A severe case of acquired hypophosphataemic osteomalacia: the perils of a missed diagnosis.
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Diagnostic Errors↗
Biomedical subjects
J Pringle
Publications and source records attributed to J Pringle.
Gross vertebral collapse associated with long-term disodium etidronate treatment for pelvic Paget's disease.
Inhibition of skeletal mineralisation is a well-recognized complication of disodium etidronate therapy that was identified in the earliest studies of its use in osteoporosis and Paget's disease. The effect is seen at lower doses in Paget's disease than in osteoporosis. Several cases of spontaneous fractures occurring in unaffected bones of Paget's patients have been reported. However, we believe the case described here is the most severe example of etidronate-induced osteomalacia published in the literature, featuring widespread vertebral collapse occurring as a consequence of nearly 10 years of uninterrupted etidronate treatment for isolated hemipelvic Paget's disease.
Aged↗
Extramedullary plasmacytoma in a horse with ptyalism and dysphagia.
A Clydesdale mare was examined for weight loss, inappetence, ptyalism, and dysphagia. The main abnormality revealed by serum biochemistry was a marked hyperglobulinemia, and protein electrophoresis revealed a monoclonal gammopathy in the gamma region. The urine was positive for Bence Jones proteins. These findings suggested a plasma cell tumor. The neoplasm could not be located with extensive antemortem examination. At postmortem, neoplastic cells morphologically compatible with plasma cells and positive for equine IgG with imunoperoxidase staining infiltrated the pericardium, mediastinal stromal tissues, adrenal glands, meninges, atrioventricular valves, aorta, abdominal and thoracic fat, and nerves, including the trigeminal nerve. The neoplastic cells invading the cranial nerves were responsible for many of the presenting signs.
Animals↗
Assessment of muscle oxygenation in the horse by near infrared spectroscopy.
This study examined the ability of near infrared spectroscopy (NIRS) to noninvasively determine changes to muscle oxygenation in the resting horse. Five horses had (NIRS) performed over extremity muscle while under general anaesthesia, first with 8 min limb ischaemia, then systemic hypoxaemia for 5 min. A second group of 6 awake horses had NIRS performed over extremity muscle while being administered hypoxic gas (F(I)O2 0.10) for 5 min, and after return to steady state, limb ischaemia was induced for an additional 5 min. In the anaesthetised horses' ischaemia induced marked and significant muscle deoxygenation of haemoglobin/myoglobin (P<0.01), with corresponding arterial saturation decreasing from 98.9 to 81.9%. Hypoxaemia induced small yet significant muscle deoxygenation (P<0.01) that was 3.2% of the ischaemia deoxygenation signal, with a corresponding decrease in arterial saturation from 98.6 to 90.4%. In the awake horses muscle deoxygenation was not detectable during hypoxia despite reduction of arterial saturation from 97.8 to 86.8%, whereas ischaemia induced rapid and significant deoxygenation of muscle (P<0.05), with corresponding reduction of venous saturation from 78.4 to 75.4%. In neither group of horses was there evidence of cytochrome aa3 reduction, despite complete ischaemia for up to 8 min. NIRS changes in the resting horse muscle clearly differed between ischaemia and hypoxaemia, and can readily show muscle deoxygenation in clinically relevant hypoxaemia in the horse under anaesthesia. Further, as the deoxygenation signal induced by ischaemia was clearly detectable above a background movement artefact, NIRS application to study of muscle oxygenation in the working horse should be explored.
Animals↗
Spinal growth and a histologic evaluation of the Risser grade in idiopathic scoliosis.
STUDY DESIGN: Thirty-four patients with idiopathic scoliosis who underwent anterior spinal surgery as part of the correction of spinal deformity were studied prospectively. Superior and inferior endplates were harvested and examined histologically for evidence of residual growth activity. This was then correlated with Risser grades, chronologic age, and pubertal status. OBJECTIVES: To clarify the correlation between Risser grade and vertebral endplate growth potential in patients with idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: The importance of longitudinal spinal growth in patients with idiopathic scoliosis and its correlation with curve progression and the crankshaft phenomenon after posterior fusion are well recognized. The Risser grade, which shows the extent of excursion of the iliac apophysis on serial plain radiographs, is commonly used to estimate residual spinal growth. However, the correlation between the Risser grade and vertebral endplate growth potential in patients with idiopathic scoliosis remains unclear. METHODS: Superior and inferior endplates were harvested from these patients and examined histologically for evidence of residual growth. This was correlated with Risser grade, chronologic age, and pubertal status. RESULTS: Risser Grade 5 was found to be the only indicator of cessation of vertebral growth in idiopathic scoliosis. Of the 14 patients with Risser Grade 4, 10 showed significant growth activity in the vertebral endplates. The reliability of Risser Grade 4 increases when combined with chronologic age and time since menarche in female patients. CONCLUSIONS: The crankshaft phenomenon is reported to occur only in patients with Risser Grade 2 or less, particularly those with open triradiate cartilages. Our findings of significant endplate growth activity, even in patients with Risser Grade 4, make it unlikely that the crankshaft phenomenon is caused purely by longitudinal spinal growth.
Adolescent↗
Spinal osteoblastoma: CT and MR imaging with pathological correlation.
OBJECTIVES: To illustrate the CT and MRI features of spinal osteoblastomas and correlate the imaging with histological findings. DESIGN: In a retrospective review the CT and MRI features of spinal osteoblastomas with respect to mineralisation, signal intensity (SI), adjacent reactive changes, enhancement following gadolinium-DTPA (5 cases) and adjacent soft tissue masses were compared and correlated with the histological findings including the degree of osteoid formation and matrix mineralisation, vascularity and surrounding reactive changes in bone and soft tissue. PATIENTS: Eleven patients (7 males and 4 females; age range 8-43 years, mean age 19.5 years) with 12 osteoblastomas (1 patient suffered a recurrence) were studied. RESULTS: All lesions showed classical features on CT with varying degrees of matrix mineralisation, whereas MRI identified mineralisation in only eight of 12 cases. MRI showed low signal intensity of the lesion on both T1- and T2-weighted sequences in several cases in the absence of heavy mineralisation. In these cases, histological examination revealed diffuse osteoid production by the tumour. All patients given gadolinium showed enhancement within the tumour on MRI. Reactive bone marrow changes were identified on MRI in 10 cases, and in five of these the changes were at multiple levels. An adjacent soft tissue mass was demonstrated in five cases, but extraosseous tumour was present histologically in only two of these. CONCLUSIONS: The MRI appearances of spinal osteoblastomas are varied and show no characteristic features. MRI may also overestimate the extent of the lesion due to extensive reactive changes and adjacent soft tissue masses. CT should continue to be the investigation of choice for the characterisation and local staging of suspected spinal osteoblastomas.
Adolescent↗
A phase II study of cisplatin, ifosfamide and doxorubicin in operable primary, axial skeletal and metastatic osteosarcoma. European Osteosarcoma Intergroup (EOI).
BACKGROUND: Despite advances in the treatment of primary limb osteosarcoma, the outcome of patients with primary metastatic and axial skeletal disease remains poor. The European Osteosarcoma Intergroup have assessed a combination chemotherapy regimen consisting of ifosfamide (IFOS) 3 g/m2/dl-2, doxorubicin (DOX) 25 mg/m2/dl-3 i.v. bolus and cisplatin (CDDP) 100 mg/m2/dl. PATIENTS AND METHODS: One hundred nine previously untreated patients with primary osteosarcoma were registered. Eligibility was confirmed in 103. At presentation, 45 eligible patients had metastatic disease, 15 axial skeletal primary tumours and 43 non-metastatic limb tumours. RESULTS: The major toxicities were myelosuppression (90%, grade 3 or 4) and nausea and vomiting (74%, grade 3 or 4). Overall mean relative dose intensity (RDI) was 80% (88% CDDP, 75% IFOS, 81% DOX). Clinical response as measured by reduction in tumour volume occurred in 36% (95% confidence interval (95% CI): 27%-47%) of primary tumours. Response of pulmonary metastases to chemotherapy was seen in 33% (95% CI: 19%-49%). Good histological response (> or = 90% necrosis of the tumour) occurred in 33% (95% CI: 22%-45%) of resected tumours. Five-year survival was 62% in limb-non-metastatic, 41% in axial skeletal and 16% in limb metastatic patients. CONCLUSIONS: This regimen is active in osteosarcoma but does not appear to be more active than the two-drug CDDP-DOX regimen currently recommended by EOI.
Adolescent↗
Near infrared spectroscopy in large animals: optical pathlength and influence of hair covering and epidermal pigmentation.
The effects of epidermal pigmentation and hair covering on the relative transparency of various animal tissues to near infrared (NIR) light were examined, and the pathlengths of NIR light through tissues at four wavelengths in the NIR range were subsequently determined. Black hair covering and black or dark-coloured hooves prevented NIR light from penetration sufficient for conduction of pathlength or NIR spectroscopy measurements. Non-pigmented hair covering of the head did not appear to be a barrier to successful NIR light transmission. Tissues sufficiently transparent to NIR light had the differential pathlength factor (DPF, i.e. the ratio of the observed light pathlength and the geometric light source-detector separation) of NIR light determined by intensity modulated spectroscopy at the wavelengths 744, 806, 834 and 860 nm. Horse gluteal muscles had DPFs of 6.2, 6.2, 6.0, and 5.6, whereas forelimb muscles had DPF of 4.7, 4.4, 4.5 and 3.9 at the respective wavelengths. Sheep heads had DPF of 7.2 +/- 0.3, 5.8 +/- 0.5, 5.5 +/- 0.4 and 4.4 +/- 0.6 (+/- SEM) for the above respective wavelengths, of which the pathlengths all differed significantly from the other, except for between 806 and 834 nm, and 834 and 860 nm. The DPF of horse hooves were 4.8 +/- 0.1, 4.8 +/- 0.1, 4.7 +/- 0.1 and 4.4 +/- 0.1 (SEM) for the above noted wavelengths, of which the pathlength at 744 and 806 nm differed from the pathlength at 860 nm (P>0.05). These results show that NIRS is possible through lighter pigmented hair and epidermal tissues, and provide DPFs of horse feet and muscle and the sheep head that enables quantitative NIRS in these species
Animals↗
Comparison of exercise variables measured during intensity of simulated training to variables at maximal effort in standardbreds.
The heart rate changes during routine training in a group of 8 actively racing Standardbreds were used to simulate the training work on a treadmill (ST) and indices of exercise compared to maximal effort (MAX) on the treadmill. The following parameters were recorded during treadmill work: heart rate, velocity, O2 consumption, respiratory and stride frequency, and stride length. Blood lactate concentrations were measured before and after each work test. Heart rate during simulated training was mean +/- s.d. 87.8 +/- 5.5% heart rate in MAX, one of the 8 horses working < 80% of maximal HR and 2 of the 8 horses working above 90% maximal heart rate. Mean +/- s.d. oxygen consumption during the ST was 75.1% +/- 8.4% MAX, but correlated poorly against percentage heart rate for individual horses (r2 = 0.02). At similar velocities for the ST and MAX, only respiratory frequency differed significantly (P > 0.05), being higher during the ST. Most horses worked at intensities based on heart rate consistent with proposed guidelines of 80-90% of maximal heart rate. However, in 3 of the 8 horses work intensity of insufficient or excessive amounts may have occurred.
Animals↗
Near infrared spectroscopy of the normal bovine claw.
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Animals↗
P-glycoprotein and metallothionein expression and resistance to chemotherapy in osteosarcoma.
The expression of the drug resistance (DR) mediators P-glycoprotein (P-gp) and the metallothioneins (MT) was assessed immunohistochemically in biopsy material from patients with high-grade malignant osteosarcoma (OS). No significant difference was found in survival rate between expressors of both P-gp and MT and non-expressors. Thus, it was concluded that lack of expression of these two drug resistance-related proteins does not appear to confer any advantage in terms of patient survival in osteosarcoma.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Radiological and clinical recurrence of giant-cell tumour of bone after the use of cement.
We have reviewed 13 operations on 11 patients using curettage and polymethylmethacrylate cement for giant-cell tumour of bone (GCT) to assess the value of radiology in the early detection of recurrence. There were four recurrences, the most specific radiological sign on plain radiography was lysis of 5 mm or more at the cement-bone interface. This preceded clinical signs by a mean of four months and was identified at a mean of 3.75 months after operation. There was not always a complete sclerotic margin around the cement, but when it was present, there was never evidence of recurrence. MRI was helpful in assessing cases with evidence of recurrence. Frequent surveillance with plain radiography should continue for one year after operation irrespective of clinical signs of recurrence. When the appearance of the plain radiographs suggests recurrence, MRI should be performed and followed by image-guided needle biopsy.
Adult↗
Doxorubicin and cisplatin with granulocyte colony-stimulating factor as adjuvant chemotherapy for osteosarcoma: phase II trial of the European Osteosarcoma Intergroup.
PURPOSE: This report describes the toxicity and feasibility of administering doxorubicin (DOX) and cisplatin (CDDP) at 2-week intervals with granulocyte colony-stimulating factor (G-CSF) to patients with osteosarcoma and the compatibility of this regimen with endoprosthetic surgery performed after three cycles. PATIENTS AND METHODS: Twenty-four patients with biopsy-proven osteosarcoma were treated with three preoperative cycles of DOX 25 mg/m2/d on days 1 to 3 and CDDP 100 mg/m2 on day 1 with G-CSF 5 micrograms/kg/d on days 4 to 14. Surgery was scheduled at week 6 to be followed by three further cycles of chemotherapy at 2-week intervals. RESULTS: Two-week chemotherapy was feasible, but delays and dose reductions only allowed 74% and 78% of the intended dose-intensity of DOX and CDDP to be administered. Thrombocytopenia accounted for 50% of delays. Significant toxicity included neutropenic sepsis, severe mucositis, prolonged nausea and vomiting, and electrolyte disturbances. Twenty-one limb-salvage procedures and one amputation were performed. There were eight episodes of excessive perioperative bleeding. CONCLUSION: Intensive 2-week chemotherapy with intercurrent surgery is feasible and allows a greater dose-intensity of chemotherapy to be administered compared with the same regimen administered at 3-week intervals without G-CSF. The toxicity is considerable, but manageable.
Adolescent↗
Neospora-induced congenital myelitis and polyradiculoneuritis in a one-month-old Holstein calf.
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Animals↗
Induction of myelin genes during peripheral nerve remyelination requires a continuous signal from the ingrowing axon.
The effect of a permanent transection on myelin gene expression in a regenerating sciatic nerve and in an adult sciatic nerve was compared to establish the degree of axonal control exerted upon Schwann cells in each population. First, the adult sciatic nerve was crushed, and the distal segment allowed to regenerate. At 12 days post-crush, the sciatic nerve was transected distal to the site of crush to disrupt the Schwann cell-axonal contacts that had reformed. Messenger RNA (mRNA) levels coding for five myelin proteins were assayed in the distal segment of the crush-transected nerve after 9 days and were compared to corresponding levels in the distal segments of sciatic nerves at 21 days post-crush and 21 days post-transection using Northern blot and slot-blot analysis. Levels of mRNAs found in the distal segment of the transected and crush-transected nerve suggested that Schwann cells in the regenerating nerve and in the mature adult nerve are equally responsive to axonal influences. The crush-transected model allowed the genes that were studied to be classified according to their response to Schwann cell-axonal contact. The levels of mRNAs were 1) down-regulated to basal levels (P0 and MBP mRNAs), 2) down-regulated to undetectable levels (myelin-associated glycoprotein mRNAs), 3) upregulated (mRNAs encoding 2'3'-cyclic nucleotide phosphodiesterase and beta-actin), or 4) not stringently controlled by the removal of Schwann cell-axonal contact (proteolipid protein mRNAs). This novel experimental model has thus provided evidence that the expression of some of the important myelin genes during peripheral nerve regeneration is dependent on continuous signals from the ingrowing axons.
Animals↗
Chemotherapy of malignant fibrous histiocytoma of bone.
BACKGROUND: Malignant fibrous histiocytoma of bone (MFHB) is a rare tumour with a 3 year survival of 30%-40% when treated with surgery alone. A small number of patients have previously been treated with pre-operative chemotherapy and responses observed. The aim of the present study was to further determine the response of MFHB to pre-operative chemotherapy. PATIENTS AND METHODS: A non-randomised study of 18 patients with MFHB. Twelve had localised disease and 6 had pulmonary metastases. In 14 patients pre-operative treatment consisted of methotrexate 8 g/m2 on day 1, ifosfamide 3 g/m2 and doxorubicin 60 mg/m2 on day 10. This regimen was given twice and twice post-operatively. A further 4 patients received cisplatin 100 mg/m2 on day 1 and doxorubicin 25 mg/m2 on days 1, 2, 3. Three cycles were given pre- and post-operatively. RESULTS: 15 patients had surgery after chemotherapy. Tumour necrosis was present in all resection specimens and ranged from 50%-100%. 7/15 had > 90% necrosis. Disease free survival is 82% for those patients with a greater than 2 year follow-up. CONCLUSION: This study confirms previous reports that MFHB is a chemosensitive tumour. In view of its rarity collaborative trials are needed to establish the optimum drug treatment including drug selection dose and duration.
Adolescent↗
A yeast gene (BEM1) necessary for cell polarization whose product contains two SH3 domains.
Cell polarization requires that a cellular axis or cell-surface site be chosen and that the cytoskeleton be organized with respect to it. Details of the link between the cytoskeleton and the chosen axis or site are not clear. Cells of the yeast Saccharomyces cerevisiae exhibit cell polarization in two phases of their life cycle, during vegetative growth and during mating, which reflects responses to intracellular and extracellular signals, respectively. Here we describe the isolation of two mutants defective specifically in cell polarization in response to peptide mating pheromones. The mutants carry special alleles (denoted bem1-s) of the BEM1 gene required for cell polarization during vegetative growth. Unlike other bem1 mutants, the bem1-s mutants are normal for vegetative growth. Complete deletion of BEM1 leads to the defect in polarization of vegetative cells seen in bem1 mutants. The predicted sequence of the BEM1 protein (Bem1p) reveals two copies of a domain (denoted SH3) that is found in many proteins associated with the cortical cytoskeleton and which may mediate binding to actin or some other component of the cell cortex. The sequence of Bem1p and the properties of mutants defective in this protein indicate that it may link the cytoskeleton to morphogenetic determinants on the cell surface.
Adaptor Proteins, Signal Transducing↗
Regulation of 2',3'-cyclic nucleotide phosphodiesterase gene expression in experimental peripheral neuropathies.
2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNPase) is an enzyme associated with central nervous system myelination. Although present in the mammalian peripheral nerve, it is not clear what its role is during myelination nor how the expression of this gene is regulated in the PNS. In this study, CNPase gene expression was studied in the crushed and permanently transected rat sciatic nerve, two models of peripheral nerve neuropathy. The Schwann cells of the crushed nerve initially demyelinate, remain in a non-myelinating condition until active regeneration induces remyelination (10-21 days after injury), whereas those of the permanently transected nerve remain in a quiescent, non-myelinating state after the initial demyelination. An increase of CNPase mRNA levels is observed during degeneration and remains high whether the peripheral nerve is regenerating or not, suggesting transcriptional activation of CNPase mRNA and/or increased CNPase mRNA stability as a response to nerve injury. In contrast, the steady state level of CNPase protein did not increase during degeneration or regeneration suggesting either negative translational regulation of CNPase gene expression or a higher turnover of this protein in the injured peripheral nerve. Furthermore, CNPase activity dropped sharply during early degeneration and remained low in the quiescent cells of the permanently transected nerve while it increased in the regenerating nerve. The results suggest that although transcriptional or post-transcriptional regulation of CNPase gene expression is not dependent on Schwann cell-axonal contact, the activity of CNPase appears to be dependent on myelination and indirectly dependent on the presence of axons in the peripheral nerve.
2',3'-Cyclic-Nucleotide Phosphodiesterases↗