Research in Medicine

Genetic cause of childhood leukemia revealed

Scientists have uncovered a genetic link specific to the risk of childhood leukaemia.

Study author Kenneth Offit, MD, MPH, Chief of the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center, said that at the very least the discovery gives us a new window into inherited causes of childhood leukemia.

Offit said that more immediately, testing for this mutation may allow affected families to prevent leukemia in future generations.

The mutation was first observed in a family treated at Memorial Sloan-Kettering of which several family members of different generations had been diagnosed with childhood acute lymphoblastic leukemia (ALL).

A second, non-related, leukemia-prone family cared for at a different hospital was later found to have the same mutation. A series of experiments were conducted confirming that the observed mutation compromised the normal function of the gene, which may increase the risk of developing ALL.

The inherited genetic mutation is located in a gene called PAX5, which is known to play a role in the development of some B cell cancers, including ALL.

The findings have been published in the journal Nature Genetics.

 

Flexible’ microneedle patch to help deliver drug sans jab

An assistant professor has created a flexible microneedle patch, which allows drugs to be delivered directly and fully through the skin.

The new patch can quicken drug delivery time while cutting waste, and can likely minimize side-effects in some cases, notable in vaccinations and cancer therapy.

Leading development of the flexible patch was Lissett Bickford, now an assistant professor and researcher of biomedical engineering and the mechanical engineering, both part of the Virginia Tech College of Engineering.

Microneedle patch technology used on the skin has existed for several years, each patch containing an array of hundreds of micron-sized needles that pierce the skin and dissolve, delivering embedded therapeutics.

Bickford, with her research team, including Chapel Hill graduate student Katherine A. Moga, were able to develop a new flexible microneedle patch that forms to the skin directly – think a regular household bandage – and then fully pierces the skin and dissolves.

Bickford said the softer, more malleable and water-soluble material also allows for more precise control over the shape, size, and composition of the patch, with little to no waste.

The study has been published in the scientific journal, Advanced Materials.

 

Heart gene therapy trial begins

Mrs Gedda, from Essex, is among 200 patients being enrolled on a gene therapy trial to test whether introducing genetic material into damaged heart cells can improve their function

It is 18 months since Carol Gedda suffered a massive heart attack. It left her with just 20% of her heart functioning. “I have a lot of trouble with stairs, and sometimes I can even run out of breath in a conversation”, says Mrs Gedda, who is 65.

She is one of at least 750,000 people in the UK with heart failure. It occurs when the heart is damaged and becomes unable to pump blood adequately.

There are treatments for the condition but nothing so far that can reverse the damage.

Mrs Gedda, from Essex, is among 200 patients being enrolled on a gene therapy trial to test whether introducing genetic material into damaged heart cells can improve their function.

Researchers at Imperial College London found that levels of the protein SERCA2a are lower in patients with heart failure.

Royal Brompton Hospital in London, where Mrs Gedda is being treated, is one of only two British centres taking part in the international study; The Golden Jubilee National Hospital in Glasgow is also involved.

Before joining the trial Mrs Gedda had baseline measurements taken for her fitness.

She walked up and down a 30m hospital corridor for six minutes – the distance she travelled was noted by one of the hospital researchers.

Her heart function was also analysed.

At Royal Brompton, the gene therapy is delivered at the NIHR biomedical research unit, via a coronary angiogram under local anaesthetic.

Trojan horse

The researchers have ‘hidden’ the gene inside a genetically modified virus which is able to latch on to heart muscle cells but is believed to be entirely harmless.

The virus acts like a Trojan horse, delivering the extra DNA into the nucleus of the heart cells.

The hope is the gene will prompt the heart cells to produce more of the SERCA2a protein and repair some of the damaged heart muscle.

Half of the patients will receive the gene therapy, while the rest will get a placebo or dummy drug.

“I’m delighted to be on the trial,” says Mrs Gedda. ” Of course I don’t know whether I’ve received the gene therapy or the placebo but it is exciting to be part of it. I have three sons and my heart problem is partly genetic so it could be helpful to my family in the future.”

The trial, known as CUPID2, is funded by the US biotechnology company, Celladon. It will be around three years before the results are known.

Dr Alexander Lyon, British Heart Foundation senior lecturer and consultant cardiologist at Royal Brompton hospital and Imperial College stresses that the treatment is far from being a cure, but says there is great excitement about the trial.

“A few patients in the United States who received the same dose we are using appear to have done extremely well.

“Importantly, early trials suggest the treatment is safe. But we need this large study before we can be sure the gene therapy really works. If we could find an effective treatment, that would be very exciting.”

David Palmer, from Norfolk was the first patient in the UK to have the treatment.

The left side of his heart is enlarged and he suffers arrhythmias – irregular heart rhythms.

He said: “My heart is forever jumping out rhythm – I don’t pass out just feel faint and very weak.

“Once I fell into a fridge in Sainsburys. I wasn’t hurt but it was a bit embarrassing.”

Mr Palmer, aged 50, says he is unsuitable for a heart transplant because he has had the condition so long, which leaves the gene therapy trial as his best hope:

“For people like me who are in the last chance saloon it gives us the opportunity to stabilise our condition and live that bit longer. It’s far from being a cure but if it works then it would be a major advance for huge numbers of patients.”

Source: http://www.bbc.co.uk/news/health-23962607

Compound reverses learning deficits in mice with down syndrome traits

Chromosomes DNA genes istock.jpgFor people with trisomy 21 – more commonly known as Down syndrome – learning and remembering important concepts can be a struggle, since some of their brain’s structures do not develop as fully as they should.

But now, researchers may have found a way to reverse the learning deficits associated with Down syndrome, after having discovered a compound that can significantly bolster cognition in mice with a condition very similar to trisomy 21.

In a new study published in the Sept. 4 issue of Science Translational Medicine, scientists injected a small molecule known as a sonic hedgehog pathway agonist into the brains of genetically engineered mice on the day of their birth.  The treatment enabled the rodents’ cerebellums to grow to a normal size, allowing them to perform just as well as unmodified mice in behavioral tests.

“We’ve been working for some time to characterize the basis for how people with trisomy 21 diverge in development from people without trisomy 21,” Roger Reeves, a professor in the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins University School of Medicine, told FoxNews.com. “One of the early things we see is that people with Down syndrome have very small cerebellums, which does a lot more things than we used to think it did.”

Down syndrome is a condition that occurs when people receive three – rather than the typical two – copies of chromosome 21. Because of this “trisomy,” Down syndrome patients have extra copies of the more than 300 genes contained in that chromosome.  This leads to a range of symptoms, including mild to moderate intellectual disability, distinct facial features, heart defects and other health problems.

Through previous research, Reeves found that another distinct trait of people with Down syndrome is a cerebellum that’s approximately 60 percent of the normal size.  In order for this important brain region to grow and form, a small population of cells in the brain must quickly divide and multiply shortly after birth. This cell population requires a specific growth factor known as the sonic hedgehog pathway to stimulate the cells, triggering them to divide.

However, the trisomic cells in people with Down syndrome do not respond as well to this growth factor, stunting the development of the cerebellum – a region of the brain found to be important in cognitive processing and emotional control.

“We thought if we could stimulate these cells a bit at birth, we could make up the deficit,” Reeves said.

To test this theory, Reeves and his research team created a series of genetically engineered mice, all of which had extra copies of about half of the genes found in chromosome 21.  According to Reeves, this caused the mice to have many of the same characteristics seen in patients with Down syndrome, such as a smaller cerebellum and learning difficulties.

The researchers then injected the mice with a sonic hedgehog pathway agonist, which stimulates the growth factor pathway needed to trigger cerebellum development.   The compound was given to the mice just once on the day of birth.

“From that one injection, we were able to normalize the growth of the cerebellum, and they continued to have a structurally normal cerebellum when they grew up,” Reeves said.

Going one step further, the researchers conducted a series of behavioral tests on the mice to better understand how normalizing this brain structure would affect their overall performance.  One of these tests was the Morris water maze test, an experiment that involves placing the mice in a pool of water and seeing how long it takes them to escape using a platform hidden below the water’s surface.  The test measures the rodents’ spatial learning and memory capabilities, which are primarily controlled by the hippocampus.

“We didn’t expect to see any results from that,” Reeves said. “We knew that the most potent effects of the growth factor were in the specific cells (in the cerebellum) we were targeting, but it turned out that the mice that got a single shot of this agonist at birth, when tested three months later, they performed just as well as their (unmodified) litter mates in the water maze test.”

The sonic hedgehog agonist has yet to be proven effective in humans with Down syndrome, and future research is needed to determine exactly how the injection improved the mice’s cognitive abilities and whether or not the agonist has any side effects.  But Reeves remains hopeful that these findings could have translational potential.

“We’re on the verge of a revolution for expanding the potential of people born with trisomy 21,” Reeves said.
Source Fox News

 

 

Turmeric – anti-nausea drug combo potent cancer killer

A new study has found that anti-nausea drug thalidomide when combined with common kitchen spice turmeric creates hybrid molecules that effectively kill multiple myeloma cells.

Thalidomide was first introduced in the 1950s as an anti-nausea medication to help control morning sickness, but was later taken off the shelves in 1962 because it was found to cause birth defects.

In the late 1990`s the drug was re-introduced as a stand-alone or combination treatment for multiple myeloma.

Turmeric, an ancient spice grown in India and other tropical regions of Asia, has a long history of use in herbal remedies and has recently been studied as a means to prevent and treat cancer, arthritis and Alzheimer`s disease.

According to the American Cancer Society, laboratory studies have shown that curcumin, an active ingredient in turmeric, interfere with several important molecular pathways and inhibit the formation of cancer-causing enzymes in rodents.

“Although thalidomide disturbs the microenvironment of tumor cells in bone marrow, it disintegrates in the body. Curcumin, also active against cancers, is limited by its poor water solubility. But the combination of thalidomide and curcumin in the hybrid molecules enhances both the cytotoxicity and solubility,” study`s lead researcher Shijun Zhang, assistant professor in the Department of Medicinal Chemistry at the VCU School of Pharmacy, said.

The study is published by the journal Organic and Biomolecular Chemistry.

Cataract surgery linked to longer life

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354 persons aged 49 years diagnosed with cataract-related vision impairment – some of whom had undergone surgery and others who had not – were assessed between 1992 and 2007.

People who have had cataract surgery to improve their sight live longer than those who choose not to undergo the procedure, according to a new study.

The research is drawn from data gathered in the Blue Mountains Eye Study, a population-based cohort study of vision and common eye diseases in an older Australian population.

A total of 354 persons aged 49 years and older and diagnosed with cataract-related vision impairment – some of whom had undergone surgery and others who had not – were assessed between 1992 and 2007.

Adjustments were made for age and gender as well as a number of mortality risk factors, including hypertension, diabetes, smoking, cardiovascular disease, body mass index and measures of frailty and comorbid disease. Follow-up visits took place after five and ten years since the baseline exam.

Jie Jin Wang, Ph.D., of the Westmead Millennium Institute and one of lead researchers of the study, said that their fiodnings suggested that correcting cataract patients` visual impairment in their daily practice results in improved outcomes beyond that of the eye and vision, and has important impacts on general health.

Wang noted one limitation of the study is that participants with cataract-related visual impairment who did not have cataract surgery could have had other health problems that prevented them from undergoing surgery, and that these other health problems could partly explain the poorer survival among non-surgical participants.

The study has been published in the journal of the American Academy of Ophthalmology.

 

Some flu vaccines promise a little more protection

Flu vaccination is no longer merely a choice between a jab in the arm or a squirt in the nose. This fall, some brands promise a little extra protection.

For the first time, certain vaccines will guard against four strains of flu rather than the usual three. Called quadrivalent vaccines, these brands may prove more popular for children than their parents. That’s because kids tend to catch the newly added strain more often.

These four-in-one vaccines are so new that they’ll make up only a fraction of the nation’s supply of flu vaccine, so if you want a dose, better start looking early.

But that’s only one of an unprecedented number of flu vaccine options available this year.

Allergic to eggs? Egg-free shots are hitting the market, too.

Plus there’s growing interest in shots brewed just for the 65-and-older crowd, and a brand that targets the needle-phobic with just a skin-deep prick.

“We’re moving away from the one-size-fits-all to choosing the best possible vaccine for an individual’s age and condition,” said Dr. Gregory Poland, an infectious disease specialist at the Mayo Clinic.

“The flip side of that,” he said, is that “this will be a confusing year” as doctors and consumers alike try to choose.

Federal health officials recommend a yearly flu vaccine for nearly everyone, starting at 6 months of age. On average, about 24,000 Americans die each flu season, according to the Centers for Disease Control and Prevention.
Read more: http://www.foxnews.com/health/2013/09/03/some-flu-vaccines-promise-little-more-protection/#ixzz2duD5QbHz

 

Researchers discover potential epilepsy drug using zebrafish

An antihistamine used to treat itching may be the key to preventing seizures in children with a rare, yet severe form of epilepsy known as Dravet Syndrome.

The discovery was made by screening hundreds of government-approved drugs in animals with the same genetic mutation as children with the disorder.  But instead of using rodents – the typical animal model for drug screenings – researchers used an unlikely test subject for their experiment: zebrafish.

According to the researchers, the antihistamine known as clemizole could be the first line approach for reducing the effects of Dravet Syndrome – a condition with very limited treatment options.

“Dravet Syndrome is a catastrophic form of childhood epilepsy, and it often leads to severe symptoms and death,” Scott Baraban, a professor of neurological surgery at the University of California, San Francisco and William K. Bowes Jr. Endowed Chair in neuroscience research, told FoxNews.com.  “Within the first year of life, children will start to have seizures and have several hundred per day.  They’ll have delays in speech, cognitive problems, ataxia, which is trouble standing… And while there are drugs that are given that reduce the effects, there aren’t too many treatment options for these kids.”

Baraban first pioneered the idea of using the small, translucent zebrafish to test drugs for epilepsy in 2005, as the zebrafish’s genome is 80 percent identical to the human genome. In order to better understand the effects of a certain drug, researchers place zebrafish larvae – which are no longer than a human eyelash – into petri dish baths filled with that drug.  Since the larvae require the water for respiration, the drug immediately enters their systems through the bath, allowing researchers to quickly observe how the fish respond.

“The fact that fish are permeable to the drug – that’s a huge advantage for drug screening,” Baraban said. “Most drugs are tested using a cell-based culture, but when drugs move on to next stage in the animal model, they’re often toxic.  So the advantage with zebrafish is we can test effectiveness and toxicity of the drug at the same time.”

Baraban decided to use this drug screening method for Dravet Syndrome after he came across a zebrafish with a mutation in the SCN1A gene, the same genetic mutation commonly associated with the epileptic disorder.  The SCN1A gene codes for a voltage activated sodium channel, which allows ions to pass through the membranes of neurons and regulate how they fire.  In Dravet Syndrome, these channels allow too many ions to pass through the neural membranes, causing the neurons to fire excessively.

Zebrafish with the SCN1A gene mutation showed the same developmental pattern as children with the mutation, moving around in erratic patterns whenever they experienced a seizure.  Just as children with Dravet Syndrome begin having seizures one year after birth, the fish began experiencing seizures three days after fertilization.  And though the fish typically died after just 10 to 12 days, Baraban said they are extremely easy to breed, yielding incredibly large cohorts for testing.

“One breeding pair will give 100 pairs of eggs, so one quarter of the offspring will have the mutation we’re interested in – and they’ll have spontaneous seizures,” Baraban said. “We decided to do a hyper approach screening, where we take a library of commercially available drugs and screened them to see if they stop the seizures in fish.”

Baraban’s team tested a random assortment of 320 compounds in a chemical library of drugs that had already been approved by the Food and Drug Administration.  Through this indiscriminate testing, they stumbled upon the antihistamine clemizole, which eliminated the seizure activity in the fish within 10 minutes of application.

The reason behind clemizole’s efficacy remains a mystery, especially since antihistamines can sometimes make seizures worse.  The researchers even tested 10 other antihistamines on the fish, but none was successful at blocking the seizures.  Baraban theorized that another biological mechanism in clemizole, apart from its antihistamine properties, is responsible for the therapeutic effects.

Because clemizole is already FDA-approved, Baraban hopes it can soon be tested in small clinical trials of people suffering from Dravet Syndrome and that it will produce little to no side effects.  He is also fairly confident the drug will be effective in humans, since the mutant zebrafish so closely mirrored humans with the condition.

“We screened (the zebrafish) with epilepsy drugs already given to kids with Dravet Syndrome, and the fish predicted the same compounds,” Baraban said.  “So the drugs that work in humans also worked in fish, and the drugs that didn’t work in humans didn’t work in the fish.  So it suggests that clemizole could be directly applicable.”

Not only is Baraban’s research inspiring for people suffering from Dravet Syndrome, but his zebrafish method could be used to find therapeutic agents for various other conditions caused by mutations in a single gene.  He said this technique offers a much more tailored approach to drug screening.

“There’s no reason you couldn’t model lots of different genetic disorders in zebrafish,” Baraban said. “So genetic forms of Alzheimer’s, Parkinson’s, they can all be modeled in zebrafish and used in drug screening.  And in the epilepsy field this is just one example.  So if you’re child has a gene mutation, we can make fish with that specific gene mutation and screen for drugs that are effective for your children.”

The research was published online in the journal Nature Communications.
source: http://www.foxnews.com/health/2013/09/03/researchers-discover-potential-epilepsy-drug-using-zebrafish/#ixzz2dtomTNDN

 

Many neurologists unaware of safety risks related to anti-epilepsy drugs

A study by Johns Hopkins researchers shows that a fifth of US neurologists appear unaware of serious drug safety risks associated with various anti-epilepsy drugs, potentially jeopardizing the health of patients who could be just as effectively treated with safer alternative medications

The findings suggest that the US Food and Drug Administration (FDA) needs a better way to communicate information to specialists about newly discovered safety risks, the researchers say, since the warnings are in many cases not getting through to doctors making important prescribing decisions.

The researchers add that while their new study, reported in the journal Epilepsy and Behavior, was focused on neurologists and anti-epilepsy drugs, they believe their findings are applicable to a wide spectrum of medical specialists and medications.

“There is poor communication from the FDA to specialists, and there’s some risk to patients because of this,” says study leader Dr Gregory L Krauss, a professor of neurology at the Johns Hopkins University School of Medicine. “Unless it’s a major change requiring the FDA to issue a black box warning on a product, important information appears to be slipping through the cracks. We need a more systematic and comprehensive method so that doctors receive updated safety warnings in a format that guarantees they will see and digest what they need to protect patients.”

Dr Krauss and his colleagues surveyed 505 neurologists from across the nation in different types of medical practices between March and July of 2012. They asked about several new safety risks for antiseizure drugs recently identified by the FDA: increased suicidal thoughts or behavior with newer agents; high risks for birth defects and cognitive impairment in offspring of mothers taking divalproex (sold by the brand name Depakote); and risks for serious hypersensitivity reactions in some patients of Asian descent starting treatment with carbamazepine (Tegretol). One in five of the neurologists surveyed said they knew of none of the risks. Those neurologists who treat two hundred epilepsy patients a year or more were most likely to know all of the risks.

Dr Krauss says he was most struck by the lack of understanding of the risk to certain Asian patients who take carbamazepine to control their seizures. The FDA in 2007 recommended that before initiating the drug in patients of Asian heritage, neurologists should screen to see if those patients have a specific haplotype, a specific section of DNA found in a few per cent of Asian people, before prescribing the drug.

The researchers found that 70 per cent of the neurologists who responded knew of the recommendation. While 147 neurologists (29.1 per cent) reported initiating carbamazepine treatment in Asian patients, only 33 of them (22.5 per cent) said they performed haplotype screening. Eighteen neurologists reported that their Asian patients developed carbamazepine-related hypersensitivity reactions — severe skin rashes that can lead to scarring, blisters in the mouth and shredding of the skin — during this time period.

“If their doctors were more educated about the risks,” Dr Krauss says, “these patients may have avoided these severe hypersensitivity reactions.”

Dr Krauss says doctors may not do the screening because it is difficult to find laboratories able to perform the haplotyping, and he notes that it may make more sense to prescribe an alternate drug to Asian patients.

The researchers found that 80 per cent of respondents knew that the FDA had newly warned that the risk of suicide with newer drugs is 4.3 per 1,000, double what had previously been believed. Seventy per cent said they counselled patients about the risk.

As for pregnancy risks related to divalproex, fewer than half of the respondents knew that a warning had been issued noting high risks of birth defects and of developmental risks in offspring (an 8 to 9 point drop in IQ). While 93 per cent of respondents reported counselling women planning pregnancies about the birth defect risks of divalproex, Dr Krauss says safer drugs should be used if possible during pregnancy.

Dr Krauss says part of the problem is the absence of a single place for neurologists to find updated risk information. Neurologists get safety information from scattered sources; only a few get emails from the FDA, while others get the information from neurology societies, from continuing medical education (CME) courses or from newly published journal articles.

“The FDA needs to do better getting the warnings to prescribing doctors,” he says. “There has to be a direct way to communicate risks without overwhelming physicians with messages.”

Source: http://www.indiamedicaltimes.com/2013/08/31/many-neurologists-unaware-of-safety-risks-related-to-anti-epilepsy-drugs/

What every mom needs to know about tonsil surgery

Tonsil exam istock.jpg

, kids who had tonsillectomies using the microdebrider method stopped taking pain medicine and returned to their normal activities sooner than those who had the electrocautery method.

More than 530,000 children under the age of 15 have their tonsils removed each year. About 80 percent have obstructive sleep problems – snoring, irregular breathing – and the rest are because of infection, according to The American Academy of Otolaryngology-Head and Neck Surgery.

If your child needs his or her tonsils removed, you might be worried about the procedure, the pain, and the recovery. Here, learn about the new way tonsillectomies are done, if it’s right for your child, and the important questions you need to be asking.

The new way tonsillectomies are done

There are several ways doctors remove tonsils, with one of the most common being the electrocautery method. Using a handheld metal probe heated by an electric current, the tonsil tissue is destroyed and bleeding is well controlled. Yet, because heat is used, the soft tissue of the throat is burned, which causes more pain and a longer recovery.

However, within the last 10 years, doctors have been using a less painful method known as PITA—Partial Intracapsular Tonsillectomy and Adenoidectomy. Using a microdebrider, the surgeon “shaves” the tonsils with a rotating blade and uses suction to stop the bleeding.

“The surgeon is removing the tonsils from what we call inside out – from the center of the throat to the side wall,” said Dr. Julie L. Wei, a pediatric otolaryngologist who practices at Nemours Children’s Hospital in Orlando, Fla.

So instead of removing all of the tonsils, about 90 percent are removed, leaving the capsule or outermost layer behind.

“There are lots of benefits to doing a partial,” said Dr. Didier L. Peron, an attending physician at Morristown Medical Center who is board-certified in otolaryngology-head and neck surgery.

For starters, the nerve endings are not exposed and there’s no damage to the arches of the throat. As a result, children experience less pain, a shorter recovery, and the chance of bleeding is reduced.

According to a study in the journal Otolaryngology-Head and Neck Surgery, kids who had tonsillectomies using the microdebrider method stopped taking pain medicine and returned to their normal activities sooner than those who had the electrocautery method.

Another study also found that kids were at less risk for bleeding and dehydration after surgery. Pain can cause children to refuse to eat or drink, and many are re-admitted to the hospital with severe dehydration, according to Peron.

Can tonsils grow back?

Not all children are good candidates for a partial tonsillectomy, particularly for those who have repeated infections like strep throat. If the tissue is left behind, “there’s a concern they can still get strep more, even though they’ve had their tonsils out,” Wei said.

And with any kind of surgery, there are risks, which include removing normal tissue like the uvula.

But perhaps one of the most significant drawbacks is regrowth. “There’s no doubt that occasionally the tonsils keep growing,” said Peron, who explained that the chances are more likely in young kids. He estimated a 10 percent chance that tonsils will grow back for 2- and 3-year-olds.

There’s one caveat to the question of re-growth, however. Often times, a pediatrician will look in a child’s mouth and see the tonsils but not the scar they’re used to seeing with the electrocautery method. They tell the family the tonsils are there, but “they never realized it was 10 times as big three years ago,” according to Wei. The family is lead to believe the tonsils grew back when actually, “it has to do with how it looks. Maybe there’s not that much regrowth at all,” she said.

The best thing to do is to return to the doctor who did the surgery for a proper evaluation. And even if they did grow back, if it’s not causing the child any problems, leave it alone.

Source: http://www.foxnews.com/health/2013/09/01/what-every-mom-needs-to-know-about-tonsil-surgery/