Brain injury-related heterotopic bone formation: treatment strategy and results.

OBJECTIVES: Heterotopic bone formation (HO) is a phenomenon occurring in some neurologically injured patients that can adversely affect their rehabilitation. The current study aimed at evaluating functional results and recurrence rates after recurrence of such lesions. DESIGN: The results of 12 excisions of HO in 9 patients were assessed. A single-dose of 750 cGy delivered 24 hr postoperatively was used in seven of nine patients. RESULTS: One year postintervention, the arc of motion averaged 92.5 degrees in the hips, 66.6 in the knees, and 60 degrees in the elbow. Despite increased uptake on bone scans in all patients, recurrence did not occur in any patient. Ambulation levels improved in four of eight hips. Ease of personal hygiene was improved in all patients, although some patients still require assistance. CONCLUSIONS: Excision of symptomatic HO is recommended if limitation of joint motion seems to hinder the patient's rehabilitation. Some motor control is desirable to achieve significant improvement in the patient's quality of life. Increased uptake on bone scans is not a contraindication to surgical excision of HO, provided the neurologic status is stabilized.

Transient bone oedema of the tibia mimicking a tumorous process.

The authors describe a distinct clinical entity consisting of bony tenderness, increased isotope uptake along the metaphyses and/or diaphyses and magnetic resonance changes simulating a bone marrow-replacing lesion. Bone biopsies indicate the presence of bone marrow fibrosis and some new bone formation. Nine such cases were prospectively evaluated according to a standardized protocol including clinical examination, x-rays, bone scan and CT scan as well as MRI scans including contrast medium injection. All patients presented with tibial tenderness. In one case the bone was noticeably thicker as compared to the other side. The ages ranged from 6 years to 64 years and 6 of the patients were female. Xrays were normal in 6/9 patients; the rest had minimal periosteal reaction, and mild intramedullary sclerosis. Uniform imaging findings were longitudinal increased uptake along the metadiaphysis of the tibia on bone scans, and increased bone marrow density on CAT scans without a fracture line. A magnetic resonance study indicated bone marrow replacement as demonstrated by an area of low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Some enhancement of signal was observed following gadolinium injection. This clinical entity, which the authors attribute to be a medullary stress reaction, is self-limited, and pain resolves within 3 months. However the radiographic changes appear to be permanent. A biopsy is not required provided no cortical penetration or soft tissue mass is demonstrated by MRI scan.

Good results of circumferential spine fusion in smokers, using autograft and allograft.

We have examined the rates of anterior interbody fusion of lumbar spine segments following fusion with a fresh frozen femoral head allograft in 25 heavy smoking patients. They were all stabilized both anteriorly and posteriorly. The indications for surgery were: degenerative disc disease, degenerative spondylolisthesis and nonunion following previous posterolateral fusion of lumbar spine segments. Only patients who had fusion of one or two lumbar segments were included. They all were stabilized posteriorly with pedicle screws and autogenic iliac bone graft. The fusion was assessed at least one year after surgery according to plan X-rays as "Solid", "Questionable" or "Failure". One patient was found at follow up not fused, in another one the fusion was "questionable" and all the other 23 patients had an anterior solid fusion. Clinically, 84% of the patients had the same or improved work status as before surgery and 68% acknowledged that they were satisfied with the surgical results. No major complications were recorded and the average length of hospitalization was 10.3 days.

Modulation of CD44 in acute lymphoblastic leukemia identifies functional and phenotypic differences of human B cell precursors.

CD44 expression and other B cell markers were analyzed in 38 samples of B cell precursors (BCP) from patients with acute lymphoblastic leukemia (ALL). According to the expression of CD10 and CD44, we established the following five stages of BCP-ALL phenotypes that may represent different forms of interaction between BCP-ALL and bone marrow-adherent cells: stage 1, CD19+, CD44bright, CD10-; stage 2, CD19+, CD44bright, CD10dim/bright; stage 3, CD19+, CD44dim, CD10bright, CD20-/+; stage 4, CD19+, CD44dim, CD10dim, CD20+; and stage 5, CD19+, CD44bright, CD10-, CD20+. Next, we analyzed the modulation of CD44 according to the expression of the different BCP-ALL phenotypes by incubating the samples under different culture conditions, including addition of stromal cells and interleukin (IL)-7. In culture, the samples in stages 1 and 2 maintained high expression of CD44 and re-expressed this molecule when cultured after trypsin treatment, indicating ongoing synthesis of CD44. Similarly, the stage 3 samples cultured in the presence of stromal cells, IL-7, or both also upregulated CD44 expression in culture. In contrast, the low expression of CD44 on the presumably more mature stage 4 samples was not modified by the addition of stromal cells or IL-7 or when cultured after trypsin treatment, suggesting that those cells had arrested CD44 synthesis. We concluded that down-modulation of CD44 occurred in association with differentiation to phenotype stages 3 and 4 and we hypothesized that this down-modulation might be associated with the exit of BCP-ALL from the bone marrow.

Intra-articular hyaluronan injections for the treatment of osteoarthritis of the knee: a randomized, double blind, placebo controlled study.

OBJECTIVE: Hyaluronic acid (HA) polymers have been found to be useful as viscosupplements for the treatment of osteoarthritis (OA) in a number of clinical studies. It appears that HA with high molecular weights (HMW) are more effective than low molecular weight HA polymers. METHODS: A single blind, initial randomized study was conducted involving two randomly selected patient groups, which received injections of either placebo or BioHy, a highly purified HMW HA produced by bacterial fermentation. HA was administered intra-articularly and several functional tests, including pain level, stiffness, and physical function, were used to score efficacy at various intervals throughout the study. RESULTS AND CONCLUSION: The results through week 20 indicate that BioHy provides relief for osteoarthritic patients without causing adverse effects, although the study was not sufficiently powered to obtain statistically significant differences between the treatment groups.

99mTc-MIBI scintigraphy in musculoskeletal tumors.

UNLABELLED: The aim of this study was to assess the value of 99mTc-hexakis2-methoxyisobutylisonitrile (MIBI) scintigraphy in patients with clinical and radiologic features of primary or metastatic musculoskeletal tumors. METHODS: The scintigraphic findings for 84 patients were compared with the surgical and histologic findings. Each patient underwent three-phase bone scanning with 99mTc-methylene diphosphonate (MDP) and dynamic and static MIBI scintigraphy. The MIBI scans were evaluated by visual and quantitative analysis. The count ratio of the lesion to the adjacent or contralateral normal area (L/N) was calculated from the region of interest drawn on the MIBI scan. The Mann-Whitney test was used to determine the differences between the uptake ratios of malignant and benign lesions. RESULTS: Although increased MDP uptake was not specific for bone malignancy, a significant difference was found between benign tumors (L/N = 1.22 +/- 0.43) and malignant tumors (L/N = 2.25 +/- 1.03) on MIBI scans. Sensitivity and specificity were 81% and 87%, respectively. Forty-six of 53 proven benign lesions did not show significant MIBI uptake. The negative predictive value was 88%. In all seven sites of pathologic fracture, significant uptake was seen. However, three malignant lesions were not detected by MIBI scintigraphy, whereas seven benign lesions showed false-positive results. CONCLUSION: The major diagnostic worth of MIBI scintigraphy is its high negative predictive value. Although not capable of replacing tissue biopsy as a definitive diagnostic modality for musculoskeletal neoplasms, MIBI scintigraphy does appear to have a role in better preoperative assessment and in distinguishing between pathologic and simple fractures.

Two freezing cycles ensure interface sterilization by cryosurgery during bone tumor resection.

Cryosurgery utilizing an argon-based system allows bone-tumor interface sterilization, while avoiding the risks of conventional cryosurgery. This study was conducted in order to evaluate the number of freezing cycles required for interface sterilization in cases of aggressive human bone tumors. Sixteen tumors were included (six chondrosarcomas, eight metastatic carcinomas, and two giant cell tumors). All occurred within long bones. In all cases a standardized marginal resection was performed. Following thorough curettage, we sampled five different locations within the tumor interface by a cylindrical hollow trephine. The interface viability was assessed using the XTT method. Quantitative histological evaluation was based on the percentage of live cells divided by total lacunae number in five random medium-power fields. One freezing cycle (5 min, -40 degrees C) reduced tumor viability to approximately 5% of prefreezing. However, there were still live specimens. Two or three freezing cycles led to complete interface sterilization. The difference between a single freezing cycle and two freezing cycles was significant (ANOVA, F = 130, P < 0.01). The difference between two freezing cycles and three freezing cycles was not significant (ANOVA, F = 0.14, P < 0.6). The results of the XTT method for the assessment of interface viability correlated well with histological evaluation of the percentage of viable cells (r = 0.89), as well as with cell culture results of frozen vs. prefreezing tumor samples. In conclusion, two freezing cycles are adequate to achieve tumor-bone interface sterilization in aggressive human bone tumors.

[Autologous chondrocyte transplantation--from science fiction to routine clinical practice].

Adult articular cartilage lacks the capacity for self-repair. The limiting factor appears to be the inability of chondrocytes to proliferate while embedded in the extracellular matrix typical of hyaline cartilage. Cartilage defects larger than 1 cm2 change articular biomechanics and lead to eventual osteoarthritis and joint destruction. During the past decade, several competing techniques have evolved to stimulate articular cartilage repair. Small lesions can be successfully treated by either micro-fracture or osteochondral cylinder grafting. The latter technique allows immediate weight bearing but leads to damage of previously uninvolved areas of articular cartilage, which limits its application to lesions of less than 2 cm2. When the damaged area is more extensive, grafting of autologous chondrocytes should be considered. First a diagnostic arthroscopy is performed to assess the damaged area and a small cartilage biopsy is taken. 6 weeks later, arthrotomy and chondrocyte transplantation are performed. In the interval, the antologous chondrocytes have expanded by 2 to 3 orders of magnitude. Our experience to date includes 10 cases with follow-up of 6 months to 5 years. Preoperative complaints of crepitation and locking disappear. There is functional improvement and pain reduction of approximately 50%. This procedure, currently limited to patients under 55 years of age with limited damage to an articular surface, for the first time allows reconstruction of damaged articular areas without resorting to allografts.

[GAG for osteoarthritis of the knee--a prospective study].

Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans due to imbalance between synthesis and degradation. The availability of glucosamine, an intermediate in mucopolysaccharide synthesis, can be rate-limiting for proteoglycan production in cartilage tissue culture. 57 patients suffering from osteoarthritis of the knee were randomized into a group treated for 4 weeks with daily i.v. glucosamine sulfate (GS) together with 800 mg chondroitin sulfate, and a placebo group. Knee pain at rest, on movement and on palpation, as well as range of knee motion were then recorded. In the GS group, there was significant reduction of clinical symptoms (p < 0.01), but no significant reduction in the placebo group. Physicians' assessment of tenderness and range of motion were significantly in favor of the GS group (p < 0.01). In those treated with glycosamine there were no adverse reactions and no changes in laboratory blood tests. We conclude that GS can be considered the drug of choice for prolonged treatment of osteoarthritis.

Autologous chondrocyte transplantation for reconstruction of isolated joint defects: the Assaf Harofeh experience.

BACKGROUND: Articular cartilage is incapable of undergoing self-repair since chondrocytes lose their mitotic ability as early as the first year of life. Defects in articular cartilage, especially in weight-bearing joints, will predictably deteriorate toward osteoarthritis. No method has been found to prevent this deterioration. Drilling of the subchondral bone can lead to fibrocartilage formation and temporary repair that slowly degrades. Animal experiments indicate that introducing proliferating chondrocytes such as cultured articular chondrocytes can reliably reconstruct joint defects. OBJECTIVES: To describe our clinical experience in culturing and transplanting autologous chondrocytes. METHODS: Biopsies were obtained from 10 patients, aged 18-45, undergoing a routine arthroscopy in which a cartilage defect was identified with indications for cartilage transplantation. The biopsies were further processed to establish chondrocyte cultures. ACT was performed in 8 of the 10 patients because of persistent symptoms for at least 2 months post-arthroscopy. All patients (6 men and 2 women) had a grade IV cartilage defect in the medial or lateral femoral condyle, and three had a defect in the trochlear region as well. Biopsies were removed from the lateral rim of the superior aspect of the femur, and cells were cultured in a clean room. Following a 2 order of magnitude expansion, cells were implanted under a periosteal flap. RESULTS: The eight patients implanted with autologous cells were followed for 6 months to 5 years (average 1 year). Complaints of giving-way, effusion and joint locking resolved in all patients, and pain as assessed by the visual analogue score was reduced by an average of 50%. Follow-up magnetic resonance imaging studies in all patients revealed that the defects were filled with tissue having similar signal characteristics to cartilage. CONCLUSIONS: Chondrocyte implantation is a procedure capable of restoring normal articular cartilage in cases with isolated joint defects. Pain can be predictably reduced, while joint locking and effusion are eliminated. The effect on osteoarthritis progression in humans has not yet been elucidated.

Eccentric compression of the spinal canal causing dominantly contralateral-side symptoms.

In this retrospective study, five patients are described in whom the dural sac at the thoracic and lumbar spine was compressed by a herniated disk or stenosis, located eccentrically in the spinal canal. In all of them, the symptoms or neurologic findings were dominantly in the limb contralateral to the side of compression. All five patients were operated on and the compressing disk or lamina was removed, resulting in immediate improvement of symptoms. In only one of the patients was the compression at the common level of L4-L5. In the remaining four patients, compression was at the low thoracic or upper lumbar spine. With the exception of one patient, the area of canal compression was greater than 50%.

Mesenchymal cells and growth factors in bunions.

Bunion formation in adults is an example of bone growth that occurs after physis closure. Bone is laid down secondary to mechanical irritation caused by foot deformity. It is a mechanism of ectopic bone formation unrelated to physeal growth. In this article, bone formation is analyzed using immunohistochemical and cell culture techniques. Using markers specific for mesenchymal cells (collagen type IIa and fibroblast growth factor receptor 3), a cell population is defined in the soft tissues that overlie the bunion and is isolated from explant cultures. The cells do not produce bone matrix in culture, and they do not express osteoblast-related antigens. Stimulation of the cells by fibroblast growth factor (FGF) 2 leads to rapid cell proliferation and phenotype change. The cells start to form humps and at the same time express alkaline phosphatase and collagen type I. Expression of collagen type IIa and fibroblast growth factor receptor 3 ceases. These series of experiments indicate that a specific population of mesenchymal cells occurs in the soft tissues that overlie the bunion. This population is capable of bone formation when stimulated by FGF, a common mediator of inflammatory processes. Thus, FGF stimulation of mesenchymal cells in soft tissues that overlie the head of the first metatarsal is a potential link between the biomechanical forces that cause hallux valgus and bunion formation.

Hartshill spinal fixation in vertebral metastasis.

Spinal fusion by Hartshill rectangle frame was used in 10 patients with spinal cord compression secondary to vertebral metastasis in the thoracic and lumbar spine, occupying mainly the posterior elements. All patients presented with pain, bone collapse, and neurologic deficit. The procedure is built on a system of sublaminar wires passed under two to three lamina above and below the decompressed area and tightened to a prebent metal frame. This procedure was relatively simple, and the immediate stabilization achieved in our patients was good. All patients experienced immediate pain relief. While only two patients were able to walk before surgery, seven were able to do so at follow-up. During a follow-up period of at least 2 years in two patients, or until death in the other eight patients, one patient had a broken wire that did not affect the correction achieved at surgery. Partial loss of correction in the sagittal plane was found in two patients who had metastasis in the lumbar spine and in another patient who had metastasis in the ninth thoracic vertebra.

[Epidural spinal abscess].

A 42-year-old man was admitted for fever and severe low back pain radiating to both legs. On MRI, an epidural spinal abscess from S1 to D10 was seen. Treatment included laminectomy, drainage of the abscess and antibiotics. Recovery was complete without neurological damage. Increased awareness of this disease may lead to diagnosis and treatment.

[Spinal and extra-spinal tumors mimicking discal herniation].

Low back pain radiating to a limb is usually caused by lumbar disc herniation. Tumors of the spinal cord or near the sciatic or femoral plexus can cause neural compression and clinical signs similar to those of disc herniation. Such tumors are usually misdiagnosed as discal herniation and appropriate treatment is delayed. We present 4 men who had tumors causing low back pain radiating to the leg: a 70-year-old with metastatic squamous cell carcinoma of the lung, a 20-year-old with aneurysmal bone cyst of the vertebral column, a 52-year-old with retroperitoneal sarcoma and a 32-year-old who also had retroperitoneal sarcoma. Diagnosis and treatment were delayed because the clinical symptoms were ascribed to lumbar disc herniation. The latter 2 patients had CT-scans showing lumbar disc herniation, but similar findings are common among asymptomatic individuals. The differential diagnosis of low back pain radiating to the leg should include tumor when there is a history of cancer, pain not relieved by conservative treatment nor by lying down, pain is increased at night, pain accompanied by weight loss, and when physical examination demonstrates injury to more than 1 nerve root. In these circumstances work-up should include EMG, radioisotope scan and CT of the pelvis.

Inflammatory reactions associated with a calcium sulfate bone substitute.

OBJECTIVES: Loss of bone substance is a major source of disability that often requires grafting. Recently developed synthetic bone grafts have generated a lot of enthusiasm due to the lack of immunological reactions and infectious disease transmission risk. The current work describes some peculiar complications related to the use of calcium sulfate granules. METHODS: 15 implantations of calcium sulfate pellets Osteoset (Wright Medical Technology) were performed following resection of bone tumors at our service during 1999. Clinical or computerized tomography scans were available in all patients. RESULTS: 3 cases were encountered in which a severe inflammatory reaction developed. In one case serous drainage and an allergic reaction obligated graft removal. In another case, inflammation resolved two months following implantation. In the last case, wound breakdown occurred. CONCLUSIONS: A sterile inflammatory response has previously hindered the use of absorbable poly-lactic and poly-glycolic acid rods. Apparently due to rapid graft resorption, the resulting calcium-rich fluid incites inflammation. The single case of an allergic reaction is interesting. An allergy to plaster of Paris is rare and related to minor additives. These were not present in the bone substitute used. Inflammatory complications should be considered when assessing the risk-benefit ratio of using different types of bone replacement materials, and comparing allogeneic grafts to synthetic ones.

Changes in proteoglycans of intervertebral disc in diabetic patients. A possible cause of increased back pain.

STUDY DESIGN: Characterization of the analytic profile of proteoglycans in the intervertebral discs at L4-L5 of nondiabetic (n = 5) and diabetic (n = 5) age-matched subjects. The discs used were discarded material from operations. OBJECTIVES: To clarify the reason for the higher risk of disc prolapse in diabetic patients. SUMMARY OF BACKGROUND DATA: The pathogenesis of diabetes results from a combination of neurologic dysfunctions and a yet undefined metabolic failure, which leads to an abnormal proteoglycan profile. METHODS: The following methods were used to determine the proteoglycan profile: the measurement of 35S-sulfate uptake per gram wet tissue into sulfated glycosaminoglycan using fresh tissue explants; extraction of proteoglycans by 4 M guanidinium chloride containing protease inhibitors, with further purification by ultracentrifugation on cesium chloride buoyant density gradient under dissociative conditions; total uronic acid and protein contents in the various gradient fractions; assessing the length of sugar side chains of isolated 35Sulfate-glycosaminoglycan molecules by separation of the glycosaminoglycan molecules on a Sepharose 6B-CL column; and paper chromatography of the final digest products of glycosaminoglycan molecules obtained by chondroitinase ABC, a glycosaminoglycan-degrading enzyme. RESULTS: The findings show that discs from normal nondiabetic subjects have 15 times the rate of 35Sulfate incorporation into glycosaminoglycan molecules than do discs of diabetic patients. The proteoglycans of diabetic patients are banded at a lower buoyant density, indicating a lowered glycosylation rate and a lower number of sugar side chains per core protein. In discs of diabetic patients, there is a slight increase in the chain length of chondroitin sulfate. Further analysis of the glycosaminoglycan chains showed a decreased amount of keratan sulfate, compared with that in nondiabetic subjects. However, the total uronic acid content of the disc tissues and the ratio of uronic acid to protein of each fraction were unchanged in diabetic patients versus that in control subjects. CONCLUSIONS: Discs in patients with diabetes have proteoglycans with lower buoyant density and substantially undersulfated glycosaminoglycan, which with the specific neurologic damage in these patients, might lead to increased susceptibility to disc prolapse.