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Biomedical subjects

A M Parfitt

Publications and source records attributed to A M Parfitt.

222 records · Page 13Linked to original sources
PubMedDate not supplied

Bone effects of space flight: analysis by quantum concept of bone remodelling.

During the manned Skylab flights mineral losses from the calcaneum and changes in external calcium balance were in the ranges found for healthy subjects at bedrest. Calcium balance reached a nadir of -200 mg/day by two months with no change thereafter; the negative balance was due to increased urinary excretion with no change in net absorption. The total calcium loss averaged 18 g in the longest flight of 84 days; the densitiometric data suggested that about two-thirds of this came from trabecular bone and about one-third from cortical bone. These data could represent reversible bone loss due to increased birth rate of normal osteoclasts and osteoblasts and consequent increase in bone turnover and in reversible mineral deficit, or irreversible bone loss due to overactive osteoclasts and/or underactive osteoblasts. If the former explanation is correct, significant bone loss is unlikely whatever the duration of future flights, except in older persons already losing bone; if the latter explanation is correct, space flights longer than six months may lead to a significant increase in fracture risk in later life. Neither terrestrial immobilization nor unwilling animals in orbit are ideal models for the effects of space flight on human bone. To choose between reversible and irreversible mechanisms of bone loss, and to determine the effects of space flight on lifelong fracture risk, future astronauts and cosmonauts must undergo adequate histologic study of bone after in vivo tetracycline labeling.

Absorptiometry, Photon↗
PubMedDate not supplied

Identification of the mineralization front: comparison of a modified toluidine blue stain with tetracycline fluorescence.

A modified toluidine blue method for identification of the mineralization front at the zone of demarcation between bone and osteoid in undecalcified, plastic-embedded sections of bone is described. The intensity of staining is increased both by increasing the pH of the solution and by increasing the duration of staining. The method is reproducible, since measurements of the extent of mineralization front on two nonadjacent sections from the same biopsy in 20 cases had a correlation coefficient of 0.98. The identification of the mineralization front by toluidine blue agrees closely with identification by means of in vivo tetracycline uptake, with a correlation coefficient of 0.97 between measurements of its extent using the two methods on adjacent sections from the same biopsy. It is likely that both toluidine blue staining at pH 6.5 and tetracycline uptake depend on some property of the most recently deposited bone mineral. With either method we find low values for the extent of mineralization front as a fraction of osteoid surface in many patients with osteoporosis. The uniformly normal values for this quantity in osteoporosis reported by other investigators may reflect different criteria for distinguishing osteoid-covered from quiescent bone surfaces.

Biopsy↗
PubMedDate not supplied

A unique case of adult hypophosphatemic osteomalacia.

A 36-year-old Russian man presented with neck and low back pain in September 1990. He was of normal stature, and there were no stigmata of rickets. The family history was negative for bone disease. He was found to have hypophosphatemia (2.3 mg/dl), impaired phosphate reabsorption (TmP/GFR 2.08), hyperphosphatasemia (254 IU/l), normocalcemia, normal vitamin D metabolite levels, and secondary hyperparathyroidism. Clinically, his spinal movements were quite impaired and there was moderate proximal muscle weakness. On skeletal radiographs, there was generalized osteosclerosis and multiple ligamentous calcifications. Transiliac biopsy was diagnostic for severe osteomalacia. He was treated with oral phosphate (240 mEq daily) and calcitriol (4 micrograms daily) with resultant very slow clinical, biochemical, and histomorphologic improvement. The patient had hypophosphatemic osteomalacia with some features of X-linked hypophosphatemia, but sporadic and of relatively late onset. The osteopenia, height loss, incapacitating weakness, and glycinuria that are characteristics of sporadic adult onset nonfamilial hypophosphatemia, with or without an associated tumor, and the low serum calcitriol levels that may be an additional characteristic of tumor-induced osteomalacia were absent. Other known causes of acquired renal tubular dysfunction were ruled out. The etiology, pathogenesis, and nosology of the disorder remain obscure, but treatment based on experience with other forms of hypophosphatemic osteomalacia was ultimately effective.

Adult↗
PubMedDate not supplied

Gompertzian growth curves in parathyroid tumours: further evidence for the set-point hypothesis.

BACKGROUND: Clinical and cell kinetic data in parathyroid tumours show that their rate of growth slows down progressively and that tumour size approaches an asymptotic value. The Gompertz equation has been widely used in oncology to model growth retardation in malignant tumours; we describe its first application to a benign tumour. METHODS: In 41 patients with radiation associated hyperparathyroidism, individual solutions were derived for the Gompertz equation: Nt = Exp[A/ a(1 - Exp - at)], where A is the rate constant (years-1) for initial exponential growth and a is the rate constant (years-1) for exponential decline in A. Input data comprised three estimates of tumour age at surgery, 100%, 75% and 50% of the time since irradiation, cell number estimated from tumour weight, and current tumour growth rate, representing the difference between current cell birth rate, estimated from the prevalence of mitotic figures, and an assumed mean rate of cell loss of 5%. RESULTS: With 100% tumour age, geometric mean values were 2.76 for A, 0.134 for a, and 0.87 g for the growth asymptote. As assumed tumour age decreased, the rate constants increased and the growth asymptotes declined from 22% to 9% greater than the geometric mean tumour weight. Depending on assumed tumour age, the rate constants were about 15-45 times smaller than in myeloma and in testicular tumours, and the growth asymptotes about 2500 and about 60 times smaller, respectively. A and a were highly correlated (r2 = 0.993), with a slope of 20.9 and no significant intercept. Depending on assumed tumour age, the geometric mean time from the initial mutation to the first cell division ranged from 39 to 92 days, much longer than in malignant tumours. CONCLUSIONS: (1) The Gompertz modelling demonstrates that both the nonprogressive clinical course and the slow growth of parathyroid tumours can be accounted for by a single mutation. (2) The extremely low values for A and a, and consequent very long delay before the first cell division, support the notion that the initial mutation does not affect a growth regulatory gene, but increases growth indirectly via an increase in secretory set-point, the clone of mutant cells behaving as if they were in a hypocalcaemic environment until the plasma calcium rises to the new set-point. (3) The clinical characteristics of radiation-induced parathyroid tumours are modelled more closely if there is a substantial delay between time of irradiation and onset of tumour growth. (4) The rate constants A and a are highly correlated because the variability of tumour weight on a logarithmic scale is much lower than the variability of the rate constants.

Adenoma↗