ABSTRACT
The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.
Subject(s)
Anxiety/blood , Anxiety/cerebrospinal fluid , Oxytocin/blood , Oxytocin/cerebrospinal fluid , Adolescent , Adult , Anxiety/psychology , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Predictive Value of Tests , Statistics as Topic , Young AdultABSTRACT
A 30-month prospective study of 27 Scandinavian boys with confirmed diagnosis of Duchenne muscular dystrophy was carried out to construct profiles of the natural history of the disease. Assessments which included measures of voluntary muscle strength and function were done at 3 monthly intervals except for the first and second which were separated by 1 month. Recently developed statistical methods for analysis of longitudinal data with repeated observations on the same individual were used avoiding the problem of induced serial correlations. This allowed for the construction of both reference and prediction profiles for the variables %MRC, motor ability, walking time for 10 m and the sum of myometry of seven muscle groups.
Subject(s)
Movement Disorders/physiopathology , Muscle Weakness/physiopathology , Muscle, Skeletal/physiopathology , Muscular Dystrophy, Duchenne/physiopathology , Child , Child, Preschool , Data Interpretation, Statistical , Disability Evaluation , Disease Progression , Humans , Linear Models , Longitudinal Studies , Male , Movement Disorders/etiology , Movement Disorders/pathology , Muscle Weakness/etiology , Muscle Weakness/pathology , Muscle, Skeletal/pathology , Muscular Dystrophy, Duchenne/pathology , Prospective StudiesABSTRACT
A 30-month prospective randomized study of 27 Scandinavian boys with confirmed diagnosis of Duchenne muscular dystrophy was done to compare the effect of passive stretching combined with the use of night splints (group A) or passive stretching (group B) on the evolution of Tendo Achilles contractures. Assessments were based on the methodology of Scott et al. (Muscle Nerve 1982;5:291-301)Analysis of the pattern and mechanism of dropout was done to eliminate bias between the two groups. Logistic regression showed that Tendo Achilles contracture was the most important variable (P=0.0020) for dropout. Methods of statistical analysis for longitudinal data avoiding induced serial correlations were used in the analysis. The expected annual change in Tendo Achilles contracture was found to be 23% less in group A than in group B after equalization for total muscle strength (%MRC).
Subject(s)
Achilles Tendon/physiopathology , Contracture/etiology , Contracture/therapy , Muscular Dystrophy, Duchenne/therapy , Child , Child, Preschool , Contracture/physiopathology , Disease Progression , Humans , Male , Muscular Dystrophy, Duchenne/complications , Muscular Dystrophy, Duchenne/physiopathology , Prospective Studies , Range of Motion, Articular/physiology , Splints , Treatment OutcomeABSTRACT
We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment.
Subject(s)
Hip Joint/surgery , Leg/surgery , Muscular Dystrophies/surgery , Biopsy , Child , Child, Preschool , Follow-Up Studies , Gait , Humans , Male , Muscle Contraction/physiology , Muscles/diagnostic imaging , Muscles/pathology , Muscular Dystrophies/diagnostic imaging , Muscular Dystrophies/pathology , Muscular Dystrophies/physiopathology , Regression Analysis , UltrasonographyABSTRACT
To evaluate the therapeutic possibilities of chronic electrical stimulation, muscle function studies and quantitative tests of physical assessment were used to monitor the response of quadriceps femoris to prolonged low frequency stimulation. Comparative studies of the maximum voluntary and electrically elicited responses of muscles of young ambulant children with Duchenne muscular dystrophy, when compared to those of normal children's muscles, revealed lower values of maximum voluntary contraction, significant slowing (P less than 0.001) of mean relaxation times and a higher resistance to fatigue testing. Intermittent chronic low frequency stimulation resulted in a significant (P less than 0.01) increase in mean maximum voluntary contraction of the stimulated muscles compared with the mean force exerted by the unstimulated control muscles. There are clear therapeutic possibilities for the use of chronic low frequency stimulation in these children.
Subject(s)
Electric Stimulation Therapy , Muscles/physiopathology , Muscular Dystrophies/therapy , Adolescent , Child , Child, Preschool , Female , Humans , Male , Muscular Dystrophies/physiopathologyABSTRACT
Juvenile dermatomyositis in fourteen children who had not responded fully to steroids and other immunosuppressants and who had had chronic active disease for an average of 3 years was successfully treated with cyclosporin. Twelve patients had serious complications of the disease or of previous treatment. The response to cyclosporin included recovery of muscle strength and function and resolution of complications. It was possible to stop steroids or to reduce the steroid dose, which had previously been difficult, in all fourteen patients. In general, a low dose of cyclosporin (2.5-7.5 mg/kg daily) was sufficient and no serious side-effects were seen.
Subject(s)
Cyclosporins/therapeutic use , Dermatomyositis/drug therapy , Child , Child, Preschool , Chronic Disease , Cyclosporins/administration & dosage , Cyclosporins/blood , Dermatomyositis/blood , Drug Administration Schedule , Drug Evaluation , Drug Therapy, Combination , Female , Follow-Up Studies , Glomerular Filtration Rate/drug effects , Humans , Prednisolone/administration & dosageABSTRACT
A study was undertaken, using methods of stabilometry to compare stability of stance in normal children (n = 37) and those with Duchenne muscular dystrophy (n = 61). The purpose of this study was to monitor changes in the locus of the center of gravity and the range and frequency of sway and to evaluate the effect of orthotic application in an attempt to obtain information that would assist further development of orthoses. In group 1, boys with Duchenne muscular dystrophy who were still walking without assistance (mean age 7.2 +/- 1.76 years), the analysis of sway showed that, between 5 and 6 years of age, the boys already had ranges of anteroposterior (A/P) and lateral (Lat) sway that were significantly greater than those found in normal children (A/P P less than 0.05, Lat P less than 0.01). In group 2, boys with Duchenne muscular dystrophy when orthoses had been introduced (n = 23, mean age 10.4 +/- 1.47 years), the center of gravity was returned to a more normal position. There was a reduction of the anteroposterior range of sway, but the lateral range of sway remained significantly greater (P less than 0.01) as did the frequency of sway in both the anteroposterior and lateral directions (A/P P less than 0.001, Lat P less than 0.001).
Subject(s)
Muscular Dystrophies/physiopathology , Postural Balance , Child , Female , Humans , Locomotion , Male , PostureABSTRACT
A randomized double-blind therapeutic trial of isaxonine was completed over a 2-year period for 20 ambulant boys with Duchenne muscular dystrophy aged 5 1/2-10 years. The effect of the drug was monitored by measurement of walking times over 28 and 150 ft, motor ability score, MRC score based on 32 muscle groups, and myometry of 7 muscle groups. The drug had no significant effect on the progression of the disease. The trial had statistical power comparable to previous larger-scale multicenter trials. This reflected the low variability in the patients in relation to the magnitude of the overall deterioration. Measurements of muscle force (myometry and MRC score) had much greater statistical power than measurements of function (motor ability score and walking times) as analyzed by our methods. These observations have important implications for the design of future trials.
Subject(s)
Muscular Dystrophies/drug therapy , Pyrimidines/therapeutic use , Child , Clinical Trials as Topic , Cohort Studies , Double-Blind Method , Humans , Locomotion , Male , Random Allocation , Regression AnalysisSubject(s)
Cerebral Palsy/therapy , Electric Stimulation Therapy , Muscles/physiology , Child, Preschool , Female , Gait , Humans , Muscle ContractionABSTRACT
A force platform was built that was shown to meet the design and operating specifications for clinical use in the application of techniques of stabilography to investigate disturbances of equilibrium in young boys with Duchenne muscular dystrophy. The force platform was tested for reliability and repeatability and results were at an acceptable level for clinical application. Further, the design of the force platform and the associated software for system operation and computation of results were usable by non-technical staff. A feasibility study reporting the effect of the application of orthoses to a group of eight boys with Duchenne muscular dystrophy, who had lost the ability to walk independently, is represented.
Subject(s)
Muscular Dystrophies/rehabilitation , Orthotic Devices , Physical Therapy Modalities/instrumentation , Postural Balance , Child , Equipment Design , Evaluation Studies as Topic , Humans , Male , Microcomputers , Muscular Dystrophies/physiopathology , Transducers, PressureABSTRACT
The effect of chronic low frequency stimulation on the tibialis anterior muscle of children with Duchenne muscular dystrophy was investigated. Baseline data from 16 boys established low values of maximum voluntary contraction which did not improve with age. Studies of the contractile properties revealed significant slowing (p less than 0.001) of mean relaxation time compared to that of normal children's muscles. There was no loss of force during fatigue testing, as in normal children, but in contrast to normal children, there was no potentiation at lower frequencies of stimulation. Intermittent chronic low frequency stimulation of muscles in six young ambulant children with Duchenne muscular dystrophy resulted in a significant increase (p less than 0.05) in mean maximum voluntary contraction compared with the mean forces exerted by the unstimulated control muscles of the contralateral leg.
Subject(s)
Electric Stimulation Therapy , Muscular Dystrophies/therapy , Adolescent , Humans , Male , Muscle Contraction , Muscular Dystrophies/genetics , Muscular Dystrophies/physiopathology , SyndromeABSTRACT
The loss of force that occurred during intermittent electrically evoked tetanic contractions was determined for the tibialis anterior muscle of normal subjects. Adult muscles showed a characteristic reduction of tension over the first two to three minutes until a steady plateau was reached. Muscles of young children showed no comparable decrease of the initial tension in response to this method of fatigue testing. After fatigue the muscles of both groups of subjects produced a higher proportion of tension at lower rates of stimulation. Following prolonged chronic low frequency stimulation at 8-10 Hz, adult muscles showed a significant increase (p less than 0.01) in fatigue resistance compared to unstimulated control: the muscles of the normal child showed no measured change. It is concluded that it is possible to alter the properties of adult human muscle by superimposed low frequency electrical stimulation.
Subject(s)
Aging , Muscle Contraction , Muscles/physiology , Adolescent , Adult , Child , Child, Preschool , Electric Stimulation , Female , Humans , Male , Middle Aged , Muscle TonusABSTRACT
Fifty-seven boys with Duchenne muscular dystrophy aged between 6 years 3 months and 13 years 6 months, who were at the point of losing the ability to walk or had recently done so, were fitted with lightweight knee-ankle-foot orthoses to re-establish walking. 47 walked well and independently in their orthoses, achieving good stability and confidence. 20 are still ambulant; the other 27 stopped walking at intervals ranging from eight to 48 months. Prolongation of walking prevented the development of scoliosis, joint contractures and deformities and also benefited the boys psychologically.
Subject(s)
Locomotion , Muscular Dystrophies/rehabilitation , Orthotic Devices , Adolescent , Child , Humans , Male , Muscular Dystrophies/complications , Muscular Dystrophies/surgery , Scoliosis/etiology , Tendons/surgery , Time FactorsSubject(s)
Muscles/physiology , Physical Therapy Modalities/instrumentation , Adolescent , Adult , Aged , Electric Stimulation , Female , Humans , Male , Middle Aged , Muscle Contraction , Muscle RelaxationABSTRACT
A protocol has been developed for the quantitative assessment of muscle function in children with muscle disease. It includes total muscle strength (% MRC) based on a clinical assessment of strength of 32 groups using the 6-point MRC grading; the force of 8 selected muscle groups measured with a specially designed electromyometer; a motor ability score based on 20 consecutive motor activities; walking times over 28 and 150 feet, and recording of muscle contractures. A 3-year sequential study of 61 boys with Duchenne dystrophy showed progressive decline of muscle strength with age, a close correlation of total strength and the motor ability score (r = 0.89), and a curvilinear relationship of muscle strength with walking times over 28 and 150 feet (r = 0.78 and 0.79, respectively). A profile of the natural progression of Duchenne dystrophy has been established which could serve as a reference base for the assessment of cases at varying ages and their response to therapy and management.
