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Biomedical subjects

H K Graham

Publications and source records attributed to H K Graham.

At least 55 records · Page 3Linked to original sources
PubMed1998

A nonsense mutation in the carboxyl-terminal domain of type X collagen causes haploinsufficiency in schmid metaphyseal chondrodysplasia.

Type X collagen is a short-chain homotrimeric collagen expressed in the hypertrophic zone of calcifying cartilage. The clustering of mutations in the carboxyl-terminal NC1 domain in Schmid metaphyseal chondrodysplasia (SMCD) suggested a critical role for this type X collagen domain, but since no direct analysis of cartilage has been conducted in SMCD patients, the mechanisms of type X collagen dysfunction remain controversial. To resolve this problem, we obtained SMCD growth plate cartilage, determined the type X collagen mutation, and analyzed the expression of mutant and normal type X collagen mRNA and protein. The mutation was a single nucleotide substitution that changed the Tyr632 codon (TAC) to a stop codon (TAA). However, analysis of the expression of the normal and mutant allele transcripts in growth plate cartilage by reverse transcription PCR, restriction enzyme mapping, and a single nucleotide primer extension assay, demonstrated that only normal mRNA was present. The lack of mutant mRNA is most likely the result of nonsense-mediated mRNA decay, a common fate for transcripts carrying premature termination mutations. Furthermore, no mutant protein was detected by immunoblotting cartilage extracts. Our data indicates that a functionally null allele leading to type X collagen haploinsufficiency is the molecular basis of SMCD in this patient.

Animals↗
PubMed1998

Skeletal anomalies in the adriamycin-exposed prenatal rat: a model for VATER association.

Vertebral and radial anomalies are prominent features of VATER (vertebral defects, anorectal anomaly, tracheoesophageal fistula with esophageal atresia, and radial dysplasia) association. It has been shown that exposure of the rat fetus to adriamycin produces a spectrum of anomalies, including esophageal atresia and other features of VATER association. We aimed to document the skeletal defects found in rats exposed to teratogenic doses of adriamycin in utero. Vertebral, rib, and limb anomalies were found in 54, 54, and 35% of these examined fetuses, respectively. The range of bone lesions seen in this animal model was similar to the range of lesions seen in infants born with VATER association.

Abnormalities, Drug-Induced↗
PubMed1998

Musculoskeletal modelling in determining the effect of botulinum toxin on the hamstrings of patients with crouch gait.

This study aimed to determine the effect of hamstring botulinum toxin A (Btx-A) injection in 10 children with crouch gait in terms of changes in muscle length and lower-limb kinematics. Before Btx-A injection limb kinematics were recorded. Maximum hamstring lengths and excursions were calculated by computer modelling of the lower limb. Data were compared with the averaged hamstring lengths of 10 control children. Hamstrings were defined as short if their length was shorter than the average maximum length minus one standard deviation. Gait analysis was repeated 2 weeks after isolated hamstring Btx-A injection. Pre- and postinjection kinematic data and muscle lengths were then compared. Four of 18 injected limbs in three subjects had short medial hamstring before injection, none of the subjects had short lateral hamstrings. Muscle excursion was significantly reduced in the short and adequate maximum muscle length groups. A significant increase in the semimembranosus and semitendinosus length in all of the injected limbs was noted. Only in the short muscle group was a significant increase in muscle excursion observed. Knee extension improved by 13 degrees in the adequate muscle length group and by 15.6 degrees in the short muscle length group. Pelvic tilt and hip flexion increased in both groups non-significantly. Average walking speed postinjection increased from 0.60 ms(-1) to 0.71 ms(-1). Short hamstrings are over-diagnosed in crouch gait. Hamstring Btx-A injection in patients with crouch gait produces significant, repeatable muscle lengthening and improved ambulatory function.

Botulinum Toxins, Type A↗
PubMed1998

Mid-trimester ultrasound diagnosis of isolated talipes equinovarus: accuracy and outcome for infants.

Seventeen fetuses were diagnosed with isolated congenital talipes equinovarus (CTEV) on mid-trimester ultrasound at the Royal Women's Hospital, Melbourne, between January, 1992 and December 1995. Sixteen of the 17 cases had an amniocentesis performed and all karyotypes were normal. The remaining case was phenotypically normal, except for a clubfoot. None of the pregnancies was complicated by any of the recognized intrauterine environmental causes of CTEV. Four of the babies were delivered prematurely and all survived the neonatal period. Six (35%) infants did not have CTEV at birth, although 2 had postural varus feet. Nine of the 11 infants who did have CTEV at birth were treated within days of birth with plaster of Paris for periods of 6 to 12 weeks. Two infants required no further treatment, 5 required orthotics and 2 required surgery. The other 2 infants with CTEV at birth were treated with orthotics at 8 weeks of age. All infants were considered to have an excellent result at the 2 year follow-up. Seven (41%) of the prospective parents received antenatal counselling by an orthopaedic surgeon and the lack of study on outcome following an ultrasound diagnosis of CTEV was the impetus for our work.

Clubfoot↗
PubMed1997

Botulinum toxin A in the hemiplegic upper limb: a double-blind trial.

In a randomised, double-blind study, the effects of intramuscular injection of botulinum toxin type A (BtA) into the upper limb were compared with those of normal saline solution in 14 patients with cerebral palsy; their mean age was 9 years. Range of movement and function were assessed before injection and at 2 and 12 weeks after injection. BtA injection significantly increased maximum active elbow and thumb extension and significantly reduced tone at wrist and elbow. The hand grasp-and-release score improved, representing a modest functional change, but fine motor function, assessed by the ability to pick up coins, did not improve and in some cases deteriorated temporarily. The most notable subjective change was the cosmetic benefit of reduced involuntary elbow flexion. The tone-reducing effect of BtA was clinically detectable in comparison with the placebo and patients and parents perceived the change as beneficial. The median of changes in the treatment group was small but the range was large, suggesting that BtA can be useful in selected patients.

Adolescent↗
PubMed1997

The influence of flexed-knee gait on the energy cost of walking in children.

There is an understanding that walking with flexed knees contributes to the increased energy cost of walking found in children with neurological conditions. To determine the influence of flexed-knee gait on energy cost of walking in a group of children without neurological abnormality, the gait patterns of 10 normal children were studied using a Vicon system and standard marker set. A telemetric system (Cosmed K2) was then used to measure the oxygen cost of walking of the same children. The tests were repeated restricting the subjects' knee extension bilaterally, using hinged braces, set to 0, 15, 30, and 45 degrees of flexion. Although the braces themselves caused a significant increase in O2 cost (mL/kg/m) (P < 0.05), due to a decrease in walking speed, no further significant increase in oxygen cost was demonstrated regardless of the degree of knee flexion imposed, despite a significant increase in measured hip flexion and ankle dorsiflexion at the 45 degrees of knee flexion setting (P < 0.05). We propose that moderate flexed-knee gait does not of itself cause an increase in the energy cost of walking and that other factors present in the physically disabled child are likely to be implicated.

Adolescent↗
PubMed1996

Measurement of oxygen consumption in disabled children by the Cosmed K2 portable telemetry system.

Measurement of the energy cost of walking in children with cerebral palsy or spina bifida is difficult due to the cumbersome nature of equipment used to assess oxygen consumption. Such information collected with a lightweight telemetric system, the Cosmed K2, correlated well with that from a non-portable breath-by-breath system associated with a treadmill. The K2 did not significantly affect regular gait pattern as measured by gait analysis, and repeatability was satisfactory. Measurement of the energy cost of walking in the individual is unreliable in detecting differences of less than 10%; comparison between groups is more useful.

Adolescent↗
PubMed1996

Energy consumption in children with spina bifida and cerebral palsy: a comparative study.

The authors looked for differences in the energy expenditure patterns of ambulant children with cerebral palsy and spina bifida. Oxygen consumption was measured according to type of cerebral palsy or level of spina bifida lesion, and in healthy children. The rate of oxygen consumption (mL/kg/min) was significantly higher in the children with diplegia than in those with hemiplegia or with spina bifida or the healthy children. Oxygen cost (mL/kg/m) was significantly higher and velocity was significantly slower in all the groups with disability than in the healthy children. The reason children with diplegia consumed more oxygen than other children when walking may be that their abnormal equilibrium reactions impaired their balance and their ability to control their walking speed.

Cerebral Palsy↗
PubMed1996

Surgical release of knee flexion contractures in myelomeningocele.

We report the results of a prospective study of the surgical release of 45 knee flexion contractures in 28 patients with myelomeningocele. The neurosegmental level was thoracic in ten patients, L1/2 in one, L3/4 in 11, and L5/S1 in six. In walkers the indication for surgery was a fixed flexion contracture impeding walking, and in non-walking patients it was a flexion contracture impeding transfers or sitting balance, or likely to do so with increasing deformity. The mean age at surgery was 6.4 years (3 to 21) and the mean period of follow-up 13 years (4 to 20). The mean knee flexion contracture before surgery was 39 (25 to 70) which improved to 5 degrees at maximum correction and to 13 degrees at latest follow-up. We conclude that surgical release of knee flexion contractures in myelomeningocele improves gait in all children who walk, particularly those with low lumbar lesions. Recurrence of knee flexion contractures after surgical release is most common in those with thoracic lesions who do not achieve independent walking.

Adolescent↗
PubMed1995

The 'floating elbow' in children. Simultaneous supracondylar fractures of the humerus and of the forearm in the same upper limb.

During a six-year period we prospectively studied eight children who presented with supracondylar fractures of the humerus and of the forearm on the same side. They were treated by prompt closed reduction, percutaneous fixation with Kirschner wires, and appropriate management of neurovascular and soft-tissue injuries. The results were assessed clinically and radiographically at a minimum of 12 months after injury. According to a clinical scoring system they were acceptable in seven children and poor in one.

Adolescent↗
PubMed1994

Botulinum toxin A prevents the development of contractures in the hereditary spastic mouse.

The hereditary spastic mouse was studied as a model of cerebral palsy in childhood to test the hypothesis that intramuscular botulinum toxin A would prevent the development of calf-muscle contractures. A prospective randomised controlled trial of calf injection with botulinum A compared with injection of normal saline was performed on juvenile mice. At maturity, the calf muscles of the spastic mice were 16 per cent shorter than those of their normal siblings. The calf muscles of spastic mice injected with botulinum toxin A grew to within 2 per cent of normal length. This difference in mature muscle length was highly significant.

Achilles Tendon↗
PubMed1994

Botulinum toxin in the management of the lower limb in cerebral palsy.

The role of intramuscular botulinum toxin A in the treatment of 26 children with cerebral palsy was evaluated. The indication for injection was the presence of a dynamic contracture of lower-limb muscles interfering with positioning or walking. Spastic target muscles were identified by clinical examination and, in ambulant children, by gait analysis. Between 50 and 320 units of botulinum toxin were injected into each muscle group to a total dose of 100 to 400 units per child. The effects of injection were monitored by repeated clinical examination and gait analysis. There were no clinically detectable systemic side-effects, and all but one patient had a reduction in tone, which occurred within three days and persisted for two to four months. There were significant improvements in ambulatory status and in sagittal-plane kinematics. In some cases these gains persisted after the tone-reducing effects of the toxin had worn off.

Adolescent↗
PubMed1993

Minimally invasive surgery for osteoid osteoma of the proximal femur.

Seven patients with osteoid osteoma of the proximal femur were treated by percutaneous excision of the nidus. The combination of preoperative localisation by tomography and intraoperative localisation by image intensifier resulted in a curative procedure with minimal bone resection in all cases, although a second operation was required in one patient.

Adolescent↗
PubMed1992

Serum and other calcium fractions in patients after severe musculoskeletal trauma.

Alterations in serum calcium fractions after trauma may be of clinical importance. For investigation of this problem, serum calcium fractions were studied prospectively in 42 patients with severe musculoskeletal injuries. The severity of trauma was assessed with the Apache II severity of disease classification system. Serum ionized calcium, total calcium, pH, albumin, and arterial blood gases were measured daily for the first five days after admission. The fat embolism syndrome developed in eight patients; they were more severely injured than the others, and they had significantly lower levels of serum ionized calcium for all five days of the study. There was a strong negative correlation between the Apache II score and serum ionized calcium. Ionized hypocalcemia has a strong association with development of the complications of severe musculoskeletal trauma, such as the fat embolism syndrome.

Adult↗
PubMed1990

Interobserver variability in grading Perthes' disease.

Fifteen independent observers of three levels of experience (consultant staff, fellows, residents) assessed 40 radiographs of children presenting with Perthes' disease using the Catterall and the Salter-Thompson grading systems. Each observer was supplied with descriptions and illustrations of the classifications and each hip was grouped by both systems by each observer. The results were statistically analysed using 'kappa' statistics. The level of interobserver agreement was higher for the Salter-Thompson system and correlated with the level of experience of the observer. Both systems can give acceptable levels of interobserver agreement, but the Salter-Thompson grouping is simpler and easier to apply in the earlier stages of the disease when treatment must be decided, and has a higher degree of reproducibility amongst more experienced observers.

Child↗