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Biomedical subjects

B J Freeman

Publications and source records attributed to B J Freeman.

At least 19 recordsLinked to original sources
PubMed2000

Mechanical initiation of intervertebral disc degeneration.

STUDY DESIGN: Mechanical testing of cadaveric lumbar motion segments. OBJECTIVES: To test the hypothesis that minor damage to a vertebral body can lead to progressive disruption of the adjacent intervertebral disc. SUMMARY OF BACKGROUND DATA: Disc degeneration involves gross structural disruption as well as cell-mediated changes in matrix composition, but there is little evidence concerning which comes first. Comparatively minor damage to a vertebral body is known to decompress the adjacent discs, and this may adversely affect both structure and cell function in the disc. METHODS: In this study, 38 cadaveric lumbar motion segments (mean age, 51 years) were subjected to complex mechanical loading to simulate typical activities in vivo while the distribution of compressive stress in the disc matrix was measured using a pressure transducer mounted in a needle 1.3 mm in diameter. "Stress profiles" were repeated after a controlled compressive overload injury had reduced motion segment height by approximately 1%. Moderate repetitive loading, appropriate for the simulation of light manual labor, then was applied to the damaged specimens for approximately 4 hours, and stress profilometry was repeated a third time. Discs then were sectioned and photographed. RESULTS: Endplate damage reduced pressure in the adjacent nucleus pulposus by 25% +/- 27% and generated peaks of compressive stress in the anulus, usually posteriorly to the nucleus. Discs 50 to 70 years of age were affected the most. Repetitive loading further decompressed the nucleus and intensified stress concentrations in the anulus, especially in simulated lordotic postures. Sagittal plane sections of 15 of the discs showed an inwardly collapsing anulus in 9 discs, extreme outward bulging of the anulus in 11 discs, and complete radial fissures in 2 discs, 1 of which allowed posterior migration of nucleus pulposus. Comparisons with the results from tissue culture experiments indicated that the observed changes in matrix compressive stress would inhibit disc cell metabolism throughout the disc, and could lead to progressive deterioration of the matrix. CONCLUSIONS: Minor damage to a vertebral body endplate leads to progressive structural changes in the adjacent intervertebral discs.

Adult↗
PubMed2000

Effects of backward bending on lumbar intervertebral discs. Relevance to physical therapy treatments for low back pain.

STUDY DESIGN: Mechanical testing of cadaveric motion segments. OBJECTIVES: To test the hypothesis that backward bending of the lumbar spine can reduce compressive stresses within lumbar intervertebral discs. SUMMARY OF BACKGROUND DATA: Lumbar extension affects the distribution of compressive stress inside normal cadaveric discs, but little is known about its effect on mechanically disrupted and degenerated discs. METHODS: Nineteen lumbar motion segments (mean donor age, 48 years) were subjected to complex mechanical loading to simulate the following postures: moderate lumbar flexion, 2 degrees of extension, 4 degrees of extension, and the neutral position (no bending). The distribution of compressive stress within the disc matrix was measured in each posture by pulling a miniature pressure transducer along the midsagittal diameter of the disc. Stress profiles were repeated after a mechanical treatment that was intended to simulate severe disc degeneration in vivo. RESULTS: The "degeneration" treatment reduced pressure in the nucleus pulposus and generated stress concentrations within the anulus, in a manner similar to that found in severely degenerated discs in vivo. When all discs were considered together, 2 degrees of extension increased the maximum compressive stress within the posterior anulus by an average of 16%, compared with the neutral posture. The size of localized stress peaks within the posterior anulus was increased by 43% (P = 0.02). In 4 degrees of extension, changes observed between 0 degree and 2 degrees were usually exaggerated. In contrast, moderate flexion tended to equalize the distribution of compressive stress. In 7 of the 19 discs, 2 degrees of lumbar extension decreased maximum compressive stress in the posterior anulus relative to the neutral posture by up to 40%. Linear regression showed that lumbar extension tended to reduce stresses in the posterior anulus in those discs that exhibited the lowest compressive stresses in the neutral posture (P = 0.003; R2 = 41%). CONCLUSIONS: The posterior anulus can be stress shielded by the neural arch in extended postures, but the effect is variable. This may explain why extension exercises can relieve low back pain in some patients.

Adult↗
PubMed2000

Anterior thoracoscopic surgery followed by posterior instrumentation and fusion in spinal deformity.

Many authors believe thoracoscopic surgery is associated with a lower level of morbidity compared to thoracotomy, for anterior release or growth arrest in spinal deformity. Others believe that anterior release achieved thoracoscopically is not as effective as that achieved with the open procedure. We evaluated the clinical results, radiological correction and morbidity following anterior thoracoscopic surgery followed by posterior instrumentation and fusion, to see whether there is any evidence for either of these beliefs. Twenty-nine patients undergoing thoracoscopic anterior release or growth arrest followed by posterior fusion and instrumentation were evaluated from a clinical and radiological viewpoint. The mean follow-up was 2 years (range 1-4 years). The average age was 16 years (range 5-26 years). The following diagnoses were present: idiopathic scoliosis (n = 17), neuromuscular scoliosis (n = 2), congenital scoliosis (n = 1), thoracic hyperkyphosis (n = 9). All patients were satisfied with cosmesis following surgery. Twenty scoliosis patients had a mean preoperative Cobb angle of 65.1 degrees (range 42 degrees-94 degrees) for the major curve, with an average flexibility of 34.5% (42.7 degrees). Post operative correction to 31.5 degrees (50.9%) and 34.4 degrees (47.1%) at maximal follow-up was noted. For nine patients with thoracic hyperkyphosis, the Cobb angle averaged 81 degrees (range 65 degrees-96 degrees), with hyperextension films showing an average correction to 65 degrees. Postoperative correction to an average of 58.6 degrees was maintained at 59.5 degrees at maximal follow-up. The average number of released levels was 5.1 (range 3-7) and the average duration of the thoracoscopic procedure was 188 min (range 120-280 min). There was a decrease in this length of time as the series progressed. No neurologic or vascular complications occurred. Postoperative complications included four recurrent pneumothoraces, one surgical emphysema, and one respiratory infection. Thoracoscopic anterior surgery appears a safe and effective technique for the treatment of paediatric and adolescent spinal deformity. A randomised controlled trial, comparing open with thoracoscopic methods, is required.

Adolescent↗
PubMed2000

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.

Adult↗
PubMed2000

Assessment in multisite randomized clinical trials of patients with autistic disorder: the Autism RUPP Network. Research Units on Pediatric Psychopharmacology.

Assessment of autistic disorder (autism) symptoms, primary and secondary, poses more challenging problems than ordinarily found in multisite randomized clinical trial (RCT) assessments. For example, subjects may be uncommunicative and extremely heterogeneous in problem presentation, and current pharmacological treatments are not likely to alter most core features of autism. The Autism Research Units on Pediatric Psychopharmacology (RUPP Autism Network) resolved some of these problems during the design of a risperidone RCT in children/adolescents. The inappropriateness of the usual anchors for a Clinical Global Impression of Severity (CGI-S) was resolved by defining uncomplicated autism without secondary symptoms as a CGI-S of 3, mildly ill. The communication problems, compromising use of the patient as an informant, were addressed by several strategies, including careful questioning of care providers, rating scales, laboratory tests, and physical exams. The broad subject heterogeneity requires outcome measures sensitive to individual change over a wide spectrum of treatment response and side effects. The problems of neuropsychologically testing nonverbal, lower functioning, sometimes noncompliant subjects requires careful instrument selection/adaptation and flexible administration techniques. The problems of assessing low-end IQs, neglected by most standardized test developers, was resolved by an algorithm of test hierarchy. Scarcity of other autism-adapted cognitive and neuropsychological tests and lack of standardization required development of a new, specially adapted battery. Reliability on the Autism Diagnostic Interview (currently the most valid diagnostic instrument) and other clinician instruments required extensive cross-site training (in-person, videotape, and teleconference sessions). Definition of a treatment responder required focus on individually relevant target symptoms, synthesis of possible modest improvements in many domains, and acceptance of attainable though imperfect goals. The assessment strategy developed is implemented in a RCT of risperidone (McDougle et al., 2000) for which the design and other methodological challenges are described elsewhere (Scahill et al., 2000). Some of these problems and solutions are partially shared with RCTs of other treatments and other disorders.

Antipsychotic Agents↗
PubMed2000

Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. Background and rationale for an initial controlled study of risperidone.

This article has reviewed the background and rationale for the choice of risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on 5-HT and DA neuronal systems, both of which have been implicated in the pathophysiology of autism. Unlike the typical antipsychotics, haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, risperidone's 5-HT2A/DA D2 ratio of receptor blockade appears to produce a lower risk of acute and chronic extrapyramidal side effects, as well as enhanced efficacy for the "negative" symptoms of autism. Indirect clinical and preclinical evidence supports the use of risperidone to treat impaired social behavior, interfering repetitive phenomena, and aggression, targets of pharmacotherapy for many patients with autism. Numerous published open-label trials in children and adolescents with autism and related PDDs and one double-blind, placebo-controlled study in adults suggest that risperidone has promise for the treatment of children and adolescents with autism. Because most of these studies have been short-term, open-label trials in small samples, however, a large-scale controlled study of risperidone in children and adolescents with autism is needed to confirm these results. Finally, because it is likely that children who demonstrate short-term benefit from risperidone will remain on the medication indefinitely, the longer-term effectiveness and safety of risperidone in this population also needs to be determined. The design of this study and the assessments used are described separately.

Adolescent↗
PubMed1999

Behavior and therapeutic efficacy of beta-glucuronidase-positive mononuclear phagocytes in a murine model of mucopolysaccharidosis type VII.

Bone marrow transplantation (BMT) is relatively effective for the treatment of lysosomal storage diseases. To better understand the contribution of specific hematopoietic lineages to the efficacy of BMT, we transplanted beta-glucuronidase-positive mononuclear phagocytes derived from either the peritoneum or from bone marrow in vitro into syngeneic recipients with mucopolysaccharidosis type VII (MPS VII). Cell surface marking studies indicate that the bone marrow-derived cells are less mature than the peritoneal macrophages. However, both cell types retain the ability to home to tissues rich in cells of the reticuloendothelial system after intravenous injection into MPS VII mice. The half-life of both types of donor macrophages is approximately 7 days, and some cells persist for at least 30 days. In several tissues, therapeutic levels of beta-glucuronidase are present, and histopathologic analysis demonstrates that lysosomal storage is dramatically reduced in the liver and spleen. Macrophages intravenously injected into newborn MPS VII mice localize to the same tissues as adult mice but are also observed in the meninges and parenchyma of the brain. These data suggest that macrophages play a significant role in the therapeutic efficacy of BMT for lysosomal storage diseases and may have implications for treatments such as gene therapy.

Animals↗
PubMed1999

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.

Adult↗
PubMed1999

Vineland Adaptive Behavior Scale scores as a function of age and initial IQ in 210 autistic children.

Human growth modeling statistics were utilized to examine how Vineland Adaptive Behavior Scale (VABS) scores changed in individuals with autistic disorder as a function of both age and initial IQ. Results revealed that subjects improved with age in all domains. The rate of growth in Communication and Daily Living Skills was related to initial IQ while rate of growth in Social Skills was not. Results should provide hope for parents and further support for the importance of functional social-communication skills in the treatment of autism.

Activities of Daily Living↗
PubMed1998

Blood loss in sequential bilateral total knee arthroplasty.

This study was devised to determine whether blood loss for sequential bilateral knee arthroplasties was the same for the first and second knees. Twenty-eight patients who underwent this procedure were studied along with a control group of patients who underwent unilateral knee arthroplasties. Blood loss was greater in the second knee by a mean of 323 mL (P < .05). The control group and the first knee showed no significant difference in blood loss. Analysis of clotting studies showed a prolongation of prothrombin time, activated partial thromboplastin time, and thrombin time after release of the first tourniquet. Possible reasons for this greater blood loss are discussed.

Aged↗
PubMed1998

The extended lateral approach to the hindfoot. Anatomical basis and surgical implications.

We have recently described an extended lateral approach to the hindfoot for the operative treatment of displaced intra-articular fractures of the calcaneum. It has the advantage of avoiding damage to the sural nerve and preserving blood supply to allow prompt healing. We dissected 15 formalin-preserved cadavers, taking photographs to show the structures of the posterolateral aspect of the hindfoot and ankle. We describe a superficial and a deep triangle: the deep triangle contains a constant posterior peroneal artery which supplies the skin of the posterolateral heel. An approach designed to expose the sural nerve will divide this important artery and cause ischaemia of the posterior skin. The extended lateral approach elevates the sural nerve in a thick flap and preserves the blood supply of the skin. We have reviewed 150 consecutive patients after the use of this approach to study the indications for operation, the quality of wound healing, any damage to the sural nerve and other complications. We recommend the careful use of this approach. Our understanding of its anatomical basis has allowed us to widen the indications for its use.

Cadaver↗
PubMed1997

Guidelines for evaluating intervention programs for children with autism.

It is now well recognized that early diagnosis and intervention improves the prognosis for children with autism. It is crucial that professionals be aware and sensitive to the needs of autistic persons and their families. We must never lose sight of the long-term goal of treatment and must not become so infatuated with any one treatment that we fail to provide the education parents need. It is incumbent upon us, as professionals, to educate parents and help them evaluate the myriad of information with which they are bombarded. In this article a framework for thinking about autism and principles of evaluation are reviewed. Components of appropriate early intervention programs are then described and guidelines for evaluating alternative treatments are provided.

Autistic Disorder↗