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Biomedical subjects

H K Graham

Publications and source records attributed to H K Graham.

At least 37 records · Page 2Linked to original sources
PubMed2001

Classification of gait patterns in spastic hemiplegia and spastic diplegia: a basis for a management algorithm.

Classifications of gait and postural patterns in spastic hemiplegia and spastic diplegiía are presented, based on the work of previous authors. The classifications are used as a biomechanical basis, linking spasticity, musculoskeletal pathology in the lower limbs, and the appropriate intervention strategies. The choice of target muscles for spasticity management, the muscle contractures requiring lengthening and the choice of orthotics are then linked to the underlying gait pattern.

Algorithms↗
PubMed2001

The effect of botulinum toxin type A and a variable hip abduction orthosis on gross motor function: a randomized controlled trial.

Hip displacement is the second most common deformity after equinus in children with cerebral palsy (CP), and may result in dislocation, pain, fixed deformity and loss of function. We studied the combined effects of intramuscular injections of botulinum toxin type A (BTX-A) to the adductors and hamstrings and a variable hip abduction orthosis (SWASH), on gross motor function, hip displacement and progression to surgery, in a randomized clinical trial. Thirty-nine children, with bilateral spastic cerebral palsy, and mean age 3 years + 2 months (range 1 year+7 months--4 years +10 months) entered the trial. Gross Motor Function Classification System (GMFCS) levels were as follows: one child was level II, 11 were level III, 13 were level IV and 14 were level V. After concealed randomization, 20 were allocated to the control group and 19 to the intervention group. Thirty-five children completed the follow up at 1 year. The novel intervention group received up to 4.0 U BOTOX/kg/muscle, 16 U/kg/body weight every 6 months plus the use of a SWASH brace. The control group received clinical best practice comprising physiotherapy but no hip abduction bracing. Both groups showed improvements in total Gross Motor Function Measure (GMFM) score [mean 6.0% BTX-A group; 6.1% Control; 95% CI -- 6.7, 6.5 (NS)], however, there was no additional treatment effect for the study group. There were similar improvements on GMFM goal scores and GMFM-66 scores, but again no additional treatment effect was observed. Multiple regression of change in total GMFM by GMFCS classification for each group showed greater improvement in the total scores from baseline in the BTX-A/SWASH treated group than the control group. In the first year, nine children (two in the intervention group and seven in the control group) required soft tissue surgery because of progressive hip migration in excess of 40%. A longer-term follow up of a larger cohort may be required to determine the effect of the combined treatment on hip displacement.

Botulinum Toxins, Type A↗
PubMed2001

Management of upper limb dysfunction in children with cerebral palsy: a systematic review.

Effective use of the upper limb can impact on educational outcomes, participation in activities of daily living and vocational options for many children with cerebral palsy (CP). This article presents the results of a systematic review of the literature on the management of upper limb dysfunction in children with CP. The range of management options includes therapies such as physiotherapy, occupational therapy, neurodevelopmental therapy and conductive education; peripheral splinting and casting; focal or generalized pharmacotherapy; and surgery to improve upper limb function or correct deformity. A literature search identified 60 papers, of which four were randomized controlled trials and 44 were prospective studies with objective outcome measures. Principal studies undertaken for each type of treatment and the efficacy of the different types of treatment were critically evaluated. In addition, the current level of evidence for each study was evaluated according to Sackett's (1989) model and ICIDH-2 classification. A close examination of two relatively new treatments for upper limb spasticity, constraint induced movement therapy and botulinum toxin type A (BTX-A) was conducted with reference to more extensive data on the efficacy of BTX-A in the lower limb.

Botulinum Toxins, Type A↗
PubMed2001

Botulinum toxin type A in the management of equinus in children with cerebral palsy: an evidence-based economic evaluation.

INTRODUCTION: The aim of this study was to compare two methods of conservative management of calf spasticity and equinus gait--intramuscular injection of botulinum toxin type A (BTX-A) and serial casting. An economic evaluation framework was adopted to assess whether BTX-A offers value for money in the management of equinus gait due to calf spasticity in children with cerebral palsy. Short- to medium-term health care costs and outcomes were estimated for the comparison. This study was embarked upon to provide clinical and economic data as part of an application to the Pharmaceutical Benefits Advisory Committee (PBAC) for the reimbursement of BOTOX by the Australian Commonwealth Government. This is the primary mechanism for reimbursement of pharmaceuticals in Australia, as they are not routinely reimbursed through health insurance companies. The perspective of the analysis was that of the Australian health system. METHODOLOGY: Randomized controlled trials (RCTs) exist comparing one treatment cycle of BTX-A with serial casting (Corry et al., 1998; Flett et al., 1999). A long-term prospective study provided data on multiple cycles of BTX-A treatment in a more naturalistic setting (Boyd et al., 1999). A simple economic modelling approach was used to establish resource utilization by treatment arm. Only direct medical costs were considered (BTX-A, medical personnel time and medical consumables). MAIN MEASURES: Clinical efficacy was obtained from the randomized controlled trials (Corry et al., 1998; Flett et al., 1999). Patient/parent preference was obtained from long-term follow-up (Corry et al., 1998) and a preference questionnaire (Flett et al., 1999). Australian treatment patterns and patient demographics were obtained from the naturalistic study (Boyd et al., 1999). RESULTS: The RCTs demonstrated equivalent efficacy of BTX-A and serial casting; however, with BTX-A the effect lasted longer and was clearly the preferred treatment. For patients with hemiplegia the costs of an episode of treatment with BTX-A or serial casting are ($AUD) $595 and $435, respectively, and thus the additional costs associated with BTX-A are $160. The corresponding costs for patients with diplegia are $1045 for BTX-A treatment and $870 for serial casting and thus the additional cost associated with BTX-A is $175. With an overall treatment duration of 3.7 years and an average treatment interval of 10 months, patients would receive an average of 5.4 treatments. Thus, for patients with hemiplegia the total additional cost, discounted at 5% annually, for BTX-A is $793. For patients with diplegia the total additional cost for BTX-A is $867. CONCLUSIONS AND CLINICAL INTERPRETATIONS: BTX-A is an effective, safe and acceptable treatment modality and is associated with only a modest increase in direct medical costs per child per year. BTX-A can be considered a valuable and cost-effective treatment in the conservative management of equinus due to calf spasticity in children with cerebral palsy. This conclusion is supported by the acceptance of the Pharmaceutical Benefits Advisory Committee (PBAC) recommendation that BOTOX should attract a full Government subsidy in Australia.

Botulinum Toxins, Type A↗
PubMed2001

Isolated calf lengthening in cerebral palsy. Outcome analysis of risk factors.

We assessed the medium-term outcome of three methods of isolated calf lengthening in cerebral palsy by clinical examination, observational gait analysis and, where appropriate, instrumented gait analysis. The procedures used were percutaneous lengthening of tendo Achillis, open Z-lengthening of tendo Achillis and lengthening of the gastrosoleus aponeurosis (Baker's procedure). We reviewed 195 procedures in 134 children; 45 had hemiplegia, 65 diplegia and 24 quadriplegia. We established the incidence of calcaneus and recurrent equinus and identified 'at-risk' groups for each. At follow-up, 42% had satisfactory calf length, 22% had recurrent equinus and 36% calcaneus. The incidence of calcaneus in girls at follow-up was significantly higher (p = 0.002) while boys had an increased rate of recurrent equinus (p = 0.012). Children with diplegia who had surgery when aged eight years or younger had a 44% risk of calcaneus, while those over eight years had a 19% risk (p = 0.046). Percutaneous lengthening of tendo Achillis in diplegia was the least predictable, only 38% having a satisfactory outcome compared with 50% in the other procedures. The incidence of recurrent equinus in hemiplegic patients was 38%. Only 4% developed calcaneus. The type of surgery did not influence the outcome in patients with hemiplegia or quadriplegia. Severity of involvement, female gender, age at operation of less than eight years and percutaneous lengthening of tendo Achillis were 'risk factors' for calcaneus. Hemiplegia, male gender, and an aponeurosis muscle lengthening increased the risk of recurrent equinus.

Achilles Tendon↗
PubMed2001

Tardy posterolateral rotatory instability of the elbow due to cubitus varus.

BACKGROUND: Cubitus varus has long been considered merely a cosmetic deformity. The purpose of this paper is to demonstrate a causal relationship between cubitus varus and instability of the elbow. METHODS: In twenty-four patients (twenty-five limbs) with a cubitus varus deformity following a pediatric distal humeral fracture or resulting from a congenital anomaly (three limbs of two patients), tardy posterolateral rotatory instability of the elbow developed approximately two to three decades after the deformity occurred. All patients presented with lateral elbow pain and recurrent instability. The average varus deformity was 15 degrees (range, 0 degrees to 35 degrees ). Surgery was performed in twenty-one patients (twenty-two limbs). Treatment consisted of reconstruction of the lateral collateral ligament and osteotomy in seven limbs, ligament reconstruction alone in ten, osteotomy alone in four, and total elbow arthroplasty in one. RESULTS: In three patients, the triceps muscle was dynamically stimulated intraoperatively to contract while resisting extension of the elbow. This produced posterolateral rotatory subluxation of the elbow, which was reversed by corrective osteotomy and lateral transposition of a portion of the medial head of the triceps that originally had been attached to the elongated, deformed medial aspect of the olecranon. At an average of three years (minimum, one year) after the operation, the result was good or excellent for nineteen of the twenty-two limbs that had undergone an operation; three limbs had persistent instability. CONCLUSIONS: With cubitus varus, the mechanical axis, the olecranon, and the triceps line of pull are all displaced medially. The repetitive external rotation torque on the ulna permitted by these deformities can stretch the lateral collateral ligament complex and lead to posterolateral rotatory instability. Thus, cubitus varus deformity secondary to supracondylar malunion or congenital deformity of the distal part of the humerus may not always be a benign condition and may have important long-term clinical implications. Operative correction can relieve symptoms of instability. The indications for preventive corrective osteotomy remain to be determined.

Adolescent↗
PubMed2000

Identification of collagen fibril fusion during vertebrate tendon morphogenesis. The process relies on unipolar fibrils and is regulated by collagen-proteoglycan interaction.

The synthesis of an extracellular matrix containing long (approximately mm in length) collagen fibrils is fundamental to the normal morphogenesis of animal tissues. In this study we have direct evidence that fibroblasts synthesise transient early fibril intermediates (approximately 1 micrometer in length) that interact by tip-to-tip fusion to generate long fibrils seen in older tissues. Examination of early collagen fibrils from tendon showed that two types of early fibrils occur: unipolar fibrils (with carboxyl (C) and amino (N) ends) and bipolar fibrils (with two N-ends). End-to-end fusion requires the C-end of a unipolar fibril. Proteoglycans coated the shafts of the fibrils but not the tips. In the absence of proteoglycans the fibrils aggregated by side-to-side interactions. Therefore, proteoglycans promote tip-to-tip fusion and inhibit side-to-side fusion. This distribution of proteoglycan along the fibril required co-assembly of collagen and proteoglycan prior to fibril assembly. The study showed that collagen fibrillogenesis is a hierarchical process that depends on the unique structure of unipolar fibrils and a novel function of proteoglycans.

Animals↗
PubMed2000

Recommendations for the use of botulinum toxin type A in the management of cerebral palsy.

Botulinum toxin type A (BTX-A) is increasingly being used for the treatment of childhood spasticity, particularly cerebral palsy. However, until very recently, all such use in this indication has been unapproved with no generally accepted treatment protocols, resulting in considerable uncertainty and variation in its use as a therapeutic agent. In view of the increasing awareness of, and interest in, this approach to the treatment of spasticity, and also the recent licensing in a number of countries of a BTX-A preparation for treating equinus deformity in children, it would seem timely to establish a framework of guidelines for the safe and efficacious use of BTX-A for treating spasticity in children. This paper represents an attempt, by a group of 15 experienced clinicians and scientists from a variety of disciplines, to arrive at a consensus and produce detailed recommendations as to appropriate patient selection and assessment, dosage, injection technique and outcome measurement. The importance of adjunctive physiotherapy, orthoses and casting is also stressed.

Animals↗
PubMed2000

Biomechanical transformation of the gastroc-soleus muscle with botulinum toxin A in children with cerebral palsy.

Objective measures (kinematics and kinetics) were used to study prospectively the effects of botulinum toxin A (BTX/A) on the gastro-soleus muscle in ambulant children with cerebral palsy. In this prospective before and after trial, 15 children with diplegia and 10 children with hemiplegia were studied (mean age 5 years 7 months, range 4 years to 9 years). A range of standardized clinical measures was undertaken but the emphasis for this report is on the three-dimensional gait analysis (3DGA) results. All children showed improvements in sagittal ankle kinematics, as has been previously reported. Two new measures of ankle kinetics were devised: ankle moment quotient (AMQ), and ankle power quotient (APQ). Before intervention, ankle moments were characterized by a 'double bump' ankle moment. A typical abnormal baseline ankle-power curve was triphasic with an initial trough of absorption followed by abnormal mid-stance power generation, instead of the usual A1 pattern, and reduced terminal stance power generation (A2). Three weeks after treatment with BTX/A alone there was a statistically significant improvement of AMQ and APQ; some patients required potentiation of BTX/A with a short period of serial casts. Both groups (BTX/A alone and BTX/A plus casting) continued to show improvement in ankle kinetics from baseline after 12 and 24 weeks. This is the first study to demonstrate improvements in the typical abnormal ankle kinetics which we believe provides evidence of the 'biomechanical transformation of muscle'.

Ankle Joint↗
PubMed2000

Analgesic effects of botulinum toxin A: a randomized, placebo-controlled clinical trial.

Postoperative pain in children with spastic cerebral palsy (CP) is often attributed to muscle spasm and is difficult to manage using opiates and benzodiazepines. Adductor-release surgery to treat or prevent hip dislocation in children with spastic CP is frequently performed and is often accompanied by severe postoperative pain and spasm. A double-blinded, randomized, placebo-controlled clinical trial of 16 patients (mean age 4.7 years) with a mainly spastic type of CP (either diplegic or quadriplegic in distribution) was used to test the hypothesis that a significant proportion of postoperative pain is secondary to muscle spasm and, therefore, might be reduced by a preoperative chemodenervation of the target surgical muscle by intramuscular injection of botulinum toxin A (BTX/A). Compared with the placebo, BTX/A was found to be associated with a reduction in mean pain scores of 74% (P<0.003), a reduction in mean analgesic requirements of approximately 50% (P<0.005), and a reduction in mean length of hospital admission of 33% (P<0.003). It was concluded that an important component of postoperative pain in the patient population is due to muscle spasm and this can be managed effectively by preoperative injection with BTX/A. These findings may have implications for the management of pain secondary to muscle spasm in other clinical settings.

Botulinum Toxins, Type A↗
PubMed1999

Botulinum toxin A in hamstring spasticity.

Hamstring injection of Botulinum toxin A (BtA) may have a role in the conservative management of flexed knee gait in cerebral palsy or in simulating the effect of surgery. Ten children who were likely to require future hamstring lengthening were injected. Short term outcome was assessed by clinical examination and 3-D gait analysis. Mean popliteal angle decreased by 16 degrees and maximum knee extension in stance increased by 8 degrees, the latter relapsing by 12 weeks. Mean pelvic tilt tended to increase suggesting that isolated hamstring weakening be approached with caution. Energy cost of walking was not significantly changed in six of the ten patients. A small increase in knee extension in stance was often associated with patient satisfaction. There are theoretical grounds for expecting an associated increased longitudinal muscle growth after BtA injection.

Botulinum Toxins, Type A↗
PubMed1999

Radial neck fractures in children: a management algorithm.

Fractures of the radial neck in children are relatively rare. The outcome is dependent not only on the injury but also on the method of treatment and the presence of any associated injury. During the past 20 years, two new minimally invasive reduction techniques have been described in an attempt to improve the prognosis, and their results have been reported. A meta-analysis of the recent literature with the focus on outcome, and a management algorithm for this rare fracture are presented.

Accidental Falls↗
PubMed1998

Collagen fibrils forming in developing tendon show an early and abrupt limitation in diameter at the growing tips.

The formation of very long and near-uniform diameter collagen fibrils is fundamental to the assembly of the extracellular matrix of animals. However, how growth in length and diameter is regulated, and how fibrils increase in diameter during development, are poorly understood. The approach in this study was to examine the tips and central shaft regions of fibrils from 12 and 18-day embryonic chick metatarsal tendon using quantitative mass mapping electron microscopy. We found that the fibrils had smoothly tapered C and N-terminal tips, which had linear axial mass distributions and were consequently parabolic in shape. An invariant feature of all tips (N and C) was an abrupt stop in lateral growth leading to a local plateau in diameter. The distance from the end of the fibril to the abrupt stop occurred at multiples of five D-periods (where D=67 nm). This implies that D-periods at the ends of fibrils are not equivalent sites for accretion, and that diameter regulation relies on surface structural features, which repeat every 5D. Mass mapping of entire fibrils at day 12 showed that, on average, the coarseness of the fibril tips was independent of fibril length, consistent with individual fibrils growing at constant tip shape. Comparison of diameters in the plateau (close to the tips) and shaft regions of the fibril showed that fibrils in day 12 tendons grow in length at constant diameter. Analysis of tendons from day 18 embryos showed that the increase in diameter at this stage of development was the result of both increases in the coarseness of the tips and continued lateral accretion of mass onto the central shafts at distances away from the growing tips. Regulated tip growth provides an attractive explanation for how cells are able to synthesise very long fibrils during the organisation of the extracellular matrix.

Animals↗
PubMed1998

Surface located procollagen N-propeptides on dermatosparactic collagen fibrils are not cleaved by procollagen N-proteinase and do not inhibit binding of decorin to the fibril surface.

Dermatosparaxis is a recessive disorder of animals (including man) which is caused by mutations in the gene for the enzyme procollagen N-proteinase and is characterised by extreme skin fragility. Partial loss of enzyme activity results in accumulation of pNcollagen (collagen with N-propeptides) and abnormal collagen fibrils in the fragile skin. How the N-propeptides persist in the tissue and how abnormal fibril morphology results in fragile skin is poorly understood. Using biochemical and quantitative mass mapping electron microscopy we showed that the collagen fibrils in the skin of a dermatosparactic calf contained 57% type I pNcollagen and 43% type I collagen and the fibrils were irregularly arranged in bundles and hieroglyphic in cross-section. Image analysis of the fibril cross-sections suggested that the deviation from circularity of dermatosparactic fibrils was caused by N-propeptides of pNcollagen being located at the fibril surface. Comparison of experimental and theoretical axial mass distributions of the fibrils showed that the N-propeptides were located to the overlap zone of the fibril D-period (where D=67 nm, the characteristic axial periodicity of collagen fibrils). Treatment of the dermatosparactic fibrils with N-proteinase did not remove the N-propeptides from the fibrils, although the N-propeptides were efficiently removed by trypsin and chymotrypsin. However, the N-propeptides were efficiently cleaved by the N-proteinase when the pNcollagen molecules were extracted from the fibrils. These results are consistent with close packing of N-propeptides at the fibril surface which prevented cleavage by the N-proteinase. Long-range axial mass determination along the fibril length showed gross non-uniformity with multiple mass bulges. Of note is the skin fragility in dermatosparaxis, and also the appearance of mass bulges along the fibril long axis symptomatic of the fragile skin of mice which lack decorin. Western blot analysis showed that the dermatosparactic fibrils bound elevated levels of the proteoglycan, compared with normal skin fibrils. The results showed that N-propeptides can distort the morphology of fibrils, that they do not inhibit binding of gap-associated macromolecules (such as decorin) and that the normal mechanical properties of skin are strongly dependent on the close association of near-cylindrical fibrils, thereby enabling maximal fibril-fibril interactions.

Animals↗