New Endoscope Sees What Lies Beneath

Sub-surface scope: A new endoscope prototype takes images below the surface of organs and tissues. The scope works through a tiny one-by-one-millimeter mirror (above) that pivots, reflecting a laser beam to produce microscopic, three-dimensional images. The current prototype is narrower than the width of a dime (below).   Credit: Huikai Xei

An infrared-based endoscope scans tissue below the surface.

By Jennifer Chu

An endoscope equipped with an infrared laser and a tiny mirror might one day help physicians diagnose early signs of cancer and other diseases and aid in surgery. A researcher at the University of Florida has designed a prototype device that captures images up to two millimeters beneath the surface of tissues, providing high-resolution, three-dimensional images at video-rate speeds.

In typical endoscopy, doctors thread a long, thin, camera-equipped fiber through a patient’s airway or gastrointestinal tract to search out abnormalities. The images, displayed on a monitor in real time, can reveal signs of infection, internal bleeding, ulcers, and tumors on tissue surfaces. But today’s endoscopes only show a superficial picture–they don’t reveal what’s going on under the surface, such as early tumor development.

“Eighty-five percent of cancers originate from the epithelium, which is about two millimeters deep,” says Huikai Xie, associate professor of electrical and computer engineering and director of the Biophotonics and Microsystems Laboratory. In addition to its potential for detecting early signs of cancer, he says, the scope might prove useful as a surgical tool, helping surgeons determine how deep a tumor is embedded in tissue. “If you need to remove the tumor, the surgeons have a hard time determining when to stop. With a real-time, high-resolution tool, they will be sure.”

John Saltzman, a gastroenterologist and director of endoscopy at Brigham and Women’s Hospital, says such a technique would help identify early signs of cancer, particularly in the esophagus. In a condition called Barett’s esophagus, for example, cells lining the esophagus undergo a change that increases the risk of cancer, says Saltzman, who is not involved in the research. “This technology would be an advantage for us to detect such abnormalities.”

Instead of a tiny camera at the tip, Xie’s endoscope is equipped with an infrared scanner and a tiny mirror, which scans tissue layer by layer to provide a three-dimensional image with microscopic resolution. The technique is based on a method called optical coherence tomography (OCT)–as a laser beams through the arm of an OCT scope, it hits tissue, and reflects some light back, while the rest scatters. Different tissues, such as cancer versus normal tissue, reflect light differently. An interferometer measures the reflected light and subtracts the scattered light. Altering the length of the arm alters the depth at which light is directly reflected back, producing images of different layers, which together form a three-dimensional image. The method is similar to ultrasound technology, and is often called “optical ultrasound.”

Article Continues - http://www.technologyreview.com/biomedicine/24052/

Long-Term Physical Activity Has an Anti-Aging Effect at the Cellular Level

New research shows that physical exercise by professional athletes leads to activation of the important enzyme telomerase and stabilizes the telomere (Credit: iStockphoto)

Intensive exercise prevented shortening of telomeres, a protective effect against aging of the cardiovascular system, according to research reported in Circulation: Journal of the American Heart Association.

Researchers measured the length of telomeres — the DNA that bookends the chromosomes and protects the ends from damage — in blood samples from two groups of professional athletes and two groups who were healthy nonsmokers, but not regular exercisers.

The telomere shortening mechanism limits cells to a fixed number of divisions and can be regarded as a “biological clock.” Gradual shortening of telomeres through cell divisions leads to aging on the cellular level and may limit lifetimes. When the telomeres become critically short the cell undergoes death. The 2009 Nobel Prize in Physiology or Medicine was awarded to researchers who discovered the nature of telomeres and how chromosomes are protected by telomeres and the enzyme telomerase.

“The most significant finding of this study is that physical exercise of the professional athletes leads to activation of the important enzyme telomerase and stabilizes the telomere,” said Ulrich Laufs, M.D., the study’s lead author and professor of clinical and experimental medicine in the department of internal medicine at Saarland University in Homburg, Germany.

“This is direct evidence of an anti-aging effect of physical exercise. Physical exercise could prevent the aging of the cardiovascular system, reflecting this molecular principle.”

Essentially, the longer telomere of athletes is an efficient telomere. The body’s cells are constantly growing and dividing and eventually dying off, a process controlled by the chromosomes within each cell. These chromosomal “end caps” — which have been likened to the tips of shoelaces, preventing them from fraying — become shorter with each cell division, and when they’re gone, the cell dies. Short telomeres limit the number of cell divisions, Laufs said. In addition, the animal studies of Laufs and colleagues show that the regulation of telomere stabilizing proteins by exercise exerts important cellular functions beyond the regulation of telomere length itself by protecting from cellular deterioration and programmed cell death.

In the clinical study, researchers analyzed 32 professional runners, average age 20, from the German National Team of Track and Field. Their average running distance was about 73 kilometers (km), a little over 45 miles, per week.

Researchers compared the young professional athletes with middle-aged athletes with a history of continuous endurance exercise since their youth. Their average age was 51 and their average distance was about 80 km, or almost 50 miles, per week.

The two groups were evaluated against untrained athletes who were healthy nonsmokers, but who did not exercise regularly. They were matched for age with the professional athletes.

The fitness level of the athletes was superior to the untrained individuals. The athletes had a slower resting heart rate, lower blood pressure and body mass index, and a more favorable cholesterol profile, researchers said.

Long-term exercise training activates telomerase and reduces telomere shortening in human leukocytes. The age-dependent telomere loss was lower in the master athletes who had performed endurance exercising for several decades.

“Our data improves the molecular understanding of the protective effects of exercise on the vessel wall and underlines the potency of physical training in reducing the impact of age-related disease,” Laufs said.

The German Research Association and the University of Saarland funded the study.

Co-authors are: Christian Werner, M.D.; Tobias Furster, medical student; Thomas Widmann, M.D.; Janine Pöss, M.D.; Christiana Roggia, Ph. D.; Milad Hanhoun, M.D.; Jürgen Scharhag, M.D.; Nicole Buchner, Ph. D.; Tim Meyer, M.D.; Willfried Kindermann, M.D.; Judith Haendeler, Ph. D. and Michael Böhm, M.D.

Story Source:

Adapted from materials provided by American Heart Association.

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Journal Reference:

1. Christian Werner, Tobias Fürster, Thomas Widmann, Janine Pöss, Cristiana Roggia, Milad Hanhoun, Jürgen Scharhag, Nicole Büchner, Tim Meyer, Wilfried Kindermann, Judith Haendeler, Michael Böhm, and Ulrich Laufs. Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall. Circulation, 2009; DOI: 10.1161/CIRCULATIONAHA.109.861005

http://www.sciencedaily.com/releases/2009/11/091130161806.htm

Tumor-Attacking Virus Strikes With ‘One-Two Punch’

Ohio State University cancer researchers have developed a tumor-attacking virus that both kills brain-tumor cells and blocks the growth of new tumor blood vessels.

Their research shows that viruses designed to kill cancer cells — oncolytic viruses — might be more effective against aggressive brain tumors if they also carry a gene for a protein that inhibits blood-vessel growth.

The protein, called vasculostatin, is normally produced in the brain. In this study, an oncolytic virus containing the gene for this protein in some cases eliminated human glioblastoma tumors growing in animals and significantly slowed tumor recurrence in others. Glioblastomas, which characteristically have a high number of blood vessels, are the most common and devastating form of human brain cancer. People diagnosed with these tumors survive less than 15 months on average after diagnosis.

“This is the first study to report the effects of vasculostatin delivery into established tumors, and it supports further development of this novel virus as a possible cancer treatment,” says study leader Balveen Kaur, associate professor of neurological surgery and a researcher with the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. “Our findings suggest that this oncolytic virus is a safe and promising strategy to pursue for the treatment of human brain tumors.

“This study shows the potential of combining an oncolytic virus with a natural blood-vessel growth inhibitor such as vasculostatin. Future studies will reveal the potential for safety and efficacy when used in combination with chemotherapy and radiation therapy,” she says.

The findings were recently published online in the journal Molecular Therapy.

Jayson Hardcastle, a graduate student in Dr. Kaur’s laboratory, injected the cancer-killing virus, called RAMBO (for Rapid Antiangiogenesis Mediated By Oncolytic virus), directly into human glioblastoma tumors growing either under the skin or in the brains of mice.

Of six animals with tumors under the skin, those treated with RAMBO survived an average of 54 days. In addition, three of the RAMBO mice were tumor-free at the end of the experiment. Control animals treated with a similar virus that lacked the vasculostatin gene, on the other hand, survived an average of 26 days and none were tumor-free.

Of the animals with a human glioblastoma in the brain, five were treated with RAMBO and lived an average of 54 days. One animal remained tumor-free for more than 120 days. Control animals, by comparison, lived an average of 26 days with no long-term survivors.

In another experiment, the investigators followed the course of tumor changes in animals with tumors in the brain. After an initial period of tumor shrinkage, the remaining cancer cells began regrowing around day 13 in animals given the virus that lacked the blood-vessel inhibitor. In animals treated with RAMBO, tumor regrowth didn’t begin until about day 39.

“With additional research, this virus could lead to a new therapeutic strategy for combating cancer,” Kaur says.

Story Source:

Adapted from materials provided by Ohio State University Medical Center.

http://www.sciencedaily.com/releases/2009/12/091201102336.htm

Scientists Reveal Malaria Parasites’ Tactics for Outwitting Our Immune Systems

This is an Anopheles gambiae mosquito sucking blood from human skin. This mosquito is the vector for malaria in Africa. (Credit: Wellcome Images)

Malaria parasites are able to disguise themselves to avoid the host’s immune system, according to research funded by the Wellcome Trust and published November 30 in the journal Proceedings of the National Academy of Sciences.

Malaria is one of the world’s biggest killers, responsible for over a million deaths every year, mainly in children and pregnant women in Africa and South-east Asia. It is caused by the malaria parasite, which is injected into the bloodstream from the salivary glands of infected mosquitoes. There are a number of different species of parasite, but the deadliest is the Plasmodium falciparum parasite, which accounts for 90 per cent of deaths from malaria.

The malaria parasite infects healthy red blood cells, where it reproduces. The P. falciparum parasite generates a family of molecules, known as PfEMP1, that are inserted into the surface of the infected red blood cells. The cells become sticky and adhere to the walls of blood vessels in tissues such as the brain. This prevents the cells being flushed through the spleen, where the parasites would be destroyed by the body’s immune system, but also restricts blood supply to vital organs.

Symptoms can differ greatly between young and older children depending on previous exposure to the parasite. In young children, the disease can be extremely serious and potentially fatal if untreated; older children and adults who have grown up in endemic areas are resistant to severe malaria but rarely develop the ability to rid their bodies of the parasite.

Each parasite has ‘recipes’ for around sixty different types of PfEMP1 molecule written into its genes. However, the exact recipes differ from parasite to parasite, so every new infection may carry a set of molecules that the immune system has not previously encountered. This has meant that in the past, researchers have ruled out the molecules as vaccine candidates. However there appear to be at least two main classes of PfEMP1 types within every parasite, suggesting different broad tactical approaches to infecting the host. The most efficient tactic or combination of tactics to use may depend on the host’s immunity.

Now, Dr George Warimwe and colleagues from the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme and the Wellcome Trust Sanger Institute, have shown that the parasites adapt their molecules depending on which antibodies it encounters in the host’s immune response. They have also found evidence to suggest that there may be a limit to the number of molecular types that are actually associated with severe disease.

“The malaria parasite is very complex, so our immune system mounts many different responses, some more effective than others and many not effective at all,” explains Dr Peter Bull from the KEMRI-Wellcome Trust Programme and the University of Oxford, who led the research. “We know that our bodies have great difficulty in completely clearing infections, which begs the question: how does the parasite manage to outwit our immune response? We have shown that, as children begin to develop antibodies to parasites, the malaria parasite changes its tactics to adapt to our defences.”

The researchers at the KEMRI-Wellcome Trust Programme studied malaria parasites in blood samples from 217 Kenyan children with malaria. They found that a group of genes coding for a particular class of PfEMP1 molecule called Cys-2 tended to be switched on when the children had a low immunity to the parasite; as immunity develops, the parasite switches on a different set of genes, effectively disguising it so that immune system cannot clear the infection

Dr Warimwe and colleagues also found an independent association between activity in Cys-2 genes and severe malaria in the children, suggesting that specific forms of the molecule may be more likely to trigger specific disease symptoms. This supports a previous study in Mali which suggested that the same class of PfEMP1 molecule was associated with cerebral malaria.

The findings could suggest a new approach to tackling malaria, in terms of both vaccine development and drug interventions, argues Dr Bull.

“If there exists a limited class of severe disease-causing variants that naturally-exposed children learn to recognise readily, this opens up the possibility of designing a vaccine against severe malaria that mimics an adult’s immune response, making the infections less dangerous. But this would still be an enormous task.

“Similarly, if we can establish what the particular class of molecules are doing, then we may be able to develop a drug to modify this function and relieve symptoms of severe disease.”

Story Source:

Adapted from materials provided by Wellcome Trust, via EurekAlert!, a service of AAAS.

http://www.sciencedaily.com/releases/2009/11/091130151325.htm

Gene-Testing Machine for Doctors

Simple testing: This disposable cartridge can detect genetic variations from blood samples. The circles lining the top and bottom are loaded with reagents for different chemical reactions. DNA is isolated from white blood cells and captured on a glass slide within the cartridge.   Credit: Nanosphere

A new device rapidly analyzes blood for medically relevant genetic variations.

By Emily Singer

A desktop instrument recently approved by the U.S. Food and Drug Administration might finally bring pharmacogenomic testing–the use of a patient’s genetic information for drug prescription decisions–to the mainstream. The device, made by Nanosphere, a startup based in Northbrook, IL, can, in a matter of hours, detect genetic variations in blood that modulate the effectiveness of some drugs. Dubbed Verigene, the technology employs a combination of microfluidics and nanotechnology, housed in a single plastic cartridge, to pull DNA from a blood sample and then screen it for the relevant sequences.

“We believe the benefit of our system is that this simple cartridge format could be run in any hospital, even a doctor’s office,” says William Moffitt, chief executive at Nanosphere. “We’re moving complex testing to the point of patient care.” Moffitt says Verigene is the first nanotechnology-based microfluidics product capable of analyzing DNA directly from a blood sample.

People can respond to drugs very differently, thanks in part to commonly occurring genetic variations in enzymes that metabolize some of the mostly highly prescribed compounds, such as heart medicines, pain medicines, and antidepressants. While doctors have widely adopted pharmacogenomic testing for prescribing some cancer drugs, such testing hasn’t yet taken hold for many other drugs whose effectiveness is modulated by genetics, including those for HIV, pain control, and epilepsy. The technology needed to detect these variations in patients has been available for years, but the process is often time-consuming and expensive. Physicians typically must send patients’ saliva or blood samples to a central lab, where the DNA is isolated, amplified, and analyzed. That process can take days or weeks.

“In some cases, it doesn’t matter if it takes a week to get a result. But in some cases we would like to have the information to choose a drug during the office visit, when the patient is right there,” says Howard McLeod, director of the Institute for Pharmacogenomics and Individualized Therapy at the University of North Carolina, Chapel Hill. “That way we can say, this drug is the one your DNA says will most likely be beneficial.”

The anticoagulant warfarin, for example, is frequently prescribed to prevent blood clots. But people metabolize the drug differently, meaning patients must be carefully monitored to make sure they don’t suffer dangerous bleeding. The FDA changed the drug’s label in 2007 to note that two specific genetic variations affect a patient’s sensitivity to the drug, but broad gene testing has not yet caught on. “Currently, available genotyping tests for warfarin pharmacogenomics require isolation of DNA from blood and testing in a molecular diagnostics laboratory certified for high-complexity testing,” says Karen Weck, director of the molecular genetics laboratory at the University of North Carolina, Chapel Hill.

Nanosphere is developing a test that can detect these variations in blood samples in an hour or two. A patient’s blood is injected into a disposable cartridge, which holds a glass slide dotted with DNA. The plastic frame also houses a system of microfluidics chambers containing the reagents for a number of chemical reactions. When the cartridge is inserted into the Verigene instrument, mechanical valves and air pressure mix the reagents in different chambers, triggering a series of reactions.

Story Continues – http://www.technologyreview.com/biomedicine/24042/

Heavy Metal Paradox Could Point Toward New Therapy for Lou Gehrig’s Disease

New discoveries have been made about how an elevated level of lead, which is a neurotoxic heavy metal, can slow the progression of amyotrophic lateral sclerosis, or Lou Gehrig’s disease — findings that could point the way to a new type of therapy.

The results surprised researchers, since lead is also a known risk factor for ALS. This paradox is still not fully understood, and at this point would not form the basis for a therapy, as lead is toxic for the nervous system. But scientists say the phenomenon may lead to promising alternative approaches to the gene therapies that are now a focus of study.

The research was just published in Neurobiology of Disease, a professional journal, by researchers from the Instituto Clemente Estable and the University of the Republic in Montevideo, Uruguay, and at Oregon State University. The research has been supported by the National Institutes of Health.

“We know that environmental exposure to lead is a risk factor for ALS,” said Joseph Beckman, holder of the Ava Helen Pauling Chair in the Linus Pauling Institute and director of the Environmental Health Sciences Center at OSU. “That’s why it’s so surprising that, according to studies done with laboratory animals, higher levels of lead appear to significantly reduce motor neuron loss and progression of ALS.”

Research will continue to explore the underlying mechanisms that may be causing this, Beckman said. But the findings also raise immediate questions about the wisdom of chelation therapy in efforts to treat ALS, which many people have tried despite no evidence that it works. Chelation therapy tries to remove heavy metals from the body, including lead.

“Many people have spent thousands of dollars on chelation therapy to treat ALS, despite a lack of scientific evidence that heavy metals are causing the disease,” Beckman said. “These findings about the potential protective mechanism of lead now raise concerns about the rationale for chelation therapy in treating ALS.”

ALS is a progressive, fatal neurodegenerative disease that causes muscle weakness and atrophy throughout the body. There is no known cure, and it affects about 2-3 out of every 100,000 people each year.

According to Beckman, some of the findings about the role of lead in this disease evolved out of collaborative research OSU is doing with universities in Uruguay, where significant numbers of children from impoverished families are suffering from lead poisoning caused by setting up camps over abandoned lead factories near Montevideo.

“In this area there are huge problems with lead poisoning, mostly in children,” Beckman said. “People are being exposed through their water, food, other environmental sources, and we’ve worked there for a number of years to learn more about the neurotoxicity of lead exposure.”

Lead appears to have some interaction with astrocytes, Beckman said, a special type of cell that is believed to influence the spread of ALS. Astrocytes are a major component of brain cells and, in healthy systems, help to support neurons, defend them against infection and injury and remove neurons when they become damaged.

This delicate process, however, may get disrupted in ALS, at which point astrocytes are believed to play a role in causing inappropriate motor neuron death.

“These systems are very carefully balanced and many factors have to work together,” Beckman said. “The proper functioning of astrocytes is essential to life, but their dysfunction may lead to disease. We think that lead somehow is modulating the neuroinflammatory actions of astrocytes and, in the case of ALS, helping to shift their balance back to one of protection, rather than damage.”

When that happens, researchers say, it appears that astrocytes can stimulate the production of “vascular endothelial growth factor,” which in turn protects motor neurons. Researchers around the world see increases in this growth factor as a possible way to help treat ALS, and most work is now focused on gene therapies to accomplish that. More research is necessary to determine the mechanisms by which lead has this protective effect, which may help to identify pharmacological targets for the disease.

The levels of lead that were therapeutic in the mice have toxic risk in adult humans, the researchers pointed out. However, as more is learned about how lead is affecting ALS, alternatives to lead might be found to accomplish the same goal.

“Available evidence supports the view that astrocytes are key targets of lead and respond to it by inducing neuroprotective pathways,” the researchers wrote in their report. “Our results suggest that lead activates a novel pathway able to reduce neuroinflammation and slow neurodegeneration in ALS.”

Story Source:

Adapted from materials provided by Oregon State University, via EurekAlert!, a service of AAAS.

http://www.sciencedaily.com/releases/2009/11/091130160709.htm

Kangaroos may hold skin cancer cure: study

AFP/File – An Australian red kangaroo is seen at Sydney Wildlife World. Kangaroos may provide the key to a potential …

SYDNEY (AFP) – Kangaroos may provide the key to a potential treatment to prevent skin cancer, Australian scientists said on Monday.

Researchers at Melbourne University are investigating whether a DNA repair enzyme found in the jumping marsupials could provide a model for preventing DNA damage linked to many skin cancers in humans.

“Other research teams have proposed a ‘dream cream’ containing the DNA repair enzyme which you could slap on your skin after a day in the sun,” scientist Linda Feketeova said.

“We are now examining whether this would be feasible by looking at the chemistry behind the DNA repair system.”

Feketeova and colleague Uta Wille, who are working in collaboration with scientists at the University of Innsbruck in Austria, are investigating whether sun-damaged human DNA can be repaired using the kangaroo model.

Using a mass spectrometer instrument, they are simulating the impact the kangaroo enzyme would have on DNA which would otherwise develop skin cancer.

“We were quite surprised that the DNA’s repair process also resulted in a number of chemical by-products, which have never been seen before,” Wille said.

“Our plan is to study these products to understand if the DNA repair enzyme could be incorporated into a safe and effective method for skin cancer prevention.”

Kangaroos are not immune from skin cancer but their special repair enzyme, which is also present in some bacteria and fish, gives their skin an additional protection that humans lack.

“As summer approaches, excessive exposure to the sun’s harmful UV (ultraviolet) light will see more than 400,000 Australians diagnosed with skin cancer,” Feketeova said.

http://news.yahoo.com/s/afp/20091130/wl_asia_afp/healthaustraliacancerkangaroos_20091130105712

Abbott’s deal with Teva keeps generic TriCor off the market yet again

Melly Alazraki

The case of Abbott Laboratories’ (ABT) cholesterol drug TriCor is quite interesting. The drug has been a blockbuster, and it has been under patent protection for decades. That’s right, decades. Now, Abbott has managed to seal a deal with generic drug maker Teva Pharmaceuticals Industries Ltd. (TEVA) that would stave off generic competition for TriCor — yet again — until March 2011 at least.

How did Abbott manage to keep TriCor under patent protection all these years? The story begins back in the 1960s, when the drug was discovered by the French company Fournier. It began selling the product in Europe in 1975 and Abbott licensed it in 1998. The drug’s underlying patent had expired by that time, but Abbott, which earns more than $1 billion in annual sales from the drug, found a way to patent it again … and again … and again.

In 1999, a generic drug company that was later acquired by Teva was about to introduce a generic version of TriCor. Abbott sued for patent infringement and the two have been in court ever since. To protect its patent, Abbott used a tactic favored by many pharmaceutical companies in their scrambles to keep drugs under patent protection: Abbott patented a new formulation for TriCor by changing the type of pill (from capsule to tablet) and the dosage. In doing so, it prevented pharmacists from automatically switching prescriptions for TriCor to a generic version. Teva’s plans for the generic version were derailed and this whole scenario repeated itself in 2002.

While Abbott denied any wrongdoing, it did agree to pay $184 million to settle litigation brought by state attorneys general and private entities alleging antitrust and unfair competition claims in connection with the sales of TriCor.

The SEC filing from Monday that disclosed the settlement with Teva didn’t disclose many details. What we know is that the deal involves the TriCor 145-milligram tablet and that it postpones the sale of a generic version of TriCor until March 28, 2011, at the earliest. Fournier S.A. also agreed to the deal. Also, under certain defined circumstances, Teva may not receive rights until July 1, 2012.

Another Loophole, Another Profit Booster

Meanwhile, last year, the Food and Drug Administration approved TriLipix, a new branded Abbott drug that is similar to TriCor but is approved for use in combination with statins, a popular class of cholesterol-lowering drug. So now Abbott is scrambling to switch patients to TriLipix from TriCor before generic versions of TriCor appear.

If you think that something smells funny here, you’re not alone. While Abbott makes essentially cosmetic changes to TriCor that allow it to somehow convince the FDA that it’s a new drug which warrants new patent protection, the ones who are left to foot the bill for the more expensive, branded drug seem to be, as always, the patients and the taxpayers.

Abbott is not paying Teva to delay the introduction of a generic version, Kelly Morrison, a company spokeswoman told DailyFinance. “There is no payment/commercial agreement as part of this — this is a pure licensing agreement,” she said, adding that “this allows Abbott to obtain certainty for our product and avoid risk and costly litigation around our patents.” But what Teva gets out of the deal to induce it to agree to this arrangement is not clear.

Many pharmaceutical companies have paid generic makers over the past decade to delay generics. The Federal Trade Commission doesn’t look kindly on such “pay-for-delay” deals: The practice ends up costing U.S. consumers $3.5 billion a year — $1.2 billion of which is paid by the government, FTC chief Jon Leibowitz said in June.

Questions of generics aside, some doctors are growing skeptical about the benefits of TriCor, with published studies showing that it failed to definitively reduce heart attacks and related heart diseases, while possibly causing kidney problems. Abbott defends the drug’s efficacy and safety.

Abbott has been able to fend off most problems when it comes to TriCor — to the delight of its shareholders. But perhaps it’s time someone took a closer look not just at generic delaying practices but also at FDA’s rulebook when it comes to issuing patents on barely modified drugs. The market could have had a generic version of TriCor since 1999. At $1 billion a year in sales, that’s a big chunk of savings that patients, insurers and taxpayers have missed out on.

http://www.dailyfinance.com/2009/12/01/abbotts-deal-with-teva-keeps-generic-tricor-off-the-market-yet/

Caterpillar Flu Vaccine Delayed

Growing immunity: These images show insect cells growing without virus genes (top) and with virus genes (bottom). Scientists say the approach can produce 100,000 doses of vaccine per week, and can be adapted for different viruses, including H1N1 (swine flu).  Credit: Protein Sciences

The FDA wants further evidence that the novel approach is completely safe.

By Jennifer Chu

A new method of making flu vaccines is faster, more efficient, and more robust than the one that has been in use for the last 50 years. It has the potential to scale up rapidly, to deal with new strains of influenza such as this year’s H1N1, and to help stem a pandemic tide. However, a U.S. Food and Drug Administration advisory panel voted in late November not to approve the technology, which involves growing key vaccine ingredients inside caterpillar cells instead of in chicken eggs, as is currently done. The FDA says that the company behind the new approach, Protein Sciences, based in Meriden, CT, needs to test it further before the method can be approved for use in the United States.

Jose Romero, chief of pediatric disease at Arkansas Children’s Hospital and a member of the 11-person FDA panel, says that, while the company has more to do in order to prove safety, the cell-based technology shows considerable promise.

“This type of technology is going to move traditional influenza vaccinology into the 21st century,” says Romero. “We recognize that there may come a day when a strain does arrive that cannot be supported by growth in traditional egg-based technology, and this and other cell-based technologies can breach that problem and provide us with another avenue for developing vaccines.”

Today’s egg-based vaccine technology is slow and unwieldy, requiring at least six months’ of production time and millions of eggs to supply enough doses for a regular flu season. If a new virus appears unexpectedly, the antiquated system wouldn’t be able to gear up fast enough to produce a new vaccine, many experts agree. What’s more, if the virus itself were derived from birds, it might reduce the supply of eggs, hampering the country’s main means of vaccine production.

For the past decade, Protein Sciences, along with a number of other companies, has been looking to cell-based vaccines as a more efficient and robust alternative. Instead of growing viruses in chicken eggs, researchers inject virus strains into insect cells. Both the virus and the cells then grow and multiply quickly in bioreactors. Scientists break the cell walls and harvest a key protein, called hemagglutinin, produced by the virus. This protein, found on the influenza virus’s outer surface, is responsible for binding to cells in the body, causing a viral infection. Scientists purify and inactivate the harvested protein so that it can stimulate an immune response without causing an infection. The protein is the main ingredient in a vaccine.

Protein Sciences’ technology is a slight variation on the conventional cell-based approach. Instead of growing live viruses, the company replicates viral DNA within cells. The genes for hemagglutinin are extracted from a dead flu virus and injected into baculovirus–a virus that infects a caterpillar called the armyworm. The baculovirus is then injected into ovary cells isolated from the armyworm. In a bioreactor, the virus eats away at cells, replicating DNA and producing hemagglutinin.

“Because the starting material is a DNA sequence, it eliminates a lot of steps you have to go through, because the flu virus itself is not part of this production process,” says John Treanor, a medical advisor to the company and professor of microbiology and immunology at the University of Rochester Medical Center in New York. “You also don’t have concerns of workers getting infected, versus using a growing virus.”

Treanor headed four clinical trials to test the vaccine for effectiveness against seasonal flu. The trials compared the effects of the company’s vaccine against a conventional one in 3,231 people aged 18 and older.

The company presented its results to the FDA advisory board. While the new vaccine was found to protect against seasonal flu symptoms in those 18 to 49, it was not possible to draw significant conclusions for older participants. Several older subjects suffered from facial swelling after receiving the vaccine, and one developed a temporary paralysis on one side of the face. This might have been a preexisting condition, but researchers couldn’t be sure if the condition was independent of the vaccine. “When you have one case, it’s hard to know,” says Treanor.

The FDA panel recommended that the company expand the patient group to determine whether the vaccine is safe in a larger, older population.

Other companies seeking FDA approval for similar cell-based vaccines include Novartis, which opened a vaccine manufacturing plant in North Carolina this week and plans to produce vaccines from dog kidney cells.

FluGen, a vaccine company based in Madison, WI, has also entered the race. It is growing flu virus in manipulated hamster ovary cells–a cell line that has already been approved by the FDA for producing drugs to treat rheumatoid arthritis. FluGen is a little behind its bigger competitors, but CEO Paul Radspinner says he will take a lesson from Protein Sciences’ experience when it comes time to seek FDA approval. “Maybe it’s a learning point,” says Radspinner. “We’ll be very careful with where we go with clinical trials where there’s a database of patients coming through, and [make sure] that preexisting conditions are being noted.”

http://www.technologyreview.com/biomedicine/24031/

Harvard study: Computers don’t save hospitals money

Hospital computer systems are often built for administrators, not doctors

By Lucas Mearian

A Harvard Medical School study that looked at some of the nation’s “most wired” hospital facilities found that computerization of those facilities hasn’t saved them any money or improved administrative efficiency.

The recently released study evaluated data on 4,000 hospitals in the U.S over a four-year period and found that the immense cost of installing and running hospital IT systems is greater than any expected cost savings. And much of the software being written for use in clinics is aimed at administrators, not doctors, nurses and lab workers.

The study comes as the federal government prepares to begin dispensing $19 billion in incentives for the health industry to roll out electronic health records systems. Beginning in 2011, the Health Information Technology for Economic and Clinical Health (HITECH) Act will provide incentive payments of up to $64,000 for each physician who deploys an electronic health records system and uses it effectively.

The problem “is mainly that computer systems are built for the accountants and managers and not built to help doctors, nurses and patients,” the report’s lead author, Dr. David Himmelstein, said in an interview with Computerworld.

Himmelstein, an associate professor at Harvard Medical School, said that in its current state, hospital computing might modestly improve the quality of health care processes, but it does not reduce overall administrative costs. “First, you spend $25 million dollars on the system itself and hire anywhere from a couple-dozen to a thousand people to run the system,” he said. “And for doctors, generally, it increases time they spend [inputting data].”

Himmelstein said that only a handful of hospitals and clinics realized even modest savings and increased efficiency — and those hospitals custom-built their systems after computer system architects conducted months of research.

He pointed to Brigham and Women’s Hospital in Boston, Latter Day Saints Hospital in Salt Lake City and Regenstrief Institute in Indianapolis as facilities with some success in deploying efficient e-health systems. That’s because they were intuitive and aimed at clinicians, not administrators.

Programmers of the successful systems told Himmelstein that they didn’t write manuals or offer training. “If you need a manual, then the system doesn’t work. If you need training, the system doesn’t work,” he said.

While many health care experts believe that computerization will improve quality of care, reduce costs and increase administrative efficiency, the Harvard Medical School report notes that no earlier studies closely examined computerization’s cost or its effect on a diverse sample of hospitals. Even hospitals on the “most wired” list “performed no better than others on quality, costs, or administrative costs,” the study found.

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