StemCell Therapy

EXTON, Pa., June 4, 2012 /PRNewswire/ -- ViroPharma Incorporated (VPHM) today announced the initiation of a Phase 2 program to evaluate maribavir for the treatment of cytomegalovirus infections in transplant recipients. The planned program will consist of two independent Phase 2 clinical studies that will include subjects at different ends of the spectrum of CMV infection or disease, namely those who have asymptomatic CMV, and those who have failed therapy with other anti-CMV agents. Maribavir was granted U.S. Orphan Drug Designation in May of 2011 for treatment of clinically significant cytomegalovirus viremia and disease in at-risk patients.

In addition, an abstract of data collected through the use of maribavir at six French transplant centers as part of a named patient program (NPP) has been accepted for the 24th International Congress of the Transplantation Society to be held on July 15th through 19th in Berlin, Germany.

"Physicians continue to see potential value in the novel mechanism of action of maribavir when used at higher doses in critically ill patients, particularly when other options have failed," stated Marc E. Uknis, MD, medical director, ViroPharma Incorporated. "The outcomes seen in a small number of the NPP patients and the previously published experience in emergency-use IND patients suggests the possibility that maribavir may provide meaningful antiviral effects in treating active CMV infection and merits further careful evaluation because of the serious unmet need in immunocompromised transplant patients."

"Asymptomatic" CMV Study ViroPharma has initiated a randomized, dose blinded multicenter Phase 2 study intended to enroll up to 160 subjects (recipients of either hematopoietic stem cell or solid organ transplant) who have demonstrated CMV viremia but do not have CMV organ disease. Further, these subjects cannot have CMV infection that is resistant to other anti-CMV agents. Subjects will be randomized to receive oral maribavir at one of three doses (400mg, 800mg or 1200mg BID) or valganciclovir for up to 12 weeks. Blood levels of CMV DNA will be monitored throughout the study, and minimum virologic responses will be required after 3 and 6 weeks of treatment to continue study drug. The study will be conducted at multiple transplant centers in 3-4 countries in Europe.

Resistant/Refractory CMV Study ViroPharma is planning to initiate a second study, a randomized, dose blinded multicenter Phase 2 study intended to enroll up to 120 subjects (recipients of either hematopoietic stem cell or solid organ transplant) who have demonstrated CMV viremia with or without CMV organ disease. All subjects will have failed to have an adequate virologic response to prior treatment with ganciclovir, valganciclovir, or foscarnet, and may have documented viral genetic resistance to any of these anti-CMV agents. Subjects will be randomized to receive oral maribavir at one of three doses (400mg, 800mg or 1200mg BID) for up to 24 weeks. Blood levels of CMV DNA will be monitored throughout the study, and minimum virologic responses will be required after 3 and 6 weeks of treatment to continue study drug. The study is planned to be conducted at multiple transplant centers in the United States.

About Maribavir Maribavir, a member of a new class of drugs called benzimidazole ribosides, is a potent and selective, orally bioavailable antiviral drug with a unique mechanism of action against cytomegalovirus and a favorable clinical safety profile. Unlike currently available anti-CMV agents that inhibit CMV DNA polymerase, maribavir inhibits viral DNA assembly and inhibits egress of viral capsids from the nucleus of infected cells. Maribavir is active in vitro against strains of CMV that are resistant to commonly used anti-CMV drugs. The previous focus of clinical development of maribavir as an anti-CMV agent was on the prevention of CMV disease in transplant patients. Results from Phase 3 studies indicated that maribavir at a dose of 100mg BID failed to meet its efficacy endpoints; however, maribavir has demonstrated a favorable safety and tolerability profile in all clinical studies to date. While Phase 3 studies of CMV prophylaxis at the 100mg BID dose did not show sufficient activity to prevent CMV disease, the overall safety profile of maribavir and limited data from cases in which open-label maribavir was used as CMV treatment suggest that higher doses may provide clinical activity. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to maribavir in May of 2011 for treatment of clinically significant cytomegalovirus viremia and disease in at-risk patients.

About Cytomegalovirus CMV is a memberof the herpesvirus group, which includes the viruses that cause chicken pox, mononucleosis, herpes labialis (cold sores), and herpes genitalis (genital herpes). Like other herpesviruses, CMV has the ability to remain dormant in the body for long periods of time. Human CMV infection rates average between 50 percent and 85 percent of adults in the U.S. by 40 years of age, but in healthy adults causes little to no apparent illness. However, in immunocompromised individuals including cancer patients, HIV patients, and transplant patients, and in children born with primary CMV infection, CMV can lead to serious disease or death. Patients who are immunosuppressed following hematopoietic stem cell (bone marrow) or solid organ transplantation are at high risk of CMV infection. In these patients, CMV can lead to severe conditions such as pneumonitis or hepatitis, or to complications such as acute or chronic rejection of a transplanted organ. While currently available systemic anti-CMV agents are effective against the virus, their use is limited by toxicities, most notably bone marrow suppression and renal impairment.

About ViroPharma Incorporated ViroPharma Incorporated is an international biopharmaceutical company committed to developing and commercializing novel solutions for physician specialists to address unmet medical needs of patients living with diseases that have few if any clinical therapeutic options. ViroPharma is developing a portfolio of therapeutics for rare and Orphan diseases including C1 esterase inhibitor deficiency, Friedreich's Ataxia, and adrenal insufficiency, cytomegalovirus (CMV); and recurrent C. difficile infection (CDI). Our goal is to provide rewarding careers to employees, to create new standards of care in the way serious diseases are treated, and to build international partnerships with the patients, advocates, and health care professionals we serve. ViroPharma's commercial products address diseases including hereditary angioedema (HAE), seizures, adrenal insufficiency and C. difficile-associated diarrhea (CDAD); for full U.S. prescribing information on our products, please download the package inserts at http://www.viropharma.com/Products.aspx; the prescribing information for other countries can be found at http://www.viropharma.com.

ViroPharma routinely posts information, including press releases, which may be important to investors in the investor relations and media sections of our company's web site, http://www.viropharma.com. The company encourages investors to consult these sections for more information on ViroPharma and our business.

Forward Looking Statements Certain statements in this press release contain forward-looking statements that involve a number of risks and uncertainties. Forward-looking statements provide our current expectations or forecasts of future events, including the therapeutic indication and use, safety, efficacy, tolerability and potential of maribavir and our focus, goals, strategy, research and development programs, and ability to develop pharmaceutical products, commercialize pharmaceutical products, and execute on our plans including clinical development activities with maribavir related to treatment of subjects with asymptomatic CMV as well as resistant / refractory CMV disease. In February 2009, based upon preliminary analysis of the data, we announced that our Phase 3 trial evaluating maribavir used as prophylaxis in allogeneic stem cell, or bone marrow, transplant patients did not achieve its primary endpoints. In addition, the study failed to meet its key secondary endpoints. Additionally, we announced that our Phase 3 trial evaluating maribavir in liver transplant patients was discontinued and that all patients on study drug were moved to current standard of care. While the current studies are in different patient populations and utilize different dosing levels, there can be no assurance that our clinical program with maribavir for the treatment of subjects with asymptomatic CMV as well as resistant / refractory CMV disease will yield positive results or support further development of maribavir for either indication. The preliminary results from a small number of NPP and emergency-use IND patients may not be predictive of the results of the studies described in this press release. The FDA or EMA may view the data regarding maribavir for the treatment of subjects with asymptomatic CMV as well as resistant / refractory CMV disease as insufficient or inconclusive, request additional data, require additional clinical studies, delay any decision past the time frames anticipated by us, limit any approved indications, or deny the approval of maribavir for the treatment of subjects with asymptomatic CMV as well as resistant / refractory CMV disease.

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ViroPharma Announces Initiation of Clinical Studies to Evaluate Maribavir for Treatment of Cytomegalovirus (CMV ...

CARLY WEEKS From Saturday's Globe and Mail Published Saturday, May. 26, 2012 6:00AM EDT

Its a straightforward pitch to expecting parents: Pay a private clinic to store your babys stem-cell-rich umbilical-cord blood, and rest assured that he or she has protection for life. Multiple sclerosis, cerebral palsy, diabetes, traumatic brain injury, stroke, brain tumours and even Alzheimers disease are just a few of the ailments stem cells may be able to treat or cure in the future.

The optimism is contagious. Tens of thousands of Canadian families have made the decision to pay thousands of dollars to bank cord blood. But beyond the websites and brochures featuring photos of smiling babies and testimonials from families, a different picture is emerging of an industry that uses inflated arguments, aggressive marketing and misleading information to convince parents to buy in.

I dont know if the families are walking away with an entirely honest picture of what theyre buying, says John Doyle, former head of blood and marrow transplants at Torontos Hospital for Sick Children. I dont think that parents truthfully understand the limits.

Theres a long-standing history of overinflated promises by the cord-blood banks, agrees Donna Wall, director of the blood and marrow transplant program at CancerCare Manitoba. I could have retired many times over if I had gotten into the business. Its just not the right thing to do.

Full of promise

The stem cells found in umbilical-cord blood have the ability to turn into red or white blood cells or blood-clotting cells. For that reason, they offer promising treatments for leukemia, lymphoma, sickle cell disease and other blood, bone, immune and metabolic disorders.

Adults also carry these stem cells, which is why Canadian Blood Services has a campaign to recruit people to join OneMatch, its network to connect stem-cell and bone-marrow donors to patients. But finding a suitable donor is much more difficult than simply matching blood types. Patient and donor cells must match 10 out of 10 human leukocyte antigens or proteins found on the surface of cells. Donor registries are limited and seldom diverse enough to serve patients of all ethnicities.

Hence the excitement over umbilical-cord-blood stem cells: Not only are they young and less likely to lead to complications, they need not match as precisely as adult cells.

This has just opened up so many more possibilities to patients in need, says Sue Smith, executive director for stem cells at Canadian Blood Services.

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Why banking on cord blood isn't necessarily a good idea

May 15, 2012

A New York Stem Cell Foundation (NYSCF) scientist has shown in new research that human embryonic stem cells can be used to grow bone tissue grafts for use in research and potential medical applications.

Dr. Darja Marolt, an investigator at the NYSCF, is the lead author of the study, which was published this week in the online edition of the Proceedings of the National Academy of Sciences (PNAS).

It is the first example of using bone cell progenitors derived from human embryonic stem cells to grow compact bone tissue in quantities large enough to repair centimeter-sized defects. When implanted in mice and studied over time, the implanted bone tissue supported blood vessel in-growth, and continued development of normal bone structure, without demonstrating any incidence of tumor growth.

This is a significant step forward in using pluripotent stem cells to repair and replace bone tissue in patients, noted the researchers. Bone replacement therapies are relevant in treating patients with a variety of conditions, wounds, birth defects, or other traumatic injuries.

Dr. Marolt conducted this research as a post-doctoral NYSCF Druckenmiller Fellow at Columbia University in the laboratory of Dr. Gordana Vunjak-Novakovic. Since conducting this work, Marolt has continued to build upon the research, developing bone grafts from induced pluripotent stem (iPS) cells.

IPS cells are similar to embryonic stem cells in that they can also give rise to nearly any type of cell in the body, but iPS cells are produced from adult cells and as such are individualized to each patient. Marolt hopes that by using iPS cells to engineer tissue, she can develop personalized bone grafts that will avoid immune rejection and other implant complications.

The New York Stem Cell Foundation conducts cutting-edge translational stem cell research in its laboratory in New York City and supports research by stem cell scientists at other leading institutions around the world.

Source: RedOrbit Staff & Wire Reports

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Human Embryonic Stem Cells Used To Grow Bone Tissue

Public release date: 9-May-2012 [ | E-mail | Share ]

Contact: Emma Mason wordmason@mac.om European Society for Radiotherapy and Oncology (ESTRO)

Barcelona, Spain: Researchers believe they may have found a way to avoid damaging salivary glands during radiotherapy treatment for head and neck cancer a discovery that could improve the quality of life of 500,000 patients a year worldwide with the disease.

Presenting their findings to the 31st conference of the European Society for Radiotherapy and Oncology (ESTRO31) [1], the researchers said that they had discovered that the stem cells essential for regenerating the parotid gland (the largest pair of salivary glands) were located mainly in its major ducts, and that these could easily be avoided during radiotherapy or given a minimal radiation dose. "This would significantly reduce complications arising from radiotherapy for head and neck cancer," said Dr Peter van Luijk, a research associate at the University Medical Center Groningen, The Netherlands.

Around 40% of patients treated for head and neck cancer suffer from the distressing side-effects of dry mouth syndrome a condition that can occur when the parotid gland stops working properly after radiation damage. This causes problems with eating, sleeping, speech, tooth loss and oral hygiene, leading to diminished quality of life, social isolation and difficulty in continuing work. Attempts to treat dry mouth syndrome and its consequences can cost hundreds or even thousands of Euros per patient per year and are mostly insufficient.

Dr van Luijk said: "Parotid gland dysfunction after radiotherapy for head and neck cancer was, and still is, a major clinical problem. During radiotherapy, attempts to minimise the risk of this complication have been aimed at reducing the average dose to the salivary gland, on the assumption that it would not make a difference where in the gland the radiation dose was reduced. However, this does not seem logical according to the anatomy of the salivary gland and, in previous work, we discovered that reductions in the radiotherapy dose to some parts of the gland allowed the parotid gland to regenerate, whereas a dose to other parts did not. Therefore, we decided to investigate the reason for these regional differences. We hypothesised that our observations could be explained by a non-uniform distribution of stem cells necessary for the long-term maintenance of organ function and affected by irradiation."

Dr van Luijk and his colleagues investigated the location of stem cells and the effects of radiotherapy to particular regions of the gland first in mouse and rat models, and then in parotid and salivary gland tissue taken from patients (after informed consent) undergoing a neck dissection for head and neck cancer.

They found that in mouse, rat and human tissue, the stem cells were predominately located in the major ducts of the parotid gland. "We have found in previous work that these stem cells are capable of regenerating a parotid gland when they have been transplanted after irradiation," said Dr van Luijk.

Dissection of the rat parotid gland and culturing of the different parts of the gland in Petri dishes showed that a greater concentration of stem cells capable of regenerating the gland were located in the centre, where the largest ducts are located. The researchers then directed high-precision irradiation at this centre part in living rats and found that it resulted in excessive reduction of saliva production, in contrast to the minimal effects observed after irradiating other parts of the gland.

Dr van Luijk explained: "The position of the stem cells in rats corresponds to the cranio-ventral extension of the gland in humans, where the excretory duct leaves the gland on the ventral, or outward-facing side. So even though the glands have different shapes in rats and humans, the stem cells are in the exact same anatomical structure."

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Stem cell sparing radiotherapy for head and neck cancer may avoid salivary gland damage

LYNCHBURG, VA --

In home video Dr. Don Hicks is documenting his ride to the hospital with his brother, Billy.

They seem relaxed and casual on the way, but what you can't tell is Don will soon save Billys life.

Fast forward months later and we catch up with Dr. Hicks in his office at Liberty University to talk about this amazing story of love and science.

"I call this story Billy and me. It's simple. Of course, Billy and I are very close he's a younger brother," Dr. Hicks explained.

Six years ago Billy was diagnosed with a rare form of leukemia.

After maintaining his health with trial medication, last year , the time had come for a stem cell transplant.

Last January, Dr. Hicks realized that his brother needed donated stem cells, so he went to a local office in Lynchburg and they did just a simple cotton swab cheek test. When the results came back the realized that he was a match, so he went to Tennessee for further testing and found he wasn't just any match he was a perfect ten out of ten.

"I spoke with the doctor and he said this is actually a cure to leukemia it's not just a chance. Either this will cure him or it will kill him, so those were the two choices," Dr. Hicks said.

He also documented the donation process.

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Liberty University professor saves brother's life with stem cell donation

Editor's Choice Academic Journal Main Category: Obesity / Weight Loss / Fitness Also Included In: Stem Cell Research;Radiology / Nuclear Medicine Article Date: 29 Mar 2012 - 6:00 PDT

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At the Society of Interventional Radiology's 37th Annual Scientific Meeting in San Francisco, Calif. scientists reported initial results from various studies, for instance a minimally invasive treatment that potentially targets hunger at its source, X-ray visible embolic beads that block arteries to the stomach and suppress hunger, whilst a third study examines using stem cells to repair vertebral disc degeneration.

Morbidly obese individuals may potentially find help in new approaches to proven interventional radiology treatments that have been assessed in two new studies.

Leading researcher, Charles Y. Kim, M.D., assistant professor of radiology at Duke University Medical Center in Durham, N.C. explained:

Our promising results led us to believe that a minimally invasive interventional radiology treatment - called bariatric arterial embolization - would allow for precise targeting of a specific portion of a person's stomach in order to decrease production of ghrelin, a hormone that causes hunger. This treatment could one day be the answer for those who have not been successful with weight loss through diet and exercise."

In an minimally invasive technique called Embolization, an interventional radiologists injects tiny particles via a thin catheter into an artery that supplies the treated area in order to block tiny vessels so that the blood supply is starved.

Kim says:

We found that when ghrelin levels decrease, appetite and hunger also decrease, causing weight loss in the treated animals relative to non-treated animals. Bariatric arterial embolization may have a future use in treating obesity in humans by significantly suppressing appetite to achieve weight loss."

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Latest Radiology Treatments For Obesity

ROCKVILLE, Md., March 28, 2012 /PRNewswire/ --Neuralstem, Inc. (NYSE Amex: CUR) announced that safety results from the first 12 patients with amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) to receive its stem cells were reported online in the peer-reviewed publication, STEM CELLS, on March 13th. "Lumbar Intraspinal Injection of Neural Stem Cells in Patients with ALS: Results of a Phase I Trial in 12 Patients" (http://www.ncbi.nlm.nih.gov/pubmed/22415942.1) reports that one patient has shown improvement in his clinical status, even though researchers caution that the study was not designed to show efficacy. Additionally, there was no evidence of accelerated disease progression due to the intervention in any of the 12 patients, who were followed from 6-18 months after they were transplanted with the cells. All of the patients, who received transplants in the lumbar (lower back) region, tolerated the treatment without any long-term complications related to either the surgery or the cells.

(Logo: http://photos.prnewswire.com/prnh/20061221/DCTH007LOGO )

The 12 patients, part of the ongoing Phase I trial to evaluate the safety of Neuralstem's stem cells and transplantation procedure in patients with ALS, were the first in the world to receive intraspinal stem cell injections. Results from these patients were also were reported at the American Academy of Neurology Annual Meeting last September.

Based on a positive safety assessment, the trial has now been approved by the FDA to progress to transplanting ALS patients in the cervical (upper back) region of the spine, where the goal is to protect the motor neurons which affect respiratory function, and possibly prolong life. The fourteenth patient was transplanted earlier this month. All patients were treated at Emory University Hospital in Atlanta, Georgia.

"For these first 12 patients, we have met the objective of the Phase I trial, demonstrating safety for both the procedure of intraspinal injection and the presence of the neural stem cells in the spinal cords of ALS patients," said Jonathan Glass, MD, lead author of the publication. "We are encouraged by these results and have now advanced our trial to injections into the cervical spinal cord, targeting the motor neurons that control respiratory function." Dr. Glass is Professor of Neurology and Pathology at Emory University School of Medicine, as well as the Director of the Emory ALS Center.

"This important peer-reviewed publication reinforces our belief that we have demonstrated a safe, reproducible and robust route of administration into the spine for these spinal cord neural stem cells," said Eva Feldman, MD, PhD, Director of the A. Alfred Taubman Medical Research Institute and Director of Research of the ALS Clinic at the University of Michigan Health System. "The publication covers data up to 18 months out from the original surgery. However, we must be cautious in interpreting this data, as this trial was neither designed nor statistically powered to study efficacy." Dr. Feldman is senior author on the study, principal investigator (PI) of the ALS trial and serves as a consultant to Neuralstem as part of her University of Michigan activities.

"As this article points out, our experience in the lumbar spinal cord has been overwhelmingly positive," commented Karl Johe, PhD, study author and Neuralstem Chairman and Chief Scientific Officer. "We have already transplanted two patients in the cervical spinal cord, where we believe we can affect patients' lives the most by improving their breathing. We are in active discussions with the FDA to increase the number of cells and the number of injections as well."

"We wish to thank the teams at Michigan and Emory for the tireless efforts required to refine this breakthrough method of administration of our neural stem cells. We'd also like to thank the patients and families involved in the trial," said Richard Garr, Neuralstem CEO and President. "The progress we have made to date is both substantial, and a true team effort."

About the Study

Safety results were reported on the first 12 patients in an ongoing Phase I study to evaluate the safety of Neuralstem's spinal cord stem cells (HSSC's), as well as the transplantation technique, in the treatment of ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

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Neuralstem ALS Stem Cell Trial Interim Results Reported in the Journal, STEM CELLS

By Uduak Grace Thomas

Users of ChimerMarker, a short tandem repeat chimerism analysis software solution marketed by SoftGenetics, are reporting a significant reduction in the time required to analyze STRs in blood samples of patients who have undergone bone marrow transplants.

The tool automates the process of assessing the chimerism ratio the proportion of donor cells relative to the host patients own cells in post-transplant cases based on the presence of STRs that are unique to both the patient and the donor, Don Kristt, head of molecular pathology at the Rabin Medical Center in Israel, explained to BioInform this week.

According to SoftGenetics, the software can be used to monitor chimerism levels in allogeneic and autologous stem cell transplants or hematopoietic stem cell transplants; bone marrow transplants; and cord and peripheral blood stem cell transplant samples.

SoftGenetics partnered with Kristt to develop the software, which it released last March (BI 3/18/2011). The company later added a module for testing fetal samples for maternal cell contamination prior to performing genetic testing for cystic fibrosis or other diseases (BI 9/2/2011).

The software provides capabilities for genotyping and chimerism analysis and tools to automatically identify donor and recipient peaks in samples following bone marrow transplants. It also calculates percent chimerism and quality metrics for single donor or double donor cases.

Dawn Wagenknecht, who supervises the HLA-Vascular Biology Laboratory at Franciscan St. Francis Health, told BioInform this week that her team was able to reduce the time required to calculate the ratio of donor to recipient cells in blood samples by as much as 85 percent.

She explained that the team ran parallel analyses of 10 blood samples using both ChimerMarker and a manual approach that the lab had used prior to purchasing the software, which involved manually sorting data generated by capillary sequencing in Excel spreadsheets, and then calculating the ratios either on the sheet or using a hand calculator.

In addition to the time savings, ChimerMarker also simplifies the analysis process because all the steps of the workflow are in a single package, she said.

The software also maintains records of the donor sample and the patients blood before transplantation so that the results from subsequent tests after transplant can be compared to the initial samples, she said.

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Labs Report 85 Percent Reduction in STR Analysis Time with SoftGenetics' ChimerMaker Software

Four-year-old Angela Irizarry was born with a single pumping chamber in her heart, a potentially lethal defect. To fix the problem, Angela is growing a new blood vessel in her body in an experimental treatment that could advance the burgeoning field of regenerative medicine.

Doctors at Yale University here implanted in Angela's chest in August a bioabsorbable tube that is designed to dissolve over time. The tube was seeded with cells, including stem cells, that had been harvested from Angela's bone marrow. Since then, the doctors say, the tube has disappeared, leaving in its place a conduit produced by Angela's cells that functions like a normal blood vessel.

"We're making a blood vessel where there wasn't one," said Dr. Christopher Breuer, the Yale pediatric surgeon who led the 12-hour procedure to implant the device. "We're inducing regeneration."

Angela, who had little stamina before the operation, now has the energy of a regular kid. She is on several medications, but Breuer and her parents think she'll be able to start school in the fall.

Scientists have long been captivated by the ability of animals such as salamanders and starfish to regrow body parts lost to injury. It was long assumed that developmental forces that create a human being in the womb are lost at birth. But recent advances in stem-cell research and tissue engineering suggest that regenerative forces can be reawakened with strategically implanted stem cells and other tissue.

This notion is fueling research at many academic laboratories and dozens of start-up companies where scientists are hoping to identify effective ways to treat maladies including heart muscle damaged from heart attacks, paralysis due to spinal cord injuries and poor-functioning kidneys and bladders.

Angela's condition, known as hypoplastic left heart syndrome, affects some 3,000 newborns in the U.S. each year. With just one pumping chamber, or ventricle, instead of the usual two, the babies can't deliver sufficient levels of oxygen to their organs and extremities, compromising their development and causing them to turn blue and suffer from a lack of energy. Without a surgical repair, says Breuer, 70 percent of them die before their first birthday.

Pediatric surgeons typically treat the condition with a series of operations called the Fontan procedure, designed to enable the heart to function without the missing ventricle. The last operation involves implanting a synthetic blood vessel made of Gore-Tex to reroute blood from the lower extremities directly to the lungs instead of through the heart. The device works, but it is prone to clotting, infection and in some cases, the need for additional surgery later in life as the child grows. The idea behind Breuer's project is that a natural conduit with the biology of a normal blood vessel would grow with the child and avoid or significantly reduce complications associated with a synthetic tube.

Angela's case "is a real milestone and broadly important for the field of tissue engineering," said Robert Langer, a researcher at Massachusetts Institute of Technology and a regenerative-medicine pioneer who isn't involved in the Yale initiative. "It gives you hope that when you combine cells with a scaffold and [put] them in the body, they will do the right thing."

Angela's heart defect was diagnosed in utero, when her mother Claudia was five months pregnant. She had her first operation when she was 5 days old, and another at 8 months. But her heart defect was taking a toll. She was shy, small for her age and lacked the stamina of a normal 3-year-old.

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To fix a heart, doctors train girl's body to grow new part

MCKINNEY (CBSDFW.COM) - If you have ever dealt with back pain, then you know how quickly it can take over your life. But some North Texans are discovering that tiny cells in their own bodies could be key to long-lasting relief.

A simple walk on a beautiful day is not something that Kim Ferracioli takes for granted, as the McKinney resident has been dealing with debilitating back pain for years due to a bad disk in her lower spine. It was so painful, she said. Everytime I would stand up or sit too long, it was just a horrible pinching feeling.

When steroid injections, physical therapy and a minimally-invasive surgery actually made the pain worse, Ferracioli decided to try a new therapy that is revolutionizing the way that doctors treat spinal injuries.

Were using your stem cells, which decreases the rate for complications, explained Dr. Rob Dickerman, a neurosurgeon and one of a few doctors in the country using a patients own stem cells to actually grow new bones from scratch. We can remove a disk and put them between the bones of the spine, and itll stimulate a fusion.

Dickerman removes stem cells from a patients hip and places them in a disk-like carrier. Once implanted into the patients spine, within three months, the stem cells begin to grow into new bone where the damaged disk was removed.

There was an automatic difference, said Ferracioli about the procedure. I could get up out of chairs. I didnt need the cane anymore.

Dickerman said that the success of these procedures are just the first steps for stem cell use in the spine. He hopes that they will soon be able to treat more serious injuries. If we can tweak these cells, Dickerman explained, to make it beneficial to these patients that for the most part have irreparable injuries, that would just be a huge advance in science.

Research is already underway in several labs around the world, transplanting a patients own stem cells to repair spinal cord injuries and even traumatic brain injuries. Dickerman hopes to see these treatments hit the mainstream within the next few years.

In the meantime, Ferracioli said that this new procedure is the only thing that gave her life back. I had to literally pull this back leg up the stairs, Ferracioli recalled. Now, I can just go no pain!

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Stem Cells Could Be Key To Back Pain Relief

For about three days in January, Matt Ladd said he didnt know whether it was day or night, what was top or bottom.

I was probably as sick as Ive ever been, said Ladd, a Billings game warden, in a telephone interview from Seattle. As things got progressively worse and worse, I was really concerned about what was going on right then.

Ladd was headed to Seattle for stem cell bone marrow transplant surgery when an infection he was being treated for worsened. The infection started around a catheter inserted into his chest to deliver chemotherapy drugs. The chemo was battling Ladds acute myeloid leukemia and myelodysplastic syndrome, which was diagnosed in September. His bone marrow wasnt producing enough red blood cells.

The chemo worked. He was in remission and on his way to Seattle for a bone marrow transplant when the infection sent him into a rapid downward spiral. Because of the location of the catheter, the infection attacked his heart valves. During the struggle with the infection, his kidneys failed, his body retained water and he swelled up.

The infection scuttled plans for the bone marrow transplant surgery. With his kidneys failing, he had to undergo dialysis. As a final insult to his immune system, he had to take more chemotherapy since the surgery had been delayed and doctors feared the MDS might return.

My body and kidneys didnt respond well to the chemo, he said.

More than a month after he was scheduled to undergo surgery, Ladd is living in an apartment north of Seattle as family members rotate caretaking duties. His wife, Maureen, a math teacher at Billings West High, is holding down the fort at home, trying to maintain a sense of normalcy for their sons, Dylan, Logan and Jack.

What was going to be a short process has become a very long process, Maureen said.

Now the Ladds are waiting to hear whether Matt and his sister, Jessica Cook, will take part in a Seattle Cancer Center Alliance study of a new method of bone marrow transplantation. Since Ladds kidneys have been injured, he would normally have to have a reduced-intensity transplant used for the elderly and those with health issues, Maureen explained.

The experimental method would treat Cook, Ladds only sibling and a bone marrow transplant match, with Lipitor prior to the surgery. The cholesterol-lowering drug has shown promise in preventing reactions to transplants. If they are accepted for the study, it would mean a further delay of surgery, since Cook would have to be on the drug for a couple of weeks prior to the operation.

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Billings game warden fights cancer complications

OTTAWA A team of Canadian researchers has been awarded $442,000 to test the world's first experimental stem-cell therapy aimed at patients who suffer from septic shock, a runaway infection of the bloodstream that's notoriously difficult to treat.

The federal grant will allow researchers from the Ottawa Hospital Research Institute to use mesenchymal stem cells, found in the bone marrow of healthy adults, to treat as many as 15 patients with septic shock.

The deadly infection occurs when toxic bacteria spreads rapidly throughout the body and over-activates the immune system, leading to multiple organ failure and death in up to 40 per cent of cases.

One in five patients admitted to intensive-care units suffers from septic shock, making it the most common illness among a hospital's sickest of the sick.

Existing treatments focus on early diagnosis and intervention before organs start to fail. Patients with septic shock require aggressive resuscitation measures, large doses of intravenous antibiotics and, often, ventilators to help them breathe.

Yet because the infection can creep up on patients rapidly and cause unpredictable complications, death from septic shock remains relatively common.

The experimental therapy aims to use donor stem cells, grown and purified at the Ottawa laboratory, to dial down the body's hyperactive immune response and reduce the cascade of inflammation that leads to organ failure.

Early results from animal studies even raise the possibility that mesenchymal cells could eliminate the bacteria that causes septic shock, although the impact on humans is not yet known.

"It's a unique feature of the stem cells," said Dr. Lauralyn McIntyre, the intensive-care physician who is leading the trial. "Certainly no other therapy in the past, other than antibiotics, has impacted the bacterial load in the system."

As with other stem cells, mesenchymal cells can turn into a variety of more specialized cells and tissues that help repair and regenerate damaged organs. And because mesenchymal cells are derived from adults, they sidestep the ethical issues arising from the destruction of human embryos needed to make embryonic stem cells.

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Canadian researchers receive grant to test stem-cell therapy for septic shock

New route of administration provides greater convenience and choice for physicians and patients

TORONTO, March 15, 2012 /CNW/ - Janssen Inc. announced today that Health Canada has approved an expanded indication for VELCADE (bortezomib) to include subcutaneous administration in the treatment of multiple myeloma, a form of blood cancer.1,2 This route of administration was studied in patients with relapsed multiple myeloma. With this approval, Canadians living with multiple myeloma can now receive a convenient, subcutaneous (under the skin) injection that allows for greater physician and patient treatment choice.3 VELCADE was first approved in Canada under a Notice of Compliance with Conditions in January 2005 for the treatment of multiple myeloma patients who have relapsed following front-line therapy and are refractory to their most recent therapy. In 2008, VELCADE was also approved as part of combination therapy for the treatment of patients with previously untreated multiple myeloma who are unsuitable for stem cell transplantation.

"The new option of the subcutaneous delivery route has the potential for more patients to benefit from bortezomib. Patients with poor venous access will have improved convenience. For patients with pre-existing peripheral neuropathy and patients at high risk for developing peripheral neuropathy this alternate route will also result in improved safety with the reduced risk of developing worsening of neuropathy," said Dr. Kevin Song, MD, FRCPC, BC Cancer Agency, Vancouver General Hospital and the Leukemia/Bone Marrow Transplant Program of BC, Vancouver. "In addition, subcutaneous delivery of bortezomib provides physicians and patients the opportunity to tailor treatment based on individual preferences and circumstances. I have no doubt that the subcutaneous delivery route will become the preferred option."

Multiple myeloma is characterized by excessive numbers of abnormal plasma cells in the bone marrow.4 Symptoms of the disease often include bone pain, fatigue, unusual bleeding (usually from the nose and gums), frequent infections and fevers, thirst, weight loss and nausea or vomiting. Multiple myeloma may also cause structural bone damage resulting in painful fractures.5 The goal of multiple myeloma treatment is to relieve symptoms, avoid complications, and prolong life.6

"Myeloma Canada endorses Health Canada's decision to approve the subcutaneous administration of VELCADE," said Aldo Del Col, Co-Founder and Executive Director of Myeloma Canada. "From a patient perspective, subcutaneous administration may reduce the risk of neuropathy, thereby allowing patients to continue their treatment to optimize clinical outcomes."

The results of an open-label, randomized, phase III non-inferiority study1 conducted with 222 patients with relapsed multiple myeloma randomly assigned to receive subcutaneous or intravenous bortezomib found that patients receiving bortezomib subcutaneously achieved a four-cycle overall response (ORR) of 42 per cent and complete response (CR) rate of six per cent, while patients receiving bortezomib intravenously achieved an ORR of 44 per cent and a CR rate of nine per cent. The overall safety profile was similar between the two arms. However, differences were observed in the incidence of peripheral neuropathy (PN). In the subcutaneous arm of the trial, six per cent of patients experienced PN of grade three or higher, compared with 16 per cent in the intravenous arm. In the subcutaneous arm, 38 per cent of patients experienced PN of all grades, compared with 53 per cent of patients in the intravenous arm. Dose reductions occurred due to drug related adverse events in 31 per cent of patients in the subcutaneous treatment group compared with 43 per cent of the intravenously treated patients.7 In the subcutaneous treatment group, 18 per cent of patients discontinued study treatment due to a drug-related adverse event compared with 23 per cent in the intravenous treatment group.8

"This new indication further supports the efficacy of bortezomib for patients living with multiple myeloma," added Dr. Song. "In addition, subcutaneous delivery may offer greater convenience to patients and healthcare providers."

About Multiple Myeloma in Canada Multiple myeloma is the second most prevalent blood cancer after non-Hodgkin's lymphoma.9 In 2011, there were approximately 7,000 Canadians living with multiple myeloma and the prevalence in Canada continues to rise.1 According to the 2011 Canadian Cancer Statistics report released by the Canadian Cancer Society, the total new cases of multiple myeloma diagnosed annually in Canada are estimated at 2,300, with the total number of deaths from multiple myeloma estimated at 1,370 annually.8 The average age at diagnosis is 62 years for men and 61 years for women, and only four per cent of cases are diagnosed in individuals under the age of 45.11

About VELCADE(bortezomib) for Injection1 VELCADE offers a completely novel approach to treating multiple myeloma by acting on a unique target in cells called the proteasome. By blocking the proteasome, VELCADE disrupts processes related to the growth and survival of cancer cells. The proteasome is a structure that exists in all cells and plays an important role in breaking down proteins that control how the cell lives and grows.

VELCADE was first approved in Canada under a Notice of Compliance with Conditions in January 2005 for the treatment of patients with multiple myeloma who have relapsed following front-line therapy and are refractory to their most recent therapy.

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Health Canada approves subcutaneous administration of VELCADE®* in multiple myeloma

Public release date: 12-Mar-2012 [ | E-mail | Share ]

Contact: Sarah Jackson sarah.jackson@the-jci.org 919-684-0620 Journal of Clinical Investigation

The liver is unique among mammalian organs in its ability to regenerate after significant tissue damage or even partial surgical removal. Laurie DeLeve and her colleagues at the University of Southern California in Los Angeles wanted to better understand which cells are specifically responsible for driving liver regeneration. A specialized cell type, known as liver sinusoidal endothelial cells, has generally been thought to promote regeneration of liver tissue. However, the DeLeve team suspected that stem cells and progenitor cells, which have the capacity to differentiate into mature cell types, might be responsible for stimulating liver regeneration by generating hepatocyte growth factor. Using a rat model system, they first identified the presence of stem and progenitor cells that give rise to liver sinusoidal endothelial cells in both the liver and the bone marrow. They next sought to determine which population of stem and progenitor cells are required for regeneration. DeLeve and colleagues found that the bone marrow-derived cells were not required for liver cell proliferation in the absence of damage. In contrast, following surgical removal of a portion of the rat liver, an infusion of bone marrow-derived progenitor cells was required for liver regeneration. These results improve our understanding of how liver tissue can regenerate following damage and may shed light on liver complications in patients with suppressed bone marrow tissue.

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TITLE: Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats

AUTHOR CONTACT: Laurie D. DeLeve University of Southern California Keck School of Medicine, Los Angeles, CA, USA Phone: 323-442-3248; Fax: 323-442-3238; E-mail: deleve@usc.edu View this article at: http://www.jci.org/articles/view/58789?key=21e2857b21106f232595

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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Restoring what's lost: Uncovering how liver tissue regenerates

Public release date: 12-Mar-2012 [ | E-mail | Share ]

Contact: Sarah Jackson press_releases@the-jci.org 919-684-0620 Journal of Clinical Investigation

EDITOR'S PICK Restoring what's lost: uncovering how liver tissue regenerates

The liver is unique among mammalian organs in its ability to regenerate after significant tissue damage or even partial surgical removal. Laurie DeLeve and her colleagues at the University of Southern California in Los Angeles wanted to better understand which cells are specifically responsible for driving liver regeneration. A specialized cell type, known as liver sinusoidal endothelial cells, has generally been thought to promote regeneration of liver tissue. However, the DeLeve team suspected that stem cells and progenitor cells, which have the capacity to differentiate into mature cell types, might be responsible for stimulating liver regeneration by generating hepatocyte growth factor. Using a rat model system, they first identified the presence of stem and progenitor cells that give rise to liver sinusoidal endothelial cells in both the liver and the bone marrow. They next sought to determine which population of stem and progenitor cells are required for regeneration. DeLeve and colleagues found that the bone marrow-derived cells were not required for liver cell proliferation in the absence of damage. In contrast, following surgical removal of a portion of the rat liver, an infusion of bone marrow-derived progenitor cells was required for liver regeneration. These results improve our understanding of how liver tissue can regenerate following damage and may shed light on liver complications in patients with suppressed bone marrow tissue.

TITLE: Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats

AUTHOR CONTACT: Laurie D. DeLeve University of Southern California Keck School of Medicine, Los Angeles, CA, USA Phone: 323-442-3248; Fax: 323-442-3238; E-mail: deleve@usc.edu

View this article at: http://www.jci.org/articles/view/58789?key=21e2857b21106f232595

ONCOLOGY New Determinant of Human Breast Cancer Metastasis Discovered

Researchers at the University of Kentucky's Markey Cancer Center in Lexington, KY have provided new insight as to why the most severe subtype of breast cancer in humans frequently metastasizes. Tumor cells can exploit a cellular program that promotes cell migration and reduces adhesion between cells to spread to distant sites in the body (metastasis). This cellular program, known as the epithelial-mesenchymal transition, is normally restricted to wound healing, tissue remodeling and embryonic development. Increasing cell motility requires a decrease in E-cadherin, which functions to promote cell-cell adhesion. Led by Binhua Zhou, the research team identified G9a as a major repressor of E-cadherin expression. They found that G9a interacts with Snail, which can repress gene expression, to modify the E-cadherin promoter and block expression of the E-cadherin gene. Their findings establish that G9a is an important determinant of metastasis in the most severe sub-type of breast cancer, and suggest the development of new therapeutics targeting this pathway could potentially disrupt the metastatic disease.

TITLE: G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer

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JCI early table of contents for March 12, 2012

Published: March 12, 2012

(NEW YORK, NY, March 11, 2012) A study by Columbia researchers suggests that cells in the patients intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

The researchconducted in micewas published 11 March 2012 in the journal Nature Genetics.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

Gut insulin cells express glucokinase, a key enzyme for glucose processing. Immunostaining detected insulin in red and glucokinase in green. Yellow marked merged colors.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai, who works in Dr. Accilis lab, is a New York Stem Cell Foundation-Druckenmiller Fellow.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

Inactivation of Foxo1, a gene important for metabolism generated insulin producing cells in small intestines of newborn mice, as detected by immunofluorescence in red.Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisionsFoxo1the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood.

Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients, Dr. Accili says.

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Columbia Researchers Find Potential Role for Gut Cells in Treating Type I Diabetes

Lindsay Porter knew she would eventually need a kidney transplant. She was 19 years old when her mother died from polycystic kidney disease -- a genetic condition that Porter had 50/50 odds of inheriting, and did.

"It didn't really affect me much until my early 30s," said Porter, an actress and mother living in Chicago. "And as I got into my 40s, my kidneys started getting very big with multiple cysts. They were huge."

Porter's kidneys weighed 16 pounds, causing an obvious bulge in her tiny frame.

"It was like two full-term babies inside me," she said, adding that people often mistook her for pregnant. "They had to be removed."

In May 2010, doctors removed Porter's overgrown and failing kidneys. Two months later, a friend gave her one of his. But it was no ordinary transplant. Along with the fist-size organ, doctors at Northwestern Memorial Hospital in Chicago transplanted bone marrow stem cells -- an experimental procedure they hoped would eliminate the need for anti-rejection drugs.

"These drugs are currently an absolute necessity, but they have a downside," said Dr. Joseph Leventhal, Porter's transplant surgeon at Northwestern Memorial Hospital and director of kidney and pancreas transplantation at Northwestern University Feinberg School of Medicine.

Anti-rejection drugs suppress the immune system, preventing it from attacking the donated organ like an infection. But suppressing the immune system makes the body vulnerable to infections and even cancer. And the drugs, which carry toxic side effects, can't ward off rejection forever. "Many individuals will still lose their transplants over time due to chronic rejection," said Leventhal.

To coax Porter's body into recognizing the new kidney as her own, Leventhal and colleagues wiped out part of her immune system and replaced it with the donor's. It took four days of chemotherapy, whole-body irradiation and a bone marrow transplant -- no walk in the park, according to Porter. But over time, the donor bone marrow stem cells gave rise to immune cells that accepted the kidney as if it was Porter's own -- a process called induced immune tolerance.

"At first I was taking 24 pills a day," said Porter, describing the "cocktail" of anti-rejection drugs needed to fend off an attack on her new kidney while the bone marrow stem cells were setting up shop. "And you really can't miss a dose. I had to set my cell phone alarm for every 12 hours every single day to remind me."

After six months, Porter started weaning herself off the drugs. And after a year, she no longer needed them at all.

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New Transplant Approach Changes Lives

A British ethics group has started a consultation on the morality of messing about in the human brain in ways that could result in thought-controlled weaponry and super-human capabilities.

The Nuffield Council on Bioethics wants to get boffins, policy-makers, regulators and anyone working with or hoping to use futuristic technologies such as brain-computer interfaces, deep brain stimulation and neural stem cell therapy to send in their views on whether poking around in our grey matter is the right thing to do.

These technologies are mostly being developed to try to help people with severe brain injuries or neurological diseases like Parkinson's disease and stroke, but they are also being picked up for military applications and to enhance normal brain functions for commercial gain.

Intervening in the brain has always raised both hopes and fears in equal measure, said Thomas Baldwin, chair of the study and Professor of Philosophy at the University of York.

Hopes of curing terrible diseases, and fears about the consequences of trying to enhance human capability beyond what is normally possible. These challenge us to think carefully about fundamental questions to do with the brain: what makes us human, what makes us an individual, and how and why do we think and behave in the way we do.

Hi-tech warfare applications creating super-soldiers who can control missiles with their minds are a particular concern for the council.

For example if brain-computer interfaces (BCIs) are used to control military aircraft or weapons from far away, who takes ultimate responsibility for the actions? Could this be blurring the line between man and machine? Baldwin asked.

BCIs, where a person's brain signals are measured and then converted into output, have already worked in a few reported cases. Medical benefits include a paralysed person being able to control their wheelchair with their mind or a computer being able to talk for people who are mute or have difficulty with speech by processing signals from their brains.

Military applications for BCIs for example, remotely controlling weapons and machines with the mind are already being researched and tested. BCIs are also being looked for their commercial value, for example, they could be used for playing video games via brain signals.

Brain stimulation, zapping the brain with electricity or magnetism in order to change brain activity, is already being used in some forms.

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Ethics profs fret over cyborg brains, mind-controlled missiles

The ethical issues around technologies that 'intervene' in the brain are set to come under scrutiny as part of a consultation by The Nuffield Council on Bioethics.

Brain-computer interfaces (BCI) are of particular concern, as they could be used in various military applications, to develop weapons or vehicles that are controlled remotely by brain signals. These are not yet in wide use but are being researched and tested, and some commercial BCI developments are already on the market.

If brain-computer interfaces are used to control military aircraft or weapons from far away, who takes ultimate responsibility for the actions? asked Thomas Baldwin, chair of the Councils study and Professor of Philosophy at the University of York. Could this be blurring the line between man and machine?

BCI measures and analyses a persons brain signals and converts them into an output such as movement. The use of BCI will sometimes require surgery to implant electrodes into a persons brain, although the most successful current developments are those that detect brain signals from the scalp, so they are less invasive.

This kind of technology can have very positive applications. For example, a person who is disabled and cannot speak might be able to move independently through a thought-controlled wheelchair, or communicate via a computer voice. There are also commercial possibilities in the gaming industry the development of thought-controlled computer games, for example.

However, many of these technologies are in the early stages of research, and Nuffield Council has raised concerns about the safety of some of the techniques that are currently in development.

The impact on a person and on their mind has to be considered, for example, are there risks of unwanted changes in mood, behaviour or personality being introduced into the brain? said Baldwin.

The consultation will also examine the ethics of deep brain stimulation, and neural stem cell therapy. Deep brain stimulation (DBS) is a form of neurostimulation that requires brain surgery to place an electrode in the brain and wires under the skin. Electric or magnetic stimuli are then applied to nerves to alter brain activity in a specific area.

DBS is currently used in the treatment of Parkinsons disease, obsessive-compulsive disorders and movement disorders such as dystonia (which causes tremors). However, possible complications include stroke, speech disorders and visual problems.

Meanwhile, neural stem cell therapy involves stem cells being injected into the brain under general anaesthetic. Researchers are looking at using this method to treat conditions such as Alzheimers or Huntingdons disease.

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Thought-controlled weapons spark ethics debate

01-02-2012 20:50 Effectively perform today's most state-of-the-art neurosurgical procedures with Youmans Neurological Surgery, 6th Edition, edited by H. Richard Winn, MD. Still the cornerstone of unquestioned guidance on surgery of the nervous system, the new edition updates you on the most exciting developments in this ever-changing field. In print and online, it provides all the cutting-edge details you need to know about functional and restorative neurosurgery (FRN)/deep brain stimulation (DBS), stem cell biology, radiological and nuclear imaging, neuro-oncology, and much more. And with nearly 100 intraoperative videos online at http://www.expertconsult.com, as well as thousands of full-color illustrations, this comprehensive, multimedia, 4-volume set remains the clinical neurosurgery reference you need to manage and avoid complications, overcome challenges, and maximize patient outcomes. Learn more at http://www.us.elsevierhealth.com

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Winn: Youmans Neurological Surgery, 6th Edition - Video