELISA" test in which LDL is separated from other lipids in the blood plasma. The LDL is then combined with an anti-oxidized LDL monoclonal antibody, which isolates oxidized LDL. A second monoclonal antibody, called anti-apolipoprotein B antibody, is used to detect additional oxidized LDL particles in the plasma. The technique is able to identify tiny amounts of LDL particles and is superior to other methods in obtaining a sensitive and accurate measurement of ox-LDL.

For the second part of the study, researchers analyzed sections of coronary arteries from 10 individuals with stable and 23 with unstable angina. The sections were taken directly from the area believed to have caused the blockage responsible for the chest pain. They gave the samples a score according to ox-LDL levels at that site. They found that individuals with unstable angina had an average ox-LDL score of 0.49 and those with stable angina had an average score of 0.07.

"Our study of atherectomy specimens clearly demonstrates that oxidized LDL is higher in the arterial plaque of patients with unstable angina compared to those with stable angina," says Ueda.

Sotirios Tsimikas, M.D., assistant professor of medicine, division of cardiology, University of California at San Diego, says this research is unique because it looks at different groups of patients using the same LDL measurements.

"The levels of oxidized LDL circulating in the blood correlate well with the severity of disease," says Tsimikas. "The sicker the patient, the higher the levels of circulating oxidized LDL, indicating that it is a marker of atherosclerotic plaques."

Atherosclerosis is a narrowing of the arteries caused by plaques on the inner lining. The plaques consist of LDL, decaying muscle cells, fibrous tissue, clumps of blood platelets and cholesterol.

When plaques are disrupted or rupture, the oxidation process is activated and is reflected in circulating LDL.

"This study addresses the controversy surrounding the protective effect of hormonal and barrier methods of contraception against PID in women," says Principal Investigator Roberta Ness, M.D., M.P.H., associate professor of epidemiology, medicine and obstetrics/gynecology. "The risk of upper genital tract infection was not reduced by any contraceptive method among women in this study. In fact, inconsistent condom use actually increased the risk of infection in this group of women."

PID is a common condition in which microorganisms spread from the lower genital tract to infect and inflame the upper genital tract, including the endometrium, fallopian tubes, ovaries and peritoneum. Women with PID have elevated rates of infertility, ectopic pregnancy and chronic pelvic pain.

Previous studies testing the ability of various contraceptive methods to protect against PID showed inconsistent results, perhaps due to the inclusion of women both with and without symptoms, and the use of older, higher-dose oral contraceptives in the studies.

The University of Pittsburgh-led study looked at contraceptive use among 563 women who had signs and symptoms of PID and who were enrolled in the PID Evaluation and Clinical Health (PEACH) Study, a randomized clinical treatment trial. Participants were between the ages of 14 and 37 and were recruited from emergency departments, clinics and STD units at each of 13 clinical sites. Each participant was interviewed and examined, and each received an endometrial biopsy and upper genital tract isolate microbiologic evaluation. According to the women, condoms were the most common method of contraception they used, followed by oral contraceptives, contraceptive injections and other barrier methods.

Inconsistent use of condoms was associated with an increased risk of upper genital tract infection (UGTI). Specifically, condom use in less than 100 percent of sexual encounters was associated with a more than two-fold increase in risk. However, UGTI rates were unaffected by use of medroxyprogesterone or oral contraceptives. Endometritis (inflammation of the uterine lining) alone, without UGTI, appears to be related to use of contraceptive injections among women with PID symptoms.

While no method offered protection against UGTI, the analysis showed that consistent condom use, when compared with no contraception use at all, led to a slightly reduced risk of both UGTI and endometritis without UGTI. Also, while oral contraceptives were not associated with a decreased risk of further infection, they were related to decreased severity of PID symptoms.

"Based on our findings in the PEACH study, hormonal and barrier contraceptives appear to play no role in reducing the risk of upper genital tract disease in women," Dr. Ness said.

The study of 87 patients at the UC Davis Cancer Center and Kaiser Permanente was conducted by Richard Kravitz, a professor of medicine and director of the UC Davis Center for Health Services Research in Primary Care, and Jennifer Wright Oliver, a medical student at UC Davis Medical Center.

"We motivated patients to be more effective when they talk with their doctors about pain," said Kravitz. "This approach has been used in people with diabetes and other chronic diseases, but ours was the first time it had been used in cancer. As an intervention, it shows promise in helping cancer patients."

An estimated 42 percent of cancer patients do not get sufficient relief from pain, not because their pain can’t be controlled but because of patient-doctor communication barriers. These include patients not knowing their options or fearing being perceived as "bad" patients for talking about pain. Some patients worry that treating pain may keep their physician from treating their cancer aggressively, said Kravitz. Others fear they will become addicted to pain medications.

In the study, counselors in the experimental group met for 15 minutes with cancer patients to design an individualized program for pain relief. They asked patients about their beliefs on pain management and had them set goals, such as being able to attend a family gathering or sleep through the night without pain. They would also rehearse what patients would ask for in future visits with their doctors.

The control group received a 15-minute educational session on pain control. In subsequent follow-ups, the patients who had received individualized coaching showed a 20 percent overall reduction in average pain. Both groups showed improvements in pain-related knowledge.

The study underscores the need to involve cancer patients more actively in pain management decisions, said Kravitz. "Health-care professionals need to determine their patient’s attitudes about pain and encourage them to discuss the subject openly," he said. "This is not necessarily easy, because patients are often reluctant to disclose their pain."

The authors recommend further study on a larger sample of cancer patients to confirm its effectiveness. Copies of all news releases from UC Davis Health System are available on the Web at http://news.ucdmc.ucdavis.edu.

Through a unique collaboration between Emory's Functional Neuroimaging Group, led by Gregory S. Berns, M.D., Ph.D., and Read Montague, M.D., Ph.D., at Baylor's Center for Theoretical Neuroscience, scientists are beginning to reveal the biological basis of the human attraction to surprising events. Sam McClure, a Baylor doctoral candidate, also contributed to the study published in the April 15 issue of the Journal of Neuroscience.

The Emory and Baylor scientists used functional magnetic resonance imaging to measure changes in human brain activity in response to a sequence of pleasurable stimuli, in this case, fruit juice and water. In the study, a computer-controlled device squirted fruit juice and water into the mouths of research participants. The patterns of juice and water squirts were either predictable or completely unpredictable.

"Until recently, scientists assumed that the neural reward pathways, which act as high-speed Internet connections to the pleasure centers of the brain, responded to what people like," said Montague. "However, when we tested this idea in brain scanning experiments, we found the reward pathways responded much more strongly to the unexpectedness of stimuli instead of their pleasurable effects." Study subjects were told nothing about what would take place. As a result, the brain was a clean slate, allowing scientists to clearly see what area of the brain was registering activity.

Contrary to the scientists' expectations, the human reward pathways in the brain responded most strongly to the unpredictable sequence of squirts. The area of the brain called the nucleus accumbens, which scientists previously have identified as a pleasure center of the brain, recorded a particularly strong response to the unexpectedness of a sequence of stimuli.

"We find that so-called pleasure centers in the brain do not react equally to any pleasurable substance, but instead react more strongly when the pleasures are unexpected," Berns said. "This means that the brain finds unexpected pleasures more rewarding than expected ones, and it may have little to do with what people say they like."

Both Berns and Montague think their work may provide a better understanding of addictive diseases and disorders of decision making in humans. They believe that the new findings may help clarify the pathways involved in addiction to drugs such as heroin and cocaine, which are known to disrupt the normal function of the nucleus accumbens Other addictive disorders such as gambling also appear to influence this same brain pathway.

The study showed that intravenous treatment with adult donor rat stromal cells (mature cells from bone marrow) allowed the rats to return to normal or near normal function within 14 days of a stroke.

“These are smart cells that selectively migrate to the site of injury and become little factories producing an array of helpful molecules to repair the tissue,” says Michael Chopp, Ph.D., professor and vice chairman of neurology at Henry Ford Health Sciences Center in Detroit, and professor of physics at Oakland University in Rochester, Michigan. “The beauty of this is that a patient could get multiple infusions.

“This study suggests that an infusion of the patient’s own stromal cells provides significant benefit to the stroke patient and are easily administered,” he says. “We believe we have a therapy that shows promise in treating stroke, Parkinson’s disease, spinal cord injury and traumatic brain injury.”

The treatment provides hope for the 600,000 people who have strokes in this country annually. Stroke remains the third leading cause of death, and a leading cause of disability.

The approach involves removing stromal cells, growing them in culture, and then infusing them back into the rat where they migrate to the site of injury - in this case the brain. Because the cells are taken from the same rat, the problem of rejection is eliminated. In previous studies of stromal cell treatment, the cells were either injected or surgically administered. This method eliminates the need for surgery and also allows for repeat treatments.

In the study, researchers tagged stromal cells with a chemical marker for tracking before re-infusing them. Cerebral strokes were induced in the rats and they were treated with a single dose of stromal cells at day one or day seven. Another group not treated with stromal cells served as controls.

The rats were given neurological, motor skill and sensory function tests before the stroke and at day one, one week and up to 35 days after the stroke. In general, the subjects treated with high dose infusions of stromal cells scored significantly better on the tests.

Additionally, biopsies revealed that the majority of the stromal cells migrated to the site of brain injury. Other cells were found around the vessels of major organs, but not within the organs, and in the bone marrow and the spleen.

Both rats treated at day one and day seven after stroke had similar recoveries. This is important, Chopp says, because it provides physicians with a time window for treatment. Some stroke patients are very unstable for the first day or two after stroke and the physicians may be reluctant to take bone marrow during this time period. Also, some patients with transient ischemic attacks (TIAs) or “mini strokes” – temporary stroke-like events caused by a temporarily-blocked blood vessel - spontaneously get better on their own.

“We found that you could wait at least seven days and get significant benefit,” notes Chopp. It is not yet clear how the procedure works. One theory is that stromal cells integrate into tissue and replace damaged cells. But more likely, Chopp believes, stromal cells may stimulate brain cells to repair themselves.

If the treatment continues to show beneficial effects in animal studies, it may provide new treatments in the future for stroke, brain trauma, spinal cord injury, and neurological diseases such as Parkinson’s disease, multiple sclerosis and even Alzheimer’s.

The researchers are applying to the National Institutes of Health for a grant for Phase I studies in humans.