Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial.

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients.

Autologous olfactory ensheathing cell transplantation in human spinal cord injury.

Olfactory ensheathing cells transplanted into the injured spinal cord in animals promote regeneration and remyelination of descending motor pathways through the site of injury and the return of motor functions. In a single-blind, Phase I clinical trial, we aimed to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. Participants were three male paraplegics, 18-55 years of age, with stable, complete thoracic injuries 6-32 months previously, with stable spinal column, no implanted prostheses, and no syrinx. Olfactory ensheathing cells were grown and purified in vitro from nasal biopsies and injected into the region of damaged spinal cord. The trial design includes a matched injury group as a control for the assessors, who are blind to treatment status. Assessments, made before transplantation and at regular intervals subsequently, include MRI, medical, neurological and psychosocial assessments, and standard American Spinal Injury Association and Functional Independence Measure assessments. One year after cell implantation, there were no medical, surgical or other complications to indicate that the procedure is unsafe. There is no evidence of spinal cord damage nor of cyst, syrinx or tumour formation. There was no neuropathic pain reported by the participants, no change in psychosocial status and no evidence of deterioration in neurological status. Participants will be followed for 3 years to confirm long-term safety and to compare neurological, functional and psychosocial outcomes with the control group. We conclude transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to one year post-implantation.

Posterior lumbar interbody fusion combined with instrumented postero-lateral fusion: 5-year results in 60 patients.

The technique of posterior lumbar interbody fusion allows decompression of the spinal canal and interbody fusion through one posterior incision. A number of techniques exist to achieve additional posterior stability. The literature reports wide variation in outcomes for these different techniques. We assessed retrospectively the clinical and radiological outcome of posterior lumbar interbody fusion (PLIF) supplemented with an instrumented postero-lateral fusion (IPLF) using a pedicle screw system. Between July 1987 and April 1997, 60 patients underwent PLIF + IPLF. Clinical outcome was measured with physical examination in the outpatient setting and a patient questionnaire (patient satisfaction, analgesic use, return to work, Oswestry Disability Index). Radiological outcome was assessed with serial radiographs. If doubt existed regarding fixation, flexion/extension radiographs and plain tomograms were performed. The mean age was 44 years (range 19-69 years). The average follow-up was 5.3 years (range 1-10 years). Eighty percent of patients returned sufficiently completed questionnaires; 83% of these patients rated their outcome as good or excellent. Fifty percent of patients were able to return to full-time employment. All patients showed radiographic evidence of stable fixation. Four patients sustained a neurological complication, three of which resolved completely. The combination of PLIF with IPLF demonstrates clinical success, a stable circumferential fixation and a low complication rate.

Cervical osteotomy for ankylosing spondylitis: an innovative variation on an existing technique.

Ankylosing spondylitis can produce severe fixed flexion deformity in the cervical spine. This deformity may be so disabling that it interferes with forward vision, chewing, swallowing and skin care under the chin. The only treatment available is an extension osteotomy of the cervical spine. Existing techniques of cervical osteotomy may be associated with risk of neurological injury. We describe a variation on an existing technique, which provides a controlled method of reduction at the osteotomy site, eliminating sagittal translation. The method employs a modular posterior cervical system consisting of lateral mass and thoracic pedicle screws linked to titanium rods. Our technique substitutes the titanium rod with a temporary malleable rod on one side, allowing controlled reduction of the osteotomy as this rod bends and slides through the thoracic clamps. Once reduction is complete definitive contoured rods are inserted to maintain the correction while fusion takes place. This method appears less hazardous by eliminating sagittal translation, and may reduce the risk of neurological injury during surgery. It achieves rigid internal fixation, obviating the need for a halo vest in the postoperative period.

The orthopaedic workforce in Queensland now and into the twenty-first century.

The objectives of this study were to determine the number and distribution of orthopaedic surgeons in Queensland at present and to assess the adequacy of trainee intake for the future. Characteristics of the orthopaedic workforce in Queensland in 1990 were analysed with regard to the total number of orthopaedic surgeons, their regional distribution, their ratio to the population and their age distribution. Similar statistics were derived for the years 1981 and 1986 and trends were examined. By projecting these trends, the number of surgeons likely to be practising in 2001 was estimated. Using projected population figures, the number of orthopaedic surgeons required in 2001 was calculated, assuming an optimum ratio of surgeons to population of one per 25,000. It was found that in 1990 sufficient orthopaedic surgeons were practising in Queensland but that there was some maldistribution. With the increased intake of five new training registrars per year, the number of orthopaedic surgeons in Queensland in 2001 should be appropriate, as long as current trends continue.