Eyelashes After Chemo

For cancer patients undergoing chemotherapy, hair loss just adds to the distress. And while more men these days like the shaved-head look, neither men nor women like the look of eyes with no lashes. After chemotherapy, lashes and brows grow back much slower than hair on the head. A study currently enrolling participants is looking at whether Latisse, a glaucoma drug shown to improve the length and thickness of eyelashes, can actually speed up the process of growing them back post-chemotherapy.

Dr. Dee Anna Glaser is professor of dermatology at Saint Louis University and lead investigator for the St. Louis site of this nine-site study. “People who have lost hair on their heads from chemotherapy can wear a wig or a hat. There’s nothing right now they can do for eyelashes that have fallen out,” she says.

The study will last one year, with a quarter of the people enrolled serving as controls for the first six months. After that, the control patients also will be given Latisse. The study is funded by Allergan, the maker of Latisse. When the more potent Lumigan was used to treat glaucoma, physicians noticed that their patients developed ‘camel lashes’ and found that if they needed only one eye treated, there was a noticeable difference in lashes between the two eyes. Allergan put the product through FDA testing with a different strength and application method, and called it Latisse in order to market it cosmetically for lashes. Before going to bed, Latisse users paint on a drop of the product with a small brush along the upper eyelid, much like applying eyeliner. Ever since it came out in its cosmetic application, dermatologists have wondered if it would help speed up the lash regrowth process for chemotherapy patients. Men or women interested in participating in the study should call 256-3436.

New Eye Implant

Some of us have good far vision, but reading has become a problem—a big one. Our arms just aren’t long enough anymore! A novel implant that goes into the cornea could change that. “Remember when we were kids? We discovered that if you looked through a pin hole in black paper, you could see all distances. This implant operates on the same principle,” notes Dr. Jay Pepose, whose Pepose Vision Institute is participating in a multi-site test of the AcuFocus corneal inlay. This black inlay, about 3.8 mm in diameter and 1/10 the thickness of a standard sheet of paper, has a hole in the middle and is inserted into the cornea via a tunnel or flap created by a laser. It is used in the non-dominant eye only.

“This inlay is based on the principle of a small aperture or F-stop of a camera,” Pepose explains. “If you look through the hole, you can see near and far at the same time. Unlike LASIK, which removes part of the cornea to correct vision, we are adding something. If there were any problem with it, it could be removed.”

In the U.S., the AcuFocus inlay is available only in a Phase-3 clinical trial. In Europe, Japan and Singapore, it is commercially available. The trial in the U.S. is slated to enroll 400 or so patients, recruiting people ages 45 to 60 who have good distance vision but impaired intermediate or close vision. They also must have less than one diopter of astigmatism to qualify.

Pepose is excited about this new product because there is not much to offer people who have only presbyopia, the lack of near-far accommodation that makes us need reading glasses as we age. The goal of the study is to allow the middle-aged person to attain all three visual distances. By using AcuFocus in only one eye, the patient sees closer distances without sacrificing clarity in far vision.

“No one in the study has had worse than 20/25 vision with this lens,” Pepose says. “Within a week and for several months, vision continues to improve. There may be some initial eye dryness, but this seems to resolve over time.” People wanting to participate can contact the Pepose Institute at peposevision.com, or to find out about all available U.S. sites, call 1-888-877-4949.

Protein & Alzheimers

While too much amyloid beta protein in the brain is linked to the development of the plaque characteristic of Alzheimer’s disease, researchers have found that too little of the protein causes learning problems and forgetfulness, other symptoms of dementia. “It’s more a matter of too much of a good thing,” says Dr. John Morley, director of geriatrics at Saint Louis University and lead researcher in the study. This finding could lead to better medications for treating Alzheimer’s disease.

He explains that 20 years of research have revealed that amyloid beta isn’t in itself a ‘bad’ protein—it’s the amount that is critical. When the brain produces too much, the excess amyloid starts to fold and create mind-robbing plaque. But having the right amount is important for memory and learning in healthy people. “It’s like cholesterol. Too much causes plaque and blockages in arteries; too little and we get other medical problems,” Morley explains. “Our research has shown that the physiologic role of amyloid beta is to enhance learning and memory. These findings are important in understanding the optimal design of drugs to treat Alzheimer’s disease.”

The research, which was published in the Sept. 11 e-edition of the Journal of Alzheimer’s Disease, showed that young, healthy mice that received low doses of amyloid beta protein improved their ability to recognize objects and successfully navigate through a maze. Conversely, mice that received a drug blocking amyloid beta protein had learning impairment. “In treating Alzheimer’s disease, we have to be careful not to lower amyloid beta too much because it will cause as many problems as if you had an excess,” Morley notes.

Much of the research on Alzheimer’s drugs has focused on antibodies to block amyloid beta. Morley says these new findings go against long-standing beliefs about amyloid beta, and they show that a better approach might be to regulate how much of the protein is produced, rather than block it entirely.

Radiation & Cervical Cancer

In the U. S., cervical cancer is the third leading cause of cancer death in women age 15 to 34. The good news for cervical cancer patients is that researchers at Washington University School of Medicine have demonstrated that targeted radiation therapy improves survival and reduces radiation-related complications. Called ‘intensity-modulated radiation therapy’ (IMRT), this has been used effectively for some time in treating cancers of the head, neck, pelvic region and nervous system. But this is the first large study to show its effectiveness in treating cervical cancer. The findings are being reported in an upcoming issue of International Journal of Radiation Oncology, Biology, and Physics.

Lead author on the study Dr. Elizabeth Kidd is a resident in radiation oncology at Barnes-Jewish Hospital. She is excited about the positive results from the study, which will hopefully encourage other treatment facilities to use IMRT on cervical cancer. The size of the study and strength of the data also have increased insurance coverage, another incentive for other institutions to adopt the practice. “One reason IMRT hasn’t been fully adopted for cervical cancer treatment is that cervical tumors are hard to distinguish from normal surrounding tissue with standard CT scans,” Kidd explains. “That uncertainty about tumor location made a whole-pelvic approach more appropriate. But now that we use PET scans, we can precisely delineate the location of the tumor and any regional metastases.”

Positron emission tomography (PET) imaging uses a glucose tracer that is highly absorbed by the primary tumor and any secondary tumors where the cancer has spread. The use of PET with CT helps ensure that the IMRT fields are precisely contoured for each patient. With conventional radiation therapy, it isn’t possible to avoid radiation exposure to healthy structures like the bowels, bladder, rectum, vagina and pelvic bones, which might later suffer complications from that exposure.

With IMRT, the radiation dose can conform more precisely to the three-dimensional shape of the tumor or lymph node being irradiated, minimizing the dose to surrounding normal tissue and organs. The IMRT is most beneficial for irradiating the pelvic lymph nodes where tumors travel and can get very close to critical pelvic structures. The study results were so compelling that the radiation oncology department has changed its treatment policies so that all cervical cancer patients received radiation using IMRT.

Diabetics & Smartphone Games

‘There’s an app for that’ has become a technology tagline in our culture. Now a group of Saint Louis University researchers has turned that glib saying into games to improve diabetes management. Saint Louis University assistant professor Maggie Jiao Ma and her colleague Cindy LeRouge, associate professor of decision sciences and information technology management, traveled to China last year for several weeks to learn more about diabetes in that country and how they could effectively use technology to improve the health of elderly diabetics.

“This did not start out as a gaming project, but we did a lot of groundwork by looking at the healthcare infrastructure in China, holding focus groups with older Chinese diabetics, and gathering input from various providers,” says LeRouge. “We found gaming was an enticing way to engage patients in managing their health.” She said she was surprised that elderly diabetics were interested in gaming, but that it has worked to their advantage.

The games vary in purpose. The researchers created a ‘food pyramid’ type of game that translates into a food pagoda and can be taken shopping or out to dinner to help maintain a healthy distribution of food types; a trivia game that increases awareness about the significance of other medical conditions in diabetes management and complications of diabetes like amputations and blindness; a game that helps them check for common symptoms as clues that they need follow-up; and an exercise game that gets people moving.

Elderly Chinese diabetics in the U.S. were also included in the planning and might be able to participate in the program, which launches next year in China. When asked, “Why a Smartphone?” LeRouge explained that it was portable, could be used to communicate with health professionals, and would work if other lines of communication were cut off. A seed grant from Microsoft Research helps fund culturally sensitive and specific tools for managing disease. China was chosen because it is the world leader in the number of elderly diabetics.

“Since we’ve done this groundwork, other countries like India have expressed an interest in a program like this, and we see wide applicability for a targeted, culturally sensitive approach here in the U.S.,” LeRouge says. “Our next steps involve researching aspects of this program that can be tweaked for other groups, such as overweight teens and tweens who may be pre-diabetic, and American Indians, who also have a high rate of diabetes. We might also be able to connect Smartphones to scales, glucose monitors and other technical tools to help providers stay in touch with high risk patients. In the U. S., 85 percent of our medical costs go to treat five chronic diseases, one of which is diabetes. This study has implications worldwide.”

Childhood Sleep Apnea

For as long as most of us can remember, tonsillectomy and adenoidectomy have been part of the treatment for childhood obstructive sleep apnea. A new study being launched hopes to determine whether improvements in sleep apnea require surgery or if some cases can be treated without it. Dr. Ron Mitchell, professor of otolaryngology at Saint Louis University and the study’s chief investigator, says the purpose is to help clinicians differentiate between those situations that need immediate surgery and those in which the child will outgrow the problem, avoiding the trauma of surgery and making better use of healthcare resources.

Saint Louis University and SSM Cardinal Glennon Children’s Medical Center are partnering in the ChildHood AdenoTonsillectomy (CHAT) study, the first research study that compares outcomes of children who undergo surgery versus those who are monitored and receive medical treatments such as nasal sprays. In addition to studying outcomes with obstructive sleep apnea treatments, CHAT will look at the connection between sleep apnea and learning problems, ADHD, pre-diabetes, high cholesterol, slow growth and obesity.

In normal weight children, obstructive sleep apnea is caused by enlarged tonsils and adenoids that restrict the size of the airway. An estimated 3 percent of all children and 30 percent of overweight or obese children have this condition. Each year, about 500,000 children have tonsillectomies to treat it, making this the most common major pediatric surgery. Sleep problems can affect daytime behavior, concentration, mood and school performance. They also can mimic symptoms of attention deficit hyperactivity disorder (ADHD). Experts have found that treating sleep apnea often improves school performance and social behaviors, and boosts energy levels.

Says Mitchell, “We want to answer some questions like: Can we say surgery cures this problem? Can we identify factors that may differentiate children who need surgery from those who don’t?” Study participants will be randomized into two groups: surgical and non-surgical, and qualified based on a sleep study and behavioral testing. Cardinal Glennon is an accredited sleep center. “Children with severe sleep apnea would not be in the study and would be recommended for surgery. Children on medication for ADHD would also not be eligible.” Mitchell says any child with ADD or ADHD should be evaluated for sleep problems. Treating those might make the behaviors go away, avoiding ADHD medication.

The study is only seven months long, and at the end of the seven months, the control children will be offered the surgical option. If, during the study, a parent feels a control child is getting worse, surgery is an option at any time. Interested parents should call 268-2700, ext. 1090.

Vitamin D & Asthma

We’ve long known that having one or both parents with asthma increases a child’s chances of developing it. Now, recent studies showing that vitamin D late in pregnancy plays a role in developing lungs—and that higher levels of maternal vitamin D may protect against asthma in their children—have led to a new multi-site study giving pregnant women with asthma extra vitamin D.

“We just don’t know and we’d love to find a definitive answer to that question,” says Dr. George Macones, head of obstetrics and gynecology at Washington University and a study co-investigator, along with Dr. Robert Strunk, pediatric asthma and allergy specialist. Macones hopes to determine whether what we consider ‘normal’ levels of vitamin D are really high enough to be protective, whether we can head off some cases of childhood asthma by providing this protection before birth, and what other things we can learn about creating a friendly uterine environment for developing babies. This research may also lead to future studies on things we can do for children after birth that can help keep them healthy, such as continuing vitamin D supplementation in high-risk children.

Childhood asthma is a big problem. The incidence has doubled in the last two decades, with about 6.7 million children suffering from asthma today, making it the most common chronic childhood illness. Vitamin D deficiency is also widespread in this country, affecting healthy children and adults, despite multivitamin intake and supplemented foods.

The Vitamin D Antenatal Asthma Reduction Trial (VDAART) is a five-year research study funded by NIH and enrolling asthmatic or allergic women between their 10th and 18th week of pregnancy, randomly divided into two groups. One group will receive a standard prenatal vitamin that contains 400 units of vitamin D, along with a 4,000-unit vitamin D supplement. The other group will receive the prenatal vitamin and a placebo. Children born during the study will be evaluated for asthma and wheezing at ages 1, 2, and 3. The study plans to enroll 870 women nationwide, with 290 to come from Washington University obstetrics clinics.

Preventing Diabetes

In the U.S., about 24 million people have diabetes, most of it type 2, the kind associated with risk factors such as obesity, inactivity, family history and ethnic predisposition. An additional 57 million overweight adults have glucose levels above normal in the pre-diabetic range, a condition that greatly increases the risk of heart attack, stroke and developing type 2 diabetes. Two multi-site studies have given us the best answer yet as to how to head off the suffering and cost of full-blown type 2 diabetes.

Dr. Neil White, a Washington University pediatric diabetes specialist at St. Louis Children’s Hospital and the principal investigator for the St. Louis site on both studies, says prevention is very effective. The first study, the Diabetes Prevention Program (DPP) completed in 2001, showed that intensive lifestyle changes, including exercise, reduced calorie and fat intake, and frequent interactions with health care providers, reduced type 2 diabetes by 58 percent over the placebo group after three years. A second group that did not implement lifestyle changes but took the oral diabetes drug metformin twice a day reduced their incidence of diabetes by 31 percent during the same period. This trial involved 3,200 overweight or obese adults with elevated glucose levels at high risk for developing diabetes. Forty-five percent of these participants were from minority groups more susceptible to developing diabetes.

The second study, the Diabetes Prevention Program Outcome Study (DPPOS), followed a high percentage of the same group that participated in the earlier study. That study ended in 2008 after following participants for 10 years. During the DPPOS five-year study period, participants from the DPP who had been on metformin continued on that drug. The other participants had group-level lifestyle change support, as compared to the one-on-one lifestyle change support from the earlier study. At the end of the DPPOS, researchers were able to say that people who made lifestyle changes delayed the onset of diabetes by four years, compared to the placebo group; and the metformin group delayed onset by two years. The benefits of lifestyle change were especially notable in the elderly. Those 60 and over lowered their rate of developing diabetes in the next 10 years by about half.

The study is now into its first year of the next five-year study period, with funding until 2014. “Changing lifestyle to better health habits, including those aimed at reduced weight, a better diet and more exercise, will have long-term and sustained impact on overall health, at least in preventing diabetes and hopefully in preventing complications associated with diabetes and prediabetes,” says White. The study has found that even slight weight loss has huge benefits, and that lifestyle changes also lower blood pressure and triglyceride levels. The current five-year study will continue to gather information on preventing diabetes, but also on the complications associated with diabetes and prediabetes over time, like eye, kidney and heart disease.

Pediatric Brain Tumor Gene

A gene mutation discovered by researchers at Washington University School of Medicine may help steer the search for drugs that block growth of a certain benign pediatric brain tumor. Dr. David Gutmann, professor of neurology and leader of the research team, is excited about this finding because there are few good treatments for this type of tumor, pilocytic astrocytoma. While it is benign, its growth in the brain causes dire physical problems: headache, nausea, vomiting, balance issues and vision impairment. “There are several problems with treating this tumor,” says Gutmann. “It tends to grow in inaccessible places and may have fingers branching out from it that prevent a surgeon from excising it completely. If we remove them, they don’t usually grow back, but they are difficult to remove and may be near sensitive structures that could cause long-lasting impairments if damaged.” Other options, including chemotherapy and radiation, have their own drawbacks for young patients.

“The problem with tumors in children is that they grow faster than the kids are growing, and we don’t want to kill all dividing cells, since that’s basically most of the body,” Gutmann notes.

His hope lies in the findings of the recent study, which identified a gene not previously associated with these tumors. That’s important, he says, because they now can think about designing treatments that alter the pathway the gene controls.

Gutmann normally studies the tumors in the context of neurofibromatosis 1 (NF1), a hereditary condition known to predispose children to tumor growth. But these tumors also occur in children who don’t have NF1, at the rate of about two to three new cases per 100,000 children a year. Gutmann’s team performed detailed genetic and genomic analyses of tumor samples from 70 patients with pilocytic astrocytoma and nine patients with NF1. That analysis led researchers to the BRAF gene, which had already been linked to other cancers.

“BRAF was a great target because the signaling pathway it controls is also controlled by neurofibromin, the protein made by the gene that is mutated in NF1 patients,” says Guttman. “This finding is exciting because a number of drugs are known to inhibit this pathway, some of which are already being tested for their ability to control the growth of other cancers. Our end goal is to arrest growth or shrink the tumor without harming other cells in the body so the kids have normal growth and development. This helps us better understand tumors and develop drugs to shut off the growth of tumor cells.”

Route to Diabetic Tissue Damage

It has been known for years that complications of diabetes are linked to the duration of the condition and high blood glucose levels. However, it has been unclear how high glucose levels cause diabetic complications. In research published this year, Washington University scientists have shed some light on how high blood sugar damages nerve tissue and cells. Senior author Dr. Joe Williamson, a retired professor of pathology and immunology, says the findings have been controversial. “What we’ve found should help fine-tune efforts to prevent diabetes-related complications such as hardening of the arteries, damage to vision and loss of nerve function. In recent years, increasing evidence indicates that high glucose levels damage the eyes, nerves, kidneys, and large and small blood vessels by increasing the formation of superoxide and creating oxidative stress.”

Normally, cells use glucose mostly to make energy through a process called glycolysis. If glucose rises too rapidly, as in uncontrolled diabetes, the body uses a different pathway, the sorbitol pathway. When the sorbitol pathway kicks in, due to uncontrolled glucose levels, it creates superoxide, an oxidant responsible for cell damage and death. Oxidants like superoxide are highly reactive chemicals that, once formed, are difficult to inactivate before they damage tissue.

Antioxidants help our body by scavenging ‘free radicals,’ as these oxidants are commonly called. Pyruvate is somewhat different because in addition to its scavenging function, it actually prevents formation of the oxidant superoxide. Sorbitol pathway inhibitors have been tried in the past, but did not block it sufficiently to prevent damage.

Pyruvate supplementation has been shown in diabetic animals to normalize vascular dysfunction caused by high glucose levels and slow cataract formation. While Williamson thinks pyruvate supplementation merits further study, the problem that must be overcome is how quickly the body metabolizes pyruvate. It may be more immediately useful in preventing diabetic damage to the eye, where it can be applied as eye drops and quickly reach the retina and lens. More effective inhibitors of the sorbitol pathway are being explored and may prevent diabetic complications in the future. For now, what this research means to patients with diabetes and their physicians is that good control of blood sugar levels is even more critical than previously thought. “We can’t afford to be lax in blood sugar management,” Williamson says.