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Thread: DIRECTORS’ SUMMARY Miami Project

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    Senior Member chastev8's Avatar
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    DIRECTORS’ SUMMARY Miami Project

    POSTTRAUMATIC SECONDARY INSULTS
    W. Dalton Dietrich, PhD Helen M. Bramlett, PhD Robert P. Yezierski, PhD Spinal cord injury (SCI) sets off a cascade of cellular and inflammatory responses that lead to loss of tissue and lack of functional recovery. Miami Project researchers have been studying these responses to identify if secondary insults increase tissue damage and worsen behavioral outcome. Immediately after SCI, people often experience problems with breathing, putting them at risk for insuf�cient oxygen to reach the blood. This can lead to hypoxia, a de�ciency of oxygen, in the cells. Additionally, the injury may cause hypotension, a low blood pressure, which may influence blood flow to the central nervous system and hyperthermia, an unusually high fever, which may increase body temperature. The purpose of these studies by Helen Bramlett, PhD and Scienti�c Director, W. Dalton Dietrich, PhD and their colleagues, was to investigate whether these secondary insults, hypoxia, hypotension or hyperthermia, influence nervous system damage. Signi�cantly more tissue damage occurred in the groups of animals that experienced hypoxia, hypotension, or hyperthermia induced during the experiments than in those that did not. These results emphasize the need for controlling the oxygen and blood flow to nervous tissue and suggest that complications of SCI, such as fever leading to spinal cord hyperthermia, may add to the severity of injury and signi�cantly affect neurological outcome. These �ndings indicate that clinical researchers should consider therapies to protect patients from secondary insults after SCI.

    IDENTIFYING AND PREVENTING THE INTRICATE INJURY MECHANISMS THAT OCCUR IMMEDIATELY AFTER SCI
    W. Dalton Dietrich, PhD John R. Bethea, PhD Robert P. Yezierski, PhD An active area of research at the Miami Project is in developing neuroprotective treatments to protect the spinal cord in the �rst hours and days after the injury. There is a belief that limiting the degree of secondary injury will limit the severity of neurological de�cits after SCI and may therefore enhance the recovery of function. Many studies provide evidence that apoptosis, an active cell-suicide program, is responsible for some cell death following SCI. Very little information is available about anti-apoptotic mechanisms that inhibit programmed cell death within the injured spinal cord. Data from John Bethea, PhD and W. Dalton Dietrich, PhD indicate that inhibitors of apoptosis do exist within the spinal cord cells which may help them survive. By gaining a better understanding of these intricate molecular, cellular, and regulatory events that occur following SCI, we may be able to design new therapeutic strategies to enhance natural healing mechanisms and to diminish those events that lead to further damage. Systemic modest hypothermia may be one such therapy. When modest systemic hypothermia was induced following SCI in rodents, the total area of spinal cord damage was reduced. The researchers, including Dr. Robert Yezierski (now at the University of Florida), also found that the hypothermia-treated rodents had preserved locomotor function. While further research is required to determine the mechanism by which hypothermia exerts its neuroprotective effect, the results suggest that this intervention is a promising strategy in treating acute SCI.

    REGENERATION AND FUNCTION OF AXONS IN SCHWANN CELL GRAFTS Mary B. Bunge, PhD Blair Calancie, PhD Brian R. Noga, PhD Martin Oudega, PhD
    It is well established that nerve �ber regeneration in the spinal cord does occur in the presence of Schwann cells inside a guidance channel. Questions as to whether these regenerating �bers can exit the other side of the guidance channel and form functional connections are issues addressed in these two studies. Drs. Noga, Calancie, and Oudega designed a study to test whether regenerated spinal cord axons are capable of carrying electrical messages. Their results demonstrate that some axons within bridges implanted in a completely transected cord are capable of being electrically stimulated and can produce measurable evoked responses. Studies such as these help to con�rm the potential for the regenerating axon, should it reach another neuron, to communicate or connect. While researchers have been encouraged that regeneration via Schwann cell bridges is achievable, they remain puzzled as to why axons entering the bridges do not continue to grow out the other side. They suspect that the �bers may not exit the bridges because inhibitory molecules form a barrier at the end of the bridge. One group of inhibitory proteins, proteoglycans, are known to inhibit axon growth. In their study, Dr. Bunge and her colleagues set out to document the presence of proteoglycans within the Schwann cell bridges. The concentration of proteoglycans in the end of the bridge where the �bers enter (rostral interface) was lower than the end where the axons need to exit (caudal interface). More proteoglycans present in the caudal interface may help explain why the axons enter the bridge but do not exit.

    PROMOTING GROWTH OF AXONS BEYOND THE AREA OF INJURY Martin Oudega, PhD Daniel J. Liebl, PhD Functional recovery after SCI most likely will require the successful regeneration and re-entry of severed axons into the spinal cord to establish re-connection with their targets. Understanding how regeneration occurs may depend on how the injury environment affects regeneration as well as knowing what happens both anatomically and genetically. Miami Project researcher, Dr. Daniel Liebl is interested in determining the genetic mechanisms by which cells regenerate and the effect that guidance molecules may have on repelling or attracting growth. By understanding the machinery by which axons regenerate, researchers hope to become better equipped to design speci�c therapies to promote regrowth. Recently, growth promoting factors, or neurotrophins, placed within the spinal cord were shown to help regenerating axons leave a Schwann cell bridge. In this study, Dr. Oudega and his colleagues placed two neurotrophins in the spinal cord beyond a Schwann cell bridge. Their results indicate that the neurotrophins helped the axons exit the bridge and penetrate the host spinal cord. While it is not yet known, this combination of neurotrophins may either directly act on the axons to promote regeneration or may act indirectly by altering the inhibitory environment of the spinal cord. In striving for successful regeneration, scientists agree that a combination of strategies to promote regrowth and abate inhibitory factors will most likely be needed for a cure for paralysis after SCI.

    PROCURING CELLS FOR TRANSPLANTATION
    Patrick M. Wood, PhD Mary B. Bunge, PhD
    An exciting strategy to promote axon growth beyond the area of injury is grafting populations of ensheathing glia (specialized support cells that help growing axons re-enter the spinal cord) at the ends of Schwann cell guidance channels. In previous studies, ensheathing glia (EG) are shown to promote regeneration, form myelin, and remyelinate axons. These cells may be an important component in the clinical treatment of central nervous system damage and demylinating diseases. It is therefore important to understand how to procure and reproduce adequate numbers of EGs. Drs. Patrick Wood and Mary B. Bunge investigated the proliferative properties of EGs. In this study, they asked whether growth factors can be used to produce EG cell populations in the laboratory. The investigation studied the effect of several growth factors on the mitogenic response (or proliferation) of adult ensheathing glia. They found that four growth factors promote proliferation and that a combination of two growth factors, heregulin and �broblast growth factor 2, had an additive effect. Because of the potential clinical importance of these cells for central nervous system repair, this new information will be useful in designing techniques for the production of suf�cient numbers of adult-derived EG for use in clinical transplantation.

    STEM CELLS: WHAT ROLE WILL THEY PLAY?
    Pantelis Tsoulfas, PhD
    Stem cells are among the hottest topics in regeneration research today and the fuel for much debate regarding the use of government funds for studies with embryonic stem cells. Stem cells have been called mother cells of the body. These unspecialized cells can mature into many types of cells including nerve cells and neural-support cells: astrocytes and oligodendrocytes. Before cells with this wide potential can be successfully used for spinal cord repair, we must understand whether they can form functional nerve cells, and whether they will do so in the injured spinal cord. In a study by Dr. Tsoulfas and former Miami Project colleague Scott Whittemore (now at the University of Louisville), stem cells from embryonic rat brain were grafted into the spinal cord. While these cells can be manipulated to form neurons in laboratory dishes, when the stem cells were placed in the spinal cord they almost exclusively developed into astrocytes. If nerve cells or oligodendrocytes are the desired cell type, the investigators concluded that the speci�c fate of the stem cells will need to be determined prior to grafting. Some success along these lines was reported this year by Dr. John W. McDonald of Washington University, Missouri. Continued research is needed to fully understand what role stems cells will have in strategies leading to a cure.

    CHARACTERIZING AND CULTIVATING CHROMAFFIN CELLS FOR GRAFTING
    Jacqueline Sagen, PhD Brian R. Noga, PhD Mary J. Eaton, PhD Central dysesthetic pain following SCI is often described as a burning, piercing or radiating sensation. Such pain can severely compromise a persons quality of life when it cannot be alleviated by conventional treatments. Laboratory research has shown that implanting adrenal medulla chromaf�n cells at the surface of the spinal cord can alleviate many symptoms of chronic pain. Miami Project researchers are studying chromaf�n cell transplants to determine the mechanism by which these cells exert their analgesic effect. Although chemical and behavioral studies have identi�ed some of the processes, until now there had been no neurophysiological studies demonstrating how the transplants effect the transmission of pain messages. Drs. Sagen, Noga, and Eaton designed an experiment to evaluate the effect that substances released by chromaf�n cells have on the activation of nerve pathways. They found that the transplants block a speci�c part of the pain pathway while having no effect on non-pain pathways. Obtaining an adequate number of primary cells for future human chromaf�n cell transplants is a challenge because it may require adrenal tissue from several organ donors. To overcome this limitation, Dr. Mary Eaton proposes the use of chromaf�n cell lines rather than primary chromaf�n cells. She utilizes genetic engineering techniques to create an immortalized cell line, that is, chromaf�n cells with the af�nity to reproduce themselves. In testing these cells in animal experiments, Dr. Eaton and colleagues found that they can effectively reverse chronic pain. With further study, the clinical use of chromaf�n cell lines may prove to be a novel approach for future pain management in people with SCI.

    CHRONIC PAIN AFTER SPINAL CORD INJURY:
    COMMON CLINICAL PATTERNS
    Eva Widerstrom-Noga, PhD, DDS Robert P. Yezierski, PhD Chronic pain is frequently reported as a reason for decreased quality of life after SCI. Some people with SCI consider their pain so severe that they would be willing to trade the chance to walk again for pain relief. The challenge in treating chronic pain is understanding the mechanisms that cause pain and designing treatments to turn them off. The Miami Project is currently considering steps to initiate clinical trials in spinal cord injured patients suffering from chronic neuropathic pain (see chromaf�n cell page.) To diagnose and understand these complex pain conditions, it is important to de�ne common patterns of pain in the experiences of people with SCI. This study sought to analyze the location, quality, intensity, and onset of pain as well as the periods of pain relief experienced following SCI. Of 330 people with SCI who reported chronic pain, 217 agreed to �ll out a detailed pain history. Of the respondents, 59.9% reported burning pain most commonly located on the front of the torso and genitals, and on the buttocks, thighs, legs and feet. Aching pain associated with the neck, shoulders and back was described by 54.4%. While these symptoms are seen in all levels of injury, there is a relationship between the location of pain and the level of spinal cord injury. People with cervical injuries more commonly reported shoulder and neck pain. About 59% reported that their most disturbing pain started within 6 months of their injury. These data and the patterns this postal survey reveals may assist in a better understanding of the mechanisms of pain following SCI and therefore, help in the design of improved treatment strategies.

    HUMAN PATHOPHYSIOLOGY
    Christine K. Thomas, PhD
    Most scientists agree that we must understand the intricate pathology of human spinal cord injury in order to design therapies directed at these speci�c pathologies. This study provides information about the changes in nerve and muscle components after injury, and leads to questions about whether the spontaneous activity seen in some muscles could in some way be useful. Dr. Christine Thomas found spontaneous movements in the thenar muscle, the muscle that controls thumb movement, in people with cervical injuries. These movements were either sporadic, like a twitch, or tonic with constant tension. Since the muscles are not quiet, are their movements usable? Can this activity be used for coordinated movement, or are they detrimental? Do they make the muscles weak? The studys results suggest that the muscle activity is generated from nerves that are connected to the muscles but have lost their input from the spinal cord. Dr. Thomas studies help to increase the understanding of the intricate physiology of nerve - muscle connections after SCI and may be important in determining how connections to these muscles could be re-established.

    IMPROVING WALKING IN CHRONIC INCOMPLETE SCI Edelle C. Field-Fote, PhD, PT
    One goal in rehabilitation research is to develop strategies to improve motor performance in people with SCI. There is clinical evidence indicating that, due to rewiring of spinal circuitry, improved sensory and motor function can occur following CNS damage. Researchers are striving to understand if novel therapies can influence this rewiring and some, including Dr. Field-Fote, suspect that the spinal cord can be taught to walk using rehabilitative interventions.
    Recent studies suggest that speci�c interventions such as body weight support (BWS) and functional electrical stimulation (FES) may influence the spinal circuitry following SCI. BWS assists with the standing phase of walking and FES with the swing phase. By combining BWS and FES, Dr. Field-Fote hypothesized that improvements in walking speed could be achieved both on the treadmill and over-ground in people with chronic incomplete SCI. Volunteers underwent gait training using BWS and FES over a treadmill at a frequency of three days per week for 3 months. All volunteers showed overall improvements in their lower extremity strength and in over-ground walking speed. This study is the �rst to report the effects of combining BWS and FES in a SCI population. In the future, when regeneration of injured spinal cord nerves is achieved, it is likely that rehabilitation will be necessary to guide and promote functional circuit development. It is hoped that motor rehabilitation training studies such as those carried out by the Miami Project will provide important baseline data to help researchers assess the effects of future drug treatment and transplantation strategies.

    [ChasteV8, I reformatted your posting so that it can be more easily read]

    [This message was edited by Wise Young on Apr 28, 2002 at 01:48 PM.]

  2. #2
    Senior Member bill j.'s Avatar
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    This might be easier to read

    POSTTRAUMATIC SECONDARY INSULTS W. Dalton Dietrich, PhD • Helen M. Bramlett, PhD • Robert P. Yezierski, PhD

    Spinal cord injury (SCI) sets off a cascade of cellular and inflammatory responses that lead to loss of tissue and lack of functional recovery. Miami Project researchers have been studying these responses to identify if secondary insults increase tissue damage and worsen behavioral outcome. Immediately after SCI, people often experience problems with breathing, putting them at risk for insufficient oxygen to reach the blood. This can lead to hypoxia, a deficiency of oxygen, in the cells. Additionally, the injury may cause hypotension, a low blood pressure, which may influence blood flow to the central nervous system and hyperthermia, an unusually high fever, which may increase body temperature. The purpose of these studies by Helen Bramlett, PhD and Scientific Director, W. Dalton Dietrich, PhD and their colleagues, was to investigate whether these secondary insults, hypoxia, hypotension or hyperthermia, influence nervous system damage.


    Significantly more tissue damage occurred in the groups of animals that experienced hypoxia, hypotension, or hyperthermia induced during the experiments than in those that did not. These results emphasize the need for controlling the oxygen and blood flow to nervous tissue and suggest that complications of SCI, such as fever leading to spinal cord hyperthermia, may add to the severity of injury and significantly affect neurological outcome. These findings indicate that clinical researchers should consider therapies to protect patients from secondary insults after SCI.

    IDENTIFYING AND PREVENTING THE INTRICATE INJURY MECHANISMS THAT OCCUR IMMEDIATELY AFTER SCI W. Dalton Dietrich, PhD • John R. Bethea, PhD • Robert P. Yezierski, PhD

    An active area of research at the Miami Project is in developing neuroprotective treatments to protect the spinal cord in the first hours and days after the injury. There is a belief that limiting the degree of secondary injury will limit the severity of neurological deficits after SCI and may therefore enhance the recovery of function.


    Many studies provide evidence that apoptosis, an active cell-suicide program, is responsible for some cell death following SCI. Very little information is available about anti-apoptotic mechanisms that inhibit programmed cell death within the injured spinal cord. Data from John Bethea, PhD and W. Dalton Dietrich, PhD indicate that inhibitors of apoptosis do exist within the spinal cord cells which may help them survive. By gaining a better understanding of these intricate molecular, cellular, and regulatory events that occur following SCI, we may be able to design new therapeutic strategies to enhance natural healing mechanisms and to diminish those events that lead to further damage.

    Systemic modest hypothermia may be one such therapy. When modest systemic hypothermia was induced following SCI in rodents, the total area of spinal cord damage was reduced. The researchers, including Dr. Robert Yezierski (now at the University of Florida), also found that the hypothermia-treated rodents had preserved locomotor function. While further research is required to determine the mechanism by which hypothermia exerts its neuroprotective effect, the results suggest that this intervention is a promising strategy in treating acute SCI.



    REGENERATION AND FUNCTION OF AXONS IN SCHWANN CELL GRAFTS Mary B. Bunge, PhD • Blair Calancie, PhD • Brian R. Noga, PhD Martin Oudega, PhD


    It is well established that nerve fiber regeneration in the spinal cord does occur in the presence of Schwann cells inside a "guidance channel." Questions as to whether these regenerating fibers can exit the other side of the guidance channel and form functional connections are issues addressed in these two studies.


    Drs. Noga, Calancie, and Oudega designed a study to test whether regenerated spinal cord axons are capable of carrying electrical messages. Their results demonstrate that some axons within "bridges" implanted in a completely transected cord are capable of being electrically stimulated and can produce measurable evoked responses. Studies such as these help to confirm the potential for the regenerating axon, should it reach another neuron, to communicate or "connect."



    While researchers have been encouraged that regeneration via Schwann cell bridges is achievable, they remain puzzled as to why axons entering the bridges do not continue to grow out the other side. They suspect that the fibers may not exit the bridges because inhibitory molecules form a barrier at the end of the bridge. One group of inhibitory proteins, proteoglycans, are known to inhibit axon growth. In their study, Dr. Bunge and her colleagues set out to document the presence of proteoglycans within the Schwann cell bridges. The concentration of proteoglycans in the end of the bridge where the fibers enter (rostral interface) was lower than the end where the axons need to exit (caudal interface). More proteoglycans present in the caudal interface may help explain why the axons enter the bridge but do not exit.



    PROMOTING GROWTH OF AXONS BEYOND THE AREA OF INJURY Martin Oudega, PhD • Daniel J. Liebl, PhD

    Functional recovery after SCI most likely will require the successful regeneration and re-entry of severed axons into the spinal cord to establish re-connection with their targets. Understanding how regeneration occurs may depend on how the injury environment affects regeneration as well as knowing what happens both anatomically and genetically. Miami Project researcher, Dr. Daniel Liebl is interested in determining the genetic mechanisms by which cells regenerate and the effect that guidance molecules may have on repelling or attracting growth. By understanding the machinery by which axons regenerate, researchers hope to become better equipped to design specific therapies to promote regrowth.


    Recently, growth promoting factors, or neurotrophins, placed within the spinal cord were shown to help regenerating axons leave a Schwann cell bridge. In this study, Dr. Oudega and his colleagues placed two neurotrophins in the spinal cord beyond a Schwann cell bridge. Their results indicate that the neurotrophins helped the axons exit the bridge and penetrate the host spinal cord. While it is not yet known, this combination of neurotrophins may either directly act on the axons to promote regeneration or may act indirectly by altering the inhibitory environment of the spinal cord. In striving for successful regeneration, scientists agree that a combination of strategies to promote regrowth and abate inhibitory factors will most likely be needed for a cure for paralysis after SCI.



    PROCURING CELLS FOR TRANSPLANTATION Patrick M. Wood, PhD • Mary B. Bunge, PhD


    An exciting strategy to promote axon growth beyond the area of injury is grafting populations of ensheathing glia (specialized support cells that help growing axons re-enter the spinal cord) at the ends of Schwann cell guidance channels. In previous studies, ensheathing glia (EG) are shown to promote regeneration, form myelin, and remyelinate axons. These cells may be an important component in the clinical treatment of central nervous system damage and demylinating diseases. It is therefore important to understand how to procure and reproduce adequate numbers of Egs.


    Drs. Patrick Wood and Mary B. Bunge investigated the proliferative properties of EGs. In this study, they asked whether growth factors can be used to produce EG cell populations in the laboratory. The investigation studied the effect of several growth factors on the mitogenic response (or proliferation) of adult ensheathing glia. They found that four growth factors promote proliferation and that a combination of two growth factors, heregulin and fibroblast growth factor 2, had an additive effect. Because of the potential clinical importance of these cells for central nervous system repair, this new information will be useful in designing techniques for the production of sufficient numbers of adult-derived EG for use in clinical transplantation.

    STEM CELLS: WHAT ROLE WILL THEY PLAY? Pantelis Tsoulfas, PhD

    Stem cells are among the hottest topics in regeneration research today and the fuel for much debate regarding the use of government funds for studies with embryonic stem cells. Stem cells have been called "mother" cells of the body. These unspecialized cells can mature into many types of cells including nerve cells and neural-support cells: astrocytes and oligodendrocytes. Before cells with this wide potential can be successfully used for spinal cord repair, we must understand whether they can form functional nerve cells, and whether they will do so in the injured spinal cord.



    In a study by Dr. Tsoulfas and former Miami Project colleague Scott Whittemore (now at the University of Louisville), stem cells from embryonic rat brain were grafted into the spinal cord. While these cells can be manipulated to form neurons in laboratory dishes, when the stem cells were placed in the spinal cord they almost exclusively developed into astrocytes. If nerve cells or oligodendrocytes are the desired cell type, the investigators concluded that the specific fate of the stem cells will need to be determined prior to grafting. Some success along these lines was reported this year by Dr. John W. McDonald of Washington University, Missouri. Continued research is needed to fully understand what role stems cells will have in strategies leading to a cure.


    CHARACTERIZING AND CULTIVATING CHROMAFFIN CELLS FOR GRAFTING - Jacqueline Sagen, PhD • Brian R. Noga, PhD • Mary J. Eaton, PhD

    Central "dysesthetic" pain following SCI is often described as a burning, piercing or radiating sensation. Such pain can severely compromise a person's quality of life when it cannot be alleviated by conventional treatments. Laboratory research has shown that implanting adrenal medulla chromaffin cells at the surface of the spinal cord can alleviate many symptoms of chronic pain.


    Miami Project researchers are studying chromaffin cell transplants to determine the mechanism by which these cells exert their analgesic effect. Although chemical and behavioral studies have identified some of the processes, until now there had been no neurophysiological studies demonstrating how the transplants effect the transmission of pain messages. Drs. Sagen, Noga, and Eaton designed an experiment to evaluate the effect that substances released by chromaffin cells have on the activation of nerve pathways. They found that the transplants block a specific part of the pain pathway while having no effect on non-pain pathways.



    Obtaining an adequate number of primary cells for future human chromaffin cell transplants is a challenge because it may require adrenal tissue from several organ donors. To overcome this limitation, Dr. Mary Eaton proposes the use of chromaffin cell lines rather than primary chromaffin cells. She utilizes genetic engineering techniques to create an immortalized cell line, that is, chromaffin cells with the affinity to reproduce themselves. In testing these cells in animal experiments, Dr. Eaton and colleagues found that they can effectively reverse chronic pain. With further study, the clinical use of chromaffin cell lines may prove to be a novel approach for future pain management in people with SCI.



    CHRONIC PAIN AFTER SPINAL CORD INJURY:
    COMMON CLINICAL PATTERNS
    Eva Widerstrom-Noga, PhD, DDS • Robert P. Yezierski, PhD


    Chronic pain is frequently reported as a reason for decreased quality of life after SCI. Some people with SCI consider their pain so severe that they would be willing to trade the chance to walk again for pain relief. The challenge in treating chronic pain is understanding the mechanisms that cause pain and designing treatments to "turn them off." The Miami Project is currently considering steps to initiate clinical trials in spinal cord injured patients suffering from chronic neuropathic pain (see chromaffin cell page.) To diagnose and understand these complex pain conditions, it is important to define common patterns of pain in the experiences of people with SCI. This study sought to analyze the location, quality, intensity, and onset of pain as well as the periods of pain relief experienced following SCI. Of 330 people with SCI who reported chronic pain, 217 agreed to fill out a detailed pain history. Of the respondents, 59.9% reported "burning" pain most commonly located on the front of the torso and genitals, and on the buttocks, thighs, legs and feet. "Aching" pain associated with the neck, shoulders and back was described by 54.4%. While these symptoms are seen in all levels of injury, there is a relationship between the location of pain and the level of spinal cord injury. People with cervical injuries more commonly reported shoulder and neck pain. About 59% reported that their most disturbing pain started within 6 months of their injury. These data and the patterns this postal survey reveals may assist in a better understanding of the mechanisms of pain following SCI and therefore, help in the design of improved treatment strategies.



    HUMAN PATHOPHYSIOLOGY
    Christine K. Thomas, PhD

    Most scientists agree that we must understand the intricate pathology of human spinal cord injury in order to design therapies directed at these specific pathologies. This study provides information about the changes in nerve and muscle components after injury, and leads to questions about whether the spontaneous activity seen in some muscles could in some way be useful. Dr. Christine Thomas found spontaneous movements in the thenar muscle, the muscle that controls thumb movement, in people with cervical injuries. These movements were either sporadic, like a twitch, or tonic with constant tension. Since the muscles are not quiet, are their movements usable? Can this activity be used for coordinated movement, or are they detrimental? Do they make the muscles weak? The study's results suggest that the muscle activity is generated from nerves that are connected to the muscles but have lost their input from the spinal cord. Dr. Thomas' studies help to increase the understanding of the intricate physiology of nerve - muscle connections after SCI and may be important in determining how connections to these muscles could be re-established.



    CLINICAL TECHNOLOGIES
    Barth A. Green, MD • Allan D.O. Levi, MD • Robert M. Quencer, MD


    Radiologists and surgeons strive to develop and apply new techniques and technologies to improve current clinical practice. Common neurosurgical techniques to treat cervical bilateral facet fracture dislocations have included prolonged cervical traction, halo-thoracic bracing, posterior wiring, and anterior plates using Casper plates. Casper plating involves placing two screws in the vertebrae to be fused. Neurosurgeons, Drs. Barth Green, Allan Levi, and their colleagues report their experience with anterior fixation with unicortical locking plates in cervical spine fracture dislocations. An advantage of this plating system is the use of only one screw in each vertebral body. In their retrospective study, they found that this procedure is effective in achieving spinal stability and offers an excellent surgical alternative in managing these types of injuries.


    While continuing to improve the initial surgical treatment in spinal cord injury, the Miami Project is also interested in developing better diagnostic capabilities. When spinal paralysis results from non-traumatic events such as transverse myelitis or spinal cord stroke, definitive radiologic diagnosis can be difficult. Magnetic Resonance Imaging (MRI) using a technology known as diffusion-weighted imaging (DWI) may provide a more definitive diagnosis. DWI has already been proven helpful in accurately diagnosing brain abnormalities. Dr. Quencer suggests, in this paper, that DWI may be useful in providing definitive diagnoses in certain spinal cord disorders and reviews the technical problems that need to be overcome in order to make use of DWI technology in the spinal cord.

    IMPROVING WALKING IN CHRONIC INCOMPLETE SCI
    Edelle C. Field-Fote, PhD, PT


    One goal in rehabilitation research is to develop strategies to improve motor performance in people with SCI. There is clinical evidence indicating that, due to rewiring of spinal circuitry, improved sensory and motor function can occur following CNS damage. Researchers are striving to understand if novel therapies can influence this rewiring and some, including Dr. Field-Fote, suspect that the spinal cord can be "taught" to walk using rehabilitative interventions.


    Recent studies suggest that specific interventions such as body weight support (BWS) and functional electrical stimulation (FES) may influence the spinal circuitry following SCI. BWS assists with the standing phase of walking and FES with the swing phase. By combining BWS and FES, Dr. Field-Fote hypothesized that improvements in walking speed could be achieved both on the treadmill and over-ground in people with chronic incomplete SCI. Volunteers underwent gait training using BWS and FES over a treadmill at a frequency of three days per week for 3 months. All volunteers showed overall improvements in their lower extremity strength and in over-ground walking speed.



    This study is the first to report the effects of combining BWS and FES in a SCI population. In the future, when regeneration of injured spinal cord nerves is achieved, it is likely that rehabilitation will be necessary to guide and promote functional circuit development. It is hoped that motor rehabilitation training studies such as those carried out by the Miami Project will provide important baseline data to help researchers assess the effects of future drug treatment and transplantation strategies.



    EXERCISE AND ITS EFFECTS ON HEALTH MAINTENANCE
    Patrick L. Jacobs, PhD • Mark S. Nash, PhD


    The opportunity for physical conditioning for most wheelchair users is limited and a lack of exercise can predispose them to the risk of progressive heart and respiratory disease. People with chronic paraplegia often have other predisposing factors to cardiovascular disease, in particular abnormal cholesterol levels where they have too much of the unhealthy LDL cholesterol and not enough of the healthy HDL cholesterol. Also, some exercise devices that are available can put users at risk for overuse injuries. Physical conditioning programs for people with spinal cord injury need to address the prevention of adverse effects as much as possible. Furthermore, in relation to future transplantation techniques to restore sensory and/or motor control, it may be important to define specific training strategies to maximize the patients' ability to benefit from restored function.


    Drs. Patrick Jacobs and Mark Nash have collaborated on designing a series of exercises called circuit resistance training (CRT), which combines strength training (weight lifting) and endurance training (armcrank ergometry). These papers and others in the series show that the intensity of exercise tested is adequate to provide cardiorespiratory benefits. They also showed that CRT can safely and effectively improve muscle strength and endurance in paraplegics. Results indicate that the levels of HDL-cholesterol decline to a more desirable level, which could mean a 25% reduction in the risk for cardiovascular disease. These results have sparked a renewed interest among rehabilitation professionals regarding health maintenance over the lifetime of persons with SCI.



    WOMEN'S ISSUES: PARENTING AND SEXUAL FUNCTION
    Craig Alexander, PhD • Marcalee Sipski, MD

    As part of several new clinical trials in SCI rehabilitation at the Miami Project and with our continued goal of improving quality of life following SCI, Drs. Alexander and Sipski have designed various studies to address women's issues. One issue relates to the impact that SCI has on child rearing, family division of labor, and decision making. Via a postal survey, data from mothers with SCI was collected and analyzed. The results indicate that in families of SCI mothers, the division of household and childcare tasks were more equally shared with their partners than in families with able-bodied mothers.


    In laboratory-based studies to characterize the impact of SCI on sexual function, these investigators recorded the subjective, genital, and physiological responses of women with SCI as well as their ability to achieve orgasm. In women with complete paralysis and damage affecting the S2-S5 spinal nerves, only 17% were able to achieve orgasm; in other levels and degrees of injury, 59% could achieve orgasm. Studies like these help in our understanding of the neurophysiology of sexual response in women with SCI, a topic that until recently has been left unstudied. Their data will assist in the development of appropriate techniques to improve sexual responsiveness and will be of value in educating women about their choices for optimum sexual function.



    PATIENT EDUCATION GUIDE RECEIVES FAVORABLE REVIEW
    Maria J. Amador, RN, CRRN • Charles M. Lynne, MD • Nancy L. Brackett, PhD


    Over the last ten years, Nancy Brackett, PhD and Charles M. Lynne, MD have gained expertise in male fertility following SCI by conducting studies to characterize the impairments in semen quality experienced by men with SCI. Maria Amador, RN, CRRN has been a member of this research team since its inception and taken responsibility for subject recruitment, education, and providing nursing care during laboratory visits. Their research results have lead to a new focus on the biochemical changes that cause impaired semen quality. To answer the need for lay reader materials on this topic, these researchers teamed up to write a review of research in their field and to provide a comprehensive listing of fertility related services offered nationwide.


    "A Guide and Resource Directory to Male Fertility following Spinal Cord Injury/Dysfunction" serves as an example of how knowledge gained through research and communicated to the lay public can make a difference in the quality of life of an individual affected by SCI. With funding from the PVA Education and Training Foundation, the authors' goal in writing this Guide was to present current and reliable information based on research findings.


    The Guide summarizes treatments available to overcome infertility and discusses the progress toward finding the cause of infertility in men with SCI. It has become clear that this publication is fulfilling a critical need for information on this topic. Since its release in September 2000, more than 2,500 copies have been distributed to individuals with SCI, rehabilitation personnel and centers throughout the United States. An equal number of copies have been downloaded from the Miami Project's website.

  3. #3
    Sorry, Bill. I didn't see your posting before I went ahead to reformat ChasteV8's message. We think the same way! Wise.

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