Biomedical subjects
R D Stevenson
Publications and source records attributed to R D Stevenson.
Apparent growth hormone deficiency in children with cerebral palsy.
Ten children with cerebral palsy (CP) and growth failure underwent assessment of the growth hormone (GH) axis, including spontaneous GH secretion, GH secretion in response to pharmacological stimulation, and circulating levels of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3). Six of the children had subnormal GH secretion consistent with GH deficiency. Subnormal growth velocity was the best clinical predictor of GH deficiency. The large percentage of these children with apparent GH deficiency is surprising. Possible mechanisms include anatomic abnormalities of the hypothalamic-pituitary axis, psychosocial deprivation, and an interaction between suboptimal nutritional status and an abnormal central nervous system.
Measurement of growth in children with developmental disabilities.
The clinical assessment of growth is a challenging, but essential, aspect of managing the health care of children with developmental disabilities. However, with standard equipment, modest training and some patience, almost all children can be measured reliably. Once reliable measurements are obtained, the interpretation or 'clinical meaning' of the measurements depends on their comparison with reference data from normal populations or, when available, with condition-specific reference data. More research is needed to improve our understanding of the clinical meaning of obtained measurements. The range of normal growth for some children with disabilities, particularly CP, remains to be defined. Research in the next ten years will, hopefully, lead to the development of growth charts for children with CP, and perhaps children with other conditions, which will facilitate the clinical interpretation of growth data and lead to improved management of health care for children with developmental disabilities.
Organ and cell allometry in Hawaiian Drosophila: how to make a big fly.
The importance of body size in predicting many aspects of an animal's biology has become well established in recent years. However, little is known about how body size evolves at the cellular level. Some published data suggest that it is cell number and not cell size that accompanies changes in organ and body size across taxa. We examined organ and cell allometry in the wing, eye and basitarsus of adult Hawaiian Drosophila, ranging in body length from 0.2 mm to 0.8 mm. Linear measurements of all three structures exhibit a positive allometry with body length. Exponents of the allometric equation were 0.96, 0.55 and 1.50 for wing, eye and basitarsus, respectively. Surface markers were used to quantify cell size of each organ. The allometric exponents for cell size as a function of organ size were 0.53, 0.68 and 0.33 for wing, eye and basitarsus, respectively. In contrast to reports in the literature on other systems, our results for Hawaiian Drosophila indicate that cell size may contribute between one third and two thirds to evolutionary changes in organ and body size.
Use of segmental measures to estimate stature in children with cerebral palsy.
BACKGROUND: The assessment of stature in children with cerebral palsy is difficult. This study tested the clinical utility of the segmental measures of upper-arm length, tibial length, and knee height as proxies for stature in children with cerebral palsy. METHODS: The study included 211 sets of measurements made in 172 children with cerebral palsy attending an outpatient clinic at a pediatric rehabilitation center during a 2-year period. Forty-three percent were female, 20% black, 31% diplegic or hemiplegic, and 52% nonambulatory. An observer measured weight, head circumference, recumbent length or standing height, upper-arm length, tibial length, knee height, midarm circumference, triceps skinfold, and subscapular skinfold. RESULTS: The correlation coefficients were as follows: upper-arm length and stature, .97 (95% confidence interval, .95 to .98) (R2 = .94); tibial length and stature, .97 (95% confidence interval, .96 to .98) (R2 = .94); and knee height and stature, .98 (95% confidence interval, .98 to .99) (R2 = .97). The linear regression equations were used to develop formulas for the estimation of stature from a segmental measure. CONCLUSIONS: Upper-arm length, tibial length, and knee height are all reliable and valid proxies for stature in children with cerebral palsy up to 12 years of age. We recommend that either knee height or tibial length be measured in the routine anthropometry of children with cerebral palsy who cannot be measured by standard techniques. Estimates of stature can then be calculated and plotted on standard growth charts.
Growth hormone deficiency in two children with cerebral palsy.
The authors describe two children with cerebral palsy and linear growth failure secondary to growth hormone deficiency. One of the children was successfully treated with growth hormone replacement therapy. His linear growth velocity increased from 3cm/year before therapy to 8.3 cm/year during the first two years of therapy. Potential complications such as worsening orthopedic status did not occur. Psychosocial benefits were noted. The authors conclude that growth hormone deficiency may play a role in linear growth failure in some children with cerebral palsy and that some of these children may benefit from growth hormone therapy.
The effects of non-nutritional factors on growth in cerebral palsy.
This study was designed to evaluate the effects of non-nutritional factors alone on the growth of children with cerebral palsy (CP). 20 children with hemiplegic CP, normal stature and normal triceps skinfold measurements had 16 different anthropometric measures performed on each side of the body (affected vs unaffected). All measures of breadth, circumference and length were significantly smaller on the affected side compared with the unaffected side. Skinfold measurements had a tendency to be larger on the affected side. These results suggest that non-nutritional factors related to disease severity have a significant influence on the growth of children with CP, even in the absence of malnutrition.
Ventilatory and gas exchange abnormalities on exercise in chronic heart failure.
The mechanism of breathlessness on exertion in patients with chronic heart failure are still not fully understood. We therefore investigated the effects of ventilatory and gas exchange abnormalities on exercise capacity in chronic heart failure. Exercise testing was performed in 30 patients with exertional breathlessness due to chronic heart failure and in 30 controls, using continuous transcutaneous blood gas monitoring. Maximal symptom-limited oxygen consumption as (V'O2) as a percentage predicted was reduced in patients (45 +/- 10%; mean +/- SD) compared to controls (87 +/- 7). The ventilatory response (minute ventilation/carbon dioxide production (V'E/V'CO2)) was significantly increased in patients compared to controls (39.9 +/- 7.7 and 25.9 +/- 3.6, respectively). The dead space to tidal volume ratio (VD/VT) was raised in patients compared to controls at rest (0.45 +/- 0.04 vs 0.35 +/- 0.02, respectively) and this persisted on exertion (0.40 +/- 0.05 in patients and 0.20 +/- 0.05 in controls). At maximal symptom-limited exercise, V'E/V'CO2 was inversely related to the % predicted V'O2 in patients, but not in controls (r = -0.62 and r = -0.24, respectively). In patients, V'E/V'CO2 was significantly correlated with VD/VT at maximum exercise (r = 0.82). Patients with chronic heart failure have a significant degree of "wasted ventilation" on exertion, which is associated with increased ventilatory response. The increased ventilatory response on exertion appears to contribute to exercise limitation in these patients.
Feeding and nutrition in children with developmental disabilities.
Feeding is a complex physiologic process that is further complicated by social and cultural influences. Feeding development, although dependent on structural integrity and neurologic maturation, is a learned progression of behaviors influenced by sensory motor development and experience. Children learn how to eat. Children with developmental disabilities frequently develop problems with feeding that can lead to malnutrition and respiratory symptoms. Feeding disorders are often the result of multiple interacting variables that have disrupted feeding development and the feeding relationship. The pediatrician who has a solid understanding of these variables can understand the problems, sort out the contributing causes, and intervene effectively.
Is evidence for homoeopathy reproducible?
We tested, under independent conditions, the reproducibility of evidence from two previous trials that homoeopathy differs from placebo. The test model was again homoeopathic immunotherapy. 28 patients with allergic asthma, most of them sensitive to house-dust mite, were randomly allocated to receive either oral homoeopathic immunotherapy to their principal allergen or identical placebo. The test treatments were given as a complement to their unaltered conventional care. A daily visual analogue scale of overall symptom intensity was the outcome measure. A difference in visual analogue score in favour of homoeopathic immunotherapy appeared within one week of starting treatment and persisted for up to 8 weeks (p = 0.003). There were similar trends in respiratory function and bronchial reactivity tests. A meta-analysis of all three trials strengthened the evidence that homoeopathy does more than placebo (p = 0.0004). Is the reproducibility of evidence in favour of homoeopathy proof of its activity or proof of the clinical trial's capacity to produce false-positive results?
Deterioration of feeding behavior following surgical treatment of drooling.
Few adverse effects of the surgical treatment of drooling are reported in the literature. This report describes a young man with severe extrapyramidal cerebral palsy and profuse drooling whose oral feeding behavior deteriorated following bilateral submandibular gland excision and parotid duct rerouting. Before surgery the patient had safe, functional oral feeding skills, and eating was enjoyable. Following surgery he developed progressive feeding difficulties, weight loss, and aspiration pneumonia. His deterioration led to the placement of a feeding gastrostomy and the end of all oral feedings. Surgery had a disturbing and apparently irreversible negative impact on the patient's quality of life.
Effect of hemiplegia on skeletal maturation.
Children with cerebral palsy have been reported to have poor growth and delayed skeletal maturation, but it is unclear whether these effects are related to the underlying brain injury or to concomitant malnutrition. This study was designed to evaluate the effects of hemiplegic cerebral palsy on skeletal maturation and growth, with the unaffected side used as each subject's control. Bilateral hand-wrist radiographs were obtained for 19 children with spastic hemiplegia. Skeletal maturation was determined in a blinded fashion with the Fels method. The skeletal age of the affected (hemiplegic) side was less than that of the unaffected (control) side in all 19 subjects; the mean difference in skeletal age was 7.3 months (p < 0.001). The delay in skeletal maturation of the affected side correlated linearly with age and upper extremity function. These findings show that brain injury results in delayed skeletal maturation independent of malnutrition. This effect on skeletal maturation may explain, in part, the reason that some children with cerebral palsy grow poorly.
Clinical correlates of linear growth in children with cerebral palsy.
The purpose of this cross-sectional study was to determine correlates of linear growth in children with cerebral palsy (CP). 171 children with CP were measured and their charts reviewed. z scores were calculated for weight (Wz) and height (Hz). Hz correlated positively with Wz and head circumference, and negatively with age, the presence of spastic quadriplegia, non-ambulation and seizures. The correlation between Hz and age was stronger when non-ambulatory children were analysed separately. Multiple linear regression resulted in only Wz and age contributing significantly to the variance in stature as measured by Hz. These results provide preliminary evidence that nutritional status is a major correlate of growth in CP. The finding that linear growth worsens with age independent of nutrition suggests that other factors also influence growth in CP.
Effect of lysophosphatidic acid on motility, polarisation and metabolic burst of human neutrophils.
The effect of lysophosphatidic acid (LPA) on human neutrophil activation was examined by a combination of automated tracking assays, cell shape measurements and assays of the metabolic burst by means of 7-dimethylamino-naphthalene-1,2-dicarbonic acid hydrazide (DNDH)-dependent chemiluminescence. LPA powerfully stimulated polarisation and motility. Polarisation became detectable at 2 microM LPA and virtually 100% of cells were polarised at 20 microM LPA. Cell motility increased with the degree of polarisation, and was diminished at high LPA concentration, but this decrease was reversed by albumin. LPA also inhibited the metabolic burst response to both n-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorobol 12-myristate 13-acetate (PMA). Inhibition of the PMA-induced metabolic burst by LPA was not affected by pertussis toxin, showing that the effect was not mediated by the pertussis toxin-sensitive heterotrimeric G protein, and that inhibition of the PMA-stimulated metabolic burst by LPA could result from a direct action of LPA on the small cytosolic GTP-binding proteins. These results indicate that lysophosphatidic acid production by thrombin-activated platelets could play a significant role in the regulation of the inflammatory response.
Dispersive locomotion of human neutrophils in response to a steroid-induced factor from monocytes.
A monocyte-derived factor that stimulates the locomotion of human neutrophils on an albumin-coated glass surface has been prepared from the culture supernatant of dexamethasone-treated human monocytes and called STMS (steroid-treated monocyte supernatant). A modified cell tracking program has been developed and the parameters of locomotion determined by the analysis of Gail and Boone for cells moving in a persistent random walk. Cells moving in uniform concentrations of STMS, interleukin-8 (IL-8) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) chosen to give a sub-maximal speed of locomotion show persistent, random and constrained random diffusion, respectively, with augmented diffusion coefficients of 0.8 +/- 0.1, 0.14 +/- 0.02 and 0.12 +/- 0.03 microns 2 per second for STMS, IL-8 and fMLP, respectively. The augmented diffusion coefficient and the underlying persistence are therefore sensitive quantitative assay parameters for STMS activity and the qualitative characteristics of locomotion allow STMS activity to be distinguished from that of all other factors tested. The contribution of lowered adhesion to locomotion was examined in a novel tilt-assay, which demonstrated that cells in the presence of STMS, but not other factors, moved down slope with significantly increased speed while maintaining contact with the substratum. The results were interpreted in terms of the bipolar form of STMS-treated cells, contrasting with multipolar forms in response to other agents. This together with low adhesiveness plus an inherent tendency of a single locomotor focus to continue motion in its original direction has been used to explain the difference between response to STMS and other factors.(ABSTRACT TRUNCATED AT 250 WORDS)
A factor released by monocytes in the presence of dexamethasone stimulates neutrophil locomotion.
1. Steroid-treated monocyte supernatants cause a dramatic increase in the speed of locomotion of human neutrophils and a significant decrease in their adhesion to protein-coated glass. In contrast, control monocyte supernatants have a smaller effect on the speed of locomotion, but cause a large increase in their adhesiveness. 2. This supernatant activity was produced equally well in the presence or absence of serum after 24 h culture at 37 degrees C with 10(-6) M dexamethasone. 3. The effect of the steroid-treated monocyte supernatants on the speed of locomotion of human peripheral blood neutrophils was not altered by rabbit polyclonal antisera against lipocortins 1-6. 4. Rabbit anti-interleukin-8 antibody which blocked the effect of IL-8 on the speed of locomotion of neutrophils did not antagonize the locomotion stimulating action of steroid-treated monocyte supernatants. 5. The exocellular release of this factor(s) by human mononuclear leucocytes suggests that it may be an in vivo mediator of the anti-inflammatory effect of glucocorticoids.
Investigation and management of pulmonary infiltrates following bone marrow transplantation: an eight year review.
BACKGROUND: Although pulmonary infiltrates are common in bone marrow transplant recipients and add significantly to the morbidity and mortality of this group of patients, there is uncertainty as to the most appropriate investigation and a lack of information on the effects of investigations on management and outcome. METHODS: All bone marrow transplant recipients from one institution referred for respiratory investigation between 1982 and 1990 were reviewed. RESULTS: Of 204 bone marrow transplant recipients 27 developed pulmonary infiltrates which failed to respond to broad spectrum antibiotics. All were examined by bronchoscopy and bronchoalveolar lavage. A specific diagnosis was made in 20 cases, 17 with an infective cause and three with a non-infective aetiology. In 17 of the 27 episodes these investigations led to a positive change in treatment, but in only five did these changes result in patient survival beyond one month. Eighteen of the 20 deaths were due to progressive respiratory failure of an infective aetiology in 14 and non-infective in four. CONCLUSIONS: Bronchoscopy and bronchoalveolar lavage are effective in establishing a diagnosis, but the impact on overall survival is disappointingly poor.