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Biomedical subjects

C T Leonard

Publications and source records attributed to C T Leonard.

31 records · Page 2Linked to original sources

Fluticasone propionate induced alterations to lung function and the immunopathology of asthma over time.

BACKGROUND: Inhaled corticosteroids are the most widely used treatment for asthma, a disease characterised by both functional and immunopathological abnormalities. This study investigated the relative effects of inhaled corticosteroids on these two features of asthma over time. METHODS: A randomised, double blind, placebo controlled, parallel group study with inhaled fluticasone propionate, (FP 2 mg daily) was conducted in 27 patients with asthma. Following baseline analysis, the study tested the effects of short term (two weeks) and longer term (eight weeks) treatment. At each time point (0, 2, and 8 weeks) lung function tests were performed and endobronchial biopsy specimens obtained to determine the distribution and number of lymphocyte, macrophage and eosinophil subsets using immunohistological analysis. Twenty three patients completed the study, 11 on FP and 12 placebo. RESULTS: FEV1, delta FEV1, FEF25-75, and FEV1/FVC all improved after two weeks of FP treatment. This improvement was maintained but not increased after eight weeks. PC20FEV1 showed a trend to increase but was not significantly improved at eight weeks. No significant changes were seen in the placebo group. The numbers of T cells, macrophages, and eosinophils in the bronchial wall were reduced by two weeks of treatment with FP but were unaltered by placebo. The improvement offered by FP continued over the eight week period. Reductions in CD4:CD8 ratio and numbers of activated (EG2+) eosinophils were only significant after eight weeks of treatment. CONCLUSIONS: These results reveal that FP influences both functional and immunopathological parameters of asthma. Temporal relationships suggest that these are parallel but not necessarily interrelated effects. While short term treatment is effective in "normalising" the functional abnormalities in asthma, the impact of FP on bronchial inflammation appears to be progressive, taking up to eight weeks and more.

Administration, Topical↗

Changes in neural modulation and motor control during voluntary movement of older individuals.

BACKGROUND: Changes in the modulation of soleus alpha motoneuron excitability, as assessed by H reflexes, and temporal sequencing of the soleus and tibialis anterior muscles during voluntary ankle dorsiflexions and plantar flexions of young (24.7 +/- 11.5; n = 13) and older (68.7 +/- 5.4; n = 13) subjects were assessed to determine potential neural mechanisms that might contribute to motor control changes associated with aging. METHODS: A repetitive stimulation (5 Hz) soleus H-reflex testing protocol and surface electromyography (EMG) were used to assess the latencies of soleus H-reflex changes in relation to tibialis anterior and soleus EMG activations of standing subjects during voluntary ankle dorsiflexions and plantar flexions at self-selected speeds. The pattern and latency of H-reflex changes in relation to EMG activity were compared between young and old subjects. RESULTS: There were no differences in the relative amount of antagonist muscle (soleus) inhibition during voluntary ankle dorsiflexions between young and old subjects (26.4% and 27.2% decrease from resting H-reflex values, respectively). Older subjects, however, required additional time to achieve these levels of inhibition. Delays in the activation of soleus H reflexes during the plantar flexion task were also observed in older subjects. Older subjects also had considerable intra- and intersubject variability in muscle temporal sequencing patterns during ankle plantar flexions. CONCLUSIONS: Although older subjects exhibited similar relative levels of alpha motoneuron inhibition and excitation during voluntary movements, this modulation was delayed when compared to younger subjects. Temporal sequencing of distal muscle activations also appears to undergo change with aging.

Adolescent↗

Human myotatic reflex development of the lower extremities.

Lower extremity (LE) myotatic reflexes were tested by percussion (taps) to the patellar and Achilles tendons. Surface electromyographic recordings were obtained from 5 LE muscles during tendon taps. Results indicated that LE myotatic reflexes underwent considerable change during early human development. The changes were non-linear and highly variable. Reflex irradiation (the presence of reflex responses in muscles other than the one being directly stimulated by a tendon tap) was present in the newborn but to a lesser extent than was in evidence later on during the first year of life. The percentage of time reflex irradiation was detected in heteronymous muscle groups appeared to achieve maximal levels during the first year and then progressively decline. The decline in reflex irradiation was most dramatic between the first and second years of life. Irradiated responses were still recorded from 2 year-old children but with less frequency than in children less than 1 year of age. With the exception of responses in muscles that were direct antagonists to the stimulated muscle, irradiation was not observed in children 3-5 years of age.

Achilles Tendon↗

Myotatic reflex responses of non-disabled children and children with spastic cerebral palsy.

Surface electromyography (EMG) was used to examine lower-extremity myotatic reflex responses following patellar or Achilles tendon taps to normally developing, non-disabled infants and to individuals with cerebral palsy (CP). Reflex irradiation was present in non-disabled infants and infants with CP under two years of age. The only significant differences in myotatic reflex responses between the two groups at this age was the higher amplitude of the directly stimulated muscle of children with CP. After two years the amplitude did not differ between groups. Reflex irradiation, however, was greatly reduced in the non-disabled children but not in the children with cerebral palsy. These findings and those of non-human animal studies indicate the possible neural mechanisms that underlie reflex irradiation of individuals with CP. The potential clinical relevance of these findings is discussed.

Achilles Tendon↗

Neural modulation of muscle contractile properties during fatigue: afferent feedback dependence.

H reflex amplitudes, an indirect measure of the excitability of the alpha motoneuron pool, were recorded from 10 males during fatigue induced by submaximal, isotonic, voluntary contractions of the soleus muscle. H reflex changes were correlated with electromyographic changes (mean power frequency (MPF); root mean square (rms EMG)), under ischemic and non-ischemic conditions. The purpose of the ischemia was to block transmission of Ia and possibly Ib afferents to assess whether changes in sensory feedback had any effect on alpha motoneuron and EMG activity during fatigue. Significant interactions were found between ischemic and non-ischemic conditions. After an initial decrease (1.21 +/- 0.56 mV to 0.54 +/- 0.39 mV), H reflex amplitudes increased during non-ischemic trials (0.54 +/- 0.39 mV to 1.13 +/- 0.84 mV). Under ischemic conditions H reflex amplitudes decreased (2.11 +/- 1.10 mV to 0.70 +/- 0.74 mV; P < 0.003). During non-ischemic conditions, MPF decreased across 5 consecutive trials (157.7 +/- 17.9 Hz to 124.7 +/- 17.2 Hz), as compared to an increase under ischemic conditions (132.8 +/- 21.2 Hz to 197.1 +/- 53.6 Hz; P < 0.001). Root mean square amplitude decreased during the non-ischemic trials (31.07 +/- 14.62 mV to 25.98 +/- 8.26 mV). A greater decrease was noted during the ischemic trials (34.00 +/- 23.61 mV to 4.95 +/- 3.77 mV; P < 0.001). Data suggest that the CNS modulates muscle contraction in order to preserve force output and neuromuscular transmission during fatigue. This modulation appears dependent on Ia and/or Ib afferent feedback.

Adult↗

Motor behavior and neural changes following perinatal and adult-onset brain damage: implications for therapeutic interventions.

This article provides information pertaining to recent scientific findings regarding neural and motor development and the effects of brain damage on that development. The article is intended to provide the clinician with new information that will assist in patient assessments and the establishment of therapeutic interventions. Clinical and scientific issues pertaining to perinatal and adult-onset brain damage are discussed.

Adult↗

Myotatic reflex development in normal children and children with cerebral palsy.

Neonatal neuronal exuberance and its retention following neonatal brain damage have been demonstrated in a number of species but not in humans. The purpose of the present ongoing study is to determine if there is any evidence of neonatal neuronal exuberance and its retention following damage to the CNS in the human. Of equal concern is the determination of the neurological mechanisms underlying abnormal movement and reflex development in children with cerebral palsy.

Achilles Tendon↗

The development of independent walking in children with cerebral palsy.

Electromyographic and kinematic data were collected during treadmill locomotion by normal infants and infants with cerebral palsy. Locomotor patterns of the infants with cerebral palsy were similar to those of normal infants during the stage of supported locomotion, but as they matured, some of the characteristics of the infant stepping pattern, such as synchronous muscle activity with excessive muscular co-contraction and short-latency reflexes at foot contact, were retained. The normal plantigrade features of adult gait did not develop in these children.

Brain↗

Deficits in reciprocal inhibition of children with cerebral palsy as revealed by H reflex testing.

Experiments were performed to determine whether spinal and supraspinal components of reciprocal inhibition (a neural mechanism responsible for the prevention of muscular co-ordination during voluntary movement) were present in groups of non-disabled children and children with cerebral palsy. Changes in the gastrocnemius-soleus H reflex were examined during voluntary dorsiflexion and plantarflexion of the ankle and during a vibration applied to the anterior tibial tendon. The results indicate that children with cerebral palsy have impairments in reciprocal inhibition, both before and during voluntary movement. These deficits, which involve damage to supraspinal centres, contribute to their inability to perform smooth, co-ordinated movements.

Adolescent↗

Consequences of damage to the sensorimotor cortex in neonatal and adult cats. I. Sparing and recovery of function.

Postural reflexes and locomotion were studied in order to assess the effects of unilateral sensorimotor cortical ablations in neonatal (1 day old) and adult cats. To document the infant lesion effect and to distinguish recovery from sparing of function, development of motor function was studied in neonatal operates and in normal littermates. Once neonatal operates achieved maturity, their motor performance was compared with that of chronic adult operates. The emergence of motor behavior during development in neonatal operates appeared to follow the same pattern as in normal animals although with a protracted time course and motor behavior did not attain the level of maturity of normal animals. Some deficits were not apparent immediately but evolved with time. Adult operates exhibited recovery of function of some behavior but neonatal operates exhibited greater recovery and sparing. Adult operates, like neonatal operates, were able to mask certain deficits by compensatory mechanisms. Kinematic analysis revealed that neonatal and adult operates often executed movements abnormally. It is hypothesized that somewhat different mechanisms underlie recovery in neonatal and adult operated animals.

Age Factors↗

Consequences of damage to the sensorimotor cortex in neonatal and adult cats. II. Maintenance of exuberant projections.

After chronic sensorimotor cortex ablations, sparing and greater recovery of function were seen in neonatally operated cats compared with adult operated cats. These results suggested that undamaged cortex in neonatal operates might display projections different from those of adult operates. Injections of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) were made in ipsilateral parietal cortex adjacent to the sensorimotor cortex ablations or in the contralateral sensorimotor cortex. No changes in the projections of the parietal cortex were seen in operated cats or in the projections of the undamaged sensorimotor cortical projections of adult operates. In contrast, the intact sensorimotor cortex of neonatal operates exhibited crossed corticothalamic and corticorubral projections not present in normal or adult operated animals, whereas the corticospinal tract (CST) was unchanged by the ablations. Analysis of neurons within the ventroanterior-ventrolateral nuclear complex of the thalamus ipsilateral to the ablation showed that the surviving cells of neonatal operates were equal in number but were, on average, larger than those of normals and adult operates. Some neurons in neonatal operates were larger than any seen in adult operates and normals. Injections of HRP/WGA were also made into the sensorimotor cortex of normal newborn animals. Dense bilateral corticothalamic and corticorubral projections were present. The CST had extended to lumbar levels by the day of birth but projections to the grey matter were sparse. Thus, bilateral projections seen in neonatal operates probably represent retention of some exuberant projections present in normal neonatal animals. The CST which exhibited no exuberant projection was unchanged by the lesion. The crossed corticothalamic and corticorubral projections are likely to play a role in sparing and recovery of function particularly in sparing of contact placing.

Animals↗

The effects of milling and processing on wheat contaminated with ochratoxin A.

Samples of sound home-grown wheat (one hard and one soft milling) were obtained, cleaned, and gamma-irradiation used to reduce numbers of viable naturally-occurring fungi. Each sample was inoculated with a toxigenic strain of Penicillium verrucosum and monitored for ochratoxin A formation. When ochratoxin A had reached a level of 60 micrograms/kg, the samples were milled into ten fractions which were analysed for ochratoxin A by an HPLC method with immunoaffinity column clean-up. Each straight-run white flour was baked into bread which was analysed in the same way. Relationships between ochratoxin A levels in naturally-contaminated wheat and the products of milling and baking were established. The recovery of ochratoxin A in wholemeal compared with the cleaned wheat was essentially complete and no significant loss occurred on baking white or wholemeal flour into bread. Recoveries in the straight-run white flours, however, were only approximately one-third for the hard wheat and two-thirds for the soft wheat of the ochratoxin A in the uncleaned wheat. The reason for this was that a much higher proportion of the ochratoxin A was found in the bran and offal fractions from hard wheat than from soft. Conversely, a much higher proportion of the ochratoxin A was found in the reduction flour from soft wheat than from hard. Scouring was examined as a possible method of decontamination of wheat prior to milling. This process removes a proportion of the pericarp (bran coat) prior to milling. The results of the study confirmed that scouring reduced the ochratoxin A level in white and wholemeal flour three-fold for both the hard and soft wheat.

Bread↗

H-reflex testing to determine the neural basis of movement disorders of neurologically impaired individuals.

The H-reflex is an indirect measure of the excitability levels of alpha motoneurons. The authors have developed an adaptation of H-reflex testing which allows the continuous monitoring of human alpha motoneuron activity during movement. The technique differs from previously used H-reflex testing techniques in that it utilizes a 5 Hz stimulation to elicit the H-reflex. This allows for continuous and concomitant H- and M-wave recordings during a movement. This is an improvement over past single stimulus techniques in that the time and discomfort associated with this type of experimentation is greatly decreased. The repetitive stimulation technique enables H-reflex testing to be used clinically with neurologically impaired patient populations. Thus far, the authors have used the repetitive H-reflex testing procedures to assess alpha motoneuron activation and reciprocal inhibition of antagonist musculature during voluntary movement and anticipatory postural control responses of non-disabled individuals and of individuals with cerebral palsy. This paper describes the methodology involved in this technique and reports the results obtained.

Adolescent↗