Nanoparticle device co. that could reduce drug-making costs gets fresh capital

Every researcher looking at drugs to cross the blood brain barrier should be rejoicing at this development. Too bad I'm not starting out in graduate school, fascinating possibilities for stroke research if only someone would take advantage of it.
http://www.medcitynews.com/2012/03/nanoparticle-device-co-that-could-reduce-drug-making-costs-gets-fresh-capital/?utm_source=rss&utm_medium=rss&utm_campaign=nanoparticle-device-co-that-could-reduce-drug-making-costs-gets-fresh-capital
A nanoparticle device company that produces devices that could reduce drug-making costs has secured follow-on funding from a Pennsylvania economic development agency.

Ben Franklin Technology Partners of Northeast Pennsylvania invested $50,000 in the business in its latest funding round and has allocated a total of $400,000 to it since 2008.

Xigo Nanotools is based in Danville, Pennsylvania and develops devices that pharmaceutical companies use for drug formulation development. The company plans to use the investment to make manufacturing preparations as it prepares to expand sales.

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Its main instrument, the Acorn Area device, is a patented, shoebox-size device that rapidly measures the wetted surface area of nanoparticles using magnetic resonance imaging. The measurements tell pharmaceutical companies both the extent and the nature of the particle liquid interface.”Drugs generally have to be dissolved in order for them to provide a therapeutic benefit and the bioavailability of drugs is directly related to their wetted surface area,” said Sean Race, the co-founder of the company.

The company was co-founded by Race and Dr. David Fairhurst in 2005, and it started selling its devices in 2010. In response to emailed questions, Race said: “Most drugs are manufactured, delivered or consumed as suspensions of particles in a liquid. … If you can re-engineer the active particle ingredient (API) particles to achieve the same therapeutic benefit at a lower concentration, then you save more money, and less drug is metabolized, so there is a secondary benefit to the consumer.”

Nanoparticle properties are key predictors of material performance and there currently are no efficient methods to measure wetted nanoparticle surface area, according to a statement from Ben Franklin that describes the company. In addition to pharmaceuticals, the device also has applications for energy, electronics and ceramics.

The company worked with Johnson & Johnson (NYSE:JNJ) to establish its first beta site.

Race added: “In addition, we can provide information about the drug formulation such as physical stability, so we are involved in formulation development as well as process development and, in the long run, quality labs, although we don’t have any applications in pharma that well advanced.”

Race said the company is seeking to raise $2 million and is in investment discussions with a few different venture groups.

The use of nanoparticles has been a growing source of interest in medicine, particularly in the past decade, since nanoparticles could potentially be directed to specific, targeted cells such as cancer cells and be used to develop more targeted, tailored treatments for individuals. Some companies are developing gold nanoparticles to treat cancer, like CytImmune. Although there has been some criticism that the market forecast for nanoparticles has been overhyped at the expense of some potential risks, the outlook is still strong.

Stroke Costs Reaching Trillions Without Action, Financial Cost of Strokes to Reach $2.2 Trillion by 2050

Only from 2006. Where is the outcry about reducing these costs by finding a cure for damaged/dead neurons? If we don't start now insurance companies will decline to pay for any stroke costs because strokes are totally preventable.
You caused your problem you can live with it. Personal responsibility and all. 

Stroke Costs Reaching Trillions Without Action, Financial Cost of Strokes to Reach $2.2 Trillion by 2050

"If our society is not going to do it for the right reasons, perhaps we can do it because it's going to be obscenely expensive."
This does make an assumption that we as a country still care about helping others. Vacines were created/used to reduce the burden of childhood diseases and that was government driven.

Rejoyce - Stroke Rehab at Home

Australia and Canada are far ahead of the US and the rest of the world on providing better access to rehab. Only 3 minutes long.
http://visions.unimelb.edu.au/episode/66
The ReJoyce workstation consists of a table-top mount, a spring-loaded arm, and hand dexterity trainer called a manipulandum assembly. The arm suspends the assembly at a comfortable height for the hands, and gives a user the freedom to move the assembly through his or her entire range of motion. The assembly features two horizontal handles, a pressure gripper, a doorknob, a key, a peg, a jar top, and two coin simulators, allowing for simulation of almost any task of daily living — from pouring a glass of orange juice to using a pen.
An Australian first University of Melbourne and Austin Health study will test home-based online rehabilitation with video games to give spinal cord injury patients the hope of regaining the movement of their hands.
More information about the launch of the Rejoyce Workstation can be found at http://newsroom.melbourne.edu/news/n-70.

Alzheimer’s Challenge 2012

An innovative stroke association would already have foundation support to issue such a challenge for stroke research and rehabilitation.
ASA or NSA??? Are you innovative or not?
https://www.alzheimerschallenge2012.com/about/about_the_challenge.php

the Challenge

The Alzheimer’s Challenge 2012 seeks the development of simple, cost-effective, consistent tools that could be easily used to assess memory, mood, thinking and activity level over time to help improve diagnosis and monitoring of people with Alzheimer’s disease. Today, easy to use, reliable, objective and cost-efficient methods to track and monitor Alzheimer’s disease -- which is not a normal part of aging -- remain an unmet need. The Alzheimer’s Challenge 2012 supports the U.S. Department of Health and Human Services (HHS) call to harness new thinking to deliver better care and better health at lower cost and provides an entrepreneurial springboard to harness new thinking and approaches to improve Alzheimer’s care.

The Alzheimer’s Challenge 2012 includes awards totaling $300,000. This incorporates $25,000 to five finalists and $175,000 to one winner of the Challenge.

Following the March 16, 2012 submission deadline, five finalists will be selected and announced by April 16, 2012. Each finalist will be awarded $25,000. Concept refinement will be completed by mid June 2012 with finalist presentations to follow. The winner of the Challenge will be announced at the end of June 2012 and awarded a $175,000 prize. Judges will be drawn from experts in the Alzheimer’s community and other related fields.

Nervous System Stem Cells Can Replace Themselves, Give Rise to Variety of Cell Types, Even Amplify

Missed this last summer, stem cells that not only create neurons but new stem cells. I need this.
http://www.hopkinsmedicine.org/news/media/releases/nervous_system_stem_cells_can_replace_themselves_give_rise_to_variety_of_cell_types_even_amplify
Johns Hopkins team has discovered in young adult mice that a lone brain stem cell is capable not only of replacing itself and giving rise to specialized neurons and glia – important types of brain cells – but also of taking a wholly unexpected path: generating two new brain stem cells.

A report on their study appears June 24 in Cell.

Although it was known that the brain has the capacity to generate both neurons, which send and receive signals, and the glial cells that surround them, it was unclear whether these various cell types came from a single source. In addition to demonstrating that a single radial glia-like (RGL) brain cell is able to generate two very different functional cell types, the Hopkins researchers, by following the fates of single cells over time, found that a single brain stem cell can even produce two stem cells like itself.

“Now we know they don’t just maintain their numbers, or go down in number, but that stem cells can amplify,” says Hongjun Song, Ph.D., professor of neurology and neuroscience and director of the Stem Cell Program in the Institute for Cell Engineering, the Johns Hopkins University School of Medicine. “If we can somehow cash in on this newly discovered property of stem cells in the brain, and find ways to intervene so they divide more, then we might actually increase their numbers instead of losing them over time, which is what normally happens, perhaps due to aging or diseases.”

The researchers’ findings hinged on a decision to single out and follow lone, radial glia-like cells, instead of labeling and monitoring entire stem cell populations in the mouse brain. They took this approach because they suspected radial glia-like cells were essentially stem cells, having been shown in previous studies to give rise to neurons.

Using mice genetically modified with special genes that color-code cells for easy labeling and tracking, the Hopkins team injected a very small amount of a chemical into about 50 mouse brains to induce extremely limited cell labeling.

“It’s a simple idea that forced us to confront a lot of complex technical issues,” Song says. “With so many millions of cells in the relatively large mouse brain, labeling a single stem cell and then chasing its family history was like finding a needle in a haystack.”

The scientists developed computer programs and devised a new imaging technique that allowed them to examine stained slices of the mouse brain and, ultimately, follow single, randomly chosen radial glia-like stem cells over time. The method allowed them to track down all the new cells derived from a single original stem cell.

“We reconstituted single stem cells’ family trees to look at the progeny they gave rise to,” says Guo-li Ming, associate professor of neurology and neuroscience and a member of the Neuroregeneration Program in the Institute for Cell Engineering. “We discovered that single cells in an intact animal nervous system absolutely do exhibit stem-cell properties; they are capable of both replicating themselves and producing different types of differentiated neural progeny.”

The team followed the fates of all the marked radial glia-like stem cells for at least a month or two, and examined some a full year later to discover that even over the long term, the “mother” cell was still generating itself as well as different kinds of progeny.

In addition, the researchers investigated how these RGLs were activated on a molecular level, focusing, in particular, on the regulatory role of an autism-associated gene called PTEN. Conventional wisdom was that deleting this gene led to an increase in stem-cell activation. However, the scientists demonstrated that was a transient effect in the mouse brains, and that, ultimately, PTEN deletion leads to stem-cell depletion.

Support for this research came from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Maryland Stem Cell Research Foundation.

UAB Explores Innovative Stroke Therapies

I wonder if this trial started in 2011 and the results.
http://www.uab.edu/uabmagazine/2010/september/stroke
In 1947, as tension between Russia and the United States threatened to erupt into nuclear war, the Bulletin of the Atomic Scientists added a new element to its cover: a stylized clock face with the hands set at seven minutes to midnight. For the past 63 years, the clock’s minute hand has moved back and forth to reflect the imminence of nuclear holocaust.
In the world of stroke care, the countdown to doomsday begins as soon as the brain’s oxygen supply is disrupted, either through a blood clot (ischemic stroke—the cause of 80 percent of strokes) or by bursting blood vessels (hemorrhagic stroke, which accounts for the other 20 percent of cases). Stroke kills more people worldwide than any other disease. It is the third leading cause of death in the United States and the leading cause of serious, long-term disability.
For years, the stroke clock was set at three hours. Patients receiving emergency treatment before that time stood a good chance of recovering significant function; after the three-hour window closed, there wasn’t much hope. But new advances in stroke treatment are steadily pushing open the treatment window and adding precious time back onto the clock. Neurologist Andrei Alexandrov, M.D., and his team at the UAB Comprehensive Stroke Research Center are contributing many of those breakthroughs, developing and testing revolutionary therapies that are effective several hours, days, and even weeks after stroke onset.

Rescue Squad:
Time Since Stroke – Up to 4.5 Hours

Left to right: Damon Patterson, Andrei Alexandrov, and Anne Alexandrov. Andrei Alexandrov is leading a team of researchers and clinicians testing innovative new stroke therapies.

One of Alexandrov’s goals is to increase use of the powerful clot-busting drug tPA (tissue plasminogen activator)—and develop new ways to enhance its effects. In 2006, the year before Alexandrov arrived at UAB, four patients received tPA; in 2009, 106 UAB patients received the drug, with very few tPA-related complications, he notes.
Although tPA is very effective at dissolving blood clots and lowering a patient’s risk of permanent disability, many physicians are reluctant to use it. Determining if a stroke victim is a viable candidate for tPA requires specialized knowledge and experience; the drug also increases the risk of bleeding, and administering it requires constant patient monitoring. Then there is its strict timeframe: tPA must be used within three hours of stroke onset—or so many physicians think. But that last restriction is no longer accurate, Alexandrov says. The American Stroke Association now supports use of tPA up to 4.5 hours from stroke onset.
UAB’s stroke unit is testing several ways to enhance tPA administration. In 2009, 40 patients at UAB were treated with intra-arterial rescue therapies, which include direct delivery of tPA to the clot in the brain, as well as use of devices capable of retrieving blood clots and stents that can keep arteries open. While there are currently no studies that show this type of treatment to be superior to tPA, it does provide an ability to treat stroke beyond the 4.5-hour window, Alexandrov says.

Interventional stroke neurologist Damon Patterson (right) and medical students in UAB's universal concept stroke unit.

The Unit When Andrei Alexandrov, M.D., joined UAB in 2007 as director of the university’s Comprehensive Stroke Research Center, one of his first moves was to establish a “universal concept stroke unit.” Whereas stroke patients were once scattered across the hospital, Alexandrov’s unit concentrates all critically ill stroke patients on the same floor—and those patients stay in the same room, with the same highly educated nursing and therapy team, from admission to discharge. The unit “is one of the first of its kind in the world,” Alexandrov notes. “This is essentially a one-stop unit with highly specialized interdisciplinary practitioners able to provide the latest scientific, evidence-based care and conduct cutting-edge clinical research.”

Alexandrov and the UAB stroke team are also leaders in the use of ultrasound to enhance tPA’s clotbusting effects. Ultrasound itself may help to break up clots in the brain’s arteries, especially in combination with tPA. In fact, two recent independent meta-analyses of this therapy—which was developed by Alexandrov—have shown it to be superior to tPA alone.
Alexandrov is now testing tiny, gas-filled “microspheres” that are delivered to the clot, then agitated using a small beam of ultrasound waves. (?Is this xenon gas? Is the gas the working object or the ultrasound?)When the ultrasound beam intercepts the bubbles it causes them to explode into the clot. In combination with tPA, these bubbles may help to break up the clot even further. In clinical trials conducted at UAB, ultrasound therapy was able to break up clots with twice the success rate of tPA alone.
Typically, tPA works primarily by partially breaking up a clot so that blood flow is established to areas of the brain deprived of oxygen; but tPA only breaks up clots completely 13 percent of the time. Alexandrov says his goal is to refine the ultrasound combo therapy to the point where 50 percent of clots are completely broken up in the ER.
But ultrasound therapy faces a major obstacle before it can achieve widespread use: Only a handful of people in the world have enough training to administer it properly. “Most stroke neurologists don’t know how to do it,” Alexandrov says. “People are excited, but few of them can use the technology.” So Alexandrov has developed an automated treatment “helmet” that fits over a patient’s head and will allow emergency-room personnel to provide the therapy with only limited prior training. “It’s just like putting on a pair of glasses,” Alexandrov says. He has been tapped by the National Institutes of Health to lead a worldwide clinical trial to test the efficacy of the helmet; the trial will launch in 2011.

Saving the Brain:
Time Since Stroke – Up to 4.5 Days

UAB interventional stroke neurologists such as Damon Patterson use new techniques to remove clots deep in the brain up to several days post-stroke.

While tPA-based therapies attack clots chemically, UAB neurologists are also exploring new ways to remove clots physically—and in the process treat stroke patients who would have been written off as hopeless cases only a few years ago. Adapting innovations originally pioneered in cardiology, interventional stroke neurologists such as Damon Patterson, M.D., are reporting fascinating advances in the new field of endovascular therapy. Using advanced imaging techniques, they guide catheters deep into the brain to remove clots and restore blood flow.
UAB is a nationally recognized leader in endovascular therapy, and its physicians frequently receive calls from other hospitals about their stroke cases, says Patterson. “We listen to their report and advise administering tPA if it’s appropriate,” he explains. “Then we rush the patient here to our cath lab in order to extend the response time window and hopefully provide a good outcome.”
Seven to eight hours post-stroke is generally regarded as the effective limit for neuro-endovascular therapy, Patterson notes, but new imaging techniques are allowing physicians to widen that timeframe. “Each person’s brain is unique and responds to a stroke in its own way,” he says. “New ways of looking at the brain quickly, such as reperfusion, allow us to determine which parts of the brain are already damaged and which parts are at risk of becoming damaged. We then use that info to determine if there is enough brain to save and if it’s going to be safe to try to save it.”
This makes rigid treatment timelines obsolete, Patterson says. “With these newer devices, we can extend the time window almost indefinitely.” Those extra hours are especially useful when treating “wakeup strokes”—when people wake up in the morning with symptoms, Patterson explains. “You have to go back to when they were last seen normal, which most of the time is when they went to bed the night before. We don’t know at what point during the night that the stroke actually started. With perfusion imaging, we might see that there is a whole bunch of brain to save and very little has been permanently damaged. It’s also wonderful because we’re able to extend time windows so that rural hospitals without these imaging capabilities can get stroke victims to us.”
UAB neurologists recently used neuro-endovascular therapy to remove a clot from a patient an unheard-of four-and-a-half days after stroke onset.

Membrane Trafficking and Endothelial-Cell Dynamics During Angiogenesis

Only 28 pages and I learned something new, vasculogenesis vs angiogenesis, I wonder which is more applicable for us survivors that have lots of dead area. Cool diagrams in the pdf, sections listed, details at the link.

http://cdn.intechweb.org/pdfs/31164.pdf
1. Introduction
The formation of new blood vessels, or neovascularization, involves multiple processes,
including cell proliferation and migration, cell-cell and cell-matrix adhesion, and tube
morphogenesis. Neovascularization can occur through one of two events: vasculogenesis,
the de novo formation of blood vessels from angioblasts; or angiogenesis, the extension of
new vessels from a pre-existing vasculature. Among these, angiogenesis in particular is
relevant throughout life; its dysregulation has been causally related to several disorders that
involve malignancy, inflammation, and ischemia. Angiogenesis is thought to depend on a
set of signaling proteins – including certain kinases, integrins and vascular endothelial
growth factor receptor-2 (VEGFR2) – that are enriched in specific plasma membrane
domains. Both physiological and pathological angiogenesis rely on intracellular trafficking,
a process that governs signaling by such proteins, as well as cell motility.
In this chapter, we discuss our current understanding of angiogenesis from the perspective
of trafficking of the membrane components that are responsible for endothelial-cell (EC) dynamics.
2. Angiogenesis: Mechanism and importance

Fig. 1. Schematic representation of a mature blood vessel. Endothelial cells at the luminal
side line tubular blood vessel. The smooth muscle cells and the pericytes that remain in
contact with the endothelial cell lining through the basement membrane strengthen this
tubular structure.
2.1 Vasculogenesis
2.2 Angiogenesis
2.3 Pathological angiogenesis
3. Ligands and receptors in angiogenesis
3.1 The VEGF-VEGFR system coordinates the process of angiogenesis
3.1.1 VEGF
3.2 VEGF receptors
3.2.1 VEGFR1
3.2.2 VEGFR2
3.2.3 VEGFR3
3.2.4 Neuropilins (NRP)
3.3 Role of the extracellular matrix (ECM) in endothelial-cell interactions during angiogenesis
3.4 Role of Integrin in endothelial-cell dynamics during angiogenesis
4. Membrane trafficking
4.1 Biosynthetic/secretory pathway
4.2 Endocytic and exocytic pathways
4.3 Endocytic trafficking of VEGFR2
4.4 Secretory transport of VEGFR2
4.5 VEGFR2 trafficking and angiogenesis

ALZConnected connects caregivers, people living with Alzheimer's

So which stroke association is going to do something like this for survivors? Or are they just going to sit back and say, 'We provide links to local stroke groups' I'm waiting, waiting, waiting!!!.
https://www.alzconnected.org/

Jumping Genes in the Brain Ensure That Even Identical Twins Are Different

So lets identify some jumping genes that can reprogram themselves to take over and recreate functionality that was damaged/died during our strokes.
http://www.scientificamerican.com/article.cfm?id=what-makes-each-brain-unique

• Genes we inherit and environmental factors both influence human behaviors. Scientists have recently discovered other underlying processes at work.
• So-called jumping genes, segments of DNA that can copy and paste them­selves into new places in the genome, can alter the activity of full-length genes. Occasionally they will turn on neighboring genes in these locations. That activity occurs more in the brain than other areas, resulting in different traits and behaviors, even in closely related individuals.
• These mobile genetic elements may also turn out to play a role in people’s disposition to psychiatric disorders.
• Researchers are now beginning to investigate whether jumping genes help us adapt to rapidly changing environmental conditions.

Peroneal FES Better than AFO for Chronic Foot Drop Patients Post-Stroke, Study Finds

The problem here is that they don't tell you what type of FES they are using; plain eStim, Bioness, WalkAide?
http://www.ptproductsonline.com/news/2012-03-07_01.asp
While walking ability of individuals with chronic foot drop phase post-stroke has been found to be better with functional electrical stimulation (FES) of the peroneal nerve than without an orthotic device, evidence is conclusive as to whether peroneal FES is also better that ankle-foot orthosis (AFO) in this regard. A recent study, published in the March 2012 issue of Physical Therapy, aims to identify potential benefits of peroneal FES as opposed to an AFO with respect to the ability to negotiate a sudden obstacle.

Led by Roos van Swigchem, PT, MSc, from the department of rehabilitation at the Radboud University Nijmegen Medical Centre and Nijmegen Centre for Evidence-Based Practice, Nijmegen, the Netherlands, the research team fitted 24 community-dwelling people with stroke who regularly used polypropylene AFO with a transcutaneous FES device. The average age of the participants was 52.6 years.

After 2 weeks and 8 weeks, the researchers tested participants’ obstacle avoidance ability by asking them to avoid 30 obstacles suddenly dropped on a treadmill in front of the affect leg as the participants walked with either FES or AFO. The obstacle avoidance success rates were determined.

According to the results, success rates were higher with FES than with AFO, especially after adjustment for individual leg muscle strength. Participants with relatively low muscle strength were found to most likely benefit from FES in regards to obstacle avoidance ability.

The researchers conclude that peroneal FES seems to be superior to an AFO when it comes to obstacle avoidance ability in community-dwelling people with stroke. However, they note that further work is needed to determine whether the results may be generalized to other groups of people with stroke.

Biochemical Switch Linked To Stroke And Heart Disease - How It Turns On

How many researchers should be jumping on this to find out how to turn this into a prevention therapy?
http://www.medicalnewstoday.com/articles/242615.php
The science journal Proceedings of the National Academy of Sciences , has reported that scientists from the University of Leicester and Cardiff University have achieved a breakthrough in understanding how a 'biochemical switch', known as P2X1, which is associated with strokes and heart disease is 'turned on'.

Professor Richard Evans of the University of Leicester's Department of Cell Physiology & Pharmacology, who led the research explained:

"P2X1 receptors are protein molecules expressed on blood platelets which are cells involved in blood clotting. Drugs that block these receptors have the potential to reduce "dangerous" blood clotting that leads to strokes and heart attacks. Our research has looked at how the P2X1 receptor is "turned on". By biochemical studies and purifying the P2X1 receptor and using an electron microscope we have 'visualized' the receptor and detected changes in its shape when it is activated.

The P2X1 receptor is made of three identical parts and we have shown that activation leads to these twisting against each other. We found that if we chemically locked the receptor to stop this twisting, then the P2X1 receptor could not be fully activated. This is important as it gives the first realistic insight into how these novel receptors are turned on."

Evans concluded saying:

"This work will help to develop drugs that can stop the P2X1 receptor being "turned on" and would be useful to prevent stroke and heart attack."

Why a Cat's Purr Can Lower Heart Attack Risk

Something that came out of the Stroke research Center at the University of Minnesota. I'll have to further check them out to see if they need some expert help with this kind of stuff.
http://www.petside.com/article/why-cats-purr-can-lower-heart-attack-risk
Cats are such a calming presence in our lives that they reduce the risk of having a heart attack by 40 percent, according to a research study.
I’m not surprised. Burying my face in my cat’s warm, silky fur has helped me calm down numerous times.
She may even be saving my life.
The study, a 10-year endeavor from the Stroke Research Center at the University of Minnesota looked at 4,435 Americans aged 30 to 75, and also found that cats reduce the risk of dying from other heart diseases and stroke by 30 percent.
More specifically, it could be a cat’s purr that’s putting hearts at ease.
Animal behavior consultant Steve Dale told the Chicago Tribune that cats use their purr as a calming mechanism to communicate with their kittens. “They’ll purr when they’re content, but they’ll also purr when they’re about to be euthanized.”
In that way, they may be communicating with us as well.
This animal connection, Dale explained, "alters our neurochemistry.” Our cats are helping us relax just like they do their own kittens.
I’ve often dismissed the idea of my tiny black cat mothering me as being silly. But I have thought about it.
For instance, when I’m particularly stressed, I have the less than delightful habit of of shooting up out of a deep sleep, gasping for breath, caught somewhere between a bad dream and my warm bed.
At these times my cat shimmers into existence without fail. She hears me and hops up to my lap from her own warm sleeping spot, purring away. She anchors me in my safe reality then helps me quickly fall back to sleep.
Thinking about this simple, but vital ritual of ours makes that 40 percent seem a lot less astounding, and the fact that not everyone has a cat more so.
If you’ve been considering adopting a cat, you might be saving two lives

Severe Brain Injury Warrants Bold Moves

And just think, there is nothing similar for stroke or its well hidden.
http://www.medpagetoday.com/CriticalCare/HeadTrauma/31525?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&eun=g424561d0r&userid=424561&email=oc1dean@yahoo.com&mu_id=

Early, aggressive treatment of patients with severe traumatic brain injury appears to be cost-effective compared with less aggressive approaches, an analytical model showed.

Compared with a routine strategy, an aggressive approach resulted in a greater gain in quality-adjusted life years (QALYs) for the average 20-year-old patient (11.7 versus 10, P<0.001), according to Robert Whitmore, MD, of the University of Pennsylvania in Philadelphia, and colleagues.

The difference lessened with increasing age, but remained significantly better for the aggressive approach even in 80-year-olds, the researchers reported online in the Journal of Neurosurgery.

Total direct and indirect lifetime costs were lower for the aggressive approach for patients up to age 60, making it the dominant strategy compared with routine care. And even for 80-year-olds, the aggressive approach would likely be cost-effective, even though it carried higher costs.

A third approach -- comfort care -- yielded the worst outcomes and higher costs that the other two strategies for most age groups.

"Despite higher initial costs for an aggressive management strategy of traumatic brain injury, the substantial improvements in patient outcome cause the total lifetime costs to be the lowest of the three treatment paradigms," Whitmore and colleagues wrote.

Although early and aggressive treatment has been associated with improved outcomes in patients with traumatic brain injury in some studies, other research has pointed to possible harm accompanied by higher costs.

To explore the cost-effectiveness of various approaches, the researchers created a decision analytical model to compare three treatment strategies for patients with severe traumatic brain injury:

• Aggressive: The Brain Trauma Foundation guidelines are followed in at least half of the patients. That includes invasive monitoring of intracranial pressure until the Glasgow Coma Scale score rises above 8 or patients follow commands, and decompressive craniectomy as indicated.
• Routine: The Brain Trauma Foundation guidelines are followed in fewer than half of the patients.
• Comfort: Patients spend a single day in the intensive care unit (but do not undergo invasive intracranial monitoring or decompressive craniectomy), which is followed by routine floor care.

Data were pooled from other studies. All care before and after hospitalization was assumed to be the same in the three groups, with differences present only in acute hospital management.

The researchers assessed outcomes based on the Glasgow Outcome Scale score at six months. The scale runs from 1 (dead), 2 (vegetative state), 3 (severely disabled), 4 (moderately disabled), and 5 (good recovery).

Compared with routine care, aggressive care resulted in a higher proportion of patients with a good recovery (28% versus 23.3%) and a lower percentage of patients who died (28% versus 41%).

In addition to resulting in better outcomes, aggressive care required lower total costs than routine care ($1,264,000 versus $1,361,000 for the average 20-year-old), a result of lower costs associated with long-term nursing care and lost productivity.

Outcomes and costs favored the aggressive approach for patients up to age 60, making it the dominant strategy, according to the researchers.

The aggressive approach was more costly than routine care for 80-year-old patients, resulting in an additional cost of $88,507 per QALY, which may or may not be considered cost-effective.

"Although the threshold [for cost-effectiveness] has long been thought to be $50,000 per QALY, recent research suggests a number considerably more than $100,000," the authors wrote. "If one uses this latter threshold, aggressive care can be considered the most cost-effective strategy for all age groups."

Comfort care was associated with the worst outcomes for all age groups and higher costs for all groups except for the 80-year-olds. That approach "should be reserved for situations in which aggressive approaches have failed or testing suggests such treatment is futile," Whitmore and colleagues wrote.

The authors acknowledged that the analysis was limited by the large number of assumptions that were made and by the lack of age-specific outcomes in patients treated aggressively for severe traumatic brain injury. They also noted that one paper from which they derived much of their data on outcomes did not include any randomized clinical trials.

Minor Trauma Led to Death in Pradaxa Patient

A friend of mine was on Pradaxa for a while and she was extremely concerned about bleeding and the lack of a reversal agent.
http://www.medpagetoday.com/Neurology/HeadTrauma/31524?utm_source=cardiodaily&utm_medium=email&utm_content=aha&utm_campaign=03-07-12&eun=gd3r&userid=424561&email=oc1dean@yahoo.com&mu_id=
A dabigatran (Pradaxa) patient's death from a brain hemorrhage following a fall has again highlighted concerns over lack of an effective reversal agent for the drug.
Despite treatment with recombinant factor VII, the 83-year-old man deteriorated rapidly as the bleeding spread across most of the left hemisphere of his brain in just six hours, according to Richard H. Schmidt, MD, PhD, of the University of Utah in Salt Lake City, and colleagues.
"Imbalance and falls are common in this population, and intracranial hemorrhage resulting even from minor trauma may occur with increasing frequency as use of this drug becomes more widespread," they warned in a case report published online in the Journal of Neurosurgery.
A high index of suspicion for catastrophic hemorrhage in dabigatran users is critical so that what limited management options there are can be started without delay, the group urged.
The direct thrombin inhibitor acts at the very end of the coagulation cascade, so factor VIIa and fresh-frozen plasma don't work. Prothrombin complex concentrate hasn't been tested outside of animal models yet.
Dialysis can remove 35% to 60% of circulating dabigatran in two to three hours, but wasn't considered until too late to be effective for the reported case.
The group recommended checking the thrombin time and starting dialysis early along with judicious IV fluids to maintain renal perfusion, which is the main route of dabigatran excretion.
"Caution is necessary, however, because patients with atrial fibrillation have tenuous intravascular volume status, and fluid overload can lead to worsening heart function," they warned in the paper.
Hematologists expressed similar concerns over lack of reversibility in a recent review of a cluster of bleeding episodes in New Zealand, largely involving older patients and those with impaired renal function.
The drug was widely hailed initially for its ability to be given at a fixed dose without the need for frequent adjustments and monitoring.
In the pivotal RE-LY trial, bleeding risks were similar to those with warfarin. But since FDA approval in 2010 for stroke prevention in atrial fibrillation, reports have surfaced of a possible excess of bleeding deaths with the drug, prompting an ongoing safety review by the FDA.
Drugmaker Boehringer Ingelheim has called these reports within what would be expected based on the clinical trial, noting that dabigatran's prescribing information cites a trend for higher major bleed rates with the 150-mg dose versus warfarin in the 75-and-older population.
In the case report, the 83-year-old man had been on 150-mg twice-daily dabigatran for new-onset atrial fibrillation for one month before the ground-level fall at home that sent him to the emergency department.
On arrival, the man was alert and responsive with a normal neurological exam and a Glasgow Coma Scale score of 15. The initial CT scan showed only small, superficial areas of hemorrhage in his right temporal lobe and left temporal and parietal lobes.
Within two hours, he developed slurred speech and his neurological state began to deteriorate rapidly. Repeat CT imaging showed significant progression of right parenchymal and left frontal hemorrhages.
The neurosurgical team members knew they had limited options to reverse the blood thinner, which had left the patient with an international normalized ratio of 1.4 and a thrombin time over 150 seconds compared with the normal 15 to 20 seconds.
Despite trying a weight-based dose of recombinant factor VII for its rapid onset of action, mental status continued to slide to the point where the man lapsed into a coma (Glasgow Coma Scale score 6) and required emergency endotracheal intubation.
His final CT scan six hours after admission showed hemorrhage encompassing most of the left hemisphere and effacing the left lateral ventricle.
The patient was transitioned to palliative care after extensive discussion with his family and died shortly thereafter.
Dabigatran is only the first in a class of direct thrombin inhibitors that may raise these problems, Schmidt's group noted.
Others are on the horizon, "and these agents will likely have similar risks for catastrophic progression of traumatic injuries," they warned.

New understanding of why brain cells die after stroke will lead to development of new treatments

Hey, only from 2003 and they give an explanation why glutamate toxicity is not really the culprit in the neuronal cascade of death.
http://www.eurekalert.org/pub_releases/2003-12/uot-nuo121903.php
Scientists at Toronto Western Hospital and the University of Toronto have found a major mechanism that causes brain cells to die from stroke. They discovered that when brain cells are deprived of oxygen and vital nutrients, as happens to parts of the brain affected by a stroke, a special channel on the surface of those brain cells is activated, triggering a lethal chain reaction. The channel, called TRPM7, when activated causes brain cells to produce large quantities of free radicals – toxic molecules that break down the cell's DNA, proteins, and other components. Free radicals also cause TRPM7 to become even more active, causing massive overproduction of free radicals, resulting in death of the brain cell.
In a study published in the December 26 issue of Cell, an international science journal, the scientists also report that they have found a way to interfere with this lethal chain reaction. While brain cells can only survive for a few minutes without oxygen, interfering with the activity of TRPM7 allows brain cells to survive for more than three hours without oxygen and vital nutrients.
With this new understanding, there is now an opportunity to develop new medications that prevent activation of the TRPM7 channel. It will take approximately three years to develop a medication.

The CT and MR images show dead brain tissue the day after a major stroke, caused by a blockage in one of the arteries that feeds the brain.

"This is a quantum leap forward in understanding how stroke causes brain damage," says Dr. Michael Tymianski, neurosurgeon at the Krembil Neuroscience Centre at Toronto Western Hospital and associate professor of surgery and physiology at the University of Toronto. "Now we can see the bigger picture of why brain cells die from stroke."
"This project is a primary example of how basic and clinical scientists can come together as an effective research team to tackle the major health problem of stroke," says Dr. John MacDonald, chair of the department of physiology, Faculty of Medicine at the University of Toronto. "We are also very excited to explore the many potential functions of TRPM7 channels in the brain."
Until now, scientists thought they understood why brain cells die when deprived of oxygen and essential nutrients. Past research suggested that the major culprit was glutamate, an amino acid normally used by brain cells to communicate by carrying signals from one brain cell to the next. Dying brain cells release glutamate, which attaches to a special channel called the NMDA receptor located on the surface of the neighbouring brain cells. This causes the NMDA channel to open and allows an influx of calcium ions into the brain cell. For years, it was thought that this sequence of events caused brain cells to die from stroke.
For this reason, many experimental medications for treating strokes were aimed at blocking the effects of glutamate on NMDA receptors. Although it worked in the lab, the medications failed to reduce brain damage in humans. Despite three decades of research that pointed to glutamate as the culprit in cell death, the failure of these medications remained a mystery. To solve this mystery, Drs. Tymianski and MacDonald went back to the drawing board and discovered that glutamate was only one part of the reason why brain cells die from stroke.
"We have significant experience in translating such basic discoveries into drugs that might help patients," says Dr. Tymianski. "With this new knowledge, we will now focus on developing medications that we can inject into stroke patients up to several hours after a stroke. These medications will prevent the consequences of activating TRPM7, extend the life of brain cells after a stroke, and help improve the outcome of patients suffering from a stroke."

This image shows the arteries from the heart to the brain. The arrow points to the area of the stroke, where the artery is blocked. This image shows the arteries from the heart to the brain. The arrow points to the area of the stroke, where the artery is blocked. Full size image available through contact

As the fourth most common cause of death in Canada, and the second leading cause of death in the world, stroke kills about 16,000 Canadians every year. Stroke is a major cause of disability, as people who survive strokes suffer irreparable damage to their brain cells. These effects can include partial paralysis, problems with thinking, problems with language, and difficulty with movement. Approximately 300,000 Canadians live with the effects of stroke. The warning signs of a stroke include sudden weakness, trouble speaking, vision problems, headache, and dizziness.

###

This research was funded by grants from the Canadian Institutes of Health Research, the Ontario Heart and Stroke Foundation, and the National Institutes of Health of the United States of America.
Toronto Western Hospital has been serving the health care needs of its culturally diverse community for more than 100 years. Today, the hospital provides highly specialized tertiary care to people from surrounding areas and across Canada. Home to the Krembil Neuroscience Centre, one of the largest combined clinical and research neurological facilities in North America, the hospital also offers a community and population health program and expertise in musculoskeletal health and arthritis. Toronto Western Hospital is one of three hospitals – including Toronto General Hospital and Princess Margaret Hospital – that make up University Health Network, a teaching hospital of the University of Toronto.
The University of Toronto (U of T), Canada's leading research university with over 60,000 students, was founded in 1872 by British royal charter. For the tenth consecutive year, U of T has taken the top spot among medical/doctoral universities in the annual Maclean's magazine university ranking. The university now comprises 31 divisions, colleges and faculties on three campuses, including 14 professional faculties, numerous research centres and Canada's largest library system – one of the top research libraries in North America. U of T's Department of Physiology is the largest and most research-intensive university physiology departments in Canada and has research and training partnerships with numerous hospital-based research institutes.
Images, diagram, and flow chart are available.
For further information or to arrange an interview, please contact:
Jennifer Kohm, Communications Specialist, Toronto Western Hospital
telephone: 416-603-5323
pager: 416-867-0770
jennifer.kohm@uhn.on.ca

Stroke rehab while sitting in a chair

I sit in a scandinavian recliner while watching TV or reading. I grasp the left armrest with my hemiparetic left hand and try to keep it there while I cross my legs. This ends up failing most of the time. While just sitting there I try to just relax my left arm/hand so it lays comfortably on the armrest. As you can see from the arrows in these pictures the wrist spasticity prevents the arm from laying down flat. This is obviously not a useful attempt at do-it-yourself therapy because there is no functional use that will ever be gained by succeeding at this.

Role of L1CAM for axon sprouting and branching

Now if we could just test this out in humans.
http://www.springerlink.com/content/k24118x274187p17/

Abstract

The central nervous system (CNS) has been traditionally considered as an organ that fails to regenerate in response to injury. Indeed, the lesioned CNS faces a number of obstacles during regeneration, including an overall non-permissive environment for axonal regeneration. However, research during the last few decades
e capability of the CNS to establish new connections. The immunoglobulin superfamily member L1CAM has been shown to promote the capability of neurons for regenerative axon sprouting and to improve behavioral outcomes after CNS injury. Here, we discuss the cell-autonomous role of L1CAM for axon sprouting in experimental rodent injury models and highlight the molecular interactions of L1CAM with ankyrins, ezrin-radixin-moesin proteins and the Sema3A/Neuropilin ligand-receptor complex in the context of axonal branching.

Physicians Order Costly, Redundant Neuroimaging for Stroke Patients, Study Says

This wouldn't be as big an issue if they would actually run these scans about a week after the event in order to come up with a definite damage diagnosis(seeing the final result of the cascade of death), and then we could finally compare therapies to a diagnosis and to each other.
Finally throw away the stupid saying, 'All strokes are different, all stroke recoveries are different. 

Physicians Order Costly, Redundant Neuroimaging for Stroke Patients, Study Says

Neuroimaging for stroke patients may be unnecessarily costly and redundant, contributing to rising costs nationwide for stroke care, according to University of Michigan research.

The research, published in the Annals of Neurology, found that 95 percent of stroke patients who received magnetic resonance imaging (MRI) also had a computed tomography (CT) scan.

"Compared to CT, MRI is a more accurate test for stroke," says James F. Burke, M.D., lead author of the study and a clinical lecturer in the University of Michigan Medical School's Department of Neurology. "But our results showed that MRI is not replacing CT as the primary stroke neuroimaging study — instead, patients are getting both.

"Minimizing the use of multiple studies could be a viable strategy to reduce costs."

The costs of inpatient stroke care have climbed by 42 percent between 1997 and 2007, an increase of $3,800 per case, Burke and his University of Michigan found. Neuroimaging — MRIs and CTs – were the largest driver of costs.

Diagnostic imaging has been the fastest growing component of total hospital costs, increasing 213 percent from 1999 to 2007.

"The data shows that neuroimaging practices in stroke are neither standardized or efficient," Burke says. "This represents an area where we have an opportunity to substantially reduce the cost of care without adversely effecting the quality of care."

Burke's research spurred an accompanying editorial in the Annals, written by editors S. Clairborne Johnson, M.D., Ph.D. and Stephen L. Hauser, M.D.

"The issue of duplicative imaging in stroke is just one example of wasteful care," the editors wrote. "Quite simply, it is very easy to order more test and to treat with more expensive therapies."

"We should track waste as another measure of quality care ... The failure to find a political solution to rising healthcare costs only increases our responsibility to become leaders and not victims."

Burke and his co-authors studied patients diagnosed with stroke from 1999 to 2008 in 11 states, studying 624,842 patients. They found wide geographic variation for the use of MRI, but overall the use of MRI jumped dramatically.

"There currently is not evidence-based guidelines that preferentially recommend either MRIs or CT," Burke says. "Understanding trends like these presented in this study are essential to determining efficient and consistent neuroimaging strategies."

Thrombotech receives FDA IND approval for THR-18 Phase IIa clinical trial in stroke victims

Anything to make tPA better. When will the stroke world get off their fixation with this drug?
http://www.news-medical.net/news/20120305/Thrombotech-receives-FDA-IND-approval-for-THR-18-Phase-IIa-clinical-trial-in-stroke-victims.aspx

Hadasit Bio-Holdings (TASE: HDST, OTC: HADSY) a publicly traded portfolio of biotech companies, all based on intellectual property developed and owned by Hadassah University Hospital, Israel's foremost medical research center, today announced Thrombotech Ltd. ("Thrombotech"), a portfolio company which Hadasit holds a 24% stake in, received an IND approval from the Food and Drug Administration (FDA) enabling the initiation of a Phase IIa clinical trial in the U.S. An IND approval is a prerequisite for clinical trials in patients in any U.S. Medical Center that is supervised and controlled by the FDA.

Thrombotech's lead product, THR-18 is designed to improve the safety and efficacy of the currently available treatment for ischemic stroke patients, tPA, by significantly decreasing the life-threatening side effects. The Phase IIa clinical trial will be used to establish THR-18's safety in treating these stroke victims. Thrombotech has already begun its Phase IIa clinical trial in a number of sites in Israel (Hadassah, Ichilov and Wolfson hospitals) and is awaiting regulatory approvals in Europe and India.

According to Global Data, a company researching the global stroke market, the global market for stroke drugs in 2008 was approximately $2.8 billion and is expected to grow at an annual rate of approximately 3.4% through 2015.

"This important regulatory approval serves as external validation for our development program and the quality of the science and management behind the company. It will enable us to recruit more patients in some of the leading medical centers specializing in stroke in the US and move towards commercialization of the therapy for this serious medical condition," said Thrombotech CEO, Dr. Ruth Ben Yakar.

Commenting on the approval, Ophir Shahaf, CEO of Hadasit Bio-Holdings stated, "We are proud to expand the clinical trial to medical centers in the US, a world leader in CNS therapeutics and stroke treatment in particular. The company's goal is to prove that its lead drug enables safe and effective treatment over a wider therapeutic window, so that more patients will benefit from stroke therapy with less detrimental side effects."

Inhalation of nitric oxide could help improve blood flow to ischemic brain

Previous research into NO received the Nobel prize.

The Nobel Assembly at Karolinska Institutet has today decided to award
the Nobel Prize in Physiology or Medicine for 1998 jointly to

Robert F. Furchgott, Louis J. Ignarro and Ferid Murad

for their discoveries concerning "nitric oxide as a signalling molecule in the cardiovascular system".

This was already referred to here in 2006
The latest here:
http://www.news-medical.net/news/20120305/Inhalation-of-nitric-oxide-could-help-improve-blood-flow-to-ischemic-brain.aspx

LMU researchers developed a new strategy for the treatment of stroke, which could help to improve blood flow to ischemic brain. Strokes are due to a localized reduction in the blood supply to the brain, mainly due to the blockage of a vessel by a blood clot.

This can lead to the death and irreversible loss of nerve cells. In about 90% of cases, no dedicated treatment is available that can effectively prevent serious damage following an acute stroke. A team led by LMU researcher Professor Nikolaus Plesnila has now shown, in an animal model, that inhalation of nitric oxide (NO), a chemical compound which is itself toxic, can improve perfusion of the brain in the aftermath of an acute stroke. Brain function in treated animals was significantly improved as compared to in controls that had not been given NO.

"In collaboration with colleagues at Harvard Medical School, we have just begun to test whether or not NO has a comparable effect in humans. If so, we could then initiate a full-scale international clinical study," says Plesnila.

"If such a trial were successful, the new therapy could be introduced into the clinic very quickly. NO is already widely used for the management of several lung diseases, and could even be administered as required in ambulances and other rescue vehicles."