p53 mutations isolated in yeast based on loss of transcription factor activity: similarities and differences from p53 mutations detected in human tumors.

p53 is a transcriptional activator that plays a key role in the integration of signals inducing cell division arrest and programmed cell death. Moreover, p53 is a tumor suppressor gene, mutations of which are the most commonly detected mutations in diverse malignancies. In order to better understand the significance of p53 mutations to human cancer, we isolated mutant alleles of p53 that had lost transcription factor activity in yeast. These mutant alleles were evaluated for their precise changes, their activity against three different p53 responsive enhancers and their ability to act in a transdominant fashion to the wild type allele. While many of the mutations isolated in yeast resembled those found in human tumors, consistent with the importance of transcription factor activity for p53 in mammalian cells, the mutational spectrum obtained was dependent upon the p53 enhancer employed for the selection. Some mutations specifically inactivated p53 in yeast for a single enhancer element. Virtually all missense mutations tested had a dominant inhibitory effect on wild type p53 in yeast. Since some of these transdominant mutations are virtually unknown in human tumors we conclude that transdominance, per se, fails to predict which mutations occur frequently in cancer.

Special devices as aids in the management of child self-mutilation in the Lesch-Nyhan syndrome.

The Lesch-Nyhan syndrome is a rare inborn error of purine metabolism associated with hyperuricacidemia, mental retardation, and an insatiable urge for self-mutilation, especially of the extremities. Insensitivity to pain and severe muscle spasms create very difficult management problems, especially for children being cared for at home. Fortunately this syndrome is rare (1 per 380,000 live births). Four known patients are under treatment in Manitoba, of which two brothers are the subject of this study. In general, the medical management of these patients has been unsuccessful, especially in controlling self-mutilation. It therefore was decided to manage these children by the use of mechanical aids. Through the utilization of custom-designed seating devices control of the self-mutilation has been obtained, reducing the burden of family care. It is now possible for the children to attend regular school on a half-day basis. They are also able to engage in community activities without the fear that a mishap will occur when not under the vigilance of the immediate family.

Mobility aids for the paraplegic child.

Paraplegic children derive many benefits from upright bracing during their growing years. Physiological advantages include the prevention of joint contractures, decreased osteoporosis, prevention of urinary tract infections, increased cardiopulmonary tolerance, and the development of trunk and head control. The quality of life is enhanced because the child has increased self-esteem and participates in group activities with greater independence. Two new devices, the stand-up wheelchair and the shuttlebug, have been employed with success in the Winnipeg Child Paraplegic Program.

Seated lumbar/pelvic alignment. A comparison between spinal cord-injured and noninjured groups.

It has been postulated that loss of voluntary trunk stability, combined with the posture imposed by the configuration of the wheelchair seat, biomechanically necessitates that a person with diminished trunk control assume an abnormal sitting posture. This posture is characterized by a long, "C"-shaped kyphotic thoracolumbar spine, an extended cervical spine, a flattened lumbar spine, and a posteriorly tilted pelvis. If lateral trunk deformities are present, trunk imbalance and pelvic deformities in the coronal (frontal) plane can exist. This study has investigated the spinal/pelvic postural alignment of a limited sample of seated spinal cord-injured people and compared the results to a similar sample of able-bodied individuals seated in the same standardized positions. The results suggests that there are distinct differences in the spinal/pelvic alignment between the two study groups. These differences and the movements that take place in the pelvic structures during active wheelchair sitting have implications relative to pressure sore prevention and postural management.

Comparative effects of posture on pressure and shear at the body-seat interface.

This study considers the effects of seated posture and body orientation on the pressure-distribution and surface shear (tangential) forces acting at the body-seat interface. Nine postures typically assumed by wheel-chair users were studied. Comparisons were made within and between two study groups, made up of 12 subjects with spinal cord injuries (SCI) and 10 nondisabled subjects. Both interface pressure and the surface shear were measured simultaneously in each of nine reproducible, seated postures. The same seat cushion was used for all trials. The Oxford Pressure Monitor, a pneumatic cell device, was used to measure and record the interface pressures. Instrumentation for measuring and recording the surface shear force was constructed specifically for the study. Analysis consisted of statistically comparing changes in pressure values and shear forces derived from eight sitting postures with reference to values recorded in a defined neutral sitting posture. The pressure-distribution findings suggest that in the postures studied SCI subjects have maximum pressures that are higher than nondisabled subjects in all postures, ranging from 6% to 46% depending on the posture. Maximum pressures can be reduced by postural changes: forward flexion to 50 degrees, -9%; backrest recline to 120 degrees, -12%; and, full body tilt, -11%. On average, the SCI group members have peak pressure gradients (PPG) that are 1.5 to 2.5 greater than the nondisabled group. The maximum reduction in PPG occurred at backrest recline of 120 degrees, -18%. Tangential shear force acts at the body-seat interface in all nine postures studied. Extrapolation of results suggests that full-body tilt to approximately 25 degrees reduces the surface shear force to near zero. In contrast, a backrest-only recline of 20 degrees causes a 25% increase in the surface shear force. These results suggest that caution must be taken when using nondisabled subjects as surrogates for people with SCI because of the inherent differences between the groups. Also, researchers and clinicians should recognize that posture and body orientation in space are additional variables that can have a profound effect on the interaction between a seated person and his or her supporting surface.

Anthropometry and design for the disabled: experiences with seating design for the cerebral palsy population.

In recent years increased emphasis has been placed on designing improved technical aids for physically disabled people. One limiting factor has been the lack of anthropometric resource data that is appropriate for use with individuals with specific disabilities, such as cerebral palsy. The purpose of this study has been to examine briefly why the anthropometric needs of disabled individuals may be different from able-bodied individuals, and to develop an anthropometric data resource that can be used in the design of seating and mobility devices for a specific segment of the disabled population. Ninety-four variables were obtained from each subject in a sample of 133 cerebral palsied individuals. Both qualitative and quantitative factors were assessed and measured, respectively. The qualitative factors are used to define the unique characteristics of the sample group. Twenty quantitative variables are analysed and the results presented in a tabular format. Eleven of the 20 variables are not available from existing able-bodied anthropometric sources, but were deemed important for use in the design process for the study population. The paper references a supplementary manual which contains the complete results, including descriptive statistical tables and scattergram plots. The paper also discusses the implications for application of the results, possible limitations of their use, and precautions that should be observed when considering extrapolations to other populations of disabled people.

Technology in the education of multiply-handicapped children.

The number of technical aids now available has allowed severely multiply-handicapped children to better participate in their education. Project TEACH (Technical-Educational Aids for Children with Handicaps), a 3-year early childhood demonstration project of the Federal Office of Education, provided ten children with seating systems, mobility aids, feeding devices, and augmentative communication aids. The children's performance of academic, motor, daily living, and communication skills as they relate to their educational program is reported as well as the model used to deliver technical services in an educational environment.

Technology for seniors' living environment: directions for product development.

In May 1991, approximately 40 world experts on technology and aging were invited to Directions '91 in Winnipeg, Canada. The focus of the 3-day seminar was on living environments for seniors and on the research and development of products to meet the needs of an aging society. The built environment--furnishings and appliances, self-care, and leisure and recreation--was targeted in both plenary and breakout sessions. This article highlights the key concerns and recommendations developed at Directions '91. The "universal design" concept is stressed, particularly as it relates to our need to rethink the design of the built environment and the products that are currently being used by seniors seeking independence and dignity in their daily living. Consideration is also given to the physiological changes that occur in the natural process of aging and how these changes need to be accommodated in products designed for the living environment.

The vacuum splint: an aid in emergency splinting of fractures.

The vacuum splint has been shown to be a simple, safe and effective method of emergency splinting of fractured extremities. The splint is simply constructed from clear vinyl sheeting and contains 2-mm. expanded polystyrene balls. Evacuation of air causes the splint to become rigid, thereby providing stability and immobilization of the limb. The splint is radiolucent, containing no obstructive metal components that would interfere with the radiographic appearance of the injured limb. The ease of application of this splint makes it especially effective for the emergency splinting of fractures in children.

Mechanical and anatomic hip flexion angles on seating children with cerebral palsy.

This study measured anatomic hip flexion angles (AHFAs) at specific and known mechanical hip flexion angles (MHFAs) (ie, seat-to-back angles) in order to determine the relationship between the two in the seated position. Six able-bodied children and 12 children with cerebral palsy were placed in eight different MHFA positions while AHFA was simultaneously measured. It was found that, although related, the hip flexion angle and the angle between the backrest and seat surface are not equal in most seated positions. The difference between AHFA and MHFA was greater in the children with cerebral palsy than in the able-bodied. The hip flexion angle of the child in the seated position should not be described as the angle between the backrest and seat surface or the angle of inclination of the backrest.

Development of a wheelchair occupant injury risk assessment method and its application in the investigation of wheelchair securement point influence on frontal crash safety.

To promote proper wheelchair securement in transportation, the proposed ANSI/RESNA Standard on Wheelchairs Used as Seats in Motor Vehicles will require that all transit wheelchairs be equipped with four securement points compatible with strap-type tiedowns. Through computer simulations, the location of these securement points has been found to influence wheelchair user response to a frontal crash. This study develops and employs an injury risk assessment method to compare the crashworthiness of various securement point configurations. The comparative injury risk assessment method is designed to predict the risk associated with internalized crash forces, as well as risk associated with secondary occupant impact with the vehicle interior. Injury criteria established by Federal Motor Vehicle Safety Standards and General Motors, along with excursion limitations set by the Society of Automotive Engineers (SAE) J2249 Wheelchair Tiedowns and Occupant Restraint Systems (WTORS) Standard were used as benchmarks for the risk assessment method. The simulation model subjected a secured commercial powerbase wheelchair with a seated 50th percentile male Hybrid III test dummy to a 20 g/30 mph crash. The occupant was restrained using pelvic and shoulder belts, and the wheelchair was secured with four strap-type tiedowns. Results indicated that securement points located 1.5 in to 2.5 in above the evaluated wheelchair's center of gravity provide the most effective occupant protection.

Development of transportable wheelchair design criteria using computer crash simulation.

The Americans with Disabilities Act (ADA) has led to an increase in disabled travelers, many of whom are unable to transfer to a vehicle seat and are required to use their wheelchair to fulfill this function. ANSI/RESNA is currently developing a transportable wheelchair standard which will identify design requirements and testing methods for wheelchairs suitable for transport. Wheelchair manufacturers should begin to modify their existing design criteria established for a normal mobility function to design criteria appropriate for a transportation function which may subject the wheelchair to large dynamic crash forces. A thorough understanding of the crash environment and its effect on the wheelchair is necessary to insure the safety of the wheelchair user. To assist manufacturers in the design effort, this study uses mathematical crash simulations to evaluate loads imposed upon a wheelchair when subjected to a 48 kph/20 g frontal crash. Using a four-point belt tiedown system to secure the wheelchair, securement point, seat, lap belt anchor, and wheel loads are evaluated under three different securement configurations. Results show that positioning of rear securement points near the wheelchair center of gravity can serve as an effective strategy for managing crash response and loadings on the wheelchair. Force ranges for each of the evaluated parameters, derived for a 50th percentile male using a simulated power wheelchair, are provided for use as a preliminary guide when designing transportable wheelchairs.

A voluntarily controlled electrohydraulic above-knee prosthesis.

Most above-knee amputees to date are using prostheses employing either constant friction or some type of programed hydraulic damping which the wearer has no control over and which limits his gait speeds. A new system was designed and tested in which voluntary control of a lower-limb prosthesis is derived from the EMG signals of residual thigh muscles in the stump. These signals, after suitable conditioning, open or close solenoid valves, which form a closed hydraulic loop around the damping cylinder in the knee joint. Thus, the amputee is able to voluntarily vary the resistance to knee flexion, from free swing to full lock, by operating valves controlling the resistance to flow around a hydraulic cylinder. The main advantages of this system are a variable and more aesthetic gait, stability over uneven terrain, and because the lock prevents only knee flexion, the amputee can rise on his prosthesis and so use a passive appendage as an active element of his skeleton. The results of this project demonstrate that the concept of an EMG voluntarily controlled hydraulic prosthesis is viable; however, continuing effort is required to make this system lighter, more compact, and cosmetically acceptable.