Search PubMed⌕ Search

Biomedical subjects

H K Graham

Publications and source records attributed to H K Graham.

At least 19 recordsLinked to original sources
PubMed2006

Spatial disruption and enhanced degradation of collagen with the transition from compensated ventricular hypertrophy to symptomatic congestive heart failure.

The cardiac extracellular matrix (ECM) maintains the structural and mechanical integrity of the myocardium. We determined the alterations in the composition of the ECM coincident with the transition from compensated left ventricular (LV) hypertrophy (LVH) to symptomatic congestive heart failure (CHF) and the mechanisms underlying such changes. Heart failure was induced in ferrets by aortic banding. Myocardial collagen content was assessed by HPLC and histological analysis. Matrix metalloproteinase (MMP) activity and tissue inhibitor of metalloproteinase (TIMP) expression were evaluated using gelatin zymography and Western blotting, respectively. LV free wall thickness increased by 29% in asymptomatic LVH and was associated with a 20% increase in interstitial fibrosis (P < 0.05). CHF was coincident with increased plasma angiotensin II levels (149 +/- 48, 40 +/- 19, and 5.6 +/- 1 pg/ml for CHF, LVH, and sham, respectively; P < 0.01, CHF vs. sham and LVH), ventricular dilatation (LV internal diameter = 15 +/- 0.4 vs. 9 +/- 0.1 mm, P < 0.05), increased active MMP-9 (3.0- and 2.2-fold increase over sham and LVH, respectively, n = 5-10 animals per group, P < 0.01), and reduced myocardial total collagen content (3.5 +/- 0.4, 2.6 +/- 0.3, and 2.2 +/- 0.3% in sham, LVH, and CHF, respectively, P < 0.05). In CHF the distribution of collagen was markedly altered, becoming punctate in nature. No difference in MMP-2 activity, TIMP-1, TIMP-2, TIMP-3, or TIMP-4 expression, or collagen cross-linking was found at any time. The present work demonstrates structural reorganization and loss of collagen from cardiac ECM during the transition to decompensated CHF. The enhanced MMP-9 activity coincident with the transition to CHF provides potential therapeutic opportunities for managing the progression from asymptomatic LVH to symptomatic CHF.

Animals↗
PubMed2006

Management of spasticity in adults: practical application of botulinum toxin.

Spasticity, characterized by increased muscle tone, exaggerated stretch reflexes, and abnormal limb posture, is a common sequel of central nervous system pathology. Historically, medicinal treatments have been of limited efficacy. This review discusses the clinical features of spasticity, the functional and pathological consequences, and treatment. It reviews the most common patterns of spasticity encountered in the upper and lower limbs and focuses on focal treatment of spastic muscles with the three commercially available botulinum toxins Botox, Dysport, and Myobloc/NeuroBloc. It addresses practical details such as muscle selection and identification, drug dilution, and doses.

Anti-Dyskinesia Agents↗
PubMed2006

Lengthening and transfer of hamstrings for a flexion deformity of the knee in children with bilateral cerebral palsy: technique and preliminary results.

Between July 2000 and April 2004, 19 patients with bilateral spastic cerebral palsy who required an assistive device to walk had combined lengthening-transfer of the medial hamstrings as part of multilevel surgery. A standardised physical examination, measurement of the Functional Mobility Scale score and video or instrumented gait analysis were performed pre- and post-operatively. Static parameters (popliteal angle, flexion deformity of the knee) and sagittal knee kinematic parameters (knee flexion at initial contact, minimum knee flexion during stance, mean knee flexion during stance) were recorded. The mean length of follow-up was 25 months (14 to 45). Statistically significant improvements in static and dynamic outcome parameters were found, corresponding to improvements in gait and functional mobility as determined by the Functional Mobility Scale. Mild hyperextension of the knee during gait developed in two patients and was controlled by adjustment of their ankle-foot orthosis. Residual flexion deformity > 10 degrees occurred in both knees of one patient and was treated by anterior distal femoral physeal stapling. Two children also showed an improvement of one level in the Gross Motor Function Classification System.

Adolescent↗
PubMed2006

Correction of severe crouch gait in patients with spastic diplegia with use of multilevel orthopaedic surgery.

BACKGROUND: Severe crouch gait in patients with spastic diplegia causes excessive loading of the patellofemoral joint and may result in anterior knee pain, gait deterioration, and progressive loss of function. Multilevel orthopaedic surgery has been used to correct severe crouch gait, but no cohort studies or long-term results have been reported, to our knowledge. METHODS: In order to be eligible for the present retrospective cohort study, a patient had to have a severe crouch gait, as defined by sagittal plane kinematic data, that had been treated with multilevel orthopaedic surgery as well as a complete clinical, radiographic, and instrumented gait analysis assessment. The surgical intervention consisted of lengthening of contracted muscle-tendon units and correction of osseous deformities, followed by the use of ground-reaction ankle-foot orthoses until stable biomechanical realignment of the lower limbs during gait was achieved. Outcome at one and five years after surgery was determined with use of selected sagittal plane kinematic and kinetic parameters and valid and reliable scales of functional mobility. Knee pain was recorded with use of a Likert scale, and all patients had radiographic examination of the knees. RESULTS: Ten subjects with severe crouch gait and a mean age of 12.0 years at the time of surgery were studied. After surgery, the patients walked in a more extended posture, with increased extension at the hip and knee and reduced dorsiflexion at the ankle. Pelvic tilt increased, and normalized walking speed was unaltered. Knee pain was diminished, and patellar fractures and avulsion injuries healed. Improvements in functional mobility were found, and, at the time of the five-year follow-up, fewer patients required the use of wheelchairs or crutches in the community than had been the case prior to intervention. CONCLUSIONS: Multilevel orthopaedic surgery for older children and adolescents with severe crouch gait is effective for relieving stress on the knee extensor mechanism, reducing knee pain, and improving function and independence.

Adolescent↗
PubMed2004

Enhanced sarcolemmal Ca2+ efflux reduces sarcoplasmic reticulum Ca2+ content and systolic Ca2+ in cardiac hypertrophy.

OBJECTIVE: Recent work has identified reductions in the systolic Ca(2+) transient in cardiac disease states. The aim of the present study was to identify the mechanisms responsible for perturbations of intracellular calcium homeostasis in isolated cardiac myocytes and determine if such changes can quantitatively explain the reduced systolic Ca(2+) transient. METHODS: Left ventricular hypertrophy (LVH) was induced by aortic coarctation in adult ferrets. Changes in intracellular Ca(2+) regulation, sarcolemmal Ca(2+) fluxes and SR function were measured in single left ventricular cardiac myocytes. RESULTS: Cardiac hypertrophy was associated with a 29% increase in action potential duration (APD(90)); a 48% reduction in the amplitude of and 19% slowing in the rate of decay of the systolic Ca(2+) transient; a 20% decrease in SR Ca(2+) content and a 36% increase in inward Na(+)-Ca(2+) exchange current for a given change in [Ca(2+)](i) (all P<0.05). Peak L-type Ca(2+) current density, integrated Ca(2+) influx and SERCA2a protein levels remained unchanged in hypertrophy. By determining the relationship between SR Ca(2+) content and systolic Ca(2+), the reduction in SR Ca(2+) content quantitatively explained the smaller systolic Ca(2+) transient. The reduced SR Ca(2+) content also accounted for a smaller fractional release of Ca(2+) from the SR and lower gain of excitation contraction coupling in cardiac hypertrophy. The increased sarcolemmal-mediated Ca(2+) efflux was sufficient to explain the reduction in SR Ca(2+) content. CONCLUSIONS: The findings indicate that the primary mechanism underlying the smaller systolic Ca(2+) transient amplitude in cardiac hypertrophy is decreased SR Ca(2+) content occurring as a consequence of reduced SR Ca(2+)-ATPase-mediated Ca(2+) uptake and increased sarcolemmal-mediated Ca(2+) efflux from the cell. The increased Na(+)-Ca(2+) exchange-mediated current for a given change in intracellular Ca(2+) concentration provides a mechanism for the development of arrhythmias in the face of a reduced SR Ca(2+) load in cardiac hypertrophy.

Action Potentials↗
PubMed2004

Sagittal gait patterns in spastic diplegia.

Classifications of gait patterns in spastic diplegia have been either qualitative, based on clinical recognition, or quantitative, based on cluster analysis of kinematic data. Qualitative classifications have been much more widely used but concerns have been raised about the validity of classifications, which are not based on quantitative data. We have carried out a cross-sectional study of 187 children with spastic diplegia who attended our gait laboratory and devised a simple classification of sagittal gait patterns based on a combination of pattern recognition and kinematic data. We then studied the evolution of gait patterns in a longitudinal study of 34 children who were followed for more than one year and demonstrated the reliability of our classification.

Adolescent↗
PubMed2004

Supramalleolar derotation osteotomy of the tibia, with T plate fixation. Technique and results in patients with neuromuscular disease.

Torsional deformities of the tibia are common in children, but in the majority both the torsion and the associated disturbance of gait resolve without intervention. There are, however, a significant number of children and adults with neuromuscular disease who present with pathological tibial torsion, which may require surgical correction. We conducted a prospective study in two centres, to investigate the outcome of supramalleolar derotation osteotomy of the tibia, using internal fixation with the AO-ASIF T plate. A range of outcome variables was collected, prospectively, for 57 patients (91 osteotomies), including thigh foot angle, foot progression angle, post-operative complications and serial radiographs. Correction of thigh foot angle and foot progression angle was satisfactory in all patients. Three major complications were recorded; one aseptic nonunion, one fracture through the osteotomy site after removal of the plate and one distal tibial growth arrest. We found that supramalleolar derotation osteotomy of the tibia, with AO-ASIF T plate fixation is an effective method for the correction of torsional deformities of the tibia and the associated disturbances of gait in children and adults with neuromuscular disease, with a 5.3% risk of major complications.

Adolescent↗
PubMed2003

Uptime normative values in children aged 8 to 15 years.

The 'Uptimer' is a custom-made lightweight battery-operated remote activity monitor that records the amount of time an individual spends in the upright position, which is also known as 'uptime'. The aims of this study were to determine levels of uptime over 24 hours and the relation between uptime and a child's age, sex, height, weight, and body mass index (BMI). Uptime was recorded in 529 normally developing children (318 females, 211 males), aged between 8 and 15 years. All children wore an Uptimer continuously for a 24-hour period that included a typical school day. Mean uptime for children in this study was 5.4 hours (SD 1.3; range 1.5 to 10.3 hours), over a 24-hour period. Uptime followed approximately a normal distribution in this population and did not have a linear relation to age, height, weight, nor BMI. Results of this study may be used as a normative database for the evaluation of uptime in children with physical disabilities.

Adolescent↗
PubMed2003

Variability in the measurement of uptime in children: a preliminary study.

OBJECTIVE: To examine variability in 'uptime' (the amount of time spent in the upright position). DESIGN: An observational study. SETTING: The community (i.e., homes and schools in the Melbourne metropolitan area). SUBJECTS: Normal children between 8 and 15 years of age (18 girls and 8 boys). EQUIPMENT: An 'uptimer', a lightweight, battery-operated remote monitor, was used to record uptime. PROCEDURE: Each child in the study wore the uptimer continuously over a 24-hour period, which included a typical day at school, on four separate occasions, one week apart. RESULTS: The variability in repeated measures of uptime in the same child (standard deviation 0.8 hours in 24 hours) was lower than the variability between the children (standard deviation 1.1 hours in 24 hours). We estimate that a single uptime measurement has reliability given by an ICC of 0.65 (95% confidence interval 0.49-0.82), which is calculated by dividing the between-child variability by the total variability (within-child and between-child variability). There were no systematic differences in mean uptime between occasions of measurement. CONCLUSION: As an estimate of the time that a child spends in the upright position, a single 24-hour period of measurement of uptime may vary considerably from one occasion to the next. However, this within-child variability is less than the variability between children. In large-scale field studies a one-off measurement of uptime may be acceptable, but in small rehabilitation studies uptime should be measured on at least three occasions.

Adolescent↗
PubMed2003

Femoral derotation osteotomy in spastic diplegia. Proximal or distal?

We describe the results of a prospective study of 28 children with spastic diplegia and in-toed gait, who had bilateral femoral derotation osteotomies undertaken at either the proximal intertrochanteric or the distal supracondylar level of the femur. Preoperative clinical evaluation and three-dimensional movement analysis determined any additional soft-tissue surgery. Distal osteotomy was faster with significantly lower blood loss than proximal osteotomy. The children in the distal group achieved independent walking earlier than those in the proximal group (6.9 +/- 1.3 v 10.7 +/- 1.7 weeks; p < 0.001). Transverse plane kinematics demonstrated clinically significant improvements in rotation of the hip and the foot progression angle in both groups. Correction of rotation of the hip was from 17 +/- 11 degrees internal to 3 +/- 9.5 degrees external in the proximal group and from 9 +/- 14 degrees internal to 4 +/- 12.4 degrees external in the distal group. Correction of the foot progression angle was from a mean of 10.0 +/- 17.3 degrees internal to 13.0 +/- 11.8 degrees external in the proximal group (p < 0.001) compared with a mean of 7.0 +/- 19.4 degrees internal to 10.0 +/- 12.2 degrees external in the distal group (p < 0.001). Femoral derotation osteotomy at both levels gives comparable excellent correction of rotation of the hip and foot progression angles in children with spastic diplegia.

Adolescent↗
PubMed2002

Duration of antibiotics in children with osteomyelitis and septic arthritis.

OBJECTIVE: To evaluate the outcomes of children with acute osteomyelitis and septic arthritis at a hospital where short-duration antibiotic treatment (< or = 3.5 weeks) was considered routine. METHODOLOGY: We carried out a retrospective chart review, with telephone interviews to follow up and determine long-term outcomes. Patients were selected to be at low risk for complications (illness < or = 14 days, no underlying disease, uncomplicated presentation). RESULTS: Thirty-two children with osteomyelitis (OM), 34 with septic arthritis (SA) and five with OM and SA (OMSA) were included. Blood cultures were positive (mainly Staphylococcus aureus) in 15% of patients who had not had prior antibiotic treatment, and microbiological confirmation (positive blood culture, Gram stain or culture of surgical specimen) was obtained in 36%. The median duration of antibiotic treatment was 5.4, 4.4 and 5.0 weeks for OM, SA and OMSA, respectively. Only 22% of patients received antibiotics for 3.5 weeks or less. Overall, the recurrence rate was 1.4%. At follow-up, only two patients had mild occasional pain at the site of the original infection; all patients had normal function. CONCLUSIONS: Contrary to expectations and local protocols, most patients were treated with conventional long-duration therapy. Patients treated for short courses had good outcomes. The low rate of complications may make randomized controlled equivalence trials unfeasible. Increasing evidence of the efficacy and safety of short-duration treatment (3-3.5 weeks) for acute, uncomplicated OM or SA in children suggests that this could be accepted as the standard treatment. However, this should be evaluated prospectively using a register, with at least 12 months' of follow-up.

Acute Disease↗
PubMed2002

Hip surveillance in children with cerebral palsy. Impact on the surgical management of spastic hip disease.

We studied prospectively the impact of a hip surveillance clinic on the management of spastic hip disease in children with cerebral palsy in a tertiary referral centre. Using a combination of primary clinical and secondary radiological screening we were able to detect spastic hip disease at an early stage in most children and to offer early surgical intervention. The principal effect on surgical practice was that more preventive surgery was carried out at a younger age and at a more appropriate stage of the disease. The need for reconstructive surgery has decreased and that for salvage surgery has been eliminated. Displacement of the hip in children with cerebral palsy meets specific criteria for a screening programme. We recommend that hip surveillance should become part of the routine management of children with cerebral palsy. The hips should be examined radiologically at 18 months of age in all children with bilateral cerebral palsy and at six- to 12-monthly intervals thereafter. A co-ordinated approach by orthopaedic surgeons and physiotherapists may be the key to successful implementation of this screening programme.

Adolescent↗
PubMed2001

STEM/TEM studies of collagen fibril assembly.

Quantitative scanning transmission electron microscopy (STEM), implemented on a conventional transmission electron microscope with STEM-attachment, has been a primary tool in our laboratory for the quantitative analysis of collagen fibril assembly in vivo and in vitro. Using this technique, a precise measurement of mass per unit length can be made at regular intervals along a fibril to generate an axial mass distribution (AMD). This in turn allows the number of collagen molecules to be calculated for every transverse section of the fibril along its entire length. All fibrils show a near-linear AMD in their tip regions. Only fibrils formed in tissue environments, however, show a characteristic abrupt change in mass slope along their tips. It appears that this tip growth characteristic is common to fibrils from evolutionarily diverse systems including vertebrate tendon and the mutable tissues of the echinoderms. Computer models of collagen fibril assembly have now been developed based on interpretation of the STEM data. Two alternative models have so far been generated for fibril growth by accretion; one is based on diffusion limited aggregation (DLA) and the other based on an interface-limited growth mechanism. Inter-fibrillar fusion can also contribute to the growth of fibrils in vertebrate tissues and STEM data indicates the presence of a tight regulation in this process. These models are fundamental for the hypotheses regarding how cells synthesise and spatially organise an extracellular matrix (ECM), rich in collagen fibrils.

Animals↗
PubMed2001

Modified technique for varus derotation osteotomy of the proximal femur in children.

BACKGROUND: The results of a study in which the Richards' intermediate hip screw and the AO (Association for the Study of Internal Fixation (ASIF)) 908 fixed-angle blade plate were compared for use in proximal femoral osteotomy in children have previously been reported. In that study loss of position at the osteotomy site was reported as a specific complication associated with the use of the Richards' intermediate hip screw. METHODS: The authors devised a simple modification of surgical technique using the Richards' intermediate hip screw to enhance the stability of the fixation. In the present article the results of a prospective study of that modified technique are reported and compared with the results of the previous study. RESULTS: During a 2-year period 24 proximal femoral osteotomies were performed on 12 children with cerebral palsy, using the modified technique by two surgeons. Only two of the 12 patients (16%) required postoperative immobilization in a hip spica cast. This represents a significant reduction in the level of spica casting when compared with the previous cohort study (61%). CONCLUSION: A simple modification of surgical technique improves the stability of fixation in proximal femoral osteotomy in children who have cerebral palsy. This resulted in a decreased need for supplementary hip spica casting and may reduce morbidity.

Bone Plates↗
PubMed2001

Botulinum toxin type A management of spasticity in the context of orthopaedic surgery for children with spastic cerebral palsy.

Cerebral palsy is the most common cause of physical disability affecting children in developed countries. Although cerebral palsy is, by definition, a 'static encephalopathy' the associated musculoskeletal pathology is progressive and current definitions are therefore somewhat inadequate. Understanding the stages of the musculoskeletal pathology is fundamental to understanding current management strategies, including spasticity management, strengthening programmes and deformity correction by orthopaedic surgery. In this review, a number of new management strategies are described, in which spasticity management by intramuscular injections of botulinum toxin type A and deformity correction, by orthopaedic surgery, are combined.

Animals↗