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Biomedical subjects

J Reeve

Publications and source records attributed to J Reeve.

At least 235 records · Page 13Linked to original sources

The relative transfer rates for sodium and xenon from gut lumen to plasma in man.

1. A whole-gut perfusion technique has been used to compare the rates of intestinal absorption of sodium and xenon. 2. The calculated transit-time spectra for sodium and xenon across the gut mucosa do not differ significantly either in mean transit time or, for the first 15 min, in shape. 3. These results support the hypothesis that the rate of transfer of sodium from the small intestinal lumen to plasma is limited by blood flow. 4. It is suggested that some features of cholera can be explained by the hypothesis.

Humans↗

A model-independent comparison of the rates of uptake and short term retention of 47Ca and 85Sr by the skeleton.

1. A method has been devised for comparing the impulse response functions of the skeleton for two or more boneseeking tracers, and for estimating the contribution made by measurement errors to the differences between any pair of impulse response functions. 2. Comparisons were made between the calculated impulse response functions for 47Ca and 85Sr obtained in simultaneous double tracer studies in sixteen subjects. Collectively the differences between the 47Ca and 85Sr functions could be accounted for entirely by measurement errors. 3. Because the calculation of an impulse response function requires fewer a priori assumptions than other forms of mathematical analysis, and automatically corrects for differences induced by recycling of tracer and non-identical rates of excretory plasma clearance of tracer, it is concluded that differences shown in previous in vivo studies between the fluxes of Ca and Sr into bone can be fully accounted for by undetermined oversimplifications in the various mathematical models used to analyse the results of those studies. 85Sr is therefore an adequate tracer for bone calcium in most in vivo studies.

Bone and Bones↗

A new tracer method for the calculation of rates of bone formation and breakdown in osteoporosis and other generalised skeletal disorders.

1. Evidence has accumulated that the rate of accretion (A) of calcium to bone is the sum of two fluxes; apposition involving the laying down of new bone and augmentation which is the result of slow exchange of non-surface bone calcium with plasma calcium pools as the result of solid state diffusion. 2. A method has been devised for separating A into its two components. It requires the use of 45Ca or, for clinical studies, 85Sr as a calcium tracer. Studies which are initiated with a combined accretion rate--calcium balance study, are concluded with an estimate of the exponent of the power function which has been found to describe the whole body retention of tracer from the second month onward. 3. The impulse response function of the skeleton for the tracer is then calculated, making the assumption that in any uniform volume of bone, osteoclastic resorption is a first order process. Making in addition certain simplifying assumptions, which are shown to have a modest influence on the final results, a mean rate of bone resorption can be calculated using a development of the well known Stewart-Hamilton formula. The apposition rate is calculated as the sum of the resorption rate and the calcium balance. Augmentation and diminution, defined as equal and opposite exchange processes, are given by the difference between A and the apposition rate. 4. The results of our first thirteen studies in normal subjects and patients with metabolic bone disease are presented, together with analyses of some data from the literature. It is concluded that the development of an atraumatic method for measuring rates of bone formation and resorption in the whole body would be an important advance in the study of metabolic bone disease, and this work is presented so that critical comparisons may be initiated between this tracer method and independent histological methods for measuring these parameters.

Bone Diseases↗

Anabolic effect of low doses of a fragment of human parathyroid hormone on the skeleton in postmenopausal osteoporosis.

Parathyroid hormone, injected daily in low dosage, exerted anabolic effects on the human skeleton, just as it does in the rat. Four postmenopausal women with primary osteoporosis were treated for six months with a synthetic fragment of human parathyroid hormone (hP.T.H. 1-34), given as a daily injection of 100 mug. This treatment caused a remarkable acceleration of bone turnover, indicated both by isotopic tracer and histological methods. At this normocalcaemic dose level, the increases in bone formation outweighed increases in resorption. Three of the four patients showed more positive calcium balances, and mean increases in calcium and phosphorus balances were statistically significant for the group as a whole, the changes being principally due to increased intestinal absorption of both elements. Many modifications of the present method of hormone administration are possible which could further increase the preponderance of anabolic effects. These results suggest that low doses of hP.T.H. 1-34, alone or in combination with other agents, may prove useful in the treatment of osteoporosis.

Absorption↗

A new method for calculating the accretion rate of bone calcium and some observations on the suitability of strontium-85 as a tracer for bone calcium.

1. A new method for calculating the accretion rate (A) of bone calcium is proposed, based on an impulse analysis of 47Ca data. The method is free of most of the assumptions inherent in previous methods of analysis and appears to give more accurate estimates. 2. In fourteen normal subjects and twelve patients with metabolic bone disease, measurements of A by the new method gave very similar results to the mineralization rate calculated by the method of Burkinshaw et al. (1969). Analysis of twelve studies performed by Neer et al. (1967) gave good agreement with their five compartment model. A close relation between A and Marshall's (1964) A5 was observed, but the latter gave systematically higher results. 3. In sixteen studies both 47Ca and 85Sr were injected simultaneously. Although there were no systematic differences between the values of A for the two tracers, the differences between individual values were greater than the known experimental errors.

Adult↗

The clinical measurement of skeletal blood flow.

1. A new method for measurement of skeletal blood flow is described which depends on the complete extraction of 18F in a single passage through bone. 2. Plasma concentration and urinary excretion are measured over a 2 h period. The technique of impulse analysis is used to determine the initial transfer rate of 18F to bone and extravascular extracellular fluid (ECF). The ECF component is evaluated by using a second tracer (51 Cr-EDTA or 82Br) and the bone transfer rate obtained by difference. The 51Cr-EDTA data also provide an estimate of glomerular filtration rate and enable a correction to be applied for urinary bladder retention when necessary. 3. Duplicate measurements of skeletal blood flow in eight normal male volunteers gave mean flows between 4-4 and 5-9% of blood volume/min, or about 4 ml min-1 100 g-1 of bone. The variation between normal subjects was least when the results were expressed as % of blood volume/min rather than ml/min, ml min-1 kg-1 or ml min-1 1-73 m-2 body surface area. The precision of the technique was estimated to be 16-4%. 4. Addition of 1-5% random noise to the input data resulted in an uncertainty of 8-5% in the measurement of skeletal blood flow, suggesting that improved precision depends on closer control of physiological variables. 5. In six patients with severe untreated Paget's disease of bone, skeletal blood flow was 8-4-15-3% of blood volume/min. The increase was significant in all cases. 6. The absorbed radiation dose is low, so that the measurement can be repeated.

Adult↗

An improved mathematical model of human thyroid hormone regulation.

1. A mathematical model has been constructed of human thyroid hormone regulation by the anterior pituitary gland, which takes account of most of the currently available experimental data. 2. Successful simulation of data on the stimulation of thyrotrophin (TSH) secretion by thyrotrophin releasing hormone (TRH) was achieved assuming that the TSH secretion rate is proportional to the logarithm of the concurrent blood TRH level. 3. Data on the regulation of triiodothyronine (T3) secretion by TSH and the inhibition of TSH secretion by thyroid hormones in contrast could not be simulated on the assumption of instantaneous proportional responses. A mixture of proportional and integral control--the latter taking account of the past history of plasma levels of the regulatory hormone--appeared to be operating at both levels. 4. The pituitary gland appears to be more sensitive to a given fractional change in TRH secretion rate than to the same fractional change in T3 plasma concentration.

Humans↗

Effects of therapy on rate of absorption of calcium from gut in disorders of calcium homoeostasis.

A development of the double-tracer calcium absorption test, in which a function is derived for single-passage entry rate from the gut with time, has been assessed in various disorders of calcium homoeostasis. Single tests are diagnostically useful in calcium malabsorption but because of the wide spectrum of normal values a single test can only moderately enhance the accuracy of the diagnosis of hypercalcaemic states made primarily by other methods. On the other hand serial studies in the same subject can be much more informative because the test is normally highly reproducible if conditions are unchanged. Serial studies play an important part in assessing the efficacy of established methods of treatment in disorders of calcium homoeostasis and should be particularly helpful in studying the effects of new forms of therapy on the absorption process.

Adult↗