Modular, tissue-specific, and biodegradable hydrogel cross-linkers for tissue engineering.

Synthetic hydrogels are investigated extensively in tissue engineering for their tunable physicochemical properties but are bioinert and lack the tissue-specific cues to produce appropriate biological responses. To introduce tissue-specific biochemical cues to these hydrogels, we have developed a modular hydrogel cross-linker, poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT), that can be functionalized with small peptide-based cues and large macromolecular cues simply by mixing PdBT in water with the appropriate biomolecules at room temperature. Cartilage- and bone-specific PdBT macromers were generated by functionalization with a cartilage-associated hydrophobic N-cadherin peptide, a hydrophilic bone morphogenetic protein peptide, and a cartilage-derived glycosaminoglycan, chondroitin sulfate. These biofunctionalized PdBT macromers can spontaneously cross-link polymers such as poly(N-isopropylacrylamide) to produce rapidly cross-linking, highly swollen, cytocompatible, and hydrolytically degradable hydrogels suitable for mesenchymal stem cell encapsulation. These favorable properties, combined with PdBT's modular design and ease of functionalization, establish strong potential for its usage in tissue engineering applications.

Continuous cardiometabolic risk score definitions in early childhood: a scoping review.

BACKGROUND: Cardiometabolic risk (CMR) in young children has been measured using various approaches, including a continuous summary score that incorporates components such as adiposity, lipids, metabolic factors and blood pressure. OBJECTIVES: The objective of this study was to comprehensively review definitions of continuous CMR scores in children <10 years of age. METHODS: A scoping review was conducted using a systematic search of four scientific databases up to June 2016. Inclusion criteria were children <10 years of age and report of a continuous CMR score. RESULTS: Ninety-one articles were included. Most studies were published from 2007 to 2016 (96%). Nearly all continuous CMR scores (90%) were calculated using the sum or the mean of z-scores, and many articles age-standardized and sex-standardized components within their own population. The mean number of variables included in the risk scores was 5 with a range of 3-11. The most commonly included score components were waist circumference (52%), triglycerides (87%), high-density lipoprotein cholesterol (67%), glucose (43%) and systolic blood pressure (52%). IMPORTANCE: Continuous CMR scores are emerging frequently in the child health literature and are calculated using numerous methods with diverse components. This heterogeneity limits comparability across studies. A harmonized definition of CMR in childhood is needed.

Effects of cycling and/or electrical stimulation on bone mineral density in children with spinal cord injury.

STUDY DESIGN: Randomized clinical trial. OBJECTIVES: To determine the effect of cycling and/or electrical stimulation on hip and knee bone mineral density (BMD) in children with spinal cord injury (SCI). SETTING: Children's hospital specializing in pediatric SCI. METHODS: A total of 30 children, aged 5-13 years, with chronic SCI were randomized to one of three interventions: functional electrical stimulation cycling (FESC), passive cycling (PC), and non-cycling, electrically stimulated exercise (ES). Each group exercised for 1 h, three times per week for 6 months at home. The hip, distal femur and proximal tibia BMD were examined via dual-energy X-ray absorptiometry (DXA) pre- and post-intervention. RESULTS: In all, 28 children completed data collection. The FESC group exhibited increases in hip, distal femur and proximal tibia BMD of 32.4, 6.62 and 10.3%, respectively. The PC group exhibited increases at the hip (29.2%), but no change at the distal femur (1.5%) or proximal tibia (-1.0%). The ES group had no change at the hip (-0.24%) and distal femur (3.3%), but a loss at the proximal tibia (-7.06%). There were no differences between groups or within groups over time. Significant negative correlations were found between baseline BMD and the amount of BMD change. CONCLUSION: Although not achieving statistical significance, hip BMD changes observed were greater than the reported 0.9-10% gains after exercise for children with and without disability. Thus, cycling with and without electrical stimulation may be beneficial for skeletal health in pediatric SCI, but further research is needed with a larger sample size.

Improved efficiency Si-photonic attenuator.

A forward-biased p-i-n diode integrated with a ridge waveguide forms a basic Si attenuator building block. Disruptive power improvement was achieved through a recessed contact configuration by limiting the amount of Si volume for carrier recombination. A device model was established by using realistic surface recombination velocities instead of effective carrier lifetime concept to understand the device physics of the afore-mentioned Si attenuator.

Implantable FES system for upright mobility and bladder and bowel function for individuals with spinal cord injury.

STUDY DESIGN: Postintervention. OBJECTIVES: To determine the effectiveness of the Praxis multifunctional implantable functional electrical stimulation (FES) system (Neopraxis Pty. Ltd, Lane Cove, NSW, Australia) to provide standing and stepping ability and bladder and bowel management for individuals with motor complete thoracic level spinal cord injuries (SCI). SETTING: Pediatric orthopedic hospital specializing in SCI. SUBJECTS: Three males, ages 17 and 21 years, with motor-complete thoracic level SCI and intact lower motor neurons to the muscles targeted for stimulation. METHODS: Each subject was successfully implanted with the Praxis FES system. All three subjects received electrodes for upright mobility and the first two subjects received additional electrodes for stimulated bladder and bowel management. Following training, subjects were evaluated in their ability to use FES for nine mobility activities. Acute and chronic experiments of the effect of stimulation on bowel and bladder function were also performed. RESULTS: All three subjects could independently stand up from the wheelchair and could walk at least 6 m using a swing through gait pattern. Two subjects were able to independently perform swing through gait for 6 min and one subject was able to independently ascend and descend stairs. Suppression of reflex bladder contractions by neuromodulation (subject 1) and stimulated contractions of the rectum (subject 2) were observed in acute experiments. When stimulation was applied over the course of several weeks, a positive effect on bowel function was measured. Stimulated bladder contractions were not achieved. CONCLUSION: The feasibility of using the Praxis FES system for upright mobility and aiding aspects of bladder and bowel function was demonstrated with three subjects with thoracic level SCI.

Patterns of lower extremity innervation in pediatric spinal cord injury.

STUDY DESIGN: Retrospective review. OBJECTIVES: To identify relationships between lower extremity innervation and level of injury, mechanism of injury, and age at injury in a pediatric population with spinal cord injury (SCI). Secondarily, relationships between innervation and completeness of injury, time since injury, race, and sex were evaluated. SETTING: Pediatric orthopedic referral hospital, Philadelphia, Pennsylvania. METHODS: Records of 190 subjects, ages 1-21 years, were reviewed. Data collected from the medical record included lower extremity muscle innervation, American Spinal Injury Association (ASIA) level and class, mechanism of injury, age at injury, time since injury, race, and sex. To determine innervation, lower extremity muscles had been tested using surface electrical stimulation and identified as being innervated or denervated. If a muscle responded weakly, strength duration testing was performed. For analysis via logistic regression, subjects were grouped based upon level and mechanism of injury. RESULTS: A relationship (P<0.0001) was found between ASIA level and lower extremity innervation of all muscles and between length of time since injury and lower extremity innervation for some muscles. Following multiple logistic regression, only ASIA level remained as an independent predictor of lower extremity innervation status. CONCLUSION: Our results show that lower extremity innervation does differ based on the level of the injury. Denervation began to be seen with injuries in the lower thoracic region and more predominantly with injuries in the lumbar region. This supports our hypothesis that the incidence of lower motor neuron injuries would increase as injuries became more caudal. Our hypotheses of a relationship between innervation status and mechanism of injury and age at injury were not supported. This information is important in determining treatment strategies, eligibility for electrical stimulation techniques, and potential regenerative strategies. SPONSORSHIP: This study was funded by Shriners Hospitals for Children, Grant #8530.

Implantation of the Freehand System during initial rehabilitation using minimally invasive techniques.

STUDY DESIGN: Series of four single subjects with and without intervention design. OBJECTIVES: To describe a minimally invasive surgical technique used to implant the Freehand System during initial spinal cord injury (SCI) rehabilitation and to report rehabilitation outcomes of four recently injured adolescents using the Freehand System. SETTING: Nonprofit children's hospital specializing in orthopedic and SCI care. METHODS: Four subjects with C5 tetraplegia between 13 and 16 years of age and between 9 and 16 weeks following traumatic SCI underwent implantation of the Freehand System using minimally invasive surgical techniques. Outcomes on muscle strength, pinch force, hand function, performance of activities of daily living and satisfaction with and without the Freehand System were collected. RESULTS: Each subject was successfully implanted with the Freehand System without perioperative complications and employed the Freehand System during therapy services and ad lib on the rehabilitation floor. At the last follow-up, every subject remained a motor candidate for the Freehand System. With the Freehand System, average lateral and palmar pinch force was 1.8 and 1.6 kg respectively; average pinch force without functional electrical stimulation (FES) was 0.29 kg. With the Freehand System, three subjects improved their rate of performance on The Upper Extremity Capabilities Questionnaire. All subjects increased their level of independence on The Quadriplegia Index of Function. On the Canadian Occupational Performance Measure (COPM) with the Freehand System, average performance and satisfaction scores improved for every patient. Three of the four subjects continued to use the system at home. CONCLUSION: This case series demonstrates that the Freehand System can vastly improve hand function and performance of rehabilitation activities within days after a minimally invasive implant procedure during initial SCI rehabilitation. Satisfaction with the Freehand System beyond initial rehabilitation is evidenced by continued use at home.

Implanted functional electrical stimulation: an alternative for standing and walking in pediatric spinal cord injury.

STUDY DESIGN: Post intervention, repeated measures design, comparing two interventions. SETTING: Orthopedic pediatric hospital specializing in spinal cord injury. METHODS: Nine subjects, ages 7-20 years, received an eight-channel implanted lower extremity functional electrical stimulation (FES) system for standing and walking. Electrodes were placed to stimulate hip and knee extension, and hip abduction and adduction. Standing and walking were achieved through constant stimulation to the implanted muscles, allowing a swing through gait pattern with an assistive device. After training with FES and long leg braces (LLB), subjects were tested in eight upright mobility activities, which were scored based upon completion time and level of independence. RESULTS: Seven subjects completed data collection. These subjects completed four activities faster (P<0.02) and five activities more independently (P<0.025) with FES as compared to LLB. Transitions between sitting and standing, which were scored in isolation for two mobility activities, were achieved faster and with more independence with FES. In addition, subjects reported preferring FES for the majority of activities. No activity required more time or more assistance to complete with FES as compared to LLB. CONCLUSION: The implanted FES system provided these subjects with enhanced functional abilities over traditional LLB and decreased the need for physical assistance by a caregiver, suggesting that it is a realistic alternative for upright mobility in a pediatric population with spinal cord injury.

Clinical evaluation of twice-daily emedastine 0.05% eye drops (Emadine eye drops) versus levocabastine 0.05% eye drops in patients with allergic conjunctivitis.

PURPOSE: The efficacy and safety of emedastine 0.05% eye drops (Emadine; Alcon Laboratories, Inc, Fort Worth, Texas), a new H(1) antagonist, were studied in comparison to levocabastine 0.05% eye drops (Livostin; Janssen-Cilag N V, Berchem, Belgium) during a twice-daily treatment schedule for 6 weeks in adult and pediatric patients with seasonal allergic conjunctivitis. METHODS: In a prospective, multicenter, randomized, double-masked, parallel group study, 222 patients with allergic conjunctivitis were randomized (221 received treatment) to either emedastine or levocabastine, instilled twice daily for 6 weeks. Patient diaries were completed four times daily (before the morning and evening instillations, at noon, and in the afternoon), and clinical examinations were conducted at regular intervals. Primary efficacy variables of ocular redness and itching and secondary efficacy variables of chemosis, eyelid swelling, patient diary data, and physician's global assessment were analyzed. RESULTS: Both emedastine and levocabastine produced a statistically significant (P =.0001) reduction in itching and redness within 5 minutes of the first instillation. All signs and symptoms improved progressively over the 6-week treatment period. After 7 days of use, and throughout the remainder of the study, emedastine was statistically superior to levocabastine (P <.006) in preventing and alleviating the signs and symptoms (itching, redness, chemosis, and eyelid swelling) of allergic conjunctivitis. CONCLUSIONS: Emedastine 0.05% eye drops administered twice daily are more efficacious than levocabastine 0.05% eye drops in the prevention and treatment of the signs and symptoms of allergic conjunctivitis in adults and children of 4 years and above. Both emedastine 0.05% eye drops and levocabastine 0.05% eye drops were well tolerated.

An implantable upper extremity neuroprosthesis in a growing child with a C5 spinal cord injury.

OBJECTIVES: To implement a functional electrical stimulation (FES) hand neuroprosthesis called the Freehand System in a growing child with spinal cord injury (SCI) using extra lead wire to accommodate limb growth, and to evaluate the performance of the Freehand System during the subject's maturation. SETTING: Pediatric orthopedic hospital specializing in SCI rehabilitation. SUBJECT: Ten-year-old female patient with a C5 level SCI. METHOD: The Freehand System was implanted. Eight electrodes were implanted to targeted forearm and hand muscles to provide grasp and release function. The lead wire associated with each electrode was pathed subcutaneously up the arm with 4 cm of extra lead distributed throughout the path to accommodate expected limb growth. All leads were attached to a stimulator placed in the upper chest. Measures of lead unwinding, limb growth, stimulated muscle strength, and hand function were made at 6 and 16 months after implant. RESULTS: By 16 months post implant, the upper limb growth plates were closed and humeral and radial bone growth combined was 2.7 cm from the time of surgery. For all eight leads, lead unwinding in the upper arm was approximately 1.2 cm and was comparable to humeral bone growth (1.4 cm). Lead unwinding in the lower arm was also measurable for the two electrodes in hand muscles. Six of eight electrodes maintained grade 3 or better stimulated muscle strength throughout the growth period according to a manual muscle test. Of the two other electrodes, one appeared to have lost function due to depletion of excess lead. However, hand function with FES was comparable at 6 and 16 months post implant suggesting that growth did not negatively impact performance with the FES system. Hand function with FES was improved over voluntary hand function as well. Using the Freehand System, a pinch force of approximately 15 N was achieved compared to 1.3 N of voluntary tenodesis pinch force. Scores on the Functional Independence Measure (FIM) increased by 9 points when FES was used as compared to voluntary function. Improvements occurred primarily in eating and grooming. Independence in writing was achieved only with FES. CONCLUSIONS: For this child, hand function with the Freehand System was sustained over the growth period and was a significant functional improvement over voluntary hand function. By using excess lead wire, the Freehand System was successfully implemented before skeletal maturity, affording the child improved hand function earlier than would be otherwise indicated.

Visualization of mismatch repair in bacterial cells.

We determined the localizations of mismatch repair proteins in living Bacillus subtilis cells. MutS-GFP colocalized with the chromosome in all cells and formed foci in a subset of cells. MutL-GFP formed foci in a subset of cells, and its localization was MutS dependent. The introduction of mismatches by growth in 2-aminopurine caused a replication-dependent increase in the number of cells with MutS and MutL foci. Approximately half of the MutS foci colocalized with DNA polymerase foci. We conclude that MutS is associated with the entire chromosome, poised to detect mismatches. After detection, it appears that mismatch repair foci assemble at mismatches as they emerge from the DNA polymerase and are then carried away from the replisome by continuing replication.

The SOS response: recent insights into umuDC-dependent mutagenesis and DNA damage tolerance.

Be they prokaryotic or eukaryotic, organisms are exposed to a multitude of deoxyribonucleic acid (DNA) damaging agents ranging from ultraviolet (UV) light to fungal metabolites, like Aflatoxin B1. Furthermore, DNA damaging agents, such as reactive oxygen species, can be produced by cells themselves as metabolic byproducts and intermediates. Together, these agents pose a constant threat to an organism's genome. As a result, organisms have evolved a number of vitally important mechanisms to repair DNA damage in a high fidelity manner. They have also evolved systems (cell cycle checkpoints) that delay the resumption of the cell cycle after DNA damage to allow more time for these accurate processes to occur. If a cell cannot repair DNA damage accurately, a mutagenic event may occur. Most bacteria, including Escherichia coli, have evolved a coordinated response to these challenges to the integrity of their genomes. In E. coli, this inducible system is termed the SOS response, and it controls both accurate and potentially mutagenic DNA repair functions [reviewed comprehensively in () and also in ()]. Recent advances have focused attention on the umuD(+)C(+)-dependent, translesion DNA synthesis (TLS) process that is responsible for SOS mutagenesis (). Here we discuss the SOS response of E. coli and concentrate in particular on the roles of the umuD(+)C(+) gene products in promoting cell survival after DNA damage via TLS and a primitive DNA damage checkpoint.

Regiochemical studies of the ring expansion reactions of hydroxy azides with cyclic ketones.

The regiochemistry of ring expansions of 2-substituted cyclic ketones using 1,2-azidoethanol and 1,3-azidopropanol was examined. It was determined that the reactions of ketones with an adjacent methyl or ethyl group are generally unselective, but that bulkier substituents lead to preferential migration of the more highly substituted carbon. In addition, it was found that ketones bearing inductively electron-withdrawing substituents (OMe, Ph, Br) undergo selective migration of the less highly substituted carbon. For some substrates, alternative reaction pathways were also identified.

Mechanism of spreading of the highly related neurofibromatosis type 1 (NF1) pseudogenes on chromosomes 2, 14 and 22.

Neurofibromatosis type 1 (NF1) is a frequent hereditary disorder that involves tissues derived from the embryonic neural crest. Besides the functional gene on chromosome arm 17q, NF1-related sequences (pseudogenes) are present on a number of chromosomes including 2, 12, 14, 15, 18, 21, and 22. We elucidated the complete nucleotide sequence of the NF1 pseudogene on chromosome 22. Only the middle part of the functional gene but not exons 21-27a, encoding the functionally important GAP-related domain of the NF1 protein, is presented in this pseudogene. In addition to the two known NF1 pseudogenes on chromosome 14 we identified two novel variants. A phylogenetic tree was constructed, from which we concluded that the NF1 pseudogenes on chromosomes 2, 14, and 22 are closely related to each other. Clones containing one of these pseudogenes cross-hybridised with the other pseudogenes in this subset, but did not reveal any in situ hybridisation with the functional NF1 gene or with NF1 pseudogenes on other chromosomes. This suggests that their hybridisation specificity is mainly determined by homologous sequences flanking the pseudogenes. Strong support for this concept was obtained by sequence analysis of the flanking regions, which revealed more than 95% homology. We hypothesise that during evolution this subset of NF1 pseudogenes initially arose by duplication and transposition of the middle part of the functional NF1 gene to chromosome 2. Subsequently, a much larger fragment, including flanking sequences, was duplicated and gave rise to the current NF1 pseudogene copies on chromosomes 14 and 22.

Endotoxin induces structure-function alterations of rat liver peroxisomes: Kupffer cells released factors as possible modulators.

We report that endotoxin treatment results in decreased amounts of peroxisomes as well as changes in structure and function of peroxisomal membranes. Peroxisomes isolated from the liver of control and treated animals showed a marked decrease in total protein, but no significant alteration in the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) protein profile. However, the Western blot study of the peroxisomal beta-oxidation enzymes and catalase showed an increase in those enzymes in the peroxisomal peak of normal density in endotoxin-treated rats. Disintegration of peroxisomal membranes by carbonate treatment from endotoxin-treated liver and change in the fluidity of peroxisomal membranes suggests alterations in peroxisomal membrane structure. No such alterations were found in mitochondrial or microsomal membranes of endotoxin-treated livers. The lipid analysis of these organelles showed that the only organelle affected was the peroxisome, with a significant decrease in the phospholipid and cholesterol concentrations. To understand the mechanism of endotoxin-mediated alterations in peroxisomes, we studied the possible role of Kupffer cell secreted soluble factors (tumor necrosis factor alpha [TNF-alpha]) on the peroxisomal structure/function. Inactivation/elimination of Kupffer cells by gadolinium chloride before endotoxin treatment did not normalize the overall peroxisomal protein amount and the lipid composition of isolated peroxisomes. However, the levels of individual protein amount in remaining peroxisomes were normalized. Endotoxin also decreased peroxisomal beta-oxidation, and this was partially restored with gadolinium treatment. These results clearly show that peroxisomes are severely affected by endotoxin treatment and suggest that the damage to this organelle may contribute, at least in part, to endotoxin-induced hepatic cytotoxicity.

A role for the umuDC gene products of Escherichia coli in increasing resistance to DNA damage in stationary phase by inhibiting the transition to exponential growth.

The umuDC gene products, whose expression is induced by DNA-damaging treatments, have been extensively characterized for their role in SOS mutagenesis. We have recently presented evidence that supports a role for the umuDC gene products in the regulation of growth after DNA damage in exponentially growing cells, analogous to a prokaryotic DNA damage checkpoint. Our further characterization of the growth inhibition at 30 degrees C associated with constitutive expression of the umuDC gene products from a multicopy plasmid has shown that the umuDC gene products specifically inhibit the transition from stationary phase to exponential growth at the restrictive temperature of 30 degrees C and that this is correlated with a rapid inhibition of DNA synthesis. These observations led to the finding that physiologically relevant levels of the umuDC gene products, expressed from a single, SOS-regulated chromosomal copy of the operon, modulate the transition to rapid growth in E. coli cells that have experienced DNA damage while in stationary phase. This activity of the umuDC gene products is correlated with an increase in survival after UV irradiation. In a distinction from SOS mutagenesis, uncleaved UmuD together with UmuC is responsible for this activity. The umuDC-dependent increase in resistance in UV-irradiated stationary-phase cells appears to involve, at least in part, counteracting a Fis-dependent activity and thereby regulating the transition to rapid growth in cells that have experienced DNA damage. Thus, the umuDC gene products appear to increase DNA damage tolerance at least partially by regulating growth after DNA damage in both exponentially growing and stationary-phase cells.

Intraperoxisomal localization of very-long-chain fatty acyl-CoA synthetase: implication in X-adrenoleukodystrophy.

X-adrenoleukodystrophy (X-ALD) is a demyelinating disorder characterized by the accumulation of saturated very-long-chain (VLC) fatty acids (>C(22:0)) due to the impaired activity of VLC acyl-CoA synthetase (VLCAS). The gene responsible for X-ALD was found to code for a peroxisomal integral membrane protein (ALDP) that belongs to the ATP binding cassette superfamily of transporters. To understand the function of ALDP and how ALDP and VLCAS interrelate in the peroxisomal beta-oxidation of VLC fatty acids we investigated the peroxisomal topology of VLCAS protein. Antibodies raised against a peptide toward the C-terminus of VLCAS as well as against the N-terminus were used to define the intraperoxisomal localization and orientation of VLCAS in peroxisomes. Indirect immunofluorescent and electron microscopic studies show that peroxisomal VLCAS is localized on the matrix side. This finding was supported by protease protection assays and Western blot analysis of isolated peroxisomes. To further address the membrane topology of VLCAS, Western blot analysis of total membranes or integral membranes prepared from microsomes and peroxisomes indicates that VLCAS is a peripheral membrane-associated protein in peroxisomes, but an integral membrane in microsomes. Moreover, peroxisomes isolated from cultured skin fibroblasts from X-ALD patients with a mutation as well as a deletion in ALDP showed a normal amount of VLCAS. The consequence of VLCAS being localized to the luminal side of peroxisomes suggests that ALDP may be involved in stabilizing VLCAS activity, possibly through protein-protein interactions, and that loss or alterations in these interactions may account for the observed loss of peroxisomal VLCAS activity in X-ALD.

Comparison of functional electrical stimulation to long leg braces for upright mobility for children with complete thoracic level spinal injuries.

OBJECTIVE: To prospectively compare functional electrical stimulation (FES) to long leg braces (LLB) as a means of upright mobility for children with motor-complete thoracic level spinal cord injuries (SCIs). DESIGN: Intrasubject group comparison of two interventions. SETTING: Nonprofit pediatric orthopedic rehabilitation facility specializing in SCI. PATIENTS OR OTHER PARTICIPANTS: Convenience sample of five children between 9 and 18 years old with motor-complete thoracic level SCI. The hip and knee extensors were excitable by electrical stimulation. INTERVENTIONS: The FES system consisted of percutaneous intramuscular electrodes implanted to the hip and knee extensors and a push-button activated stimulator worn about the waist. Standing was accomplished by simultaneous stimulation of all implanted muscles. For foot and ankle stability, either ankle-foot orthoses (AFO) or supramalleolar orthoses were used. The LLB system consisted of a custom knee-ankle foot orthosis (KAFO) for four subjects and a custom reciprocating gait orthosis (RGO) for one subject who required bracing at the hip. For both interventions, either a front-wheeled walker or Lofstrand crutches were used as assistive devices. Each subject was trained in the use of both FES and LLB in seven standardized upright mobility activities: stand and reach, high transfer, toilet transfer, floor to stand, 6-meter walk, stair ascent, and stair descent. MAIN OUTCOME MEASURES: For each mobility activity, five repeated measures of level of independence, using the 7-point Functional Independence Measure (FIM) scale, and time to completion were recorded for each intervention. Subjects were also asked which intervention they preferred. RESULTS: For 94% of comparisons, subjects required equal (70%) or less (24%) assistance using FES as compared with LLB. Six of the seven mobility activities required less time to complete using FES, two activities at significant levels. The FES system was preferred in 62% of the cases, LLB were desired 27% of the time, and there was no preference in 11% of the cases. CONCLUSIONS: The FES system generally provided equal or greater independence in seven mobility activities as compared with LLB, provided faster sit-to-stand times, and was preferred over LLB in a majority of cases. Follow-up evaluations of both modes of upright mobility are needed to compare long-term performance and satisfaction.

Evaluation of the lower motor neuron integrity of upper extremity muscles in high level spinal cord injury.

PURPOSE: To evaluate the lower motor neuron (LMN) integrity of upper extremity muscles of persons with high tetraplegia (C1-C4) in order to determine muscles available for stimulation. METHODS: Fourteen subjects (23 arms) were evaluated for LMN integrity. Muscles that elicited a functional response (grade 3 or better) to surface electrical stimulation were considered to have intact LMN and good candidates for FES. Strength-duration (S-D) curves were generated on muscles that showed weak (less than grade 3) or no response to surface stimulation. Muscles were considered denervated if S-D curves were discontinuous or depicted steep, increasing amplitude for pulse durations greater than 1 m. RESULTS: Muscles for grasp and release had intact LMN in 19 of 23 (83%) arms. The wrist extensors and flexors and pronator were excitable in 17 (74%), 20 (87%) and 19 (83%) arms, respectively. The supinator demonstrated LMN lesion in 80% of the arms. Over 90% of the biceps muscles were unresponsive to electrical stimulation and 85% and 87% of the deltoid and supraspinatus muscles, respectively, were not electrically excitable. The latissimus dorsi and triceps muscles were typically innervated (78% and 91%, respectively) and slightly more than half (52%) of the pectoralis major muscles were excitable. CONCLUSION: These data suggest that application of FES in high tetraplegia for hand and arm function would require augmentation because of the inability to stimulate the elbow flexors, deltoid and rotator cuff muscles. These data also show that several paralyzed proximal muscles with intact LMN that have been historically transferred to address shoulder paralysis in other patient populations are available for transfer and stimulation in the population with high level spinal injuries.