NATIONAL INSTITUTES OF HEALTH

16.4.2001

News releases received by email from the NIH

*  OFFSPRING OF MEN WITH BIRTH DEFECTS
   TWICE AS LIKELY TO HAVE DEFECTS, TOO
*  NHGRI RESEARCHERS DEVELOP GENE TEST THAT DIFFERENTIATES
   BREAST CANCER TYPES
*  RESEARCHERS SEEK WOMEN WITH PREMATURE OVARIAN FAILURE FOR
   TESTOSTERONE REPLACEMENT STUDY
*  NIEHS INITIATES CLINICAL CENTER RESEARCH GROUP
   TO STUDY AND TREAT AUTOIMMUNE MUSCLE DISORDERS
*  FAUCI PRESENTS ROADMAP FOR INFECTIOUS DISEASE RESEARCH IN 21ST CENTURY
*  NHLBI LAUNCHES SLEEP AND CHILDREN EDUCATION PROGRAM
   WITH GARFIELD THE CAT AS  "SPOKESCAT"
*  METHAMPHETAMINE ABUSE LEADS TO LONG-LASTING CHANGES
   IN THE HUMAN BRAIN THAT ARE LINKED TO IMPAIRED COORDINATION
   AND MEMORY
*  NIDA TO ANNOUNCE NEW PUBLIC HEALTH INITIATIVE:
   "PRESCRIPTION DRUGS: MISUSE, ABUSE, AND ADDICTION"
*  MOUSE GENE TRAP HELPS DECIPHER BRAIN'S WIRING DIAGRAM
*  STUDY CONFIRMS GENDER DIFFERENCES IN PROGRESSION FROM HIV TO AIDS
*  TWIN STUDY REVEALS GENETIC LINK TO MUSICAL PITCH RECOGNITION
*  NIAAA LAUNCHES COMBINE CLINICAL TRIAL
*  NEW PRIME-BOOST HIV VACCINE STRATEGY SHOWS PROMISE IN MONKEYS
*  DON'T GET RID OF THAT CAT YET, SAY ASTHMA RESEARCHERS
*  INNOVATIVE TECHNOLOGY HELPS PUBLIC TOUCH TREASURES:
   NATIONAL LIBRARY OF MEDICINE TO LAUNCH "TURNING THE PAGES"
*  STUDENTS BRAINSTORM WITH NEUROSCIENTISTS
   BRAIN AWARENESS WEEK PROGRAMS TO BE HELD MARCH 14-15
*  EXPLORING YOUR BRAIN
*  TECHNOLOGY IS SHAPING THE FUTURE OF HEALTH CARE
   "Telemedicine and Telecommunications: Options for the New Century"
*  NIH CONSENSUS PANEL WILL WEIGH EVIDENCE ON BEST WAYS
   TO PREVENT, DETECT, AND TREAT TOOTH DECAY
*  ADVANCE DIRECTIVES FOUND KEY TO REDUCING STRESS FOR
   FAMILIES OF HOSPITALIZED PATIENTS AT THE END OF LIFE
*  NEW TOOLS FOR HEALTH CARE PROVIDERS AND THE PUBLIC TO
   COMBAT OVERWEIGHT AND OBESITY
*  NEW RESEARCH REGISTRY TO EXAMINE RHEUMATOID ARTHRITIS IN
   AFRICAN AMERICANS
*  SCIENTISTS IDENTIFY PROCESS THAT PLAYS KEY ROLE IN
   BRAIN CHANGES INVOLVED IN COCAINE ADDICTION
*  TRANSPLANTS OF SIBLING STEM CELLS SHOW PROMISE FOR IMMUNE DISORDER
*  POPULAR PAIN ANALGESICS FOUND TO AFFECT CENTRAL NERVOUS SYSTEM
*  FEDERAL GOVERNMENT MAKES FINAL CALL FOR DATA, PUBLIC
   COMMENT BEFORE WRITING NEW REPORT ON CANCER-CAUSING SUBSTANCES

National Institute of Environmental Health Sciences

NIH NEWS RELEASE

EMBARGOED FOR RELEASE:
Tuesday, February 13, 2001
4:00 p.m. EST

Media Contact: Bill Grigg
(301) 402-3378, (301) 496-35112

OFFSPRING OF MEN WITH BIRTH DEFECTS TWICE AS LIKELY TO HAVE DEFECTS, TOO

Men born with a birth defect have a substantially increased risk of having a child with a birth defect, a large population study revealed today. Compared with other fathers, the risk was doubled.

The second-generation risk also appeared higher -- at least for dissimilar birth defects -- than for the offspring of mothers who had been born with birth defects.

Scientists at the U.S. National Institute of Environmental Health Sciences and Norway's University of Bergen reviewed Norwegian births since 1967. They compared 12,000 men who had been born with a recognized defect with nearly a half- million unaffected men. The scientists reported today in the "Journal of the American Medical Association" for Feb. 14 that the men had fathered 1,265 children and that:

--Twenty-one of these children (1.6 percent) had been born with the same defect as their father's. This is about seven times the risk of those same defects in the general population but is about the same risk as a previous study showed for the children of women with birth defects.

--However, the children of fathers with birth defects also had a higher risk of having different, unrelated birth defects. Forty-three children (3.4 percent) had defects that were not like their father's, compared to an expected number of 24 (1.9 percent). This result was in contrast to the findings of the previous women's study in which the children of women with defects appeared to have no increased risk of babies with defects different from the mother's.

--The total risk of birth defects was 5.1 percent among the offspring of fathers with defects, or twice the 2.1 percent risk of the offspring of other fathers. The risk was spread out across categories of defects, not concentrated in any one category.

"Five percent of children with birth defects is not a whole lot," Allen J. Wilcox, M.D., Ph.D., said, "but it still is more than double what we see in the children of unaffected fathers."

Dr. Wilcox is chief of epidemiology at the National Institute of Environmental Health Sciences, one of the U.S. National Institutes of Health.

"What surprised us," Dr. Wilcox continued, "is that the children of the affected fathers had a higher risk of all kinds of defects, not just the same defect as their father. In our earlier study of women with birth defects, this did not appear to be the case: The children seemed to have no special risk of birth defects except for the specific defect of the mother."

Dr. Wilcox' co-researchers are Rolv T. Lie, Ph.D., and Rolv Skjaerven, Ph.D., both professors at the University of Bergen. Their studies are based on the Medical Birth Registry of Norway which links the birth records of fathers, mothers and offspring through the Norwegian system of unique personal identification numbers.

The investigators grouped the birth defects recorded into 24 categories. Cleft lip, genitalia defects, limb defects and clubfoot (in which the foot is twisted out of position) were the four most common recurring defects that recurred in the offspring of affected fathers. In many cases, these defects can be surgically repaired.

In their report, the three said they had expected an excess in defects of the same type as the fathers because many birth defects are heritable. They said they had no explanation for the increased rate of dissimilar effects.

In the study, boys with birth defects had a lower-than- normal survival rate to age 20. Even if they survived to adulthood, they were 30 percent less likely to father a child than other men. This pattern of reduced reproduction (which the authors said presumably reflects social factors as well as biological) had also been seen among affected women.

The scientists said the higher death rates among babies with birth defects, as well as the reduced likelihood that the survivors will have children, reduces the impact of parents with defects on the next generation.

"We also need to put this into perspective," Dr. Wilcox said. "More than 95 percent of all babies with birth defects are born to parents who have no known birth defects themselves. Measles, a lack of folate in the diet, and heavy alcohol use are factors for some defects, but the causes of most birth defects, environmental as well as genetic, are not known. We have a lot to learn - still - about the cause and prevention of birth defects."

Dr. Wilcox can be reached at (919) 541-4660, and will be available for interviews beginning Monday, February 12.

National Human Genome Research Institute

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Wednesday, February 21, 2001
5:00 p.m. EST

Contact:
Geoff Spencer
301-402-0911

NHGRI RESEARCHERS DEVELOP GENE TEST THAT DIFFERENTIATES BREAST CANCER TYPES

Technique Can Distinguish Hereditary from Non-Hereditary Tumors; May Lead To New Diagnostic Tests, Future Treatments

BETHESDA, MD -- According to their report in the current issue of "The New England Journal of Medicine", scientists at the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) have developed a new genetic test that, for the first time, can easily distinguish between hereditary and sporadic forms of breast cancer. This new approach should make it possible for physicians to quickly and accurately diagnose the cause of an individual woman's disease and may ultimately guide decisions about the most effective treatment.

The international team of researchers, led by Dr. Jeffrey Trent, NHGRI's scientific director and head of the NHGRI Cancer Genetics laboratory, used a new technique called gene-expression profiling to differentiate between breast tumors that were caused by inherited genetic changes and those that were not. Based on a laboratory method that uses a type of DNA chip called a microarray, the researchers simultaneously assessed how active some 6,000 genes within breast cancer cells were, altogether making nearly 250,000 measurements. The study revealed clear differences in the patterns of gene activity in breast tumors, patterns that can be as unique as a fingerprint, pinpointing into which group a woman's cancer belongs.

"This powerful new technology gives us a snapshot of exactly which genes are active in a tumor cell," Trent says. "Over the last few decades, scientists have made important progress in understanding the molecular origins of cancer by studying one gene at a time. Now we can look at thousands, and even tens of thousands of genes as they interact to produce a tumor. This capability will have important implications for both diagnosis and treatment."

GENETICS OF BREAST CANCER

Earlier insights tended to give a fairly static view of the genetic changes that produced a tumor. The current study demonstrates the power of a dynamic analysis that shows the interaction of many genes within a cell's metabolic pathways. In what may become a new research and diagnostic trend, the team has established that it can differentiate between hereditary and non-hereditary breast cancer by studying thousands of genes simultaneously.

Physicians have long known that breast cancer can run in families. Approximately 5 to 10 percent of breast tumors are hereditary; the remaining cases are caused by genetic changes that occur during a woman's life and are commonly called sporadic. In the mid 1990s, scientists identified mutations in genes now called BRCA1 and BRCA2 that are the major cause of the hereditary form of the disease. Women inheriting these mutations have a 40 to 85 percent lifetime risk of developing breast cancer, as well as an increased risk of ovarian cancer.

Telling the tumor types apart is not easy with traditional techniques. "When you look at these tumors under a microscope, based on their shapes and other features, it is very difficult to tell which tumors are caused by BRCA1, and virtually impossible to distinguish cancer caused by BRCA2 from those caused by non-inherited mutations," says another of the study's senior authors, Dr. Ake Borg of the University of Lund. Furthermore, the BRCA1 and BRCA2 genes are very large, and searching through them for mutations is both complicated and expensive.

To determine whether gene profiling could tell the difference between sporadic tumors and those with BRCA1 or BRCA2 mutations, the research team examined samples of tumors that had been surgically removed from 22 breast cancer patients at the University of Lund in Lund, Sweden. Fifteen of the women were known to have hereditary breast cancer based on family history and other analyses. Of the 15, seven had mutations in BRCA1; eight had mutations in BRCA2. The control group was comprised of eight women with sporadic cases that had no evidence of any family history of the disease.

When the team examined the gene-expression profiles for the 22 patients using the microarray analyses, they were able to quickly and accurately differentiate the BRCA1 from the BRCA2 inherited changes as well as the non-inherited genetic changes.

"We were surprised that we could separate the groups as well as we could," says Ingrid Hedenfalk, one of the two lead authors of the study and a doctoral student visiting NHGRI from the University of Lund. Placing patients in the proper diagnostic category can be critical to a successful treatment. For example, women shown to be carrying BRCA1 or BRCA2 mutations are at high risk for second breast cancers, and for ovarian cancer, and thus need very close follow-up.

MICROARRAY ANALYSIS

The team's approach relied on a cutting edge technology called a DNA microarray, or sometimes, a gene chip. The microarray itself is merely a glass slide with tiny dots of DNA from different genes arranged in a grid-like array. Using microarrays, the activity of thousands of known genes can be quickly tested in a cell sample.

To perform the analysis, scientists isolate a special collection of molecules from the test cells called messenger RNA or mRNA. These molecules are produced by active genes and indicate which of the estimated 30,000 genes are "turned on" in a cell. The information in the messenger RNAs can be converted into a form of DNA called complementary DNA or cDNA -- kind of like copying a music CD to digital audiotape; same information, just in a different form. A fluorescent label can be added to the cDNA made from the test cells. A robot then systematically deposits a sample of the cDNA onto the glass slide. If the sample contains cDNA that matches a particular gene on the microarray, the cDNA sticks to that spot on the array, like two pieces of Velcro coming together. Unmatched cDNA is washed away.

Automated computerized detectors then measure the amount of fluorescence for each spot. The brighter the fluorescence, the more cDNA has attached to the known gene, and the more active the gene must be in that tissue sample. The result appears as a pattern of spots that are either bright or dark, showing whether the known gene is active or inactive in the tumor cell.

"Our gene expression profiling technology reveals a pattern, a kind of fingerprint for each tumor type," Dr. Trent says. "The fingerprint shows us key genes involved in tumor development and progression."

Because of the number of gene samples, and the number of patients tested, the study produced almost a quarter million data points. To handle the huge amounts of information generated by this process, the researchers turned to computer-based statistical analyses. With the help of statisticians from the NIH's National Cancer Institute, Agilent Laboratories, and Texas A & M University, the researchers were able to show that the differences between the groups of genes from the cancer cells were, indeed, statistically significant.

DIAGNOSTIC IMPACT

In a surprising twist, the scientists found their gene- profiling technique to be so good that it found a previously unrecognized rare event among the classically diagnosed tumors. Among the control tumors that had been originally diagnosed as non-hereditary, one tumor showed a gene-profile that made it look like a hereditary form of the disease caused by mutations in the BRCA1 gene.

After careful ethical advice was obtained, the researchers decided to re-contact the patient to ask for permission to do additional testing. The researchers then sequenced her BRCA1 gene and found no mutations. This puzzling result lead the team to test for a newly discovered mechanism that appears to contribute to the cause of some forms of cancer, even when a critical gene is not mutated. Instead, the gene is somehow abnormally turned off. Scientists call this recently discovered phenomenon gene silencing.

"We discovered that even though the spelling of her BRCA1 gene was normal, it was silenced due to a non-inherited mechanism called methylation," Dr. Trent says. Methylation previously has been identified as a way that a cell may temporarily or reversibly silence the activity of a gene. It remains unclear just what caused the methylation to silence this patient's BRCA1 gene and essentially turn it off. Nevertheless, Dr. Trent says, several recent studies by researchers elsewhere have shown that gene methylation may be involved in a number of different cancers, including breast and colon cancer, and may be a more common mechanism for tumor formation than previously thought.

FUTURE DIRECTIONS

Although the research team initially tested thousands of genes to find the pattern associated with the hereditary and nonhereditary forms of breast cancer, computational techniques helped them reduce the number of genes needed to a much more manageable number. "In fact," says co-lead author Hedenfalk, "we were able to narrow the number of genes needed to separate the three groups to just 50 or so."

"Not unexpectedly, these critical genes turn out to be involved in various aspects of cancer progression," says Dr. David Duggan, the study's other co-lead author. These aspects include mechanisms controlling the repair of damaged DNA, cell division, cell death, and other important cellular housekeeping functions.

These 50 or 60 genes are obvious candidates for further research to understand the molecular basis of cancer and are potential targets for the development of new drug treatments. "If you were trying to develop a therapeutic that selected hereditary breast cancer," Dr. Trent says, "these genes would be a good place to start."

The study also sheds new light on how breast cancer develops. "Even though BRCA1 and BRCA2 look nothing like each other in terms of their DNA sequence, they can cause the same net effect -- increased susceptibility to both breast and ovarian cancer," Dr. Borg says. By looking at the kinds of cellular genes that are active in these cancer cells, "our results indicate that these two types of inherited genetic changes use quite different pathways, or series of biochemical steps, to cause the same devastation."

Results from the study may also help researchers find additional genes involved in breast cancer. In August 2000, an NHGRI-led team reported finding evidence for a third hereditary breast cancer gene in certain Nordic families. By using gene expression profiling to study these families, the researchers hope to narrow their search for this, and possibly, other genes involved in breast cancer.

Already, the research is being hailed by leading cancer specialists as a breakthrough in basic science with potentially broad clinical applications.

"This very important research by a superb group begins to better clarify the different functions of these hereditary breast cancer genes BRCA1 and BRCA2," said Dr. Dan Von Hoff, director of the Arizona Cancer Center in Tucson, Arizona. "This pioneering piece of microarray work will enable us to better design prevention and therapy strategies for patients with hereditary breast cancer and, I suspect, for many other cancers as their genetic basis becomes elucidated."

For NHGRI Director Dr. Francis Collins, the discovery provides a glimpse of the future of genome research. "This work is an excellent example of the kind of research that will characterize the next phase of the Human Genome Project, as scientists move from sequencing the entire human genetic code to understanding the functions of genes in health and disease," he says.

Members of the research team include (in order of the study's list of authors) NHGRI's Ingrid Hedenfalk, David Duggan, and Yidong Chen; Michael Radmacher of the National Cancer Institute (NCI); Michael Bittner of NHGRI; Richard Simon of NCI; Paul Meltzer of NHGRI; Barry Gusterson of the University of Glasgow, United Kingdom; Manel Esteller of the Johns Hopkins Oncology Center; Olli-P. Kallioniemi and Benjamin Wilfond of NHGRI; Ake Borg of the University of Lund, Sweden; and Jeffrey Trent, of NHGRI.

Other authors include Mark Raffeld of NCI; Zohar Yakhini and Amir Ben-Dor, both of Agilent Laboratories; Edward Dougherty of Texas A & M University; Juha Kononen of NHGRI; Lukas Bubendorf of NHGRI and the University of Basel, Switzerland; Wilfrid Fehrle and Stefania Pittaluga, both of NCI; Sofia Gruvberger, Niklas Loman, Oskar Johannsson, and Hakan Olsson, all of the University of Lund; and Guido Sauter of the University of Basel.

Their report, "Gene-Expression Profiles in Hereditary Breast Cancer," Hedenfalk, et. al.,appears in the Feb. 22, 2001, issue of the "New England Journal of Medicine", 244:539-548.

National Institute of Child Health and Human Development

NIH NEWS RELEASE

FOR IMMEDIATE RELEASE
Monday, February 26, 2001

Contact (Press Only):
Robert Bock
(301) 496-5133

RESEARCHERS SEEK WOMEN WITH PREMATURE OVARIAN FAILURE FOR TESTOSTERONE REPLACEMENT STUDY

NOTE TO PRODUCERS: An audio story on this release is available from the NIH Radio News Service at 1-800-633-3425 and at http://www.radiospace.com/nihhome.htm The story will remain on the 800 line through March 2 and on the website for the next 30 days.

Researchers at the National Institute of Child Health and Human Development (NICHD) are recruiting women who have premature ovarian failure -- formerly known as premature menopause -- to determine if restoring testosterone will help prevent osteoporosis.

According to Lawrence M. Nelson, M.D., head of NICHD's Unit on Gynecologic Endocrinology, the women will receive testosterone in addition to the combination of replacement hormones (estrogen and progestin) prescribed for women with premature ovarian failure. The testosterone will be delivered through a patch worn on the skin.

"Many women who experience premature ovarian failure don't realize how important it is to replace the hormones that the ovary no longer provides," Dr. Nelson said. "We're testing a new method to improve replacing these ovarian hormones."

Normally, the ovaries produce both estrogen and testosterone, Dr. Nelson explained. Some young women become deficient in these hormones because their ovaries, for unknown reasons, stop working prematurely. When this happens before age 40, the condition is known as premature ovarian failure. Testosterone is believed to be important for a woman's health but is not typically replaced in women who have low levels of this hormone. Many experts believe that testosterone plays a key role in maintaining a woman's sexual desire and other aspects of sexual function, and may contribute to her bone and muscle mass, strength, energy level, and a positive sense of well being. Testosterone may also benefit some aspects of memory.

"We know that women with premature ovarian failure as a group have decreased testosterone levels," says Sophia Kalantaridou, M.D., Ph.D., the study's lead investigator. "This study is primarily designed to determine if returning their testosterone levels to normal through the use of this testosterone skin patch will help them better maintain bone density." The research is being conducted by the Gynecologic Endocrinology Unit at the National Institutes of Health in Bethesda, Maryland under a Collaborative Research and Development Agreement between the National Institutes of Health and Procter and Gamble Pharmaceuticals.

Women who volunteer for the study will have the opportunity to come to NIH to be evaluated by a team of physician experts in premature ovarian failure. The evaluation will be provided at no charge, and, in most cases, patients will be reimbursed for their travel expenses.

"By participating, study volunteers will help answer questions about how best to treat patients with premature ovarian failure," Dr. Nelson said. "We also take patient education seriously, and will do our utmost to help volunteers develop a thorough understanding of their condition."

The researchers plan to recruit three groups of 55 women each. The first group of women with premature ovarian failure will wear an experimental skin patch that delivers the amount of testosterone normally produced by the ovary in healthy young women. These women will be compared to a second group of women with premature ovarian failure who will wear a placebo patch (a patch that delivers no hormone). Women in both groups will also wear a patch that delivers estrogen and take tablets containing the hormone progestin. These two groups of women will be compared with a third group of women who have normal ovarian function. All the women in the study will receive periodic scans to measure bone density as well as tests of cognition, mood, well being, sexual function, dry eye, and body composition.

PATIENT CONTACT INFORMATION:

For information on how to participate in the study, potential volunteers with premature ovarian failure -- as well as women with normally functioning ovaries -- between the ages of 18 and 42 may contact Vien Vanderhoof by calling toll free at 877-206-0911.

The NICHD is part of the National Institutes of Health, the biomedical research arm of the Federal government. The Institute sponsors research on development before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD website, http://www.nichd.nih.gov , or from the NICHD Clearinghouse, 1-800-370-2943; E-mail NICHDClearinghouse@mail.nih.gov

Previous releases relating to premature ovarian failure are available at: http://www.nichd.nih.gov/new/releases/matergene.htm

http://www.nichd.nih.gov/new/releases/pofcal.html

National Institute of Environmental Health Sciences

NIH NEWS RELEASE

FOR IMMEDIATE RELEASE:
Monday, February 26, 2001

NIEHS Contact:
Tom Hawkins
(919) 541-1402

NIEHS INITIATES CLINICAL CENTER RESEARCH GROUP TO STUDY AND TREAT AUTOIMMUNE MUSCLE DISORDERS

The National Institute of Environmental Health Sciences, headquartered in Research Triangle Park, N.C., has established a clinical research group at the Clinical Center, the research hospital of its parent agency, the National Institutes of Health, in Bethesda, Md.

The research group will work with NIEHS Director of Clinical Research Perry Blackshear, M.D., D.Phil., to continue studies on the cause and treatment of the autoimmune disease myositis and to initiate new investigations into the role of genetics and the environment in the development of other autoimmune diseases.

Myositis is a chronic, incurable, potentially fatal disease of children and adults and is thought to be triggered in genetically predisposed individuals

after exposure to certain environmental agents. It is an autoimmune disorder that results in inflammation and weakness of muscles throughout the body, including those that function in breathing and digestion, and sometimes affects the heart muscle itself.

It can cause death by asphyxiation and by other means. It is estimated that

there are at least 30,000 cases in the U.S., although myositis, like other autoimmune diseases, is often under-diagnosed. Symptoms include muscle weakness and pain, and environmental triggers may include certain drugs or infections, and even sunlight.

The group will expand its work to study other autoimmune diseases with suspected environmental components which could include rheumatoid arthritis, lupus, diabetes, multiple sclerosis, scleroderma, and autoimmune thyroid disease, as well as other environmentally triggered disorders. They will also act as a liaison to clinical studies for NIEHS basic researchers and serve as a resource for recruiting subjects to a variety of investigations being planned at NIEHS.

"Members of the group will work in collaboration with their colleagues at the NIEHS campus in North Carolina and those in other Institutes at the Clinical

Center at NIH," Dr. Blackshear said. "We feel that the environmental health

sciences have matured to the point where they merit a presence at the Clinical Center."

Previously, NIEHS has pursued clinical research through grants, contracts and collaborations with private, city or academic hospitals, often with facilities nearby in North Carolina, and those efforts will continue. The Institute's Epidemiology Branch is among those with decades of groundbreaking research to its credit. NIEHS was established in North Carolina in 1966, first as the NIH Division of Environmental Health Sciences, and was elevated to Institute status in 1969.

Heading the NIEHS Environmental Autoimmunity Group will be Frederick W. Miller, M.D., Ph.D., assisted by Lisa G. Rider, M.D., whose research interests include rheumatic diseases in children. Researcher Terrance P. O'Hanlon, Ph.D., and

postdoctoral fellow Ejaz A. Shamin, M.D., will join them. The group plans to expand as the research program develops. The four current members join NIEHS from the Food and Drug Administration, where they are temporarily located until May.

NIEHS Director Kenneth Olden, Ph.D., emphasized the benefits for public health in the establishment of the Environmental Autoimmunity Group. "This research aims directly at a better understanding of environmental diseases, better diagnosis and treatment for patients, and better concepts for prevention of disease in the first place."

The new research group begins its work in the existing facilities of the Warren Grant Magnuson Clinical Center, where most patients will be seen on an out- patient basis, but ward beds will be available as needed. Patients are accepted into research protocols at the Clinical Center through referrals by their physicians. Looking ahead, NIEHS has reserved offices and clinics in the new Mark O. Hatfield Clinical Research Center, an 850,000 square foot facility under construction on the NIH campus. That new research hospital facility is scheduled to be occupied in 2003.

National Institute of Allergy and Infectious Diseases

NIH NEWS ADVISORY

FOR IMMEDIATE RELEASE
Monday, February 26, 2001

Contact:
Greg Folkers,
Office of the Director, NIAID
(301) 496-2263
gfolkers@nih.gov

FAUCI PRESENTS ROADMAP FOR INFECTIOUS DISEASE RESEARCH IN 21ST CENTURY

A generation ago, it was suggested that the time had come to "close the book" on infectious diseases. With the availability of a growing arsenal of antibiotics and vaccines, some policymakers argued that biomedical research resources should be diverted from infectious diseases to other concerns.

Today, the folly of this position is clear: infectious diseases are the second leading cause of death and the leading cause of disability-adjusted life years worldwide (one disability-adjusted life year is one lost year of healthy life). Together, the five leading infectious causes of death -- acute lower respiratory infections, HIV/AIDS, diarrheal diseases, tuberculosis, and malaria -- took more than 11.5 million lives in 1999 alone.

Rather than becoming a minor concern, "The discipline of infectious diseases will assume added prominence in the 21st century in both developed and developing nations," writes Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases in the March 1 "Clinical Infectious Diseases". "To an unprecedented extent, issues related to infectious diseases in the context of global health are on the agendas of world leaders, health policymakers, and philanthropies."

He notes that infectious diseases, long viewed solely as humanitarian concerns, are now seen by leaders in the context of foreign policy because of their deleterious effects on economic development and political stability. He suggests that infectious diseases and the biological sciences will be increasingly important to the development and execution of foreign policy in the 21st century.

In his article, Dr. Fauci reviews key scientific challenges facing infectious disease researchers in the new millennium, including the following:

--The threat of emerging and re-emerging diseases. Recent examples include the HIV/AIDS pandemic, West Nile virus in the United States, "mad cow" disease and new variant Creutzfeldt-Jakob disease in Europe, and the ever-present threat of pandemic influenza

--The spread of drug resistance seen in all classes of microbial pathogens

--The need for a better understanding of certain chronic diseases once considered to be "non-infectious," such as ulcers and certain cancers, which are actually caused directly or indirectly by infectious microbes

--The threat of bioterrorism

Fortunately, Dr. Fauci writes, "Interest in global health has led to increasing levels of financial support, which, combined with recent technological advances, provide extraordinary opportunities for infectious disease research in the 21st century."

In the 21st century, the technological advances that will serve as the foundation for the control of established, emerging, and re-emerging diseases will include:

--Genomics and proteomics

--Synthetic chemistry/robotics

--Computer/mathematical modeling

--Molecular epidemiology

--Genetic epidemiology

--Information technology

In particular, Dr. Fauci notes that "the sequencing of human and microbial genomes and advances in functional genomics will underpin significant progress in many areas, including understanding human predisposition and susceptibility to disease, microbial pathogenesis, and the development new diagnostics, vaccines, and therapies."

Dr. Fauci's article, entitled "Infectious Diseases: Considerations for the 21st Century" is a shortened and edited version of an address Dr. Fauci delivered at the 38th annual meeting of the Infectious Diseases Society of America on September 7, 2000 in New Orleans. Video of the lecture is available at http://www.niaid.nih.gov/director/director.htm

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov

The National Institute of Allergy and Infectious Diseases is a component of the National Institutes of Health, U.S. Department of Health and Human Services.

National Heart, Lung, and Blood Institute

NIH NEWS RELEASE

FOR IMMEDIATE RELEASE:
Tuesday, February 27, 2001

Contact:
NHLBI Communications Office
(301) 496-4236

NHLBI LAUNCHES SLEEP AND CHILDREN EDUCATION PROGRAM WITH GARFIELD THE CAT AS "SPOKESCAT"

At Least Nine Hours Sleep Each Night Recommended for Children

The National Heart, Lung, and Blood Institute (NHLBI) today launched a major five-year educational initiative to reach young children -- their parents, teachers, and health care providers -- with the message that adequate nighttime sleep -- at least nine hours each night -- is important to their health, performance, and safety.

At a press conference attended by Garfield the Cat, three Garfield sleep contest winners, 80 D.C. elementary school children, and others, NHLBI Director Dr. Claude Lenfant announced that the campaign is bringing together national and local organizations concerned about children's health and education to implement educational strategies to create greater public awareness of the importance of sleep for young children. The goal is to instill in children -- and the adults who most influence them -- the understanding that sleep is important to doing your best in whatever you do, including school activities, sports and other extracurricular activities, and good family relationships and friendships.

According to Lenfant, "We want young children to understand that they need at least nine hours of restful sleep each night and to establish a good night's sleep as a lifelong habit. Adequate sleep is associated with good health and performance, as well as fewer accidents, an even more critical issue when children reach adolescence and need to be aware of the dangers of drowsy driving."

Lenfant also announced that Garfield creator Jim Davis and his studio, PAWS, Inc., are co-sponsoring this initiative. "Garfield has tremendous appeal to people of all ages, and messages from Garfield about the importance of sleep should have particular resonance for young children, as well as their parents," he said.

Sleep problems are estimated to affect about 70 million Americans of every age, race, and socioeconomic level, and there is a growing body of scientific evidence showing that inadequate sleep results in tiredness, difficulties with focused attention, irritability, easy frustration, and difficulty modulating impulses and emotions. This is as true for children as it is for adults, although little attention has been paid to the problem of sleep in children.

The campaign is being implemented by the National Center on Sleep Disorders Research (NCSDR), which was created by the Congress in 1993 as an office of the NHLBI. Dr. Carl E. Hunt, Director of the NCSDR, explained that "Sleep disorders are often not recognized in children, and symptoms related to sleep deprivation may be erroneously attributed to hyperactivity or behavior disorders, to boredom with school, or to today's hectic lifestyles."

The campaign's theme is Sleep Well. Do Well., and the goal is to encourage children to get at least nine hours of sleep each night. Said Hunt, "The message is that getting enough sleep each night will help you do your best in whatever you do. This speaks to their need for achievement -- in school, in sports, in whatever is important to them."

PAWS, Inc. representative Kim Campbell, joined by Garfield, the campaign's "Star Sleeper," read a letter from Jim Davis, stating "Garfield and I and the folks at PAWS, Inc. are delighted to play a role in this important campaign to teach kids that a good night's sleep is important if you want to do well in school and in sports and be in top form."

Garfield also joined Lenfant in presenting awards to the top three winners of the Garfield "Star Sleeper" contest, which was posted on the NCSDR and PAWS Web Sites in early October 2000: 10-year-old Katie Seamon from Pittsburgh, PA; Xavier Powers, age 8, from Alliance, OH; and 8-year-old Danny Strohman from Duluth, MN.

The two-month contest, which attracted scores of entries from throughout the U.S., challenged children in grades one through five to write the ending for a comic strip which showed Garfield lamenting that he had stayed up too late last night and was so tired today that he did something wrong or silly. The winning entries were: "Kissed Nermal instead of my mirror," from Seamon; "Wore my gloves for shoes and shoes for gloves," provided by Powers; and "Fell asleep in my lasagna pan," submitted by Strohman.

Each child received a large version of the Garfield comic strip with the ending that he or she had suggested. The strip was specially drawn and signed by Davis. The winners also received copies of a new Garfield Star Sleeper Fun Pad, a 48-page book of games and puzzles with embedded sleep messages, and a 16-inch tall plush Garfield doll in his "Star Sleeper" jammies.

The Fun Pad will be distributed to children ages 7-11 through school, youth, and physician groups to educate them about the importance of sleep and good sleep habits. An interactive online version, as well as other sleep education materials, is available on the NHLBI Sleep Web Site at www.nhlbi.nih.gov/sleep. The plush doll will be used for promotional purposes. Both can be ordered through the NHLBI Online catalog at www.nhlbi.nih.gov.

An important component of the campaign is partnerships with organizations concerned about children's health and education that will help extend the campaign's messages to their own constituents. Organizations that have already agreed to be part of the campaign include the National Association of Elementary School Principals (NAESP), the American Academy of Pediatrics (AAP), the American Academy of Sleep Medicine (AASM), and the Capital Children's Museum where the event was held.

Frederick N. Brown, Associate Executive Director for Professional Services of the NAESP recalled that during his 24 years as an elementary school principal, he often observed children who were asleep in class or too tired to concentrate. "It is our hope that early intervention with sleep education messages will help our youngsters understand the importance of sleep so that they will incorporate good sleep habits into their lifestyles at an early point in their lives," he said.

Another partnering organization is the World Public Charter School (WPCS), a Washington, DC elementary school that is part of the Capital Children's Museum. WPCS first grade teacher Philip Duarte and his first grade students demonstrated a classroom session on sleep. To emphasize that an environment conducive to sleep is important, the children were asked to name items that they need to help them get a good night's sleep, just as Garfield needs his teddy bear and his blanket.

The NHLBI is part of the National Institutes of Health in Bethesda, MD.

National Institute on Drug Abuse

NIH NEWS RELEASE

EMBARGOED FOR RELEASE:
Thursday, March 1, 2001

Contact:
Beverly Jackson
Michelle Muth
301-443-6245

METHAMPHETAMINE ABUSE LEADS TO LONG-LASTING CHANGES IN THE HUMAN BRAIN THAT ARE LINKED TO IMPAIRED COORDINATION AND MEMORY

Methamphetamine, a highly addictive stimulant drug, whose abuse has reached epidemic proportions in many parts of the United States, causes long-term changes in the human brain that are associated with impaired memory and motor coordination, according to a study published in the March 2001 issue of the "American Journal of Psychiatry". Researchers found that these effects are seen even in methamphetamine addicts who have been off the drug for 10 months or more. A second study by the same research group reveals additional long-lasting brain changes caused by the drug, including an unexpected increase in cellular activity in certain areas of the brain.

"These findings show a direct relationship between changes in brain chemistry in methamphetamine abusers and functional changes in behavior," says Dr. Alan I. Leshner, director of the National Institute on Drug Abuse (NIDA). "The results underscore the serious nature of methamphetamine abuse and emphasize the need to alert users and potential users to the long-lasting, profound effects of this drug."

NIDA funded the research with the NIH National Center for Research Resources, the US Department of Energy, and the White House Office of National Drug Control Policy.

Methamphetamine, also known as "speed," "meth" or "chalk" (and, in its smoked form, as "ice," "crystal" or "glass"), can be smoked, snorted, injected or taken orally. The drug, often made in clandestine laboratories from inexpensive over-the-counter ingredients, is widely abused by diverse groups, including young adults who attend "raves" or private clubs, motorcycle gang members, male and female commercial sex workers, and bisexual and homosexual men.

In one study, researchers led by Dr. Nora D. Volkow of Brookhaven National Laboratory in Upton, NY, and the State University of New York at Stony Brook used an imaging technique called positron emission tomography (PET) scanning to measure the levels of molecules called dopamine transporters in the brains of 15 former methamphetamine abusers and 18 healthy comparison subjects (controls). The number of dopamine transporters (DAT) marks the presence of nerve cells that are part of a brain circuit that transmits signals using the chemical dopamine, which plays a role in movement control and feelings of pleasure. The researchers administered a battery of tests to assess attention, memory, mood, general intelligence and motor function.

Results showed that, on average, DAT levels in the striatum of the brain were 24 percent lower in methamphetamine abusers than in control subjects. Like other addictive drugs, methamphetamine is known to trigger short-term release of high levels of dopamine, which stimulates brain cells in the dopamine circuit, thereby enhancing mood and body movement. But previous animal studies show that long- term exposure to methamphetamine damages dopamine-producing brain cells and leads to reduced dopamine levels. The current finding of reduced DAT levels in chronic methamphetamine abusers indicates that in humans, too, the drug causes dysfunction in dopamine circuits, Dr. Volkow says.

Particularly noteworthy, she says, is the finding that "the lower the levels [of DAT], the worse the performance in motor tasks and the worse the performance in tasks of verbal learning" used to assess memory. "That is telling us chronic methamphetamine use is affecting many functions of the brain in a negative way."

In a second study, Dr. Volkow and her colleagues used PET scanning to measure glucose metabolism in the brains of the same group of methamphetamine abusers and in control subjects. Glucose metabolism is a measure of brain cell activity, and reduced glucose metabolism can be a very sensitive indicator of brain damage and an early indicator of neurodegenerative disease.

To their surprise, the researchers saw a marked overall increase in glucose metabolism in the brains of methamphetamine abusers, suggesting an inflammatory reaction. This effect was most marked in the parietal cortex region, which is involved in sensation and in spatial perception. Animal studies show this area to be particularly sensitive to the damaging effects of methamphetamine.

However, after controlling for this overall increase in metabolism in the methamphetamine abusers, the investigators showed that metabolism was significantly reduced in two brain regions -- the thalamus and striatum. These regions are involved in dopamine signaling, but the parietal cortex is not involved in the dopamine pathway. Thus, Dr. Volkow says, the results of this study add to the researchers' findings "by clearly documenting that the changes that are produced by methamphetamine are not limited to the dopamine system."

Questions remain about whether the effects of methamphetamine abuse on the human brain are permanent, and whether these effects can predispose some people to develop neurodegenerative diseases later in life.

NOTE TO REPORTERS: The full text of these articles appears in the March 2001 issue of the "American Journal of Psychiatry" ("Am J Psychiatry", Volume 158, Number 3, pgs. 377-382; 383-389) will be available on the journal's Web site, www.ajp.psychiatryonline.org.

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health effects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and other topics can be ordered free of charge in English and Spanish by calling NIDA Infofax at 1-888-NIH-NIDA (644- 6432) or 1-888-TTY-NIDA (889-6432) for the deaf. These fact sheets and further information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov

National Institute on Drug Abuse

NIH NEWS ADVISORY

FOR IMMEDIATE RELEASE:
Wednesday, March 7, 2001

Contact:
Beverly Jackson
Michelle Muth
301-443-6245

SAVE-THE-DATE

NIDA TO ANNOUNCE NEW PUBLIC HEALTH INITIATIVE: "PRESCRIPTION DRUGS: MISUSE, ABUSE, AND ADDICTION"

News Conference and Research Update
Tuesday, April 10, 2001

WHAT: A press conference, followed by a research update, to raise awareness, and discuss and refine a research agenda for addressing recent trends in the misuse and abuse of prescription drugs in the United States.

WHO: The National Institute on Drug Abuse, a component of the National Institutes of Health, with a coalition of public and private organizations.

WHEN: TUESDAY, APRIL 10, 2001 10:00 AM: PRESS CONFERENCE 1:00 PM: RESEARCH UPDATE

WHERE: National Press Club -- Holeman Lounge 529 14th St. NW, 13th Floor Washington, D.C.

WHY: An estimated 4 million people 12 years or older used controlled sedatives, stimulants, or opiates for non- medical reasons in 1999, with almost half of them reporting that they used prescription drugs non-medically for the first time in the previous year. NIDA's initiative will seek to increase awareness of this disturbing trend in the misuse and abuse of prescription drugs and to promote additional research on this topic.

MEDIA ARE INVITED TO ATTEND. For more information and to register, call the NIDA Press Office, 301-443-6245.

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and other topics can be ordered free of charge in English and Spanish through NIDA Infofax at 1-888-NIH-NIDA (644-6432) or 1-888-TTY-NIDA (889-6432) for the deaf. These fact sheets and further information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov

National Institute of Mental Health

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Wednesday, March 7, 2001
2:00 p.m. EST

Contact:

Jules Asher
(301) 443-4536
jasher@nih.gov

MOUSE GENE TRAP HELPS DECIPHER BRAIN'S WIRING DIAGRAM

Researchers funded by the National Institute of Mental Health (NIMH) have perfected a way to discover the wiring diagram of the mammalian brain. The technique, a type of gene trap, provides a shortcut for identifying - from among the tangled trillions of neural connections -- just the machinery involved in wiring up the brain during early development. NIMH grantee Marc Tessier-Lavigne, Ph.D. ( http://www.hhmi.org/research/investigators/tessierlavigne.html ), Howard Hughes Medical Institute (HHMI), and University of California, San Francisco (UCSF), and collaborator William Skarnes, Ph.D., University of California, Berkeley (UC Berkeley), and colleagues, report on the first mammalian "in vivo" discoveries using the technique in the March 8, 2001 "Nature".

The researchers bill the new technique, called a PLAP secretory trap screen, as a tool for finding a needle in a haystack. The trick: attach a molecular tag to the needle. Through the magic of genetic engineering, lines of mice are bred to express telltale mutations. Brain neurons ( http://www.sfn.org/backgrounders/communication.html ) harboring particular wiring molecules are revealed by a blue tint, while their tentacle-like extensions, or axons ( http://www.sfn.org/backgrounders/communication.html ), are colored purple.

Intricate guidance mechanisms have evolved to insure that the brain gets wired up correctly during critical periods in early development. Mistakes in this process, resulting in circuitry gone awry, are hypothesized to occur in neurodevelopmental disorders like schizophrenia ( http://www.nimh.nih.gov/publicat/schizmenu.cfm ) and autism ( http://www.nimh.nih.gov/publicat/autismmenu.cfm ).

Like ships wending their way to distant ports, embryonic neurons migrate to their appointed destinations in the brain and spinal column with help from navigation systems in their axons. Axons establish connections, or synapses, with remote target cells, networking some 100 billion neurons in humans. Growth cones at the axon tip steer a weaving course, taking their cues from chemical attractants and repellents secreted by guidance cells that serve as the lighthouses and buoys of central nervous system development. Receptor proteins on the axons act as the growth cones' antennae for receiving these signals. Researchers face a daunting task in identifying such axon guidance system components and the genes that code for them, thought to number in the hundreds or thousands.

"There's such complexity, and many of the standard methods, such as chemically inducing a mutation or molecularly knocking out a single gene, take too long," explained Tessier-Lavigne. "In addition, wiring defects can be very difficult to detect against a background of normal projections." In the same time it takes to perform a single gene knockout study, gene traps might net dozens or hundreds of genes. However, due to randomness integral to the methodology, it's not possible to target a particular molecule in advance.

"It starts out as somewhat of a 'fishing expedition,' but ultimately yields an invaluable molecular map of axonal projections by simultaneously mutating genes of interest and labeling the neurons expressing them," added Skarnes. The two laboratories are participating in an effort to develop a bank of mutant mouse lines - accessible at ( http://www.genetrap.org ) -- expressing particular populations of labeled axons as a resource for the neuroscience community.

In the current study, Tessier-Lavigne, Skarnes and colleagues demonstrated, for the first time "in vivo", an axon guidance role for a repellent guidance chemical, Sema6A, and clarified the guidance function of a growth cone receptor, EphA4. They inserted into mouse embryonic stem cells a marker, called a "secretory trap" vector, initially developed by Skarnes, that creates a mutation in genes likely to code for axon guidance molecules. To make the resultant subtle wiring defects stand out against a background of normal axonal projections, they added to the vector a second marker, PLAP (human placental alkaline phosphatase). They then used the genetically modified stem cells to breed lines of mice expressing the marker, which, after chemical staining, turns neuron cell bodies blue and axons purple.

As expected, some PLAP-labeled axons had different projection patterns in animals with the mutation, when compared with normal animals. Of 120 known genes trapped, 13 are thought to play a role in neuronal guidance, and the researchers predict that at least a comparable proportion of new genes netted in future studies likely will similarly code for brain wiring proteins. The technique "makes it possible not only to develop a map of the normal wiring pattern of the brain, but also to screen systematically for changes in this map in mutant animals," note the researchers. They have observed "remarkable diversity" of axonal projection patterns among some 40 lines of mice produced to date. In lines where the mutations do not interfere with the animals' survival, the researchers hope to screen for defects in behaviors, such as learning and memory, stress responses, etc. that might reflect underlying defects in the brain that might be traceable to specific genes. The technique's "full impact will come from its application on a large scale to sample as much of the genome as possible," write the researchers.

Also participating in the study were: Philip Leighton, Kevin Mitchell, Lisa Goodrich and Xiaowei Lu of HHMI / UCSF, and Kathy Pinson and Paul Scherz of UC Berkeley.

The National Institute of Mental Health (NIMH) is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.

National Institute on Drug Abuse

National Institute of Allergy and Infectious Diseases

NIH NEWS RELEASE

EMBARGOED FOR RELEASE:
Wednesday, March 7, 2001
5:00 p.m. EST

Contact:
Michelle Muth, Beverly Jackson
NIDA (301) 443-6245

Greg Roa, NIAID
(301) 402-1663
groa@niaid.nih.gov

STUDY CONFIRMS GENDER DIFFERENCES IN PROGRESSION FROM HIV TO AIDS

Despite Differences in "Viral Load," Men and Women Develop AIDS at the Same Rate

During the first years of HIV infection, women have significantly lower amounts of the virus in their blood than do men, according to one of the largest studies ever to examine gender-specific differences of HIV infection. Despite their lower initial viral levels, women suffer the loss of immune cells and develop AIDS just as swiftly as men. The findings, reported in the March 8 issue of "The New England Journal of Medicine", lend further support to recent changes in the criteria used to help doctors tailor anti-HIV drug therapy to delay the onset of AIDS.

Through a collaboration funded by the National Institute on Drug Abuse (NIDA), investigators from the National Institute of Allergy and Infectious Diseases (NIAID) and the Johns Hopkins University monitored more than 200 participants in the AIDS Linked to the Intravenous Experience (ALIVE) cohort.

"We established the ALIVE cohort in 1988 as a natural history study of HIV disease among injection drug users," explains NIDA Director Alan I. Leshner, Ph.D. "The current research evaluated the risk of progression to AIDS by measuring several factors, including the amount of virus in the blood, known as viral load."

The researchers found that the median initial viral load of the women who progressed to AIDS was almost five times lower than that of the men who progressed to AIDS.

"Despite early differences in viral load among men and women, as time went on, both men and women had a similar risk of developing AIDS," says Timothy Sterling, M.D., assistant professor of medicine and epidemiology at Hopkins and the first author on the study. "In addition, men and women experienced a similar rate of loss of their CD4+ T cells, the immune cells that decrease as a result of HIV infection."

Senior co-author Thomas C. Quinn, M.D., a senior investigator in NIAID's Laboratory of Immunoregulation and professor of medicine at Hopkins, says, "Previous studies in men have shown that initial viral load can be used to gauge their likelihood of progression to AIDS, but these data confirm that the initial viral load is much lower in women than in men and consequently not as predictive for women."

Between 1988 and 1998, the team followed a group of 156 men and 46 women who became HIV positive. During that time, 29 men and 15 women developed AIDS. The research team measured the volunteers' HIV load at regular intervals, starting from around the time they became infected with HIV and continuing for several years afterwards.

The investigators found that the women who developed AIDS had a median initial viral load of 17,149 copies of virus per milliliter (ml) of blood, about 4.5 times lower than the level found in men who progressed to AIDS, whose average was 77,822 copies/ml. Even men in the group who never developed AIDS had a higher median initial viral load of 40,634 copies/ml.

The women's lower levels meant that early after HIV infection a smaller percentage of them would have been eligible to start treatment with anti-HIV drugs. That calculation of eligibility relied upon clinical recommendations that were available at the time of the study. Such recommendations, which are reviewed regularly, have been updated recently.

"This research forms part of the body of data reviewed in forming the latest HIV treatment guidelines," says Anthony S. Fauci, M.D., director of NIAID. "It's important to conduct such studies that can give us a clearer picture of the unique challenges HIV/AIDS poses to women's health, because so many new cases of this disease are occurring among women, and among minority women in particular."

While the study sheds light on the effects of gender differences on viral load, Dr. Quinn notes that the best point at which to start anti-HIV drug treatments is still not known. Many other related questions remain -- why are women's initial viral loads so much lower than men's? Are hormonal differences the key? Why do their levels rise after the initial years? "More studies on the dynamics of HIV infection could give us a better idea of when to start drug therapy to delay the onset of AIDS in people with HIV. Then we can help them have longer and healthier lives, which is our ultimate goal," says Dr. Quinn.

NIDA and NIAID are components of the National Institutes of Health (NIH). NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. NIDA carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Reference: T Sterling et al. Initial plasma HIV-1 RNA levels and progression to AIDS in women and men. "The New England Journal of Medicine" 344(10):720-25 (2001). Press releases, fact sheets and other information about the health effects of drugs of abuse can be found on NIDA's homepage at http://www.drugabuse.gov or can be ordered free of charge in English and Spanish by calling NIDA Infofax at 1-888-NIH-NIDA (644-6432) or 1-888-TTY-NIDA (889-6432) for the deaf.

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov

NATIONAL INSTITUTES OF HEALTH

National Institute on Deafness and Other Communication Disorders

NIH NEWS RELEASE

EMBARGOED FOR RELEASE:
Thursday, March 8, 2001
2:00 p.m. EST

Contacts: Marin Allen, Ph.D.
(301) 496-7243
marin_allen@nih.gov

TWIN STUDY REVEALS GENETIC LINK TO MUSICAL PITCH RECOGNITION

Variation in the ability of humans to recognize musical pitch appears to be primarily due to highly heritable differences in auditory neural functions.

These functions are not measured by conventional audiologic methods, according to the lead article in "Science", March 9, 2001.

Controlling for environmental differences, two teams in an international collaboration employed a twin study to determine the extent to which genes and/or environment influence musical pitch recognition ability. A twin study can discriminate the effects of environment from those of genes. The collaboration between scientists at the National Institute on Deafness and Other Communication Disorders and a team at the Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital in London employed an updated Distorted Tunes Test (DTT) and a standard Five Minute Hearing Test to (FMHT) used to help identify subjects with possible confounding hearing loss.

The DTT was developed in the 1940s, but was updated and validated for the current U.S. and British populations. To test the validity of the updated DTT, first, 50 unrelated males and 50 unrelated females were tested on the new DTT. The distribution scores on males and females did not differ. Test and re-test scores on the same individual were highly correlated, which confirmed that the updated DTT is reproducible in individuals.

The updated DTT was recorded on a compact disc and presented to all subjects in the same setting. Subjects were presented with 26 short popular melodies, ranging in length from 12 to 26 notes. Tunes were presented once, and after each presentation, subjects were asked to score whether the melody was correct or incorrect and whether they were familiar or unfamiliar with that melody.

A total of 284 female Caucasian twin pairs; 136 identical and 148 non-identical twins aged 18-74, participated in the study. The twins were part of an ongoing study of common complex diseases, were unaware of the specific hypothesis tested, and were not screened for IQ, musical training or musical experience.

Following the FMHT and the DTT, the teams subjected the data to genetic model fitting techniques using a structural equation modeling package. This was applied to determine estimates of the genetic and environmental factors. Model fitting allows separation of the observed phenotypic variance into additive or dominant genetic components and common and unique environment. The last also includes measurement error.

Heritability estimates the extent to which variation in a trait in a population can be explained by genetic variation. Heritability for pitch recognition was estimated at 71-80%, depending upon how subjects were categorized. No dominant genetic effect nor significant effect of shared environment were detected. The heritability estimates observed for measures of deficit in pitch perception were very substantial and are high or higher than those for many complex traits in humans.

Dennis Drayna, lead author on the paper and a special expert, section on Genetics of Human Communication, Laboratory of Molecular Biology at NIDCD, notes "Since the FMHT serves as a rough estimate of peripheral hearing, its poor correlation with DTT suggest that musical pitch perception is largely independent of peripheral hearing. This would mean that variation in pitch perception originates in portions of the auditory system that are not dependent upon peripheral hearing, " adding, "the next important steps are finding the number of genes involved and the relative effects of those genes."

"Drs. Drayna (NIDCD) and Spector (St. Thomas') have demonstrated the importance of applying genetic approaches to biochemical or cellular mechanisms underlying neural function. Genetic modeling will yield substantial new understanding of the mechanisms applied to human communication research," said James F. Battey, Jr. M.D., Director of the NIDCD.

The Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, uncovers the genetic basis of common diseases and traits associated with aging using twins. The unit has already made progress on the genetic basis of a number of diseases, including, osteoporosis, back pain, osteoarthritis, cataract, obesity, blood clotting, hypertension and asthma.

NIDCD conducts and supports research and research training in the normal mechanisms and diseases and disorders of human communication. Within NIDCD's research efforts, scientists are using molecular genetics to understand both the normal and disease processes of human communication and the effects of inheritance and environment on those processes. NIDCD is one of the Institutes of the National Institutes of Health.

To arrange an interview with Dr. Drayna, please, contact the Office of Health Communication and Public Liaison at 301-496-7243.

NATIONAL INSTITUTES OF HEALTH

National Institute on Alcohol Abuse and Alcoholism

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Thursday, March 8, 2001
*8:00 a.m. EST

Contact: NIAAA Press (301) 443-9970
Ann Bradley (301) 443-0595

NIAAA LAUNCHES COMBINE CLINICAL TRIAL

Eleven universities to test behavioral and pharmacologic treatments for alcoholism

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) today announces the start of Combining Medications and Behavioral Interventions (COMBINE), a nationwide study that targets persons with the diagnosis alcohol dependence, commonly known as alcoholism. COMBINE is the first national study to evaluate the effectiveness of behavioral treatments alone and in combination with medications. It begins at a time when advances in genetics, neuroscience and treatment research are forging new directions for alcoholism treatment and building expectations among patients, clinical practitioners and the public for improved treatment outcomes.

"More than 8 million American adults meet clinical criteria for alcoholism, a condition characterized by an abnormal appetite for alcohol that leads to significant impairment--tolerance, impaired control over intake, physical dependence and, often, severe craving following sustained abstinence," said NIAAA Director Enoch Gordis, M.D. "Of persons who receive treatment, as many as 50 percent relapse at least once and a minority achieve long-term remission of disease. Identifying and developing effective treatments is the first priority of alcoholism research."

Over the next 24 months at eleven treatment research centers across the United States, the COMBINE study will recruit and randomize 1,375 people who meet current diagnostic criteria for alcohol dependence. Participants will receive one or both of two behavioral treatments (moderate-intensity and lower-intensity) and one or both of two medications (naltrexone and acamprosate) or a placebo. They will attend outpatient sessions for 4 months, then return for three followup visits over the subsequent 12 months.

"COMBINE is based on the accumulated knowledge of two decades in which NIAAA researchers have applied rigorous clinical trial methodology to test treatments for alcoholism," said Richard K. Fuller, M.D., Director of NIAAA's Division of Clinical and Prevention Research. "In 1996, Project MATCH, another benchmark multisite national trial, demonstrated the effectiveness of facilitated mutual-help involvement and two professionally delivered behavioral treatments [see "NIAAA Reports Project MATCH Main Findings" ( http://silk.nih.gov/silk/niaaa1/releases/match.htm ) at Press Releases]."

"Also during the past decade, research on medications to treat alcoholism has rapidly expanded as neuroscientists have advanced understanding of the biology of drinking behavior. From among the most promising pharmacologic and behavioral treatments, COMBINE is expected to define the optimal treatment combinations," said Raymond F. Anton, M.D., Medical University of South Carolina. Dr. Anton serves as chairperson of the COMBINE Steering Committee, a position held previously by Stephanie S. O'Malley, Ph.D., Yale University School of Medicine.

According to current research, the most promising pharmacologic treatments are naltrexone, approved by the U.S. Food and Drug Administration in 1994, and acamprosate, in use in Europe for about 14 years and currently under review by the U.S. Food and Drug Administration. Naltrexone, an opioid blocker, interferes with brain neurotransmitter systems that produce the rewarding effects of alcohol. Researchers have shown that naltrexone-treated patients are less likely to relapse to heavy drinking. Acamprosate is believed to normalize abnormalities in the glutamate (NMDA) and GABA neurotransmitter systems involved in alcohol withdrawal and may ease the discomfort of abstinence, thereby helping to prevent drinking. Among other questions, COMBINE will explore whether treatment effectiveness is improved by pairing a medication that reduces the risk of any drinking with one that reduces the risk of heavy drinking.

The moderate-intensity behavioral treatment developed for COMBINE integrates motivational enhancement therapy, cognitive-behavioral skills training and facilitated patient involvement in mutual-help groups such as Alcoholics Anonymous-treatments shown by NIAAA's Project MATCH to increase abstinent days and reduce heavy drinking. The lower-intensity behavioral treatment is designed to support sobriety, enhance medication compliance, and be incorporated into the daily routine of health care practitioners in primary and managed care settings.

"Alcoholism results from an interplay of drinker characteristics, including intrinsic neurochemical factors, some of which may be genetically modulated, with environmental risk factors. From brain imaging studies, we know that both medications and behavioral treatments can influence brain function and resulting behaviors. Our expectation is that the behavioral and pharmacologic treatments being tested in COMBINE will complement and perhaps enhance one another," Dr. Gordis said.

The most severe condition in the spectrum of alcohol problems, alcoholism affects about 13 percent of Americans at some time in their lives. Chronic, heavy drinkers are prone to cirrhosis and other liver diseases, neurological disorders, cardiovascular damage, pancreatic disease, and certain cancers. Approximately one in four urban hospital beds is occupied by a patient being treated for the consequences of drinking.

In addition to the 8 million Americans with alcohol dependence, about 6 million meet diagnostic criteria for alcohol abuse disorder, a pattern of harmful or hazardous drinking that persists despite interpersonal, social, employment, or legal problems but does not entail physiological addiction. Millions more engage in risky drinking patterns that could lead to alcohol problems, including impaired productivity, property damage, and injuries.

More than one-half of adult Americans have direct family experience of alcohol problems, which cost American society more than 100,000 lives and approximately $185 billion each year.

The COMBINE study is recruiting people aged 18 years and older. Persons interested in participating may determine their geographic eligibility by calling 866-80-STUDY after *8:00 AM (EST) March 8. Participants must be willing to be screened for alcoholism and be abstinent for a minimum of 4 and a maximum of 21 days prior to entering the study. There is no cost for participating in the COMBINE study.

One of 25 institutes and centers at the National Institutes of Health, NIAAA is the lead Federal entity for research on the causes, consequences, prevention and treatment of alcoholism, alcohol abuse, and alcohol-related problems. Through an integrated, multidisciplinary program, NIAAA supports and conducts more than 90 percent of alcohol research in the United States. The results of NIAAA research contribute directly to the treatment and prevention of alcohol problems and the formulation of national health policy.

For interviews with Dr. Gordis, Dr. Fuller and the COMBINE principal investigators, telephone the NIAAA Press Office, (301) 443-9970 or (301) 443-0595. For additional information about alcohol research, please visit http://www.niaaa.nih.gov

COMBINE SITES AND PRINCIPAL INVESTIGATORS

Medical University of South Carolina

Charleston, SC

Raymond F. Anton, M.D.

Boston University
Boston, MA
Domenic Ciraulo, M.D.

University of Washington

Seattle, WA

Dennis M. Donovan, M.D.

University of Texas San Antonio, TX

Bankole Johnson, M.D., Ph.D.

University of Miami Miami, FL Barbara J. Mason, Ph.D.

University of New Mexico

Albuquerque, NM William R. Miller, Ph.D.

Yale University New Haven, CT Stephanie S. O'Malley, Ph.D.

University of Pennsylvania

Philadelphia, PA

Helen M. Pettinati, Ph.D.

Brown University Providence, RI

Robert Swift, M.D., Ph.D.

Harvard University Boston, MA Roger D. Weiss, M.D.

University of Wisconsin-Milwaukee

Milwaukee, WI

Allen Zweben, D.S.W.

COORDINATING CENTER University of North Carolina Chapel Hill, NC James D. Hosking, Ph.D.

NIAAA STAFF COLLABORATOR Bethesda, MD Margaret E. Mattson, Ph.D.

National Institute of Allergy and Infectious Diseases

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Thursday, March 8, 2001
2:00 p.m. EST

Contact: NIAID Office of Communications
and Public Liaison
(301) 402-1663

NEW PRIME-BOOST HIV VACCINE STRATEGY SHOWS PROMISE IN MONKEYS

A team of academic and government researchers reports today on a promising new "prime-boost" HIV vaccine approach that is currently on a development fast-track for human clinical trials. This vaccination strategy kept an HIV-like virus in check in monkeys, even when the animals were exposed to very high virus doses months after immunization. The study appears March 9 in "Science Express", an online publication of the journal "Science".

Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), which funded the research, praises the recent findings. "This latest study provides some of the best evidence to date that a preventive HIV vaccine may protect against AIDS. Although the vaccine did not prevent infection, it continues to keep the virus at nearly undetectable levels for at least several months. We do not yet know if this vaccine will work in humans, but plans for the necessary clinical studies are under way."

Scientists from Atlanta's Emory University and NIAID combined two vaccines in a strategy they hoped might be effective and then evaluated that strategy in monkeys. Both vaccines were designed against SHIV, a virus containing components of HIV and the related monkey virus, simian immunodeficiency virus (SIV). SHIV mimics HIV infection and causes serious illness in macaque monkeys. The hybrid virus allows researchers to study the reactions of the immune system to the vaccines and the virus.

In the study reported today, 23 of 24 vaccinated monkeys suppressed the virus to nearly undetectable levels during the 20-week follow-up. Virus levels in the one animal were intermittently higher but still more than 100 times lower than those in four control animals that had not received the vaccine. By 28 weeks, all four control animals had developed AIDS-related opportunistic infections and were euthanized, whereas all 24 animals receiving vaccine remain alive and healthy.

The Emory team developed the first component of the vaccine strategy, a circular piece of DNA designed to carry genes for both SIV and HIV proteins. When this DNA is injected into monkeys, an immune response against SHIV is triggered. The scientists then boosted the immune response with a second vaccine, developed by NIAID's Bernard Moss, M.D., Ph.D., and his colleagues. To construct the second vaccine, the researchers added the same genes to a virus called MVA. This virus, a modified version of vaccinia virus that cannot reproduce in human cells, was first produced in the 1960s as a safe, effective smallpox vaccine. Later research led by Dr. Moss, who is chief of NIAID's Laboratory of Viral Diseases, further developed the virus for use as a vehicle to ferry genes into the body.

Both vaccines lack certain HIV genes to ensure against formation of HIV itself, so there is no chance of HIV infection due to vaccination. "Our results show that we can protect monkeys against an HIV-like virus using an immunization scheme that is practical for use in people," explains study director Harriet Robinson, Ph.D., chief of the division of microbiology and immunology at Emory University's Yerkes Regional Primate Research Center.

In the current study, researchers combined the DNA and MVA vaccines in a prime-boost fashion. In theory, the DNA vaccine primes the immune response, alerting the body's defenses to a SHIV invasion and preparing against subsequent attacks. The MVA booster then kicks the immune system into high gear by mimicking a viral infection. The researchers hoped a combination regimen of the two vaccines would strengthen the immune system's ability to remember how SHIV looks and launch a rapid defense if infection occurred.

The investigators vaccinated four groups of Rhesus macaque monkeys, each group receiving different dosages of vaccines or different routes of injection. The monkeys were compared with four unvaccinated animals. The researchers waited seven months after vaccination and then infected all the macaques with a high dose of SHIV. "Most other studies challenge after several weeks," says Dr. Moss, "but a vaccine that only protects for a short time is not very helpful. We extended the post-vaccination time to check long-term efficacy." Dr. Moss also stresses another important feature of their vaccine strategy: the monkeys were infected by applying the virus in the rectum. "The majority of HIV infections occur when the virus crosses mucous membranes, so we needed to see if our vaccine would work against this route of infection."

Although all 28 monkeys were infected, the vaccinated monkeys showed lower initial SHIV levels and quickly began to suppress the virus further. Twenty weeks after infection, the amount of virus in the bloodstream of the vaccinated monkeys was on average 2,000 times lower than controls. The researchers continue to monitor virus levels in these animals.

"These are among the very best outcomes we have seen in an animal model," says Peggy Johnston, Ph.D., NIAID's assistant director for HIV vaccines, "and we are using NIH's developmental resources and the HIV Vaccine Trials Network (HVTN) to move these and other promising vaccines into human trials in the United States and elsewhere as quickly as possible."

Both teams have already constructed HIV versions of the DNA and MVA vaccines, and human clinical trials are currently planned for the coming year. The rapid progress of these products and their future entry into clinical trials is being supported by NIAID through a range of programs put into place to fast-track HIV vaccines through the various stages of basic and preclinical research, product development and production, and clinical trials.

NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

NOTE TO RADIO EDITORS: A 60-second audio report about this study will be available from the NIH Radio News Service beginning on Thursday, March 8, at 2:00 p.m. The actuality will feature Dr. Peggy Johnston. The report will be available at 1-800-633-3425 and at http://www.radiospace.com

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov

The National Institute of Allergy and Infectious Diseases is a component of the National Institutes of Health, U.S. Department of Health and Human Services

National Institute of Allergy and Infectious Diseases

NIH NEWS ADVISORY

EMBARGOED FOR RELEASE
Thursday, March 8, 2001
6:30 p.m. EST

Contact: Jeffrey Minerd
NIAID Office of Communications
and Public Liaison
(301) 402-1663

DON'T GET RID OF THAT CAT YET, SAY ASTHMA RESEARCHERS

Parents who worry that their household cat might trigger asthma in their children shouldn't be too quick to get rid of the pet, according to a study that appears in the March 10 issue of "The Lancet". The study shows that high levels of cat allergen in the home decrease the risk of asthma, apparently by altering the immune response to cats.

The study, funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), begins to uncover the immune system processes behind this phenomenon. This work was also supported by the National Institute of Environmental Health Sciences (NIEHS).

For many allergens, such as the house dust mite, the higher the level of exposure, the higher the likelihood of a person producing "allergic" antibodies (called immunglobulin E or IgE antibodies). High allergen levels also increase a person's risk of becoming allergic and developing asthma.

Thomas A. Platts-Mills, M.D., Ph.D., and colleagues at the University of Virginia's Asthma and Allergic Diseases Center have shown that cat exposure is different. The researchers measured the levels of antibodies to cat allergen in 226 children, aged 12 to 14 years, and tested the children for asthma. They also measured the amount of cat allergens in the children's homes and discovered that low-to-moderate amounts of cat allergen seemed to trigger allergy, but high amounts reduced both IgE antibodies and the likelihood of asthma.

"This result alters the advice we give patients," says Dr. Platts-Mills. "I would not recommend that parents get rid of their cat because they are concerned their child might develop asthma. However, high exposure to cat allergen appears to be protective for some children and a risk factor for others. If the child is wheezing and has a positive skin test to cat allergen, then you should get rid of your cat."

The high levels of cat allergen prompted the children's immune systems to predominantly make immunoglobulin G (IgG) and IgG4 antibodies rather than IgE, explains Marshall Plaut, M.D., chief of the allergic mechanisms section at NIAID. "This research sheds more light on the relationship between allergen exposure and asthma. When investigators further understand this process, it might lead to new treatments for asthma."

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov

--------------------------------
Reference:
T Platts-Mills et al. Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a populations-based cross-sectional study. "The Lancet" 357:752-56 (2001).

National Library of Medicine

NIH NEWS RELEASE

FOR IMMEDIATE RELEASE
Monday, March 12, 2001

CONTACT:
Robert Mehnert or
Kathleen Cravedi
(301) 496-6308
publicinfo@nlm.nih.gov

INNOVATIVE TECHNOLOGY HELPS PUBLIC TOUCH TREASURES: NATIONAL LIBRARY OF MEDICINE TO LAUNCH "TURNING THE PAGES"

(Bethesda, Md.) -- Did you ever go to a historical exhibit and see a fascinating old book locked in a museum case? It was probably carefully propped open to display just two pages. Did you wish you could actually leaf through it? Now you can.

The first U.S. site of "Turning the Pages," a remarkable program developed at the British Library, is the National Library of Medicine (NLM), in Bethesda, Maryland. On March 16, 2001, the NLM will unveil a digitally browsable "Elizabeth Blackwell's Curious Herbal", published between 1737 and 1739.

"TURNING THE PAGES" WILL BE DEMONSTRATED TO REPORTERS ON FRIDAY, MARCH 16, 2001, FROM 9:30 A.M. TO 3:30 P.M. THERE WILL BE A LIVE TRANSATLANTIC CEREMONY AT 1:30 P.M., FEATURING DONALD A.B. LINDBERG, M.D., DIRECTOR OF THE NLM, IN BETHESDA, AND LYNNE BRINDLEY, CHIEF EXECUTIVE OF THE BRITISH LIBRARY, IN LONDON.

"Turning the Pages" uses computer animation, high-quality digitized images, and touch screen technology to simulate the action of turning the pages of a book. "The sensation of actually leafing through a rare volume is uncannily real," said NLM Director Donald A.B. Lindberg, M.D. "It reveals the significance and beauty of rare volumes in a way never before possible, and we are grateful to the British Library for creating the system and letting us be the first to use it in this country," he added.

Besides looking at the beautiful drawings by moving a finger across the screen and moving forward or backward in the volume, the "reader" can touch an icon on each page and zoom in on any portion of a page as desired. The U.K. Design Council voted the "Turning the Pages" system a "Millennium Product," leading to it being displayed at the Department of Trade and Industry.

The first book in the U.S. to be available this way, the Blackwell herbal has a curious history. It is notable both for its beautiful illustrations of medicinal plants and the fact that Elizabeth Blackwell undertook its creation and publication to raise money to satisfy her husband's debts and have him released from debtors prison. Color plates depict 30 plants ranging from the common dandelion, used as a diuretic, to the tomato, which was brought to Europe from the Americas and thought to be good for inflammations.

Lynne Brindley commented: "Our Library has worked closely with the National Library of Medicine since 1966 when it was the first International MEDLARS Center. The British Library was the first organization in Europe to offer MEDLINE as an online service in the mid 1970s. It gives me, therefore, particular pleasure to continue this close association through the project to digitize Elizabeth Blackwell's Herbal and to bring the Library's award-winning Turning the Pages technology to the U.S. We look forward to further digital collaborations."

This is the first of several volumes for which the NLM plans to employ this technology. The second will be Vesalius's "Humani corporis fabrica" ("on the construction of the human body"), which is illustrated with detailed, precise anatomical drawings made from dissections carried out personally by the author. This is the first truly modern anatomical text.

The National Library of Medicine, a part of the National Institutes of Health, is the world's largest library of the health sciences. The address of the Library is 8600 Rockville Pike in Bethesda, Maryland. The ceremony will be in Building 38A, the Lister Hill Center. The Library has an extensive Website at http://www.nlm.nih.gov that provides a great variety of information for the public and for health professionals.

NOTE TO MEDIA: For photographs and video, get in touch with the Library's Office of Communications and Public Liaison at publicinfo@nlm.nih.gov

National Institute of Mental Health

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Monday, March 12, 2001

Contact:
Constance Burr
(301) 443-4536

STUDENTS BRAINSTORM WITH NEUROSCIENTISTS
BRAIN AWARENESS WEEK PROGRAMS TO BE HELD MARCH 14-15

Local junior high school students will find out just what makes their brains tick in activities co-sponsored by the National Institutes of Health and the Dana Alliance for Brain Initiatives. An educational brain trust of students and scientists, the program will take place at the National Museum of Health and Medicine, March 14 and 15, 2001, from 9:30 a.m. to 2:00 p.m. each day.

Students will explore the brain at work with some of the nation's top scientists. They will have the chance to examine real brains, see brain images during thinking, acting, or feeling, and learn how to train their brains. They will play games, solve puzzles, and ask questions like: Why can I remember baseball scores but forget where I put my keys? How does alcohol affect the brain? Are girls' and boys' brains different?

"Brain Awareness Week," March 12-18, is an international event with 46 countries and some 1,250 organizations participating. It was launched by the Dana Alliance in 1995 to inform the public about the importance of brain research. The National Museum of Health and Medicine program is part of a new Partners in Education project to encourage student interest in neuroscience.

During the two-day program, Dr. Steven Hyman, Director, National Institute of Mental Health (NIMH), will present "The Promise of Neuroscience." Dr. Enoch Gordis, Director, National Institute on Alcohol Abuse and Alcoholism, will talk about "Understanding Alcohol: What Science Tells Us." On March 15, Dr. Alan Leshner, Director, National Institute on Drug Abuse, will talk about "The Science of Drug Abuse and Addiction: What Do We Know?" Dr. Audrey Penn, Deputy Director, National Institute of Neurological Disorders and Stroke, will address "Know Your Brain." Students will also meet scientists in smaller groups around the museum.

--National Institute of Mental Health scientist Beth Molloy, Director of the Twin Project, will explain the "Wonders of the Brain." She will present some amazing and puzzling features of the human brain, highlighting its function, development, and peculiarities. Illustrations will show how brains can play tricks on us.

--National Institute of Neurological Disorders and Stroke scientists Dr. Cheryl Kitt and Dr. Lynn Hudson will present "Know Your Brain," showing students brain slices through a microscope, magnetic resonance imaging (MRI) on a light box, brain samples with magnifying glasses, and fun with brain teasers.

--National Institute on Aging scientists Dr. Elisabeth Koss and Dr. Judith Finkelstein will talk about "How We Use Our Brain," focusing on taste, smell, hearing, and thinking. Their props and handouts will pinpoint areas of sensation and perception in the body's most complex organ.

--National Institute on Alcohol Abuse and Alcoholism scientist Dr. Dennis Twombly will use a brain model with flashing lights to help students understand how neurons change in "The Drunken Brain." Students will navigate an obstacle course wearing Fatal Vision Goggles to simulate a drunken state.

--National Institute on Drug Abuse scientists Drs. Cathrine Sasek, Nancy Pilotte, Angela Martinelli, and Suman A. Rao will talk about abused drugs, such as cocaine and marijuana, and their actions in the brain and body. Students will learn how abused drugs operate in the brain in "Who Wants to Be a Neuroscientist?"

--National Museum of Health and Medicine Neuroanatomical Curator Archie Fobbs will address "What Is a Normal Brain?" Students will see normal and diseased brains and have the opportunity to examine a real brain that has been preserved through a process called "plastination."

The program will be given on Wednesday, March, 14, with students from Stuart Hobson Middle School, Hart Middle School, and Backus Middle School; on Thursday, March 15, with students from McFarland Middle School, Capitol Hill Day School, Shepherd Elementary School and Grace Episcopal Day School.

The National Museum of Health and Medicine, founded as the Army Medical Museum in 1862 to study and improve medical conditions during the American Civil War, is a division of the Armed Forces Institute of Pathology. The Museum's Neuroanatomical Collection includes some 37,000 specimens used widely for research and education. Open daily except Christmas from 10 a.m. to 5:30 p.m., the museum is located at Walter Reed Medical Center, 6900 Georgia Avenue and Elder Street, N.W., Washington, D.C. Admission is free ( http://www.natmedmuse.afip.org/ ).

The Dana Alliance for Brain Initiatives is a nonprofit organization of more than 190 preeminent neuroscientists, including seven Nobel Laureates, who are committed to advance education about the public benefits of brain research. The Dana Alliance is supported by the Charles A. Dana Foundation, a private, philanthropic organization with interests in neuroscience and education.

The National Institutes of Health is the Federal agency dedicated to biomedical research, and the participating Institutes are the premier supporters of research on the brain and nervous system. The NIH is located in Bethesda, MD.

Contacts: NIH - Constance Burr (NIMH) 301-443-4536; Margo Warren (NINDS) 301-496-5751; Anne Decker (NIA) 301-496-1752; Michelle Muth (NIDA) 301-443-6245; Diane Miller (NIAAA) 301-443-3860. National Museum of Health and Medicine - Janet Burns, 202-782-2673; Dana Alliance for Brain Initiatives - Karen Graham, 301-951-9177

National Institute of Mental Health

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Monday, March 12, 2001

Contact:
Constance Burr
(301) 443-4536

EXPLORING YOUR BRAIN

Dr. Eric Haseltine, an executive at Walt Disney Imagineering and a neuroscientist, will address college and high school students at the National Institutes of Health (NIH) on March 14 at 7 p.m. Dr. Haseltine's talk, "The Fantastic Voyage: Let Neuroscience Take You on a Thrilling Expedition into Your Own Brain," is featured in a special program for students hosted by The National Institute of Mental Health (NIMH) at Natcher Auditorium on the NIH campus. The program highlights Brain Awareness Week, an annual event that informs the public about the importance of brain research.

Following Dr. Haseltine's presentation, NIH neuroscientists will discuss what brought them to research, neuroscience, and NIH. NIMH Director Dr. Steven Hyman will moderate the panel. The speakers aim to stimulate interest in research and show how science crosses disciplines and offers exceptional career opportunities. Students will have the opportunity to talk one-on-one with these scientists about how their goals and passions can advance the frontiers of brain science.

More than 125 schools and college in Washington, D.C., Maryland, and Virginia have been notified about the program. Additional information is available at http://www.nimh.nih.gov/events/fantastic.cfm

Brain Awareness Week is an international effort led by the Dana Alliance for Brain Initiatives, a nonprofit organization of more than 190 neuroscientists, including seven Nobel Laureates, who are committed to advance education about the public benefits of brain research. Five Institutes sponsor Brain Awareness Week activities: NIMH, the National Institute of Neurological Disorders and Stroke, The National Institute on Aging, The National Institute on Drug Abuse, and the National Institute on Alcohol Abuse and Alcoholism.

NIMH is part of NIH, the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U. S. Department of Health and Human Services. For more information about NIMH and its research programs, visit the NIMH web site http://www.nimh.nih.gov

National Library of Medicine

NIH NEWS RELEASE

FOR IMMEDIATE RELEASE
Monday, March 12, 2001

CONTACT:
Robert Mehnert or
Kathleen Cravedi
(301) 496-6308
publicinfo@nlm.nih.gov

TECHNOLOGY IS SHAPING THE FUTURE OF HEALTH CARE

(Bethesda, Md.)-- An ambulance in Maryland relays real time information and images to a trauma center while en route, allowing a stroke patient to receive vital care during a critical time known as the "golden hour." Parents of a premature baby in Boston are able to monitor their child from their home and have the same equipment used by the hospital to provide educational and emotional support to the parents following the baby's discharge. In California, consumers are able to quickly access their private medical records via a secure Web site.

These are just some of the latest developments in health care technology that researchers will be discussing at the National Library of Medicine's symposium, "Telemedicine and Telecommunications: Options for the New Century." The meeting will be held on March 13-14, 2001 at the Natcher Conference Center at the National Institutes of Health in Bethesda, Maryland. More detailed information about the meeting is available at http://www.nlm.nih.gov/research/telesymp.html

NLM has funded 19 telemedicine projects since 1993, many of which will be highlighted at the conference. The purpose of the research is to evaluate the use of communications technology in the implementation and performance of telemedicine activities, and examine the impact of telemedicine on medical care in terms of cost, quality, and access.

"Through the National Telemedicine Project, we have found that the right information delivered at the appropriate time can have a positive effect on health outcomes. With the Next Generation Internet just around the corner, telemedicine is beginning to realize its potential," said Donald A. B. Lindberg, M.D., Director of the National Library of Medicine.

"In this age of the Internet and virtual reality, telemedicine and telecommunications have the potential to be part of nearly every aspect of health care -- from consumer and provider education to the actual diagnosis and treatment of disease," said Dr. Michael Ackerman, head of NLM's Office of High Performance Computing and Communications and co-chair of the symposium.

Dr. Douglas Perednia, a medical internist and dermatologist, will be providing the keynote address at the meeting. His work began in the 1980's with research on the early detection of melanoma through computerized analysis of skin images. Dr. Perednia will discuss telehealth's slow migration into mainstream health care.

The National Library of Medicine began major funding for telemedicine-related activities in 1993 as part of the Federal High Performance Computing and Communications (HPCC) program. In 1996, NLM inaugurated the NLM National Telemedicine Initiative under the HPCC program. This conference brings together the NLM-funded investigators to discuss results obtained and lessons learned from their research projects.

The Library's activities in this field are continuing through the current funding of projects that assess the use of Next-Generation Internet technology for health applications, including telemedicine. Results from these studies will be reported in detail at a future time; however, general information is available at www.nlm.nih.gov/research/ngiinit.html.

NOTE TO REPORTERS: An ambulance equipped to relay real- time information and images to a hospital trauma center while en route will be available for demonstration at 10:30 a.m., Tuesday, March 13, 2001.

Members of the media are invited to attend. Press inquiries should be directed by phone to Kathy Cravedi or Bob Mehnert at 301 496-6308 or by e-mail to publicinfo@nlm.nih.gov

Office of the Director (OD)

Office of Medical Applications of Research (OMAR)

NIH NEWS ADVISORY

FOR IMMEDIATE RELEASE
Wednesday, March 14, 2001

Contacts:
John Bowersox, NIH/OMAR
(301) 496-4819
bowersoj@od.nih.gov

Jody Dove, NIDCR
(301) 594-7558
dovej@mail.nih.gov

NIH CONSENSUS PANEL WILL WEIGH EVIDENCE ON BEST WAYS TO PREVENT, DETECT, AND TREAT TOOTH DECAY

The National Institutes of Health (NIH) will hold a Consensus Development Conference on Diagnosis and Management of Dental Caries Throughout Life on March 26-28, 2001. The conference takes place in the William H. Natcher Building auditorium on the NIH campus in Bethesda, Maryland and concludes with a news conference at 1:00 p.m. ET on Wednesday, March 28, 2001.

Although great strides have been made in dental health in recent decades, dental caries, or tooth decay, remains common in the United States. Nearly 20 percent of children between the ages of 2 and 4 have had tooth decay and almost 80 percent of young people have had a cavity -- a late manifestation of tooth decay -- by age 17. More than two- thirds of adults ages 35 to 44 years have lost at least one permanent tooth due to decay, while one-fourth of those ages 65 to 74 have lost all of their natural teeth.

Water fluoridation, dental sealants, and regular professional dental care are among the safe and effective, though underused, measures currently available for preventing and treating dental caries. Scientific research continues to fuel remarkable progress in our understanding of the best ways to diagnose, treat, and prevent dental caries.

This conference will examine the current state of dental caries research to help health care providers and the general public make informed decisions about this important health issue. During the first day-and-a-half of the conference, experts will present the latest dental caries research findings to an independent, non-Federal consensus development panel. After weighing all of the scientific evidence, the panel will draft a statement that will be presented to the conference audience on the third day. The panel's statement will address the following key questions:

--What are the best methods for detecting early and advanced dental caries (validity and feasibility of traditional methods; validity and feasibility of emerging methods)?

--What are the best indicators for an increased risk of dental caries?

--What are the best methods available for the primary prevention of dental caries initiation throughout life?

--What are the best treatments available for reversing or arresting the progression of early dental caries?

--How should clinical decisions regarding prevention and/or treatment be affected by detection methods and risk assessment?

--What are promising new research directions for the prevention, diagnosis, and treatment of dental caries?

The panel will present its draft statement to the public for comment at 9:00 a.m. on Wednesday, March 28. Following this public comment session, the panel will release its revised consensus statement at a news conference at 1:00 p.m. and take questions from the media.

The consensus statement is the report of an independent panel and is not a policy statement of the NIH or the Federal Government.

The primary sponsors of this meeting are the National Institute of Dental and Craniofacial Research and the NIH Office of Medical Applications of Research. Cosponsors include the National Institute on Aging and the U.S. Food and Drug Administration.

Additional information about this conference, including the meeting agenda, local area hotels, and directions to NIH, is available at the NIH Consensus Development Program Web site at http://consensus.nih.gov

NOTE TO TV EDITORS: The news conference at 1 p.m. on Wednesday, March 28 will be broadcast live via satellite on the following coordinates: Telstar 6, Transponder 21; C- Band; Download Frequency=4120 vertical; Polarity=93 Degrees West. (Test time 12:30 - 1:00 p.m.)

NOTE TO RADIO EDITORS: An audio report of the conference results will be available after 4 p.m. March 28, 2001 from the NIH Radio News Service by calling 1-800-MED-DIAL (1- 800-633-3425).

NIH Videocasting will broadcast the conference live on the Internet. Go to the NIH Videocast Web site -- http://videocast.nih.gov/ -- any day during the conference and look for the link to the conference under "Today's Events."

If you require any assistance or assistive devices to participate in this conference, please contact Prospect Associates at 301-592-3320, or via e-mail at dentalcaries@prospectassoc.com , at least 48 hours before the conference.

The Office of the Director is a component of the National Institutes of Health, U.S. Department of Health and Human Services.

National Institute of Nursing Research

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Thursday, March 15, 2001

Contact:
Linda Cook
National Institute of Nursing Research
(301) 496-0209
lc59t@nih.gov

Jim Newman
Oregon Health Sciences University
(503) 494-4158
newmanj@ohsu.edu

ADVANCE DIRECTIVES FOUND KEY TO REDUCING STRESS FOR FAMILIES OF HOSPITALIZED PATIENTS AT THE END OF LIFE

Researchers from the Oregon Health Sciences University report that stress levels have been measured as extremely high for family members who must decide whether or not life support should be withdrawn from relatives too incapacitated to decide for themselves. Reported levels of stress are twice as high as those due to other serious crises, such as ferry or construction disasters, or losing a home to fire. Stress was least severe when patients' written advance directives were available and most severe in the absence of written or verbal directives. Funded by the National Institute of Nursing Research (NINR), the study results appear in the March/April issue of the journal "Nursing Research".

"An advance directive can be very helpful for families making decisions about end of life issues," said NINR Director Patricia A. Grady, PhD, RN. NINR coordinates NIH end-of-life/palliative care research, a relatively new area of science. Dr. Grady indicated that less than 20 percent of adults have advance directives, "which means we must find strategies to significantly increase their use to diminish stress for both patients and families going through life's final phase."

The study focused on 74 family members whose relatives had recently died in hospitals. The researchers focused on hospital deaths because decisions to start and stop life support more often occur in hospitals. Families were interviewed twice -- at one to two months after the death of their relatives and again at six to nine months afterwards. Their responses indicated that half a year later their stress was still high but had notably improved. Information was also collected from the doctors and nurses who had cared for the patients.

The researchers also studied how families made decisions. In the absence of advance directives, families were more likely to push for prolonging life for the patient even when the treatments were not working and the patient was suffering. When the patient had a written advance directive to guide the family, the family was more comfortable focusing on the patient's quality of life as the guide to reaching the decision to stop life-sustaining treatments.

Virginia Tilden, DNSc, RN, the principal investigator of the study, stated "With advance directives, families are able to concentrate on improving the patient's quality of life during the time left, rather than futilely prolonging life, with high risk of making patients suffer unnecessarily."

Susan Tolle, M.D., a co-investigator of the study, indicated that "nurses and doctors can play a strong role in encouraging patients before they become gravely ill to complete advance directives and to discuss them with their families. This will reduce stress on their families down the road."

According to the study, families indicated that ending life support was the "hardest thing I have ever done in my life." Typical sentiments were "I wouldn't wish this [reaching a decision] on my worst enemy," and "I can't remember what went on because I was so upset."

Other study findings indicated that clinicians and families believed that poor quality of life and patient preference not to suffer were about equal in importance in deciding whether to withdraw life support. But families gave prolongation of life a stronger consideration than did clinicians. Both groups indicated a patient's preference, if known, was first among considerations about ending life support.

The National Institute of Nursing Research is a component of the National Institutes of Health, U.S. Department of Health and Human Services.

National Heart, Lung, and Blood Institute

NIH NEWS RELEASE

EMBARGOED FOR RELEASE:
Thursday, March 15, 2001

Contact:
NHLBI Communications Office
(301) 496-4236

NEW TOOLS FOR HEALTH CARE PROVIDERS AND THE PUBLIC TO COMBAT OVERWEIGHT AND OBESITY

A "practical guide" to help health care providers manage the treatment of their overweight and obese patients, an online interactive menu planner, and consumer tips on behavior change for weight management are some of the new tools being unveiled by the National Heart, Lung, and Blood Institute (NHLBI) this month to help tackle America's battle of the bulge.

The need for these tools couldn't be more pressing. Recent statistics from the National Health and Nutrition Examination Survey (NHANES) show that between 1994 and 1999 the U.S. experienced a 5 percent increase in the number of adults who are overweight or obese.

"This is 61 percent of the U.S. adult population -- almost 108 million people -- who because of their weight are at greater risk for several major diseases including heart disease, stroke, diabetes, and cancer," said NHLBI Director Dr. Claude Lenfant.

To help these people and their health care team, NHLBI's Obesity Education Initiative in cooperation with the North American Association for the Study of Obesity convened a working group to prepare "The Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults". Based on the clinical guidelines released by NHLBI in 1998, the practical guide is just that -- a practical manual with tools and tips for weight loss.

"This guide gives health care providers the fundamentals needed to evaluate and treat this important health problem and contains information which has not been provided elsewhere in their training," said Dr. Louis J. Aronne, chair of the committee that developed the guide and clinical associate professor of medicine at Weill-Cornell Medical College in New York City.

The guide's new features, which were not in the original obesity guidelines, include a 10-step plan and a quick reference tool to help physicians assess, classify, and treat overweight and obesity. The guide also includes detailed sections on dietary therapy, physical activity, and behavior therapy. In addition, the handbook discusses the appropriate use of weight loss drugs (with recommended doses of specific drugs) and indications for surgery as a treatment for obesity.

A key section of the guide is the appendices, which were written for patients and include practical information on diet, physical activity, and tools for behavior change. There is also a weight management chart, sample walking and jogging programs, and tips for dining out, shopping, and cooking.

"All of these tools reflect the fact that simple, small changes in the way we eat and engage in physical activity can add up over time to a healthier weight," said Karen Donato, coordinator of the NHLBI's Obesity Education Initiative.

Consumers -- and health care professionals -- can find all of these tools online on the NHLBI Web site (www.nhlbi.nih.gov). The Institute's Web site will also post a PalmOS (R) format version of the practical guide. In addition, the site already contains a body mass index (BMI) calculator for PalmOS (R) devices. The calculator accepts English or metric input and includes a BMI classification table for adults.

A new feature on the Institute's Web site is the ultimate "cyber" tool for devising low calorie meals -- an interactive menu planner. The menu planner allows the user to plan a single meal or a whole day's meals. To use the planner, you choose your total calories for the day, and select a meal. You then select foods from a list, according to the food groups included in the American Dietetic Association/American Diabetes Association exchange list. Finally, you choose the number of servings you want and the calories are calculated for you.

"It's easy and it actually makes calorie counting fun," said Donato who suggested consumers try the site during March -- National Nutrition Month.

To interview Ms. Donato, contact the NHLBI Communications Office at 301-496-4236. To interview Dr. Aronne, call 212- 583-1000. To order a printed version of the guide, call the NHLBI Health Information Center at 301-592-8573 or order online from the NHLBI catalog: http://emall.nhlbihin.net/ A single copy is $5.00. The consumer appendices in the guide have been compiled into a document called "Clinical Guidelines: Highlights for Patients". This document is $1.00 per copy.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH NEWS RELEASE

FOR IMMEDIATE RELEASE
Wednesday, March 14, 2001

Contacts:
Kelli Carrington or Susan Bettendorf
Office of Communications and Public Liaison, NIAMS
(301) 496-8190

NEW RESEARCH REGISTRY TO EXAMINE RHEUMATOID ARTHRITIS IN AFRICAN AMERICANS

Four major academic medical centers in the southeast United States will soon be gathering data for investigators interested in the genetics of rheumatoid arthritis (RA) in African Americans, with support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The Institute, a component of the National Institutes of Health (NIH), has awarded a research contract for the Consortium for the Longitudinal Evaluations of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry to the University of Alabama at Birmingham (UAB). Other participating centers are Emory University, the Medical University of South Carolina and the University of North Carolina.

The registry will provide clinical and x-ray data and DNA to help scientists analyze genetic and nongenetic factors that might predict disease course and outcomes of RA in this population. Certain genes that play a role in the immune system are associated with a tendency to develop RA. Some individuals without these genes may develop this disease, while others who possess the genes never develop RA. Scientists believe that some environmental factors may play a part, triggering the disease process in people whose genetic makeup makes them susceptible to RA.

The investigators intend to register 600 participants. Since there are currently no ongoing studies evaluating early RA in African Americans, the investigators have focused on this population. African Americans are underrepresented in most clinical studies, including current observational studies of people with RA. "Identifying any factor, genetic or otherwise, that may predispose an individual to rheumatoid arthritis or provide clues to an individual's disease outcome will greatly improve our efforts to treat and ultimately prevent this disease which affects so many people," said Stephen I. Katz, M.D., Ph.D., NIAMS director.

"This registry of African Americans with early RA will be critical in identifying risk factors, including genetic and environmental, that point to a more aggressive disease process," said Larry Moreland, M.D., principal investigator of the CLEAR Registry. "Ultimately, the ability to identify patients very early in the disease process who might have a worse long-term outcome will allow physicians to provide better treatments for these patients."

Participating investigators are S. Louis Bridges, Jr., M.D., Ph.D., co-director of CLEAR at UAB; Doyt L. Conn, M.D., and Janet McNicholl, M.D., at Emory University, Atlanta, Ga.; Edwin Smith, M.D., and Gary Gilkeson, M.D., at the Medical University of South Carolina, Charleston; and Beth Jonas, M.D., and Leigh Callahan, Ph.D., at the University of North Carolina, Chapel Hill.

RA is an autoimmune disease, in which the body's immune system attacks its own tissues. It occurs in all races and ethnic groups, and affects about two to three times as many women as men. Scientists estimate that RA affects the lives of one percent of the adult population in the United States, although young adults and children can also be affected. Symptoms and severity vary greatly among individuals, and may include inflammation, pain, swelling, stiffness and progressive loss of function in the joints. It may also cause fatigue, occasional fever and a general sense of not feeling well. In some cases, the internal organs and systems can become involved and ultimately damaged.

Patient enrollment for the registry is projected to begin in late spring 2001. The project is funded under NIH contract # N01-AR-0-2247.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is a component of the National Institutes of Health. The mission of the NIAMS is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call our information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.nih.gov/niams

To interview Dr. Larry Moreland, contact Joy Carter, Office of Media Relations, University of Alabama at Birmingham, at 205-934-1676.

To enroll in the registry, contact one of the following individuals who will direct you to the appropriate representative in each participating state:

Tina Parkhill (205-934-9368; e-mail: tina.parkhill@ccc.uab.edu) or Fannie Johnson, R.N. (205-934-7427; e-mail: fannie.johnson@ccc.uab.edu) The Spain Rehabilitation Center University of Alabama, Birmingham Arthritis Center Clinical Intervention Program SRC 068, ZIP 7201 1717 6th Avenue South Birmingham, AL 35294 fax: 205-975-5554

National Institute on Drug Abuse

NIH NEWS RELEASE

EMBARGOED FOR RELEASE:
Wednesday, March 14, 2001
2:00 p.m. EST

Contact:
Beverly Jackson
Michelle Muth
301-443-6245

SCIENTISTS IDENTIFY PROCESS THAT PLAYS KEY ROLE IN BRAIN CHANGES INVOLVED IN COCAINE ADDICTION

Researchers supported by the National Institute on Drug Abuse (NIDA) have identified a process in the brain that may underlie addiction to cocaine and other drugs of abuse. Their research indicates that repeated exposure to cocaine causes a change at the level of gene expression that leads to altered levels of a specific brain protein called cyclin-dependent kinase 5 (Cdk5). The same group of researchers previously found that Cdk5 regulates the action of dopamine, a chemical messenger in the brain associated with the cocaine's pleasurable "rush" and with addiction to cocaine and other drugs. The Cdk5-related process leads to changes in brain cells that are thought to play a key role in cocaine addiction.

Dr. James Bibb, Dr. Paul Greengard, and colleagues at the Rockefeller University in New York City, together with Dr. Eric Nestler at the University of Texas Southwest Medical Center in Dallas, report their findings in the March 15 issue of the journal "Nature".

"This research provides a valuable insight into the step- by-step molecular adaptations that the brain makes in response to drugs," says NIDA Director Dr. Alan I. Leshner. "These adaptations result in long term changes at the cellular level that are involved in the development of addiction."

Dr. Bibb and his colleagues found that, in dopamine- sensitive brain cells of rodents, exposure to cocaine causes gene-mediated increases in levels of delta-FosB, a protein that in turn triggers increases in Cdk5 levels. Mice genetically engineered to "overexpress" delta-FosB as well as rats injected with cocaine for 8 days showed elevated levels of Cdk5 compared with rats injected with a saline solution. The cocaine-exposed rats also exhibited increases in motor activity following cocaine administration, consistent with cocaine's stimulant actions. In rats treated daily with roscovitine, a compound that inhibits the action of Cdk5, motor activity one hour after cocaine exposure was nearly double that of rats that were not treated with the Cdk5 inhibitor. These behavioral findings indicate that cocaine-induced increases in Cdk5 levels may dampen the brain's response to cocaine exposure, which would lead cocaine abusers to use more of the drug to achieve the desired effect.

"These results suggest that delta-FosB-mediated changes in Cdk5 levels and the resulting alterations in dopamine signaling in brain cells contribute to adaptive changes in the brain related to cocaine addiction," Dr. Bibb says.

NOTE TO REPORTERS: The full text of this article will be available on "Nature's" Web site at www.nature.com/nature.

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and other topics can be ordered free of charge in English and Spanish through NIDA Infofax at 1-888-NIH-NIDA (644-6432) or 1-888-TTY-NIDA (889-6432) for the deaf. These fact sheets and further information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov

National Institute of Allergy and Infectious Diseases

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Wednesday, March 21, 2001
5:00 p.m. EST

Contact: Laurie K. Doepel
(301) 402-1663
doepel@nih.gov

TRANSPLANTS OF SIBLING STEM CELLS SHOW PROMISE FOR IMMUNE DISORDER

National Institutes of Health (NIH) researchers have used a novel bone marrow transplantation procedure to successfully transfer stem cells from immunologically matched siblings into a small group of people who have a rare, inherited immune disorder. The disorder, chronic granulomatous disease (CGD), leaves individuals vulnerable to life- threatening infections and inflammatory growths, or granulomas, which can damage the lungs, liver and other organs. Although it is too soon to claim that the patients have been cured, the data so far suggest that for patients in whom the transplant was successful, the immune system is functioning significantly better than before treatment, the investigators say.

"Non-myleloablative stem cell transplantation has previously shown promise in leukemia and kidney cancer patients," comments Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), "but this is the first clinical trial of this strategy in a series of patients who have an inherited immune disorder." The low-intensity stem cell transplantation procedure, which uses no radiation, is less risky than conventional stem cell transplantation because only some rather than all of the patient's bone marrow cells are wiped out before the individual receives the transplant. As a result, the transplanted patients have a mixture of their own and their sibling's immune cells.

Results of the CGD study, led by Mitchell E. Horwitz, M.D., and Harry L. Malech, M.D., of NIAID's Laboratory of Host Defenses, appear in the March 22 issue of "The New England Journal of Medicine".

CGD affects more than 1,000 people in the United States and an estimated 25,000 people worldwide. It is caused by several different gene mutations that prevent white blood cells called neutrophils from making oxygen compounds that kill bacteria and fungi. Based on studies of people with various types of the mutation, the researchers project that restoring just 10 percent of neutrophils to proper function may stave off recurrent CGD infections.

Recent advances in treating CGD based on an immune-based therapy and antibiotics have extended infection-free intervals and survival time in CGD patients. But many people with the disorder still suffer recurrent bouts of potentially deadly infections as well as a compromised quality of life. Both the infections and the drugs taken to control them can damage vital organs over time. In the United States, between 2 and 5 percent of those affected by CGD die each year.

During the past two decades, the NIAID group has made several important contributions to understanding the genetics and underlying pathology of CGD, and they and others have developed various treatment strategies to reduce the frequency of infections in people with the disorder.

In the "NEJM" study, the NIAID group attempted to move their efforts one giant step forward. "We wanted to determine," says Dr. Malech, "if there are ways to permanently restore proper immune cell functioning without attempting to correct the underlying genetic defect." Dr. Horwitz notes, "We will not know whether this treatment is a potential cure until we follow these patients for several more years. But we are encouraged by the freedom from infection and markedly improved quality of life that have come to the patients who have been successfully transplanted."

Conventional stem cell transplants require that the recipients' bone marrow be knocked out with highly toxic drugs before the transplant procedure to reduce the chances that the graft will be rejected. Because that early step carries a significant risk of serious complications and death, such transplants are most often considered a last- resort option for the sickest CGD patients.

To improve the odds of survival, Dr. Horwitz took the non- myleloablative stem cell transplantation strategy that his colleague A. John Barrett, M.D., from the National Heart, Lung and Blood Institute (NHLBI), pioneered in kidney cancer and leukemia patients and tailored it to CGD patients. Although conditioning regimens associated with low-intensity stem cell transplants are less toxic that those of conventional stem cell transplants, the risk of graft-versus-host disease (GVHD) after the transplant is similar for the two procedures.

Donor T cells present in the stem cell graft are known to cause GVHD. To rid the graft of T cells, Dr. Horwitz turned to the stem cell processing expertise of Elizabeth J. Read, M.D., and her colleagues in the NIH Clinical Center Department of Transfusion Medicine. But T cells are necessary to help fight infection and facilitate transplantation of the donor stem cells. So Dr. Horwitz gradually began reintroducing donor T cells into the patients beginning about one month after the transplant. Their goal in this study was to achieve a stable presence of transplanted donor cells.

"In developing this strategy, we were walking a fine line between the deleterious and beneficial effects of donor T cells," explains Dr. Horwitz. "Without the re-infusion of donor T cells, 70 to 80 percent of the grafts would be rejected," he says. "We had to gradually add back donor T cells over time, enough to prevent rejection but not so much as to cause graft-versus-host disease."

The study enrolled 10 people with severe CGD between the ages of 5 and 36. Six of the study patients had complete engraftment of donor stem cells, and another two had partial engraftment. Overall, the transplant worked best in the five children who were 12 years old or younger, only one of whom experienced a mild case of GVHD. Three adults enrolled in the study died. One death was related to GVHD, one was caused by an infection, and the third was due to complications of a second transplantation after the first was immunologically rejected.

In the median 18 months of follow-up, the investigators have observed only one serious infection characteristic of a patient with CGD disease. In addition, they have seen resolution of pre-existing granulomas. Complete immune reconstitution after stem cell transplantation, Dr. Horwitz notes, can take more than one year.

Despite fewer side effects, the new approach to stem cell transplantation still carries considerable risks, the investigators concede. In the future, they will fine-tune the procedure to further reduce the risks. Dr. Horwitz is planning a new trial that will focus on younger patients with severe CGD. They will be infused with fewer sibling T cells in an attempt to achieve a permanent mixture of sibling and patient blood cells, which data from the current trial indicates will increase the chances of improving immune function and avoiding GVHD.

In an "NEJM" editorial about the research, R. Alan B. Ezekowitz, M.D., Ch.B., D.Phil., of Massachusetts General Hospital concludes, "It seems that we are at the threshold of real advances in therapies for inherited disorders....These new techniques may allow the cure of a wide range of inherited disorders in the next decade."

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov

References: ME Horwitz et al. Treatment of chronic granulomatous disease with nonmyeloblative conditioning and a T-cell- depleted hematopoietic allograft. "The New England Journal of Medicine" 344:881-88 (2001).

RAB Ezekowitz. What is the best way to treat inherited disorders? "The New England Journal of Medicine" 344:926- 27 (2001).

National Institute of Neurological

Disorders and Stroke

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Wednesday, March 21, 2001
2:00 p.m. EST

Contact:
Paul Girolami
301-496-5751

POPULAR PAIN ANALGESICS FOUND TO AFFECT CENTRAL NERVOUS SYSTEM

Study Identifies Both Peripheral and CNS Mechanisms of Action of NSAID Use

Widely prescribed pain killers that provide relief with minimal side effects may have more pain-relieving properties than previously identified. A new study funded by the National Institute of Neurological Disorders and Stroke (NINDS) shows that non-steroidal anti-inflammatory drugs, or NSAIDs, not only relieve pain at the local (peripheral) site of inflammation but in fact affect the entire central nervous system. Results of the study appear in the March 22, 2001, issue of "Nature".

NSAIDs reduce sensitivity of nerves in the central nervous system by inhibiting production of the Cox-2 enzyme responsible for pain and inflammation. Two prescription drugs introduced last year that target Cox-2 proved to be blockbuster pain relievers, but their mechanism of action was not understood until now.

A research team led by Clifford J. Woolf, M.D., Ph.D., at Massachusetts General Hospital in Boston used an animal model to study Cox-2's role in inflammatory pain. When inflammation occurred, researchers found Cox-2 throughout the central nervous system, as well as at the local site of inflammation. They also found that inhibiting Cox-2 production within the spinal cord and brain decreased pain and reduced hypersensitivity to normal sensations such as touch. Researchers now believe the widespread distribution of Cox-2 within the central nervous system may contribute to muscle and joint pain, depression, lethargy, and loss of appetite that often occur with inflammation and infection.

"The findings indicate new treatment options for arthritis and other inflammatory pain conditions," said Cheryl A. Kitt, Ph.D., program director for pain research at the NINDS. "Targeting the central nervous system when using NSAIDs, rather than the specific peripheral pain site, may result in more effective pain relief."

The NINDS, part of the National Institutes of Health in Bethesda, Maryland, is the nation's leading supporter of research on the brain and nervous system. The NINDS is now celebrating its 50th anniversary.

This release will be posted on EurekAlert! at http://www.eurekalert.org and on the NINDS website at http://ninds.nih.gov/news_and_events/index.htm

National Institute of Environmental Health Sciences

NIH NEWS RELEASE

FOR IMMEDIATE RELEASE:
Thursday, March 22, 2001

NIEHS Media Contact:
Bill Grigg,
(301) 402-3378

FEDERAL GOVERNMENT MAKES FINAL CALL FOR DATA, PUBLIC COMMENT BEFORE WRITING NEW REPORT ON CANCER-CAUSING SUBSTANCES

Do estrogens, wood dust, a common solvent called trichloroethylene, the flavoring methyleugenol and the antibiotic chloramphenicol cause human cancer under some circumstances? The National Toxicology Program, headquartered at the National Institute of Environmental Health Sciences, today sought final public comments and data on these and several other substances and exposures before recommending whether to list them as human carcinogens in the federal government's tenth and newest "Report on Carcinogens".

Comments will be accepted for 60 days.

Last year, two federal science committees and one public peer review panel with non-government members looked at eight nominated substances. The three scientific review committees evaluated available, published data relevant to listing these substances as "known" or, with less complete data, as "reasonably anticipated to be" causes of human cancer. Here are the substances reviewed:

--TRICHLOROETHYLENE. This widely used metal degreasing solvent was unanimously recommended for upgrading from "reasonably anticipated" to listing as a "known" human carcinogen by one government panel, the NIEHS Review Committee, but the upgrade was turned down, 4 to 3, by the second government panel representing other agencies and regulators, and by the public panel. If not upgraded, trichloroethylene would continue to be listed as "reasonably anticipated to be a human carcinogen."

--ESTROGENS. Steroidal estrogens, which are used in some post-menopausal therapy and as oral contraceptives, were recommended as "known" human carcinogens by unanimous votes of the two government panels and 8 to 1 by the public panel. Conjugated estrogens, a subgroup of the broad group of steroidal estrogens, are already listed as "known" and drug labeling or package inserts discuss the possible side- effects that occur in some people.

--WOOD DUST. All three panels, after reviewing the data, unanimously recommended wood dust, produced in furniture and cabinet manufacturing, as a "known" human carcinogen.

--UV RADIATION, UVA, UVB AND UVC. All three panels voted unanimously to recommend broad spectrum ultraviolet radiation, whether from the sun or from artificial sources, be listed as a "known" human carcinogen. The lengths, UVA, UVB and UVC were each recommended for listing as "reasonably anticipated to be a human carcinogen."

--METHYLEUGENOL. All three panels recommended this flavoring, traces of which are used in some jellies, baked goods, nonalcoholic beverages, chewing gum, candy and ice cream, be listed as "reasonably anticipated" to be a human carcinogen. Methyleugenol is also used as a fragrance in many perfumes and cosmetics and occurs naturally in many foods.

--CHLORAMPHENICOL. All three panels (with one person abstaining in one of the panels) unanimously recommended the highly restricted antibiotic chloramphenicol be listed as "reasonably anticipated to be a human carcinogen." The drug is considered a "last resort" antibiotic under certain circumstances where other antibiotics have failed.

--NICKEL AND CERTAIN NICKEL ALLOYS. Used in commercial operations for more than 100 years, metallic nickel and certain of its alloys were recommended as "reasonably anticipated" by a vote of 6 to 2 in the initial NIEHS committee, but the second and third panels voted against the alloys being listed, recommending only that nickel itself be listed.

--TALC. Natural mineral talc containing a distinctive fiber shape, called asbestiform fibers, was approved for listing as a known human carcinogen by the NIEHS panel but rejected by the second government panel, which voted 6 to 2 for its listing as "reasonably anticipated to be a human carcinogen." The public panel split 5 to 5 on whether it should even be listed as "reasonably." The two government panels recommended that talc that does NOT contain asbestiform fibers should be listed as "reasonably anticipated to be a human carcinogen" but the public panel voted 7 to 3 that it not be listed at all. This last panel did not consider studies linking ovarian cancer and talc because it was not clear whether the talc contained asbestiform fibers or not.

Additional information can be obtained from the NTP Home Page web site at http://ntp-server.niehs.nih.gov/ or by contacting C. W. Jameson, NTP Mail drop EC-14, P.O. Box 12233, Research Triangle Park, NC 27709; phone: (919) 541- 4096, fax: (919) 541-0144, email: jameson@niehs.nih.gov Comments also should be addressed to Dr. Jameson.

The "Report on Carcinogens" is a Congressionally mandated listing of known human carcinogens and reasonably anticipated human carcinogens and its preparation is delegated to the NTP by the Department of Health and Human Services. The law states that the reports should provide available information on the nature of exposures, the estimated number of persons exposed and the extent to which the implementation of current federal regulations decreases the risk to the public.

NIEHS/NTP plans to publish the tenth report next year.

Further details appear in the "Federal Register", Vol. 66, No. 43, pages 13334-13338.