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Biomedical subjects

J A Pringle

Publications and source records attributed to J A Pringle.

At least 19 recordsLinked to original sources

Malignant round cell tumours of bone: atypical clinical and imaging features.

OBJECTIVE: To describe the clinical, radiological and MRI features of six atypical cases of histologically proven appendicular Ewing sarcoma/primitive neuroectodermal tumour (PNET). DESIGN: Retrospective review of case notes and available imaging was carried out. PATIENTS: Six patients (4 male, 2 female; mean age 27 years, range 19-44 years), presenting over a 77-month period, were identified from the Bone Tumour Register. All had unusual clinical and imaging features for Ewing sarcoma/PNET. RESULTS AND CONCLUSIONS: Four tumours were centred on the distal femoral metaphysis, one in the proximal tibial metaphysis and one in the distal tibial metaphysis. Plain radiographs were available in four cases and showed minor cortical changes. MRI demonstrated a relatively small, eccentrically located intraosseous component with a large, eccentric extraosseous component. Extension into the epiphysis was seen in three cases and into the adjacent joint in two cases. Intraosseous "skip" metastases were present in three cases. The clinical and imaging features were atypical for conventional intraosseous Ewing sarcoma/PNET and the exact site of origin (intraosseous, periosteal or soft-tissue) was unclear.

Adult↗

Ultrasound-guided needle biopsy of primary bone tumours.

Needle biopsy is an established technique for the histological diagnosis of bone tumours, usually guided by fluoroscopy or CT. Surface lesions and aggressive tumours which have extended through the cortex are also amenable to imaging with ultrasound (US). We have assessed the diagnostic accuracy of US-guided Trucut needle biopsy in a consecutive series of patients referred to a Bone Tumour Unit with suspected primary bone tumours. Of 144 patients (83 men, 61 women; mean age 34.7 years) referred over a period of two years, 63 were considered suitable for US-guided biopsy. This was based on the presence of a relatively large extraosseous component, seen typically in osteosarcoma and malignant round-cell tumours. The results of needle biopsy were compared with those of surgical biopsy. The diagnostic accuracy was 98.4%, with only a single failed biopsy. Thus, in a selected group of patients, US is a very reliable technique of guidance for percutaneous needle biopsy of bone tumours.

Adolescent↗

Langerhans' cell histiocytosis of the spine: use of MRI in guiding biopsy.

The MRI features of two cases of spinal Langerhans' cell histiocytosis with multilevel involvement are presented in which MRI was of help in differentiating active from inactive healing lesions by the demonstration of signal changes in the vertebral body marrow of the active lesion, manifest as low signal intensity on T1-weighted sequences and high signal intensity on T2-weighted sequences. This distinction could not be made by plain radiography or bone scintigraphy. In cases where biopsy is required for diagnosis, MRI is recommended to guide the biopsy towards levels suggestive of active involvement.

Biopsy, Needle↗

The need for specialist review of pathology in paediatric cancer.

A retrospective histopathological review of 2104 cases of solid tumour was carried out to assess the variability in diagnosis of childhood cancer. Cases were subject to three independent, concurrent opinions from a national panel of specialist pathologists. The conformity between them was analysed using the percentage of agreement and the kappa statistic (kappa), a measure of the level of agreement beyond that which could occur by chance alone, and weighted kappa (w kappa), which demonstrates the degree of variation between opinions. The major groupings of the Birch-Marsden classification were used within which tumours were assigned for kappa analysis according to the clinical significance of the differential diagnoses. The mean agreement for all tumours together was 90%; kappa = 0.82, w kappa = 0.82. Retinoblastoma achieved the highest kappa value (1.0) and lymphoma the lowest (0.66). Of the cases, 16.5% had their original diagnoses amended and the panel confirmed the original diagnosis of paediatric pathologists in 89% of cases compared with 78% for general pathologists. The varying levels of agreement between experts confirm the difficulty of diagnosis in some tumour types, suggesting justification for specialist review in most diagnoses. Specialist training in paediatric pathology is also recommended.

Child↗

Spinal osteoblastoma: relationship between paravertebral muscle abnormalities and scoliosis.

OBJECTIVE: To illustrate the variety of paravertebral muscle abnormalities as seen on computed tomography (CT) or magnetic resonance imaging (MRI) in association with spinal osteoblastomas and correlate the findings with the presence of scoliosis. DESIGN: In a retrospective study the clinical notes, plain radiographic, CT and/or MRI features were reviewed for the presence of scoliosis and paravertebral muscle abnormality (either inflammation or atrophy). PATIENTS: Twelve patients (7 male, 5 female) with a mean age of 17 years were studied. Three lesions occurred in the cervical spine, five in the thoracic spine and four in the lumbar spine. RESULTS AND CONCLUSIONS: Nine patients had scoliosis. All patients with a thoracic or lumbar lesion and scoliosis (n = 8) had an associated abnormality of the paravertebral muscles (usually atrophy with fatty replacement). One patient with a lumbar lesion and no scoliosis had normal paravertebral muscles. One patient with a cervical lesion had thoracic scoliosis but no muscle abnormality in the cervical region, while two patients with cervical lesions and no scoliosis showed muscle abnormalities. The results support the clinical hypothesis that scoliosis in patients with spinal osteoblastoma is due to paravertebral muscle spasm, although this would not appear to be the case for cervical lesions.

Adolescent↗

Unusual imaging findings in association with spinal osteoblastoma.

This paper describes four patients with spinal osteoblastoma that had unusual imaging features. Two cases arose in the cervical spine and two in the thoracic spine. Three tumours were associated with diffuse sclerosis of the vertebral body (an 'ivory vertebra'). All of these lesions either arose in the vertebral body or extended into the body from the adjacent pedicle. Reactive sclerosis at multiple levels was seen in three cases (one involving adjacent vertebral bodies, two involving adjacent pedicles or laminae and one involving multiple ribs). Osteophyte formation was identified bridging the disc space on the concave side of a scoliosis in two cases. Another case had an unusual scintigraphic appearance with an area of linear activity adjacent to the tumour. The finding of an 'ivory vertebra' in a child or young adult should raise the possibility of osteoblastoma involving the vertebral body, especially if there is an associated scoliosis.

Adult↗

Long-term survival and strain-specific tolerance induction in rat-to-mouse neonatal islet xenografts.

These studies were designed to determine (1) if culture-isolated, neonatal rat islets are capable of inducing xenogeneic tolerance in mice and (2) whether this tolerance is species- or strain-specific. We attempted to induce xenogeneic tolerance by transplanting culture-isolated neonatal FSH islets to 26 diabetic C57B1/6 recipients. These animals received one injection of ALS at the time of transplant. Fifteen (58%) animals remained reversed by xenotransplant for > 173 days. To assess the development of strain or species-specific tolerance, 14 of the animals bearing long-term surviving FSH grafts were divided into 3 treatment groups. Animals in group 1 were nephrectomized to remove the initial graft and then retransplanted with uncultured, adult FSH islets; animals in group 2 were retransplanted with uncultured, adult FSH islets without nephrectomy; and group 3 animals were nephrectomized and retransplanted with uncultured, adult third-party islets (WF). In naive controls, adult FSH islets were rejected in 9 +/- 2 days. The MST for adult FSH grafts transplanted to nephrectomized recipients was 104 +/- 54 days, with 4 out of 5 (80%) surviving until sacrifice 90-171 days posttransplant. The MST for FSH grafts transplanted to nonnephrectomized recipients was 120 +/- 70 days with 3 out of 4 (75%) surviving until sacrifice 143-154 days posttransplant. Thus, it appears that the initial neonatal FSH transplant induced the development of immune tolerance to highly immunogenic FSH islet tissue. In contrast, the MST for third-party adult WF grafts was 27 +/- 13 days compared with an MST of 36 +/- 24 days in naive controls. Thus, it appears that the xenogeneic tolerance induced by neonatal FSH islets was strain rather than species-specific. Factors such as the close evolutionary relationship between rats and mice, the neonatal condition of the initial graft, and its relative lack of donor APCs are included in a discussion of possible mechanisms of tolerance induction.

Animals↗

Human osteoclastomas contain multiple forms of cathepsin B.

During bone resorption, the osteoclast secretes hydrolytic enzymes into the sealing zone which it creates between itself and the bone surface. Since this environment is acidic, proteinases active at low pH must therefore be responsible for degrading the bone matrix, which is largely composed of type I collagen. To investigate these enzymes, we have used human osteoclastomas as the starting material. Sequential chromatography on S-Sepharose, phenyl-Sepharose, heparin-Sepharose and Sephacryl S-200HR resulted in the separation of six cysteine proteinase activities. These proteinases have Mr values ranging from 20,000 to 42,000. The pH profiles of activity showed optima between 3.5-6.0 for both synthetic substrates and type I collagen. All the proteinases were able to degrade soluble and insoluble type I collagen. The kinetics of hydrolysis using Z-Phe-Arg-NHMec and Bz-Phe-Val-Arg-NHMec as substrates resulted in values within the range expected for cathepsin B. The six activities were all inhibited by the cysteine proteinase inhibitors antipain, chymostatin, leupeptin and E-64. The rate constants of inactivation using Z-Phe-Tyr-(O-t-Bu)CHN2 were also similar to the published rates for cathepsin B. Antibodies to cathepsin B reacted with all activities. These antibodies localised the enzyme activities to the osteoclast within the tumour. Northern blotting using a cDNA probe to cathepsin B revealed three species of mRNA transcripts. These results suggest that multiple forms of cathepsin B-like proteinases are involved in osteoclastic bone resorption.

Amino Acid Sequence↗

Production and characterization of new monoclonal antibodies to human osteoclasts.

Two monoclonal antibodies raised against human osteoclastoma were found to show antiosteoclastic activity on frozen sections of tumor. Immunoreactivity was localized on the membrane surface. These antibodies exhibited no activity against tissue macrophages and human visceral tissue except kidney, where they stained tubules but not glomeruli. In addition, no activity was observed against rabbit or rat osteoclasts, suggesting that they might react with unique epitopes on human osteoclasts.

Animals↗

Damaged ligaments at the craniocervical junction presenting as an extradural tumour: a differential diagnosis in the elderly.

An extradural mass at the craniocervical junction causing progressive neurological disability in five elderly patients is described. The lesion, which might be confused with a meningioma or other tumour, is composed of amorphous degenerate fibrocartilaginous material and could be due to degeneration of the ligaments responsible for atlanto-axial stability. Recognition of the condition early is important as the patient's clinical condition will deteriorate without decompression. Anterior transoral removal is relatively simple, unlike surgery for tumours in the area, and will not destabilise the craniovertebral junction. It is likely that a proportion of these lesions are undetected, misdiagnosed or untreated to the detriment of the patient.

Aged↗

Needle biopsy of musculoskeletal lesions. A review of 208 procedures.

Needle biopsies, performed on 208 consecutive patients and interpreted at the London Bone Tumour Service over a two-year period, were reviewed. A correct diagnosis was reached in 97% (133 out of 137) using this technique alone. Needle biopsy is safe and accurate when undertaken in consultation within a bone tumour service; it offers considerable advantages to both patient and surgeon over conventional open biopsy.

Biopsy, Needle↗

Purification and characterization of a tartrate-resistant acid phosphatase from human osteoclastomas.

Tartrate-resistant acid phosphatase is one of the major enzymes produced and secreted by osteoclasts. To obtain sufficient enzyme for biochemical characterization, we have purified this enzyme from human osteoclastomas by sequential chromatography on SP-Sephadex, CM-Sephadex, hydroxylapatite, Sephadex G-150 and concanavalin A-Sepharose. The purification over the original tumour extract was about 2000-fold, with a yield of 10%. The enzyme appeared to be homogeneous when assessed by SDS/polyacrylamide-gel electrophoresis. Both gel filtration and SDS/polyacrylamide-gel electrophoresis indicated an Mr of about 30,000. The reduced and alkylated enzyme consists of two subunits with Mrs of 15,000 and 17,500. The N-terminal amino acid sequence of both subunits indicates that there is a high degree of identity between the osteoclastoma enzyme and similar enzymes purified from spleen and uterus. Using 4-methylumbelliferyl phosphate as substrate, the specific activity of the purified enzyme was 387 units.mg-1, and the Km was 284 microns. The pH optimum was 5.7. Unlike similar enzymes purified from human and bovine bone, osteoclastoma acid phosphatase is not activated by reducing agents (2-mercaptoethanol or ascorbic acid). The enzyme contains 4.8 mol of Fe2+/3+, 0.3 mol of Mn2+ and 1.7 mol of Mg2+ per mol of enzyme. Although the enzyme loses 50% of its activity in the presence of EDTA, it is not inhibited by the iron chelator 1,10-phenanthroline. However, the enzyme is activated to a small extent by Mn2+ and Mg2+. Using a variety of substrates and inhibitors, we demonstrate that there are differences between the osteoclastoma acid phosphatase and the enzyme purified from other sources.

Acid Phosphatase↗

Bone resorption in vitro: macrophages and giant cells from failed total hip replacement versus osteoclasts.

Macrophages and giant cells which ingested material particles in loosening of total hip prostheses were tested for their ability to resorb bone in vitro, using osteoclasts as the control. Macrophages and giant cells did not form pits or resorption lacunae on the bone substrates as osteoclasts did. The results support the view that around implants also bone resorption is mediated by osteoclasts. A role of macrophages in the attachment phase of bone resorption is suggested.

Animals↗

The role of macrophages and giant cells in loosening of joint replacement.

Macrophages and foreign-body giant cells from the bone-cement interface of loosened joint replacement were assayed for direct bone resorption in an in vitro experimental model. Human osteoclasts from giant cell tumors and experimental animal osteoclasts were not capable of resorbing the bone under experimental conditions, but osteoclasts are. It is suggested that macrophages and giant cells in loosened implants may initiate bone resorption, removing the extra-cellular barrier that normally protects mineral crystals from osteoclastic recognition.

Aged↗