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Biomedical subjects

R Wootton

Publications and source records attributed to R Wootton.

At least 181 records · Page 10Linked to original sources
PubMed1979

Fractured neck of femur in the elderly: an attempt to identify patients at risk.

1. During a 15-month period, 110 elderly patients admitted with fractured neck of femur were studied in comparison with 72 elderly control patients undergoing elective surgery admitted over the same period to the same orthopaedic wards. 2. A striking finding was the marked similarity of all variables measured in the fracture and control groups. The principal differences between the two populations were that the fracture patients had a lower mean forearm bone mineral content, and that their serum concentrations of albumin, globulin and phosphate were reduced. 3. Neither measurements of radioisotopic calcium absorption, nor those of the serum concentrations of calcium, 25-hydroxy-vitamin D3 nor alkaline phosphatase provided satisfactory discrimination between the groups. 4. Several indices were devised, based on linear combinations of the test results obtained, in an attempt to predict the liability to future fractures of patients being considered for prophylactic therapy with oestrogens or other drugs. However, further work is required to define an index of improved predictive power and to evaluate it prospectively.

Aged↗
PubMed1979

Species differences in the binding of compounds designed to fit a site of known structure in adult human haemoglobin.

1. Oxygen dissociation curves are reported for human haemoglobins A1, FII, FI, A1c and Raleigh (beta1 valine leads to acetylalanine) and for horse haemoglobin in the absence and presence of 2,3-diphosphoglycerate (DPG), or 4,4'-diformyl-2-bibenzyl oxyacetic acid, or the bisulphite addition compound of the latter. 2. These haemoglobins were selected because their amino acid sequences are different at the DPG receptor site of human adult deoxyhaemoglobin. 3. The size of the shifts of the dissociation curves are in the sequence expected from the postulated numbers of interactions made by each compound with each haemoglobin type, based on the assumption of a common receptor site for the three compounds. 4. Multiple linear regression analysis shows that the free energies of interaction of the compounds with the haemoglobins may be predicted, to a first approximation, by summing the number of ionic and covalent bonds predicted for each effector-receptor combination, a reversible covalent bond contributing about twice as much energy (-6.78 kJmol-1) as an ionic interaction (-3.14 kJmol-1).

Adult↗
PubMed1978

Skeletal blood flow in Paget's disease of bone and its response to calcitonin therapy.

1. Blood flow to the skeleton was measured by the 18F clearance method of Wooton, Reeve & Veall (1976) in 24 patients with untreated Paget's disease. In every patient but one, resting skeletal blood flow was increased. There was a significant positive correlation between skeletal blood flow and serum alkaline phosphatase and between skeletal blood flow and urinary total hydroxyproline excretion. 2. Fourteen patients were re-studied after they had received short-term (7 days or less) or long-term (7 weeks or more) calcitonin. Skeletal blood flow, alkaline phosphatase and urinary hydroxy-proline excretion fell towards normal in every case. There was some evidence from the short-term studies that calcitonin produced a more rapid fall in skeletal blood flow than in alkaline phosphatase. 3. Glomerular filtration rate appeared to increase transiently in response to calcitonin.

Alkaline Phosphatase↗
PubMed1978

A quantitative analysis of the effects of 2,3-diphosphoglycerate, adenosine triphosphate and inositol hexaphosphate on the oxygen dissociation curve of human haemoglobin.

1. Oxygen dissociation curves have been measured for human haemoglobin solutions with different concentrations of the allosteric effectors 2,3-diphosphoglycerate, adenosine triphosphate and inositol hexaphosphate. 2. Each effector produces a concentration dependent right shift of the oxygen dissociation curve, but a point is reached where the shift is maximal and increasing the effector concentration has no further effect. 3. Mathematical models based on the Monod, Wyman & Changeux (1965) treatment of allosteric proteins have been fitted to the data. For each compound the simple two-state model and its extension to take account of subunit inequivalence were shown to be inadequate, and a better fit was obtained by allowing the effector to lower the oxygen affinity of the deoxy conformational state as well as binding preferentially to this conformation.

Adenosine Triphosphate↗
PubMed1978

A computer simulation study of optimal thyroid radiation protection during investigations involving the administration of radioiodine-labelled pharmaceuticals.

The administration of iodide for thyroid blocking is now known to carry its own risks, at least in certain categories of patients. We have therefore made a theoretical study by computer simulation of the efficacy of various thyroid blocking regimes. In the case of injected 125I- or 131I-iodide, substantial thyroid protection may theoretically be achieved by a single oral dose of inorganic iodide, for example a 90% reduction in radiation dose is produced by only 20 mg iodide. Repeating the initial blocking dose is of little value. A single blocking dose, however, affords poor protection against radioiodine released from labelled plasma proteins. Both for short-lived proteins such as fibrinogen, and for the longer-lived proteins such as albumin, the optimum dosage schedule appears to be stable iodide given daily for two to three weeks. For instance, 10 mg daily for a fortnight will reduce thyroid irradiation by a factor of ten following injection of 125I-fibrinogen.

Albumins↗
PubMed1977

Influence of lipid concentrations and age on transfer of plasma lipoprotein into human arterial intima.

Transfer of low-density lipoprotein (L.D.L.2) from plasma to arterial intima was studied in 16 patients undergoing arterial surgery. Autologous labelled lipoprotein was used to demonstrate that L.D.L.2 enters the intima from plasma. Net flux of L.D.L.2 appeared to increase with age. Within each age-group the net flux of L.D.L.2 showed a pronounced positive correlation with plasma-L.D.L.-cholesterol concentrations. This may account in part for the association between hypercholesterolaemia and the development of atherosclerosis.

Adult↗
PubMed1977

The effect of 2,3-diphosphoglycerate on the oxygen dissociation curve of human haemoglobin.

1. Oxygen dissociation curves for concentrated human haemoglobin solutions (1.6 mmol dm-3 in haem) have been measured by mixing known quantities of oxy- and deoxyhaemoglobin solutions and measuring the resulting partial pressure of oxygen with an oxygen electrode. 2. Observations in the presence of 2,3-diphosphoglycerate support previous conclusions derived from experiments at low haemoglobin concentrations, the validity of which has been questioned. 3. The two affinity state model of Monod, Wyman & Changeux (1965) does not fully describe the actions of 2,3-diphosphoglycerate and a model in which this allosteric effector not only binds preferentially to the T state but also lowers the oxygen affinity of this state gives an improved fit to the data.

Allosteric Site↗
PubMed1977

Measurement of placental blood flow in the pig and its relation to placental and fetal weight.

In 12 pregnant sows (Sus scrofa domestica), containing 144 live fetuses, placental blood flow was measured by the indicator fractionation technique using radioactive microspheres. In 8 of these litters, which contained 96 live fetuses, placental blood flow as obtained in absolute units. Significant positive correlations were observed between placental blood flow and placental weight, between placental blood flow and fetal weight, and between placental weight and fetal weight. It is clear that the runt, by comparison with his littermates, has a low birthweight in association with a small placenta and a low placental blood flow.

Animals↗
PubMed1976

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↗
PubMed1976

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↗
PubMed1976

Physicochemical-activity relationships in asymmetrical analogues of methoxychlor.

Compounds of the general formula 2-aryl-2-(p-methoxyphenyl)-1,1,1-trichloroethane have been prepared and tested for toxicity toward houseflies, pretreated for 1 h with 2mug of piperonyl butoxide. The majority of the compounds synthesized were chosen with the aid of computer programs designed to ensurewell-spread sets of minimally correlated physicochemical parameter values. A nonlinear two-dimensional representation was used to map the active region of physiochemical parameter space and a regression equation was obtained relating the observed toxicity to a combination of these physicochemical parameters. The equation indicates that toxicity increases with the hydrophobicity of the molecules but is decreased markedly by the introduction of bulky substituents into the ortho positions of the benzene ring and less markedly by bulky substituents in the meta and para positions. Substituents which donate electrons to the benzene ring by the "resonance" effect favor high toxicity. The equation performs well in forecasting the toxicity of further members of the series.

Animals↗
PubMed1976

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↗