September 2006 Newsletter

The Friends of the National Institute of Dental and Craniofacial Research (FNIDCR) online newsletter is a membership benefit. Permission is granted to repost this publication only with inclusion of the header. Past issues are posted on www.fnidcr.org/news.html

While Congress was taking a break from the Washington summer heat, the Friends hosted and sponsored several events and patient advocacy meetings. From celebrating the National Foundation for Ectodermal Dysplasia’s 25th anniversary to promoting the 7th International Conference on Moebius Syndrome, the Friends were proud to be a part of an active season of oral health research. Additionally, the Friends held a booth at the annual Congressional Health Fair. Close to 800 participants—and several Members of Congress—received toothbrushes, tooth paste and oral health research information.

After Labor Day, the Friends will join its partners in continuing to advance the need for biomedical research. We'll keep you informed of the Friends' activities.

Mitochondrial DNA Sequencing Tool Update
High-tech laboratory tools, like computers, are often updated publicly as their analytical capabilities expand. In the September issue of the "Journal of Molecular Diagnostics," NIH grantees report they have developed a second generation, "lab on a silicon chip," called the MitoChip v2.0 that for the first time rapidly and reliably sequences all mitochondrial DNA. Mitochondria, the energy-producing organelles that power our cells, are unique because they are equipped with their own genetic instructions distinct from the DNA stored in the cell nucleus.

The authors say their full-sequence chip will be a key tool in accelerating research on mitochondrial DNA, a growing area of scientific interest. This interest stems from data that suggests natural sequence variations and/or mutations in each person's mitochondrial DNA could be biologically informative in fields as diverse as cancer diagnostics, gerontology, and criminal forensics.

According to Dr. Joseph Califano, a scientist at Johns Hopkins University School of Medicine in Baltimore and senior author on the paper, the MitoChip v2.0 showed in his group's hands better sensitivity that its predecessor to sequence variations in head and neck cancer samples. The v2.0 also detected nearly three dozen variations in the non-coding D-loop, long considered to be a sequencing no-man's land and which the original MitoChip did not include.

"At this point, we don't foresee a MitoChip v3.0," said Califano, whose research was supported by the NIH's National Institute of Dental and Craniofacial Research. "The v2.0 is a very good tool in that we've also arrayed 500 of the most common haplotypes -- or grouped patterns of known DNA variations -- banked in the mitochondrial public database."

"The real interesting thing is nobody has been able to study these D-loop alterations very well," said Califano "They clearly occur in tumor cells, and there is some type of selection process for them. But their functional significance has been hard to know. Now, you can sequence the D loop so readily and begin to look harder for associations in certain cancers."

"Investing in NIH is Ensuring a Healthier Future"
Thank you for your comments to me and to the NIH staff after the first desk-to-desk this spring. As I have gone out to many of our constituency organizations, our advisory councils, and in talking to the public and the press over the past two months, I have felt that it is very important to share progress with you on a regular basis. Here are a just a few data-driven examples of return on investment in medical research:

What has an investment of only $2.60 per year for each American yielded? This investment through the National Institute of Neurological Disorders and Stroke has seen the death rates from stroke decline by over 70% in the last thirty years.
For an investment of approximately $3.70 per year in the National Heart, Lung, and Blood Institute research, we have experienced a 63% decrease in mortality for coronary disease and, over thirty years, a $2.6 trillion return.
And for cancer research, the average investment in federal research per American has been approximately $8.60 per year over the past 30 years. The results?
For the first time in recorded history, annual cancer deaths in the United States have fallen. And there are 10 million survivors, due, in part, to improved effectiveness of early detection and screening. Thanks to the doubling, new targeted, minimally invasive treatments for cancer multiplied, and new drugs were developed for cancer prevention.
For the public investment in the research supported by the National Institute of Child Health and Human Development of $2.20 each year, the U.S. rate of mother-to-child transmission of HIV reduced from 27% to just above 1%, and there has been elimination of or reduction of several causes of mental retardation; SIDS deaths reduced by more than 50% in 10 years are among examples of progress from the NIH investment.
Due to HIV/AIDS research, 30,000 U.S. deaths have been prevented each year since 1996 through an annual investment per American of $5 per year.

As I have gone out to talk with various groups, I have noticed that there are some myths which persist in the community. So, I want to describe to you the realities of the funding situation and discuss with you our strategies to respond to challenging times.

Pioneered social science in dentistry, international oral health research
NIH Record, July 2006
The way Dr. Lois Cohen tells it, it was happenstance that she got her first post doc position at the PHS Division of Dental Health (DDH). Some colleagues suggested her for a job there and she was quickly recruited. "I figured, why be in Washington if you can’t have access to national problems, national data, and really have a chance to do something significant?" So the newly minted Ph.D. began her career as a social science analyst in DDH and over the years became a driving force for incorporating social science research into dentistry and expanding interdisciplinary oral health research around the globe. Dr. Cohen, who most recently served as Director of NIDCR’s Office of International Health, retired on June 2 after 42 years of government service; 30 of those years were spent at NIDCR.

"Lois has been instrumental over the years in advancing our Institute’s mission domestically and internationally," said NIDCR Director Lawrence Tabak, D.D.S., Ph.D. "She's a dedicated and forward thinking researcher and science administrator whose contributions to the Institute and the field of oral health research are numerous and wide-ranging. Lois has been a leader in integrating the application of the social and behavioral sciences into research for the study of oral health, which has ultimately helped improve public health both in the U.S. and around the world."

Dr. Cohen's early work concentrated on the social, behavioral, cultural, and economic factors that influence oral disease development and oral health care delivery. The Division was vibrant and active, she said, but there were challenges. "It was definitely a challenge being a woman in a then male dominated working environment," she said. "And also being a non-dentist in a dental world; there were always certain avenues that were blocked." She added, "But the very fact that the Division leadership sought out social and behavioral scientists to address their issues was an over-riding incentive for me."

While at DDH, she and her colleagues devised strategies to help overcome the public's reluctance to adopt water fluoridation as well as to encourage use of topical fluorides and dental sealants in private practices. Her initial studies focused on incentives and barriers facing practicing dentists to adopt techniques for the early detection of oral cancer. Dr. Cohen also launched two international studies in collaboration with the World Health Organization (WHO) that looked at which national delivery models of care resulted in better oral health status.

In 1976, NIDR Director David Scott recruited Dr. Cohen to advise on the relationship between dental health and the social and behavioral sciences. As an advisor, and subsequently as director of the Office of Planning, Evaluation, and Communications from 1983-1989, she incorporated social and behavioral research into the strategic plans for the Institute and pioneered major evaluations of the Institute's portfolios in caries research, craniofacial anomalies, biomaterials and centers.

In 1989 she was selected to head the Institute's extramural research program, which faced restricted funds and a budget that was stagnant. "It was not unlike today," she said. "We needed to figure out ways to keep our enterprise strong and to move the science forward during that time." To circumvent the budget issues, she worked with the EPMC community to facilitate public-private partnerships that would help leverage the agency's resources. Those models for collaborative funding continue to guide other agencies as well.

Most recently, Dr. Cohen was Director of NIDCR's Office of International Health (OIH), ensuring that global health issues were addressed by global oral health research. "Take Noma, or oral gangrene," said Dr. Cohen of the condition prevalent in Africa. "Why do we study it since we have hardly any cases here?" She explains, "Because you have to understand what it is to be able to prevent it. And, as we all know, diseases can cross borders -- they don't respect geopolitical boundaries." The OIH also served as a WHO Collaborating Center for Dental and Craniofacial Research, functioning as a liaison with agencies involved in global oral health research and training both here and abroad.

A native of Philadelphia, Dr. Cohen received a B.A. in sociology from the University of Pennsylvania and an M.S. and Ph.D. in sociology from Purdue University.

She has received numerous honors and awards and her 'alma mater', Purdue University, conferred its first honorary doctorate to a sociologist in 1989 for her work related to dental health research globally. She also is an honorary member of the American Dental Association, an honorary fellow of the American and International Colleges of Dentistry, and has received numerous distinguished career achievement awards from the International Association for Dental Research, the DC Sociological Society and other related domestic and international professional associations.

In retirement she says she may return to ceramics as well as explore other crafts, and is looking forward to more time for reading and extra time with friends and family. In general, she says, she hopes to lead a "more balanced existence."

Although officially retired, Dr. Cohen has been asked to stay and consult for NIDCR part-time. "I'm very committed to what we do here," she says. "What we're about is so important and I love being a part of it."

NIDCR Funds a $19 Million TMJ Study
Who is at Risk for TMJ?
For too many years people have looked for the cause of TMJ problems--it was your bite, your teeth grinding at night, your wisdom teeth extractions, your cradling the phone between your ear and your neck…not to mention the "it's all in your head" school that blamed your jaw problem on you and your neuroses. Researchers now know that TMJ disorders are "multifactorial'--they happen when a number of factors come together, each contributing a part and interacting to increase the risk that a person may develop a painful and malfunctioning jaw. Hints at what some of these factors are were reported in a research project summarized in the last TMJ Communiqué. The study showed that women who were initially symptom free, but who developed TMJ disorders in the course of the 3-year study, were almost 3 times as likely to have a genetic variant of an enzyme that predisposed them to heightened pain sensitivity, compared to the women who did not develop a TMJ problem.

The OPPERA study. The pain researcher who led that study, Dr. William Maixner of the University of North Carolina (UNC), and his colleague, Dr. David Savitz, professor and chair of epidemiology at UNC's School of Public Health, are the co-directors of a 7-year $19.1 million project that will recruit 3,200 men and women between the ages of 18 and 44 in a prospective study to explore genetic, physiological, environmental, and psychological factors that may increase the risk for TMJ. Collaborating with Drs. Maixner and Savitz are scientists at three other academic sites: Drs. Roger Fillingam at the University of Florida (Gainesville), Richard Orbach at the State University of New York, Buffalo, and Joel Greenspan and Ronald Dubner (a member of The TMJA's Board of Scientific Advisors) at the University of Maryland in Baltimore. The project, called Orofacial Pain: Prospective Evaluation for Risk Assessment or OPPERA, is the largest prospective study of TMJ ever. It is funded by the National Institutes of Health and the National Institute of Dental and Craniofacial Research (NIDCR) as a cooperative agreement, which allows NIDCR staff to play an active role in the course of the study.

Volunteers who pass the initial screening tests to rule out pre-existing conditions (including pregnancy), will form the major cohort group of 3,200 healthy subjects. It is expected that some of those applying may already be diagnosed with TMJ disorders. The researchers will select the first 192 of these volunteers with TMJDs and pair them with healthy controls to constitute a so-called "case control" subgroup for analysis. Data collected for the cohort of healthy volunteers will include sociodemographics (age, sex, ethnicity, etc), pain sensitivity studies, resting arterial blood pressure, genotyping (looking at selected candidate genes associated with pain sensitivity), and some psychological profiling. Women in the cohort will be asked to keep a daily diary measuring variations in their experience of pain and other physical symptoms. These data, along with quarterly health updates and yearly re-screenings, will constitute the vast store of information that will be collected and analyzed through a Data Coordinating Center directed by Battelle Memorial Institute. Based on previous studies, the investigators anticipate that some 200 individuals will develop a first-onset TMJ problem in the course of the study. These individuals will be offered advice and referral for treatment. It is, of course, a mining of their data in comparison with the TMJD-free subjects that is the key to the success of the project. To quote Maixner, "We firmly believe that this study will significantly improve our understanding of the risk determinants for this condition and related disorders. In so doing we hope to make substantial and rapid progress in developing new diagnostic procedures and treatment strategies for our patients."

Newswise -- Mayo Clinic ear, nose and throat surgeons have developed a promising new process for mandible (lower jaw) reconstruction following removal of oral cancer. Details will be presented June 28 at the International Federation of Head and Neck Oncologic Societies meeting in Prague, Czech Republic, www.ifhnos2006.cz.

"We think this new process can be a huge advantage for patients and a good tool for reconstructive surgeons," says Daniel Price, M.D., Mayo Clinic ear, nose and throat surgery resident and lead study investigator. "We're excited about it. It will not completely replace the current mandible reconstruction method -- transfer of bone -- but down the road, I think that this method of reconstruction will be done regularly in patients with cancer involving the mandible."

Patients who might be candidates for the new reconstructive and treatment procedure have oral cancer involving part of the mandible. To completely remove the tumor surgically, surgeons have to remove part of the mandible. Without reconstructive surgery, patients would have difficulty eating and speaking, and would develop a significant facial deformity, says Eric Moore, M.D., Mayo Clinic ear, nose and throat surgeon and senior study investigator.

The new method, which the investigators tested in rabbits, used distraction osteogenesis after tumor removal surgery to restore the missing portion of a patient’s jaw. With distraction osteogenesis, the surgeon made a cut at one of the remaining ends of the patient's jawbone. As the break healed, the first phase of growth, soft tissue, appeared. The surgeon then stretched the pliable soft tissue under the tension of a device to fill in the gap in the patient's jaw. Within 24 hours of completing the stretching process, physicians started administering radiation therapy to the mandible to decrease the likelihood of cancer recurrence. As the soft tissue healed, it hardened into bone. The investigators found that the radiation therapy, which they had suspected could interrupt the bone consolidation prior to the study, had no ill effects on the bone's healing.

"Patients with large oral tumors should have radiation therapy after surgery to decrease the chances of cancer recurrence," says Dr. Price. "Radiation needs to be completed 13 to 14 weeks after the patient’s cancer diagnosis to achieve maximum effect. As these patients require mandible reconstruction after tumor removal, we wanted to find a way to get both the radiation and the reconstruction done quickly and concurrently."

Dr. Price says that it is also preferable to start the reconstruction when the tumor is removed, as demonstrated in this method, rather than wait until radiation therapy is completed, because immediate reconstruction minimizes scar tissue and is better tolerated by the patient.

The standard procedure for jaw reconstruction following removal of an oral cancer is transfer of bone from the patient’s fibula in the leg, along with surrounding muscle, skin and the supplying vessels. Although the aesthetic and functional result for the mandible can be good, this procedure has drawbacks, including:

The surgery takes all day to complete and is expensive
The patient has a second surgical site to heal (leg and mandible) and is less mobile post-surgery
In male patients, the transfer of fibula and surrounding skin can lead to the appearance of leg hair inside the patient's mouth
The surgery is not feasible for patients who do not have healthy vessels in their legs
The aesthetic result in the leg post-surgery is less than ideal
The surgery can inadvertently damage the leg's nerves, leaving the patient with some leg weakness
The fibula bone can die following transfer

"If we could avoid the whole process of going to another part of the body in order to reconstruct a patient's jaw, it would be best," says Dr. Moore.

Drs. Price and Moore had been performing similar distraction osteogenesis in children born with small jawbones and wondered about the feasibility of using the procedure for adult oral cancer patients. Thus, they embarked on this research project to test it in animals and have tried this method on human oral cancer patients who were not appropriate candidates for the fibula transfer surgery. They have also utilized the method in patients who have benign tumors or who have suffered a trauma.

The patients who have had distraction osteogenesis performed by Drs. Price and Moore compared the level of discomfort to having orthodontic braces. The devices used for the stretching procedure are submerged and not visible.

The next step in this research, according to Dr. Price, is to study the distraction osteogenesis plus radiation therapy method in larger animals, comparing them to animals who are given distraction osteogenesis without radiation therapy.

Report Explores the Impact of Methamphetamine Use on Family Well-Being and Systemic Reforms to Address the Problem

From Maternal and Child Health Library
www.mchlibrary.info/alert/archives.html
Meth and Child Welfare: Promising Solutions for Children, Parents, and Grandparents provides a set of recommendations to improve the child welfare system's ability to counteract the impact of methamphetamine (meth) use on children, families, and communities. The report, produced by Generations United with support from the Pew Charitable Trusts, discusses the unique problems faced by child welfare agencies and others as they respond to increased meth use. The report then presents information about new knowledge, models, and best practices emerging from states about how to keep children safe, promote family reunification, and find children permanent homes when they cannot live with their parents. The report concludes with six policy recommendations for federal support in helping child welfare agencies capitalize on the inherent resiliency of the families and communities with which they work. The report is available at ipath.gu.org/documents/A0/Meth_Child_Welfare_Final_cover.pdf.

U.S. Children
This study determined whether age-specific body mass index might be associated with dental caries in U.S. children and adolescents (ages 2-17), controlling for relevant demographic and socioeconomic status factors. Overweight was not associated with increased prevalence of dental caries in either primary or permanent dentition or with dental caries severity in primary dentition.

Oral Health Behaviors of Children in Low and High Socioeconomic Status Families

This study compared patterns of oral health behaviors between children of low- and high-socioeconomic status (SES) participating in the Iowa Fluoride Study. Children in the low-SES group consistently consumed more sugared beverages (soda pop and powder-based beverages) during their first 8 years of life than did their higher-SES counterparts. In addition, children in the low-SES group consumed more juice and juice drinks during the first year of life, suggesting a pattern of higher sweet-beverage consumption beginning very early in life. There were few differences in home-water-fluoride level, toothpaste use, or toothbrushing frequency between groups, however, and only modest differences in dental visits.

New Models of Pain Relevant to the Trigeminal System (R21)
(RFA-DE-07-007)
National Institute of Dental and Craniofacial Research
Application Receipt Date(s): November 21, 2006
grants.nih.gov/grants/guide/rfa-files/RFA-DE-07-007.html

Health Promotion Research Directed to Improving the Oral Health of Women and Their Infants (R21)
(RFA-DE-07-008)
National Institute of Dental and Craniofacial Research
Application Receipt Date(s): January 19, 2007
grants.nih.gov/grants/guide/rfa-files/RFA-DE-07-008.html