PHYS THER
Vol. 84, No. 11, November 2004, pp. 1056-1086
Thirty-Fifth Mary McMillan Lecture |
Braving New Worlds: To Conquer, to Endure
Marilyn Moffat
M Moffat, PT, PhD, FAPTA, CSCS, is Professor of Physical Therapy, New York University, New York, NY. She also is director of the Professional Doctoral Program and the Master's Program in Pathokinesiology and is in private practice.
Address all correspondence to Dr Moffat at Physical Therapy Department, New York University, 380 Second Ave, 4th Floor, New York, NY 10010 (USA) (mm8{at}nyu.edu)
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Abstract
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Marilyn Moffat, PT, PhD, FAPTA, CSCS
Dr Moffat has had a tremendous impact on the physical therapy profession as a visionary leader, a distinguished educator, and an accomplished clinician, administrator, and researcher. She has served as editor of Physical Therapy and, as an elected member of APTA's House of Delegates, has been instrumental in providing direction for the future of the profession. She has served as a member of innumerable committees, task forces, and boards of directors at every level within the Association. In 1991, she was elected President of APTA for the first of 2 consecutive terms.
As President, Dr Moffat spearheaded the development of the Association's Guide to Physical Therapist Practice, and she later served as a project editor of the Guide's second edition and was heavily involved in the development of the Interactive Guide on CD-ROM. Dr Moffat has worked tirelessly since 1977, when she first spoke about the professional doctoral degree for physical therapists, to lead the profession through a process of redefining the role of the physical therapist for the future and ensuring that the highest level of practice would be achieved as a requisite for assuming the title "Doctor of Physical Therapy."
As a delegate to the World Confederation for Physical Therapy, Dr Moffat has provided leadership to the international community of physical therapists. She served as APTA's voting delegate to the WCPT General Meeting, on the Executive Committee of the WCPT as the North America/Caribbean Region representative, and as a member of the Task Force on the International Definition of Physical Therapy. Dr Moffat has given more than 800 professional presentations worldwide and has taught and consulted in Taiwan, Thailand, Burma, Puerto Rico, Vietnam, Hong Kong, and Wuhan in China. For her demonstrated worldwide leadership in physical therapy, she was honored with WCPT's Mildred Elson Award for International Leadership in Physical Therapy.
Dr Moffat has been the recipient of many APTA honors and awards. She has been recognized with APTA's Lucy Blair Service Award and as a Catherine Worthingham Fellow. She has received 2 diversity awards from the Advisory Panel on Minority Affairs, the R Charles Harker Policy Maker Award from APTA's Health Policy and Administration Section, and the Robert Dicus Outstanding Service Award from APTA's Private Practice Section. The most significant acknowledgments of her lifelong commitment to service are the New York Chapter's Dr Marilyn Moffat Distinguished Service Award and APTA's newly created Marilyn Moffat Leadership Award.
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Introduction
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To be selected as the 35th recipient of the Mary McMillan Lecture Award is a most humbling experience, as I join the ranks of some of the most respected and honored members, both past and present, of our profession. I began my physical therapy career the year the first McMillan Lecture Award was given and am in the wonderful position of having personally known every one of my 34 predecessors: Mildred Elson, who served as an inspiration for much of my involvement in the international aspects of physical therapist practice; Catherine Worthingham, whose major study on physical therapy education I had the honor of publishing when I was editor of our Journal; Ruby Decker; Emma Vogel; Helen Kaiser; Margaret Rood, whose McMillan Lecture many of us will never forget; Lucy Blair, with whom I worked at the national office; Maggie Knott; Lucille Daniels; Helen Hislop, with whom I had many hours of, let's say, "bantering" in the early days concerning a professional doctoral degree for physical therapists, which I supported from as early as 1977; Jane Carlin, to whom I had the pleasure of personally bringing the Catherine Worthingham Fellow Award; Mary Clyde Singleton, with whom I worked closely when I was editor of Physical Therapy; Margaret Moore, who was such a strong figure in physical therapy education in my early days; Helen Blood; Florence Kendall, who continues to be a larger-than-life role model for all of us even at the age of 94 years; Sue Hirt; Dottie Voss, who with Maggie Knott and others paved the way for approaching movement from a different perspective; Nancy Watts, with whom I shared time at many educational conferences; Eugene Michels—Mike—who challenged all of us to validate what we do; Geanie Johnson, who has been a professional and personal counselor for many years; Dot Pinkston, who I got to know, not only as a physical therapist, but also as a cook, during my first editorial board meeting in a 3-bedroom house in Laguna Beach; Charles Magistro, who has been a friend and confidant for many years and who even put up with my miniskirts at national office; Ruth Wood, whose sense of humor and good nature I have so appreciated, especially when she had to put up with me as a roommate at an international meeting; Don Lehmkuhl, another friend and pioneer in recognizing the importance of research in our profession; Bob Bartlett, who, of this entire group, is the physical therapist who I have known the longest—we were both graduates of New York University, both at Rusk Institute, both New York Chapter Presidents, and both APTA Presidents—a lifelong professional friend and mentor; Marylou Barnes, who is another individual with the best sense of humor and who dedicated so much of herself to the profession; Gary Soderberg, with whom I spent 11 hours literally glued to his hip in a station wagon as 6 of us attempted to get from an APTA Committee on Physical Therapy Education Meeting in Washington to Nashville, Tennessee, in the worst snowstorm DC had ever seen—a great friend and supporter; Bella J May, who showed me that you could attend an APTA conference, work hard, and still find time to exercise; Shirley Sahrmann, with whom I shared many exciting times in the House of Delegates as we both supported diagnosis and practice without referral; Suzann Campbell; Ruth Purtilo; Jules Rothstein, who was one of my students and who has made his mark on our professional publications; Steve Wolf, who showed us that collaborative research was certainly possible and evidence-based practice a necessity; and last, but not least, Pam Duncan. Our profession owes a great debt of gratitude to each and every one of these individuals.
I have the fantastic opportunity of looking at braving new worlds, to conquer and to endure. The turn of the century and the millennium was a rare moment in time, a chance to dream about the possibilities of the future, a chance to look at how we must function in this evolving world, and a chance to look at how we must ensure the viability of our profession. We will be confronted with major changes as a result of these brave new frontiers and concomitant technological revolutions that may change or make obsolete many of the disorders with which we have historically dealt, as well as many of the traditional patterns of physical therapy service delivery that we have known.
To begin, I will highlight some of the exciting new developments. Terms that are increasingly being used, some still not in dictionaries—"stem cell biology," "tissue-engineered implants," "immunogenetics," "tissue-inductive factors," "gene-transfer technologies," "convergence of cellular and electronic research," "tissue scaffolding," and "virtual reality"—are paving the way for potential changes that were until recently considered science fiction. And then we must look to how we conquer and endure as our profession reaches toward its 90th anniversary.
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Cardiovascular/Pulmonary Developments
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Vascular
Let's begin with the cardiovascular and pulmonary systems. Peripheral vascular disease is treated in numerous ways by opening blocked vessels. In many cases, angioplasty can be performed without surgery. Stent grafts inserted into blood vessels bypass diseased arteries (Fig. 1).
Thrombolytic therapy uses clot-busting drugs delivered to the blockage to treat deep vein thrombosis, phlebitis, venous stasis disease, and pulmonary embolism. These drugs are frequently combined with other treatments, such as angioplasty.1 The treatment of pulmonary embolism uses percutaneous thrombectomy, whereby a catheter to the clot uses a device to break up the clot into easily absorbed pieces.2,3 Deep vein thrombosis is managed in several ways, including laser,4 radio frequency energy,5 sclerotherapy,5 phlebectomy,6 and endoscopic repair for cases of vascular disease with ulceration.7
Cardiac
Drugs used for decreasing or removing cholesterol will continue to be developed. Recently, 47 patients with atherosclerotic heart disease were given a synthetic version of high-density lipoprotein. At the end of only a 5-week clinical trial, coronary artery plaque formation was reduced by an average of 4.2%.8,9
Studies continue to look at those things that portend heart disease. Elevated C-reactive protein levels have been shown to be related to cardiovascular risk.10 High levels of lipoprotein-associated phospholipase A2 have been noted before individuals actually had coronary events.11 Homocysteine was a promising indicator initially, but later studies have been disappointing.12 Fibrinogen levels were thought to be predictors of heart disease, but recent data suggest that they may not be.13 High levels of lipoprotein(a) are generally showing a strong tie to heart disease risk.14
Robotic–computer-assisted heart surgery and minimally invasive heart surgery, or off-pump coronary artery bypass graft (CABG) or beating heart bypass surgery, will continue to be refined. Evidence points to reducing the risk of complications and decreasing the incidence of neurocognitive dysfunction.15
A National Institutes of Health (NIH) study is looking at the implantation of autologous skeletal myoblasts into myocardial scar tissue areas to enhance myocardial performance. Preliminary data indicate that the implantation also may be done at the same time as CABG surgery, leading to increased myocardial muscle performance.16
Stem cell research will appear repeatedly throughout this presentation. Injections of adult stem cells into damaged myocardial tissue in patients with severe congestive heart failure at the time they were undergoing off-pump cardiac bypass surgery improved cardiac function. Ejection fractions went from below 35% preoperatively to 44% to 50% at 6-month follow-up.17
Injecting stem cells using minimally invasive techniques in patients with inoperable congestive heart failure is being investigated. Other work will give stem cells to patients with implanted heart-assist devices who are awaiting cardiac transplant.
Some reports support the use of bone marrow stem cells to regenerate heart cells and blood vessels. Researchers18,19 showed that transplantation of a person's own stem cells through direct intracoronary injection increased blood flow and metabolism in the myocardial cells in failing hearts and increased cardiac function.
Stem cells were used to lower pulmonary arterial hypertension in rats. The vascular progenitor cells from the rats' marrow actually engrafted into the microcirculation and formed tiny new blood vessels in the pulmonary circulatory system.20
On another front, researchers have found a strong relationship between the severity of heart disease and the level of circulating endothelial progenitor cells. They feel that it might soon be possible to prevent atherosclerosis by injecting progenitor cells into patients and that the possibility exists of retraining a patient's own stem cells to differentiate into progenitor cells that can repair damaged arteries.21
Pulmonary
Transplantation of human adult stem cells in damaged lung tissue results in spontaneous regeneration of lung cells. The concept that circulating stem cells are actually going into organ tissue and repairing damage has far-reaching implications for the treatment of many lung diseases, such as emphysema and cystic fibrosis.22
Progress continues in attempting to treat the gene abnormality that causes cystic fibrosis.23 The effectiveness of an investigational gene-transfer aerosolized agent is being investigated in individuals with mild to moderate cystic fibrosis because earlier results displayed a positive trend in lung function.24 Others are looking at a unique form of gene therapy using compacted DNA with the hope of producing a protein to correct the basic defect in cystic fibrosis.25
Stroke
The initial management of stroke is aimed at treating the "brain attack" and intervening with urgency to reduce morbidity and mortality. Treatment is directed at dissolving blood clots, opening narrowed carotid arteries, treating ruptured blood vessels in the brain, and determining what is occurring at a cellular level.
Dissolving clots is done in the period immediately following a stroke. Tissue plasminogen activator (tPA) is administered within the first 3 hours of the stroke to break up or reduce the size of clots.26,27
When therapy cannot be initiated within 3 hours or when treatment with tPA is not sufficient, intra-arterial thrombolysis may be used. Tissue plasminogen activator or other clot-busting drugs, such as prourokinase, are delivered directly to the site of the clot. In the largest ongoing clinical trial, 40% of patients treated with prourokinase reported excellent recovery after 90 days compared with only 25% of patients who did not get the treatment. In addition, clogged arteries were successfully opened in 66% of patients treated with intra-arterial thrombolysis compared with 18% who were not.28 If a stroke is the result of atherosclerotic narrowing of the carotid arteries, follow-up angioplasty and stenting may be needed to open the blocked artery and prevent another stroke.29
Treatment of ruptured vessels is done using embolization, in which a clotting agent is delivered to the hemorrhagic area. This technique is used for patients at high risk for brain surgery or when the location of the rupture makes surgery difficult. The technique can be used to treat aneurysms and arteriovenous malformations before they rupture.30
Treatment of stroke is increasingly being looked at from the cellular level. Mechanisms of neurotoxicity due to particular amino acids are being investigated. Many new drugs, especially the neurotransmitters, have the potential to reduce the damage and mediate its effects. Studies also are being conducted on how glial cells die, and these results will undoubtedly open new possibilities for treatment. Animals that received a protein called E-selectin on a regular schedule had almost no strokes compared with those that did not receive it.31
From a therapeutic standpoint, alternatives are under study. Technology has led to the development of robotic stroke therapy that augments physical therapy (Fig. 2). Robotic devices ultimately may result in substantial improvements in the speed and quality of recovery. Robotic systems can assist or resist elbow and shoulder motions in three-dimensional (3-D) space and have a bimanual mode to enable users to practice mirror imaging of upper-extremity exercises. Preliminary results have shown improvements in the level and speed of recovery of functional performance of individuals with hemiplegic upper-extremity impairments.32–35
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Figure 2. Robotic stroke therapy. Photograph courtesy of Laura Wulf/Massachusetts Institute of Technology, Cambridge, Mass.
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The use of a mechanized gait trainer for 4 weeks with physical therapy for subjects with hemiparesis who were chronic wheelchair users resulted in improvement of gait ability in all subjects.36 Velocity, cadence, and stride length improved. The kinesiologic electromyogram of selected lower-limb muscles revealed a more physiologic pattern.36 Researchers are currently looking at robotic-assisted gait training with an exoskeletal system for facilitating the recovery of stable walking patterns in patients who have had a stroke (Fig. 3).37
Constraint-induced, movement-based therapy has been shown to improve motor function and the use of the upper extremity in individuals with hemiparesis, even after chronic stroke (Fig. 4). Overcoming learned nonuse and inducing use-dependent cortical reorganization appear to be responsible for this improvement. Currently, research is under way to design instrumentation to enable patients to do the program at home.38–41
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Figure 4. Constraint-induced movement therapy for cerebrovascular accident. Photograph courtesy of University of Southern California, Los Angeles, Calif.
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Studies now being funded are looking into whether combining exercises with anesthesia that blocks both motor and sensory function may improve hand movements,42 whether administration of amphetamines with rehabilitation speeds motor recovery after a stroke,43 and whether the use of transcranial magnetic stimulation or transcranial direct current stimulation coupled with exercise enhances performance of patients with chronic stroke.44,45
Diabetes
Stem cell use also is under consideration in the management of diabetes. Insulin-producing cells for transplantation can be generated from adult pancreatic stem cells.46
Technological advances for administration of insulin will be in the areas of implantable pumps, transdermal applications, and inhaled or oral spray insulin. New drugs will emerge aimed at both diabetes and obesity. The roles of exercise and diet will continue to be important.
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Musculoskeletal Developments
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The World Health Organization, working with the Bone and Joint Decade, hopes to help nations prepare for the increasing numbers of individuals with musculoskeletal disabilities.47 Innovative tissue-engineering tools will alter the treatment of many musculoskeletal disorders. Cell destiny may be tantalizingly manipulated. The use of stem cells, microprocessors, advanced computer integration, tissue-inductive factors, new biomaterials, and gene-transfer technologies will break new ground.
Amputations
The management of patients with amputations has undergone revolutionary changes. These changes have included the use of space-age materials such as silicones, titanium, and carbon fiber, state-of-the-art technology in computer-aided design and computer-aided manufacture (Fig. 5), finite element analysis using computational methodologies to determine when a prosthesis is tight enough to be stable without causing tissue damage, and myoelectric circuitry.
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Figure 5. Computer-aided design (left) and computer-aided manufacture (right). Photographs courtesy of Dr Ping He, Department of Biomedical, Industrial and Human Factors Engineering, Wright State University, Dayton, Ohio.
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Spring-loaded shock absorbers make participation in sports such as rock climbing realistic.48 Innovative intersection of the human body and prosthetic technology enables sprinting and long-distance running (Fig. 6).49 There is no doubt that the prosthetic limbs of tomorrow will mimic human limbs in ways we never thought possible.
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Figure 6. Athletic skills of people with an amputation: (above, left) during long-distance running (photograph courtesy of Giovanna Nigro-Chacon, Mendocino, Calif), and (right) during sprinting (photograph courtesy of Scott Sabolicj, Prosthetics & Research, Oklahoma City, Okla).
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Microprocessors in prosthetic knee joints control the swing of the prosthesis. They can recognize when the wearer is losing balance and automatically adjust the knee to prevent a fall (Fig. 7). These "intelligent" prosthetic devices, along with miniaturization, new power sources, and more complex computer control systems, will enable the user to concentrate on normal activities without limitations.50
Advanced lower-extremity prostheses have myoelectric control with transducers on the bottom of the foot that send electrical signals to the residual limb, which picks up the signals and transmits them to the brain, just like a natural foot. The brain then knows the pressure on different parts of the sole.51,52
Research is under way on the use of myoelectric signals to control dexterous robotic and prosthetic hands (Fig. 8). This research may eventually lead to comfortable, lightweight, and relatively inexpensive prosthetic hands acting in a nearly lifelike manner in response to the myoelectric signatures of as many as 6 different grips. Cylindrical, precision, hook, and lateral grasping modes are currently available.53–55 In the future, prosthetic limbs will allow more sense of feel to both the hands and feet, and they will even be able to detect soft, rough, cold, and hot.
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Figure 8. Dexterous robotic prosthetic hand. Photograph courtesy of William Gruver, The Intelligent Robotics and Manufacturing Systems Laboratory, School of Engineering, Simon Fraser University, Burnaby, British Columbia, Canada.
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Work has been under way with direct attachment of prosthetic limbs into the residual bone, similar to tooth implants, called osseointegration (Fig. 9). The need for weight bearing through prosthetic sockets is eliminated. Thus, we are seeing the convergence of cellular and electronic research and an era of prosthetics that will be part person and part machine.56–58
A fascinating phenomenon related to limb amputation is the scientific investigation of animals that are able to regenerate amputated limbs. Although most have been invertebrates, a newt, which is a type of salamander and a vertebrate, is able to regenerate a limb in approximately 3 weeks after amputation. Being able to grow new tissue and organs has incredible implications for people with amputations.59
Fractures
Fracture healing is a major concern for physical therapists. Demineralized bone matrix, a sterile tissue gel, has been harvested from donor bones. It is mixed with pulverized allograft and delivered to the fracture site to provide the osteoinduction or scaffolding upon which osteogenesis can occur.60
A nanotechnology invention of injectable calcium phosphate-based biomaterial—that is, a "flowable" bone cement—is capable of stabilizing a fractured bone within 5 to 15 minutes. Because of its superior compressive strength, it can be used for both weight-bearing and non–weight-bearing bones. This new material will potentially be used for vertebroplasties to stabilize osteoporotic spinal fractures, eliminating the current side effects found using polymethyl methacrylate.61
Studies suggest that early treatment of spinal fractures with vertebroplasty can strengthen the spine, prevent further fractures, and improve posture.62 Technological approaches to vertebroplasty (Fig. 10) include the use of new materials that will convert to bone and stimulate bone growth. Vertebroplasty also may be used preventively in the future to treat fragile vertebra. Researchers hope that "kyphoplasty," involving injecting biomaterial into a small balloon in a collapsed vertebra, will restore or prevent height loss.62
Although these techniques have been applied to vertebral fractures, the future management of all fractures may be achieved by gluing them together, rather than through the use of multiple types of hardware from plates to screws and joint replacement.
Cartilage, Tendon, and Meniscal Repair
Technological advances in the area of cartilage, tendon, and meniscal repair include the work on a new class of bioabsorbable polymers for practical implant materials. Cartilage regeneration is being investigated, as is seeding of chondrocytes into a synthetic matrix that can be molded into a cartilage defect. The cartilage would be grown in vitro, implanted into the body to be absorbed, and replaced with hyaline-like cartilage.63,64
Recombinant versions of human collagen have been produced for bone and cartilage repair. More than 20 different types of collagen have been identified within the human genome, opening up new possibilities for tissue scaffolding.65
Patch grafts of porcine small intestine are being used for meniscal repair and regeneration. The graft allows ingrowth of human cells, acts as a scaffold, and will have its use in thin, weakened tissues, for example, with chronic, old quadriceps femoris muscle ruptures and rotator cuff tears.64
A tissue-engineering strategy, using mechanical and biological approaches, has been developed to repair ruptured anterior cruciate ligaments by engineering new ligament strands—as seen against the quarter (Fig. 11). The ligament is custom-engineered from a patient's or donor's adult bone marrow stem cells.66
Chains of amino acids, or peptides, are being used with collagen scaffolding to treat injured cartilage from a cellular level. Viscoelastic products from polymers and hyaluronic acid products are being studied for their roles in protecting, healing, and repairing cartilage and soft tissues. Research has shown that bone morphogenetic proteins linked to a collagen carrier induce new tendon/ligament formation.67,68
The use of mesenchymal stem cells for healing cartilaginous, osseous, and tendon defects has been studied for more than 10 years.69 Stem cells have been experimentally used to create cartilaginous tissue for repair and regeneration. So far, the stem cells have been implanted in meniscus defects in rabbits with good success.70 Experimentation has been done to evaluate the potential of mesenchymal stem cells in the treatment of osteogenesis imperfecta.71
Intervertebral Disks
Artificial intervertebral disks have been implanted for several years in Europe and Asia as an alternative to fusion, preserving spinal motion and perhaps delaying degenerative changes in surrounding spinal segments (Fig. 12). Data from experimental clinical trials in the United States are indicating shorter operative times and earlier return to work.72
Tissue engineering may advance the treatment of intervertebral disks. The possibility exists that implantation of cell-gels or the use of bone morphogenic proteins may restore intervertebral disks. Bone morphogenic proteins also are being used to produce a spinal fusion.73 Gene therapy may well be the next avenue of investigation for spinal fusion.74
Osteoarthritis
Arthritis currently affects nearly 1 of every 6 people, and it is estimated that, by 2020, almost 1 in 5 people will be affected. The management of osteoarthritis is affected by technological advances. Autologous cartilage transplantation via arthroscopic surgery is a possible treatment for traumatic articular cartilage defects.75,76
Investigators are searching for genes that appear to be related to certain forms of inherited arthritis and that would lead to new treatment. Researchers also feel that osteoarthritis is well suited to local gene therapy, whereby genes are introduced intra-articularly into the synovium and cartilage. This gene therapy may lead to blocking joint damage and promoting repair.77
The use of glucosamine and chondroitin sulfate supplements continues to undergo investigation. A 3-year international study of 212 patients showed that patients taking glucosamine felt 20% better and that the knee joints were spaced almost as evenly as when the study began.78
A meta-analysis to assess the efficacy of glucosamine and chrondroitin on knee osteoarthritis revealed that glucosamine improved joint space narrowing and both supplements reduced pain and stiffness and improved physical functioning and joint mobility.79 In 2000, the NIH awarded a $6.6 million grant to direct a 4-year clinical trial investigating the effects of glucosamine and chondroitin on 1,600 patients.80
A tissue-engineering biotechnology company is hoping to enable stem cell technology to grow cartilage from skin. The company's initial goal is to be able to cure the majority of arthritic joints. According to a company spokesperson, "Dermal fibroblasts can easily be acquired directly from the patient's skin and can easily be multiplied prior to conversion into cartilage forming cells."81
Another interesting avenue of research has been with sea cucumbers, which have no internal skeleton but do have a connective tissue that is dense and fibrous and can change back and forth from flexible to stiff (Fig. 13). Using this connective tissue for repairing a torn Achilles tendon would simply be done by using this substance as an ointment to form new bonds between the collagen fibrils at the site of the tear—no gap, no scar, and no loss of strength.82
Osteoporosis
Hibernating black bears are being studied because they do not undergo bone density loss during their 3 to 5 months of hibernation. Researchers83 are investigating calcitonin and parathyroid hormones in bears and humans that may lead to new therapies.
Researchers have succeeded at inducing early (pre-fat) cells to become fully developed bone cells.84 In all of us, cells in the bone marrow must decide whether to become a bone cell or a fat cell. As people age, the number of cells available to make this decision decreases, and most of those cells become fat cells, a contributing factor for osteoporosis. This approach could have important implications in promoting bone regeneration.84
Genetic engineering, a combination of gene therapy and tissue engineering, is reported to result in the delivery of genetically modified stem cells and is thought to eventually provide new avenues of treatment for osteoporosis.85 However, with mice studies failing to show major osteoblastic activity in situations of estrogen deficiency, an osteoinductive carrier or some other cell-inducing agent with the mesenchymal stem cells may need to be added to achieve significant bone regeneration.86 Investigation also is under way to determine the ability of adult stem cells to restore normal bone physiology.87
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Neuromuscular Developments
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Technology will affect the physical therapist management of patients with neuromuscular dysfunction. Mapping of the brain has given us greater insight into this central mechanism for human performance (Fig. 14). Electroencephalographic analyses revealing the interdependence of brain areas shed new light on our ever-growing body of knowledge concerning brain function (Fig. 15). Functional magnetic resonance imaging in real time reveals which portions of the brain are activated and when (Fig. 16).
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Figure 14. Brain mapping. Photograph courtesy of Paul Thompson, Kiralee Hayashi, and Arthur Toga, University of California at Los Angeles, Los Angeles, Calif.
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Figure 15. Interdependences in electroencephalographic activities of different brain areas: (a) general words, (b) listening, (c) reading, and (d) speaking. Photographs courtesy of Jochen Arnhold and Peter Grassberger, NIC-FG Vielteilchenphysik; and Klaus Lehnertz and Christian E Elger, Epileptologische Klinik, Universitat Bonn, Bonn, Germany.
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Figure 16. Functional magnetic resonance imaging in real time. Photograph courtesy of Stefan Posse, Institut für Medizin, Forschungszentrum, Jülich, Germany.
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Multiple Sclerosis
The immune system protein known as "osteopontin" was noted in 2001 to be a critical factor in the immune attack of multiple sclerosis and its progression.88 Currently, work is on the development of a DNA vaccine to tone down osteopontin.89
High levels of genes that had previously been found only in bones, allergic responses, and pregnancy were found in patients with multiple sclerosis. Among the genes that were overexpressed in multiple sclerosis were a histamine receptor and proteins associated with pregnancy. These results could lead to the regular use of antihistamines to treat these patients.90 Statins, the cholesterol-lowering drugs, also have been used in the treatment of multiple sclerosis and have reduced the size and number of brain lesions.91
Researchers have identified molecules that underlie nerve fiber degeneration in patients with secondary progressive multiple sclerosis. In autopsy studies, they found a strong link between nerve damage and the presence of 2 molecules, a sodium channel and a sodium-calcium exchanger. These findings may lead to new therapies.92 Investigation also is under way in the treatment of patients with multiple sclerosis using autologous stem cell transplantation.93
Research will determine the role of genetic risk factors and their modification and the role of environmental triggering factors, such as viruses or toxins in multiple sclerosis. Identification of factors involved in the immune attack in the brain and spinal cord, such as cellular and subcellular targets and the T cells, is needed.
Muscular Dystrophy
Scientists may soon be able to influence muscle formation in patients with muscular dystrophy because they have found that enzyme inhibitors can switch the pathway of muscle precursor cells or myoblasts from simply reproducing themselves to becoming mature cells that form muscle fibers or myotubules.94 Further research will be directed at discovering whether the cells induced to form muscle will restore muscle function when transplanted into a mouse model.94 The finding that limb-girdle muscular dystrophy, type 2B, is caused by a genetic deficiency of the protein dysferlin may ultimately lead to the first effective treatments.95
Experimenters continue to evaluate the potential of mesenchymal stem cells in the treatment of Duchenne muscular dystrophy. They have managed to use stem cells to strengthen the muscles of mice with a form of muscular dystrophy.96 Researchers are hoping to combine the power of stem cells and gene therapy to develop a treatment to combat muscular dystrophy.97
Parkinson Disease
Innovative treatments for Parkinson disease include the use of genetics, deep brain stimulation, new drugs, surgical ablation, and cell implantation. Familial genetic mutations have been found in Parkinson disease, and encoding proteins, such as parkin, are creating new genetic ways to define the disease.98 However, the role of genetic factors that have been established in early-onset forms of familiar parkinsonism is not clear in late-onset Parkinson disease.99 Gene-by-gene interactions are important in Parkinson disease susceptibility.100 Inhibition of the subthalamic nucleus via deep brain stimulation suppresses the symptoms in animal models of Parkinson disease, and high-frequency chronic stimulation does the same in humans.101
Neurotrophic proteins appear to protect nerve cells from the early death that prompts Parkinson disease. Patients who received a neurotrophic factor directly into the putamen had improved motor performance while they were off medication, improved functioning in activities of daily living, and reduced medication-induced dyskinesia.102
Neuroprotective agents, such as naturally occurring enzymes that appear to deactivate "free radicals," may be linked to the damage done to the nerve cells in Parkinson disease. Neuroprotective drugs that block biochemical pathways leading to cell death are under investigation.103
Researchers have studied the implant of fetal pig neural tissues into the brain to restore the degenerated area. In clinical trials, a reduction in symptoms was observed in younger patients implanted with the pig tissues.104,105
The genetic code of individual cells has been modified to create dopamine-producing cells from other cells, including those from the skin.106 Mouse stem cells transformed into neurons transplanted into a rat model were shown to form functional connections and reduce disease symptoms.107 The use of selected stem cells continues to be investigated in Parkinson disease.108–110
Cerebral Palsy
Brain repair through the use of stem cells for the treatment of cerebral palsy is an area forging fascinating research activities (Fig. 17). Precursor neural cells grown in the lab generate mature neurons and glial cells. After the transplantation into the brains of young mice, the neural precursor cells give rise to functioning neurons and astrocytes, a star-shaped cell of the brain and spinal cord. Researchers have shown in mice that mature stem cells from the bone marrow will migrate to the site of brain injury. Further investigation will attempt to see if putting additional stem cells in the circulatory system of mice with ischemic brain injury can augment the repair of brain tissue.111 In addition, work will look at the particular types of stem cell (eg, hematopoietic or marrow stromal cells) to see if one is more effective than the other.112
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Figure 17. Stem cells. Photograph courtesy of Su-Chun Zhang, MD, PhD, University of Wisconsin, Madison, Wis.
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Research has shown that bleeding in the brain unleashes dangerously high amounts of glutamate. Although glutamate is normally used in the brain for communication, too much overstimulates the brain's cells and causes destruction. Scientists are now looking closely at glutamate to detect how its release harms brain tissue and spreads the damage.113
Investigators are attempting to ascertain if certain drugs may prevent neonatal stroke. Some of these promising drugs appear to reduce the excess production of dangerous chemicals in the brain and may help control brain blood flow and volume.113
Scientists are working to develop new drugs—and new ways of using existing drugs—to help relieve the symptoms of cerebral palsy. The use of implanted pumps that deliver a constant supply of antispasticity drugs into the fluid around the spinal cord is being explored, in the hope of improving effectiveness and reducing side effects.113
Training devices (eg, stationary bicycles and treadmills linked to sensory stimulation) for providing input into the brain also are increasingly supported modes of enhancing function in individuals with cerebral palsy. The Lite Gait system (Fig. 18, left)* and the WalkAble (Fig. 18, right)* are 2 such units on the market.114 The SMART Walker (Fig. 19)
was developed to enable children with cerebral palsy to stand, ambulate with hands-free support, and explore their environment.115 The use of constraint-induced movement therapy for children with hemiparesis has been shown to result in acquisition of more new motor skills, increased amount and quality of movement of the affected arm at home, and increased unprompted use of the affected upper extremity, all of which were maintained for over 6 months (Fig. 20).116
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Figure 18. Training devices for enhancing function in individuals with cerebral palsy: (left) Lite Gait 100 MX, (right) WalkAble. Photographs courtesy of Mobility Research, Tempe, Ariz.
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Figure 20. Constraint-induced movement therapy for a child with cerebral palsy. Photograph courtesy of the University of Alabama at Birmingham Civitan International Research Center, Pediatric Neuromotor Research Clinic, Birmingham, Ala.
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Spinal Cord Injury and Other Paralytic Disorders
One reads the stories of the remarkable activity that Christopher Reeve (Fig. 21) has exhibited. His ability to voluntarily move body parts and feel 9 years after his spinal cord injury must make us all rethink those things we learned in school about spinal cord injuries. Intensive physical therapy utilizing functional electrical stimulation, water therapy, harnessed weight bearing, breathing exercises, and cardiovascular/aerobic training has resulted in movement activities not thought possible. As early as 2002, rats have been given neuronal stem cells after extensive spinal cord resection and have shown some functional recovery.117 As these factors are investigated carefully, other technological advances also will help individuals with spinal cord and other paralytic disorders.
Long leg orthoses are currently available that lock the knee when needed during stance and unlock it during swing. The use of tubular stainless steel allows for the development of very lightweight, but extremely strong, orthotic devices.118
Neuroprostheses were surgically implanted in a group of volunteers who have paraplegia with long-standing paralysis (Fig. 22). The neuroprothesis enabled standing, transfers, release of a hand from a support device for object manipulation, and performance of a swing-to gait with a walker.119
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Figure 22. Implantable neuroprostheses: (left) implanted neuroprosthetic functional electrical stimulation (FES) unit, (right) radiograph of implanted neuroprosthetic FES unit. Photographs courtesy of the Cleveland FES Center, Cleveland, Ohio (http://fescenter.case.edu).
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The next generation of technology in the use of implantable neuroprosthetic systems for upper-extremity function will be based on the earlier work of the Freehand system,
which is no longer produced.120–122 The new systems hopefully will allow finer hand control, active extension of the elbow, or improved sensory feedback strategies. Study has shown that the addition of a triceps muscle electrode to the neuroprosthetic hand grasps can increase arm extension and controllable workspace.123
Since 1999, the use of cortical signals to control neuroprosthetic devices for patients with paralysis has been investigated. A miniaturized neuroprosthesis is under development that will be suitable for implantation into the brain. This type of device will potentially eliminate all external signal and power wiring devices now needed for neuroprostheses.124–126
Research is under way involving advances made in detecting neural signals and translating them into command signals to control devices. Tiny probes were implanted into several brain regions of 2 rhesus monkeys. Each monkey learned to move a joystick that controlled a cursor on a computer screen. To get a drink of juice, the monkey had to move the cursor to a ball target when it appeared on the screen (Fig. 23, left). Electrical patterns from the monkey's brain were collected as it performed the tasks. When the monkey was skilled at the task, the joystick was disconnected. Initially, the monkey jiggled the stick and just stared at the screen. Even though the joystick was not working, the monkey's reaching and grasping motor plans were being sent to a computer, which translated those signals into movements on screen. Suddenly, the monkey realized that it could guide the cursor and grasp an object on the screen just by thinking it (Fig. 23, right). The monkey's arm dropped, and the muscles no longer contracted. We see the monkey's ability to move a robot arm with thoughts, thus bringing the merger of mind and machine one step closer, and a potentially major innovative approach to management of patients with spinal cord lesions or paralysis from other causes.127,128
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Figure 23. Setup for detecting neural signals and translating them into command signals to control devices: (left) monkey moving joystick to move cursor to target, (right) monkey without joystick translating brain neural signals into command signals to control devices. Illustrations courtesy of Miguel Nicolelis, MD, PhD, Department of Neurobiology, Duke University Medical Center, Durham, NC.
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Exoskeleton Technology
Research has demonstrated that the spinal cord may be able to learn to initiate steps without input from the brain through a new therapy called "locomotor training." Robomedica is testing a robotic step-training device for retraining individuals with neurologic impairments to walk (Fig. 24). The device will monitor and record patient progress and demonstrate measurable results.129
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Figure 24. Robotic step-training devices for individuals with neurologic impairments: (left) RoboKnee, (right) RoboWalker. Photographs courtesy of Yobotics Inc, Cincinnati, Ohio.
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Exoskeleton technology has endless possibilities for many patients with paralysis, especially of the lower extremities. The RoboKnee
is being tested as a motorized brace. Sensors in the shoe and along the leg detect the pressure being exerted by the leg onto the ground and detect muscle movement. Requiring only partial movement of the legs, the RoboKnee can do up to 80% of the work of the legs while walking and climbing. Thus, for patients who had poliomyelitis or those who have muscular dystrophy, this type of device may be invaluable.130
An exoskeleton for elderly people also has been developed. The Hybrid Assistive Leg|| is a robotic suit with joint-angle sensors, myoelectric sensors, and floor sensors that enable elderly people or those with physical disabilities to walk at a speed of 4 km/h with little physical effort, climb stairs, and sit and stand (Fig. 25). Everything is built into a backpack. Faint muscle signals must at this stage be present. The eventual aim is to make a suit that is thin enough to be worn like underwear and allow the user to run and freely move the upper extremities.131
Wheelchair Technology
Seating systems are increasingly adapted through computerized technology. Computer analysis of peak pressures during sitting and the times at which they occur facilitate the correct seat to prevent skin breakdown (Fig. 26).132
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Figure 26. Seating systems adapted through computer technology: (left) ClinSeat system in place, (right) seating pressure profile shown using the ClinSeat system. Photographs courtesy of Tekscan Inc, South Boston, Mass.
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Wheelchair technology is progressing. The Computer-Controlled Power Wheelchair Navigation System# remembers paths that have been laid out for it. The wheelchair is initially maneuvered through the patient's operational environments, and all of the destinations are programmed into the computer. An ultrasound profile is assigned so that the patient can approach solid objects (eg, the edge of the user's desk) as required on the computer pathway to get from point A to point B. The patient selects the desired destination from a menu with a chin switch, voice, eyelids, or pointer, and the chair proceeds to that location (Fig. 27).133–135
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Figure 27. Computer-Controlled Power Wheelchair Navigation System, current version, prototype developed at the Vision, Dexterity and Control Laboratory at the University of Notre Dame. Photograph courtesy of Vision, Dexterity and Control Laboratory at University of Notre Dame, Notre Dame, Ind.
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Wheelchairs will navigate previously inaccessible places. The iBOT** is a wheelchair that is capable of going into four-wheel drive, going over stones, going over logs, climbing stairs, elevating, and balancing on 2 wheels (Fig. 28).136
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Figure 28. INDEPENDENCE iBOT Mobility System: (a) stair climbing, (b) elevation, and (c) over logs. Photographs courtesy of Independence Technology LLC, Warren, NJ, © 2004 (www.ibotnow.com).
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The Human Genome Project
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The Human Genome Project (HGP) was an international research effort to sequence and map all of the Homo sapiens genes—together known as the genome (Fig. 29). The project gave us the chance to read nature's complete genetic blueprint for building a human being. The ultimate quest is to understand the role it plays in health to be better able to diagnose, treat, and prevent disease. One of the latest projects is to develop a new kind of map of the human genome to hasten the discovery of the variant genes thought to underlie common diseases such as diabetes, asthma, and cancer.137
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Technological Developments in Physical Therapy
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Physical Therapist Examination
Physical therapist examination will witness many changes in the sophistication and the reliability and validity of data obtained with the instruments used for tests and measurements. Three-dimensional gait analysis (Fig. 30, left) and biomechanical studies (Fig. 30, right) are vital for quantifying an individual's performance.138,139 The use of moving platforms is one way that a patient's balance control can be assessed. Stimuli are given through the platform and through virtual reality situations (Fig. 31).140 The use of optical motion capture for gait analysis has helped speed diagnosis and treatment for patients with cerebral palsy (Fig. 32).141
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Figure 30. Biomechanical 3-dimensional gait analysis studies. Images courtesy of Vicon Motion Systems, Lake Forest, Calif.
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Figure 32. Optical motion capture for a patient with cerebral palsy. Image courtesy of Vicon Motion Systems, Lake Forest, Calif.
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Force scan (F-scan) units (Fig. 33) provide increasing data about gait parameters.142 Fiber optic sensors will generate data on the range of motion of body parts as seen in an analysis of finger flexion.143 Gloves will sense joint angles (Fig 34).144 For examination of range of motion, wounds, muscle bulk, and chest expansion, the FastSCAN, a 3-D handheld laser scanner, now with a stylus option, instantly provides an exact replica of the scanned object on the computer screen (Fig. 35).145
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Introduction
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