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Biomedical subjects

J Crosbie

Publications and source records attributed to J Crosbie.

At least 19 recordsLinked to original sources

Inter-limb coordination in bimanual reach-to-grasp following stroke.

Purpose. To determine the extent to which inter-limb coordination in the execution of unimanual and bimanual tasks was impaired following stroke.Methods. Thirteen stroke survivors aged 55 - 77 years and 13 healthy, neurologically intact participants aged 57 - 86 years performed a unimanual and two bimanual tasks involving the relocation of single and paired objects. Movements were recorded using electromagnetic sensors attached to the wrists and a series of micro switches placed under the objects. Main outcome measures included time to complete components of the tasks; comparison between sides; deviation of the hands from a linear trajectory; coordination of the two sides as indicated by relative phase angle.Results. Stroke survivors took longer to complete the bimanual tasks, but did not deviate from the optimal trajectories more than the healthy participants. Both groups performed unimanual tasks faster than bimanual and stroke participants were only slightly less synchronised when performing bimanual tasks.Conclusions. In conclusion, in a group of stroke patients with reasonable strength, inter-limb coordination was mildly impaired. This impairment in coordination was not due to lateral deviation of the impaired limb.

Aged↗

Association of the glutamate receptor subunit gene GRIN2B with attention-deficit/hyperactivity disorder.

The glutamatergic signaling pathway represents an ideal candidate susceptibility system for attention-deficit/hyperactivity disorder (ADHD). Disruption of specific N-methyl-D-aspartate-type glutamate receptor subunit genes (GRIN1, 2A-D) in mice leads to significant alterations in cognitive and/or locomotor behavior including impairments in latent learning, spatial memory tasks and hyperactivity. Here, we tested for association of GRIN2B variants with ADHD, by genotyping nine single nucleotide polymorphisms (SNPs) in 205 nuclear families identified through probands with ADHD. Transmission of alleles from heterozygous parents to affected offspring was examined using the transmission/disequilibrium test. Quantitative trait analyses for the ADHD symptom dimensions [inattentive (IA) and hyperactive/impulsive (HI)] and cognitive measures of verbal working memory and verbal short-term memory were performed using the fbat program. Three SNPs showed significantly biased transmission (P < 0.05), with the strongest evidence of association found for rs2,284,411 (chi(2)= 7.903, 1 degree of freedom, P= 0.005). Quantitative trait analyses showed associations of these markers with both the IA and the HI symptom dimensions of ADHD but not with the cognitive measures of verbal short-term memory or verbal working memory. Our data suggest an association between variations in the GRIN2B subunit gene and ADHD as measured categorically or as a quantitatively distributed trait.

Adult↗

The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder.

The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.

Animals↗

Association of the calcyon gene (DRD1IP) with attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a childhood-onset disorder characterized by marked inattention, hyperactivity and impulsivity. The dopaminergic system has been hypothesized to be involved in the development of ADHD. Positive associations have been found for the dopamine receptors D1 and D5 genes, suggesting that other genes involved in D1/D5 signalling may also contribute to ADHD. In this study, we tested the calcyon gene (DRD1IP), which encodes a brain-specific D1-interacting protein involved in D1/D5 receptors calcium signalling, for association with ADHD. The inheritance of nine polymorphisms in the calcyon gene was examined in a sample of 215 nuclear families, with 260 affected children, using the transmission/disequilibrium test. The most common haplotype, designated C1, demonstrated significant evidence for excess transmission. Quantitative trait analyses of this haplotype showed significant relationships with both the inattentive (parent's rating, P=0.006; teacher's rating, P=0.003) and hyperactive/impulsive (parent's rating, P=0.004) dimensions of the disorder. Two of the nine marker alleles included in haplotype C1, rs4838721A located approximately 10 kb 5' of the gene and rs2275723C located 10 bp upstream of the exon 5 acceptor splice site, also showed significant evidence for association when analysed individually. As these two variants are not predicted to alter calcyon function, we screened the gene exons by sequencing. No variation in the coding region was identified, suggesting that a causal variant allele resides elsewhere in a regulatory sequence of the gene. These findings support the proposed involvement of the calcyon gene in ADHD and implicate haplotype C1 as containing a risk allele.

Adolescent↗

Pilonidal sinus of the penis.

A pilonidal sinus is a subcutaneous sinus containing hair. It is most commonly found in the natal cleft of hirsute men. Here we describe the unusual finding of a pilonidal sinus arising on the male foreskin.

Humans↗

Linkage of the dopamine receptor D1 gene to attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has a strong genetic basis, and evidence from human and animal studies suggests the dopamine receptor D1 gene, DRD1, to be a good candidate for involvement. Here, we tested for linkage of DRD1 to ADHD by examining the inheritance of four biallelic DRD1 polymorphisms [D1P.5 (-1251HaeIII), D1P.6 (-800HaeIII), D1.1 (-48DdeI) and D1.7 (+1403Bsp1286I)] in a sample of 156 ADHD families. Owing to linkage disequilibrium between alleles at the four markers, only three haplotypes are common in our sample. Using the transmission/disequilibrium test (TDT), we observed a strong bias for transmission of Haplotype 3 (1.1.1.2) from heterozygous parents to their affected children (P=0.008). Furthermore, using quantitative trait TDT analyses, we found significant and positive relationships between Haplotype 3 transmission and the inattentive symptoms, but not the hyperactive/impulsive symptoms, of ADHD. These findings support the proposed involvement of DRD1 in ADHD, and implicate Haplotype 3, in particular, as containing a potential risk factor for the inattentive symptom dimension of the disorder. Since none of the four marker alleles comprising Haplotype 3 is predicted to alter DRD1 function, we hypothesize that a functional DRD1 variant, conferring susceptibility to ADHD, is on this haplotype. To search for such a variant we screened the DRD1 coding region, by sequencing, focusing on the children who showed preferential transmission of Haplotype 3. DNA from 41 children was analysed, and no sequence variations were identified, indicating that the putative DRD1 risk variant for ADHD resides outside of the coding region of the gene.

Adolescent↗

Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region.

The glutamate system may be involved in the development of attention-deficit/hyperactivity disorder (ADHD) based on animal models and the role of N-methyl-D-aspartate receptors (NMDAR) in cognition and motor processes. A follow-up study of the first genome scan for ADHD identified significant evidence for linkage to the 16p13 region. The glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the NMDA receptor, resides in this region and a recent study has reported an association between this gene and ADHD. We tested for linkage between the alleles and haplotypes of four polymorphisms at the GRIN2A locus and ADHD in our sample of 183 nuclear families with 229 affected children. In contrast to previous findings, we did not identify any evidence for a relationship of these markers and ADHD. Owing to the role of GRIN2A in aspects of cognition, we investigated the relationship of this gene to the cognitive phenotypes of inhibitory control, verbal short-term memory and verbal working memory. There was no significant evidence of linkage between GRIN2A and these phenotypes. While the results were not significant in our sample, the previous association finding suggests that further study of this gene is warranted.

Adolescent↗

Effect of elbow flexion contractures on the ability of people with C5 and C6 tetraplegia to lift.

BACKGROUND AND PURPOSE: It is commonly assumed that minor elbow flexion contractures prevent people with C5-C6 tetraplegia and paralysis of the triceps brachii muscles from bearing full body weight through their upper limbs. The aim of the present study was to determine the effect of simulated bilateral elbow flexion contractures on the ability of these individuals to bear weight through their upper limbs and to determine whether full passive elbow extension is truly critical for lifting body weight. METHOD: A biomechanical study was performed. Body weight lifted was measured under conditions that simulated bilateral elbow flexion contractures. Five people with motor complete C6 tetraplegia and one person with motor complete C5 tetraplegia, all with bilateral paralysis of the triceps brachii muscles, were recruited to the study. Subjects were fitted with bilateral elbow splints that restricted elbow extension but did not restrain elbow flexion nor prevent the elbow from collapsing, and were seated on an instrumented platform that measured vertical forces under the buttocks. Subjects pushed down through their hands and lifted under five different conditions, namely: with no elbow splints; with bilateral elbow splints adjusted to restrict elbow extension by 5-10 degrees; by 15-20 degrees; by 25-30 degrees and with bilateral elbow splints adjusted to allow unrestricted movement of the elbow joint. Maximal weight lifted from under the buttocks, for each condition, was expressed in relation to weight under the buttocks during unsupported sitting (that is, 'seated body weight'). RESULTS: Subjects lifted progressively less weight from under their buttocks as passive elbow restriction was progressively restricted. However, one subject lifted all his seated body weight when elbow extension was restricted by 5-10 degrees and another lifted all his seated body weight when elbow extension was restricted by 5-10 degrees and 15-20 degrees. CONCLUSIONS: Minor elbow flexion contractures will not alone prevent people with tetraplegia and paralysis of the triceps brachii muscles from lifting. Full passive elbow extension is not critical for the performance of this task.

Adult↗

Normative data for passive ankle plantarflexion--dorsiflexion flexibility.

OBJECTIVE: To describe the normal distribution parameters for measures of passive ankle plantarflexion-dorsiflexion flexibility obtained from a large sample of able-bodied young adult subjects. DESIGN: Seven variables were assessed and descriptive analyses were conducted. BACKGROUND: While assessment of plantarflexion-dorsiflexion flexibility is an important component of a clinical examination of plantarflexion contracture, there is limited normative data available that can be used as a reference for clinical decision-making. METHODS: Data were collected from 300 able-bodied male and female subjects aged between 15 and 34 years. Both ankles were measured. Load-displacement curves were collected using a manually controlled instrumented footplate. Six variables were extracted from these curves: passive torque at zero and 10 deg, passive stiffness at zero and 10 deg, and two coefficients from an equation fitted to the curve (i.e., k and b). The seventh variable, passive dorsiflexion range of motion, was quantified using a clinical procedure. RESULTS: Flexibility variables did not differ between the left and right ankles, nor between the dominant and non-dominant legs. All variables were normally distributed. These distributions can, therefore, be adequately described using their mean and standard deviation values. CONCLUSIONS: This study has substantially increased the available database on plantarflexion-dorsiflexion flexibility and forms the basis of norm-referenced clinical tests.

Adolescent↗

Hand function of C6 and C7 tetraplegics 1 - 16 years following injury.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To quantify the hand function of C6 and C7 tetraplegics 1 - 16 years after injury. SETTING: Patients were assessed in their homes. METHODS: Medical records of patients admitted to the Prince Henry Hospital Spinal Injuries Unit between 1984 and 1999 were used to identify all patients with C6 or C7 tetraplegia at 3 months post injury. Sixty-five patients (107 hands) were identified in this way. Forty-seven patients (81 hands) were located and agreed to partake in the study, and seven (nine hands) had died. Thus 81% of patients (83% of hands) still alive at follow-up were assessed. MAIN OUTCOME MEASURES: Unilateral hand function was assessed with the Grasp and Release Test (GRT) and a 10 item Activities of Daily Living (ADL) Test. Prevalance and severity of contractures, lateral grasp (key grip) strength and extensibility of the extrinsic finger flexor muscles were also determined. RESULTS: All hands except one had been managed without surgical intervention. The median number of ADL tasks successfully completed was 9/10 (interquartile range=8 - 10) and the median number of objects successfully manipulated in the GRT was 3/6 (IQ range=3 - 5). Lateral grasp was poor (74% and 75% of hands could not use a lateral grasp to move the paperweight or depress the fork in the GRT, respectively), and the prevalence of contractures was low (53% of hands had full passive range of motion). CONCLUSION: In the long term, most C6 and C7 tetraplegics attain a high level of hand function despite poor lateral grasps.

Activities of Daily Living↗

Deficient inhibition as a marker for familial ADHD.

OBJECTIVE: The authors investigated whether deficient inhibitory control, as measured by the stop-signal paradigm, delineates a familial subgroup of attention deficit hyperactivity disorder (ADHD). METHOD: Subjects were 54 ADHD children defined as having poor or good inhibition (on the basis of stop-signal paradigm performance) and 26 healthy comparison children. Family history of ADHD and measures of neurobiological and psychosocial risk were compared among the three groups. RESULTS: ADHD was significantly more prevalent in the families of the children with ADHD who exhibited poor inhibition (48.1%) than in the families of those exhibiting good inhibition (18.5%) or in the families of healthy comparison children (7.7%). No differences in neurobiological or psychosocial risk were found for the three groups. CONCLUSIONS: Deficient inhibition delineates a familial subtype of ADHD. Psychosocial and neurobiological factors did not account for inclusion in the good inhibition group and did not act conjointly with inhibition to increase the risk for ADHD in the poor inhibition group. This study demonstrates that cognitive measures such as a laboratory measure of inhibition can serve as phenotype markers for genetic analyses.

Analysis of Variance↗

Physical therapy is effective for patients with osteoarthritis of the knee: a randomized controlled clinical trial.

OBJECTIVE: To assess the effectiveness of physical therapy, given either as an individually attended treatment or in a small group format, in terms of pain, physical function, and health related quality of life for patients with osteoarthritis (OA) of the knee. METHODS: After 2 baseline assessments, 126 patients were randomized into one of 3 allocation arms: individual treatments (n = 43), small group format program (n = 40), and waiting list control (n = 43). After reassessment at 8 weeks, patients allocated to waiting list control were randomized into one of the 2 active treatment arms. Assessments included both self-report measures (WOMAC, SF-36) and objective measures of physical performance (gait analysis and muscle strength). RESULTS: Both physical therapy treatment allocations resulted in significant improvements in pain, physical function, and health related quality of life above the control group (standardized response mean 0.36 to 0.65). Improvements in the self-report measures were substantiated by significant correlated improvements in knee extensor strength and fast walking speed (rho 0.36-0.42). There were no significant differences in effectiveness between the 2 physical therapy allocations for any of the measured outcomes. Improvements gained were maintained for at least 2 months. Responsiveness to treatment was modified by loss of medial joint space width, the interaction being significant for physical function, gait, and knee extensor strength. CONCLUSION: Physical therapy, either as an individually delivered treatment or in a small group format, is an effective intervention for patients with knee OA. Responsiveness to this 8 week intervention was modified by loss of medial joint space width.

Aged↗

A randomized controlled trial of a passive accessory joint mobilization on acute ankle inversion sprains.

BACKGROUND AND PURPOSE: Passive joint mobilization is commonly used by physical therapists as an intervention for acute ankle inversion sprains. A randomized controlled trial with blinded assessors was conducted to investigate the effect of a specific joint mobilization, the anteroposterior glide on the talus, on increasing pain-free dorsiflexion and 3 gait variables: stride speed (gait speed), step length, and single support time. SUBJECTS: Forty-one subjects with acute ankle inversion sprains (<72 hours) and no other injury to the lower limb entered the trial. METHODS: Subjects were randomly assigned to 1 of 2 treatment groups. The control group received a protocol of rest, ice, compression, and elevation (RICE). The experimental group received the anteroposterior mobilization, using a force that avoided incurring any increase in pain, in addition to the RICE protocol. Subjects in both groups were treated every second day for a maximum of 2 weeks or until the discharge criteria were met, and all subjects were given a home program of continued RICE application. Outcomes were measured before and after each treatment. RESULTS: The results showed that the experimental group required fewer treatment sessions than the control group to achieve full pain-free dorsiflexion. The experimental group had greater improvement in range of movement before and after each of the first 3 treatment sessions. The experimental group also had greater increases in stride speed during the first and third treatment sessions. DISCUSSION AND CONCLUSION Addition of a talocrural mobilization to the RICE protocol in the management of ankle inversion injuries necessitated fewer treatments to achieve pain-free dorsiflexion and to improve stride speed more than RICE alone. Improvement in step length symmetry and single support time was similar in both groups.

Acute Disease↗

A randomized trial assessing the effects of 4 weeks of daily stretching on ankle mobility in patients with spinal cord injuries.

OBJECTIVE: To determine the effect of 4 weeks of 30 minutes of daily stretching on ankle mobility in patients with recent spinal cord injuries (SCIs). DESIGN: Assessor-blinded randomized controlled trial. SETTING: Two spinal injury units in Sydney, Australia. PATIENTS: Consecutive sample of 14 recently injured patients with paraplegia and quadriplegia. INTERVENTION: Treated ankles were stretched continuously into dorsiflexion with a torque of 7.5 N x m for 30 minutes each weekday for 4 weeks. Contralateral ankles received no stretches. MAIN OUTCOME MEASURES: Passive torque-angle curves for both ankles were obtained at study commencement, then at weeks 2, 4, and 5 (ie, during, at the end of, and 1 week after the stretching program). Torque-angle measurements were obtained with the knee extended and flexed. Mean values for parameters (baseline angle, angle at 10 N x m, slope) describing the characteristics of the torque-angle curves were derived for each knee position. Changes from pretest to each subsequent test were calculated, as well as 95% confidence intervals (CIs) for differences in these changes between stretched and controlled ankles. RESULTS: The stretching intervention did not significantly change any of the 3 parameters describing the torque-angle curves of the ankle in either knee position. At the beginning of the study, the mean (+/-SD) angles obtained with the application of a standardized torque with the knee extended for the control and stretch ankles were 105 degrees (+/- 10.4 degrees) and 106 degrees (+/- 9.8 degrees), respectively. After 4 weeks, these values were 106 degrees (+/- 10.6 degrees) and 107 degrees (+/- 10.6 degrees) (mean difference in change of angle = 0 degrees; 95% CI, -3.3 degrees to 3.3 degrees). CONCLUSION: Thirty minutes of daily stretching for 4 weeks does not significantly change ankle mobility in recently injured patients with SCIs.

Adult↗

Biomechanical analysis of a weight-relief maneuver in C5 and C6 quadriplegia.

OBJECTIVE: To determine the kinematics and kinetics of performing a weight-relief maneuver in persons with C5 and C6 quadriplegia. STUDY DESIGN: A three-dimensional kinematic and kinetic analysis was performed on the upward phase of a weight-relief maneuver with the use of a motion analysis system, two force platforms, and an instrumented seat. Electromyography (EMG) data were collected from the upper pectoralis, anterior deltoid, latissimus dorsi, and biceps brachii muscles of the right upper limb. SETTING: Biomechanics laboratory. SUBJECTS: Seven persons with C5 and C6 quadriplegia (ASIA A and B) with "flickers" (grade 1/5) or less in wrist flexor and triceps brachii muscles. MAIN OUTCOME MEASURES: Angular displacements and associated moments of the shoulder, elbow, and wrist, kinematic variables describing the position and displacement of the trunk and upper limbs, and EMG data. RESULTS: Subjects lifted from a forward flexed posture with their arms adducted against their trunks. During the course of lifting, they flexed their shoulders and wrists and extended their elbows. They generated peak mean (+/- SE) shoulder and elbow flexor moments of .65 (+/-.04) and .41 (+/-.06) N x m x kg(-1), respectively. Shoulder adductor moments increased over the course of the lift. The median (and interquartile range) mean EMG activity in the upper pectoralis and the anterior deltoid muscles were 63% (35%-76%) and 44% (36%-49%) of EMG obtained during maximal voluntary contractions, respectively. CONCLUSION: Persons with quadriplegia with paralysis of the triceps brachii muscles lift themselves by generating active shoulder flexor and adductor moments. They also rely on wrist flexor moments that are generated by the stretch of the wrist flexor muscles.

Adult↗

Contribution of thixotropy, spasticity, and contracture to ankle stiffness after stroke.

OBJECTIVES: Increased resistance to stretch of muscles after stroke may be the result of centrally mediated neural factors such as spasticity or local, peripheral factors such as muscle contracture or thixotropy. The aim was to investigate evidence for an abnormal thixotropic response and compare this with two other factors-contracture and spasticity-which could potentially contribute to muscle stiffness after stroke. METHODS: Thirty patients with stroke whose calf muscles were assessed clinically as stiff and 10 neurologically normal subjects were recruited. To measure thixotropy, their calf muscles were stretched through two cycles after two prestretch conditions: one in which the muscles were maintained in a shortened position and one in which they were maintained in a lengthened position. Spasticity was defined as the presence of tonic stretch reflexes in relaxed muscles. Contracture was defined as being present when maximum passive ankle dorsiflexion fell at least 2 SD below the mean value of the control subjects. RESULTS: Both controls and patients with stroke exhibited a thixotropic response but this was no greater in the patients than the controls. About one third of the patients displayed muscle contracture and most exhibited spasticity. Contracture made a significant contribution (p=0.006) to the clinical measure of calf muscle stiffness while spasticity made a significant contribution (p=0.004) to the laboratory measure of calf muscle stiffness. CONCLUSIONS: Measuring thixotropy at the level of joint movement was sufficiently sensitive to determine the thixotropic response in both neurologically normal subjects and patients impaired after stroke. The thixotropic response was not higher than normal after stroke, suggesting that whereas thixotropy may produce enough immediate resistance to impede movement in those who are very weak, it is not a substantial contributor to long term muscle stiffness. Contracture did significantly contribute to muscle stiffness, supporting the importance of prevention of contracture after stroke. Spasticity contributed to muscle stiffness only when the limb was moved quickly.

Aged↗

Stimulus control and generalization of point-loss punishment with humans.

Two experiments demonstrated stimulus control and generalization of conditioned punishment with humans. In both studies, responses first were reinforced with points exchangeable for money on a variable-interval schedule in the presence of one line length (S(D)). Next, a second line length was introduced, and point loss followed every response in the presence of that line (S(D)p). In the final training condition, points were deducted at session end. Response rate was lower in the presence of the S(D)p despite equal rates of points for money in the presence of both stimuli. In generalization testing for Experiment 1, the two lines were included in a 10-line continuum; S(D)p fell in the middle and the trained SD was at one end. Lines were presented randomly, and point delivery and loss contingencies were as in training but with points available in the presence of all lines. For all subjects, response rates were lowest around S(D)p and increased towards the SD end of the continuum. Because testing included only one or two lines beyond S(D), this pattern did not rule out S(D) generalization. Thus, in Experiment 2, stimuli beyond S(D) were added to generalization tests. Response rates did not decrease as a function of distance from S(D), clarifying the demonstration of punishment generalization.

Adult↗

Effects of reduced ankle dorsiflexion following lateral ligament sprain on temporal and spatial gait parameters.

Partial rupture of the lateral ligament complex of the ankle is the commonest soft tissue injury affecting the lower limb. The effect of the limitation of motion at the ankle, particularly of dorsiflexion, on gait is unclear. In this study, 34 subjects were measured during their recovery from a partial rupture of the lateral ligament for both range of dorsiflexion and the temporal and spatial parameters of walking. Consistent relationships were identified between the range and the gait variables which were in concordance with the characteristics expected from an antalgic gait pattern.

Adolescent↗