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 brain injury society
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Spring/Summer 1999 Issue

BI Society Website
Serving Acquired (Includes Traumatic)
Brain Injured Individuals and Their Families

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Volume 2, Number 4 "WE ARE HERE WHEN YOU NEED US."

Spring/Summer Issue 1999

EDITORIAL STAFF

Anita Adamski, CEO- Summit Marketing, Lisa Capone, K. Menucha Fogel, BS,SDS, Joan Pereira-Wyer, MS, LS

 

INTERDISCIPLINARY BRAIN INJURY EVALUATION ISSUES

Edwin F. Richter, III, MD

Brain injury can cause a wide variety of impairments. Vision, balance, attention, concentration, memory, impulse control, and language skills are among the many potential problem areas. These clinical deficits can lead to significant functional problems, with poor performance in various routine activities. Concurrent problems, such as headache or neck pain, can further worsen the situation.

One of the results of brain injury may be difficulty with self-assessment. Limited awareness of deficits clouds some individuals’ perceptions of reality. They may assume that any problems they encounter are only due to external factors. Since loud noise, for example, may exacerbate some brain injury symptoms, it can be tempting for some patients to attribute mistakes at work to a noisy environment. They might ignore the fact that they had no problems in that setting before their injury. These difficulties might not be clearly reported to medical personnel during routine assessments, since patients and others around them may overlook the relationship to a brain injury.

Even when accurate histories of functional problems are reported, little can be accomplished unless the significance is recognized. Inexperienced or inattentive health care providers may dismiss complaints of difficulty grocery shopping as trivial or irrelevant. The more appropriate response would be to begin looking at the abilities required to perform the task, in search of any evident deficiencies. Difficulty finding the energy to shop, preparing a grocery list, travelling to the store, scanning the shelves, reading labels, lifting packages, coping with crowds, or managing money are all potential components of the problem. Each of these activities can be made more difficult by more than one type of impairment seen after brain injury. This reinforces the need for detailed assessments.

Rehabilitation teams face special challenges when assessing the effects of brain injury. Team members should not attempt to work in isolation. Results of a written test can be interpreted better if visual acuity, scanning ability, and language comprehension have also been assessed. Performance on testing may also be worse if a patient had several demanding tests earlier that day. Awareness of psychosocial issues should also be shared, as altered mood may influence performance. Since functional deficits may result from combinations of underlying impairments, professionals trained in any given discipline may need input from colleagues with different areas of special expertise.

Interdisciplinary approaches to brain injury evaluations are theoretically desirable. Shared expertise across professional disciplines can enhance understanding of current problems, leading to better treatment plans. Practical obstacles may interfere with this concept. Some patients are seen by a large number of physicians, including internists, neurologists, neurosurgeons, neuroophthalmologists, orthopedists, otolaryngologists, physiatrists, psychiatrists, urologists, and others. Problems with vision may be addressed by optometrists. Psychologists may look at cognitive and/or emotional issues. Physical therapists (including vestibular therapists), occupational therapists, speech therapists, social workers, and vocational counselors are among the clinicians who may become involved. Patients may be seeing many different professionals, making communication between them difficult at best. Differences of opinion may arise, which can be disturbing to all concerned.

Fragmentation of evaluation may occur for various reasons. Initial assessment may be done at an emergency room, from where ambulatory patients may be given referrals to outpatient clinics. Some patients then seek the care of their primary care physician, who may then refer to specialists. They may also receive referrals from lawyers to clinicians, who may only perform evaluations in some cases. (Such patients may encounter difficulty when they subsequently seek treatment elsewhere, if insurance funds have been exhausted.) The process may be complicated if an insurance plan limits coverage to a specific panel of providers, or imposes other requirements.

Patients may opt to change some or all of their clinicians for various reasons. One concern is that they may become impatient while undergoing extensive evaluations. In some situations, this is appropriate, such as when a physician orders an extensive battery of tests but seems unable or unwilling to explain how the results could help with treatment. In other cases, patients may fail to appreciate that a treating clinician needs to form their own picture of the assessment, rather than relying solely on the reports of others. Professional jargon may also hinder clear communication. Use of different medical terminology might imply a dispute among team members where none exists.

There is no perfect solution to the problems that hinder evaluation of brain injury survivors. All parties concerned should make every possible effort to facilitate communication. Continuing professional education and community outreach programs should be supported.

Edwin F. Richter, III, MD, Clinical Associate Professor; New York University Medical School, Attending Phsyican; Rusk Insitutite for Rehabilitation Medicine, Manhattan, New York, Chairman; Brain Injury Society Medical Adviosry Board, Brooklyn, New York

NEUROLOGICAL APPROACH TO THE DIAGNOSISAND ASSESSMENT OF TRAUMATIC BRAIN INJURY

Rolland S. Parker, Ph.D.

Brain Injury is under-estimeated as a puiblic health and persona problem. It results in a distrubance of adaptation, ie.e, the capacity to cope with one's enviornment in all integrated fashion. Therefore, the issues in issues in assessing a case of known or alleged traumatic bran injury (TBI) are extremely complex. Codification of neurobehavioral information provides a sound basis for establishing or negating the diagnosis of brain trauma, exploring hypotheses concerning particular dysfunctions, preparing a treatment plan, and providing forensic information concerning need for compensation or damages. Adaptive behavior can be organized into a Taxonomy of Neurobehavioral Systems (below). Each system comprises related activites, and in somei instances is based upon a common neurological network. This is a useful guide to codifying informatin at various stages of examination. Organizing behavior this way has numerous advantages:

Rolland S. Parker, Ph.D.,Neuropsychologist, Adjunct Professor New York University Medical School, President, New York Academy of Traumatic Brain Injury, , Manhattan, NY

 

ORGANIZATIONAL STRATEGIES FOR JUNIOR HIGH SCHOOL STUDENTS

Teri De Stefano, MS, Sp. Ed.

Organizational problems are common in Traumatic Brain Injury. Previous to a Traumatic Brain Injury, individuals have reported being able to complete seveal activiites. Afterwards problems organizing and sequencing result in the ability to complete tasks.

The effect of Traumatic Brain Injury on students may manifest as a difficulty expressing previous knowledge due to language or organizational problems. The age a which the injury likely to demonstrate attention deficit disorder - hypreactivity, distractivity, or short attention span. Middle and high school students can be agitated, hostile, or short attention span. Young children and frontal lobe injuries often go undetected since adults adolescence deficit skills become more apparent. There complex tasks need to be broken down and taught to students.

The rate of processing information may impact the following: difficulty shifting from one topic to another, seems to be on a previous topic; difficulty keeping up with the information presented; difficulty with simultaneous processing - taking notes and listening; or takes longer to process information due to complex material.

Cognitive deficits in the classroom can be the following: difficulty getting all the materials for a class; poor organziation of notes; difficulty searching memory in an organized way and retrieving stored information and wordd; difficulty analyzing a task into parts; or difficulty seeing relationships ( ex: similarities/differences).

Therefore compensory strategies are useful to structure the environment and to maximize learning potential. For example: use an organzer with critical checkpoints (homework, due date, when completed); assign one task at a time; use of graphic organizers, assign a buddy to work directlywith the student; use tiem line, outlines, graphs to structure thinking processes visually; allow additional time for completion of assignments; reduce distractions; use of color coded organizational system; use highlighters; use daily planners and monthly calendars and limit directions.

Terry De Stefano, MS, Sp. Ed, Licensed New York State Teachers License, United Federation of Teachers Member, Teacher Specialist - Traumatic Brain Injury Students.

TRAUMATIC BRAIN INJURY

Real DEFINITIONS AND UNDERSTANDING FOR THE LAYPERSON

K. Menucha Fogel, B.S., SDS, Founder/Executive Vice President, Brain Injury Society

Traumatic Brain Injury is an insult to the brain. To understand why the brain is hurt is to understand the structure of the skull and the brain itself.

The skull (cranium) is made of a hard substance called bone. It thrives and is maintained by proper care, as it is a living mechanism.

The brain is hurt. Cells of the brain are injured or damaged. The cells have either died or are temporarily and/or permanently damaged. First indicators can be: being dazed, unsteady, lack of coordination, slurred speech or inability to understand conversation, inability to do daily activities, irritability, depression, lack of interest in life or social activities. Speaking can be incoherent. Some incontinence can be accompanied with this and in women lossof their mentrual cycle. This is usual after brain injury and is often temporary.

Clinton to Offer Prescription Benefit Plan

By ALICE ANN LOVE

.c The Associated Press

WASHINGTON (June 29) - Retirees would pay $24 a month if they want to take advantage of a new $2,000-a-year prescription drug benefit that is a centerpiece of President Clinton's long-awaited proposal to bolster Medicare, sources familiar with the plan say.

The new benefit, which would cover 50 percent of prescription drug costs up to the $2,000 annual cap, would be available as an option for retirees beginning in 2002. The monthly premium would rise gradually to $44 and the cap to $5,000 by 2008.

That premium increase would in part be to account for inflation, said the sources, who spoke Monday night only on condition of anonymity.

Medicare recipients already are paying a $45.50 monthly premium to cover doctor's office visits.

Those familiar with details floated by the administration on Capitol Hill said Clinton also would propose to help low-income beneficiaries pay the premium for drug coverage.

The Medicare plan, which the administration has outlined broadly and Clinton was scheduled to flesh out today, ''will have many specifics and many of them will be controversial,'' top White House economic adviser Gene Sperling said.

On Monday, the administration released new predictions of federal government surpluses - $1.1 trillion more than expected - that Clinton said would make it easier to avert a cash shortage likely to face the health insurance program for the elderly and disabled in 2015.

The president proposed using $794 billion of those surpluses for Medicare, saying ''our new, large surplus will help us to strengthen and modernized Medicare while providing a prescription drug benefit.''

But administration officials warn that tough choices still had to be made in putting together the plan. Medicare beneficiaries who choose the drug benefits that Clinton will propose, for example, would have to pay new out-of-pocket fees.

''It asks people to pay a modest premium and some cost sharing for a benefit that is far better than they'd get in the private sector,'' said Sperling.

Other money for the drug benefit, he said, will come from changes in the way Medicare does business with health care providers - for example, occasionally replacing complex government payment formulas with competitive bidding.

Congressional Republicans, who want to reserve some government surpluses for income tax cuts, have been skeptical about how Clinton will come up with money to add an expensive new benefit to the already cash-strapped Medicare program.

And it's unclear whether the president's plan can win the public and industry support he will need to get politically perilous Medicare changes through a Congress already nervous about the 2000 elections.

The American Association of Retired Persons, the nation's largest organization of older adults, supports the concept of a new Medicare prescription drug benefit. But senior AARP lobbyist Patricia Smith said among outstanding concerns is how much Medicare clients will be asked to pay out of pocket.

''Will Medicare beneficiaries judge this to be affordable? I think the only way we're going to find out is through the political process,'' said Smith.

Meanwhile, drug makers are worried about how the government will decide which drugs to cover at what prices.

''It is important that the plan not include government price controls and that the choice of medicine be left to the doctor and the patient and not to a government clerk in Washington,'' said Alan F. Holmer, president of the Pharmaceutical Research and Manufacturers Association.

Other health care providers, including hospitals and HMOs, worry that Medicare money to pay for drugs will be squeezed from their own budgets even as they struggle to adjust to payment cuts Congress approved two years ago to help balance the federal budget.

''What we have seen is an erosion of purchasing power,'' said Karen Ignagni, president of the American Association of Health Plans. ''Job one is to deal with the stability of the program. Job two is to talk about additional benefits.''

One of the main challenges the Clinton administration faced in trying to design a Medicare drug benefit was to make it fit Medicare's budget, while also making it a better deal for senior citizens than private supplemental insurance known as Medigap that many buy now.

Drug coverage accounts for about $90 a month of premiums charged for most Medigap policies, which generally cover 50 percent of prescription costs after a $250 deductible is reached. Annual caps on Medigap drug coverage vary up to a maximum of $3,000.

AP-NY-06-29-99 0139EDT

Copyright 1999 The Associated Press. The information contained in the AP news report may not be published, broadcast, rewritten or otherwise distributed without the prior written authority of The Associated Press. All active hyperlinks have been inserted by AOL.

MANAGEMENT OF CONCUSSION IN SPORTS

Statement from James P. Kelly, MD

Pat LaFontaine's Neurologist and Director of the Brain Injury Program at the Rehab Institute of Chicago

I applaud Pat LaFontaine's courage and wisdom for recognizing that his brain is more important to his life than another MV Paward or record. When he returned to play this past season, I advised him that while he had recovered from his devastating concussion in 1997, he was more vulnerable than ever and another concussion could end his career. He took that chance and had a record breaking year before he suffered an other concussion in March.

Behind his decision is an important message for every athlete, amateur or professional. THERE IS NO SUCH THING AS A MINOR CONCUSSION! Athletes - as well as their coaches, trainers, doctors and, yes, their parents - must recognize that a concussion should never be trivialized by such expressions as a "ding" to the head, or "getting their bell rung." A concussion is at least as serious an injury as a sprain or a deep bruise, and potentially much, much more serious.

A single concussion may not require a player to sit out the rest of the game, but he or she should not be allowed to return to the game until the severity of the injury has been assessed. What is particularly dangerous is sustaining a second concussion before fully recovering from a first one.

As we see with Pat, a concussion can end a career. It can destroy dreams and aspirations. And as at least a dozen families of young athletes discovered last year, a concussion can kill.

There is another message in Pat's retirement for those who set the rules that govern play in our sports leagues: Shots to the head must be outlawed and penalized with suspension, and even expulsion, from the sport. The seriousness of concussion needs to be addressed with serious consequences for those who inflict them. As we see, a career can be ended by concussion. So should the career of habitual head injury perpetrators.

I encourage everyone engaged in managing the care of athletes to familiarize themselves with the American Academy of Neurology's guidelines for "Managing Concussion in Sports." Use this tool to help you properly assess an athlete's head injury and determine whether or when it's safe to send the player back into the game. Your proper management of concussion could save a career...and a life.

MILD BLOWS, DINGERS AND BELL RINGERS

By Anthony S. Morgan M.D.

In the world of sports, the year 1994 will stand out historically for the baseball and hockey strikes and as the year George Forman captured the heavy-weight title at the age of 45. We the public have been better able to understand these events through the eyes of media. Those of us in the field of injury prevention and injury control must acknowledge the media's ability to finally heighten public awareness about the dangers of football injuries, the most important of which is brain injury, preferably called concussions in the football arena.

On a Thanksgiving weekend last year, the New York Jets faced the Miami Dolphins. The game had to be halted because wide receiver Rob Moore, while catching a pass, was tackled with enough force to put him in a stupor. His symptoms were consistent with a diagnosis of mild brain injury. He experienced confusion, dizziness, nausea and headaches. In this current football year, we have seen quarterbacks such as Troy Aikman for the Dallas Cowboys, Dave Brown for the New York Giants and Vinnie Testaverde for the Cleveland Browns all sustain mild brain injuries, with some players sustaining head injuries more than once. Most of the injuries that football players sustain are referred to as "mild blows," "dingers" or "bell ringers." However, despite the reluctance of the football world, plain and simple, these injuries should be referred to as mild brain injuries. Most notably, these injuries have the ability to alter the career moves of a football player. For example, Jets receiver Al Toon retired in 1992 after sustaining ten career concussions. According to the National Football League Commissioner's office, the player concussions occur at a rate of about one in every 3-5 games. The incidence of concussions may be no more common than in past years, but fortunately there is now a heightened awareness among coaches, players and team physicians.

At the high school level, it has been estimated that each season one in every five high school football players sustains a concussion. Given that there are approximately 1.5 million high school football players in the United States each year, more than 250,000 concussions occur annually.

Definition and Mechanism

A concussion is defined by the Professional Football Athletic Trauma Society as a "jarring injury of the brain resulting in dysfunction." To date there is no universal agreement on the definition of concussion. The Committee of Head Injury Nomenclature of the Congress of Neurological Surgeons defines concussion as "a clinical syndrome characterized by immediate and transient post-traumatic impairments of neurofunctions, such as alteration of consciousness, disturbances of vision, disequilibrium, etc. due to the brain stem involvement." The primary mechanisms for the concussion are thought to be due to the following:

1) Rotation acceleration -- This is best demonstrated by a hit on the chin in which rotation in 3 different planes can occur.

2) Rapid deceleration -- This occurs with abrupt landing or stopping.

3) Sequential acceleration/deceleration -- A common example of which is whiplash where the head is catching up to the torso in a cervical extension/flexing motion.

All of these mechanisms have the potential for histopathological findings such as:

1) Disruption of axons by traction or shearing.

2) Mitral infarct from hemorrhage or ischemia.

3) Interstitial edema (brain swelling).

4) Cicatrix formation (scarring).

It should be pointed out that the magnitude of forces involved in the mechanism does not always correlate with the severity of histopathology, which in turn may not correlate with the athlete's level of function.

Evaluation

It is imperative that concussions not be taken for granted. The injured athlete requires an immediate neurological evaluation. In the case of an athlete who has sustained an altered level of consciousness, the team physician must be assured that the athlete has an adequate airway, is breathing steadily and has a good pulse. Immediately following this assessment, a team physician should then concentrate on assessing the neurological status of the athlete. The physical examination should begin by ascertaining whether the athlete is alert, confused or unconscious. In addition, pupillary findings should be documented. There should be a testing of the cranial nerves, deep tendon reflexes, sensation, motor function, memory, concentration and attention.

Complications

The major morbidity associated with a concussion is Post-Concussive Syndrome. The common symptoms are headaches, tinnitus (ringing or buzzing in the ear), disequilibrium, easy fatigability, irritability and impairment of memory and concentration.

A potentially lethal consequence of concussion is Second-Impact Syndrome. A player who has not fully recovered from a previous concussion and then sustains even a minor head trauma can develop fatal brain swelling. The brain loses vascular autoregulation, resulting in massive vascular engorgement, swelling, herniation and death. This underscores the need for a player to be fully symptom-free before returning to play.

Prevention

The first step to preventing a injury is recognition. For the year 1994, the media has helped crystallize the impact of concussions in the world of football. The next phase is education. For example, the education of coaches on proper techniques of tackling and blocking is necessary. It has been shown that head up tackling rather than head first is safer and more efficient. Another important factor is the physical conditioning of the athlete. It is well known that the better the physical conditioning, the less chance of injuries. Equipment is extremely important, starting with the proper fit to help reduce brain injuries. An additional answer is the helmet. Make the helmet better to absorb the blow to the brain. Currently, a. inflatable sack within the helmet designed to decrease impact of blows to the brain is available.

Finally, it is important that team physicians and trainers take a very proactive role in protecting the athlete from primary and secondary injuries. Physicians and trainers must be well trained and qualified at both professional and amateur level. With the collaboration of physicians, trainers, coaches and athletes, the issue of brain injury in football should ultimately become a minor or non-existent issue

 

VISUAL DYSFUNCTION RELATED TO MTBI

The Visual System involves complex actions and interactions of the eyes and the brain. To simplify this description, the Visual System is being placed into three areas of function: acuity, perception, and eye movement. Any one of these functions can be impaired without impairment to the remaining two functions. Or, all functions may be impaired as the result of MTBI. The extent of injury will depend upon the force to and location of trauma in the brain. Dysfunction in any of these areas may contribute to headaches, fatigue, and/or dizziness.

Acuity or How Sharply You See

The Eye and the Optic Nerve

As light enters the eye it travels through the cornea, lens and retina (the neural part of the eye). At this point, the image of what is being seen is processed, reversed and transmitted along the optic tracts (visual pathways). The image is carried via the optic tracts through the brain to the Occipital Lobe (primary visual cortex) at the back of the brain.

The eye can be injured by a direct blow which may injure the cornea, lens, retina, and/or optic tract. Blurred vision or partial visual loss can result from this injury which may be transient or improve with treatment or may be permanent.

Perception or Interpreting What you See

The Occipital Lobe

This lobe sits at the back of the brain and receives the images transmitted to it from the optic tracts. A blow to the occipital lobe (back of the head) may result in an inability to make sense of what you see (visual agnosia) in your environment or read in a book or newspaper. The worst result would be "cortical blindness", an inability to see anything secondary to impaired interpretation of what is seen. This condition may be permanent or transient.

Control of Eye Movements

The superior colliculus and paramedian pontine reticular formation (brainstem)

Each eye has approximately six muscles. Each muscle independently controls an eye movement. Each muscle is individually controlled by one of three Cranial Nerves: III, IV, and VI. Normal eye movements are synchronized to present reflections onto the retina to result in a single image. If any one or all of the three Cranial Nerves are damaged the eye movement and synchronization are altered and two images may be seen. This is double vision or diplopia. Double vision may exist in all fields of vision or only in certain areas.

Independently activated eye movements involve different areas of the brain:

Other vision problems related to MTBI

 

MESSAGES RECEIVED FROM THE WHITE HOUSE

THE WHITE HOUSE

Office of the Press Secretary

______________________________________________________________________

For Immediate Release March 30, 1999

PASSOVER, 1999

Warm greetings to all those observing Passover.

This sacred holiday commemorates God's liberation of the Israelites from slavery and the beginning of the Jewish people's exodus from Egypt to the Promised Land. Their journey through the desert was long and difficult, but they were guided by the light of their faith and sustained by their dream of liberty. When at last they arrived in the Promised Land, they rejoiced in their freedom to worship God, to rebuild their communities, and to raise their children in the traditions and beliefs of the Jewish religion.

As a people who have always cherished the values of faith and freedom, all Americans can draw inspiration from the story of Passover. It reminds us of our ongoing journey to build our own Promised Land, where all people

are free to worship according to their conscience and where our children can grow up safe from the shadows of intolerance and oppression.

As families across the nation and around the world gather to remember the liberation of the Israelites and to teach a new generation the ancient tradition of the Passover Seder and the reading of the Haggadah, let us all give thanks for God's sustaining love and for the Jewish heritage that has so strengthened and enriched our national life.

Hillary joins me in extending best wishes for a joyous Passover celebration.

WILLIAM J. CLINTON

 

 

THE WHITE HOUSE

Office of the Press Secretary

________________________________________________________________________

For Immediate Release April 2,1999

EASTER, 1999

Warm greetings to everyone celebrating Easter.

Today Christians across America and around the world commemorate with great joy the central mystery of their faith: the Resurrection of Jesus. In this season, we celebrate Christ's victory over sin and death, and we rejoice in the new life that He won for us through His suffering, death, and rising from the dead.

That new life empowers us to overcome sin and to recognize our capacity for forgiveness and love. We have seen in our own communities and in other nations across the globe the violence and human tragedy spawned by hatred, intolerance, and fear born of ignorance. If we are to destroy the roots of hatred, we must examine our own hearts and actions and learn what we can and must do to build just communities united in understanding and mutual respect. May this sacred season of renewal, hope, and new beginnings inspire our efforts and light our way to a brighter, more

peaceful future.

Hillary joins me in extending best wishes for a blessed and joyous Easter celebration.

WILLIAM J. CLINTON

 

POSTTRAUMATIC STRESS DISORDER

PTSD is one of the anxiety disorders. Symptoms of PTSD develop in people who have experienced an event that is outside the range of usual human suffering and that would be extremely stressful for nearly anybody. Such an event would impose "a serious harm or threat to one's life or physical integrity, a serious threat to one's children, spouse, or other close relatives or friends." PTSD may develop after seeing sudden destruction of the patient's home or the entire community, or witnessing someone's being killed or injured. (DSM-IV, 1994).

The traumatic events that can trigger PTSD may be classified into several categories. First, the person may experience naturally occurring disaster, such as earthquakes, floods or volcano eruptions. Second, the disorder may be precipitated by tragic accidents, such as air crash, very serious car accident. Third, the stressor can be one of category of manmade catastrophes, which may be exemplified by wars, concentration camps and torture. The rape trauma syndrome is a special case of PTSD. in which the rape victim suffers from symptoms caused by the experience of sexual assault (DSM-IV, 1994).

The symptoms are similar for all types of PTSD. Obviously, not all patients who suffer from PTSD experience all the symptoms. Also, the symptoms vary slightly according to the precipitating trauma. The DSM-IV (1994) states these symptoms:

1.recurrent, persistent and distressing re-experiencing of the trauma through distressing recollections, dreams, sudden acting and feeling as if the event was reoccurring (reliving the trauma, illusions, hallucinations, flashbacks)

2.persistent avoidance of stimuli that remind of the trauma, for example, the patient avoids thoughts and feelings associated with the trauma, or he/she may avoid situations and activities that arouse the traumatic recollections

3.psychogenic amnesia

4.numbing of general responsiveness (that was not present before the trauma occurred), for example, the patients show markedly diminished interest in significant activities; they may feel detachment or estrangement from others; their range of affect may be restricted or they may have sense of a foreshortened future

5.persistent symptoms of increased arousal, which involve irritability and outburst of anger, troubled concentrating, hypervigilance, exaggerated startle response; they show physiological reaction to events or situations that symbolize or resemble the trauma

6.the disturbance causes significant distress or impairment in social, occupational, or other important area of functioning

7.patient has to experience symptoms for at least one month before PTSD may be diagnosed

IN THE NEWS

DISCOVERY BOLSTERS A HOPE FOR REGENERATION

By NICHOLAS WADE

April 2, 1999 New York Times The concept of regenerative medicine -- using the body's own stem cells and growth factors to repair tissues -- has come closer to reality with a discovery about the special human cells from which all bone and connective tissues are derived.

The discovery bolsters the hope that the cells can in principle be used to repair bone, cartilage, tendon and many other injured or aged tissues. The cells would in many cases be derived from the patient's own bone marrow and thus present no problem of immune rejection.

Moving one step closer to helping the human body regenerate tissue.

Biologists at Osiris Therapeutics, a privately held biotechnology company in Baltimore, Md., have shown that the cells, called human mesenchymal stem cells, can be converted into bone cells, cartilage cells, fat cells and the stroma cells in the bone marrow that provide support for blood-forming cells.

The company, named after the ancient Egyptian god of regrowth and rejuvenation, also has identified special factors that can be used in the laboratory to drive the cells down each of these distinct lineages. Its work is described in Friday's issue of Science magazine.

Dr. Daniel R. Marshak, Osiris' chief scientific officer, said the mesenchymal stem cells could be formulated so that, when inserted in the right place in the body, they would change into the appropriate tissue.

Tests in animals show that when the cells are grown on ceramic and put into bone, they turn into bone-forming cells. If grown in a gel and inserted into cartilage, they metamorphose into cartilage cells. If injected into the bloodstream, the cells take up residence in the bone and turn into stroma cells.

There is no way of knowing how soon treatments derived from the techniques will be available, but a clinical trial is now under way with breast cancer patients to explore the cells' stroma-forming abilities. Lack of stroma to support blood-forming cells may be why the bone marrow transplants given to cancer patients after chemotherapy are not always successful.

With Novartis AG, the Swiss pharmaceutical company, Osiris also plans to test in humans the cells' abilities to form new bone, tendon and cartilage.

The cells can also be converted to fat cells, which could prove useful in cosmetic surgery and possibly as material for breast implants.

Dr. Mark F. Pittenger, who identified the various factors needed to convert the cells into bone, cartilage, and fat, said he is now working to change them into heart-muscle cells. People are born with a fixed number of heart-muscle cells and the heart grows by enlargement of these cells, not by growing more.

"We hope at the least we could prevent some of the scarring after a heart attack by implanting new cells," Pittenger said.

The human mesenchymal stem cells found in adult bone marrow are derived from the mesoderm, one of the three tissue types of the early embryo and the source of all the body's bone and connective tissue. The adult stem cells evidently retain much, and possibly all, of the mesoderm's magical plasticity, giving the Osiris biologists a wide range of tissue fates to explore for the cells.

Stem cell biologists independent of the company said the new report represented a promising advance, even though it remains to be seen if the clinical applications will work as hoped.

Dr. David J. Anderson of the California Institute of Technology said it was a "very important result" to have trained the stem cells to form different lineages in the laboratory. Dr. Ronald McKay of the National Institutes of Health described the Osiris report as a "very serious and interesting contribution."

Both Osiris and Dr. William Haseltine, president of Human Genome Sciences, have laid trademark claims to the evocative phrase "regenerative medicine," the idea that stem cells and the growth factors that shape their fate may provide a radically new approach to healing.

"The fundamental concept is that if we learn enough about how the body regenerates itself, we can use those same mechanisms to regenerate tissues that are damaged or worn down by age," Haseltine said.

In cases where the body's own repair mechanisms fail, however, are extra stem cells all that is needed to overcome the problem?

Marshak of Osiris said that often the body might not be able to get enough of its mesenchymal stem cells to an injury in time, especially in cartilage, for example, which has no blood supply, or when a large area of bone is missing.

McKay said the prospects for regenerative medicine and the clinical usefulness of stem cells were likely to depend on how deeply the genetic rules for fashioning an animal body are embedded in the cell's hereditary programming.

"If the cells have constant access to these rules, then the answer is that through this door we will go into a universe where there is real control over reshaping human tissues."

There is reason to be optimistic about the clinical uses of stem cells "but advances are not going to come as day follows night," said Dr. Robert Weinberg, a cancer biologist at the Whitehead Institute in Cambridge, Mass. Weinberg noted that complex tissues are formed by the interaction of many different types of cell, and that even though stem cells can be driven down certain lineages in the laboratory, it is not yet clear that the body will provide the same cocktail of factors.

"With the exception of certain special cell types like skin, the ability to reconstruct complex tissues is still years ahead of us, but work like this will be viewed as pioneering five to ten years down the road," he said, referring to the Osiris report.

 

HOUSE MEMBERS PROTEST USE OF FEDERAL MONEY IN RESEARCH ON STEM CELL RESEARCH

By NICHOLAS WADE

February 17, 1999, New York Times, In a letter, 70 members of the House of Representatives have asked the secretary of the Department of Health and Human Services to rescind a ruling that federal money may be used for research on human embryonic stem cells, the primordial cells from which all the tissues of the body are developed.

Human embryonic stem cells were isolated and cultivated for the first time last year in work that scientists have hailed as a first step to novel and far-reaching therapies, particularly to replace aged or damaged human tissues.

But the manner of obtaining the embryonic stem cells is viewed as morally unacceptable by opponents of abortion, including the National Conference of Catholic Bishops. The stem cells were derived by one group of biologists from long-frozen embryos that had been created in fertility clinics in excess of the patients' needs and by another group from aborted fetuses.

The congressional letter to Health and Human Services Secretary Donna Shalala was drafted by the House pro-life caucus, chaired by Rep. Christopher Smith, R-N.J., and James Barcia, D-Mich. Most of its signatories, including Tom DeLay, R-Texas, the majority whip, and Richard Armey, R-Texas, the majority leader, and Henry Hyde, R-Ill., are anti-abortion Republicans, although eight Democrats are also among the signers.

The letter says that the position of the Department of Health and Human Services on stem cell research, enunciated in a ruling last month by Harriet S. Rabb, the department's general counsel, "would violate both the letter and spirit of the federal law" that bars federal support for research in which human embryos are destroyed.

The department has said federally supported biologists may not derive stem cells from embryos -- the specific prohibition of the law -- but may conduct research on the stem cells derived by other scientists using private funds.

The House letter asserts that Congress' ban on federal funds to derive the cells obviously extended to research conducted on such cells.

A spokeswoman for the department, Laurie Boeder, said it could not comment on the House letter without further study.

Congress' ban on federal financing for embryo research has been exerted in the form of a rider attached for the last three years to the appropriations bill that sets the budget for the National Institutes of Health. The rider has originated in the House, from Rep. Jay Dickey, R-Ark. But U.S. Sen. Arlen Specter, R-Pa., the chairman of the Senate appropriations subcommittee that handles NIH, is a strong supporter of stem cell research, as is the ranking minority member, Sen. Tom Harkin, R-Iowa.

Specter said on Tuesday that "we are in very deep water" on the issues raised by the House members and that he would hold a hearing on their concerns

"But what we are looking at in broader terms is the possible cure for major diseases like Parkinson's, Alzheimer's, cancer and heart disease, from the use of what are essentially discarded embryos," Specter said. Researchers hope stem cell research will lead to ways to grow replacement tissues for use in people with these and other conditions.

Specter said he had taken time out from the impeachment proceedings against President Clinton to discuss stem cell research with Dr. Harold Varmus, the director of the National Institutes of Health. In his view, Varmus should continue reviewing research applications while the House members' letter is being considered.

Richard Doerflinger, associate director for policy development at the National Conference of Catholic Bishops, said the House members' letter accorded with arguments he had made at two recent hearings on stem cell research held by Specter. He said the disagreement was not a clash between science and religion but "a clash between obtaining medical progress in morally acceptable and morally unacceptable means."

 

CURB ON EMBRYO RESEARCH DOES NOT COVER STEM CELLS, AGENCY RULES

By NICHOLAS WADE

January 20, 1999 New York Times, Federally financed researchers will soon be able to work on human embryonic stem cells, the source cells from which the embryo develops, as a result of a ruling Tuesday by the Department of Health and Human Services that a congressional ban on human embryo research does not apply to the cells.

The decision was hailed as "an accurate interpretation of bad law," by the American Society for Reproductive Medicine and denounced by the National Conference of Catholic Bishops as a loophole that "violates the spirit of current law."

In its ruling, the department's Office of General Counsel said that because the cells by themselves do not have the capacity to develop into a human being, they cannot be considered embryos.

Human embryonic stem cells, isolated for the first time in November, are capable of developing into any of the body's cell types and thus have great potential for repairing any damaged tissue, such as failing heart muscles or the type of brain cells lost in Parkinson's disease.

The many biological researchers who receive their funds from the federal government have been unable to study human embryonic stem cells because of a congressional ban, originating in the House, that has been attached every year since 1995 to bills authorizing spending for the National Institutes of Health, the principal supporter of biomedical research.

The ban states that no federal funds may be used for "research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero." In a statement issued in November, Rep. Jay Dickey, R-Ark., said human embryonic stem cells should not be excluded from the ban.

The embryonic stem cells described in November by Dr. James Thomson of the University of Wisconsin were derived in from human embryos created in surplus amounts in a fertility clinic. Deriving the cells is legal, provided it is not done with federal funds. Dr. Harold Varmus, director of the National Institutes of Health, said it would still be illegal for researchers to use federal funds to derive their own stem cells in this way. But they can now use federal funds to work on the cells Thomson has already obtained.

"The prospect of doing amazingly interesting science is really quite wonderful," Varmus said. But research cannot begin, he said, until the NIH has drawn up guidelines to ensure that researchers do not do prohibited research, such as generating new embryos

Sen. Tom Harkin, D-Iowa, who in December called for speedy issuance of the ruling, said the decision would move researchers closer to finding cures for many diseases. "The government should not issue blanket bans on medical research," he said.

But the circumstance that federally-supported scientists can now conduct research on cells that they cannot legally derive was seized upon by Richard Doerflinger, associate director for policy development at the National Conference of Catholic Bishops. "They will destroy the embryos with private funds and experiment on the tissue with public funds," he said. Doerflinger believes that the medical benefits expected from stem cell research could be obtained with embryonic stem cells derived from spontaneously aborted fetuses. A pocket of embryonic stem cells, known as embryonic germline cells, is preserved in the fetus as a source to generate egg or sperm cells. One of the two lines of embryonic stem cells announced last November was developed by Dr. John Gearhart of Johns Hopkins University, who obtained the cells from aborted fetuses, but they were induced abortions, not spontaneous ones.

Doerflinger said that Gearhart's type of human embryonic stem cells would be acceptable had they been obtained from spontaneously aborted fetuses.

In a written statement he said, "The Clinton administration now seeks to do indirectly what Congress has forbidden it do to directly: Provide federal support for research in which human embryos are created and destroyed."

 

PARENT CELLS FOUND IN BRAIN MAY BE KEY TO NERVE REPAIR

By NICHOLAS WADE

January 8, 1999, New York Times, Scientists in Sweden have identified for the first time the parent cells that give rise to many and maybe all of the different cell types in the adult brain. These neural stem cells, as they are called, are of great interest because, if they could be manipulated appropriately, they would be the obvious repair kit for replacing damaged neural tissues in everything from spinal cord injuries to Parkinson's disease.

The Swedish biologists worked with rats, but now that the cells' hiding place in the rat brain is known, the human counterpart cells are strongly expected to lie in the same place.

Discovery of the cells, announced by Dr. Jonas Frisen and colleagues at the Karolinska Institute in Stockholm in an article published in Friday's Cell, is part of a fundamental change in brain biology. Until recently, it had been thought that the brain never renewed itself or added new cells after gaining its mature form. The belief implied that the brain did not possess stem cells, the source cells from which tissues like blood and skin can constantly renew themselves.

This dogma started to crack when biologists showed in 1992 that a small percentage of cells in brain extracts could divide and develop into the principal types of brain cell. Much work has since been done on brain stem cells acquired by grinding up whole animal brains. But no one knew where in the brain the stem cells come from.

In their paper, Frisen and his team say they have now identified the brain's stem cells. The cells were already known as ependymal cells, described by one biologist as the most boring cells in the brain because their function is simply to line the cavities of the ventricles and spinal cord which hold the spinal fluid.

These cavity-lining cells are differentiated, meaning that they have taken up a mature form. In contrast, all stem cells identified so far are general, multipurpose cells, uncommitted to any specific fate.

Earlier experiments showed the cavity-lining cells did not divide, confirming their uninteresting nature. But Frisen has found the cells do divide, though at too slow a rate for the earlier tests to detect. Their progeny cells divide rapidly and can differentiate into both neurons and the support cells that are found copiously throughout the brain.

Frisen has found that neurons derived from the cavity-lining cells can migrate from the cavity surface and replace cells in the rat's olfactory bulb or smell-analysis unit, the one brain region known to undergo a rapid turnover of nerve cells.

The Clark Kent/Superman existence of the cavity-lining cells has surprised biologists. "You'd never guess it in a million years," said Dr. Ben Barres, a developmental biologist at Stanford University.

But the identification makes sense, he said, because in the developing embryo the brain cells grow out from stem cells that line a hollow tube. As the organism matures, the tube becomes the ventricles and spinal cord, and the stem cells disappear. It now seems they stay in place but turn into cavity-liners.

Frisen has found that the cavity-lining cells start dividing in earnest when the spinal cord is injured. They then turn into the support cells that make up much of the scar in spinal cord injuries.

"That's really cool because it wasn't clear where the glial cells in scar tissue were coming from," Barres said, referring to the support cells.

Frisen said he hoped to find out how the cavity-lining cells could be induced to make neurons instead of support cells at injury sites. If so, a new approach to spinal cord injury might be developed.

The neural stem cells may also prove relevant to treating Parkinson's disease, which is caused by the death of dopamine-producing cells in a certain region of the brain. Embryonic cells, such as those derived from fetuses, will develop into these cells if placed in the dopamine region. But ethical problems aside, there are not enough fetuses available to treat everyone.

Frisen said the big advantage of the neural stem cells "is that maybe you could use the patient's own stem cells, avoiding both the ethical and immunological problems." The cells would be obtained through a biopsy of the cavity-lining cells of the spinal cord, assuming these prove to be the human reservoir of neural stem cells.

Frisen identified the brain stem cells through his studies of spinal cord injuries. He noticed that some of the cells at the injury site were making a substance called nestin, which had been shown by Dr. Ron McKay of the National Institutes of Health to be produced by brain stem cells. The clue made him suspect the cavity-liner cells were also the stem cells, a thesis it has taken four years to establish.

The neural stem cells are descendants of the primordial stem cells that form in the earliest embryo.

 

SCIENTISTS CULTIVATE CELLS AT ROOT OF HUMAN LIFE

By NICHOLAS WADE

November 6, 1998 New York Times Pushing the frontiers of biology closer to the central mystery of life, scientists have for the first time picked out and cultivated the primordial human cells from which an entire individual is created.

The cells, derived from fertilized human eggs just before they would have been implanted in the uterus, have the power to develop into many of the 210 different types of cell in the body -- and probably all of them. Because they can divide indefinitely when grown outside the body without signs of age that afflict other cells, biologists refer to them as immortal.

Eventually, researchers hope to use the cells to grow tissue for human transplants and introduce genes into the body to remedy inherited disease.

But there is a thicket of ethical and legal issues, as well as technical problems, to be tackled. The cells are obtained from embryos created at in-vitro fertilization clinics and so far do not seem definably different from the handful of primordial cells from which an entire individual is created.

Though the scientists involved in the work consider use of the cells justified because they come from embryos that would otherwise have been discarded, other believe the cells have a special status in that they retain the potential to develop into an individual, and that the use of the cells may draw criticism if this status is not taken into account.

The new cells, known as human embryonic stem cells, have eluded capture until now because they exist in this state only fleetingly before turning into more specialized cells, and need special ingredients to be kept alive outside the body.

The cells have many possible uses, of which the most promising is to grow new tissue, of any kind, for transplant into a patient's body. The cells may also offer effective routes to human cloning, although both the researchers and their sponsor deny any interest in this application. Another likely use is in gene therapy, the insertion of new or modified genes into body tissue.

Two forms of human embryonic cells have been developed, one by a team under Dr. James A. Thomson of the University of Wisconsin in Madison, the other by Dr. John Gearhart and colleagues at the Johns Hopkins University School of Medicine in Baltimore, Md. Dr. Thomson's work is reported in this week's issue of Science, Dr. Gearhart's in the Proceedings of the National Academy of Sciences.

Congress in 1995 banned Federal financing of research on fetal cells, including those derived from embryos, and the university researchers whose work was announced today were funded by the Geron Corporation of Menlo Park, Calif., a biotechnology company that specializes in anti-aging research.

The research "has potential health benefits which I think are extremely promising, and I am sorry that the law prevented us from supporting it," said Dr. Harold Varmus, director of the National Institutes of Health.

Cells Are Specialized as They Develop

After an egg is fertilized, it divides several times and forms a blastocyst, a hollow sphere with a blob of 15 to 20 cells, known as the inner cell mass, piled up against one wall. It is from these cells that the embryo develops. Dr. Thomson grew his embryonic stem cells from the inner cell mass of blastocysts that had been left over from fertility treatments and were due to be discarded. The donors of the blastocysts granted permission for them to be used in research.

As an embryo grows and develops, its cells become irreversibly committed to their fates as specialized components of the body's organs. A pocket of cells, known as embryonic germ cells, is protected from the commitment process so as to create the next generation of eggs and sperm. Dr. Gearhart's group has developed embryonic stem cells from the germ cells of aborted fetuses. The cells developed by the two groups may well be equivalent but this has yet to be proved.

If researchers are able to use the cells to grow new tissues, the work could alleviate the shortage of livers and other organs for transplant. Cultures of the cells in the laboratory could be nudged down different developmental pathways to become heart or bone marrow or pancreatic cells. Before reaching their final stages, the about-to-become heart cells, for example, could be injected into a patient's ailing heart. Guided then by the body's own internal regulatory signals, the cells would develop into new, young heart tissue, supplementing or replacing the heart cells already there.

The same approach should in principle work with any tissue of the body. Human embryonic stem cells would thus serve as a universal spare parts system. Because the cells grow and divide indefinitely in the laboratory, very few blastocysts would be needed.

Many technical problems remain to be resolved. The art of directing embryonic stem cells down specific pathways is in its infancy. But heart muscle cells have been grown from mouse embryonic stem cells and successfully integrated with the heart tissue of a living mouse.

Dr. Thomson in 1995 isolated the embryonic stem cells of a monkey, and Geron intends to do pilot experiments in these cells.

Another problem lies in making grafted cells compatible with the patient's immune system.

Dr. Thomas B. Okarma, Geron's vice president for research, said Geron would explore several ways of doing this. One, the least preferred, would be to set up a bank with enough different human embryonic cells that most patients could be matched. Another would be to suppress the self-recognition genes that make the stem cells appear foreign to the patient's immune system or, more elegantly, to replace them with copies of the patient's own self-recognition genes.

A third, approach would be to convert one of the patient's own body cells back to embryonic form by fusing it with a human embryonic stem cell whose own nucleus had been removed. Embryonic cells may have the power, not yet understood, to rescue an adult cell's nucleus from its specialized state by flicking all the switches on its DNA back to default mode. This reprogramming of DNA is presumably what happened when mice were cloned in July from adult cells.

ETHICAL CONCERNS PREVENT SOME TESTS

The ethical status of the cells is also likely to be a matter of discussion. They cannot become a fetus, as their blastocyst no longer exists, yet they are very similar, if not identical, to the 20 or so primordial cells from which the embryo develops.

Both research groups refer to their cells as "pluripotent" because, when injected into a mouse with no immune system, the cells develop into many of the major tissues of the body. The tissues are disorganized and do not develop into a normal embryo.

The cells may also be "totipotent," meaning they can form every one of the body's cell types. The test for totipotency, developed with mouse embryonic stem cells, is to inject stem cells into another blastocyst. A normal mouse will usually develop, but it is composed of a patchwork of cells, some from the blastocyst and some from the injected embryonic stem cells, proving the stem cells retain all their powers.

It would be unethical to perform such an experiment on people, but if it could be done, it seems likely that the human embryonic cells cultured by the researchers would also prove to be totipotent. If so, they may be capable in principle of contributing to the generation of a new individual.

But ethicists say great care must be taken in work involving human embryonic cells.

"Any time you take a cell off a blastocyst, that cell could be used itself to create a human being, so some groups in our society believe in making it transplantable you have derailed it into becoming a kidney or some other tissue," Dr. Lori Andrews, an expert on the laws governing reproductive technology at the Chicago Kent College of Law, said.

"Some researchers say, 'It's just a bunch of cells, why should people care?' But that totally avoids the fact that some people do care, and I'm concerned that if the researchers don't take into consideration the variety of viewpoints about embryos, they might ultimately end up with more restrictive regulations."

Geron, which has exclusive licenses to use the cells, under patents held by the researchers' universities, says it regards them as qualitatively different from other cells used in research.

"Because these cells are derived from human blastocysts there is a moral authority here, so we take these cells seriously," Dr. Okarma, of Geron, said.

Dr. Okarma said he believes that use of the cells is justified because they are something less than a living embryo, and life-saving treatments may be derived from them. "We are not saying the ends justify the means, but that given that the moral authority of these cells is subordinate to that of the embryo, the work we contemplate with them is appropriate," he said.

But Dr. Gearhart said he did not consider the cells that he and Dr. Thomson have isolated to have a special moral status because "they cannot form a fetus -- you cannot take one of these cells and form a being out of it."

Still, Dr. Gearhart said he would not argue with the view of Dr. Okarma at Geron that the cells had a different standing from ordinary cells. Dr. Johnson, too, said that they were "special cells."

Dr. Kevin T. Fitzgerald, a geneticist and Jesuit priest at Loyola University Medical School, said that if the human embryonic stem cells are totipotent, "then you are disrupting the viability of life and we are back to the question of how to justify destroying life for the purposes of scientific advancement."

The new cells may well reawaken fears of human cloning, although many ethicists have now come around to believing that the public's fears, despite science fiction writers' portrayal of clonal armies of frenzied despots, are largely beside the point. Many experts now predict human cloning is more likely to end up as a rare treatment offered in fertility clinics, no different from others like in-vitro fertilization and egg donation in that they were first bitterly denounced and are now regarded as routine.

"Human cloning will likely also be accepted once it becomes a reality. Most of today's ethical arguments against it were previously used against in-vitro fertilization and turned out to be false," writes Dorothy C. Wertz, a bioethicist at the Shriver Center, in the current issue of Gene Letter.

The availability of human embryonic stem cells suggests a quite different possibility to biologists, who are well aware of how mouse embryonic stem cells have long been used to generate genetically altered mice.

The belief that humans can now be modified like the mouse "will be the kneejerk reaction of the academic community," Dr. Thomson said.

He said human embryonic stem cells were unlikely to be used in this way because there were more promising approaches for gene therapy in people. For one thing, the mouse method requires the creation of many embryos in order to obtain the few in which new genes integrate in exactly the correct position, as well as the breeding of a male and female mouse that have been genetically altered. In its present form, the technique is evidently inapplicable to humans.

FEDERAL LAW SHIFTS RESEARCH TO INDUSTRY

The National Institutes of Health and the university scientists it funds often play a leading role in reviewing new biomedical technologies.

But because of the Federal funding ban, university scientists cannot get Government support to study human embryonic stem cells. But industry can do whatever research it pleases, without necessarily obtaining government approval. Academic biologists believe this asymmetry is unfortunate and that the new technique would receive better and more detached review if the agency and its scientists could take part in the discussion.

Dr. Varmus said that an expert panel on human embryo research had recommended to the health institutes that attempts to derive stem cells from human embryos should be permitted, but Federal efforts along this line were thwarted in 1995, with the Congressional funding ban. Dr. Varmus said he believed the public "will see how important the benefits of this research might be."

A Senate bill to ban human cloning was defeated in February this year, the principal argument of its opponents being that its overly broad language would prohibit promising research on human embryonic stem cells.

In any event, any ultimate use of human embryonic stem cells may face legal hurdles in the nine states that have outright bans on research on human fetal tissues, Dr. Andrews said.

Some laws also prohibit payment for embryos, a restriction that might extend to cells and tissues derived from embryos.

A POSSIBILITY OF ETERNAL CELLS

The technique reported today reaches to the central mysteries of life and death. As biologists have recently begun to understand, the body's cells are not inherently mortal. They become mortal only when committed to developing into one or another of the body's mature cell types. These specialized cells have mostly lost the ability to grow and divide, but a few, typically those of the skin and intestinal lining, can divide in culture about 50 times and then die.

In January this year, biologists at Geron learned how to manipulate the section of DNA that marks off the 50 or so permissible divisions. By reversing the changes in this section of DNA, called the telomere, they created lines of cells that divided well beyond the usual limit and are still going strong, while retaining their youthful vigor and appearance. Biologists refer to these cultured cells as immortal because they are expected to grow and divide indefinitely.

Embyronic stem cells are also immortal because, until they become committed to specialized fates, their telomeres are renewed each time they divide. Unlike ordinary cells, they grow indefinitely in culture.

In the lineage of living organisms, they cycle indefinitely from the embryo to the germ line to a new embryo, forever avoiding specialization into the mortal cell types that comprise the body.

Geron biologists believe they can manipulate the telomeres of the human embryonic stem cells so that the cells stay immortal even as they turn into specialized tissues. Can the mortal body therefore be repaired with new, tissues that remain youthful indefinitely? "Exactly," Dr. Okarma said.

Critics have said it would be folly to tamper with the telomere division-counting system because it probably arose in evolution as the body's last-ditch defense against any runaway cell likely to become a cancer. Dr. Okarma said that new experiments had largely laid this concern to rest by showing that telomerised cells are no more likely to become malignant than are normal cells.

These grand schemes may or may not come to pass, but the techniques now at hand for manipulating human embryonic stem cells will at least allow them to be seriously attempted.

 

ALZHEIMER-RELATED GENE AFFECTS RECOVERY FROM HEAD INJURY

ST. PAUL, MN – Survivors of traumatic brain injuries are less likely to recover well if they have the gene variant ApoE-4, or apolipoprotein E-4, according to a study published in the current issue of Neurology, the scientific journal of the American Academy of Neurology. The ApoE-4 gene type is also associated with an increased risk for the development of Alzheimer’s disease.

In the study, 69 people who suffered blunt head injuries were evaluated for six to eight months by researchers in Israel.

Those who did not adequately recover from the brain damage were 5.6 times more likely to have the ApoE-4 gene than those who did recover well, according to study author Zeev Groswasser, MD, MPH, of Tel Aviv University. A good recovery was considered the ability to live independently and the lack of language or behavioral problems and severe cognitive abnormalities.

"This study shows that a person’s genetic constitution is important in the ability to recover from trauma to the brain," Groswasser said. "This could be very important in tailoring the proper treatment to each patient and in identifying patients who need more intensive rehabilitation after an injury."

Only one of the 27 study participants with the ApoE-4 gene had an excellent recovery, compared to 13 of the 42 participants without the E-4 gene. Those with the E-4 gene were also more likely to remain unconscious following the brain injury for more than seven days.

Apolipoprotein E is a type of protein that carries cholesterol and fats in the blood. People inherit different types of the gene – type 1, 2, 3 or 4. The protein produced by the gene helps cells repair damaged membranes, or cell walls, by transferring the fats needed to repair the walls. But people with the ApoE-4 gene have a decreased ability to transfer the fats properly, according to Groswasser.

Grosswasser said methods need to be developed to treat people with ApoE-4 to improve the cell repair ability. "Also more effective treatments need to be developed for such patients during recovery from traumatic brain injury," he said. "This could include gene therapy, which could perhaps prevent development of Alzheimer’s disease."

Improving care for patients with traumatic brain injuries and other neurological disorders is the goal of the American Academy of Neurology, an association of more than 15,000 neurologists and neuroscience professionals.

American Academy of Neurology: Editor’s Note: Neurology is now published 18 times per year, with two issues in January, March, April, July, September and October. This study is published in the second January issue.

 

SEIZURES CAUSED BY VIDEO GAMES AND TELEVISION LINKED TO TV SCREEN FREQUENCY

ST. PAUL, MN (March 23, 1998) Seizures caused by video games and television occur less often when higher frequency screens are used, according to a study published in the March issue of Neurology, the scientific journal of the American Academy of Neurology.

Seizures triggered by flashing or flickering lights affect about 10 percent of all new epilepsy patients ages seven to 19, according to the study. In a recent, well-publicized case, more than 700 people in Japan, mainly children, suffered epilepsy-type symptoms after watching a popular cartoon.

The frequency of flashing light that makes up a television image is measured in hertz, or flashes per second. The study was conducted in Europe, where screens operate on a lower frequency than in the United States and are more likely to trigger seizures. In Europe, 50 Hz screens are used; in the United States, 60 Hz screens are used.

In the study, 30 people with prior sensitivity to television or video games - 23 with a history of seizures -- were tested with conventional European 50 Hz screens and 100 Hz screens during television viewing and video game playing. With the 50 Hz screens, more than half of the participants showed signs of seizures during tests of brain activity, or electroencephalograms (EEGs). With the 100 Hz screen, only one participant showed signs of seizure.

In addition, with the 50 Hz screen, moving closer to the screen caused more people to have reactions. With the 100 Hz screen, there was no difference based on distance from the screen, according to neurologist Federico Vigevano, MD, of Bambino Gesù Children's Hospital in Rome, Italy.

Improving care for patients with epilepsy and other neurological disorders through education and research is the goal of the American Academy of Neurology, an association of more than 15,000 neurologists and neuroscience professionals.

LONG-TERM NERVE STIMULATION REDUCES EPILEPTIC SEIZURES

Minneapolis, MN (April 28, 1998) -- Epilepsy patients with an implanted device that electrically stimulates the left vagus nerve in the neck continue to have fewer seizures after three years with few side effects, according to a study released during the American Academy of Neurology's 50th Anniversary Annual Meeting, April 25 - May 2, in Minneapolis, MN.

George Morris, MD, study co-author and a neurologist at the Medical College of Wisconsin in Milwaukee, said, "We examined the long-term progress of the patients, including the effect vagus nerve stimulation had on seizure frequency and whether or not that positive effect would be sustained over time. We found evidence of continued seizure reduction and few side effects, most of which diminished over time."

The study followed 253 epilepsy patients who received the implants between 1988 and 1995. After one year, 95 percent of the patients in the study continued receiving stimulation. At two years, 82 percent were still involved in the study and 69 percent after three years. Reduction in seizure frequency improved from 31 percent at one year, to 41 percent at two years and 40 percent at three years.

The impulse generator implanted in the patient's chest stimulates the left vagus nerve in the neck for 30 seconds at five-minute intervals, 24 hours per day. The vagus nerve is the main thoroughfare for communication between the brain and major internal organs.

"Appropriate adjustments in the stimulation intervals must to be made for each patient to optimize the benefit," said Morris. "By the second year the dose may be more accurate, which may account for the improvements in seizure reduction reported during the second and third years. Another explanation is that this therapy works through a long-term modification of seizure pathways, and that it takes time to affect."

Morris said patient continuation rates were high, in part because less than 10 percent reported adverse effects. Side effects reported included hoarseness, headache and shortness of breath, all of which decreased in frequency by the third year. Researchers also noted that twice as many patients decreased their seizure medication over the three years as those who increased it.

"Vagus nerve stimulation is a viable and safe, long-term alternative for some epilepsy patients," said Morris. "The stimulation does not interact with other epilepsy medications, allowing patients to continue other therapies."

Vagus nerve stimulation was approved for use in epilepsy patients in the United States in August 1996. Epilepsy, a brain dysfunction typically manifested by attacks of altered awareness or convulsive seizures, is estimated to affect more than two million Americans.

The American Academy of Neurology, an association of more than 15,000 neurologists and neuroscience professionals, is celebrating its 50th year of improving patient care for people with neurological disease through education and research.

NEW GUIDELINES OFFER RECOMMENDATIONS FOR WOMEN WITH EPILEPSY

ST. PAUL, MN - New guidelines may help women with epilepsy make decisions about contraception, pregnancy and breast-feeding while managing the disease. The guidelines were issued by the American Academy of Neurology in the October issue of its scientific journal, Neurology.

"The issues are complex for the more than one million women with epilepsy in the United States," said neurologist and co-author Catherine Zahn, MD, of the University of Toronto. "Many women and their health care providers need more information about these issues. It's heartbreaking to hear about women who've been told they should never have children because of their epilepsy or their medications."

The issues include:

Birth defects - The drugs women take to control their seizures can increase the risk of birth defects. The risk of major defects is two to three times higher than the general population risk of approximately two percent. That risk must be weighed against the risks of seizures to mother and fetus, Zahn said.

"Overall, women should be optimistic," she said. "Most women with epilepsy who become pregnant will have successful pregnancies and healthy babies."

Recommendations:

•Using only one antiepileptic drug should be the goal of women of childbearing age, as women taking multiple medications may be at higher risk for children with birth defects.

•All women of childbearing age should take folic acid supplements; this recommendation is especially important for women with epilepsy, Zahn said. Folic acid supplementation has been shown to decrease the risk of neural tube defects such as spina bifida in infants of women without epilepsy. Women taking some antiepileptic drugs have an increased risk of having a child with this defect.

Contraception - Some epilepsy drugs can decrease the effectiveness of oral contraceptives. "Even given this reduced effectiveness, oral contraceptives are still as effective as IUDs and more effective than barrier methods such as condoms, when user error is factored in," Zahn said.

Recommendation:

•Women and their doctors should discuss this decreased effectiveness in determining the preferred method of birth control.

Breast-feeding - As with all medications, epilepsy drugs will appear in small amounts in breast milk, but this usually does not affect the baby.

Recommendations:

•Overall, the benefits of breast-feeding for the infant and the mother are felt to outweigh the small risk of adverse effects due to epilepsy drugs, Zahn said, and breast-feeding can be advocated as an option for women with epilepsy.

•Drugs that are sedating for the mother may cause drowsiness and poor feeding in the baby; those babies should be closely monitored.

Research - The report also calls for more research in several areas.

•For example, information isn't available regarding the risk of birth defects with several new drugs approved for use in epilepsy in the last five years.

•In another area, many women report that changes in their seizure frequency are related to their menstrual cycle. "Animal studies have shown that estrogen can increase brain seizure activity and progesterone can suppress this activity," Zahn said. "But not enough research has been done on this relationship and how it could be manipulated to reduce seizure frequency in some women."

Researchers also recommend that women with epilepsy develop and maintain a strong relationship with a neurologist or other health care professional knowledgeable about these issues.

To develop the guidelines, researchers conducted a search of 30 years of scientific literature for information on women with epilepsy. The American Academy of Neurology developed the guidelines in conjunction with the American Epilepsy Society, the Epilepsy Foundation of American and the Child Neurology Society.

Each month an article will be published on What is Traumatic Brain Injury. This is done as each month new victims are introduced to traumatic brain injury and it is the victims’ need that Brain Injury Society is concerned with. Articles will also be repeated, as to inform and empower the new victims and families of traumatic brain injury with information and a resource organization to reach out to.

 

SYMTOMOLOGIES OF TRAUMATIC BRAIN INJURY?

A person with mild traumatic brain injury is a person who has had a traumatically induced physiological disruption of brain function. Such injury is manifested by at least one of the following (Source: Definition of the American Congress of Rehabilitation Medicine Journal Head Trauma Rehabilitation 1993:8(3)86-7):

1.any period of loss of consciousness;

2.any loss of memory for events immediately before or after the accident;

3.any alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused); and

4.focal neurological deficit(s) that may or may not be transient; but where the severity of the injury does not exceed the following:

•post-traumatic amnesia (PTA) not greater than 24 hours.

•after 30 minutes, an initial Glasgow Coma Scale (GCS) of  13-15; and

•loss of consciousness of approximately 30 minutes or less.

CAUSES OF TRAUMATIC BRAIN INJURY

(1) the head being struck, and/or

(2) the head striking an object, and/or

(3) the brain undergoing movement in the skull without any direct external trauma to the head.

WHAT HAPPENS TO THE BRAIN IN A TRAUMATIC BRAIN INJURY?

The individual brain fibers can be damaged by:

1.Direct impact of the brain upon the skull caused by an object striking the skull (i.e., baseball bat hitting the skull);

2.The skull striking an object (i.e., running into a wall);

3.The brain undergoing movement in the skull without direct impact to the head (i.e., shaking).

If the brain is damaged at the point of impact, it is known as a coup injury.

If the brain is damaged on the opposite side. it is known as a contracoup injury.

Individual fibers can be damaged by stretching and tearing when the brain moves (shearing).

These same fibers can also be damaged because of pressure changes caused by the movement of the brain in the closed skull cavity (cavitation).

WHAT TYPE OF ACCIDENTS CAN CAUSE A TRAUMATIC BRAIN INJURY?

Typically, traumatic brain injuries occur in falls, auto accidents, sporting accidents, recreational and leisure activities or being struck by an oncoming object. They can also occur from violent shaking, (shaken baby syndrome), from falls in playgrounds, unsafe equipment or surfaces, by being struck by a car or by failing to wear a safety helmet while riding a bicycle, skating, skiing, skateboarding, horseback riding or playing football.

Shaken baby syndrome (shaking the head vigorously) where the infant’s brain is damaged by shaking is a perfect example of a type of situation where TBI occurs.

Broadly-speaking, any type of accident can cause a traumatic brain injury. Any type of traumatic impact event that causes excess movement of the head, or causes the head to strike an object or be struck by an object causes brain injury.

LOSE Of CONSCIOUSNESS (LOC)

The American Academy of Neurology has defined "concussion" as any alteration in consciousness. It can be (Source: Neurology 1997: 48:581-585):

Concussion is defined as the following:

1.A vacant stare (befuddled facial expression);

2.Delayed verbal and motor responses (slow to answer questions or follow instructions); 3.Confusion and inability to focus attention (easily distracted and unable to follow through with normal activities);

4.Disorientation (walking in the wrong direction; unaware of time, date and place); 5.Slurred or incoherent speech (making disjointed or incomprehensible statements); 6.Gross observable incoordination (stumbling, inability to walk tandem/straight line); 7.Emotions out of proportion to circumstances (distraught, crying for no apparent reason);

8.Memory deficits (exhibited by the athlete repeatedly asking the same question that has already been answered, or inability to memorize and recall 3 of 3 words or 3 of 3 objects in 5 minutes); and

9.Any period of loss of consciousness (paralytic coma, unresponsiveness to arousal).

WHAT ARE THE DISABILITIES ASSOCIATED WITH TRAUMATIC BRAIN INJURY?

The disability that an individual sustains depends upon the portion of the brain that was injured. Because the frontal and temporal lobes of the brain are exposed to the sharp protrusions on the inside surface of the skull, they are most prone to injury.

The most frequently observed symptoms are:

1.Loss of memory

2.Diminished concentration

3.Impaired perception

4.Impulsive behavior

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