NIH
The neurologist whose writing opened a popular window on a medical “awakening” of the human mind shared his personal awakening after receiving a terminal cancer diagnosis.
Readers responded to Oliver Sacks’ “My Own Life” with gratitude.
Wednesday, April 29, 2015
Tuesday, April 28, 2015
Hormone Therapy for Multiple Sclerosis
Have you heard of Hormone Therapy for MS, such as Estrogen Therapy? Hormone Therapy for MS
Estrogen therapy is recommended primarily for the management of menopause. Some contraceptive pills also include estrogen. New research shows potential benefits of this therapy for MS as well.
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Link: http://eepurl.com/0ALk1
Stem Cell Fraud
Winnipeg Free Press - ONLINE EDITION
City man who ran stem-cell trial for MS patients fabricated credentials, overstated results
By: Melissa Martin and Mary Agnes Welch
Posted: 01/13/2015
City man who ran stem-cell trial for MS patients fabricated credentials, overstated results
By: Melissa Martin and Mary Agnes Welch
Posted: 01/13/2015
IN DEPTH
A copy of Doug Broeska’s LinkedIn profile
An example of an email Doug Broeska sent to patients to convince them to join the stem cell therapy
Letter from the Independent Ethics Committee in Pune, India, asking Doug Broeska to step down as principal investigator
Related story: MS clinic's practices stir alarm: It's allegedly 'pressuring' patients to go to India for controversial 'liberation' treatment (Melissa Martin, January 2011)
A post on the CSVI Clinic’s website slamming Free Press reporter Melissa Martin after her 2011 story on Doug Broeska and the clinic.
Proof from the University of Manitobathat Broeska didn't earn a PhD there.
Promotional video for Regenetek, which convinced many patients to join:
Sharon Nordstrom to pay $38,000 for a treatment she hoped would keep her multiple-sclerosis symptoms at bay, that money paid for what she hoped would be a life-changing stem-cell procedure at a hospital in Pune, India.
It was part of what she, and nearly 70 other patients from Manitoba and from as far away as Australia, believed was a clinical study helmed by a brilliant Winnipeg medical researcher with a PhD, who said the procedure could stop MS in its tracks.
Soon after her return in May, Nordstrom began to uncover troubling facts. Doug Broeska, whom patients reverently call "Dr. Doug," has no recognized medical credentials.
Regenetek Research, his company based out of a spartan office on Chevrier Boulevard, boasted credentials and positive medical results that didn’t add up. Patients who were once ardent supporters were attacked as saboteurs or shills for "Big Pharma" and threatened with removal from the study after they asked questions.
A Free Press investigation has found Broeska fabricated his credentials, including his PhD, and overstated the effects of the stem-cell treatment, for which he often charged desperately ill people $45,000.
Four patients spoke to the Free Press on the record, saying they got no benefit from the treatment, got none of the followup common in clinical trials — such as MRIs or physical acuity tests — and believe they are victims of fraud.
Patients, doctors in India and now Canadian officials are questioning the claims of Winnipeg researcher Doug Broeska and his $45,000 stem-cell therapy for MS sufferers.
At least two of Regenetek’s former patients have complained to the RCMP, and sources say the Canada Revenue Agency is investigating, though CRA officials would not confirm that. Last week, Regenetek’s website, Broeska’s LinkedIn page and a "patient-run" Facebook group were taken down.
The most disturbing evidence is a letter, dated Dec. 10 and obtained by the Free Press, in which the chairman of the medical ethics committee at the Inamdar Hospital in Pune ordered Broeska to step down as principal investigator of the stem-cell study, warning his lack of credentials and followup "violated international ethical standards."
The committee said its conclusions were based on information from an investigation done by the Indian Council of Medical Research, along with numerous study-related complaints.
The letter documents the committee’s concerns, including that Broeska, who previously ran a lumber business, is not a qualified health practitioner and doesn’t have sufficient experience in stem-cell research or neurology to oversee the studies. The committee said diagnosis of the diseases of some patients had been manipulated in the studies investigated.
Most worrisome, the ethics committee said it had been informed study patients were being "enforced/blackmailed to stop certain life-saving medicines," without scientific justification.
"Your appointment as Principal Investigator has significant potential to jeopardize patient safety and patient rights," the letter to Broeska stated.
Letter result of a 'mix-up,' says Broeska
Broeska, who is in the Caribbean on business for several days, said in an email he was terminated only because it was decided to have a local principal investigator stationed in India. He also said the concerns about the clinical trial related to research at another Indian hospital entirely.
"(A)s I understand it, there was a mix-up of institutions as well as a distortion of material facts after which the Indian side explained the situation," said Broeska by email. "I did not know about this enquiry, about these unauthorized therapies at other hospitals, and I was not there to answer allegations."
In a phone interview Monday, Regenetek spokesman David Audley said the stem-cell treatments are legal and ethical in India, and the company is now seeking similar ethics approval in North America.
"What’s going on with these treatments right now is perfectly legal in the jurisdiction where it’s happening," said Audley, noting the clinical trial has approval from the Pune hospital’s ethics board.
Audley refused to provide the inclusion and exclusion criteria for the clinical trial or what followup is mandated.
"I’m not going to go into the specifics of the clinical study, because it’s an ongoing clinical study," said Audley. "We’re not going to go into the details about the structure of our clinical trials, nor are we going to go into detail about how the clinical study is being managed or the outcomes are being collected. That’s all part of Regenetek’s protocol."
'This smells fishy': patient
The Free Press investigation into Broeska and Regenetek Research uncovered misrepresentations, evasions and belligerent behaviour toward patients that support the concerns raised by the hospital’s ethics board and by patients who believe Broeska’s business is medical tourism masquerading as research.
Robert Freelove’s wife, Lynn, had the stem-cell treatment last year and saw no change at all to her MS. Their Regenetek paperwork said to expect regular followups roughly every three months, so they waited for word about MRIs, medical exams, patient questionnaires or any kind of scientific measurement that Lynn had made progress.
"It’s been over seven months, and they’ve not contacted us at all," said Freelove, who lives in the Vancouver area. "This smells fishy. I just can’t get to the bottom of it."
Since the couple returned from India, they have followed some of the questions raised by other patients online, and Freelove said he was even more concerned when it appeared Broeska disqualified vocal patients.
"They have been kicking people out of the trial for voicing an opinion," said Freelove. "To me, that doesn’t sound like a proper trial."
70 have already sought treatment
Though Broeska was careful to avoid using the word "cure," he repeatedly touted the "curative" effects of stem-cell treatment, saying every patient in his studies was making a "return to health."
Some prospective patients, in a race against time and the degenerative effects of their disease, began calling Broeska’s program a "miracle treatment."
By this month, more than 70 patients had sought treatment through Regenetek, and Broeska said the company hoped to qualify as many as 300. Plans to open a satellite clinic in Trinidad are underway.
Some patients emptied their retirement funds, mortgaged their homes or launched community fundraisers to help raise the cash to get their veins opened and stem cells implanted. Nordstrom and her husband used cash set aside to buy a specialized van.
At 55, MS had ravaged Nordstrom’s body, attacked her bladder and bowel control and forced her to use a wheelchair outside her house and a walker inside. When she started reading what Broeska wrote about the treatment’s success — it would "halt the disease process," he said — she began to dream of dancing again.
"The thought of getting better overrode the common sense," said Nordstrom, who lives south of Saskatoon. "I didn’t just fall for it. I talked a lot with Doug. We looked into it, but not as in-depth as I should have."
Half of the 10 patients the Free Press contacted said they experienced some improvements following the stem-cell treatment, and even the four who didn’t said they still believe stem cells hold real hope for MS and ALS sufferers.
Punted from trial
In May 2014, Nordstrom flew to India to receive the treatment at Inamdar Hospital in Pune. Broeska told her the first thing that would improve after the procedure would be her bladder and bowel control. She felt so confident after their discussions, she didn’t take incontinence supplies for the trip home.
"There was nothing he didn’t think this could cure," she said. "He targeted everyone’s weaknesses and appealed to that."
After their two-week stay in India, she saw no change to her MS. Nordstrom and her husband had to make a pit stop in Germany to stock up on adult diapers. The promised followup contact with researchers also evaporated.
In June, Nordstrom sent an email to the Regenetek founder expressing her frustration with his silence.
In reply, Broeska sent an angry email, suggesting she was now punted from the clinical trial because of her "uncompromisingly hard feelings" that "may have already created a significant recall bias."
That email was the last contact Nordstrom had with Broeska or anyone from the clinical trial.
Study’s validity can’t be verified
Regenetek, located on Chevrier Boulevard, calls itself a private, not-for-profit medical research company that is conducting stem-cell clinical trials on MS and ALS patients at a partner hospital in Pune, India. The treatment costs between $30,000 and $45,000. Roughly 70 people have already paid for and had the treatment.
Doug Broeska’s credentials
In his LinkedIn profile, now removed, Broeska says he has a B.Sc. and a PhD from the University of Manitoba. He has signed emails with those designations. The U of M’s registrar’s office said although Broeska attended the Faculty of Arts for one year and the Faculty of Agriculture for two, he was not awarded any degrees.
In reply to repeated questions from the Free Press, Broeska said Monday he received his PhD in 2012 from "Brightland University," which may not exist. There is a website for Brightland University that lists its administrator as David Miller with UDP International.
That company, University Degrees Program, was a well-known degree mill operating dozens of fraudulent institutions. The U.S. Federal Trade Commission shut down many of its sites in 2003, though it remained active on a smaller scale.
The International Cellular Medicine Society
In several emails to patients and in the company’s promotional material, Broeska claims he is a member of the society. The ICMS’s executive director, Reed Davis, said he could find no evidence Broeska was or is a member.
Institutional review boards
Those are independent ethical review panels, often associated with hospitals or medical societies, that review clinical trials to make sure they are on the up and up. The credibility of any IRB must be assessed, because doctors or researchers can create their own "independent" IRB and use it to give their research an aura of legitimacy.
In emails, on Facebook and on the Regenetek website, Broeska frequently makes reference to his IRB approvals. It’s difficult to track the maze of acronyms and verify these.
In a Facebook post last fall, Broeska said, "We have several Institutional Research Board (IRB) accreditations. The therapeutic protocol adheres to all rules and guidelines for such therapeutic research as laid down by the International Cellular Medicine Society (ICMS) and the World Medical Association."
In an email to patient Kathleen Jaynes, Broeska claimed he had approval from the ICMS’s ethics committee. Reed Davis, head of the ICMS, searched his files and consulted with his board and could find no record of Regenetek or Broeska having applied for or received ethics approval for the clinical trial.
More recently, Regenetek’s website said "as of March 16, 2014, Institutional Review Board approval has been granted by the US-based International Cell Surgical Society (ICSS)." The ICSS is a very new organization, founded by David Audley, now Regenetek’s spokesman and partner. Last week, the ICSS’s address, listed online, matched that of David Audley. Documents suggest Regenetek’s study does have approval from the ethics committee at the Indian hospital in Pune.
In an email to the Free Press Friday, Broeska said his treatment "is a legitimate and duly registered clinical study based out of India."
"However, we are also in the process of having the clinical study registered in the U.S., through the IRB (registration pending)."
The World Medical Association
In several emails to patients, Broeska makes reference to the World Medical Association and its rules, particularly its rules allowing patients to pay for clinical trials.
"Patient funding of medical research is permitted as an ethical practice by convention in accordance with the World Medical Association...," Broeska wrote to a patient in 2013. That is "absolutely not true" said the WMA’s London-based spokesman, Nigel Duncan.
The ethical guidelines for stem-cell research in India, as laid out by the Indian Council of Medical Research, prohibit patients paying for clinical-trial treatment.
Clinical-trials registry
Regenetek’s study is not listed on any registries, in North America or in India. On active Facebook sites, patients have frequently asked why Regenetek’s trial is not listed on the National Institutes of Health’s registry or on the Indian Council of Medical Research’s clinical-trials registry.
Late last month, a "patient-run" Facebook site dedicated to Regenetek’s research was abruptly shut down following a heated discussion on this topic.
Paul O’Connor, a neurologist and the national scientific and clinical adviser for the MS Society of Canada, said patients should be wary of clinical trials not listed on registries, ideally the NIH’s. "I wouldn’t be comfortable," he said.
In a post last Wednesday on Regenetek’s official Facebook site, spokesman David Audley said he is "conducting a full audit and review to assure regulatory compliance" so Regenetek can apply to the NIH’s registry.
Efficacy of outcomes
Broeska frequently represents the success of his stem-cell treatment, stopping short of calling it a cure. "As a result of our translational research, we are currently the ONLY therapeutic research project world-wide where patients under study are demonstrating consistent and significant long-term improvements in both mitigation of the disease itself and the recovery of neurological deficits," he wrote in an email to a patient.
More recently, on Regenetek’s website, Broeska wrote: "Patient outcomes over the past 30 months have been compelling. Each and every one of over 60 patients in the trial has demonstrated significant functional improvement with enduring effect. Many have returned to complete health without symptoms, and some have been declared ‘disease-free’ by their neurologist."
There are at least six patients who say they have had no lasting effects from the stem-cell treatments. The Free Press has spoken to four on the record. At least one, Alberta’s Lee Chuckry, believes the stress of travelling to India and his frustration with Regenetek’s aftercare made his MS worse.
Marketing
Marketing or promoting clinical trials is banned in Canada. But, Broeska repeatedly asked patients to post positive experiences on an active "patient-run" Facebook page and later hired a marketing expert to create professional-quality videos showing patients who experienced significant recoveries. Those videos are available on his website, on YouTube and on Facebook. Of the nine patients who spoke to the Free Press about their treatment, nearly all said the videos helped convince them Regenetek’s stem-cell treatment was credible.
Broeska told the Free Press participation in the study is "voluntary, highly confidential and by word of mouth. Regenetek did not advertise or solicit for participants in the clinical study."
Disqualifying patients
Three of the four patients who spoke on the record, including Sharon Nordstrom, say they were "disqualified" from the study for raising questions about Regenetek’s methods, Broeska’s credentials and especially the lack of followup care and assessment. Broeska denied any patients were disqualified because they criticized him or Regenetek.
In Nordstrom’s case, her final contact with Broeska was an email on June 16, 2014, about a month after she had returned from India and began asking questions about the lack of followup care or monitoring.
"I really don’t appreciate the tone you’ve taken in this email considering the fact that I work from 12-16 hours per day for all of the patients including you, and for the purpose of extending the research into physiotherapy," Broeska wrote.
"If you take personal effrontery at the fact that I can’t simply schedule myself to sit in front of the telephone and dial in the hope of getting through to you, then there’s nothing more I can do for you. From your email it doesn’t seem that you care to continue in the research program. Furthermore, your uncompromisingly hard feelings over a perceived slight may have already created a significant recall bias that won’t permit your continued participation. I am now required to send this email off to the other physicians in our group for review and I must report it to the Ethics Committee for comment and advice."
The MS Society’s senior neurologist, Paul O’Connor, said disqualifying patients from a clinical trial after treatment is simply not done.
"You follow the patients for the entire duration of the study, no matter how they’re doing," said O’Connor. "Otherwise, you bias the results."
melissa.martin@freepress.mb.ca, maryagnes.welch@freepress.mb.ca
Regenetek, a Canadian company that arranged for patients to travel to India for an experimental stem cell treatment under the guise of a certified medical clinical trial.
Over the last several weeks, the Canadian press has revealed that the man behind Regenetek, Mr. Doug Broeska, allegedly misrepresented his credentials, the qualifications and abilities of his company to conduct a valid medical clinical study, and cajoled, bullied, and berated patients who dared question his authority or the veracity of his claims (click here).
It must be said that while some of the patients who underwent the Regenetek’s stem cell therapy in India received no benefit, others have reported good results, and that’s where this story gets tricky.
Though Regenetek and Doug Broeska may turn out to be complete shams, the stem cell therapy the company was hawking may have value, at least according to patients who claim to have seen benefit from it (click here).
Source: http://www.winnipegfreepress.com/breakingnews/Sufferers-feel-swindled-288496041.html?cx_navSource=d-top-story
Monday, April 27, 2015
Oliver Sacks has cancer
By OLIVER SACKS FEB. 19, 2015
Credit Hanna Barczyk
The Opinion Pages| Op-Ed Contributor
My Own Life
Oliver Sacks on Learning He Has Terminal Cancer
A MONTH ago, I felt that I was in good health, even robust health. At 81, I still swim a mile a day. But my luck has run out — a few weeks ago I learned that I have multiple metastases in the liver. Nine years ago it was discovered that I had a rare tumor of the eye, an ocular melanoma. Although the radiation and lasering to remove the tumor ultimately left me blind in that eye, only in very rare cases do such tumors metastasize. I am among the unlucky 2 percent.
I feel grateful that I have been granted nine years of good health and productivity since the original diagnosis, but now I am face to face with dying. The cancer occupies a third of my liver, and though its advance may be slowed, this particular sort of cancer cannot be halted.
It is up to me now to choose how to live out the months that remain to me. I have to live in the richest, deepest, most productive way I can. In this I am encouraged by the words of one of my favorite philosophers, David Hume, who, upon learning that he was mortally ill at age 65, wrote a short autobiography in a single day in April of 1776. He titled it “My Own Life.”
“I now reckon upon a speedy dissolution,” he wrote. “I have suffered very little pain from my disorder; and what is more strange, have, notwithstanding the great decline of my person, never suffered a moment’s abatement of my spirits. I possess the same ardour as ever in study, and the same gaiety in company.”
I have been lucky enough to live past 80, and the 15 years allotted to me beyond Hume’s three score and five have been equally rich in work and love. In that time, I have published five books and completed an autobiography (rather longer than Hume’s few pages) to be published this spring; I have several other books nearly finished.
Hume continued, “I am ... a man of mild dispositions, of command of temper, of an open, social, and cheerful humour, capable of attachment, but little susceptible of enmity, and of great moderation in all my passions.”
Here I depart from Hume. While I have enjoyed loving relationships and friendships and have no real enmities, I cannot say (nor would anyone who knows me say) that I am a man of mild dispositions. On the contrary, I am a man of vehement disposition, with violent enthusiasms, and extreme immoderation in all my passions.
And yet, one line from Hume’s essay strikes me as especially true: “It is difficult,” he wrote, “to be more detached from life than I am at present.”
Over the last few days, I have been able to see my life as from a great altitude, as a sort of landscape, and with a deepening sense of the connection of all its parts. This does not mean I am finished with life.
On the contrary, I feel intensely alive, and I want and hope in the time that remains to deepen my friendships, to say farewell to those I love, to write more, to travel if I have the strength, to achieve new levels of understanding and insight.
This will involve audacity, clarity and plain speaking; trying to straighten my accounts with the world. But there will be time, too, for some fun (and even some silliness, as well).
I feel a sudden clear focus and perspective. There is no time for anything inessential. I must focus on myself, my work and my friends. I shall no longer look at “NewsHour” every night. I shall no longer pay any attention to politics or arguments about global warming.
This is not indifference but detachment — I still care deeply about the Middle East, about global warming, about growing inequality, but these are no longer my business; they belong to the future. I rejoice when I meet gifted young people — even the one who biopsied and diagnosed my metastases. I feel the future is in good hands.
I have been increasingly conscious, for the last 10 years or so, of deaths among my contemporaries. My generation is on the way out, and each death I have felt as an abruption, a tearing away of part of myself. There will be no one like us when we are gone, but then there is no one like anyone else, ever. When people die, they cannot be replaced. They leave holes that cannot be filled, for it is the fate — the genetic and neural fate — of every human being to be a unique individual, to find his own path, to live his own life, to die his own death.
I cannot pretend I am without fear. But my predominant feeling is one of gratitude. I have loved and been loved; I have been given much and I have given something in return; I have read and traveled and thought and written. I have had an intercourse with the world, the special intercourse of writers and readers.
Above all, I have been a sentient being, a thinking animal, on this beautiful planet, and that in itself has been an enormous privilege and adventure.
.........................................
Oliver Sacks, a professor of neurology at the New York University School of Medicine, is the author of many books, including “Awakenings” and “The Man Who Mistook His Wife for a Hat.”
A version of this op-ed appears in print on February 19, 2015, on page A25 of the New York edition with the headline: My Own Life.
Source: http://www.nytimes.com/2015/02/19/opinion/oliver-sacks-on-learning-he-has-terminal-cancer.html
Readers Respond: On ‘My Own Life’
“I have been able to see my life as from a great altitude, as a sort of landscape, and with a deepening sense of the connection of all its parts,” Mr. Sacks wrote. “I feel intensely alive, and I want and hope in the time that remains to deepen my friendships, to say farewell to those I love, to write more, to travel if I have the strength, to achieve new levels of understanding and insight.”
A science writer, a former medical student, the mother of a child with autism, a man on his “way out” and a man who, by chance, shared an airport lunch table with Mr. Sacks were among those who shared their own adventures of the mind.
At least one skeptic weighed in.
At least one skeptic weighed in.
As a young student engaged in the history of science, SAS from Newton, Mass., wrote, “your books inspired, delighted and amazed me. When I had a child, I would read passages out loud to my daughter, who is now studying to become a neuroscientist. Your words have become part of the fabric of our lives.”
Mr. Sacks wrote of an intense sense of purpose in his remaining days, familiar in the literature of death and dying. “I feel a sudden clear focus and perspective,” he wrote. “There is no time for anything inessential.”
Daily marvels took on shape in comments, too.
“Each morning I observe the sun as it begins its glorious show. I observe flowers as they open, and our fish as they wander our pond,” Richard Schmidt wrote from Concord, N.C. “I observe our grandchildren, as they change each day. All is wonder.”
One reader said Mr. Sacks’s recitation of books written and manuscripts pending seemed out of place. The neurologist’s joys and intensity, rather than inspire him, brought to mind the shortcomings in his own life.
“It is depressing because it highlights my own lack of human connections and significant accomplishments,,” A. Davey wrote from Portland. “How can those of us who have suffered from isolation and disappointment take any comfort or guidance from these words?”
A former medical student of Mr. Sacks’s described the imposing bearded figure of the onetime weight lifter riding a motorcycle through New York City, and illustrated the humor of his gentle mentor.
“On demonstrating the gag response on me, to which I didn’t gag, he remarked: ‘Either you are missing the response or being very polite,’” Donald Green of Reading, Mass., wrote of one lesson. “He respectfully introduced us to patients who were later portrayed in ‘Awakenings.’ It was eerie to have your memory jogged by a movie of something you had observed so closely years before.”
A reader with a terminal diagnosis of his own said reading Mr. Sacks’s work, he “learned about migraine; mysterious, Parkinsonian sleep; your British Jewish family; hallucination; music; and, above all, human idiosyncrasy,” G wrote from Virginia. “Your voice is clear and kind and, as I like to think, has inspired kindness in my own soul.”
A mother whose child has autism and “a brilliant, very alive mind” wrote to appreciate Mr. Sacks “for helping open minds to all of the wonderful human possibility expressed in the idea of neurodiversity.”
A New Yorker recounted a time at a California airport when an older man asked to sit at his table as they awaited their plane to the city. “As he sat quietly, eating his chicken noodle soup and crackers, I couldn’t help but notice that he looked familiar,” wrote Phillip from New York City, who realized eventually that he was sitting with the best-selling author. “Fortunately, I was prepared, having just finished reading ‘An Anthropologist on Mars’ and ‘Uncle Tungsten.’ … He even gave me a sneak preview of his forthcoming book on music.”
Mr. Sacks wrote that watching his generation fade out has pained him.
“Each death I have felt as an abruption, a tearing away of part of myself,” he wrote. “It is the fate — the genetic and neural fate — of every human being to be a unique individual, to find his own path, to live his own life, to die his own death.”
Despite the pending abruption, some readers said Mr. Sacks’ life will continue to inspire imagination.
“I heard something at a friend’s funeral not too long ago about immortality — that we do live forever, and not just as memories,”Elizabeth Fuller wrote from Peterborough, N.H. “What we have done, said, and written lives on in ways big and small, often subconsciously, in those whose lives we have touched.”
Source: http://op-talk.blogs.nytimes.com/2015/02/23/readers-respond-on-my-own-life/?emc=edit_ty_20150224&nl=opinion&nlid=59725256&_r=0
Biomarkers For Chronic Fatigue Syndrome Found
Those with chronic fatigue syndrome - now systemic exertion intolerance disease - vary in their immune systems
http://www.nytimes.
http://www.nytimes.
Study on Chronic Fatigue May Help With Diagnoses
By DAVID TULLERFEB. 27, 2015
The immune systems of people with chronic fatigue syndrome differ from those of healthy people, and patients with recent diagnoses can be distinguished from those who have had the condition for longer, researchers reported on Friday.
The findings do not have immediate clinical applications for patients, experts said. But the biomarkers discovered by the scientists may eventually form the basis of the first diagnostic test for the illness.
“A biomarker has been the goal for much of the research for the last 15 years, so it’s really excellent that they have found something they consider significant,” said Dr. Birgitta Evengard, a professor of clinical microbiology at Umea University in Sweden and an expert on the illness.
The findings still need to be replicated in other labs with other groups of patients, cautioned Dr. Evengard, who was not involved in the research.
The study was published online in a new open-access journal called Science Advances, just two weeks after the Institute of Medicine proposed a new name for the illness — “systemic exertion intolerance disease” — and new diagnostic criteria to better identify patients. The authors of a report put out by the institute described the illness as a biological disorder and said the central symptom was “post-exertional malaise,” a sustained relapse after minimal activity.
Chronic fatigue syndrome is also called myalgic encephalomyelitis, which means “muscle pain with brain and spinal cord inflammation,” and is often referred to as ME/CFS. An estimated one million Americans may have the condition, and some are homebound for years.
For the study, the research team — which included scientists from Columbia, Stanford and Harvard — tested the blood of 298 patients with the syndrome, and 348 healthy people who served as a control group, for 51 cytokines, substances that function as messengers for the immune system. When the team compared all the patients with all the healthy controls, they found no significant differences between the two groups.
But after dividing the patients into two cohorts — those who had been sick for less than three years and those who had been sick longer — they found sharp differences. And both sets of patients were different from healthy controls.
Patients who had been ill for less than three years had “a prominent activation” of cytokines that influence inflammation in the body compared with other study subjects, the scientists found.
Those sick for longer than three years exhibited dampened cytokine activity, which the researchers interpreted as a possible sign of premature immune-system aging.
“There are biological markers that can be detected in the blood soon after the onset of the disease, and this has very important diagnostic implications,” said Dr. Mady Hornig, an associate professor of epidemiology at Columbia University and lead author of the new study.
Most cases of ME/CFS occur after an acute viral infection. Some researchers have speculated that the infection, or an environmental exposure or other trauma, sets off an immune response that increases cytokine production. The immune system, however, does not return to normal functioning once the threat has passed.
The underlying cause of the syndrome is unknown, and current treatments generally aim for symptom relief. Some medications already in use affect the cytokines that were shown to be active in patients, Dr. Hornig said. Those drugs would be obvious candidates to test in clinical trials, she said.
The research team plans to publish data later this year on changes in individual cytokine profiles over time, tracking more closely how they fluctuate with the reported severity of symptoms and other factors, Dr. Hornig said.
A version of this article appears in print on February 28, 2015, on page A12 of the New York edition with the headline: Study on Chronic Fatigue May Help With Diagnoses.
Celexa Withdrawal
Mental Health Blog
Celexa (Citalopram) Withdrawal Symptoms: How Long Will They Last?
Celexa (Citalopram) is a drug used to help treat symptoms of major depression. It is considered an SSRI (selective-serotonin reuptake inhibitor) which means it influences the serotonin in the brain to help ward off depressive symptoms.
It is also used as an off-label treatment for anxiety disorders, panic attacks, and obsessive compulsive disorder (OCD). For many individuals, this drug is effective and serves the intended purpose of treating depression.
The problem with Celexa is that many people find that it leads to unbearable side effects including: weight gain and sexual dysfunction. Not only can this drug provoke unwanted side effects, in some cases it just doesn’t work as well as expected. There have also been disputes as to whether the R-stereoisomer of the drug has any effect. Some have argued that it is better to take Lexapro, which is essentially Celexa without the R-stereoisomer.
In any regard, most people that take Celexa will end up wanting to withdraw from it eventually. Most people do not want to be on antidepressants for life in order to cope with depression. There are simply too many side effects and most people notice that the antidepressant effects tend to wear off over time. In any event,
The problem with Celexa is that many people find that it leads to unbearable side effects including: weight gain and sexual dysfunction. Not only can this drug provoke unwanted side effects, in some cases it just doesn’t work as well as expected. There have also been disputes as to whether the R-stereoisomer of the drug has any effect. Some have argued that it is better to take Lexapro, which is essentially Celexa without the R-stereoisomer.
In any regard, most people that take Celexa will end up wanting to withdraw from it eventually. Most people do not want to be on antidepressants for life in order to cope with depression. There are simply too many side effects and most people notice that the antidepressant effects tend to wear off over time. In any event,
if you withdraw from this medication, it is pretty much guaranteed that you are going to experience withdrawal symptoms.
Factors that influence Celexa withdrawal include:
There are various factors that play a role in influencing withdrawal from any psychiatric medication. These factors include things like: time span, dosage, your physiology, and whether you decided to quit cold turkey or conducted a gradual taper.
1. Time Span
How long were you taking Celexa? In general, the longer you take an antidepressant, the more difficult it will be to withdraw from. Your brain becomes accustomed to getting the extra serotonin activity as a result of the SSRI that you are taking. When you stop the drug, your brain isn’t get the extra serotonin that it was getting and may have a tough time readjusting to functioning without Celexa.
2. Dosage (10 mg, 20 mg, 40 mg)
Most of the time people are on a 20 mg dose of Celexa, but it can be administered at doses up to 40 mg per day. Some people may be on smaller doses than 20 mg, but in general, 20 mg is considered the standard dose. In most cases, the greater the amount of the drug that you have taken, the tougher it is to withdraw from.
3. Individual Physiology
In many cases, withdrawal symptoms are largely due to individual reactions to the drug. One person may experience extreme withdrawal symptoms that last months, while another person may feel back to 100% after a couple weeks of discontinuation. Many individual factors including: withdrawal sensitivity, environment, social support, and physiology can have an influence. If you experience a more extreme withdrawal than most, it could be largely due to individual differences.
4. Cold Turkey vs. Tapering
How did you quit taking Celexa? Did you stop abruptly without conducting a gradual taper? Or did you conduct a gradual taper over the course of a couple months? In most cases, the more slowly and cautiously you taper off of this medication, the easier it is to readjust to functioning without the drug.
If you quit cold turkey, it leaves most people in a state of mental disarray and chaos and the symptoms may be more severe. If you were on a high dose of Celexa (i.e. 40 mg), the weaning process should take longer than someone on 10 mg.
Celexa Withdrawal Symptoms: List of Possibilities
Below are a list of common symptoms that you may experience upon withdrawal from Celexa. Understand that you may experience a few of the symptoms, none of the symptoms, or most of the symptoms – it all depends on your individual circumstances. This list was created to help people so that they know what may occur during withdrawal.
Anxiety: The anxiety that you experience during withdrawal may be pretty severe. It may be so severe that you feel nervous everywhere you go and/or have panic attacks. This is a result of your brain being left without reuptake inhibition of serotonin.
Brain zaps: Most SSRI’s can lead to a person experiencing “brain zaps” or electrical shock sensations upon withdrawal. These can be very uncomfortable and actually feel like your head is plugged into an electrical socket. Just know that these will subside the longer you are off the drug.
Concentration problems: Many people report that they are unable to focus during withdrawal. It may be difficult to complete work-related tasks or school work during withdrawal. In many cases the concentration problems are due to the fact that physical symptoms distract our mental focus. Additionally a person may feel mentally slow and/or foggy when they stop the medication – this is likely due to changes in levels of neurotransmitters.
Confusion: Your cognitive functioning can become impaired when you quit taking Celexa to the point of experiencing general confusion. This confusion may be a result of memory retrieval problems, but could also just be confused thinking.
Crying spells: Some people report increased depression to the point of crying spells. Low serotonin can cause people to cry excessively. You may cry more than you have in your entire life during a withdrawal. Know that these spells will lessen in severity and eventually stop.
Depression: Most people feel significantly worse when they stop taking Celexa in regards to depression. Many people feel as if their depression is actually worse than before they took this medication. This is a result of their brain no longer inhibiting the re-uptake of serotonin to the degree that occurred on the medication. It will take an extended period of time to fully recover from the withdrawal depression.
Diarrhea: Some people experience an upset stomach to the point of diarrhea during their withdrawal. This is not as common of a symptom as others, but can be difficult to deal with if you are dealing with this. An easy solution for coping with this is to get some over-the-counter Imodium.
Dizziness: Feeling dizzy is one of the most common symptoms to experience during SSRI withdrawal. If you suddenly stop taking Celexa cold turkey, the dizziness is thought to be longer lasting and more profound than during a gradual taper. Either way, you are likely going to experience some degree of dizziness when you quit. The longer you are off the drug, the more this symptom will improve.
Fatigue: You may feel excessively fatigued for awhile after you quit Celexa. It may be difficult to get out of bed in the morning or even make it through a work day. The tiredness and lethargy may be pretty severe. Just recognize that this will gradually improve and your energy levels will start to return over time.
Headaches: This is another classic symptom of SSRI withdrawal. Some people feel minor headaches for awhile, yet for others the headaches are pounding and feel more like migraines. Having a headache with dizziness is certainly uncomfortable – but both of these will gradually improve.
Insomnia: Since some people take Celexa for treating insomnia, it is no wonder that they may actually experience insomnia when they stop taking it. Additionally even if you have never had insomnia before taking this drug, you may experience it during withdrawal.
Irritability: Most people report a high amount of irritability in the first few weeks when they discontinue this drug. This is because the brain no longer is receiving the calming effect of the drug and it can be difficult to regulate emotions.
Memory problems: It is common to experience memory problems to the point that you think you have lost your memory. Although you haven’t likely lost any memory, your thinking may be impaired so that your memory retrieval is impaired. As you recover during withdrawal, this will eventually heal itself.
Mood swings: It’s very common to have bad mood swings when you stop taking Celexa. One minute you may feel pretty good, the next you may feel more depressed than ever. Just understand that these mood swings are all part of withdrawal. They may persist for a long time, but will eventually subside.
Nausea: Some people experience nausea when they first quit this drug. You may feel nauseated all day and in some cases, want to vomit. Most people do not have nausea extreme enough to lead to vomiting, but it can be a tough withdrawal symptom to deal with.
Sleep changes: It is very likely that your sleep cycle will be affected when you withdraw from this drug. You may notice that you have crazy dreams and/or that you aren’t able to get a good night’s sleep. You may sleep during the day and be unable to fall asleep at night. Just know that things will return to normal if given enough time.
Suicidal thoughts: It is very common to experience suicidal thoughts when discontinuing an antidepressant. Any SSRI that is withdrawn from is likely to lead a person to feeling suicidal. Many doctors view this as a worsening in depression, when in reality it is a result of antidepressants causing suicidality upon withdrawal.
Weight changes: Most people gain weight when they take Celexa – this is a result of serotonin changes. When a person stops taking this drug, they will likely drop the weight that they gained while taking the drug. For more information read about antidepressants and weight gain.
Celexa Withdrawal Timeline: How long does it last?
Most doctors will tell you that the withdrawal symptoms should subside within a few weeks of withdrawal. If your symptoms subside within a few weeks, consider yourself lucky and in the minority. Most people experience withdrawal effects over a month after they have quit their medication. I recommend giving yourself at least 90 days before evaluating the withdrawal symptoms.
I have gone through my fair share of antidepressant withdrawals – including that from Celexa and have found that three months time is good for re-evaluation. The problem for most people is that the symptoms are so severe in the first few weeks of withdrawal that they feel as if their life will never be the same. During withdrawal it is important to do your best not to get caught up in the symptoms – rather focus on what you can do to recover as fast as possible.
Things that will help you recover quicker include: eating healthy, forcing yourself to get some light exercise, and getting a proper night’s sleep. If you are struggling to come to terms with symptoms and/or cope, be sure to talk to a therapist or professional about what you are experiencing. It can also be very helpful to talk to others on forums that are also going through Celexa withdrawal – many people that have experienced it are better to talk to because they actually “get it.”
Sunday, April 26, 2015
Jon Kabat Zinn - Wherever You Go There You Are Full Audiobook
Published on Nov 10, 2014
Jon Kabat Zinn - Wherever You Go There You Are Full Audiobook
NO COPYRIGHT INFRINGEMENT INTENDED
ALL CONTENT BELONGS TO THEIR RESPECTIVE OWNERS.
THIS IS FOR EDUCATIONAL AND TRANSFORMATIVE PURPOSE
NO COPYRIGHT INFRINGEMENT INTENDED
ALL CONTENT BELONGS TO THEIR RESPECTIVE OWNERS.
THIS IS FOR EDUCATIONAL AND TRANSFORMATIVE PURPOSE
Older Really Can Mean Wiser
HEALTH | MIND
Older Really Can Mean Wiser
By BENEDICT CAREYMARCH 16, 2015
Behind all those canned compliments for older adults — spry! wily! wise! — is an appreciation for something that scientists have had a hard time characterizing: mental faculties that improve with age.
Knowledge is a large part of the equation, of course. People who are middle-aged and older tend to know more than young adults, by virtue of having been around longer, and score higher on vocabulary tests, crossword puzzles and other measures of so-called crystallized intelligence.
Still, young adults who consult their elders (mostly when desperate) don’t do so just to gather facts, solve crosswords or borrow a credit card. Nor, generally, are they looking for help with short-term memory or puzzle solving. Those abilities, called fluid intelligence, peak in the 20s.
No, the older brain offers something more, according to a new paper in the journal Psychological Science. Elements of social judgment and short-term memory, important pieces of the cognitive puzzle, may peak later in life than previously thought.
The postdoctoral fellows Joshua Hartshorne of M.I.T. and Laura Germine of Harvard and Massachusetts General Hospital analyzed a huge trove of scores on cognitive tests taken by people of all ages. The researchers found that the broad split in age-related cognition — fluid in the young, crystallized in the old — masked several important nuances.
“This dichotomy between early peaks and later peaks is way too coarse,” Dr. Hartshorne said. “There are a lot more patterns going on, and we need to take those into account to fully understand the effects of age on cognition.”
The new paper is hardly the first challenge to the scientific literature on age-related decline, and it won’t be the last. A year ago, German scientists argued that cognitive “deficits” in aging were caused largely by the accumulation of knowledge — that is, the brain slows down because it has to search a larger mental library of facts. That idea has stirred some debate among scientists.
Experts said the new analysis raised a different question: Are there distinct, independent elements of memory and cognition that peak at varying times of life?
“I think they have more work to do to demonstrate that that’s the case,” said Denise Park, a professor of behavior and brain science at the University of Texas at Dallas. “But this is a provocative paper, and it’s going to have an impact on the field.”
The strength of the new analysis is partly in its data. The study evaluated historic scores from the popular Wechsler intelligence test, and compared them with more recent results from tens of thousands of people who took short cognitive tests on the authors’ websites, testmybrain.org and gameswithwords.org. The one drawback of this approach is that, because it didn’t follow the same people over a lifetime, it might have missed the effect of different cultural experiences, said K. Warner Schaie, a researcher at Penn State University.
But most previous studies have not been nearly as large, or had such a range of ages. Participants on the websites were 10 to 89 years old, and they took a large battery of tests, measuring skills like memory for abstract symbols and strings of digits, problem solving, and facility reading emotions from strangers’ eyes.
At least as important, the researchers looked at the effect of age on each type of test. Previous research had often grouped related tests together, on the assumption that they captured a single underlying attribute in the same way a coach might rate, say, athleticism based on a person’s speed, strength and vertical leaping ability.
The result of the new approach? “We found different abilities really maturing or ripening at different ages,” Dr. Germine said. “It’s a much richer picture of the life span than just calling it aging.”
Processing speed — the quickness with which someone can manipulate digits, words or images, as if on a mental sketch board — generally peaks in the late teens, Dr. Germine and Dr. Hartshorne confirmed, and memory for some things, like names, does so in the early 20s. But the capacity of that sketch board, called working memory, peaks at least a decade later and is slow to decline. In particular, the ability to recall faces and do some mental manipulation of numbers peaked about age 30, the study found, “a fact difficult to assimilate into the fluid/crystalized intelligence dichotomy.”
The researchers also analyzed results from the Reading the Mind in the Eyes test. The test involves looking at snapshots of strangers’ eyes on a computer screen and determining their moods from a menu of options like “tentative,” “uncertain” and “skeptical.”
“It’s not an easy test, and you’re not sure afterward how well you did,” Dr. Germine said. “I thought I’d done poorly but in fact did pretty well.” Yet people in their 40s or 50s consistently did the best, the study found, and the skill declined very slowly later in life.
The picture that emerges from these findings is of an older brain that moves more slowly than its younger self, but is just as accurate in many areas and more adept at reading others’ moods — on top of being more knowledgeable. That’s a handy combination, given that so many important decisions people make intimately affects others.
No one needs a cognitive scientist to explain that it’s better to approach a boss about a raise when he or she is in a good mood. But the older mind may be better able to head off interpersonal misjudgments and to navigate tricky situations.
“As in, ‘that person’s not happy with all your quick thinking and young person’s processing speed — he’s about to punch you,’” said Zach Hambrick, a psychology professor at Michigan State University.
The details of this more textured picture of the aging brain are still far from clear, and social measures like the Reading the Mind in the Eyes test have not been used much in this kind of research, Dr. Hambrick and other experts said. And it is not apparent from the new analysis whether changes in cognition with age result from a single cause — like a decline in the speed of neural transmission — or to multiple ones.
But for now, the new research at least gives some meaning to the empty adjective “wily.”
A version of this article appears in print on March 17, 2015, on page D3 of the New York edition with the headline: Older Really Can Mean Wiser.
Source: http://www.nytimes.com/2015/03/17/health/older-really-can-mean-wiser.html?WT.mc_id=2015-APRIL-INYT-INTL_REG_ENG-0407-0411&WT.mc_ev=click&ad-keywords=IntlAudDev
A sceptical view of human adult neurogenesis
Does your brain produce new cells?
A sceptical view of human adult neurogenesis
Mo Costandi
Thursday 23 February 2012
Here's the original draft of a feature article from New Scientist, about adult neurogenesis in the human brain.
Neurogenesis refers to the production of new nerve cells. Everyone wants to believe the human brain continues to produce new cells throughout life. But the evidence for this is thin and several prominent researchers are very sceptical about it.
At the MRC Centre for Developmental Neurobiology,
Fountain of eternal youth?
For much of the past century, it was thought that the production of new neurons – neurogenesis – was restricted to embryonic development. "Once development was ended," wrote Santiago Ramón y Cajal, the father of modern neuroscience, "the founts of growth… dried up irrevocably. In the adult, the nerve paths are… immutable. Everything may die, nothing may be regenerated."
This became the central dogma of neuroscience, but the view began to change in the 1980s, when Fernando Nottebohm of Rockefeller University published the first clear evidence of adult neurogenesis in the vertebrate brain.
Nottebohm showed that the adult canary brain undergoes seasonal changes in size. Males sing to serenade females, but the song-producing brain regions decrease dramatically in size after breeding season. The following spring, they are regenerated by neurogenesis so the male can learn new songs.
In fact, Joseph Altman of the Massachusetts Institute of Technology had reported evidence of adult neurogenesis in the 1960s, in the hippocampus of adult rats and guinea pigs and cortex of cats, but his work was ignored and then ridiculed.
In fact, Joseph Altman of the Massachusetts Institute of Technology had reported evidence of adult neurogenesis in the 1960s, in the hippocampus of adult rats and guinea pigs and cortex of cats, but his work was ignored and then ridiculed.
"Altman started the idea of adult neurogenesis, but his data weren't convincing," says Nottebohm. "Our results showed, beyond reasonable doubt, that neurons are born in adulthood and incorporated into existing circuits. They brought to an end most resistance against the idea."
Evidence of adult neurogenesis in mammals quickly followed. In 1992, Samuel Weiss and Brent Reynolds of the University of Calgary isolated neural stem cells from the brains of adult mice and showed that they can generate neurons and astrocytes when grown in a Petri dish. This was confirmed by Fred Gage of the Salk Institute.
Evidence of adult neurogenesis in mammals quickly followed. In 1992, Samuel Weiss and Brent Reynolds of the University of Calgary isolated neural stem cells from the brains of adult mice and showed that they can generate neurons and astrocytes when grown in a Petri dish. This was confirmed by Fred Gage of the Salk Institute.
In collaboration with various colleagues, Gage also showed that
exercise and environmental enrichment increase the rate of adult neurogenesis, and that the number of new cells produced declines with age. Thousands of studies have now been published, and it is widely accepted that the adult mouse brain continues to produce new neurons.
From mice to monkeys and men
In the late 1990s, Elizabeth Gould of Princeton University reported evidence of adult neurogenesis in the monkey hippocampus, and showed that stress decreases stem cell division in the dentate gyrus. The monkey brain is much bigger than that of rodents, however, and the process is protracted. Fewer cells are produced, they migrate larger distances and take longer to mature. According to one recent study by researchers from the University of Illinois, new cells in the macaque dentate gyrus take at least six months to mature fully.
Adult neurogenesis is implicated in depression and Alzheimer's disease, both of which involve hippocampal shrinkage. The anti-depressants Prozac and imipramine stimulate hippocampal neurogenesis in adult mice and some of their effects depend on the new cells. They also make immature hippocampal cells derived from human embryos divide in the Petri dish.
It is now taken for granted that adult neurogenesis occurs in humans, and the idea has revolutionized the way we think about the brain. It is widely believed that physical and mental exercise can stimulate hippocampal neurogenesis that offsets age-related cognitive decline and may protect against depression and Alzheimer's.
From mice to monkeys and men
In the late 1990s, Elizabeth Gould of Princeton University reported evidence of adult neurogenesis in the monkey hippocampus, and showed that stress decreases stem cell division in the dentate gyrus. The monkey brain is much bigger than that of rodents, however, and the process is protracted. Fewer cells are produced, they migrate larger distances and take longer to mature. According to one recent study by researchers from the University of Illinois, new cells in the macaque dentate gyrus take at least six months to mature fully.
Adult neurogenesis is implicated in depression and Alzheimer's disease, both of which involve hippocampal shrinkage. The anti-depressants Prozac and imipramine stimulate hippocampal neurogenesis in adult mice and some of their effects depend on the new cells. They also make immature hippocampal cells derived from human embryos divide in the Petri dish.
It is now taken for granted that adult neurogenesis occurs in humans, and the idea has revolutionized the way we think about the brain. It is widely believed that physical and mental exercise can stimulate hippocampal neurogenesis that offsets age-related cognitive decline and may protect against depression and Alzheimer's.
"Everyone wants to believe that functional neurogenesis happens in adult humans," says Lumsden.
"Everyone wants to believe that we can repair damaged brains, but there's precious little evidence for it."
The biggest sceptic is Pasko Rakic, who revealed how newborn cells migrate in the developing brain in a series of classic experiments performed in the early 1970s.
The biggest sceptic is Pasko Rakic, who revealed how newborn cells migrate in the developing brain in a series of classic experiments performed in the early 1970s.
Rakic injected macaque monkey fetuses with radioactive thymidine and sliced their brains into hundreds of ultra-thin sections. He identified migrating neurons by their newly-synthesized, radioactive DNA and painstakingly reconstructed the sections, to show that the cells climb onto elongated cells called radial glia, which span the thickness of the tube to contact its inner and outer surfaces and they then crawl, amoeba-like, along the radial glial fibres to the outer surface. His hand-drawn diagrams depicting the process appear in textbooks to this day.
Now chairman of Yale's neurobiology department and director of the Kavli Institute for Neuroscience, Rakic has been extremely critical of some of the adult neurogenesis research. He points out that BrdU can induce cell division, and also labels dying cells, which synthesize DNA just before they die, so cannot give accurate counts of newborn cells in adult brain tissue. This can be overcome by double staining with other antibodies, to verify that BrdU-labelled cells are indeed dividing.
Rakic has published evidence both for and against adult neurogenesis in macaques. He estimates that neurons added to the adult human hippocampus take a year to mature, and argues that anti-depressants cannot work by stimulating neurogenesis because their effects take about a month to kick in.
"Rakic was reasonable in demanding higher levels of proof," says Nottebohm, "but he railed against adult neurogenesis so aggressively that to many it struck as a defence of the old dogma. As a participant in the battles, I found him too negative and not particularly perceptive. His own work used animals housed under conditions that inhibit the formation and survival of new neurons."
Nottebohm and others say that Rakic has held back adult neurogenesis research, but according to Gage, he has been "an important driver for making the field more rigorous. He challenges the weakness in their work and it's up to researchers in the field to address them." But Gage notes that immature neurons derived from mouse stem cells are more active than their mature counterparts, so an extended maturation period may actually be beneficial. "I'm not surprised that maturation would take longer in humans, but the other way to look at it is that newborn cells have an extended period of plasticity."
Rakic's scepticism is, however, supported by the scientific evidence – or rather, lack of it.
In 1998, Gage and the late Peter Eriksson examined the brains of five cancer patients who had been injected with BrdU for diagnostic purposes. They treated the hippocampal tissue with antibodies against BrdU and proteins synthesized by immature neurons, and found some staining in the dentate gyrus. This was the first evidence that the adult human brain contains newborn neurons, but the researchers emphasized that it did not show that the cells are functional.
Others have isolated stem cells from various regions of the adult human brain. These cells have a limited capacity for self-renewal when grown in the lab, but can generate mature astrocytes, oligodendrocytes and neurons with normal electrical properties.
In 2006, Jonas Frisén of the Karolinska Institute and colleagues examined the cortex in autopsied brains of seven adults. They looked for radioactive carbon from Cold War nuclear bomb tests, which accumulates in newly-synthesized DNA, but detected only atmospheric levels, and concluded that neurogenesis does not occur in the cortex.
More recently, Gerd Kempermann of the Center for Regenerative Therapies in Dresden and colleagues examined brains from 54 individuals aged up to 100, using antibodies for multiple proteins, and found small numbers of newborn hippocampal cells in all of them. "It appears to be the same as in rodents," says Kempermann. "There's very steep decline in early life but you end up with a very low level that is maintained. We saw small numbers of cells, but we saw them up to very old age."
But Arturo Alvarez-Buylla, a professor in the Department of Neurological Surgery at the University of California, San Francisco, isn't entirely convinced. "Gage and Erikkson provided evidence that some proliferation occurs in the adult hippocampus," he says, "but this has to be treated with caution, because some of the labelled cells might have been dying."
Alvarez-Buylla obtained his Ph.D. working on songbirds with Nottebohm before turning his attention to rodents, where he showed that newborn neurons migrate long distances to the olfactory bulb. He has since published several studies suggesting that this migration probably does not occur in adult humans. Working with Nader Sanai, director the Barrow Brain Tumor Research Center in Phoenix, Arizona, he has examined the brains of approximately 100 people of all ages, and a similar number of tissue samples removed during neurosurgery.
They identified a 'ribbon' of astrocytes in the walls of the lateral ventricles which produce immature neurons, astrocytes and oligodendrocytes and which has not been seen in other species. They also identified the RMS in infants, and found that it contains small numbers of migrating cells, as well as a previously unidentified migratory pathway, which branches off from the RMS to enter the prefrontal cortex.
According to their data, migration occurs in both streams postnatally, but declines steeply by 18 months of age and has almost completely disappeared by early adulthood. "We concluded that if migration occurs then it is very scarce," says Alvarez-Buylla, "and that cells are not forming large bundles that migrate to the olfactory bulb." The data conflict with those of a 2007 study by Erikkson and Maurice Curtis, who saw a robust RMS containing large numbers of migrating cells, but were confirmed last year by Chinese researchers, who found small numbers of migrating neurons in the adult RMS, but no new cells in the olfactory bulb itself.
"How much neurogenesis occurs in older people, and how much it contributes to local plasticity, are still open questions," says Alvarez-Buylla. "There is controversy over how much cell renewal there is in the hippocampus and how persistent the stem cells are throughout life. If they decline with age they're not really self-renewing."
Overall, the few available studies suggest that the fountain of youth is reduced to a mere trickle in adults. There is no evidence whatsoever for adult neurogenesis in the human cortex; the existence of the RMS in adults is still disputed, and evidence for hippocampal neurogenesis is very thin on the ground. If the hippocampus does produce new cells, are there enough to be any significance?
Kempermann believes there are: "The network requires very few cells to be added and still be functionally relevant," he says. Other adult neurogenesis researchers also believe that small numbers of cells could be relevant to the function of the hippocampus. But this question remains unanswered, and the possibility that the number of cells produced is not large enough to be functionally significant has serious implications for popular claims, such as that exercise can improve memory, and also for the new view of the brain that has been adopted so quickly.
"One side-effect of having a large and complex brain is that you wouldn't want naïve newcomers barging in," says Lumsden. "How would new neurons usefully integrate into complex neural networks? If anything, evolution would have made damn sure that mechanisms exist to eliminate these party-crashers. Lack of neurogenesis after the connectional plan of the brain is complete would be a selective advantage."
The brain may, therefore, favour stability over plasticity. Human adult neurogenesis may be an evolutionary relic, and one that comes at a very high cost, as stem cells in the adult human brain likely contribute to brain tumour formation.
There's still hope
"Rakic was mostly correct," says Nottebohm. "Until now, the overwhelming evidence is that most neurons are formed early in development, including a short while after birth." But even if functional adult neurogenesis does not occur in the human brain, or if the numbers of cells produced are too small to be of any significance, there is still hope that neural stem cells could be of therapeutic value.
"Rakic missed what was central about the argument," Nottebohm continues. "There is a rich collection of neural stem cells that continue to generate new neurons in adulthood. This is of the greatest importance. It shows, in principle, that this reservoir might be exploited for purposes of brain repair."
To this end, researchers are exploring two approaches to develop neural stem cell-based therapies for neurological conditions, although any such treatments are still a long way off. One approach is to coax the brain's stem cells to generate neurons that migrate to injured or diseased sites. The other is to transplant lab-grown neurons of specified types directly into the brain. Indeed, neurons derived from human neural stem cells can differentiate into fully functional neurons when transplanted into foetal rat brain, and can now be tracked in live animals using magnetic resonance imaging.
"We found the first evidence for replaceable neurons," says Nottebohm, "and I have no doubt that a whole new field will emerge around this concept. I'm sure this will have a profound effect sooner or later. This is just the beginning."
Source: http://www.theguardian.com/science/neurophilosophy/2012/feb/23/brain-new-cells-adult-neurogenesis
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Now chairman of Yale's neurobiology department and director of the Kavli Institute for Neuroscience, Rakic has been extremely critical of some of the adult neurogenesis research. He points out that BrdU can induce cell division, and also labels dying cells, which synthesize DNA just before they die, so cannot give accurate counts of newborn cells in adult brain tissue. This can be overcome by double staining with other antibodies, to verify that BrdU-labelled cells are indeed dividing.
Rakic has published evidence both for and against adult neurogenesis in macaques. He estimates that neurons added to the adult human hippocampus take a year to mature, and argues that anti-depressants cannot work by stimulating neurogenesis because their effects take about a month to kick in.
"Rakic was reasonable in demanding higher levels of proof," says Nottebohm, "but he railed against adult neurogenesis so aggressively that to many it struck as a defence of the old dogma. As a participant in the battles, I found him too negative and not particularly perceptive. His own work used animals housed under conditions that inhibit the formation and survival of new neurons."
Nottebohm and others say that Rakic has held back adult neurogenesis research, but according to Gage, he has been "an important driver for making the field more rigorous. He challenges the weakness in their work and it's up to researchers in the field to address them." But Gage notes that immature neurons derived from mouse stem cells are more active than their mature counterparts, so an extended maturation period may actually be beneficial. "I'm not surprised that maturation would take longer in humans, but the other way to look at it is that newborn cells have an extended period of plasticity."
Rakic's scepticism is, however, supported by the scientific evidence – or rather, lack of it.
In 1998, Gage and the late Peter Eriksson examined the brains of five cancer patients who had been injected with BrdU for diagnostic purposes. They treated the hippocampal tissue with antibodies against BrdU and proteins synthesized by immature neurons, and found some staining in the dentate gyrus. This was the first evidence that the adult human brain contains newborn neurons, but the researchers emphasized that it did not show that the cells are functional.
Others have isolated stem cells from various regions of the adult human brain. These cells have a limited capacity for self-renewal when grown in the lab, but can generate mature astrocytes, oligodendrocytes and neurons with normal electrical properties.
In 2006, Jonas Frisén of the Karolinska Institute and colleagues examined the cortex in autopsied brains of seven adults. They looked for radioactive carbon from Cold War nuclear bomb tests, which accumulates in newly-synthesized DNA, but detected only atmospheric levels, and concluded that neurogenesis does not occur in the cortex.
More recently, Gerd Kempermann of the Center for Regenerative Therapies in Dresden and colleagues examined brains from 54 individuals aged up to 100, using antibodies for multiple proteins, and found small numbers of newborn hippocampal cells in all of them. "It appears to be the same as in rodents," says Kempermann. "There's very steep decline in early life but you end up with a very low level that is maintained. We saw small numbers of cells, but we saw them up to very old age."
But Arturo Alvarez-Buylla, a professor in the Department of Neurological Surgery at the University of California, San Francisco, isn't entirely convinced. "Gage and Erikkson provided evidence that some proliferation occurs in the adult hippocampus," he says, "but this has to be treated with caution, because some of the labelled cells might have been dying."
Alvarez-Buylla obtained his Ph.D. working on songbirds with Nottebohm before turning his attention to rodents, where he showed that newborn neurons migrate long distances to the olfactory bulb. He has since published several studies suggesting that this migration probably does not occur in adult humans. Working with Nader Sanai, director the Barrow Brain Tumor Research Center in Phoenix, Arizona, he has examined the brains of approximately 100 people of all ages, and a similar number of tissue samples removed during neurosurgery.
They identified a 'ribbon' of astrocytes in the walls of the lateral ventricles which produce immature neurons, astrocytes and oligodendrocytes and which has not been seen in other species. They also identified the RMS in infants, and found that it contains small numbers of migrating cells, as well as a previously unidentified migratory pathway, which branches off from the RMS to enter the prefrontal cortex.
According to their data, migration occurs in both streams postnatally, but declines steeply by 18 months of age and has almost completely disappeared by early adulthood. "We concluded that if migration occurs then it is very scarce," says Alvarez-Buylla, "and that cells are not forming large bundles that migrate to the olfactory bulb." The data conflict with those of a 2007 study by Erikkson and Maurice Curtis, who saw a robust RMS containing large numbers of migrating cells, but were confirmed last year by Chinese researchers, who found small numbers of migrating neurons in the adult RMS, but no new cells in the olfactory bulb itself.
"How much neurogenesis occurs in older people, and how much it contributes to local plasticity, are still open questions," says Alvarez-Buylla. "There is controversy over how much cell renewal there is in the hippocampus and how persistent the stem cells are throughout life. If they decline with age they're not really self-renewing."
Overall, the few available studies suggest that the fountain of youth is reduced to a mere trickle in adults. There is no evidence whatsoever for adult neurogenesis in the human cortex; the existence of the RMS in adults is still disputed, and evidence for hippocampal neurogenesis is very thin on the ground. If the hippocampus does produce new cells, are there enough to be any significance?
Kempermann believes there are: "The network requires very few cells to be added and still be functionally relevant," he says. Other adult neurogenesis researchers also believe that small numbers of cells could be relevant to the function of the hippocampus. But this question remains unanswered, and the possibility that the number of cells produced is not large enough to be functionally significant has serious implications for popular claims, such as that exercise can improve memory, and also for the new view of the brain that has been adopted so quickly.
"One side-effect of having a large and complex brain is that you wouldn't want naïve newcomers barging in," says Lumsden. "How would new neurons usefully integrate into complex neural networks? If anything, evolution would have made damn sure that mechanisms exist to eliminate these party-crashers. Lack of neurogenesis after the connectional plan of the brain is complete would be a selective advantage."
The brain may, therefore, favour stability over plasticity. Human adult neurogenesis may be an evolutionary relic, and one that comes at a very high cost, as stem cells in the adult human brain likely contribute to brain tumour formation.
There's still hope
"Rakic was mostly correct," says Nottebohm. "Until now, the overwhelming evidence is that most neurons are formed early in development, including a short while after birth." But even if functional adult neurogenesis does not occur in the human brain, or if the numbers of cells produced are too small to be of any significance, there is still hope that neural stem cells could be of therapeutic value.
"Rakic missed what was central about the argument," Nottebohm continues. "There is a rich collection of neural stem cells that continue to generate new neurons in adulthood. This is of the greatest importance. It shows, in principle, that this reservoir might be exploited for purposes of brain repair."
To this end, researchers are exploring two approaches to develop neural stem cell-based therapies for neurological conditions, although any such treatments are still a long way off. One approach is to coax the brain's stem cells to generate neurons that migrate to injured or diseased sites. The other is to transplant lab-grown neurons of specified types directly into the brain. Indeed, neurons derived from human neural stem cells can differentiate into fully functional neurons when transplanted into foetal rat brain, and can now be tracked in live animals using magnetic resonance imaging.
"We found the first evidence for replaceable neurons," says Nottebohm, "and I have no doubt that a whole new field will emerge around this concept. I'm sure this will have a profound effect sooner or later. This is just the beginning."
Source: http://www.theguardian.com/science/neurophilosophy/2012/feb/23/brain-new-cells-adult-neurogenesis
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