Osteogenesis imperfecta: fractures of the femur when testing for congenital dislocation of the hip.
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Biomedical subjects
Publications and source records attributed to C R Paterson.
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The management of patients with asymptomatic hyperparathyroidism remains controversial. This study examined the extent to which the presence of prospect of bone disease should influence treatment. Bone mineral content (BMC) of the distal forearm was measured by single photon absorptiometry in 67 patients with mild hyperparathyroidism. Twenty-six patients treated surgically and 17 managed conservatively were reviewed regularly for up to 4 years. Eighty per cent of patients had a baseline fat-corrected BMC within the local reference interval for age and sex, but about 75 per cent of values fell below the mean. BMC at the 'distal' site of the surgically treated patients improved or stabilized, but a continuing decline was seen in the patients managed conservatively (P less than 0.01). Differences were small and concern about future osteoporotic fracture should seldom be a major factor in making decisions about surgical correction of mild hyperparathyroidism.
We determined the rate of change of bone mineral content (BMC) in the distal forearm of 89 healthy postmenopausal women by single-photon absorptiometry. The BMC measurements were taken at 6- or 12-monthly intervals for up to 4 years. Urinary oestrogen excretion and anthropometry were assessed at the time of the first BMC measurement. Urinary oestradiol glucuronide (E2G) excretion was related to the rate of change of 'proximal' BMC in women 1-7 years past the menopause (r = 0.52, p less than 0.01). Body mass index was less highly correlated with the rate of change of BMC in these women (r = 0.41, p less than 0.05). We conclude that urinary E2G excretion could contribute to a screening procedure for the assessment in women soon after the menopause of the risk of osteoporotic fracture in later life.
We measured urinary pyridinoline and deoxy-pyridinoline by high performance liquid chromatography, and urinary oestrogens by radioimmunoassay, in 68 healthy postmenopausal women to evaluate these assays for the prediction soon after the menopause of the risk of developing osteoporotic fractures in later life. Change in forearm bone mineral content was assessed by single photon absorptiometry over 4 years. Although there was no significant correlation between the pyridinium crosslinks and urinary oestrogens, we found that up to 58% of the variation in the rate of loss of bone mineral content in women soon after the menopause could be explained by pyridinoline and oestradiol glucuronide assays together with body mass index. Measurement of the urinary pyridinium crosslinks and oestradiol glucuronide may make a significant contribution to a biochemical screening procedure for future osteoporotic fracture.
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Eighty-eight healthy post-menopausal women were divided into two groups, one of 35 subjects who had undergone menopause up to 9 years previously and the second of 53 subjects who were 10 or more years post-menopausal. In each individual we related the bone mineral content (BMC), measured by single photon absorptiometry in the distal forearm, to anthropometric variables and urinary oestrogen excretion. There was a positive association between BMC and both urinary oestrogen excretion and anthropometric variables, but this was statistically significant only in the older women. As expected, BMC in the distal forearm decreased with advancing age, the fall being greatest in the first 9 years after the menopause. We concluded that although a single measurement of urinary oestrogen and anthropometric variables does not provide enough information to predict an individual's BMC, the values obtained may prove of use, along with a single BMC determination, in helping to predict the rate of bone loss.
Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastases in bone or elsewhere after 1 year's subsequent follow up. Eight out of the ten patients with metastases had crosslink excretion values higher than the reference interval, but so did some patients without known metastatic disease. For both crosslinks there was a clear correlation with serum alkaline phosphatase activity measured at about the same time. We consider that measurement of urinary collagen crosslink assays may have a place in the early detection of metastatic spread to bone.
Analyses of the urinary concentration relative to creatinine of the collagen crosslinks, pyridinoline (Pyd) and deoxy-pyridinoline (Dpd) were made in 47 patients with metabolic bone diseases to assess the validity of these assays as indicators of bone resorption. The mean values for patients with Paget's disease of bone, primary hyperparathyroidism and osteomalacia were significantly higher (P less than 0.001) than those for age-matched healthy individuals. During treatment of Paget's disease with bisphosphonates, there was a steady decline in the urinary concentration of the crosslinks to the normal range; this change occurred earlier than for serum alkaline phosphatase. There were significant correlations (P less than 0.01) between the concentrations of both crosslinks and the corresponding values for hydroxyproline. At lower crosslink concentrations, however, these relationships were less marked due to large variations in hydroxyproline values. The results show that measurements of urinary Pyd and Dpd provide clinically applicable indices of bone resorption that are more specific than other markers.
Very limited information is available on the normal size of the anterior fontanelle but this measurement may be of value in the early diagnosis for example of bone diseases, and of hypothyroidism. The purpose of this study was to provide a reference range applicable to the first two years of life, using a larger sample population than previous studies. Measurements were made of the anterior-posterior and transverse dimensions in 334 full term infants between birth and the age of 24 months. Despite the wide variation, both in size and age of closure, it proved possible to define a reference range and also, for the first time, to present a centile chart.
A two-stage chromatographic procedure has been devised for the measurement of 7-dehydrocholesterol in human skin. Extracts containing ergosterol as internal standard underwent preparative chromatography on a Spherisorb S5W column using hexane-1% isopropanol as solvent, and an eluted fraction was analysed with an Ultrasphere 5-microns ODS column with methanol-tetrahydrofuran-17.5 mM KH2PO4 (95:1:4, v/v) as solvent and using an amperometric detector at 1.7 V. 7-Dehydrocholesterol could be reliably assayed in human skin samples as small as 5 mm in diameter. In hospital patients skin 7-dehydrocholesterol concentrations ranged from 12 to 81 micrograms/g dry weight.
Blood was collected by venepuncture from nine healthy subjects over a ten minute period before applying a standard tourniquet, and over a ten minute period afterwards. Plasma ionised calcium was unaltered by the tourniquet, whereas total calcium, total protein and albumin in serum increased modestly. However, there was no effect on total calcium adjusted for albumin. Even without albumin adjustment the change in total calcium was negligible within one minute of the application of the tourniquet. We consider that in ordinary clinical practice, there is no need to perform venepuncture for calcium assays without a tourniquet.
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Using readily available biochemical assays of plasma and urine constituents, we have defined discriminant functions useful as a guide to the differential diagnosis of patients with hypercalcemia. The decreasing rank order of contribution of the variables to the discriminant functions was as follows: plasma albumin, plasma phosphate, plasma chloride, log10 (calcium excretion per liter of glomerular filtrate), and log10 (plasma gamma-glutamyltransferase). Discriminant functions have been defined for patients with values for plasma creatinine above and below 185 mumol/L, and for practical conditions in which plasma and urine samples, or plasma samples only, are available.
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The case of a 65 year old female with myasthenia gravis and hypercalcaemia is presented. Failure of medical control of the myasthenia necessitated thymectomy at which time parathyroid exploration was also carried out. This revealed parathyroid hyperplasia and a thymoma. This association has not been previously documented in the literature.
Psychiatric symptoms are well recognized as a feature of patients with primary hyperparathyroidism. We have applied a standardized psychiatric interview to 15 patients before and after surgery. Thirteen had a lower 'psychiatric score' (less psychiatric morbidity) after surgery and improvements were particularly seen in symptoms of fatigue, depression, irritability, sleep disturbance and lack of concentration. The levels of intellectual impairment and of anxiety were unchanged after surgery. The 'psychiatric scores' in an additional group of 21 hyperparathyroid patients, in whom a decision to treat conservatively had been made independently, were similar to those in the surgically treated patients after surgery. Among all the untreated patients no relationship was found between overall 'psychiatric score' and serum levels of calcium or parathyrin.
We have measured urinary excretion of free immunoreactive oestrone and oestradiol and their respective glucuronides in relation to creatinine in early morning samples in 132 fit, active postmenopausal women. None of the oestrogen/creatinine ratios was significantly correlated either with age or with years since menopause. However, we did demonstrate significant positive correlations between the levels of all four oestrogens and the body mass index, weight and fat mass. These results are similar to those obtained by other workers for plasma or serum oestrogen levels. Since assessment of oestrogenic status from plasma or serum may call for several samples to allow for the rapid minute-to-minute variation in levels, urinary oestrogenic assays as described may provide a valuable non-invasive measurement of oestrogenic status. Such measurements may have a place in the identification of women at greater risk of developing symptomatic osteoporosis in later life.