Henry Ford News Feed - Research

Diabetes Drug Ups Risk for Fractures in Women

MEDIA CONTACT: Krista Hopson
khopson1@hfhs.org

STUDY: Diabetes Drug Ups Risk for Bone Fractures in Older Women

DETROIT - A Henry Ford Hospital study finds women with type 2 diabetes who take a commonly prescribed class of medications to treat insulin resistance may be at a higher risk for developing bone fractures.

After taking a thiazolidinedione (TZD) for one year, women are 50 percent more likely to have a bone fracture than patients not taking TZDs, according to study results. And those at the greatest risk for fractures from TZD use are women older than 65.

"Older women are already at a higher risk of osteoporosis and osteoporosis-related fractures, which might explain why they appeared to be the most affected by TZDs," says study senior author L. Keoki Williams, M.D., MPH, Center for Health Services Research and Department of Internal Medicine at Henry Ford Hospital.

The study - one of the largest groups to examine the longitudinal relationship between TZD use and fractures - appears in this month's issue of The Journal of Clinical Endocrinology & Metabolism.

TZDs such as pioglitazone and rosiglitazone help keep blood glucose levels on target by decreasing insulin resistance and making body tissues more sensitive to insulin's effects. TZDs also cut down on the amount of glucose made by the liver in patients with type 2 diabetes.

But in recent years, TZDs have been linked to bone loss and increasing fracture risk. Complicating matters, type 2 diabetes and insulin use are also associated with an increased risk for fractures.

To determine the relationship between TZD use and fracture risk in patients with type 2 diabetes, Dr. Williams and his colleagues conducted a retrospective study from Jan. 2, 2000 to May 31, 2007 of 19,070 Henry Ford patients. Among the study group, 9,620 were women and 9,450 were men.

During the study period, 4,511 patients had at least one prescription fill for a TZD. The researchers used electronically maintained medical claims data to identify non-traumatic bone fractures. The increased risk in women appeared after approximately one year of TZD use.

The location of the fractures in this group also was unique. Typically, osteoporosis-related fractures involve the vertebra and hip. This study, however, found TZD use in women to be associated with fractures of the upper extremity and distal lower extremity. Similar findings were observed in treated women older than 65, who were shown to have a 70 percent increased risk for developing fractures. Men, regardless of age, were not at an increased risk for fractures.

"Although two recent studies suggest that men may also be at increased risk for fractures after TZD exposure, we did not observe this association for men, despite having nearly equal numbers of men and women in our study," says study co-author Zeina A. Habib, M.D.
African-American race-ethnicity was protective for fractures when compared with other race-ethnic groups, which were predominately Caucasian.

"Fractures are just one of a growing number of problems associated with these medications. Henry Ford and other researchers have previously found that this class of medications also can increase risk of congestive heart failure hospitalization," says Dr. Williams.

Dr. Williams notes that there are other medication options available to treat insulin resistance in patients with type 2 diabetes.

"TZDs may put some patients at increased risk for other health issues, and I encourage patients to talk with their physician about other suitable options," says Dr. Williams. "If the physician feels the patient should be placed on a TZD, routine screening for bone loss and prophylactic therapy to prevent bone loss and fractures may also be needed."

Reference: "Thiazolidinedione Use and the Longitudinal Risk of Fractures in Patients with Type 2 Diabetes Mellitus." The Journal of Clinical Endocrinology & Metabolism.

Funding: Henry Ford Hospital, and grants from the National Heart, Lung and Blood Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

Acupuncture Reduces Hot Flashes for Breast Cancer Patients

MEDIA CONTACT:
Krista Hopson
khopson1@hfhs.org

STUDY: Acupuncture Reduces Hot Flashes, Improves Sex Drive for Breast Cancer Patients

DETROIT - Not only is acupuncture as effective as drug therapy at reducing hot flashes in breast cancer patients, it has the added benefit of potentially increasing a woman's sex drive and improving her sense of well-being, according to a Henry Ford Hospital study.

Study results show that acupuncture, when compared to drug therapy, has a longer-lasting effect on the reduction of hot flashes and night sweats for women receiving hormone therapy for breast cancer treatment. Women also report that acupuncture improves their energy and clarity of thought.

The study, published online this week in the Journal of Oncology, is the first randomly controlled trial to compare acupuncture and drug therapy in this way.

"Acupuncture offers patients a safe, effective and durable treatment option for hot flashes, something that affects the majority of breast cancer survivors. Compared to drug therapy, acupuncture actually has benefits, as opposed to more side effects," says study lead author Eleanor Walker, M.D., division director of breast services in the Department of Radiation Oncology at Henry Ford Hospital.

According to the National Cancer Institute, one in eight women will develop breast cancer in her lifetime. For these women, conventional medical treatment involves chemotherapy and five years of hormone therapy. With such a long course of treatment, side effects of hormone therapy such as vasomotor symptoms - hot flashes and night sweats - can become a major cause of decreased quality of life, and even discontinuation of treatment.

Venlafaxine (Effexor) has been the drug therapy of choice to manage these common and debilitating side effects associated with breast cancer treatment. Venlafixine, however, comes with its own set of side-effects: dry mouth, decreased appetite, nausea and constipation.

Since acupuncture has been shown to effectively reduce hot flashes in menopausal women, Dr. Walker and her research team decided to test the use of acupuncture to combat vasomotor symptoms in breast cancer patients as an alternative to drug therapy.

To compare the two options, 50 patients were recruited from oncology clinics at Henry Ford. Patients were randomly assigned to receive either acupuncture or venlafaxine treatment for 12 weeks. The drug therapy group took venlafaxine orally each night, 37.5mg the first week and then 75mg for the remaining 11 weeks. The other group received acupuncture treatments twice per week for the first four weeks, and then once a week for the remaining eight weeks.

At the end of 12 weeks, all patients stopped their therapy and were followed for one year. Patients kept a diary to record the number and severity of hot flashes, and took surveys to measure their overall health and mental health.

The study found that both groups initially experienced a 50 percent decline in hot flashes and depressive symptoms, indicating that acupuncture is as effective as drug therapy.

Differences, however, between the two groups began to emerge two weeks post-treatment: The acupuncture group continued to experience minimal hot flashes, while the drug therapy group had a significant increase in hot flashes. The acupuncture group did not experience an increase in the frequency of their hot flashes until three months post-treatment.

Reference: "Acupuncture versus Venlafaxine for the Management of Vasomotor Symptoms in Hormone Receptor Positive Breast Cancer Patients: A Randomized Controlled Trial." Journal of Clinical Oncology.

Funding: Susan G. Komen Foundation

Simulated Training for Ultrasound Procedures Improves Safety

MEDIA CONTACT:
Krista Hopson
Krista.Hopson@hfhs.org

STUDY: Simulated Training for Ultrasound-Guided Procedures Improves Safety without Risk to Patients

DETROIT - Using mannequins to teach doctors-in-training how to do ultrasound-guided procedures is an effective way to improve their skills without compromising patient care and safety, according to a new study from Henry Ford Hospital.

The study shows that this simulation-based training course can be a valuable tool to improve medical residents' knowledge, dexterity and confidence for performing some of the more common ultrasound-guided procedures, including breast biopsies, liver biopsies, thyroid biopsies and the removal of fluid in the body. Plus, a simulated model allows for standardization of medical education.

"The mannequins allow us to simulate actual ultrasound guided procedures, which offers residents a unique training opportunity prior to working on real patients," says study co-author John W. Bonnett, M.D., a radiologist at Henry Ford Hospital. "Ultimately, the residents in our study became more proficient and efficient in performing these procedures."

Study results were presented by co-author Mishal Mendirata Lala, M.D., at the Radiological Society of North America Annual Meeting, taking place Nov. 29 - Dec. 4 in Chicago.

For the study, researchers enrolled 29 radiology residents from all four levels of training. The residents were given written, video, and live interactive training from staff on the basics of ultrasound guided procedures.

Residents had six months to practice these skills at the 12,000-square-foot Center for Simulation, Education and Research at Henry Ford Hospital, the largest surgery simulation center in the Midwest. The facility houses two operating theatres, six clinical rooms, a minimally invasive procedure lab with more than 30 stations, and two classrooms. Fully-equipped, reconfigurable rooms simulate surgery, labor and delivery, intensive care, emergency and routine hospital scenarios.

As part of the study, residents used phantom mannequins that contained both hypo- and hyperechoic nodules to simulate the ultrasound procedure. Written and practical examinations were given before and after training to assess for changes in competency and proficiency.

Study results show a significant improvement between the residents' pre- and post-test scores on both the written and practical exams. After training, residents also demonstrated improved dexterity in the technical aspects of ultrasound guided procedures.

On the survey questionnaire, residents said that the course improved their knowledge level and technical ability for ultrasound guided procedures. It also boosted their confidence for performing biopsies.
In all, the researchers say, this additional simulation training translates to improved patient care and safety, as well as patient satisfaction, decreased risk of complications, decreased procedural time, and the ability to improvise in difficult or unexpected situations.

As a result of these study findings, Henry Ford Hospital has expanded this course to include simulated training for CT-guided interventional procedures.

Funding: Henry Ford Hospital

Does Race, Income Predict Prostate Cancer Outcome?

MEDIA CONTACT:
Krista Hopson
khopson1@hfhs.org

Does Race, Income Predict Prostate Cancer Outcome?

CHICAGO - A patient's socioeconomic status (income, martial status and race) has absolutely no impact on his outcome following curative radiation therapy for the treatment of prostate cancer, according to a new study from Henry Ford Hospital in Detroit.

"This study offers an extremely important message for all patients with prostate cancer who receive radiation therapy," says Benjamin Movsas, M.D., senior study author and chair of the Department of Radiation Oncology at Henry Ford Hospital in Detroit. "Despite the fact that there was a large difference in income based on race, none of the socioeconomic status factors predicted for outcome. All patients did equally well, based on the known prognostic factors."

The study is being presented Nov. 4 at the 51st Annual American Society for Radiation Oncology (ASTRO) meeting in Chicago. It is unique in that nearly 50 percent of patients in the analysis are African American.

Previous studies on socioeconomic status and cancer outcomes done by other groups have had conflicting results, according to study lead author Farzan Siddiqui, M.D., Ph.D., with the Department of Radiation Oncology at Henry Ford Hospital.

One study, for example, suggested that African Americans with breast or colon cancer do much worse than white patients because they receive care at hospitals with less expertise. Another showed that men with prostate cancer who are married have better outcomes than those who are unmarried or without a partner. And yet other studies suggested that hospitals with large minority patient populations have higher mortality for cancer.

"Henry Ford Hospital treats a large number of African American patients and has excellent cancer outcomes, so we really began to question results from many of these prior studies," says Dr. Siddiqui. "One of the issues is that many of these studies include a relatively small percentage of African American patients. In comparison, almost half of our study group was African American, which allowed us to do a more accurate assessment of how socioeconomic status affects prostate cancer outcomes."

The study included 788 Henry Ford Hospital patients with localized prostate cancer who were treated with external beam radiation therapy. Among those in the study, 48.5 percent were African American with a median household income $36,917, and 46 percent were white with a median household income of $60,190. The patients' ages ranged from 44 to 90.

While there was a large difference in median household income among African Americans and whites, none of the socioeconomic factors examined predicted for patient outcome. Only known disease risk factors determined overall survival or biochemical (PSA) control rates.

"Our results suggest if patients are properly cared for and managed that their race, income and marital status should not affect their outcome," says Dr. Siddiqui.

About Prostate Cancer & Radiation Therapy
Prostate cancer affects one in six men in the United States, but according to the American Cancer Society only one in 35 will die of it. The majority of all prostate cancer are diagnosed in men older than 65.

Radiation therapy involves administering high-energy X-rays to kill cancer cells. With external beam radiation therapy, the radiation is focused on the prostate gland from a source outside the body. Each treatment lasts only a few minutes, and is noninvasive and is painless.

Study authors: Along with Siddiqui and Movsas, co-authors from Henry Ford Hospital are Ramy Ibrahim; Mohamed A. Elshaikh, M.D; Lois Lamerator, Ph.D.; Mei Lu, Ph.D.; Deepka Pradhan, M.D.; Eleanor M. Walker, M.D.; Hans Stricker, M.D.; and Svend O. Freytag, Ph.D.

Reference: "Does Socioeconomic Status (SES) Influence Outcome in Prostate Cancer Patients Treated with External Beam Radiation Therapy (EBRT)?" Abstract # 1431. ASTRO 2009.

Preventative Brain Radiation for Lung Cancer Patients

MEDIA CONTACT:
Krista Hopson
khopson1@hfhs.org

Preventative Brain Radiation for Lung Cancer Patients:
The Benefits and Risks

CHICAGO - A new study is taking a closer look at the benefits versus risks for lung cancer patients to undergo preventative brain radiation therapy as a means to stop cancer from spreading to the brain.

Study results show that while preventative brain radiation for patients with non-small cell lung cancer - the most common form of lung cancer - does reduce the chance of developing brain metastases, it impacts some short-term and long-term memory.

The study also reveals that preventative brain radiation does not increase survival and has no significant impact on quality of life, says study co-investigator Benjamin Movsas, M.D., chair of the Department of Radiation Oncology at Henry Ford Hospital in Detroit.

"These findings offer a more complete perspective regarding this intervention for patients with non-small cell lung cancer," Movsas says. "We now need to develop strategies to help shift the benefit-risk ratio for this treatment."

Dr. Movsas will present the study results Nov. 2 at the plenary session for the 51st annual American Society for Radiation Oncology (ASTRO) meeting. Out of nearly 1,000 abstracts submitted, only a handful of study abstracts, including the one from Henry Ford, were selected for the ASTRO plenary session.

The study is part of a national Radiation Therapy Oncology Group (RTOG) analysis of prophylactic cranial irradiation for patients with stage III non-small cell lung cancer.

Previous studies have found this preventative type of external beam radiation therapy that treats the entire brain - known as prophylactic cranial irradiation (PCI) - can reduce the risk of cancer spreading to the brain in patients with non-small cell lung cancer, as well as its sister disease, small-cell lung cancer. The risk of cancer developing in the brain increases as people with non-small cell lung cancer live longer with more effective treatments.

To learn more about how PCI impacts a patient's quality of life and cognitive function, Dr. Movsas and his colleagues tracked the progress of 340 patients with stage III non-small cell lung cancer for one year after receiving PCI, a 10-minute treatment that occurs once a day for two to three weeks.

The study finds that patients with non-small cell lung cancer treated with PCI have a significantly decreased risk of developing brain metastases by 10 percent (from 18 percent to 8 percent), compared with those who did not receive the treatment.

Although there was no significant impact on quality of life, patients who underwent PCI had a greater decline in immediate memory recall and delayed memory recall than patients who did not have PCI.

"This study offers patients a look at both sides of the coin with this treatment, allowing them to make an informed decision about their care," says Dr. Movsas. "Now that we have a more complete perspective and know the challenges, we need to move forward to develop strategies to reduce the risk of neurocognitive changes after brain radiation."

Already a RTOG study is underway to test memantine, a medication approved for Alzheimer's disease, to see if it may help improve memory following brain radiation.

Dr. Movsas notes the potential for exploring other strategies, such as using newer radiation technologies like intensity modulated radiation therapy, for a more precise treatment that will spare parts of the brain associated with memory.

About Non-Small Cell Lung Cancer
Non-small cell lung cancer is a disease in which cancer cells form in the tissues of the lung. With non-small cell lung cancer, cancer tends to spread in the earlier phase of the disease to other organs, including the brain.

According to the American Cancer Society, about eight to nine out of 10 cases of all lung cancers are the non-small cell type. There are three main sub-types of non-small cell: Squamous cell carcinoma, which make up about 25 percent to 30 percent of all lung cancers; adenocarcinoma, which accounts for about 40 percent of lung cancers and is usually found in the outer part of the lung; and large-cell carcinoma, which accounts for about 10 percent to 15 percent of lung cancers.

Smoking tobacco is the major risk factor for developing lung cancer. Possible signs of lung cancer include a cough that doesn't go away and/or shortness of breath, according to the National Cancer Institute.

Reference: "Phase III Study of Prophylactic Cranial Irradiation versus Observation in Patients with Stage III Non-Small Cell Lung Cancer: Neurocognitive and Quality of Life Analysis of RTOG 0214." ASTRO 2009.

Funding: National Cancer Institute grants (RTOG U10 CA21661 and CCOP U10 CA37422).

MRSA Strain Linked to High Death Rates

CONTACT: David Olejarz
Oct. 31, 2009 313.874.4094
Dolejar1@hfhs.org

Henry Ford Hospital Study: A MRSA Strain Linked to High Death Rates

DETROIT - A strain of MRSA that causes bloodstream infections is five times more lethal than other strains and has shown to have some resistance to the potent antibiotic drug vancomycin used to treat MRSA, according to a Henry Ford Hospital study.

The study found that 50 percent of the patients infected with the strain died within 30 days compared to 11 percent of patients infected with other MRSA strains.

The average 30-day mortality rate for MRSA bloodstream infections ranges from 10 percent to 30 percent.

Researchers say the strain USA600 contains unique characteristics that may be linked to the high mortality rate. But they say it is unclear whether other factors like the patients' older age, diseases or the spread of infection contributed to the poor outcomes collectively or with other factors. The average age of patients with the USA600 strain was 64; the average age of patients with other MRSA strains was 52.

The study is being presented at the 47th annual meeting of the Infectious Diseases Society of America Oct. 29-Nov.1 in Philadelphia.

"While many MRSA strains are associated with poor outcomes, the USA600 strain has shown to be more lethal and cause high mortality rates," says Carol Moore, PharmD., a research investigator in Henry Ford's Division of Infectious Diseases and lead author of the study.

"In light of the potential for the spread of this virulent and resistant strain and its associated mortality, it is essential that more effort be directed to better understanding this strain to develop measures for managing it."

MRSA, or Methicillin-resistant Staphylococcus aureus, is a bacterium that is resistant to common antibiotics like penicillin. It can cause skin, bloodstream and surgical wound infections and pneumonia. The majority of infections occur among patients in hospitals or other health care settings, though a growing number of infections are being acquired by otherwise healthy people outside those settings.

MRSA strains can be resistant to many drugs, though they are typically susceptible to the antibiotic vancomycin. MRSA infections are often treated with vancomycin administered intravenously. The USA600 strain in this study was shown to be more resistant to vancomycin.

The study was funded by Henry Ford Hospital.

Genes Signal Late-Stage Laryngeal Cancer, Poor Outcome

CONTACT: Krista Hopson
khopson1@hfhs.org
(313) 874-7207

Study: Genes Signal Late-Stage Laryngeal Cancer, Poorer Outcome

SAN DIEGO - Researchers at Henry Ford Hospital have identified tumor-suppressing genes that may provide a more accurate diagnosis of disease stage and survival for laryngeal cancer patients than current standards.

The study finds genetic abnormalities of the ESR1(estrogen specific receptor 1) gene and the HIC1 (hypermethylated in cancer 1) gene are predictors of late-stage laryngeal cancer and shorter survival, respectively, for patients with the disease.

Study results will be presented Wednesday, Oct. 7 at the American Academy of Otolaryngology-Head & Neck Surgery Foundation Annual Meeting & OTO EXPO.

"These two genes provide some insight into the biology of the tumor," says study senior author Maria J. Worsham, Ph.D., director of research in the Department of Otolaryngology at Henry Ford Hospital. "Loss of gene function as a result of abnormal methylation of promoter regions of tumor suppressor genes can be reversed by drugs that can restore normal gene function, opening the door to other treatment options for patients with laryngeal cancer."

Similar to previous studies on laryngeal cancer, the Henry Ford study also shows that African Americans are more likely to be diagnosed with late-stage laryngeal cancer.

This year alone, the American Cancer Society estimates 12,290 new cases of laryngeal cancer - cancers that start in the voice box - will be diagnosed.

Following diagnosis, the cancer stage is currently assessed based on tumor size and how far it's spread within the voice box, and whether the cancer has spread to lymph nodes or other organs. The stage (0-4) of the cancer helps health care providers make a prognosis for survival and determine a possible course for treatment.

For the study, Henry Ford researcher and lead author Josena Stephen, M.D., and Dr. Worsham looked at 80 patients with laryngeal squamous cell cancer who were diagnosed between 1996 and 2008. Forty percent of the study group was African American.

Using tissue DNA samples the researchers examined the methylation status of 24 tumor suppressor genes and tested for the presence of the human papilloma virus (HPV). DNA methylation - a type of chemical modification of DNA where a methyl group (CH3) can be added (hypermethylation) or removed (hypomethylation) - allows the researchers to look for genetic abnormalities within tumor samples.

The study found:

Abnormal DNA methylation of ESR1 predicted late stage disease.
African Americans are more likely to have advanced stage disease than their Caucasian counterparts, a finding consistent with previous research.
Abnormal DNA methylation of HIC1, late stage disease, and vascular invasion were predictors of shorter survival.
The median survival for patients in the study group was 4.2 years.
HPV was much higher in this group of patients (37 percent), supporting the role of HPV in laryngeal cancer.The majority of patients were either current or past smokers and alcohol users, again confirming the role these factors play in laryngeal cancer.

"When this research crosses from the lab to clinical care, the contribution of specific gene changes will assist in improving the accuracy of cancer staging and length of survival for laryngeal cancer patients," explains Dr. Worsham.

"So if a patient comes in with stage 1, based on current standards, and then we find methylation of ESR1, the patient may have underpinnings of a more aggressive tumor with characteristics that are more in line with a stage 3 or stage 4 diagnosis, refining treatment options."

Reference: "DNA Hypermethylation Markers of Poor Outcome in Laryngeal Cancer," 2009 AAO - HNSF Annual Meeting & OTO Expo.

Research Support: Grant R01 NIH DE 15990

Henry Ford Launches Gene Therapy Study for Parkinson's Disease

CONTACT: Dwight Angell
(313) 876-8709
Dwight.Angell@hfhs.org

Henry Ford West Bloomfield Hospital Launches Gene Therapy Study for Parkinson's Disease

WEST BLOOMFIELD - A Michigan hospital is embarking on a research study for advanced Parkinson's disease using a state-of-the-art treatment called gene transfer.

The clinical trial will test whether gene transfer therapy is able to restore better mobility in Parkinson's patients who have lost responsiveness to drug therapy.

"The start of this clinical trial provides hope to a Parkinson's disease patient population that has had a long-standing need for better treatment options," says Henry Ford West Bloomfield Hospital neurologist Peter LeWitt, M.D., who is internationally known for his research on Parkinson's disease.

Of the eight sites in the United States involved in the study, Henry Ford West Bloomfield Hospital, part of the Henry Ford Health System, is the only Michigan institution testing this experimental therapy.

Parkinson's disease is a degenerative disorder of the central nervous system that causes tremors and impairs a person's motor skills, speech, balance and posture. Its cause is unknown and it affects 1 percent to 2 percent of people over the age of 60.
A small region deep within the brain is the source for the symptoms of Parkinson's disease. When brain neurons in this part of the brain begin to die, these cells can no longer manufacture the molecule dopamine, a chemical critical for controlling movement.

Among patients with Parkinson's disease, the pace and extent of progression in neurologic deficits can greatly vary. The burden on quality of life spans a wide spectrum too, Dr. LeWitt says, from minimal discomfort and disability to marked impairment of capabilities such as independence, safety and communication.

Most current therapies and research approaches target dopamine to treat motor symptoms associated with Parkinson's disease. In contrast, the focus of the current gene therapy strategy is on increasing GABA, a brain neurotransmitter that regulates movement. In Parkinson's disease, GABA is reduced in an area of the brain called the subthalamic nucleus, causing it to be overactive. Investigators feel this might be a better way to help advanced Parkinson's disease.

For the clinical trial, the gene therapy product rAAV-GAD will be placed into the subthalamic nucleus by a surgical procedure. The gene transfer is done through a catheter that is removed shortly after its placement. Participants will be assessed post-treatment at multiple intervals. As an alternative to this experimental treatment, patients with advanced Parkinson's disease have the option of deep brain stimulation. This also involves a surgical procedure in which a pacemaker-like device is placed in the brain to help in control of Parkinson's disease symptoms.

Dr. LeWitt notes that the Henry Ford Parkinson's Disease and Movement Disorders Program is devoted to bringing the most promising therapies. This program is also working with experimental approaches for slowing progression of Parkinson's disease.

To learn more about the study, call 248-355-2452.

About Henry Ford Parkinson's Disease and Movement Disorders Program
The Henry Ford Parkinson's Disease and Movement Disorders Program is a Center of Excellence based in Southfield and at other Henry Ford locations. It provides treatment and research for Parkinson's disease, tremors, and other movement disorders.

The Henry Ford program provides routine diagnostic services and treatment for Parkinson's disease, as well as several investigational studies for new treatments. Research carried out is searching for better treatments and possible ways to arrest the progression of Parkinson's disease, including neuroprotection strategies and an upcoming gene therapy clinical trial.

The New Buzz on Detecting Tinnitus

CONTACT: Krista Hopson
khopson1@hfhs.org

Study: The New Buzz on Detecting Tinnitus

SAN DIEGO - It's a ringing, a buzzing, a hissing or a clicking - and the patient is the only one who can hear it. Complicating matters, physicians can rarely pinpoint the source of tinnitus, a chronic ringing of the head or ears that can be as quiet as a whisper or as loud as a jackhammer.

Now a Henry Ford Hospital study finds that a non-invasive imaging technique can actually aid in the diagnosis of tinnitus and may detect a reduction in symptoms after different treatments, offering hope to the more than 50 million patients with tinnitus.

"Until now, we had no way of pinpointing the specific location of tinnitus in the brain," says study co-author Michael D. Seidman, M.D., F.A.C.S., director of the Division of Otologic/Neurotolgic Surgery in the Department of Otolaryngology-Head & Neck Surgery at Henry Ford Hospital.

This imaging technique, magnetoencephalography (MEG), can determine the site of perception of tinnitus in the brain, which could in turn allow physicians to target the area with electrical or chemical therapies to lessen symptoms, according to study results presented at the American Academy of Otolaryngology-Head & Neck Surgery Foundation Annual Meeting & OTO EXPO.

"Since MEG can detect brain activity occurring at each instant in time, we are able to detect brain activity involved in the network or flow of information across the brain over a 10-minute time interval," explains co-author Susan M. Bowyer, Ph.D. bioscientific senior researcher, Department of Neurology at Henry Ford Hospital. "Using MEG, we can actually see the areas in the brain that are generating the patient's tinnitus, which allows us to target it and treat it."

Imaging techniques currently used to study tinnitus in the brain - PET and fMRI - provide a general location but are not successful at determining the specific site in the brain that is generating tinnitus symptoms.

MEG, by comparison, measures the very small magnetic fields generated by intracellular electrical currents in the neurons of the brain. Only 20 sites in the U.S., including Henry Ford, are equipped with a MEG scanner. MEG is presently used at these sites for pre-surgical brain mapping for patients undergoing surgery for brain tumor removal or Epilepsy treatment.

"With PET and fMRI, most of the auditory cortex of the brain lights up with activity during imaging. MEG, however, is a much more sophisticated machine and it can identify a specific tone or topic point, so only a small area in the brain lights up. It's like having the lights on in only the city of Detroit, compared to having the lights on in the entire state of Michigan," explains Dr. Seidman, director of the Otolaryngology Research Laboratory and co-director of the Tinnitus Center at Henry Ford.

For the study, Dr. Seidman and his colleagues collected MEG results from 17 patients with tinnitus and 10 patients without tinnitus. MEG data were collected for 10 minutes, and then digitally filtered. Study participants wore ear plugs to eliminate outside sounds, and kept their eyes open and fixated on one point on the ceiling in the room during testing.

With tinnitus patients who have ringing in one ear (unilateral tinnitus), MEG imaging detected the greatest amount of activity in the auditory cortex on the opposite site of the brain from their perceived tinnitus. For patients with ringing in the head or both ears (bilateral tinnitus), MEG imaging revealed activity in both hemispheres of the brain, with greater activity appearing in the opposite side of the brain of the strongest perception of tinnitus.

Patients without tinnitus had multiple small active areas in the brain, but no particular areas were found to be highly coherent during the 10-minute MEG scan.

Ultimately, Dr. Seidman says the study establishes MEG as an effective clinical tool for localizing the probably source of tinnitus in patients' brains. It also has the potential to assist with the development of future interventional strategies to alleviate tinnitus.

About Tinnitus
The American Tinnitus Association estimates that more than 50 million Americans experience tinnitus to some degree; about 12 million have severe enough tinnitus to seek medical attention; and about two million patients are so seriously debilitated that they cannot function on a day-to-day basis.

The exact physiological cause or causes of tinnitus are not known. There are, however, several likely sources, all of which are known to trigger or worsen tinnitus, including exposure to loud noises, wax build-up in the ear, ear or sinus infections, head and neck trauma, and certain disorders, such as hypo- or hyperthyroidism, Lyme disease, fibromyalgia, and thoracic outlet syndrome can have tinnitus as a symptom.

Although there is no known cure for tinnitus, Henry Ford offers several options for coping with the condition, including hearing aids, sound generators and medication, and all come with ongoing counseling. The goal is to provide patients with relief from their tinnitus and a better quality of life.

Reference: "Detection of Tinnitus by MEG Using Coherence Imaging," 2009 AAO - HNSF Annual Meeting & OTO Expo.

Research Support: NIH/NINDS Grant R01-NS30914

EDITOR'S NOTE: In addition to presenting results from the MEG study, Dr. Seidman's other roles at the 2009 AAO - HNSF Annual Meeting & OTO EXPO include chairing the Board of Governor's Leg. Rep. Committee; moderating a panel for the International Tinnitus Forum; chairing the Committee for Integrative Medicine; taking part in the CPOP and ANS committees; and running for Chair of the Board of Governors.

Study Finds 231 New Genes Associated With Head, Neck Cancer

CONTACT: Krista Hopson
khopson1@hfhs.org

Study Finds 231 New Genes Associated With Head & Neck Cancer

SAN DIEGO - A Henry Ford Hospital study has identified 231 new genes associated with head and neck cancer, one of the most deadly cancers responsible for 2.1 percent of all cancer deaths in the United States.

Previously, only 33 genes were reported associated with head and neck cancer.

"These new genes should advance selection of head and neck-specific gene targets, opening the door to promising new molecular strategies for the early detection and treatment of head and neck cancer," says study lead author Maria J. Worsham, Ph.D., director of research in the Department of Otolaryngology at Henry Ford Hospital. "It also may offer the opportunity to help monitor disease progression and a patient's response to treatment."

Results from the study were presented at the American Academy of Otolaryngology-Head & Neck Surgery Foundation Annual Meeting & OTO EXPO in San Diego.

This year alone, more than 55,000 Americans will develop head and neck cancer, which includes cancers of the mouth, nose, sinuses, salivary glands, throat and lymph nodes in the neck; nearly 13,000 of them will die from it.

According to the National Cancer Institute, 85 percent of head and neck cancers are linked to tobacco use. People who use both tobacco and alcohol are at greater risk for developing these cancers than people who use either tobacco or alcohol alone.

Treatment for head and neck cancer varies based on the location and stage of the tumor, but most often includes surgery, radiation therapy or chemotherapy.

To identify new genes that could ultimately aid in future diagnosis and treatment of head and neck cancer, Dr. Worsham's study used a whole-genome methylation approach to detect genes with altered promoter gene regions due to DNA methylation. DNA methylation - a type of chemical modification of DNA where a methyl group (CH3) can be added (hypermethylation) or removed (hypomethylation) - allows the researchers to look for genetic abnormalities within tumor samples.

Using five DNA samples from tumor tissue, the researchers looked for 1,043 possible cancer genes. Those genes were cross-examined with those already reported in PubMeth, a cancer methylation database. Of the 441 genes in the database, only 33 genes were referenced in connection with head and neck cancer.

In all, the whole-genome methylation approach revealed 231 potential new genes not previously reported in head and neck cancer. Of those, 50 percent were present in three or more of the DNA samples, and 20 percent were represented in all five samples.

"DNA methylation is emerging as one of the most promising molecular strategies for early detection of cancer, independent of its role in tumor development," says Dr. Worsham. "Abnormal methylation can result in shutting off or silencing gene function. However, treatment with more recent drugs can reverse abnormal DNA methylation patterns, reactivating silenced genes, and restoring normal gene function. Therefore, a validated head and neck cancer-specific gene panel is likely to signify potential demethylation treatment targets."

Reference: "DNA Hypermethylation Markers of Poor Outcome in Laryngeal Cancer," 2009 AAO - HNSF Annual Meeting & OTO Expo. The study will be presented by Dr. Worsham at 1:30 p.m. ET/10:30 a.m. PT Sunday, Oct. 4.

Research Support: Grant R01 NIH DE 15990