Preliminary report into the function of the shoulder using a novel imaging and motion capture approach.

REASONS FOR PERFORMING STUDY: The function of the forelimb is fundamental to understanding both sound and pathological locomotion. The precise movements of the equine shoulder are hidden by layers of skin and muscle and hence the shoulder is normally modelled as a simple pivot during locomotion which assumes that any translational motion is negligible. OBJECTIVES: To record and quantify the sliding motion of the scapula during locomotion, using a novel imaging technique. METHODS: Scapula motion during locomotion in the horse was calculated by tracking the ripple of the shoulder blade's movement under an array of markers placed over the soft tissue. RESULTS: Interstride variability was low. Sliding of up to 80 mm in the plane of progression (cranio-caudal) was observed; however, the limits of motion varied by <5 mm in the gaits examined, despite variations in stride length. Stride length appeared to be increased by scapula rotation in the plane of progression, and this flexion-extension was largest in trot and was not significantly different between walk and canter. This was in agreement with the distance travelled by the trunk whilst the hoof was on the ground. Substantial sliding in a dorsal-ventral direction was shown and varied with the gait used, both in magnitude and timing, possibly providing a shock absorption mechanism. The sliding did not increase as much as would be expected in canter and this coincided with a more lateral positioning of the scapula and increased impact on the ribcage. CONCLUSIONS: It has been assumed that scapula-thoracic sliding increases stride length and hence economically increases locomotor speed. The extra motion of the scapula recorded appeared to absorb shock from forelimb impact and maintain the economy of locomotion, but did not increase with speed and the muscular pretensioning implied could actually impair ventilation.

The role of tendon stiffness in development of equine locomotion with age.

REASONS FOR PERFORMING STUDY: The flexor tendons support the metacarpophalangeal (MCP) and distal interphalangeal (DIP) joints during stance phase and since tendon stiffness and strain changes with age, it is likely that kinematics are also age-dependent. HYPOTHESIS: Maximum MCP and DIP angles decrease in the young horse, plateau in the mature horse and increase towards senescence. METHODS: The distal limbs of 57 walking horses age 3-212 months were filmed and digitised with an automated tracking system. Maximum MCP and DIP angles during stance phase were used to calculate strain in the superficial and deep digital flexor tendons. Horses were divided into 3 age groups; young (3-35 months), mature (36-99 months) and older horses (100-212 months). Pearson's correlation coefficients were calculated to determine the relationship between age and kinematics. RESULTS: Tendon strain decreased in young horses, stayed constant in mature horses and increased in older horses. Joint angles showed significant negative correlation in young horses, with coefficients of -0.88 (MCP) and -0.81 (DIP). In mature horses, correlations were not significant (P = 0.2 for MCP; P = 0.5 for DIP). In older horses, angles showed significant positive correlation, with coefficients of 0.62 (MCP) and 0.48 (DIP). CONCLUSIONS: Joint angles decreased in the young horse as tendon stiffness increases, remained constant in the mature horse where tendon stiffness is constant and increased in older horses as tendons weakens and stiffness decreases. Strain patterns were similar to those found in vitro. POTENTIAL RELEVANCE: Changing tendon stiffness appeared to influence the development and degeneration of gait. This has implications for studying musculoskeletal development, especially for identification of normal and pathological development.

Prediction of the hip joint centre in adults, children, and patients with cerebral palsy based on magnetic resonance imaging.

The location of the hip joint centre (HJC) is required for calculations of hip moments, the location and orientation of the femur, and muscle lengths and lever arms. In clinical gait analysis, the HJC is normally estimated using regression equations based on normative data obtained from adult populations. There is limited relevant anthropometric data available for children, despite the fact that clinical gait analysis is predominantly used for the assessment of children with cerebral palsy. In this study, pelvic MRI scans were taken of eight adults (ages 23-40), 14 healthy children (ages 5-13) and 10 children with spastic diplegic cerebral palsy (ages 6-13). Relevant anatomical landmarks were located in the scans, and the HJC location in pelvic coordinates was found by fitting a sphere to points identified on the femoral head. The predictions of three common regression equations for HJC location were compared to those found directly from MRI. Maximum absolute errors of 31 mm were found in adults, 26 mm in children, and 31 mm in the cerebral palsy group. Results from regression analysis and leave-one-out cross-validation techniques on the MRI data suggested that the best predictors of HJC location were: pelvic depth for the antero-posterior direction; pelvic width and leg length for the supero-inferior direction; and pelvic depth and pelvic width for the medio-lateral direction. For single-variable regression, the exclusion of leg length and pelvic depth from the latter two regression equations is proposed. Regression equations could be generalised across adults, children and the cerebral palsy group.

Successful HSCT using nonradiotherapy-based conditioning regimens and alternative donors in patients with Fanconi anaemia--experience in a single UK centre.

Seven children with Fanconi anaemia (FA) (five female, two male), who had not undergone transformation, received nine haemopoietic stem cell transplantation (HSCT) between 2000 and 2004. Conditioning regimen was: fludarabine 25-30 mg/m2/day for 5 days, antilymphocyte globulin 12.5 mg/kg/day for 3 days and cyclophosphamide 5-7.5 mg/kg/day for 4 days. Radiation was not used. One male patient who had multiple HSCT and one female who was retransplanted, received slightly different conditioning regimens. Four patients received fully matched unrelated umbilical cord blood (UCB), two matched unrelated peripheral blood stem cell (PBSC) grafts, and three haploidentical T-cell-depleted (TCD) PBSC grafts. None of the patients had any significant conditioning-related toxicity or severe infections. All engrafted within 2-3 weeks. One patient rejected her first HSCT after 10 weeks and had a second successful transplant from the same donor. One male patient rejected his TCD haploidentical HSCT from his mother, and subsequently had a successful fully matched unrelated UCB transplant. Rejection rate was 22%. Acute and chronic graft-versus-host disease (GVHD) was seen in 77 and 22% patients. In all, 57% patients developed autoimmune complications, all of which have resolved. All patients are well with stable or full donor chimerism after a median follow-up of 37 months (range 13-54).

The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the medical research council UKALLR1 study.

We have examined the toxicity and overall outcome of the Medical Research Council UKALL R1 protocol for 256 patients with relapsed childhood acute lymphoblastic leukaemia (ALL). Second remission was achieved in over 95% of patients. Two patients died during induction and seven patients died of resistant disease. The overall actuarial event-free survival (EFS) at 5 years for all patients experiencing a first relapse was 46% (95% CI 40-52). Duration of first remission, site of relapse, age at diagnosis and sex emerged as factors of prognostic significance. Five-year EFS was only 7% for children relapsing in the bone marrow within 2 years of diagnosis, but was 77% for those relapsing without bone marrow involvement > 2.5 years from diagnosis. All analyses in this report are by treatment received. For those receiving chemotherapy alone, the 5-year EFS was 48%; for autologous bone marrow transplantation (BMT), the 5-year EFS was 47%; for unrelated donor BMT, it was 52%; and for related donor BMT, the 5-year EFS was 45%. The groups, however, were not comparable with respect to risk factor profile, and therefore direct comparison of EFS is misleading. Adjustment for time to transplant and prognostic factors was used to reduce the effects of biases between treatment groups, but did not suggest benefit for any particular treatment. There was failure of our planned randomization scheme in this trial with only 9% of those eligible being randomized, which highlights the difficulties in running randomized trials especially in patients who have relapsed from a previous trial. The optimal treatment for relapsed ALL therefore remains uncertain. Alternative approaches are clearly needed for those with early bone marrow relapse if outcome is to improve.

Congenital thrombophilia and thrombosis: a study in a single centre.

AIM: To identify the incidence of congenital thrombophilia in a cohort of children presenting with symptomatic thromboembolism. METHOD: A review of children with thromboembolism investigated for thrombophilia over a 12 month period. SUBJECTS: Thirty children with thromboembolic episodes and 16 of their family members. MEASUREMENTS AND DATA COLLECTION: Data were collected on age at diagnosis, underlying diagnosis, site of thrombosis, associated precipitating factors, occurrence of other thromboembolic events, and family history. Investigations included measurement of protein C activity, total and free protein S antigen, antithrombin III activity, screening for factor V Leiden and prothrombin 20210A, urinary homocysteine estimation, and a screen for lupus anticoagulant. RESULTS: Twenty seven of 30 patients had one or more risk factors present at the time of thromboembolism. Eighty three per cent had acquired precipitating factors present, and 43% had underlying congenital thrombophilia. CONCLUSIONS: There was a high incidence of congenital thrombophilia in this group of patients with symptomatic thromboembolism. These findings emphasise the importance of such defects in the pathogenesis of childhood thrombosis, and suggest that full thrombophilia investigations should be performed on all children presenting with thromboembolic disease.

Red cell exchange in sickle cell disease.

Red cell exchange transfusion is frequently of use in the management of patients with sickle cell disease either electively or therapeutically. Modern cell separators allow this procedure to be performed rapidly, effectively and safely. These machines have a number of advantages over manual exchange procedures. The patient remains isovolaemic, there is little loss of plasma or platelets, the procedure is relatively short and in elective circumstances can be performed on an outpatient basis. In this series 66 exchanges were performed on 21 patients with an overall increase in HbA of 70%. The COBE Spectra gave a mean increase in HbA of 77%, with the majority of patients achieving an HbA of > 90% post exchange. Automated redcell exchange was well tolerated by most patients, and adverse effects were limited to symptoms of hypocalcaemia which were easily treated, and to transfusion reactions. Cell separators can therefore be recommended for exchange transfusion in patients with sickle cell disease, who require an increase in HbA levels either prophylactically or therapeutically. They are safe, effective, easy and quick to use.

Wiskott Aldrich syndrome presenting as congenital thrombocytopenia.

The application of molecular biology to haematology has provided the opportunity to revisit previous diagnoses, many of which can now be redefined. This report is on a local family previously diagnosed and published as having X-linked thrombocytopenia in 1974, and shows how the application of molecular screening has confirmed the true diagnosis of Wiskott Aldrich syndrome.

Use of donor lymphocytes in extramedullary relapse of childhood acute lymphoblastic leukaemia following bone marrow transplantation.

Relapse is the commonest cause of treatment failure following bone marrow transplantation for malignant haematological disease. Treatment options are limited and often unsuccessful, with remissions, if achieved, being short-lived. Donor lymphocyte infusions have been used in the treatment of relapsing CML for several years, with good results being obtained. Use of this form of adoptive immunotherapy however, has been much less successful in patients with acute leukaemias, with acute lymphoblastic leukaemia appearing to be particularly resistant. We report the successful use of a donor lymphocyte infusion in a patient with isolated extramedullary relapse of acute lymphoblastic leukaemia post bone marrow transplantation.