Biomedical subjects

R Wootton

Publications and source records attributed to R Wootton.

At least 127 records · Page 7Linked to original sources

PubMed1988

Errors in bone blood flow measured with microspheres due to sample preparation technique.

An experiment was carried out to examine the effect of boiling the carcass on the subsequent microsphere content of the skeleton. Intracardiac injections of radioactive microspheres were made in five rabbits and the animals killed humanely. The tibia and femur were then removed from one lower limb by dissection, and from the other after boiling it in a pressure cooker. The mean radioactivity in the bones was significantly less following boiling: 61% (SD 14) of the control tibia and 56% (SD 11) of the control femur. As a methodological check, the radioactivity in the bones of left and right legs was compared after both had been removed by boiling. In three animals, the mean activity (left compared with right) was 101% (SD 6) in the tibia and 100% (SD 3) in the femur. Boiling the carcass led to a substantial reduction in the microsphere content of the bones and cannot be recommended as a method of sample preparation for quantitative bone blood flow work.

Animals↗

PubMed1988

Glucose homeostasis in the newborn. Effects of oral feeding on response to fasting and intravenous glucose infusion in neonatal piglets.

The effect of oral feeding on the response to fasting and to an intravenous glucose infusion was investigated in neonatal piglets. Piglets, which had received no food at birth, reduced both their rates of glucose appearance and glucose utilisation (at 24 h: 43 +/- 3.5 mumol/min in previously fed piglets and 28 +/- 6 mumol/min in fasted piglets; at 48 h: 45 +/- 3.5 mumol/min in previously fed piglets and 25 +/- 5 mumol/min in fasted piglets). This reduction in glucose turnover was not associated with a fall in plasma glucose concentration, and all groups of piglets were normoglycaemic at the start of the study. An intravenous infusion of glucose (100 mumol/kg/min) resulted in suppression of hepatic glucose output and an increase in the glucose utilisation rate. Piglets, which had received no food at birth, had lower absolute rates of glucose utilisation throughout the period of infusion. The present study indicates that major changes in glucose turnover rates may occur prior to these being reflected in changes in blood glucose concentration. The results also indicate that oral feeding affects both steady-state glucose turnover and the response to an intravenous glucose infusion.

Administration, Oral↗

PubMed1988

Skeletal blood flow, iliac histomorphometry, and strontium kinetics in osteoporosis: a relationship between blood flow and corrected apposition rate.

In 20 untreated patients with idiopathic or postmenopausal osteoporosis, kinetic studies of skeletal blood flow (using 18F) and bone turnover (using 85Sr) were combined with dynamic histomorphometry performed on transiliac biopsies taken within 6 weeks of each other. In 8 patients the combined studies were repeated after treatment. A further 5 patients were studied only while receiving treatment. As expected, skeletal blood flow measured by 18F correlated with an index of 85Sr uptake into the exchangeable pools of bone. Additionally and independently, skeletal blood flow correlated with an index of the work rate of the osteoblasts in each multicellular unit of bone (the corrected apposition rate of Parfitt). These correlations were statistically significant in both the untreated patients (P less than 0.05) and the whole group (P less than 0.001). Further indices related to bone turnover at the level of the skeleton as a whole were significantly associated with skeletal blood flow only in the combined group.

Aged↗

PubMed1988

An analgesiometry system for use in rabbits with some preliminary data on the effects of buprenorphine and lofentanil.

A low cost infrared skin heating system has been designed to measure the efficacy of analgesics in rabbits. Following construction of a prototype, it was used to assess the effect of buprenorphine given subcutaneously and per rectum. Buprenorphine administered subcutaneously has a rapid onset of action, but its duration (8-10 h) appears slightly shorter than has been suggested previously; rectal administration appears to prolong its effect. Preliminary data show that lofentanil has a longer duration of action than buprenorphine and it may prove, therefore, to be a valuable long-acting analgesic in the rabbit.

Analgesia↗

PubMed1987

Skeletal blood flow in metabolic disorders of the skeleton.

Results are presented of measurements of skeletal blood flow made in 80 patients with painful benign or malignant diseases of the skeleton, excluding patients with Paget's disease. In crush fracture osteoporosis, total bone blood flow was slightly lower than normal although skeletal perfusion was normal. High values of bone blood flow were seen in 14/20 patients with osteomalacia and 3/12 patients with primary hyperparathyroidism. Very high values, comparable to those seen in the most severely affected patients with Paget's disease, were seen in polyostotic fibrous dysplasia, 2 out of 4 cases of Engelmann's disease and 1 out of 3 cases of renal osteodystrophy. Results were less elevated in myositis ossificans, secondary skeletal involvement with breast and prostatic carcinomata, myelomatosis and sympathetic osteodystrophy.

Adolescent↗

PubMed1987

A method for quantifying lipoprotein flux rates between plasma and arterial intima in vivo.

A new method is proposed for measuring in vivo the rates of transfer of plasma lipoprotein into and out of arterial intima in man. The technique requires the injection of a lipoprotein which can be labelled with two different tracers, followed by a single arterial sample during elective surgery. The feasibility of the method was tested by computer simulation and it was found that measurement uncertainties of the order of those likely in practice produced uncertainties of 7% SD in the calculated influx and 16% SD in the calculated efflux rates. The principal assumption, that lipoprotein in arterial intima can be modelled as a single compartment system, was tested in a preliminary study in an anaesthetised dog: reasonable evidence of monocompartmental behaviour was obtained. The new method was used in a preliminary study of three patients undergoing elective arterial surgery. Low density lipoprotein (LDL) labelled with 125I was injected about 24 h before surgery, followed by 131I-labelled LDL 4 to 6 h before surgery. The radioactivities of washed extracts of arterial intima were then measured in a gamma counter. LDL flux rates were higher in atherosclerotic specimens than in less seriously diseased or normal tissue, and were highest in the most hyperlipidaemic patient.

Animals↗

PubMed1987

A comparison in neonatal piglets of model-dependent and model-independent methods for measuring glucose turnover.

Steady state glucose turnover was measured in 53 conscious, unrestrained neonatal piglets by two different methods using 3H-labelled glucose as the tracer. In the first, model-dependent method, the plasma tracer concentrations following a spike injection of tracer were fitted in various different ways and the turnover was calculated from the area under the fitted curve extrapolated to infinity. Both exponential curves and negative power functions of time were fitted by non-linear least squares. In the second, model-independent method, tracer was infused continuously and turnover calculated from its equilibrium concentration. Conditions during 34 of the 53 experiments failed various tests of the steady state and the data were therefore discarded. In the remaining 19, glucose turnover measured by the different methods agreed fairly well. Although there was little difference between the results obtained by a two-exponential curve fit, by those obtained when the fast component was ignored, by a single exponential curve fit, and by the results from fitting a negative power function of time, the conventional two-exponential curve is to be preferred. There was a suggestion that at high turnover rates, the injection result underestimated the infusion result, assuming the latter to represent the reference method. This might have been due to extrapolation errors in the injection technique, either in the first few minutes following injection, or in the interval after the last sample. However, the notional volumes of distribution of the tracer suggest that the terminal phase of tracer elimination is in fact slightly faster than that predicted on the basis of samples taken during the first 120 min post-injection.

Animals↗

PubMed1987

Effect of diazoxide or glucagon on hepatic glucose production rate during extreme neonatal hypoglycaemia.

The relation between hepatic glucose production rate (HGPR) and plasma concentrations of insulin and glucagon was investigated in four term neonates who had severe hypoglycaemia. The hepatic glucose production rate was less than 20% of normal for fasting term neonates in all four babies and yet insulin concentrations were never greater than 12 microU/ml; two babies had very low glucagon concentrations (less than 60 ng/l). Two further neonates with similar histories also had plasma glucagon concentrations that were also extremely low (less than 20 ng/l). A single intravenous bolus of glucagon caused a rapid rise in hepatic glucose production rate towards the normal range, which was sustained for many hours after the bolus had been given. Diazoxide given to one baby suppressed previously 'normal' insulin concentrations still further (4.2 to less than 1.6 microU/ml) and thereby restored the hepatic glucose production rate to normal. In view of the normal plasma insulin concentrations at a time when the hepatic glucose production rate was reduced, we feel that the absolute concentration of insulin may be less important than the insulin/glucagon molar ratio in the control of glucose homeostasis in this group of infants. The changing of this ratio by means of boluses of glucagon may be useful in preventing rebound hypoglycaemia, which so often occurs when dextrose infusions are reduced either accidentally or in an attempt to restart oral feeds.

Blood Glucose↗

PubMed1987

Glucose homeostasis in the newborn: effects of an intravenous glucose infusion in normal and intra-uterine growth-retarded neonatal piglets.

Disturbances of glucose homeostasis are a common clinical problem in low birth weight human infants. Previous studies have demonstrated that the intra-uterine growth-retarded piglet is a suitable animal model for the study of such problems. The effects of an intravenous glucose infusion on glucose homeostasis have been studied in normal and intrauterine growth-retarded neonatal piglets using a non-steady state tracer technique. Despite suppression of hepatic glucose output, hyperglycaemia (plasma glucose greater than 10.0 mmol/l) developed in the majority of animals. The hyperglycaemia resulted from a failure to increase glucose utilisation adequately in response to the glucose infusion. Growth-retarded animals had an impaired ability to increase their rate of glucose utilisation, although, in common with the normally grown animals, they demonstrated a graded response to different infusion rates of glucose.

Animals↗

PubMed1987

Record-keeping requirements of the Animals (Scientific Procedures) Act 1986 and how to meet them.

The new Animals (Scientific Procedures) Act 1986 has significant implications in terms of record keeping. In many designated establishments, however, most of the records are already collected as part of good working practice and the new Act merely formalizes this situation. Recording the required information may be tedious, but it can be carried out using either a paper-based system or its computerized equivalent. The new legislation imposes no additional record-keeping requirements on personal licence holders and the real burden falls on the project licence holder, particularly for large projects involving several personal licence holders. In the case of an animal house operating a computerized system, considerable assistance with project record keeping can be given by the designated establishment and project status reports will be very helpful in this respect. Computerization also enables automatic production of cage labels which ensures uniformity of labelling and compliance with the Home Office guidelines.

Animal Welfare↗

PubMed1987

Rationalization and computerization of the drug supply to an animal unit.

Drug stocks in an animal unit were rationalized by discarding out-of-date or unwanted items and drawing up an approved stock list. A computerized system of stock control which enables a regular and accurate inventory of pharmaceuticals to be made was then established. In addition, the paperwork required for reordering drugs is produced automatically. Pharmaceuticals to a total value of 1650 pounds were discarded during the rationalization phase. The value of drugs stocked in the animal unit then stabilized at about one-third of previous levels. In the first 6 months of operation of the new system drug expenditure fell by about 40% in comparison with the same period 1 year previously. The drug stock control system has proved economical to operate and accurate, and can be run by persons without computer expertise. Valuable savings in both cost and labour have resulted. Effective management of drug expenditure by the animal unit is now possible.

Animals↗

PubMed1987

Increased half-life of gammaglobulin after prolonged intravenous replacement therapy.

The half-life of total IgG and antibodies to cytomegalovirus and pneumococcal polysaccharide type III was consistently prolonged after a 9 month course of intravenous gammaglobulin treatment in three patients with 'primary' hypogammaglobulinaemia. The half-life of antibody to tetanus toxoid showed no consistent pattern. These data are at variance with the traditional dogma that IgG half-life is inversely related to serum IgG concentration. They suggest that patients on intravenous gammaglobulin therapy are likely to need less, rather than more, infusions when their serum IgG has risen to within the physiological range.

Adult↗

PubMed1986

Reduction in potency and reversal of left-shifting activity of BW12C with the major and minor components of chicken hemoglobin.

The effects of the left-shifting, anti-sickling compound BW12C (5-(2-formyl-3-hydroxyphenoxy)pentanoic acid) on the oxygen saturation curve of whole chicken blood and the isolated major (AII) and minor (AI) components of chicken hemoglobin have been studied. The results support the postulated major binding mode for BW12C to human hemoglobin of bridging between the alpha-chain terminal amino groups in the oxy conformation with an important hydrophobic component contributed mainly by Pro 77 alpha residues. In chicken AII (Pro 77 alpha----Ser) BW12C still left-shifts at high concentrations but its potency is greatly reduced (at least 10-fold). In chicken AI (Pro 77 alpha----Ser and Val 1 alpha----Met) BW12C is a right-shifter with a potency comparable to that of 2,3-diphosphoglycerate suggesting that binding at the beta-chain termini in the deoxy conformation is now dominant with alpha-chain binding no longer significant.

Aldehydes↗

PubMed1986

Characterization of the binding of the anti-sickling compound, BW12C, to haemoglobin.

The anti-sickling agent BW12C [Beddell, Goodford, Kneen, White, Wilkinson & Wootton (1984) Br. J. Pharmacol. 82, 397-407] was designed to left-shift the oxygen saturation curve of haemoglobin (HbA) by preferential binding to the oxy conformation at a single site between the terminal amino groups of the alpha-chains through Schiff's base formation, ionic and hydrophobic interactions. In the present work, Schiff's base linkages formed with [14C]BW12C were reduced with NaBH4 and the alpha- and beta-globin chains separated. Under oxy conditions at a molar ratio of 2:1, the covalently bound BW12C is localized almost exclusively on a single alpha-chain; tryptic digestion confirms the terminal amino group (alpha 1-valine) as the reaction site, in accord with the design hypothesis. However, about half the labelled BW12C is released on tetramer disruption, suggesting the presence of additional non-covalent binding. Under deoxy conditions, alpha- and beta-chains are labelled approximately equally, and at higher molar ratios additional binding in both oxy and deoxy conditions is seen. Isoelectric-focusing studies under oxy conditions show a complex pattern of modified bands for both HbA and HbA1c (blocked beta-terminal amino groups) but no modification for HbA carbamylated at both alpha- and beta-terminal amino groups or at the alpha-chains only, again confirming the alpha-terminal amino region as the main interaction site. Equilibrium dialysis measurements under oxy conditions indicate two strong binding sites with a binding constant of less than 10(-6) M and a number of weaker binding sites. The present data thus confirm that BW12C binds at the intended locus but reveal additional non-covalent binding at an undefined site, and weaker binding through Schiff's base formation with other amino groups.

Aldehydes↗

PubMed1986

The single-passage extraction of 18F in rabbit bone.

The only clinically applicable method for the quantitative measurement of blood flow to the skeleton which has so far been developed rests on the assumption that the initial extraction of the bone-seeking isotope 18F from blood by bone is known and constant. Previous work to measure the single-passage extraction ratio of this isotope in rabbit bone has been criticised, so a novel technique has been developed in which isotope recirculation cannot occur. In addition, the post mortem uptake of isotope from surrounding tissues and the vascular tracer content of the bone can be monitored. The apparent extraction ratios of two bone-seeking isotopes, 85Sr and 18F, were measured in nine animals, and extrapolated to the time of death from both the time at which dissection of the bones began (giving a maximum value) and the time at which it ended (giving a minimum). Mean blood flow to the femur was 0.562 ml min-1 (SD = 0.170, n = 15) and mean blood flow to the tibia was 0.290 ml min-1 (SD = 0.140, n = 12). Statistical analysis of the results showed that there were significant differences in the extrapolated ratio between animals and significantly higher extraction of isotope in the tibia than in the femur. There was no significant difference between the extraction of 85Sr and that of 18F. The best estimate of the single-passage extraction ratio of 85Sr and 18F which can be made, therefore, is that in rabbit femur it is 0.88 (SE 0.04) and in the rabbit tibia it is 1.08 (SE 0.04). Post mortem uptake of isotope increases the apparent extraction ratio by about 1% per minute.

Animals↗

PubMed1986

Towards the computerized animal house: the Newcastle University Animal House Management System.

A suite of computer programs (available from the Laboratory Animal Science Association) has been written to carry out much of the routine administration of a central animal house facility. Principal functions include stock control and accounting. The programs are fully portable and can be implemented on almost any microcomputer. They are protected against data-entry errors and can be used by staff who have little or no computer experience. In 10 months' use at the Comparative Biology Centre, the Newcastle University Animal House Management System has become an indispensable management tool. The system has also been successfully implemented at Bath University.

Accounting↗

PubMed1985

ITA, a portable program for the interactive analysis of data from tracer experiments.

ITA is a portable program for analysing data from tracer experiments, most of the mathematical and graphical work being carried out by subroutines from the NAG and DASL libraries. The program can be used in batch or interactive mode, commands being typed in an English-like language, in free format. Data can be entered from a terminal keyboard or read from a file, and can be validated by printing or plotting them. Erroneous values can be corrected by appropriate editing. Analysis can involve elementary statistics, multiple-isotope crossover corrections, convolution or deconvolution, polyexponential curve-fitting, spline interpolation and/or compartmental analysis. On those installations with the appropriate hardware, high-resolution graphs can be drawn.

Biometry↗

PubMed1985

Reduction of skeletal blood flow in Paget's disease with disodium etidronate therapy.

Fourteen patients with Paget's disease of bone were treated with disodium etidronate in doses of 5 to 7 mg/kg per day. Skeletal blood flow (SBF), was measured by the modified 18F clearance technique of Wootton et al. (1976) before treatment and again during treatment. In 10 patients restudied 3-4 months after the start of therapy, SBF had fallen by a mean of 21% of the initial value, and the individual differences correlated well with the individual reductions in serum alkaline phosphatase (r = 0.77, P less than 0.01). The results were similar to those seen in an earlier study in patients treated with calcitonin. However, no early reduction in SBF was seen in six repeat studies performed at the end of the second week of treatment, in contrast with our previous findings with calcitonin.

Alkaline Phosphatase↗