A group of researchers from Universidad Carlos III de Madrid (UC3M) has presented a new algorithm that uses a new method to analyse the information obtained from electroencephalograms to detect neurodegenerative diseases, such as epilepsy, using the bioelectric signals of the brain.

The research project is a joint effort among engineers and doctors from UC3M, the Clínica Universitaria de Navarra and Universidad Pública de Navarra. It began as a collaborative project designed to discover and interpret bioelectric phenomenon originating in the cerebral cortex. The objective of this research was to apply these studies to the analysis of different pathologies such as Parkinson’s disease, Alzheimer or epilepsy. Electroencephalography was used as a means of obtaining cerebral signals. This technique uses electrodes placed on the surface of the scalp to perform a test that measures and records the electrical activity generated in the brain.

The first results recorded by the scientists were promising and showed a need to reduce the amount of information obtained from electroencephalograms due to the fact that the analysis of all the data requires a great deal of time and large processing capacity. In order to achieve this aim more efficiently, the scientists designed an algorithm that allows them to extract the most relevant characteristics of the signals associated with epilepsy. Thus, they are able to detect and classify more quickly epileptic seizures as well as determine which parts or areas of the brain are affected the most. “The advantage of this method is that it allows us to detect, classify or identify neurological diseases with a small amount of information” says Carlos Guerrero Mosquera, one of the researchers from the Department of Signal and Communications Theory (Departamento de Teoría de la Señal y Comunicaciones) at UC3M. He adds, “Electroencephalograms contain a lot of information and what we are looking for is to try to improve the efficiency of the tasks carried out by analysing small amounts of information through the use of the most important data received from the signals.”

Presentation to the public

This new method, published recently in the journal Medical & Biological Engineering & Computing, has been compared to other techniques and the results of this analysis will be presented at the International Conference of the IEEE Engineering in Medicine and Biology Society. This event, which is one of the most important biomedical engineering conferences, will take place in Buenos Aires (Argentina) from the 31st August until 4th September. In general terms, this method can be divided into four fundamental processes: the acquisition of a signal through the use of electroencephalography, cleaning or pre-processing of the signal in order to eliminate noise and the extraction/selection of characteristics depending on how the information will be used. “The detection of data should follow a linear procedure but for the moment, we use databases”, Carlos Guerrero points out. “At a later date, when the application shows positive results, we will try to reduce processing costs by the selection of specific characteristics.”

The researchers explain that this method extracts information about the time and frequency pattern of the signal in a new and simple way. This makes it easier to detect and classify segments with epilepsy and opens up the possibility of applying the algorithm to other pathologies. “Initially this method was developed to classify and detect epileptic seizures, but in the future we wish to apply it to other neurodegenerative diseases such as Parkinson’s, Alzheimer or the analysis of different sleep disorders,” Guerrero explains.

—

On the Net:

• Universidad Carlos III de Madrid
• Medical & Biological Engineering & Computing

First completed clinical trial results out today in the Journal of Psychopharmacology

MDMA (±3,4-methylenedioxymethamphetamine, also known as Ecstasy), may one day offer hope for individuals with posttraumatic stress disorder (PTSD), even people for whom other treatments have failed. Clinical trial results out today in the Journal of Psychopharmacology, published by SAGE, suggests that MDMA can be administered to subjects with PTSD without evidence of harm and could offer sufferers a vital window with reduced fear responses where psychotherapy can take effect.

Before MDMA became used recreationally under the street name Ecstasy, hundreds of psychiatrists and psychotherapists around the world administered MDMA as a catalyst to psychotherapy. MDMA was criminalized in the US in 1985 (it had been illegal in the UK since 1977). Several decades later, this study is the first completed randomised, double-blinded clinical trial to evaluate MDMA as a therapeutic adjunct in any patient population.

Belmont, MA-based Rick Doblin, Ph.D., President of the Multidisciplinary Association for Psychedelic Studies (www.maps.org, a non-profit psychedelic and medical marijuana research and educational organization that sponsored the study), together with South Carolina-based psychiatrist Michael Mithoefer, MD and colleagues, conducted a pilot Phase II clinical trial with 20 patients with chronic PTSD persisting for an average of over 19 years. Prior to enrolling in the MDMA study, subjects were required to have received, and failed to obtain relief, from both psychotherapy and psychopharmacology.

Participants treated with a combination of MDMA and psychotherapy saw clinically and statistically significant improvements in their PTSD ““ over 80% of the trial group no longer met the diagnostic criteria for PTSD, stipulated in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV-TR) following the trial, compared to only 25% of the placebo group. In addition, all three subjects who reported being unable to work due to PTSD were able to return to work following treatment with MDMA.

The trial centred on two eight-hour psychotherapy sessions scheduled about 3-5 weeks apart, where 12 subjects received MDMA, and eight took a placebo. Subjects were also given psychotherapy on a weekly basis before and after each experimental session. A blinded, independent rater tested each subject using a PTSD scale at baseline, and at intervals four days after each session and two months after the second session. The clinical response was significant ““ 10 of the 12 in the treatment group responded to the treatment compared with just two of the eight in the placebo group. During the trial, the subjects did not experience any drug-related Serious Adverse Events (SAEs), nor any adverse neurocognitive effects or clinically significant blood pressure or temperature increases.

After the two-month follow-up, subjects in the placebo group were offered the option to participate in the treatment process again, to receive MDMA on an open-label basis, acting as their own controls. Seven of the eight placebo subjects elected to receive MDMA-assisted psychotherapy, with successful treatment outcomes similar to the subjects initially randomized to MDMA.

PTSD involves exaggerated and uncontrolled fear responses. To treat these, psychotherapists need to help sufferers revisit traumatic experiences. But patients often suffer intolerable feelings when they revisit the trauma, or numb themselves emotionally, resulting in the psychotherapy having little effect. The goal of using MDMA is to temporarily reduce fear and increase trust without inhibiting emotions, especially painful emotions, allowing these patients a window where psychotherapy for their PTSD is effective.

MDMA’s pharmacological effects include serotonin release, 5HT2 receptor stimulation and increase in levels of the neurohormones oxytocin, prolactin and cortisol.

Importantly, this trial involved concentrated periods of patient-therapist contact (31 hours over two months) including two all-day therapy sessions and overnight stays in the clinic. “These are not usual features of psychotherapy practice in the outpatient setting,” says Michael Mithoefer. MDMA-assisted psychotherapy would require special clinics equipped for longer treatment sessions and overnight stays if an MDMA-based treatment were approved. “This method also involves patient preparation and close follow-up to support further processing of emotions and integration of cognitive shifts that may occur,” Mithoefer adds, stressing that these are vital for safety and therapeutic effect.

Measures like these may prove a price worth paying, however, to alleviate the debilitating effects of PTSD on sufferers in future.

The authors caution that the study does have limitations ““ for example they did not look at gender and ethnic factors in their sample selection. Another important limitation was that most participants and trial investigators guessed accurately whether they were in the treatment or the placebo group. The placebo had no psychoactive effect and investigators could detect raised blood pressure and other symptoms in the MDMA group. A long-term follow-up to the study just published, evaluating subjects an average of about 40 months post-treatment, is underway.

The investigators have now received the go ahead from the US Food and Drug Administration (FDA) for a protocol for a three-arm, dose-response design that they expect will result in successful blinding. This new study is for US veterans with war-related PTSD, most from Iraq and Afghanistan and a few from Vietnam. MAPS is currently sponsoring MDMA/PTSD Phase 2 pilot studies in Switzerland and Israel, and is working to start additional pilot studies in Canada, Jordan and Spain.

—

On the Net:

• SAGE Publications UK
• Journal of Psychopharmacology

Researchers at Georgia Institute of Technology and Emory University have invented a painless vaccine-delivery system that may one day allow flu shots to be delivered by mail. 

The new system replaces a conventional large needle with hundreds of tiny dissolvable ones embedded in a skin patch, and may even generate a better immune response than a conventional shot.

The microneedles come attached to a Band-Aid like skin patch, and are so small they cannot be felt.  They scarcely penetrate the skin before dissolving and releasing their vaccine.

Mark Prausnitz of Georgia Institute of Technology, who led the research in collaboration with researchers at Emory University, likened the business side of the patch to fine sandpaper.

Some medications that are already available, such as nicotine patches that help people quit smoking, work by simply allowing the medication to be absorbed by the skin.  However, attempts to use this approach to deliver a flu vaccine have been unsuccessful so far.

But the Georgia Tech vaccine is different in that it is still injected, but the microscopic size of the needles mean the shots do not hurt, and that no specialized training is required to administer them.

“The goal has been a means to administer the vaccine that is patient friendly,” Mr. Prausnitz told The Associated Press (AP).

Indeed, the approach does away with two of the biggest problems associated with vaccines: patients’ fear of needles, and disposal of leftover hypodermic needles.

The researchers wanted to find a solution that was “not only not hurting or looking scary, but that patients could self-administer,” he said.

The dissolvable needles mean there are no leftover sharp needles, something of particular importance for those who may administer the vaccine themselves at home, he explained.

Such a system might make people more likely to get the vaccine, he said.

The patch has already been tested on mice, and the researchers are seeking additional funding to begin tests in people.  If the human tests are successful, the new patch could be available for use in five years, Prausnitz said.

The tiny microneedles are 650 microns (three-hundredths of an inch) in length, with 100 placed on the patch used in the mouse study — enough to successfully deliver the proper amount of vaccine. 

The patch is placed on the skin for 5 to 15 minutes, but can remain longer without doing any damage, Prausnitz said.

Doctors recommend that nearly everyone get a flu vaccine every year, but many people don’t because it can be inconvenient.  However, if people can receive their shot in the mail, or perhaps at a local pharmacy, they may choose to do so, Prausnitz said. 

When asked if the term “microneedle” might still make some “shot averse” people nervous, Prausnitz said he was confident that marketers would develop a better term before the new system would hit the market.

The research was supported by the National Institutes of Health, and was reported online July 18 in the journal Nature Medicine.

—

Image 1: An array of 36 dissolving microneedles is shown here on a fingertip for size comparison. (Credit: Jeong-Woo Lee)

Image 2: This is the first image in a sequence showing how the microneedles dissolve in the skin. This image shows the microneedles before application to the skin. (Credit: Sean Sullivan)

Image 3: This image shows microneedles that have partially dissolved one minute after being pressed into pig skin. (Credit: Sean Sullivan)

—

On the Net:

• A summary of the report can be viewed here
• Georgia Institute of Technology’s Laboratory of Drug Delivery

Contrary to Leo Tolstoy’s famous observation that “happy families are all alike; every unhappy family is unhappy in its own way,” a new psychology study confirms that unhappy families, in fact, are unhappy in two distinct ways. And these dual patterns of unhealthy family relationships lead to a host of specific difficulties for children during their early school years.

“Families can be a support and resource for children as they enter school, or they can be a source of stress, distraction, and maladaptive behavior,” says Melissa Sturge-Apple, the lead researcher on the paper and an assistant professor of psychology at the University of Rochester.

“This study shows that cold and controlling family environments are linked to a growing cascade of difficulties for children in their first three years of school, from aggressive and disruptive behavior to depression and alienation,” Sturge-Apple explains. “The study also finds that children from families marked by high levels of conflict and intrusive parenting increasingly struggle with anxiety and social withdrawal as they navigate their early school years.”

The three-year study, published July 15 in Child Development, examines relationship patterns in 234 families with six-year-old children. The research team identified three distinct family profiles: one happy, termed cohesive, and two unhappy, termed disengaged and enmeshed.

Cohesive families are characterized by harmonious interactions, emotional warmth, and firm but flexible roles for parents and children. “Think the Cosby family,” says Sturge-Apple, offering an example from the popular TV series about the affable Huxtable family.

Enmeshed families, by contrast, may be emotionally involved and display modest amounts of warmth, but they struggle with high levels of hostility, destructive meddling, and a limited sense of the family as a team. Sturge-Apple points to the emotionally messy Barone family in the family sitcom Everybody Loves Raymond as a good example of an enmeshed family.

Finally, disengaged families, as the name implies, are marked by cold, controlling, and withdrawn relationships. The seemingly pleasant suburban family in the movie Ordinary People provides a classic illustration of a disengaged family, according to the authors. Reacting to the death of their oldest son, the parents in the film retreat emotionally, creating a barren home environment in which feelings cannot be discussed.

Although the study demonstrates solid evidence of a family-school connection, the authors caution that dysfunctional family relationships are not responsible for all or even most behavior difficulties in school. Other risk factors, such as high-crime neighborhoods, high-poverty schools, troubled peer circles, and genetic traits also influence whether one child develops more problems than another child, explains co-author Patrick Davies, professor of psychology at the University of Rochester.

The new study builds on the long-established family systems theory, which consistently has identified the three types of families using clinical observations. This study, however, is the first to empirically confirm their existence across multiple relationships within the family: in the marriage, in child-parent interactions, and among all three together, says Davies. “We were really able to look at the big picture of the family,” he adds, “and what was striking was that these family relationship patterns were not only stable across different relationships but also across time, with very few families switching patterns.”

The research found that children from disengaged homes began their education with higher levels of aggressive and disruptive behavior and more difficulty focusing on learning and cooperating with the classroom rules. These destructive behaviors grew worse as the child progressed through school.

By contrast, children from enmeshed home environments entered school with no more disciplinary problems or depression and withdrawal than their peers from cohesive families. But as children from both enmeshed and disengaged homes continued in school they began to suffer higher levels of anxiety and feelings of loneliness and alienation from peers and teachers. The authors conclude that, “children in the early school years may be especially vulnerable to the destructive relationship patterns of enmeshed families.”

In the study, families were assessed using parent and teacher reports and through direct observation in the lab. Families came to the lab each year for two visits spaced one week apart. Both parents and the child played Jenga, an interactive game, for 15 minutes, and on alternate weeks each parent interacted alone with the child for five minutes of play and five minutes of clean up. Parents were also asked to discuss two topics picked to elicit disagreement. The sessions were videotaped and evaluated for behavior patterns.

The study examined how the parents related to one another, noting any aggression, withdrawal, or avoidance and observing their ability to work as a team in the presence of the child. The researchers coded the emotional availability of the parent toward the child, whether he or she provided praise and approval or simply ignored the youngster during shared activities. Observers also followed how the child related to his or her mother and father, noting whether attempts made to engage the parents were brief and half-hearted or sustained and enthusiastic.

Funded by the National Institute of Mental Health, the study was co-authored by E. Mark Cummings, professor and Notre Dame Chair in Psychology at the University of Notre Dame.

—

On the Net:

• University of Rochester
• Child Development

Study shows significant variations in spoon capacity

Medical experts have warned parents that using domestic spoons to dispense children’s medicine could lead to overdoses after discovering that some hold two to three times as much as others.

The study in the August issue of IJCP, the International Journal of Clinical Practice, looked at 71 teaspoons and 49 tablespoons collected from 25 households in Attica, Greece.

It found that the capacity of the teaspoons ranged from 2.5ml to 7.3ml, with an average and median volume of 4.4ml. The capacity of the tablespoons ranged from 6.7ml to 13.4ml, with an average of 10.4ml and a median of 10.3ml.

“The variations between the domestic spoon sizes was considerable and in some case bore no relation to the proper calibrated spoons included in many commercially available children’s medicines” says Professor Matthew E Falagas, Director of the Alfa Institute of Biomedical Sciences in Athens, Greece.

“A parent using one of the biggest domestic teaspoons would be giving their child 192 per cent more medicine than a parent using the smallest teaspoon and the difference was 100 per cent for the tablespoons. This increases the chance of a child receiving an overdose or indeed too little medication.”

The 25 women who took part in the study were aged between 24 and 84 with an average age of 48. Most had between one and three different teaspoons and tablespoons in their house, but two women had as many as six different teaspoons and one of those also had five different tablespoons.

“We not only found wide variations between households, we also found considerable differences within households” says Professor Falagas.

The researchers were also keen to see whether there were any differences when five of the women were asked to dispense liquid from a calibrated 5ml medicine spoon. They found that only one dispensed the correct dose of liquid, with three dispensing 4.8ml and one 4.9ml.

As a result of their findings, the researchers, from Athens and Boston, USA, are urging parents to use calibrated medicine syringes to dispense liquid medication to children. This method is also more effective if children are very young or reluctant to take medicine, as a spoon can be pushed away and spilt, leaving the parent unsure about how much the child has actually taken.

“Dosing and administering medication to children is different from adults” says Professor Falagas. “Pediatric dosages need to be adjusted to age and body weight and, as a result, children are considered to be more vulnerable to dosage errors than adults.

“Our research clearly shows that using domestic teaspoons and tablespoons can result in children receiving considerably more or less medicine than they need.

“Low-cost medicine syringes are widely available from pharmacists, very easy to use and will give parents greater confidence that they have dispensed the correct dose.”

The authors also suggest that adults avoid using domestic spoons for themselves.

“Although adults do not face the same risk levels as children, we would still advise them to use properly calibrated spoons or cups if they take any liquid medicine.”

Reference: Inaccuracies in dosing drugs with teaspoons and tablespoons. Falagas et al. IJCP. 64.9, pp1185-1189. (August 2010). DOI: 10.1111/j.1742-1241.2010.02402.x

—

On the Net:

Read the article online

Researchers from Baylor College of Medicine’s Scott Department of Urology, Department of Molecular and Cellular Biology and the NCI-designated Dan L. Duncan Cancer Center are leading major efforts in bladder cancer research, both in the clinical and lab setting.

Find out more about important advances in drug development, new theories about bladder cancer stem cells and the biology of the bladder from BCM researchers Dr. Guru Sonpavde, clinical assistant professor of medicine ““ hematology and oncology, Dr. Keith Syson Chan, assistant professor of urology and of molecular and cellular biology, Dr. Carolyn Smith, assistant professor of molecular and cellular biology and Dr. Seth Lerner, professor of urology.

Drug development

There are a host of drugs, new and old, being studied as potential treatments for bladder cancer. Sonpavde is involved in a variety of clinical and laboratory trials that have tested a host of new therapies.

“Advanced stage metastatic bladder cancer (muscle invading) is generally not curable with currently available chemotherapy,” said Sonpavde. “We really need to improve upon the standard approach to treatment of muscle-invading bladder cancer still confined to the bladder, which typically includes the removal of the bladder and some form of chemotherapy with radiation for those unable to undergo bladder removal surgery.”

Sonpavde outlined some of the lab and clinical work he has been involved with at BCM. In one lab-based study, BCM researchers focused on a drug called Sutent, already approved by the U.S. Food and Drug Administration for advanced kidney and gastrointestinal cancers. In the bladder cancer model, the drug was shown to block tumor cell growth by inhibiting certain cell signaling pathways that promote blood vessel growth. “Basically, this “Ëœanti-angiogenic treatment’ slowed down the cancer cell division,” said Sonpavde.

The team has also studied a drug called Sprycel, already approved by the FDA for the treatment of chronic myeloid leukemia. Also a cell signaling inhibitor, in the bladder cancer model, the drug targets a tumor growth-promoting molecule called SRC. “We found that the inhibition of SRC signaling activity in a type of cancer that over-expressed SRC slowed growth of cancer with this drug.”

Sonpavde and his research team recently received funding for a laboratory bladder cancer study from Cephalon, a company developing a new drug called CEP-11981. The compound inhibits angiogenesis (the formation of new blood vessels).

He also obtained support and funding from Celgene to study lenalidomide (Revlimid) in a laboratory bladder cancer model. This drug is FDA approved for multiple myeloma and myelodysplastic syndromes and appears to work by inhibiting blood vessel growth, as well as promoting the immune system.

In one clinical trial Sonpavde calls a “window of opportunity,” the team is studying the effect of Sprycel in the neoadjuvant setting ““ chemotherapy or radiation given to patients prior to surgery. The trial will involve patients waiting for a cystectomy (removal of the bladder) to see if the drug can block some tumor growth promoting signaling pathways. “This is a new design,” said Sonpavde. “These patients would otherwise have been waiting for surgery for three, sometimes four weeks without drug activity.”

BCM has collaborated with the Hoosier Oncology Group, which is affiliated with Indiana University, to conduct these trials in a consortium of academic institutions.

In other clinical trials, the researchers are looking at a new combination including chemotherapy plus Sutent prior to cystectomy, and studying the effect of Tamoxifen (an estrogen receptor) for metastatic bladder cancer that continues growing after previous chemotherapy. Tamoxifen has previously been approved for breast cancer and showed promising activity in the bladder cancer animal models in Drs. Lerner, Sonpavde and Smith’s laboratory.

“These are new designs that hold a lot of promise for future treatment of the disease,” said Sonpavde. “We hope to have exciting new contributions for the field.”

Additionally, Sonpavde is involved in studying the natural history of bladder cancer after surgery to remove the bladder cancer. Such studies of large numbers of patients will help identify patients with a higher risk of future recurrence of cancer that might require more aggressive therapy following surgery.

New theories

The study of cancer stem cells, the cells that are resistant to conventional therapies (chemotherapy, radiation) is an emerging area of research. Chan has focused his research on a promising new theory regarding cancer stem cells. Chan and his team have isolated bladder cancer stem cells and are studying how to better attack them and improve targeted therapy.

“Non-invasive bladder cancer is quite curable,” said Chan. “But 15 percent of these cases will progress to invasive cancer. We currently have no good clinical or prognostic markers for predicting this progression.”

Using invasive bladder cancer tumor samples, cancer stem cells are isolated following removal of the bladder. “We hypothesize that though a large portion of the cancer was removed, the tumor-initiating cells will prompt recurrence and metastasis.”

Chan and his team performed a genetic analysis on cancer stem cells and found a gene signature that can separate invasive from non-invasive cancer. “If the cancer stem cell signature is present in patients with non-invasive, then we have a good signature for predicting those that will become invasive.”

The team has also identified a protein CD47 that is highly expressed in cancer stem cells. “This protein is an inhibitory or “Ëœdon’t eat me’ signal on cancer cells for immune cell macrophages, or cells that are able to engulf foreign materials,” said Chan. “When this protein is blocked by an antibody, the can eat the cancer cells.”

Chan said the research is significant because preclinical results using this antibody led to slow down of tumor growth.

In addition to looking at what is happening inside the cells, Chan and his team are looking at the tumor microenvironment. “There are certain factors in the microenvironment that support these cells,” said Chan. “We are seeking to understand what those are.”

Understanding the biology of the bladder

Smith and her team focus on another area they believe may unlock clues about the overall biology of the human bladder ““ the role of estrogen receptors.

Estrogen receptors are proteins that estrogen binds to. Estrogens are sex steroids present in males and females that stimulate the development and maintenance of many different tissues.

“There are two forms of estrogen receptors ““ alpha and beta,” said Smith. “We found that estrogen receptor beta was expressed in human bladder tumors.” Very little alpha was found.

The direction of this research is significant because researchers believe they could use this form of estrogen receptor as a target to control the growth of bladder cancer cells.

In experiments with bladder cancer cells, as well as animal models, the team has shown that estrogen receptor inhibitors (anti-estrogens) slow the growth of bladder cancer cells.

Smith and her team have also collected similar results in a cancer prevention model. “The recurrence rate of bladder cancer is high and there is a strong need to develop additional approaches to stopping this cancer from coming back.”

Using selective estrogen receptor modulators, or SERMS, the researchers can block estrogen receptor action in certain parts of the body.

“From a pharmacologic perspective, this class of drugs is very interesting and holds a lot of promise for research,” said Smith. “They do not inhibit estrogen action everywhere in the body ““ for example, men and women need estrogen to keep their bones protected ““ but are effective in specific organs.” In this case, the bladder, Smith said.

“We are very interested in better defining the role of estrogen receptors in the biology of the bladder,” said Smith. “We want to know how they work in normal bladder and bladder cancer, and how to best target the receptors to block bladder cancer development and growth.”

—

On the Net:

• BCM

Silicon oil absorbs 50 percent of radioactive rays

Eye cancer patients face an unenviable dilemma. They must enter treatment knowing that their surgeon’s strategy to kill the deadly tumor with radiation may also sacrifice their eyesight.

Now, UCLA researchers have discovered that a commonly used substance called silicon oil shields the eye and appears to protect vision in patients undergoing radiation therapy for ocular melanoma. The American Medical Association’s Archives of Ophthalmology publishes the findings in its July edition.

“Vision loss is a devastating yet common side effect of radiation therapy,” said Dr. Tara McCannel, assistant professor of ophthalmology and director of the UCLA Ophthalmic Oncology Center at the Jules Stein Eye Institute. “Until recently, physicians focused on killing the tumor and considered vision loss secondary. Our results suggest that silicon oil offers a safe tool for protecting the patient’s vision during radiation.”

Ocular melanoma forms in the pigmented layers under the retina and is the most common eye cancer to strike adults. The National Eye Institute reports some 2,000 newly diagnosed cases of the cancer, roughly seven in 1 million people, each year. The cause remains unknown.

Surgeons treat ocular melanoma by stitching a gold plaque containing radioactive seeds to the white of the eye and removing it a few days later. While radiation kills the cancer cells, it also causes irreversible injury to the optic nerve fibers and macula, the section of the retina responsible for central vision.

Radiation damage to the macula weakens the blood vessels feeding the eye, causing bleeds and wiping out circulation. Even when the radiation successfully destroys the tumor, the eye structures remain extremely fragile and prone to atrophy, which can lead to vision loss. “If patients survive the cancer, more than half will suffer vision loss in the treated eye six months to three years later,” said McCannel, a vitreoretinal surgeon who is also a member of UCLA’s Jonsson Comprehensive Cancer Center. The risk for blindness increases over time.

The UCLA technique takes place immediately before the patient’s eye is exposed to radiation.

Patients first undergo an exam to measure baseline vision before treatment. McCannel next removes the vitreous gel, which supports the interior shape of the eye. She replaces the gel with silicon oil, an FDA-approved substance often used to hold the retina in place during surgery to repair retinal detachment.

After removing the radiation plaque from the treated eye, she flushes the oil away with saline, which is eventually replaced by the patient’s natural fluids.

“We discovered that silicon oil absorbs nearly 50 percent of the radiation,” she said. “The substance acts like a physical shield, reducing the amount of radioactive rays that reach the back and sides of the eye. We hope that silicon oil’s ability to block radiation translates into better vision for patients down the road.”

Already widely used in retinal surgery, the oil doesn’t interfere with the tumor’s treatment, and its transparency allows both the surgeon and the patient to see through it.

The UCLA team used three approaches to demonstrate that silicon oil absorbs 50 percent of the radiation rays. While more long-term research is needed, early follow-up with McCannel’s patients showed that their vision returned to baseline levels without interfering with their tumors’ response to radiation therapy.

—

On the Net:

• University of California – Los Angeles

Next, researchers will study whether treating neuropsychiatric symptoms in MCI can delay the onset of dementia

A new Mayo Clinic study found that apathy and depression significantly predict an individual’s progression from mild cognitive impairment (MCI), a disorder of the brain that affects nerve cells involved in thinking abilities, to dementia, including Alzheimer’s disease and Lewy body dementia. The study was presented at the International Conference on Alzheimer’s Disease in Honolulu on July 11, 2010.

“An important area of study is the identification of biomarkers and clinical predictors for the progression from normal cognition to mild cognitive impairment and mild cognitive impairment to dementia,” says Yonas E. Geda, M.D., a Mayo Clinic neuropsychiatrist and the study’s lead investigator. “We knew from previous smaller studies that neuropsychiatric symptoms like depression, apathy and agitation seem to predict progression from mild cognitive impairment to dementia, so we set out to look at this hypothesis in a population-based setting with a larger sample size.”

Depression and apathy are neuropsychiatric symptoms that are often difficult to distinguish, according to Dr. Geda. Depression causes changes in mood, thinking, physical well-being and behavior, while apathy is loss of motivation without associated feelings of being depressed or blue.

As part of the Mayo Clinic Study of Aging, Dr. Geda and a team of Mayo Clinic researchers identified 358 individuals with mild cognitive impairment and used a questionnaire to collect data on depression and apathy. Then, they prospectively followed individuals to the outcome of dementia (a median of 2.8 years). Among 87 individuals with depression, 30 (34.5 percent) developed dementia. Of the 271 individuals without depression, 59 (21.8 percent) developed dementia. Among 60 individuals with apathy, 22 (36.7 percent) developed dementia. Of the 298 individuals without apathy, 67 (22.5 percent) developed dementia.

After adjusting for age, gender and education, the researchers found that the individuals with mild cognitive impairment and depression had a 66 percent increased risk of developing dementia than those individuals with mild cognitive impairment without depression. Likewise, the individuals with mild cognitive impairment and apathy had a 99 percent increased risk of developing dementia than those individuals with mild cognitive impairment without apathy.

“These findings highlight the importance of thoroughly evaluating newly-diagnosed patients with mild cognitive impairment for neuropsychiatric symptoms. The next step is to conduct a study to find out if treatment of depression or apathy in MCI may delay the onset of dementia,” says Dr. Geda. “This delay could have a huge impact on the quality of life for individual patients and their families, not to mention the broad public health implications of delaying the societal and economic burden of dementia. In fact, a previous biostatistics study from our colleagues at Johns Hopkins indicated that delaying dementia by a mere one year could reduce the prevalence of Alzheimer’s disease by nearly 800,000 million fewer cases in 2050.”

—

On the Net:

• Mayo Clinic

Findings hold important implications for cancer therapy

The application of nanotechnology in the field of drug delivery has attracted much attention in recent years. In cancer research, nanotechnology holds great promise for the development of targeted, localized delivery of anticancer drugs, in which only cancer cells are affected.

Such targeted-therapy methods would represent a major advance over current chemotherapy, in which anticancer drugs are distributed throughout the body, attacking healthy cells along with cancer cells and causing a number of adverse side effects.

By carrying out comprehensive studies on mice with human tumors, UCLA scientists have obtained results that move the research one step closer to this goal. In a paper published July 8 in the journal Small, researchers at UCLA’s California NanoSystems Institute and Jonsson Comprehensive Cancer Center demonstrate that mesoporous silica nanoparticles (MSNs), tiny particles with thousands of pores, can store and deliver chemotherapeutic drugs in vivo and effectively suppress tumors in mice.

The researchers also showed that MSNs accumulate almost exclusively in tumors after administration and that the nanoparticles are excreted from the body after they have delivered their chemotherapeutic drugs.

The study was conducted jointly in the laboratories of Fuyu Tamanoi, a UCLA professor of microbiology, immunology and molecular genetics and director of the signal transduction and therapeutics program at UCLA’s Jonsson Comprehensive Cancer Center, and Jeffrey Zink, a UCLA professor of chemistry and biochemistry. Tamanoi and Zink are researchers at the California NanoSystems Institute (CNSI) and are two of the co-directors of the CNSI’s Nano Machine Center for Targeted Delivery and On-Demand Release. The lead investigator on the research is Jie Lu, a postdoctoral fellow in Tamanoi’s lab. Monty Liong and Zongxi Li, researchers from Zink’s lab, also contributed to this work.

In the study, researchers found that MSNs circulate in the bloodstream for extended periods of time and accumulate predominantly in tumors. The tumor accumulation could be further improved by attaching a targeting moiety to MSNs, the researchers said.

The treatment of mice with camptothecin-loaded MSNs led to shrinkage and regression of xenograft tumors. By the end of the treatment, the mice were essentially tumor free, and acute and long-term toxicity of MSNs to the mice was negligible. Mice with breast cancer were used in this study, but the researchers have recently obtained similar results using mice with human pancreatic cancer.

“Our present study shows, for the first time, that MSNs are effective for anticancer drug delivery and that the capacity for tumor suppression is significant,” Tamanoi said.

“Two properties of these nanoparticles are important,” Lu said. “First, their ability to accumulate in tumors is excellent. They appear to evade the surveillance mechanism that normally removes materials foreign to the body. Second, most of the nanoparticles that were injected into the mice were excreted out through urine and feces within four days. The latter results are quite interesting and might explain the low toxicity observed in the biocompatabilty experiments we conducted.”

Researchers at the Nano Machine Center for Targeted Delivery and On-Demand Release are modifying MSNs “” which are easily modifiable “” so that the nanoparticles can be equipped with nanomachines. For example, nanovalves are being attached at the opening of the pores to control the release of anticancer drugs. In addition, the interior of the pores is being modified so that the light-induced release of anticancer drugs can be achieved.

“We can modify both the particles themselves and also the attachments on the particles in a wide variety of ways, which makes this material particularly attractive for engineering drug-delivery vehicles,” Zink said.

The team is now planning future research that involves testing MSNs in a variety of animal-model systems and carrying out extensive studies on the safety of MSNs.

“Comprehensive investigation with practical dosages which are adequate and suitable for in vivo delivery of anticancer drugs is needed before MSNs can reach clinics as a drug-delivery system,” Tamanoi said.

—

On the Net:

• University of California – Los Angeles
• Small

Early knowledge of hepatocellular carcinoma (HCC) response to transcatheter arterial chemoembolization (TACE) is crucial for determining treatment success, timing of repeat treatment, and patient prognosis. Currently, magnetic resonance imaging (MRI) is used 1-3 mo after treatment to evaluate anatomical tumor response, based upon changes in tumor size and contrast-agent enhancement. Alternatively, diffusion-weighted imaging (DWI) can be used as a functional imaging technique to depict thermally induced motion of water molecules. The extent of water mobility within biological tissues can be quantified by a parameter called the apparent diffusion coefficient (ADC). Recently, ADC values have been shown to change within days to weeks after therapy, which is earlier than changes seen by conventional HCC anatomical size assessment. However, no studies to date have reported the intra-procedural characteristics of ADC and whether these values can predict future tumor response at the time of chemoembolization.

A research article to be published on July 7, 2010 in the World Journal of Gastroenterology addresses this question. The research team led by Professor Reed A Omary, from Department of Radiology, Northwestern University, Chicago, used functional magnetic resonance imaging (MRI) to measure changes in tumor activity at the time of treatment, and compared them to tumor structural changes on conventional MRI at standard 1- and 3-mo follow-up periods.

Their results suggest that patients whose intra-procedural ADC values increase or decrease by > 15% are more likely to have a favorable anatomical tumor response 1 mo later.

This result is encouraging because early knowledge of HCC response after initial therapy is essential to revise prognosis and guide future therapy. Use of DWI and ADC mapping in conjunction with traditional anatomical imaging evaluation could further improve tumor response interpretation and subsequent treatment planning. At present, MR/Interventional radiology suites permit the acquisition of immediate quantitative functional imaging changes, in both tumor perfusion and now diffusion. Which of these two functional parameters is more effective as an intra-procedural biomarker to tailor HCC therapy awaits verification by future studies.

—

On the Net:

• World Journal of Gastroenterology

Patients spared severe arthritis, ankle fusion over 9-year follow up

A surgery developed at Hospital for Special Surgery can improve patient outcomes in individuals with severe adult flat foot deformity, a problem that is increasingly being seen in hospitals across the country. Patients who undergo the new surgery have better long-term outcome and mobility than those who undergo traditional surgery. The paper will be presented at the annual meeting of the American Orthopaedic Foot and Ankle Society (AOFAS, abstract 348) in National Harbor, Md., on July 8.

“Before this study, we were not sure whether you could salvage patients with flat foot and ankle deformity and correct their ankle as well as their foot deformity,” said Jonathan Deland, M.D., chief of the Department of Foot and Ankle Surgery at Hospital for Special Surgery (HSS). “Now we know that with this technique you can save the ankle, and it provides a correction of the deformity even at nine years after surgery.” Dr. Deland developed the surgery and is senior author of the study.

Adult acquired flat foot deformity is basically a severe type of flat foot that develops for unknown reasons in individuals who have had flat feet all their life. It is more prevalent in women and those who are overweight, and it usually develops in individuals in their 40s and 50s. In stage I of the deformity, the tendon that runs along the inside of the ankle begins to degenerate. In stage II, the arch starts to fail, and a person develops a more severe case of flat foot. As the arch continues to collapse and the flat foot becomes more pronounced, mobility becomes difficult, and the foot becomes stiff, which is considered stage III.

In the most severe stage, stage IV, the ankle starts tilting and is at risk of developing arthritis as a result of the deformity. “These people have tremendous flat foot to the point that their ankle is involved,” said Scott Ellis, M.D., foot and ankle orthopedic surgeon at HSS and first author of the study. In these people, the extreme flat foot has injured the deltoid ligament, a strong, flat triangular ligament that is located on the inside of the ankle that provides support to prevent the ankle from over pronating. In stage IV, the deltoid ligament has become stretched and incompetent, which is what allows the ankle to tilt.

If the ankle deformity is severe and symptomatic enough, then surgeons either perform an ankle replacement, which is very difficult, or, more commonly, fuse the ankle. “The fusion is not ideal because it takes all the motion away in the ankle in a patient who already has a foot problem,” Dr. Ellis said. “Imagine walking without motion in your ankle. It changes your gait and it leads to arthritis in the other joints of the foot over time, eight to 10 years down the line, because you start having to use those joints to take up the slack of motion that is not occurring in the ankle.”

In the new surgery for stage IV deformity developed at HSS, surgeons not only reconstruct the flat foot deformity, but they also reconstruct the deltoid ligament using a tendon that runs along the outside of the calf called the peroneus longus. A person can function without their peroneus longus. Alternatively, the peroneus longus can be kept and a cadaver tendon used.

In the study presented at the AOFAS meeting, HSS investigators conducted the new surgery in five patients, four men and one woman, and monitored the surgery’s success. The mean age was 67 years. Patients underwent X-rays that showed the surgery improved the alignment in the ankle and the effects were long-lasting. “The X-rays showed the maintenance of the correction of the tilt. The alignment was still improved nine years later,” Dr. Ellis said. Patients had excellent mobility at eight to 10 years following the surgery and none of the patients had arthritis.

Doctors also measured outcomes through several questionnaires including the Foot and Ankle Orthopedic Survey, an outcome scale that assessed 42 items divided among six categories. The average FAOS scores were 61.4 for symptoms, 1.5 for stiffness, 78.3 for pain, 87.9 for function/daily living, 71.7 for function/sports/recreational activities, and 42.1 for quality of life. “The FAOS scores were good,” Dr. Ellis said.

Patients were asked how far they could walk in blocks or miles and the cohort of patients was able to walk an average of 25 blocks (range 10 to 40), equivalent to 1.25 miles, after surgery. Two patients continued to play golf without significant problems, another exercised regularly on a treadmill, one was involved in circuit training, and the final patient played volleyball, although he did notice some stiffness. All patients reported they were satisfied with the procedure and, given the result, would have the operation again.

Dr. Ellis says he thinks the new surgery may be increasingly useful with stage IV flat foot deformity. No surgeons that the authors know of at other hospitals are currently using the surgery. The procedure is expected to become more popular. “I see a lot of this deformity in my office. It’s one of the major problems I deal with,” Dr. Ellis said, pointing out that it is very prevalent.

—

On the Net:

• Hospital for Special Surgery

The muscle weakness and coordination problems sometimes seen in patients with neonatal diabetes ““ a rare, inherited form of diabetes ““ are caused by problems in the brain rather than the muscles, according to research published today. The findings could pave the way for the development of improved treatments for the disease.

Neonatal diabetes affects one in 100,000 infants in the UK. It usually begins in the first six months of a child’s life and can be accompanied by development defects affecting speech, movement, and cognitive function.

In 2004, Professor Frances Ashcroft at the University of Oxford and Professor Andrew Hattersley at the Peninsula Medical School discovered that the condition was caused by a genetic defect which produces an overactive version of a protein, which acts as a potassium channel known as the KATP channel. This channel controls the release of insulin from the beta cells of the pancreas and when the channel becomes overactive, it prevents the release of insulin. Lack of insulin, which controls the blood sugar level, results in diabetes.

As a result of this work, patients with neonatal diabetes were not only able to be diagnosed more accurately, but it was also possible to switch them from insulin injections to sulfonylurea tablets. Sulfonylurea drugs, which had already been in use for type 2 diabetes for over fifty years, shut the open KATP channels, thus stimulating insulin release.

“As well as having problems secreting insulin, around one in five children with neonatal diabetes tend to develop more slowly than most and have problems walking and talking,” explains Professor Ashcroft. “Sulfonylurea revolutionised treatment for these children, allowing them to take a pill to control their diabetes rather than daily insulin injections. In many cases, the drugs also improve their neurological problems and a few children started to walk or talk shortly after switching medication.”

However, sulfonylurea drugs did not always restore muscle function to normal and in some patients they were ineffective.

To investigate the cause of the muscle problems, Professor Ashcroft and her colleagues at the University of Oxford developed two mouse models in which the genetic defect found in the patients was inserted into either the muscle cells or the nerve cells, respectively. The research, funded by the Wellcome Trust and the Royal Society, is published today in the journal Science.

When the KATP channel was overactive in the muscles, the mice had no problems with moving. However, when the channel malfunctioned in the central nervous system ““ the brain and the nerves ““ the mice had impaired muscle strength, disturbed balance and movement, and showed hyperactivity.

“Our results suggest that the problems that children with neonatal diabetes have with muscle weakness and coordination occurs in their nerve cells, but not in their muscle cells,” says first author of the study Rebecca Clark, a Wellcome Trust PhD student. “This has implications for how we might improve treatments for this condition.”

“For sulfonylureas to be able to shut down the defective potassium channels in the brain, they must first cross the blood-brain barrier,” explains Professor Ashcroft. “This means we need to use drugs that are able to enter the brain effectively.”

Professor Ashcroft and colleagues say that the findings should help them focus in on which areas of the brain are affected by the defective KATP channel, and that they can now use their mouse model to look at how the patients’ genetic defect affects cognitive function.

—

On the Net:

• Wellcome Trust

 The most common ““ and under-diagnosed ““ genetic disease in humans just may be a cause of the worst form of macular degeneration, Medical College of Georgia researchers report.

They are pursuing a link between hemochromatosis, which results in iron overload, and the wet form of macular degeneration, the leading cause of blindness in people 60 and older. They suspect that too much iron, known to wreak cumulative havoc on the body’s organs, hastens normal aging of the eyes.

If they are correct, avoiding the most severe consequences of a disease that robs the central vision could be as simple as donating blood a couple times annually to reduce iron levels, said Dr. Vadivel Ganapathy, chairman of the MCG School of Medicine Department of Biochemistry and Molecular Biology.

A $1.5 million grant from the National Eye Institute is enabling the MCG scientists to define the impact of hemochromatosis on the eye’s form and function. Support from MCG’s Vision Discovery Institute is enabling screening for its causative genetic mutation in the blood of healthy individuals and those with macular degeneration.

“If this is a predisposing risk for macular degeneration, we have a very useful tool for screening patients,” said Dr. Julian Nussbaum, a retinal specialist who chairs the School of Medicine’s Department of Ophthalmology and co-directs MCG’s Vision Discovery Institute. “We can give patients information right off the bat that may help them.”

While linking iron overload to eye disease may seem odd, they have in common the result of too much of a good thing. The eyes need light to see and the body needs iron to deliver oxygen but the price of both is increased oxidative stress, Ganapathy said. “You need oxygen and you need iron to make this bad molecule,” he said of oxygen radicals that can destroy tissue down to the DNA.

Light alone takes a slow toll on the retina, which converts it into electrical impulses sent to the brain via the optic nerve. This is despite multiple built-in safeguards such as filters in the cornea and lens that protect against the most harmful rays, like ultraviolet light, and a yellow pigment that provides extra protection for the most central point of vision. Retinal pigmented epithelial cells, which nourish sight-enabling cells in the retina, help gobble up and dump any resulting tissue trash into the circulation for elimination. Leftovers show up as fatty, yellow deposits called drusen.

Everyone experiences some age-related vision changes and accumulation of harmless levels of drusen, Nussbaum said.

But when byproducts start accumulating under the retinal pigment epithelium, the risk increases for the wet form of macular degeneration in which fragile new blood vessels grow underneath the retina, leak and cloud vision. The question is why some people’s condition worsens.

“We see it in one patient and it may stay that way for 20 years. We see it in another patient and within five years their vision has functionally started to decrease,” said Dr. Emory Patterson, an MCG School of Medicine graduate completing his ophthalmology residency at MCG who is helping with the clinical study.

Ganapathy first determined that the eye had the means to tightly regulate iron levels. Most organs don’t have their own system rather the small intestine regulates absorption of the iron consumed in foods like beans and tofu.

But Ganapathy found the same genetic mutation that causes hemochromatosis in a back layer of the retina, which comes in contact with the blood. A mutation in this HFE gene impairs a protein that regulates iron absorption. The finding in the mouse eye and human retinal pigmented epithelial cells was published in 2004 in Investigative Ophthalmology and Visual Science.

His lab now has animal models for hemochromatosis as well as juvenile hemochromatosis, which is caused by a different genetic defect and produces much earlier symptoms.

In the retina of the models, he’s finding increased expression of vascular endothelial growth factors, or VEGF, that enable new blood vessel growth. This growth is the hallmark of the wet form of macular degeneration. In fact, anti-VEGF therapies are the most potent treatments available.

“I tell patients that caught early, they have a 92 percent chance of stabilizing their vision with anti-VEGF therapy but they only have about a 38 percent chance of improving their vision,” Nussbaum said. “But at least we can treat it. I also remind them there is not a cure. It’s similar to cancer therapy: we can put them into remission but we don’t know if it will come back.”

Most people absorb about 10 percent of the iron they consume. Symptoms such as joint pain, fatigue, lack of energy, abdominal pain, loss of sex drive and heart problems indicate excess absorption although many with the condition have no symptoms when diagnosed.

—

On the Net:

• Medical College of Georgia

Football players often receive a g-force of 103 when hit during a game

Head injury expert Kim Gorgens, a neuropsychologist at the University of Denver (DU), says that most concussions deliver 95 g’s to the human body upon impact. G-force is a unit of force equal to the force exerted by gravity. In addition, the average football player receives 103 g’s when hit during a game. In comparison, the average g-force experienced by military fighter pilots is nine g’s.

Gorgens discussed the impact of concussions on children during a recent presentation at TEDxDU on the University of Denver campus. TEDx stands for Technology, Entertainment and Design and is an independently organized event licensed by the internationally recognized TED organization.

To watch Gorgens’ full presentation, visit www.tedxdu.com.

Also appearing at TEDxDU was internationally-known still photographer Aaron Huey. Huey̢蠫a DU graduate̢蠫visually chronicled the plight of Native Americans. Specifically, Huey relates the fight for survival on the Pine Ridge Indian Reservation. Aaron began photographing on Pine Ridge as part of a story on poverty in America, but it has captured his passion for five years.

TEDxDU featured 18 speakers and performers discussing the world’s most pressing issues from clean water and combating poverty to legal reform and HIV/AIDS.

“DU wants to be part of the solution,” Chancellor Robert Coombe says. “We are committed to tackling the great challenges of the day and TEDxDU allows us to be purposeful in creating awareness around the global issues facing our world.”

Presentations included the world’s fastest electric motorcycle and new research being conducted on Lou Gehrig’s disease. Other presenters were Stephen Brackett and Jamie Laurie, known to their fans as Brer Rabbit and Jonny 5 of the Denver-based band Flobots, and The Spirituals Project Choir.

—

On the Net:

• University of Denver

Scientists studying swingers say that they have higher rates of sexually transmitted infections (STIs) than prostitutes.

Dutch researchers said that older swingers are particularly vulnerable and yet this group is largely ignored by healthcare services.

The scientists wrote in the journal Sexually Transmitted Infections that there was a risk that swingers could act as an STI “transmission bridge to the entire population.”

“Although exact estimates are unavailable, the swingers’ population is probably large,” wrote Anne-Marie Niekamp, who worked on the study with colleagues from Maastricht University.

The researchers analyzed the numbers of patients seeking treatment in 2007 and 2008 at three sexual health clinics in South Limburg in the Netherlands.

The clinics have recorded whether a patient is a swinger since the start of 2007, in an attempt to track infection rates among this group.  Estimates say that the swinger population could include many millions across the world.

Scientists studied just under 9,000 consultations at three clinics that took place.  One in nine of the patients was a swinger, with an average age of 43.

They found that combined rates of Chlamydia and gonorrhea were just over 10 percent among straight people, 14 percent among gay men, just under 5 percent in female prostitution, and 10.4 percent among swingers.  Female swingers had higher infections rates than male swingers.

One in 10 older swingers had Chlamydia and about one in 20 had gonorrhea.

Chlamydia is most commonly found in women and 70 percent of cases show no symptoms.  The bacterial infection leads to pelvic inflammatory disease, ectopic pregnancy and infertility.  Gonorrhea is another bacterial infection that can lead to infertility if left untreated.

Niekamp said that young straight people, gay men and prostitutes were relatively easy for healthcare service to identify and target for advice and help, but swingers were generally a hidden community.

“That makes them very hard to reach,” she said in a telephone interview with Reuters. “Because they are so hidden and in some ways also stigmatized, it is hard for them to come forward for STI testing and treatment.”

—

On the Net:

• Sexually Transmitted Infections
• Maastricht University

On Wednesday, French lawmakers passed legislation that will ban baby bottles containing the chemical Bisphenol A from being developed.

However, the deputies stopped short of banning the chemical from all plastics.

BPA is suspected of harming human development.  It is used in the production of polycarbonated plastics and epoxy resins found in baby bottles, plastic containers, the lining of cans used for food and beverages, and in dental sealants.

BPA can leach from plastics, causing serious health problems such as breast cancer, obesity and the early onset of puberty.

The U.S. Food and Drug Administration and the European Food Safety Authority have both said that the chemical is safe in the amounts used in products like baby bottles.

    * A new study has created a preliminary neurobehavioral profile of fetal alcohol spectrum disorders (FASD).
    * Researchers selected 22 of 547 neuropsychological variables for analysis based on their ability to distinguish children with heavy prenatal alcohol exposure (PAE) from unexposed children.
    * Results suggest that executive functioning and spatial processing are especially sensitive in children with suspected or known PAE.

A continuum of physical, mental, and behavioral damage is caused by prenatal alcohol exposure (PAE) and is referred to by the non-diagnostic term, fetal alcohol spectrum disorders (FASD). While the identification of children along the continuum of FASD is complicated, it is also necessary in order to assist more precise diagnoses and/or better treatment options. A new study has constructed a preliminary neurobehavioral profile of FASD using neuropsychological data from a multisite study, finding that executive functioning and spatial processing are especially sensitive to alcohol exposure.

Results will be published in the September 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“In some cases, children with heavy PAE meet criteria for fetal alcohol syndrome (FAS), which can be identified by trained professionals,” explained Sarah N. Mattson, a professor of psychology at San Diego State University and corresponding author for the study. “However, the majority of children with heavy PAE do not meet these criteria and cannot be identified by physical features alone. The goal of this study was to determine a neurobehavioral profile that could be used to help identify these children, even when the physical features of alcohol exposure are absent.”

“Having a good sense of which behavioral manifestations of PAE are most consistent will be of tremendous advantage in the diagnosis of FASD,” added John H. Hannigan, deputy director of the Merrill Palmer Skillman Institute for Child and Family Development at Wayne State University in Detroit. “It is difficult to diagnose children who do not show the facial features characteristic of FAS, in part because neurobehavioral outcomes can be so variable, sometimes requiring large numbers of tests to be done. The current study is important because it boiled down 500+ measures to about 20 that converged mostly on two kinds of outcomes.”

Researchers analyzed data taken from two sites of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, an interdisciplinary study of FASD. Study participants were between the ages of seven and 21 years of age at the time of their neuropsychological assessments, and were divided into two groups: children with heavy PAE (n=79) and unexposed children (n=60). The alcohol-exposed group included children with (n=41) and without (n=38) FAS, which falls at the severe end of the FASD spectrum. Out of 547 neuropsychological variables, 22 were selected for analysis based on their ability to distinguish children with heavy prenatal alcohol exposure from unexposed controls.

“Our results told us that we could use some of our neuropsychological tests to distinguish alcohol-exposed subjects from controls with a high degree of accuracy,” said Mattson. “When children with FAS and controls were examined, 92 percent of the subjects were correctly classified. When we included alcohol-exposed children without FAS and controls, 85 percent of the subjects were classified. The measures that were most useful in this classification were measures of executive function and spatial processing “¦ which tells us that although deficits are reported in a variety of neuropsychological domains, it may be that some are more valuable that others in distinguishing alcohol-exposed children from controls.”

“‘Executive function’ refers to abilities which allow a person to self-monitor or self-direct what they should focus on, call to memory, and think about,” explained Hannigan. “Poor executive function can impair the ability to plan ahead, inhibit responding, or correct one’s behavior in response to feedback. Poor spatial processing means not only that FASD children may lose their way, but these abilities may also be related through underlying brain processes to problems with math, verbal abilities, and abstraction.”

Both Mattson and Hannigan noted the generalizing strength of these results ““ having found similar outcomes in children across diverse populations from San Diego, California and Helsinki, Finland ““ as well as the greater power of these results versus IQ in distinguishing among the groups.

“Identification of an FASD ‘behavioral phenotype’ or profile has been a prime goal of research since FAS was first described in 1973,” said Hannigan. “This profile is important because having specific neurobehavioral outcomes that are most reliably related to PAE not only aids diagnosis, but also can allow researchers to better focus their time and resources on devising interventions.”

Hannigan added that the range and magnitude of neurobehavioral problems examined by this study is a reminder that even modest prenatal alcohol consumption can have life-long negative consequences on brain function and behavior in children, even without leading to full FAS. “Thus, primary care providers have an obligation to ask about their patients’ drinking, to advise them to avoid drinking during pregnancy, and to refer for appropriate intervention all women who drink at risk levels and have difficulty stopping or limiting their drinking,” he said.

“While this study is one important step in improving diagnosis of FASD, future steps are also important,” said Hannigan. “For example, testing of the generated profile in diverse populations in order to compare how well it can uniquely identify children with PAE compared to children with other developmental disorders.”

—

On the Net:

• Alcoholism: Clinical & Experimental Research

Surveillance colonoscopy is effective and cost-effective when targeted to high-risk patients, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute. However, overuse of surveillance colonoscopy could be excessively costly or even harmful.

“Surveillance colonoscopy is a widely accepted and utilized practice that has the potential to decrease the burden of colorectal cancer. Yet, this practice also carries considerable monetary and resource costs as well as the risk of procedure-related complications,” said Sameer Dev Saini, MD, MS, of the Ann Arbor VA Health Services Research & Development Center of Excellence and lead author of the study. “Despite these concerns, data supporting the long-term effectiveness of surveillance colonoscopy and the choice of optimal surveillance strategy are limited.”

Current guidelines recommend that patients with colonic adenomas undergo periodic surveillance colonoscopy. Surveillance colonoscopies are performed to examine the colon after a colorectal abnormality, either cancerous or benign, has been detected and removed. But, is doing so cost effective? Dr. Saini and colleagues sought to answer this question by using existing data to make projections about the effectiveness and cost utility of surveillance. They developed a Markov model based on published literature to study various surveillance strategies from the perspective of a long-term payor (the target population was 50-year-old patients with newly diagnosed colonic adenomas followed until death).

According to study results, colonoscopy every three years in high-risk patients and every 10 years in low-risk patients (3/10 strategy) was more costly, but also more effective than no surveillance (incremental cost-effectiveness ratio [ICER] of $5,743 per quality-adjusted life year [QALY] gained). A cost-utility analysis suggested that the 3/10 strategy is the optimal strategy under the vast majority of clinical circumstances.

A 3/5 strategy (colonoscopy every three years in high-risk patients and every five years in low-risk patients) was considerably more costly, but only marginally more effective (ICER of $296,266 per QALY). This strategy may be reasonable in populations in which a low-risk subgroup cannot be reliably identified or if the miss rate for advanced adenomas is believed to be very high (at least 14 percent). Compared to the 3/10 strategy, the 3/5 strategy resulted in five fewer cancers and one fewer cancer-related death per 1,000 patients entering surveillance.

A 3/3 strategy (colonoscopy every three years in both high- and low-risk patients), which may be attractive to gastroenterologists with medico-legal concerns over missed neoplasia, is cost-ineffective and potentially harmful in comparison to less intensive surveillance. Compared to the 3/5 strategy, the 3/3 strategy resulted in two fewer cancers and one fewer cancer-related death per 1,000 patients entering surveillance.

In the future, improvements in risk stratification could further enhance physicians’ ability to target surveillance to those patients most likely to benefit from this practice.

—

On the Net:

• American Gastroenterological Association
• Gastroenterology

Coffee and tea drinkers may not need to worry about indulging ““ high and moderate consumption of tea and moderate coffee consumption are linked with reduced heart disease, according to a study published in Arteriosclerosis, Thrombosis, and Vascular Biology: Journal of the American Heart Association.

Researchers in The Netherlands found:

* Drinking more than six cups of tea per day was associated with a 36 percent lower risk of heart disease compared to those who drank less than one cup of tea per day.

* Drinking three to six cups of tea per day was associated with a 45 percent reduced risk of death from heart disease, compared to consumption of less than one cup per day.

And for coffee they found:

* Coffee drinkers with a modest intake, two to four cups per day, had a 20 percent lower risk of heart disease compared to those drinking less than two cups or more than four cups.

* Although not considered significant, moderate coffee consumption slightly reduced the risk of heart disease death and deaths from all causes.

Researchers also found that neither coffee nor tea consumption affected stroke risk.

“While previous studies have shown that coffee and tea seem to reduce the risk of heart disease, evidence on stroke risk and the risk of death from heart disease was not conclusive,” said Yvonne T. van der Schouw, Ph.D., study senior author and professor of chronic disease epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands. “Our results found the benefits of drinking coffee and tea occur without increasing risk of stroke or death from all causes.

Van der Schouw and colleagues used a questionnaire to evaluate coffee and tea consumption among 37,514 participants. They followed the participants for 13 years for occurrences of cardiovascular disease and death.

Study limitations included self-reported tea and coffee consumption, and the lack of specific information on the type of tea participants drank. However, black tea accounts for 78 percent of the total tea consumed in The Netherlands and green tea accounts for 4.6 percent. Coffee and tea drinkers have very different health behaviors, researchers note. Many coffee drinkers tend to also smoke and have a less healthy diet compared to tea drinkers.

Researchers suggest that the cardiovascular benefit of drinking tea may be explained by antioxidants. Flavonoids in tea are thought to contribute to reduced risk, but the underlying mechanism is still not known.

Co-authors are: J. Margot de Koning Gans, M.D.; Cuno S.P.M. Uiterwaal, M.D., Ph.D.; Joline W.J. Beulens, Ph.D.; Jolanda M.A. Boer, Ph.D.; Diederick E. Grobbee, M.D., Ph.D.; and W.M. Monique Verschuren, Ph.D. Author disclosures and funding sources are in the study.

—

On the Net:

• Arteriosclerosis, Thrombosis, and Vascular Biology