The precision of a modern method for body compartment measurements using multiple isotopes.

Using readily available beta and gamma detectors, combined measurements of exchangeable sodium, exchangeable potassium, total body water and extracellular fluid volume using the isotopes 24Na, 43K, 3H and 35S were made in ten normal subjects. These measurements were repeated 1-6 weeks later so that an index of precision for each isotope study could be calculated. For such measurements the precision was 55 mmol for exchangeable sodium, 149 mmol for exchangeable potassium, 1.26 litres for total body water and 1.11 litres for extracellular fluid volume. The precision of our method is the best so far reported using readily available apparatus. These results may encourage further studies on different pathological conditions in man to be undertaken in peripheral laboratories.

Measurement of propofol concentration in sheep blood and plasma: effect of storage at different temperatures.

In planning a study of the pharmacokinetics of propofol in sheep, contradictions were noted in the literature with regard to loss of propofol during storage of blood samples. This prompted a study of such loss from samples of sheep blood and plasma during storage at room temperature, +4 degrees C and -20 degrees C, for up to 17 days, over a range of concentrations from 1 to 20 micrograms/mL. Samples were drawn from 22 different sheep. Analysis was by the method of Adam et al. (1981). The best estimate of the overall mean loss rate was 0.7% per day with 95% confidence limits of 0.3% to 1.2% per day. The loss rate increased nonsignificantly with storage temperature. There were very small nonsignificant differences of loss rate between plasma and blood, between different concentrations, and between genders. There were significant differences of loss rate between sheep--up to about 2% per day in blood or plasma from any one sheep.

The quantitative distribution of nebulized antibiotic in the lung in cystic fibrosis.

Nebulized antibiotic therapy in cystic fibrosis is an established procedure. The present study was designed to quantitate deposition, and assess its relation to the disease state. Twenty seven children and young adults with cystic fibrosis (mean 11.6 years, range 4-23 years, 12 females) were studied to establish the quantity and pattern of deposition of nebulized tobramycin in the respiratory tract. A single (120 mg) dose of nebulized 99 m technetium-labelled tobramycin was administered, and imaged with a gamma-camera. The mean penetration index (which compares the distribution of 81 m-Krypton gas with Tc-radioaerosol) was also used to measure peripheral deposition efficiency. The aerosol mass median diameter (MMAD) for the compressor-nebulizer system used was 5.3 u, measured with the Malvern Mastersizer. Serial sputum samples were fluroimmunoassayed for tobramycin in nine patients. A mean of 8.0 (SEM 1.0) mg tobramycin reached the lungs. There was no relationship between the total pulmonary deposition and indices of pulmonary damage in cystic fibrosis. Sixteen percent of the lung tobramycin reached the periphery. The greater the lung damage as indicated by FEV1 and Chrispin-Norman scores, the smaller the proportion of pulmonary tobramycin that reached the periphery. The mean penetration index increased with increase in the FRC, but bore no relation to other respiratory function tests or to chest X-ray scores. Sputum tobramycin concentrations reached levels bactericidal for Pseudomonas aeruginosa. Airway obstruction and damage affected the proportion of pulmonary tobramycin reaching the periphery. The proportion of tobramycin reaching the lungs was small and variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Compartmental analysis of cerebrospinal fluid transfer and absorption in simulated hydrocephalus.

A mathematical model of the cerebrospinal fluid (CSF) flow dynamics found in hydrocephalic infants with myelomeningocele lesions was constructed using criteria obtained from analogous clinical situations where 125I-labelled and 131I-labelled ortho-iodobenzoyl-amino-acetic acid (hippuran) had been employed to measure CSF flow dynamics. The quantitative results from this study allowed clinical data to be assessed and the importance of various CSF transfer mechanisms to be discussed. Our mathematical model indicates that the majority of radiopharmaceutical passes from the cerebral reservoir (the ventricles) into the blood. Experimental evidence indicates that the principal mechanism responsible for this movement is the bulk flow of CSF between its sites of production in the choroid plexus and absorption by the arachnoid villi.

The natural history and aetiology of deep vein thrombosis after total hip replacement.

A study of the natural history and aetiology of deep vein thrombosis in 499 patients after total hip replacement is presented. Deep vein thrombosis was diagnosed by scanning the leg for 125Iodine-labelled fibrinogen for a period of 14 to 18 days and by ascending phlebography. It has been shown that deep vein thrombosis occurs ater than in patients who have undergone abdominal operations, and the risk period is longer. The peak of onset of thrombosis is on the fourth day after the hip replacement. Attempts at prophylaxis using subcutaneous heparin or intermittent pneumatic compression of the calves delay the appearance of thrombosis. Analysis of possible aetiology factors shows that the age of the patient, the degenerative disease of the hip, the surgical approach, and under-transfusion of blood, all have a significant effect on the incidence of thrombosis.

Algodystrophy and osteoporosis after tibial fractures.

We made a prospective study of the incidence and natural history of algodystrophy and associated changes in bone mineral density in the ankles and feet of 60 consecutive patients who had suffered unilateral fractures of the tibial shaft. At bone union, 18 patients showed signs of algodystrophy. Its development was independent of the type of fracture management and of the severity of injury. Patients with algodystrophy lost significantly more bone mineral than did those without but the degree of this loss was independent of the type of treatment and of the time to fracture union. In most cases the symptoms resolved within six months of fracture union but in four patients they were still present at one year and two of these had not returned to work.

Regional pulmonary perfusion in horses: a comparison between anaesthetised and conscious standing animals.

The regional perfusion to the lungs of 14 ponies was studied using radioactively labelled microspheres injected intravenously. It was found that within half an hour of induction of anaesthesia the perfusion to the dependent lung had decreased significantly from the values in the standing animal. When anaesthesia was maintained for more than two and a half hours, however, the lung perfusions were not significantly different from the standing values when the animals were lying in lateral or supine recumbency.

Distribution of cardiac output in anaesthetised horses.

The radioactive microsphere method was used to determine the distribution of cardiac output in six anaesthetised ponies. Simultaneous measurements of cardiac output allowed calculation of the tissue perfusions (ml/min/100 g). Allowing for the fact that measurements were carried out on animals under halothane anaesthesia and which had respiratory acidosis, the results were comparable with published values for other species.

A "standard horse" for use in physiologically based mathematical modelling.

Standard data for the horse which can be used in physiologically based mathematical computer modelling are presented. The data includes figures for tissue mass, density and perfusion, obtained by measurement mainly from horses weighing 200 to 300 kg. Other related parameters such as mean transit times and tissue blood volume have been calculated and included in the actual values listed for a 250 kg horse.

Muscle perfusion in the horse.

Muscle perfusion was studied in conscious and anaesthetised horses by monitoring the clearance of a locally injected bolus of saline containing radioactive xenon (133Xe). The mean of all the measurements made from the brachiocephalicus and semimembranosus muscles in conscious subjects was 1.29 ml/min/100 g while in anaesthetised subjects it was 0.40 ml/min/100 g. The significance of these results is discussed in relation to the clinical occurrence of post anaesthetic myositis.

Efficacy of fixed minidose warfarin prophylaxis in total hip replacement.

OBJECTIVE: To determine whether a small fixed perioperative dose of warfarin would prevent deep vein thrombosis after total hip replacement. DESIGN: Prospective, randomised, double blind placebo controlled trial. SETTING: Winford Orthopaedic Hospital, Bristol. SUBJECTS: 148 patients having primary total hip replacement. INTERVENTION: Warfarin 1 mg given daily for one week before and three weeks after surgery. MAIN OUTCOME MEASURE: Deep vein thrombosis diagnosed by the iodine-125 labelled fibrinogen uptake method. RESULTS: Deep vein thrombosis occurred in 25 (34%) of the patients given warfarin and 19 (26%) of the controls (difference 8%; 95% confidence interval -6.8% to 22.8%). CONCLUSION: Fixed minidose warfarin does not prevent deep vein thrombosis after total hip replacement.

The radiation dose to man following the intravenous injection of radiosulphate (Na2(35)SO4).

An estimation of the radiation dose to mans' testes, the critical organ, for radiosulphate (Na2(35)SO4) has been made by a combination of studies on rats and human volunteers. The radiation dose to rats testes and the rate of disappearance of radiosulphate from the blood and urine of humans have been increased. The calculated radiation dose of 7.7 muGy/MBq to mans' testes is lower than previously reported.

Tissue blood content in anaesthetised sheep and horses.

The blood content of tissue in eight anaesthetized sheep and three anaesthetized horses was measured using chromium labelled autologous red blood cells. 2. Approximately half the total blood volume was found to be distributed within the body tissues and, with the exception of the spleen and fat, the distribution was similar in these two species.

Tissue perfusion in anaesthetised sheep.

1. Tissue perfusion was measured in seven sheep by the radioactive microsphere method. 2. The sheep were anaesthetised and ventilated to a near normal arterial carbon dioxide tension. 3. Cardiac output was measured utilizing the Fick principle as applied to thermodilution and at the end of the investigation the sheep were killed by an overdose of anaesthetic. 4. The results were compared with previously published values for conscious sheep and anaesthetised horses and found to be similar when known variations in body composition and physiology were considered.

Tissue/blood and tissue/water partition coefficients for propofol in sheep.

The primary objective of this study was to determine in vivo tissue/blood partition coefficients of propofol for use in physiological modelling of its pharmacokinetics. The sheep was used as an animal model. In the main series of experiments, crossbred ewes received a bolus of propofol 1% (Diprivan) followed by an infusion during which blood concentrations were measured at intervals. After 2 h, the sheep were killed with an injection of potassium chloride, and tissue samples were taken for storage at -20 degrees C and subsequent analysis. Tissue/blood partition coefficients depend on the amount of triglyceride which accumulates in blood from the propofol vehicle; for blood, free of added triglyceride, the following coefficients were calculated: brain, 3.23; heart, 5.94; kidney, 2.46; spleen, 1.86; semimembranosus muscle, > or = 1.61; triceps muscle, > or = 1.47. Calculated tissue/water coefficients were 35 times greater. There was indirect evidence of extraction of propofol by the lungs.

Albumin metabolism in elderly patients.

Hypoalbuminemia, without any apparent cause, is occasionally seen in elderly patients. Eleven patients (6 with plasma albumin of over 3 gm% and 5 with plasma albumin of 3 gm% or less), who had no evidence of liver disease or nephrosis and whose dietic history suggested that they were taking adequate amounts of protein were investigated, using 131I human serum albumin. None were acutely ill and their age ranged from 70 to 86 years. It was found that elderly subjects with plasma albumin level of 3 gm% or less had significantly reduced albumin pools and an increased fractional catabolic rate. It is suggested that this may be due to an impairment of the control of degradation in these patients. There was no increased gut loss of albumin in 3 hypoalbuminemic patients investigated with 131I-PVP.

The effect of xylazine on plasma thromboxane B2 concentration in sheep.

alpha 2-adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep. It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet aggregation were to follow platelet activation in response to the administration of alpha 2 agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B2 concentrations before and after the intravenous administration of the alpha 2-agonist drug xylazine at a dose of 0.1 mg/kg. It was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride (0.125 mg/kg), an alpha 2-adrenoceptor antagonist.

Pharmacokinetics of thiopentone in the horse.

The pharmacokinetics of thiopentone sodium administered intravenously as a single dose (11 mg/kg) were studied in acepromazine pre-medicated horses and ponies in which anaesthesia was maintained with either halothane (Group 1) or isoflurane (Group 2). The results showed that the disposition kinetics of thiopentone in horses and ponies were best described by a three-compartment open model. In plasma, a very short initial distribution phase in both horses and ponies, half-life 1.4 +/- 1.2 min (mean +/- SD) and 1.3 +/- 0.7 min, respectively, was obtained, which was followed by a second comparatively slower redistribution phase, half-life 16 +/- 12 min and 11 +/- 5 min, respectively. The volume of distribution for the drug was large, especially in the ponies which received isoflurane (1127 +/- 86 ml/kg), compared to the horses which received halothane (742 +/- 89 ml/kg). The drug had a somewhat shorter elimination half-life in the horses (147 +/- 21 min) than in than ponies (222 +/- 44 min), but no obvious difference in clearance of the drug was observed between the horses (3.5 +/- 0.5 ml/min/kg) and ponies (3.6 +/- 0.8 ml/min/kg).

99Tcm-Sn pyrophosphate scanning in suspected acute myocardial infarction using a mobile rectilinear scanner.

99Tcm stannous pyrophosphate injected intravenously gives a positive image of freshly damaged myocardium but not of normal or scarred myocardium. It is safe, cheap and generally available. One hundred and forty patients admitted to hospital with possible myocardial infarction were scanned with a mobile rectilinear scanner of the type available in most district general hospitals. When the diagnosis of infarction was definite on clinical, electrocardiographic and enzyme criteria the anterior scan was positive in 31 out of 36 patients (86%); and when it was probable, the scan was positive in 28 out of 41 (68%) and when it was doubtful the scan was positive in 23 out of 63 (37%). The optimum time for scanning was between the second and seventh days. Pyrophosphate scanning is a very valuable investigation even though it is not an absolute discriminator of myocardial infarction. It is useful in assessing patients with atypical or doubtful symptoms of infarction where the ECG is already abnormal or where there are other causes of raised enzyme concentrations. False negative scans are not common, but a negative scan does not outweigh strong alternative evidence of infarction. Positive scans occur in some patients with unstable angina without confirmatory evidence of infarction. Positive scans due to extracardiac lesions are distinguished readily.