Paralysed man Darek Fidyka, walks again after breakthrough treatment

A paralysed man can walk again after receiving revolutionary treatment which one of the British scientists responsible hailed as a breakthrough "more impressive than a man walking on the Moon," although others urged caution.

Darek Fidyka was paralysed from the chest down, but can now walk using a frame after nerve cells from his nose were transplanted into his severed spinal column in Poland, according to research published Tuesday in the journal Cell Transplantation.

"When there's nothing, you can't feel almost half of your body. You're helpless, lost," the patient, who is now recovering at the Akron Neuro-Rehabilitation Centre in Wroclaw, told reporters, who filmed his remarkable recovery.

"When it (the feeling) begins to come back, you feel you've started your life all over again, as if you are reborn," said the 40-year-old Polish man, whose injuries were caused by a knife attack in 2010.

"It's an incredible feeling, difficult to describe," he added.

Olfactory ensheathing cells (OECs), which form part of the sense of smell, were used in the treatment as they are pathway cells that enable nearby nerve fibres to be regenerated.

Pawel Tabakow, consultant neurosurgeon at Wroclaw University, led a team of surgeons in removing one of the patient's olfactory bulbs before transplanting cultured cells into the spinal cord in the treatment's two crucial operations.

He said to reporters that the patient was "exhausted" by the documentary filming schedule, which lasted a year.

'Be very prudent'

The scientists involved think that the cells, implanted above and below the injury, enabled damaged fibres to reconnect, although other researchers have reacted more sceptically.

"What we've done is establish a principle, nerve fibres can grow back and restore function, provided we give them a bridge," said Geoff Raisman, chair of neural regeneration at University College London's Institute of Neurology, who led the British research team working on the joint project.

"To me, this is more impressive than a man walking on the Moon. I believe this is the moment when paralysis can be reversed."

But other scientists were far more cautious, saying it was important to await the results of clinical testing with more cases.

"We have to be very prudent," said Alain Privat from France's health and medical research institute Inserm.

Simone Di Giovanni, head of restorative neuroscience at Imperial College London, added that there was "no evidence that the transplant is responsible for the reported neurological improvement".

This assertion was disputed by Wagih El-Masri, a professor of spinal surgery at Keele University in Britain, who was an independent assessor on the Polish case.

"It is clear that on the balance of probability, the changes are due to the treatment," he said, adding that there was only a one percent chance that the recovery would have occurred due to other factors.

"As a clinician with 40 years' experience, I would strongly support that this line of research is pursued without raising the hopes too much of patients," he said.

'Significant progress'

For two years after his injury, Fidyka showed no sign of recovery despite intensive five-hour physiotherapy sessions.

The first signs of improvement came three months after the surgery, when his left thigh began putting on muscle.

Three months later, Fidyka was able to take his first steps with the aid of parallel bars and leg braces.

He can now walk outside using a frame and has also recovered some feeling in his bladder and bowel.

The research was funded by the UK Stem Cell Foundation and the Nicholls Spinal Injury Foundation (NSIF), set up by chef David Nicholls after his son Daniel was paralysed in a 2003 swimming accident.

"When Dan had his accident I made him a promise that, one day, he would walk again," Nicholls told the BBC.

"The results with Darek show we are making significant progress towards that goal."
NSIF has given £1 million ($1.6 million, 1.26 million euros) to researchers in London and £240,000 to the team in Poland. Both camps say they will not seek to profit from the research.

They hope to raise enough money to hold clinical trials on 10 patients in Britain and Poland.

More information: Tabakow, P.; Raisman, G.; Fortuna, W.; Czyz, M.; Huber, J.; Li, D.; Szewczyk, P.; Okurowski, S.; Miedzybrodzki, R.; Czapiga, B.; Salomon, B.; Halon, A.; Li, Y.; Lipiec, J.; Kulczyk, A.; Jarmundowicz, W. Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplant. Appeared or available on-line: October 21, 2014. www.ingentaconnect.com/content… T-1239_Tabakow_et_al

Multi-Drug Resistant Tuberculosis (TB) treatment a Global threat

The World Health Organisation (WHO) and the Global Fund to Fight AIDS, TB and Malaria says that strains of tuberculosis with resistance to multiple drugs could spread widely and highlight an annual need of at least $1.6 billion in international funding for treatment and prevention of the disease.

Dr. Margaret Chan, director-general of WHO, and Dr. Mark Dybul, executive director of the Global Fund, said that the only way to carry out the urgent work of identifying all new cases of tuberculosis, while simultaneously making progress against the most serious existing cases, will be to mobilize significant funding from domestic sources and international donors.

With the overwhelming majority of international funding for tuberculosis coming through the Global Fund, they said, it is imperative that efforts to raise money be effective this year. Growing alarm about the threat of multi-drug resistant TB, also known as MDR-TB, is making that even more pressing.

“We are treading water at a time when we desperately need to scale up our response to MDR-TB,” says Chan. “We have gained a lot of ground in TB control through international collaboration, but it can easily be lost if we do not act now.”

WHO and the Global Fund have identified an anticipated gap of $1.6 billion in annual international support for the fight against tuberculosis in 118 low- and middle-income countries on top of an estimated $3.2 billion that could be provided by the countries themselves.

Filling this gap could enable full treatment for 17 million TB and multidrug-resistant TB patients and save 6 million lives between 2014-2016.

“It is critical that we raise the funding that is urgently needed to control this disease,” says Dybul. “If we don’t act now, our costs could skyrocket. It is invest now or pay forever.”

Chan and Dybul spoke to the media in Geneva in advance of World TB Day on March 24, which commemorates the day in 1882 when Dr. Robert Koch discovered the mycobacterium that causes tuberculosis.

Read more on TB Research in the European Respiratory Journal

PreDICT TB: Europeans fight Pulmonary Tuberculosis (TB) with innovative technique

A European team of scientists is working on making new tuberculosis treatments a reality by developing better diagnostic imaging technology. 

The study is supported by the PREDICT-TB ('Model-based preclinical development of anti-tuberculosis drug combinations') project, which has clinched almost EUR 14.8 million from the Innovative Medicines Initiative (IMI) under the EU's Seventh Framework Programme (FP7).

IMI is a public-private partnership between the EU and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

The PREDICT-TB team is working together with the European pharmaceutical industry; the project's coordinator is the United Kingdom-based GlaxoSmithKline, one of the world's leading pharmaceutical companies.

Results will help the many patients suffering from this airborne infectious disease: almost 9 million people worldwide currently have tuberculosis.

The researchers are developing a set of in vitro and in vivo trials that will give them the information they need to make key decisions about effective treatments. They also plan to optimise the clinical studies of novel combinations of drugs to fight this disease.

'These data will, first, offer us an early evaluation of the efficiency of the combinations of drugs used to treat tuberculosis, and second, they will allow us to optimise the clinical studies with patients,' said Juan José Vaquero from the Bioengineering and Aerospace Engineering Department at the Carlos III University of Madrid (UC3M) in Spain, one of the PREDICT-TB partners.

The UC3M group is researching and developing the new preclinical imaging technology, and is working on methods for processing and analysing images for the assessment and follow-up of illness in animal models.

'We are going to develop new in vivo molecular image devices and also work on the synthesis of very specific probes for the biomarkers of this illness that have been identified by other partners in the consortium,' Professor José Vaquero said.

'We are collaborating very closely with GlaxoSmithKline, whose laboratories are going to use our equipment, as well as with specialists from the Infectious Disease and Microbiology Service of Gregorio Marañón University General Hospital in Madrid, who have a great deal of experience working with both the biology and the clinical aspects of tuberculosis. This facilitates the transformation of our results into clinical applications.'

The objective of UC3M, in the short term, is to develop a tomographic X-ray technique that screens quickly yet inexpensively.

This technique will give researchers the opportunity to keep an eye on the evolution of the disease and to determine how effective the treatments are in animal models.

The team's long-term objective team is to perfect this technique and make it more sensitive and specific.

Positron emission tomography (PET) will be included, a nuclear medicine imaging technique that generates a three-dimensional image for pictures of functional processes in the body. Quantitative measurements can be taken with this more sensitive technique.

The group also plans to introduce changes in imaging technology to ensure that better resolution is obtained. 'This way, with just one examination, we will be able to visualise the complete lung of a rat or guinea pig, with enough detail to detect the disease at its earliest possible stage,' Professor José Vaquero explained.

The PREDICT-TB project is pioneering research in tuberculosis by investigating the use of quantitative molecular imaging.

Each year, tuberculosis affects 5 million patients in developing countries. A cure is possible for only 60 % of them, and one of the biggest challenges in fighting tuberculosis is to ensure that patients are treated for 6 to 24 months. Both support and financing for trials are limited. For more information, please visit:

Innovative Medicines Initiative (IMI): http://www.imi.europa.eu/

Dietary Changes and Milk fats alter gut bacteria leading to degenerative abdominal disease

The rise of inflammatory bowel diseases could be down to our shifting diets causing a "boom in bad bacteria", according to US researchers.

Mouse experiments detailed in the journal Nature linked certain fats, bacteria in the gut and the onset of inflammatory diseases.

The researchers said the high-fat diet changed the way food was digested and encouraged harmful bacteria.

Microbiologists said modifying gut bacteria might treat the disease.

Inflammatory bowel diseases (IBDs), such as Crohn's and ulcerative colitis, affect one in every 350 people in the UK. When the gut becomes inflamed it can lead to abdominal pain and diarrhoea.

The researchers at the University of Chicago said the incidence of the diseases was increasing rapidly.

They used genetically modified mice which were more likely to develop IBDs. One in three developed colitis when fed either low-fat diets or meals high in polyunsaturated fats. This jumped to nearly two in three in those fed a diet high in saturated milk fats, which are in many processed foods.

They also suggest an effective means of dealing with such diseases, by simply reshaping the microbial balance of the gut”

Dr Roy Sleator Cork Institute of Technology

These saturated fats are hard for the body to digest and it responds by pumping more bile into the gut.

This changes the gut environment and leads to a change in the bacteria growing there, the researchers said.

Treatments

One bacterium in particular, Bilophila wadsworthia, was identified. It thrives in the extra bile produced to break down the fats. It went from being incredibly rare to nearly 6% of all bacteria in the gut in the high-fat diet.

Prof Eugene Chang, of the University of Chicago, said: "Unfortunately, these can be harmful bacteria. Presented with a rich source of sulphur, they bloom, and when they do, they are capable of activating the immune system of genetically prone individuals."

However, he said this could lead to possible treatments as the gut bacteria could be "reshaped" without "significantly affecting the lifestyles of individuals who are genetically prone to these diseases".

Commenting on the research, Dr Roy Sleator, from the Cork Institute of Technology, said: "Not only do the authors provide, what is in my opinion, the first credible explanation as to how Western diet contributes to the unusually high incidence in inflammatory bowel disease; they also suggest an effective means of dealing with such diseases, by simply reshaping the microbial balance of the gut."

Fight nematode parasites with compounds in worms

Worms are important decomposers in soil, but in humans they spell trouble. Parasitic nematodes infect some 2 billion people.

Researchers are hopeful the discovery of a new class of molecules could lead to prevention and treatments for worm parasites.

(Credit: Image of "Caenorhabditis elegans" via Shutterstock)

Hookworms, whipworms, Ascaris, Guinea worms, and trichina worms are just a few parasitic nematodes that infect some 2 billion people.

Researchers report that nematodes use the newly discovered class of small molecules to signal such processes as growing, developing, mating, and moving toward or away from an area.

“All of these nematodes speak the same chemical language,” through the use of compounds called ascarosides, says study co-author Frank Schroeder, a research scientist at the Boyce Thompson Institute for Plant Research and adjunct assistant professor at Cornell University.

The study, published online in the journal Current Biology, was led by Stephan von Reuss, a postdoctoral associate in Schroeder’s lab, and Andrea Choe, a postdoctoral scholar in the lab of co-author Paul Sternberg, a biologist at the (WormLab) California Institute of Technology.

Since nematodes are the only known organisms to use ascarosides, “we don’t have to be afraid of interfering with similar biochemistry in animals, plants, or humans,” Schroeder says, as researchers seek to identify species-specific ascaroside molecules that may enable novel approaches to deter or disrupt the survival or reproduction of parasitic worms.

Researchers in Schroeder’s lab have already filed for three patents, one that covers the structures of various ascarosides, one that covers ascarosides for use as agents to protect plants, and one that makes claims to how to use the compounds to treat or prevent human disease.

The researchers first discovered ascarosides as a signaling molecule in C. elegans, a nematode used as a model organism to study cell, developmental, and nervous system biology, as well as human aging and diabetes.

“We then thought, if C. elegans uses this chemical language, perhaps other nematodes do too,” Schroeder says.

Raed the full report here:  DOI: 10.1016/j.cub.2012.03.024

Malaria treatment: Impact on disease risk for babies

The UK NHS Information Video is very good at explaining Malaria infections and preventative actions you can take, but it does not go into details of how it affects young women, pregnant women and young breast-feeding mothers.

Recent research has indicated that Mothers who receive treatment for malaria infection could pass on lower levels of natural immunity to their babies.

Edinburgh University experts found mice treated with malaria infection drugs before they became pregnant passed on fewer antibodies to their young.

Full-blown malaria gives the immune system the chance to produce protective antibodies to pass on.

However, it is thought the drug treatment shortens the process.

The mothers benefit while children's immunity is decreased, putting them at greater risk.

The researchers said their results highlighted the need to look at how treatment might be tailored most effectively for women and their babies.

Malaria affects millions of people worldwide, mainly in developing countries. One child dies from the disease in Africa every minute.

Dr Vincent Staszewski, of Edinburgh University's school of biological sciences, said: "How an infection plays out in an individual can impact on the immunity of the next generation.

"Some treatments against disease before or during pregnancy might be beneficial for maternal health but impair infant survival."

The study, published in Proceedings of the Royal Society B, was funded by the Wellcome Trust and the Royal Society.

Safer cancer treatments: Case Studies

A new piece of medical technology unveiled by NPL will help improve the success rates of radiotherapy cancer treatments.

The new clinical electron linear accelerator (linac), a £1.5 million government-funded investment, will help ensure patients are treated with accurate doses of radiation.

Radiotherapy is used to treat cancer by using ionising radiation such as high-energy X-rays or electron beams to destroy cancer cells.

Every hospital needs to ensure that its radiotherapy equipment is stable and accurate because delivering correct radiation doses is critical.

If the dose is too low, the cancer may continue to grow. If they are too high, the patient may be endangered by healthy tissue being damaged.

NPL's new clinical linac’s ability to provide highly stable beams and accurate doses will enable calibrations with smaller uncertainties.

The new technology allows it to calibrate the full range of beam qualities currently in therapeutic use in the UK in a very short period of time. This will allow hospitals to deliver more accurate and effective radiation doses to cancer patients.

The new facility helps the UK respond to a recent report from the National Radiotherapy Advisory Group which states that the UK has a huge gap between the number of people treated with radiotherapy and optimal treatment levels.

For further information, please contact James Manning

Find out more about NPL's research in Ionising Radiation

Daily drug restores sight to hereditary blind

A hereditary form of blindness has been delayed or reversed for the first time by a daily drug treatment. The drug is the first to benefit people with a disease of their mitochondria, the energy powerhouses of cells.

There had been no way to halt the rapid onset of blindness in people with the most common mitochondrial disease, called Leber's hereditary optic neuropathy. It strikes men in their twenties, leading to total blindness within three to six months of the first symptoms appearing.

But after receiving a drug called idebenone for six months, some people whose sight had begun to deteriorate reported drastic improvements in their vision that continued after the trial ended.

In the trial, 55 people received idebenone and 30 were given a placebo. After six months, 11 people who received idebenone could read an extra two lines on a standard vision chart – and nine people who could not read any letters at the outset could by the end.

"This is not a cure, but it's a significant effect," says team leader Patrick Chinnery of Newcastle University in the UK.

Successful treatment

It is also the first time that an inherited mitochondrial disease has been successfully treated. "This trial tells us there's hope for this and other mitochondrial diseases," says Chinnery.

The drug didn't work for everyone. The beneficiaries were those who, at the outset, had better vision in one eye than the other. Chinnery thinks this disparity means the disease is only just beginning to progress, and so is more treatable.

The disease strikes retinal ganglion cells that connect the light-sensitive cells of the retina to the brain via the optic nerve. Damage results from failure of mitochondrial enzymes to deliver electrons efficiently through the chain of reactions that generate energy. Idebenone is thought to deputise for these defective enzymes.

Chinnery says there were no serious side effects to the drug, and suggests that if carriers of the mutations can be identified through genetic testing, it might be possible to prevent blindness by giving the drug before symptoms develop.

He adds that it may be possible to use idebenone to treat other mitochondrial diseases. One possible candidate is Melas syndrome, a disorder resulting from defects in the ability of mitochondrial enzymes to clear lactic acid "waste" from cells, leading to brain swelling, heart and muscle weakness and a variety of other symptoms.

"It's a great first step, and the suggestion that some patients benefit justifies further trials," says Robin Ali of University College London, who is head of an ongoing gene therapy study in 12 people with Leber's congenital amaurosis, a non-mitochondrial congenital form of childhood blindness.

Journal reference: Brain, DOI: 10.1093/brain/awr170

Targeted cancer therapy kills prostate tumor cells

A new targeted therapy for prostate cancer halts tumor growth in animals with advanced prostate cancer that is resistant to hormone therapy, a new study finds.

The results will be presented Saturday at The Endocrine Society’s 93rd Annual Meeting in Boston.

“This targeted therapy may provide a treatment breakthrough that will extend the lives of men with advanced, hormone-refractory prostate cancer,” said lead investigator Shuk-mei Ho, PhD, chairwoman of the Department of Environmental Health at the University of Cincinnati.

Men with prostate cancer that has recurred or has spread outside the prostate routinely receive androgen deprivation therapy, which blocks the action of the male hormones.

This castration occurs through surgical removal of both testes or more often with medications. Although effective, this hormone-blocking treatment eventually stops working in some patients, Ho said.

“These patients are left with very few treatment options and usually succumb quickly to the disease,” she said.

Ho’s team previously found they can inhibit the growth of prostate cancer cell lines in culture by targeting and activating a protein called G protein-coupled receptor 30 (GPR30) using the experimental drug G-1, a GPR30 agonist, or stimulator.

In their new study, funded by the Veterans Affairs and the National Institutes of Health, Ho and her co-workers tested G-1 in an animal model of castration-resistant prostate cancer.

They implanted human prostate cancer cells beneath the skin of male mice. The established tumor regressed upon castration and after the cancer relapsed, they injected the mice with a low dose of G-1.

They also gave G-1 to noncastrated, or “intact,” male mice that had prostate tumors. In these intact mice that still had male hormones, G-1 did not stop growth of the prostate tumors or cause substantial death of tumor cells (necrosis), they found.

“Surprisingly, G-1 was highly effective in halting the growth of the tumors that re-emerged after castration,” Ho said.

The castration-resistant tumors showed a 65 percent necrosis. These mice had increased expression of GPR30 after castration, which Ho believes sensitised prostate tumors to the cell growth-inhibiting effects of G-1.

“These results mean G-1 won’t work without androgen deprivation therapy,” she said.

Therefore, Ho reported, the window of time when this targeted therapy might be effective for treating hormone-resistant prostate cancer is after androgen deprivation therapy.

She said she believes G-1 can make androgen blockade more effective. G-1 caused no harm to the prostate or other vital organs in mice, she added.

Although GPR30 may have a role in cell growth in female tissues, Ho said it appears to have the opposite effect in men with hormone-resistant prostate cancer.

“The beauty of this GPR30 is that it does not have any estrogen, and so it will not cause any estrogen related side effects.” she said.

Major breakthrough in preventing premature birth

A groundbreaking clinical study of a new method for preventing premature birth in millions of women each year, published in the medical journal Ultrasound in Obstetrics & Gynecology, shows that the rate of early pre-term delivery in women (<33 weeks) can be reduced by 45%, simply by treating pregnant women at risk with a low-cost gel of natural progesterone during the mid-trimester of pregnancy until term.

The peer-reviewed findings were led by the Perinatology Research Branch of the National Institutes of Health, housed by the Wayne State University School of Medicine at Hutzel Hospital in Detroit. The findings are certain to have substantial impact on the practice of medicine, according to the principal investigator of the three-year clinical trial.

The study is entitled Vaginal progesterone reduces the rate of pre-term birth in women with a sonographic short cervix: a multicenter, randomised, double-blind, placebo-controlled trial. “The study published today offers hope to women, families and children,” said Dr. Roberto Romero, Chief of the Perinatology Research Branch of the NIH.

“Worldwide, more than 12 million premature babies (500,000 of them in the US) are born each year, and the results are often tragic. Our clinical study clearly shows that it is possible to identify women at risk and reduce the rate of pre-term delivery by nearly half, simply by treating women who have a short cervix with a natural hormone – progesterone.” Dr. Romero, principal investigator of the study, and Sonia S. Hassan, M.D., the lead author of the study.

Sonia S. Hassan is an associate professor of obstetrics and gynecology in the WSU School of Medicine. He also pointed out that numerous studies (many by the PRB) over the past decade have shown that ultrasound of the uterine cervix can identify pregnant women who are at high risk for pre-term delivery.

The ultrasound examination is simple to perform, painless, and can be performed between the 19th and 24th weeks of pregnancy. Pregnant women with a short cervix (one that is < 20mm) are at very high risk for preterm delivery.

Dr. Romero added that, once a high-risk mother for pre-term delivery has been identified, she can be offered treatment with progesterone. Of major interest is that progesterone reduced the risk of preterm delivery not only at <33 weeks, but also at <28 weeks (one of the secondary endpoints of the study).

It also reduced the rate of infant respiratory distress syndrome, the most common complication of premature babies. “We believe that the data in our study speaks for itself – and we predict that it will have major implications for obstetrics.”
 
Read more here

NASA Light Technology Successfully Reduces Bone Marrow Cancer Patients Painful Side Effects

A NASA technology originally developed for plant growth experiments on space shuttle missions has successfully reduced the painful side effects resulting from chemotherapy and radiation treatment in bone marrow and stem cell transplant patients.

In a two-year clinical trial, cancer patients undergoing bone marrow or stem cell transplants were given a far red/near infrared Light Emitting Diode treatment called High Emissivity Aluminiferous Luminescent Substrate, or HEALS, to treat oral mucositis -- a common and extremely painful side effect of chemotherapy and radiation treatment.

The trial concluded that there is a 96 percent chance that the improvement in pain of those in the high-risk patient group was the result of the HEALS treatment.

"Using this technology as a healing agent was phenomenal," said Dr. Donna Salzman, clinical trial principal investigator and director of clinical services and education at the Bone Marrow Transplant and Cellular Therapy Unit at the University of Alabama at Birmingham Hospital. "The HEALS device was well tolerated with no adverse affects to our bone marrow and stem cell transplant patients."

The HEALS device, known as the WARP 75 light delivery system, can provide a cost-effective therapy since the device itself is less expensive than a day at the hospital and a proactive therapy for symptoms of mucositis that are currently difficult to treat without additional, negative side effects.

The device could offer patients several benefits: better nutrition since eating can be difficult with painful mouth and throat sores; less narcotic use to treat mouth and throat pain; and an increase in patient morale -- all of which can contribute to shorter hospital stays and less potential for infection, added Salzman.

LEDs are light sources releasing energy in the form of photons. They release long wavelengths of light that stimulate cells to aid in healing. HEALS technology allows LED chips to function at their maximum irradiancy without emitting heat. NASA is interested in using HEALS technology for medical uses to improve healing in space and for long-term human spaceflight.

NASA - NASA Light Technology Successfully Reduces Cancer Patients Painful Side Effects from Radiation and Chemotherapy

New Research: Prostrate Cancer Tumour Imaging

More than 200,000 men are diagnosed with prostate cancer each year and 28,000 die from it, making it one of the most common cancer in men nationwide and also one of the leading causes of cancer death in men, according to the Centres for Disease Control.

Yet the disease ranges widely in its rate of growth and aggressiveness, according to John Kurhanewicz, PhD, a UCSF expert in prostate cancer imaging. As a result, there is great debate over the ideal strategy for treating the disease, he said, leaving patients with a difficult and potentially life-changing decision over how aggressively to respond to the disease.

“This test could give both physicians and patients the information they need to make that decision,” said Kurhanewicz, whose work with Dan Vigneron, PhD, and their colleagues from the UCSF Department of Radiology and Biomedical Imaging first linked a prostate tumour’s production of lactate to tumour aggressiveness. Other researchers also have linked that lactate production to tumour aggressiveness and response to therapy in other cancers.

The method uses compounds involved in normal tissue function — in this case, pyruvate, which is a naturally occurring by-product of glucose, and lactate, also known as lactic acid — and uses newly developed equipment to increase the visibility of those compounds by a factor of 50,000 in a magnetic resonance imaging (MRI) scanner.

That process requires pyruvate to be prepared in a strong magnetic field at a temperature of minus 272O C, then rapidly warmed to body temperature and transferred to the patient in an MRI scanner before the polarisation decays back to its native state.

The result is a highly defined and clear image of the tumour’s outline, as well as a graph of the amount of pyruvate in the tumour and the rate at which the tumour converts the pyruvate into lactate.

The sterile production process requires a dedicated clinical pharmacist with the knowledge of both quality control and of clinical practice.

The procedure must take place within minutes, which meant integrating a clean room into the scanning facility. QB3 also worked with GE Healthcare in designing Byers Hall, in which the Surbeck Laboratory of Advanced Imaging is housed, to accommodate the extremely strong magnetic field of the MRI scanner and enable time-sensitive experiments.

“All of that insight is why we moved this technology to Northern California,” said Jonathan Murray, general manager, Metabolic Imaging at GE Healthcare. “This is a huge accomplishment UCSF and QB3 have achieved.

They brought together the best engineering from UC Berkeley and the best bioscience and pharmacy knowledge from UCSF, and are now demonstrating the technology in a world-renowned academic medical centre.

We are delighted with the speed of progress of this collaboration. The science is very exciting.”

Dry AMD treatment: diabetics may escape PDR

Proven Arthritis Drug Shows Promise versus Dry AMD:

While ophthalmologists can turn to several medications for patients with vision-threatening “wet” age-related macular degeneration (AMD), there are no effective treatments for advanced “dry” AMD, the more common form.

Today a research group led by Jason S. Slakter, MD, New York University School of Medicine, reports on a phase-two clinical trial of fenretinide, a synthetic derivative of vitamin A.

Risk of developing wet AMD decreased almost two-fold in dry AMD patients who took the medication. Geographic atrophy (GA) lesion growth was also reduced in the fenretinide group.

This reduced growth correlated with lowered blood levels of the biomarker retinol binding protein (RBP) — an indication that fenretinide was working. Patients whose RBP decreased 60 percent or more also had the most significant reductions in lesion growth.

GA lesions degrade the area of the eye called the retinal pigment epithelium (RPE), which can result in significant vision loss.

Advanced AMD, in either wet or dry form, can destroy the detailed, central vision we need to recognize faces, read, drive, and enjoy daily life. It is a major cause of vision loss in the United States.

In the advanced wet form abnormal new blood vessels develop under the retina, then bleed or leak fluid and form scars. Advanced dry AMD sometimes abruptly converts to the wet form.

Fenretinide works on three key AMD disease mechanisms: it has strong anti-inflammatory properties, inhibits abnormal blood vessel growth (angiogenesis) and reduces vitamin-A derived toxins such as A2E and lipofuscin. These toxins accumulate in the RPE and interfere with its ability to nourish light-receptor cells in the retina.

“Evidence from our study and others points to fenretinide’s potential to treat and prevent diseases of the retina,” Dr. Slakter said.

Visit the American Opthamology Academy’s Web site at www.aao.org

Treatment of retinal conditions

“Retinal disease is highly prevalent among older individuals, and both age-related macular degeneration (AMD) and diabetic retinopathy account for more than half the irreversible blindness in older Americans. The prevalence of both macular degeneration and diabetic retinopathy increases with age, and the number of Americans affected by these conditions is expected to increase substantially as the number of Americans older than 65 years doubles from 2010 to 2040,” the authors write as background information in the article.

“The last decade has seen substantial changes in the treatment options available for many retinal diseases, particularly in the treatment of neovascular AMD,” a form of the disease involving abnormal blood vessel growth in the eye.

Pradeep Y. Ramulu, M.D., M.H.S., Ph.D., of Wilmer Eye Institute, Johns Hopkins University, Baltimore, and colleagues analyzed Medicare fee-for-service data claims filed between 1997 and 2007. Overall, the number of retinal procedures performed increased 192 percent. Increases occurred each year except between 1997 and 1998; the largest year-to-year increase in volume, 20 percent, occurred between 2006 and 2007.

“Procedure volumes changed most markedly for treatments directed toward neovascular AMD,” the authors write. New treatments for this condition include intravitreal therapy — injections of drugs administered directly into the eye — of antibodies that block the formation of new blood vessels. Between 1997 and 2001, fewer than 5,000 such injections were performed each year. However, rates more than doubled each year through 2006, increasing between 2001 (when 4,215 of these procedures were performed) and 2007 (when injections totaled 812,413).

Photodynamic therapy, a laser treatment for neovascular AMD approved in 2000, peaked in 2004 with 133,565 procedures and then decreased 83 percent to 22,675 procedures in 2007. Laser treatment of choroidal lesions (potentially cancerous eye tumors) and neovascular AMD also decreased 83 percent, from a peak of 82,089 in 1999 to 13,821 in 2007.

Vitrectomy — surgical removal of the gel inside the eye, used to treat retinal detachments — increased 72 percent, from 11,212 in 1997 to 19,923 in 2007. Scleral buckling, a treatment for the same condition involving placing a silicon buckle around the eye, can be performed with or without vitrectomy. Scleral buckling alone became less common during the study period (a 69 percent decrease, from 8,691 to 2,660).

“Observing use patterns adds value, because it demonstrates how disease is treated and can be used to identify possible discrepancies between the best evidence-based treatments for a condition (as defined by clinical trials and meta-analyses from the literature) and current practice patterns,” the authors conclude. “In this report, we observe that intravitreal injections of pharmacologic agents have gained widespread acceptance for the treatment of neovascular AMD and that vitrectomy is being increasingly applied to a wide range of retinal conditions.”

(Arch Ophthalmol. 2010;128[10]:1335-1340. Available pre-embargo to the media at www.jamamedia.org.)

Research finds surgery outperforms drug therapy in treatment of benign prostatic hyperplasia

Research finds surgery outperforms drug therapy in treatment of benign prostatic hyperplasia — Science Blog

A 17-year-long community study looking at symptoms of enlarged prostate in over 2,000 men age 40 to 79 years suggests that surgery for benign prostatic hyperplasia (BPH) offers more relief from incontinence and obstruction symptoms than treatment from drug-based therapy, according to a new study by researchers at Mayo Clinic. The researchers presented their results today at the annual meeting of the American Urological Association.

Overall, results show:

* Urinary incontinence was a common condition, coexisting with BPH/lower urinary tract symptoms.
* In the community setting, patients with the highest symptom scores were most likely to receive surgical intervention.
* Symptoms stabilised and did not get worse after treatment of all kinds.
* Patients who underwent transurethral resection of the prostate (TURP) had the greatest decrease in both symptoms and incontinence compared to other treatment groups. Pre-TURP the incontinence rate was 64.5 percent and post-TURP it was 41.9 percent.

Significance
The findings provide large-sample, long-term data comparing the effectiveness of medical versus surgical treatments in a large, general population, as compared to small, select clinical populations of men. “Our data fills a gap in the research record that can be used by physicians and patients to evaluate management options,” says Amy Krambeck, M.D., Mayo Clinic urologist and lead study investigator. “Because it’s a large community-based study of more than 2,100 men, it includes the entire broad range of male health. This suggests the results are stronger in terms of being generalised and applied to other men.”

Background
BPH and lower urinary tract symptoms, such as frequent urge to urinate or leakage, are common. By age 60, an estimated 50 percent of all men suffer from enlarged prostate symptoms; by age 90, about 80 percent do. Multiple treatments exist but data comparing drug therapy to surgery are lacking, making clinical decisions vulnerable to subjective factors.

About the Study
From 1990 through 2007, the study enrolled 2,184 healthy men, age 40-79, living in Olmsted County, Minn., All participants completed surveys every other year about their urinary symptoms and the treatments they received. From this information, the investigators examined urinary problems and incontinence before and after different types of treatment.

Results showed that of the 2,184 men:

* 1,574 (72%) received no treatment for BPH symptoms.
* 307 (14%) took alpha adrenergic receptor blockers (α-ARs).
* 195 (9%) took the medication 5-alpha-reductase inhibitors (ARIs).
* 23 (1%) received surgical laser vaporization.
* 85 (4%) received surgical transurethral resection of the prostate (TURP).

Comments Dr. Krambeck: “After intervention, the greatest improvement in symptom score was seen in the TURP group, followed by laser vaporisation, then the drugs, 5 alpha reductase inhibitors and alpha adrenergic receptor blockers.

Only the surgical TURP group reported a decrease in incontinence – pre-TURP the incontinence rate was 64.5 percent and post-TURP it was 41.9 percent.”

This reduction in incontinence rates is significant when compared to the increase in reported incontinence in the patients receiving both forms of medical therapy and no change in symptoms for patients receiving laser vaporization.

Glaucoma's unique protein expression could enhance diagnosis and treatment

An eye under pressure appears to express a unique set of proteins that physicians hope will one day help them better diagnose and treat glaucoma.

Glaucoma, the second leading cause of blindness worldwide, tends to progress silently until decreased vision indicates trouble, said Dr. Kathryn Bollinger, Medical College of Georgia clinician-scientist specializing in glaucoma.

But inside fluid-filled eyeballs, a changing protein profile -- 30 with significant increases and 17 with significant decreases identified among hundreds of proteins present -- appears to also give a heads-up, Bollinger reported during the Association for Research in Vision and Ophthalmology Annual Meeting April 30-May 6. The MCG ophthalmologist received the 2010 ARVO/Alcon Early Career Clinician-Scientist Research Award for the study.

With glaucoma, elevated pressures inside the eyeball stress the optic nerve and nerve arms -- called axons ? that reach out to communicate with the brain. Over time, increased pressure can kill nerve cells and axons and decrease vision. "At this point, we don't have a regenerative strategy," Bollinger said.

The pressure results from an imbalance in fluid production and loss. In a healthy eye, the fluid, called the aqueous humor, moves continually from the back to the front of the eye where it exits ? mostly via a natural tract between the iris and cornea ? first into spongy tissue near the cornea's base called the trabecular meshwork then into the venous system and back into the body.

In open-angle glaucoma, the most common type in this country, the tract remains open but fluid still backs up and scientists suspect changes in the permeability of the trabecular meshwork may be to blame. Topical glaucoma treatments work by reducing fluid production or increasing outflow through a secondary drainage system, also near the front of the eye. Ophthalmologists such as Bollinger can also create a new pathway surgically if needed.

To get a better picture of what happens to the trabecular meshwork, Bollinger examined tissues from the outflow tracts and trabecular meshwork of patients with and without glaucoma. She added TGF-?, a protein and inflammatory element known as a cytokine that is consistently found at high levels in patients with open-angle glaucoma. After comparing treated and untreated tissue, she found that TGF-? resulted in a similarly unique protein pattern. Current therapies don't target TGF-? or its effects in the trabecular meshwork.

Next steps include identifying additional proteins expressed in glaucoma, determining the impact of the unique protein profile on the trabecular meshwork and clarifyingTGF-?'s normal role inside the eye, Bollinger said.

Risk factors for glaucoma include age, a family history and black and Asian ethnicity.


Link: http://www.mcg.edu

US Scientists ID key Ebola virus structure

Scripps Research Institute scientists say they've identified the structure of a key Ebola virus protein -- a major step that might help lead to a treatment.

The Ebola virus, although rare, is one of the deadliest viruses on Earth, killing 50 percent to 90 percent of those infected, scientists said.

There is currently no cure for Ebola hemorrhagic fever, no vaccine and no drug therapy. But the researchers said their finding of how a key component of the Ebola virus, called VP35, blocks the human immune system, allowing the virus uncontrolled replication, is an important advancement in understanding how the deadly virus works.

"After infection, the virus and immune system are in a race," said Associate Professor Erica Ollmann Saphire, who led the three-year study. "If the virus can hide its molecular signatures, it can suppress immune responses and replicate unchecked. This new understanding of the mechanism that Ebola virus uses to evade the immune system opens the door for developing drug therapies."

A signature of Ebola virus infection is its double-stranded RNA, which, when detected by immune system proteins, triggers a full immune response. The new research describes how the VP35 protein of the Ebola virus masks the double-stranded RNA to prevent the immune response.

The study is detailed in the early online edition of the Proceedings of the National Academy of Sciences. Read More.....

The Buteyko method for Asthma treatment - revisited

Normally, during an asthma attack, people panic and breathe quickly and as deeply as they can, exhaling more and more carbon dioxide. The breathing rate is controlled not by the amount of oxygen in the blood but by the amount of carbon dioxide, the gas that regulates the acid-base level of the blood.

Dr. Buteyko concluded that hyperventilation — breathing too fast and too deeply — could be the underlying cause of asthma, making it worse by lowering the level of carbon dioxide in the blood so much that the airways constrict to conserve it.

This technique may seem counterintuitive: when short of breath or overly stressed, instead of taking a deep breath, the Buteyko method instructs people to breathe shallowly and slowly through the nose, breaking the vicious cycle of rapid, gasping breaths, airway constriction and increased wheezing.

Benefits to swimmers
Swimmers have to stop to catch their breath after a few lengths of the pool because they take long deep breaths with every other stroke, whereas if you take in small puffs of air after several strokes, you can swim for longer, almost indefinitely, without becoming winded.