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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.

With the possible exception of ECF, body electrolyte spaces and pools can be measured with fair accuracy and are useful in their proper experimental context. The use of improved tracer techniques and mathematical analysis to study transfer rates between pools and the physiological factors which influence these rates offer a promising means of further progress in this field.

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.

1. Radiocalcium absorption was measured in duplicate in 10 subjects by the double-isotope method, with calcium as the oral carrier (2.5 mmol). Analysis of variance gave 95% confidence limits for a single measurement of fractional absorption and maximum absorption rate in a given individual of ±16.5% of administered dose and ±18.2% of dose/h respectively. 2. The size of these within individual variations suggests that alterations in the rate of calcium absorption-5-contribute to the week-to-week stabilization of some other controlled variable, such as plasma concentration of calcium. 3. In six of the subjects, calcium absorption was also measured with calcium loads at concentrations of 0.5, 5.0 and 20 mmol. Significant falls in fractional absorption, maximum absorption rate and mean transfer rate occurred as the load increased, together with a rise in mean transit time. Although between-individual differences at a given load were considerable, given a single-test result with a known carrier load, it is possible to predict quite accurately the results which would be obtained if a different carrier load were to be given.

Statistical analysis has been used to find the best relationship between mean transit time calculated from corrected (blood-background subtracted) renograms and empirical indices measured directly from the standard renogram. The best formula of those compared for estimating mean transit time when both time-to-peak and % maximum activity at 15 min are known is Y=0.17+0.49X1+0.003X2, where Y is a dependent variable and X1 and X2 are predictor variables.

Brain-blood partition coefficients for 133Xe were measured on 20 brain tumour specimens. Substantial variations were found from the values previously reported for normal brain, implying that the use of normal values for calculating tumour blood flow from 133Xe washout data can result in significant errors.

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 this hypothesis.

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 (51Cr-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.

1. We have measured the total plasma clearance, renal clearance and equilibrium distribution volume of [14C]oxalate, and the urinary oxalate excretion rate and plasma oxalate levels at approximately 6 month intervals for up to 2.5 years in five patients with primary hyperoxaluria. The renal clearance and distribution volumes of [99mTc]DTPA (diethylenetriaminepenta-acetate) were measured simultaneously to provide estimates of glomerular filtration rate (GFR) and extracellular fluid volume (ECF). The same measurements were made on each of five normal volunteers. 2. Clearances and distribution volumes were measured with a modified single injection technique. 3. The oxalate clearance was two to three times the simultaneously measured GFR in the patients and control subjects. The renal clearance of oxalate was less than the total plasma clearance in the patients. The oxalate distribution volume was approximately 1.5 times the ECF in both the patients and controls. Only small changes were observed over a 2.5 years period in these particular patients. 4. The plasma oxalate concentration was derived from the urinary oxalate excretion rate and the plasma [14C]oxalate clearance. It was raised in the patients. The oxalate removal rate was derived from the total plasma clearance and the plasma oxalate concentration.

1. We have measured the plasma oxalate concentration (POx), urinary oxalate excretion (UOx), oxalate equilibrium distribution volume (ODV), oxalate metabolic pool size [(ODV) × (POx)], total plasma oxalate clearance (PCOx), renal (or dialyser) oxalate clearance (RCOx), non-renal oxalate clearance (NRCOx) and the tissue oxalate accretion rate (TOA)= [(NRCOx) × (POx)] in three patients with severe renal failure due to primary hyperoxaluria who were being treated by peritoneal dialysis or haemodialysis, or by renal transplantation. The clearance (either GFR or dialyser) of [99mTc]diethylenetriaminepenta-acetate (DTPA) and the extracellular fluid volume (ECF) measured as [99mTc]DTPA distribution volume were also determined. 2. Negligible amounts of 14C were found in faeces or as 14CO2 in expired air and hence (NRCOx) = (PCOx-RCOx). 3. Haemodialysis removed oxalate more efficiently than peritoneal dialysis in the patient where a direct comparison was possible. Neither treatment could keep up with the TOA when performed for clinically acceptable times. 4. The plasma oxalate concentrations calculated from 14C clearance through the dialyser and the chemically determined concentration of the oxalate in the dialysate were in the range 111–146 μmol/l. This is higher than in normals and in hyperoxaluric patients who are not in renal failure. Hence, although the ODV and ECF are similar to those of hyperoxaluric patients without renal failure and normal control subjects, the oxalate metabolic pool (ODV × POx) is grossly enlarged. 5. In the patient treated by renal transplantation, the oxalate pool size diminished concurrently with the resumption of oxalate excretion but expanded again as renal function decreased due to oxalosis. 6. The quantitative data show that dialysis procedures can only be a temporary holding operation and the prognosis with transplantation remains bad unless excessive oxalate production can be controlled.

A method for compensating for crosstalk between nuclear counters and its application to a multidetector gamma counter is described. The standardisation procedure employed measures the relative efficiency of each detector for a sample within that detector and for the same detector when the sample is located in each of the other detectors. Results with a 12-element detector system show that the stored calibration data obtained in this way can be applied successfully to correct the observed count rates for crosstalk as well as detector sensitivity differences when using gamma emitters having energies up to 1.3 MeV.

The metabolism of any tissue is dependent on its blood supply, and the possibility exists that control of its blood supply forms one method of regulating the metabolism of bone. However, it has not previously been possible to measure skeletal blood flow (SBF) in man, for lack of a suitable technique. Use of the plasma clearance of a bone-seeking tracer (8) for instance, lacks full validation.

An apparatus is described, consisting of six large γ-ray counters connected in parallel to a suitable counting ratemeter. It will detect about 0·01 μC and will accurately measure quantities of the order of 1 μC of I131 or Na24 in samples of urine up to 2 litres and of faeces up to 500 gms. without it being necessary to open the containers. P32 can be detected in microcurie amounts by bremsstrahlung, thus simplifying the monitoring of excreta from P32 therapy patients. The use of this equipment for measurements in live laboratory animals is suggested. In practice, a considerable saving of time and effort is effected by the use of this method.

No consistent correlation was found Summary between bilateral regional cerebral-cortex perfusion-rates and the clinical and radiological findings in 34 patients with extracranial cerebrovascular disease. In 10 of these patients the effect of operation was examined. The removal of severe stenosis in a major extracranial vessel did not improve the regional cerebral-cortex perfusion-rate.

1. Double-tracer studies have been carried out in order to investigate the validity of a whole-gut perfusion technique for the measurement of gut lumen-to-plasma and plasma-to-gut lumen sodium fluxes in man. 2. The use of two tracers permits differentiation between the unabsorbed orally administered sodium in the stools and the sodium which has been absorbed and resecreted. The latter is by no means negligible and may amount to some 30% of the recovered material. 3. The available data do not permit the calculation of the absolute values of the bidirectional fluxes without the introduction of some assumption concerning the reabsorption of the sodium which crosses from the plasma to the gut lumen. It is assumed here that this sodium is absorbed by the gut to the same extent as the orally administered material. Analysis of the kinetics of sodium transfer from mouth to stool direct and via the blood plasma in normal subjects and patients with diarrhoea provided experimental evidence confirming the correctness of this assumption. 4. In eleven normal volunteers the gut lumen-to-plasma flow of sodium averaged 13.0 mmol min−1, implying that the observed absorption averaging 1.65 mmol min−1 represents a relatively small imbalance between the bidirectional fluxes. Although one patient with post-gastrectomy dumping syndrome had high fluxes and another with malabsorption following gut resection gave low values, it is suggested that changes in the fluxes in the same patient are more significant than isolated observations on individuals. 5. Granted the validity of the primary assumption, a considerably simpler technique may be used for clinical and field studies which is sufficiently accurate for most purposes and employs a single tracer.

Deconvolution techniques used in circulation studies have been compared by generating synthetic curves with known parameters and analysing them by digital and analogue methods. The digital computer technique introduces a systematic error which can only be reduced to reasonable proportions when prohibitively long computer times are used. The analogue computer gives results of sufficient accuracy for clinical purposes which can be available within minutes of completing a measurement.

Intestinal calcium absorption was measured by the oral administration of calcium47 (in milk as a carrier) to 15 normals and 30 patients and by following the blood concentration at two hours, the twenty four hour urine excretion and cumulative faecal excretion of the isotope. Simultaneous calcium balances allowed an estimate of calcium absorption to be made and this correlated with the blood and faecal data once an allowance was made for the endogenous secretion. This was found to be highly variable, mean values in the patients being 300 mg/24 hours. A slow type of intestinal absorption was found in the osteoporotic group of patients.

The advantages of using iodine-132 instead of iodine-131 in clinical applications are discussed. Its use in diagnostic tests can result in a reduction of the radiation dosage to the patient by at least a factor of 15 and in some cases, of the order of 100. It is compared with iodine-131 in thyroid tests, in plasma-volume determinations, in haemodynamic studies, and in the localization of placental sites and its use, with iodine-131, in double tracer studies is considered. The production of tellurium-132, which is the mother substance of iodine-132, from the fission products of uranium is described, and a method is given for the separation of iodine from tellurium, using only simple, normally available apparatus.

Summary It is now possible to measure the absorption of calcium from the gut and the rate of endogenous secretion with the aid of tracer techniques. Bone accretion and resorption rates can be measured provided it is assumed that there is no return of tracer from the bone once it has been incorporated and that there is a time after administration of the tracer when the plasma level of tracer reflects the size of the ‘not bone’ pool. It is suggested that there is little to choose between the various published compartmental models, since they all involve the same basic assumptions. The measurement of changes in total body calcium by neutron activation analysis is thought to be of considerable potential value for long-term studies. Short-term studies of skeletal metabolism under steady-state conditions have not provided much useful clinical information or further insight into calcium metabolism. Further progress depends on the development of more sophisticated models capable of analysing data obtained under non-steady-state conditions with a view to studying the homeostatic mechanisms involved. for this purpose the use of analogue computer techniques is recommended.

The electrical and mechanical requirements are discussed from the points of view of designer and user. Instruments described in detail are: (1) A 4-channel logarithmic ratemeter employing Geiger counters and used typically for blood circulation investigations; (2) Clinical monitor using a Geiger counter, for tests not requiring high accuracy and where compactness and porta. bility are desirable; (3) Recording count-rate meter employing a scintillation counter, particularly useful for recording transient phenomena lasting only a few seconds; (4) Standard s-y ionization chamber for checking the activities of solutions of radioactive isotopes.

At the Geneva Conference on the Peaceful Uses of Atomic Energy, from August 8 to 20, 1955, some 450 papers were read and discussed, and apparently a further 600 which were not read are to be included in the Proceedings. Any report such as this can necessarily only be a record of a few personal impressions, and those requiring more detailed information should refer to the Proceedings which are about to be published by the United Nations Organisation. Five of the 16 volumes are to deal with medical applications of isotopes, biological actions of radiations, biochemical and physiological studies, safety precautions and dosimetry. In the following report the numbers of the papers referred to are given in brackets. Practically all the applications of radioactive isotopes in medicine which were discussed at the Conference have been published previously in various clinical journals. However, owing to language difficulties and the inaccessibility of the relevant publications the greater part of the work done in t...

The relative solubilities of trace amounts of 133Xe at 37? C in human plasma, red blood cells, grey and white matter of the brain, and in homogenized whole brain have been determined. From these data the tissue/blood partition coefficients for cortex, white matter and whole brain have been calculated as a function of haematocrit. On the basis of the measured 133Xe solubilities it is estimated that the human brain consists of 60?3?6?3% grey matter and the remainder white matter.

The use of radioactive isotopes for measurements of body electrolyte content and turnover rate is briefly reviewed. Some of the more useful radioactivity measuring techniques are discussed including methods for double traces investigations and for the direct measurement of whole body radioactivity content.

For many years the M.R.C. Isotope Panel has authorized the use of radiopharmaceuticals with the proviso that the thyroid gland be blocked when appropriate. However, the actual procedures or policies to be followed have not been formally stated and the working party was asked to study the present information and to report to the panel. The working party recommends that when activities of technetium-labelled radiopharmaceuticals below 5 mCi are being administered there is no requirement to use a thyroid blocking agent. Where activities higher than 5 mCi are being administered, thyroid blocking agents should be administered when they do not conflict with the objectives of the test, e.g. the visualization of the thyroid. The working party recommends that the blocking agent to be used should be either 50–100 mg of potassium perchlorate administered intravenously at the time of the injection of the radiopharmaceutical or 200–400 mg administered orally half an hour to an hour before the test. There is good clini...

Whole-bowel perfusion with the addition of isotope labelling has been used to study sodium-ion transport across the intestinal mucosa in human cholera. The site of maximal disturbance of ion transfer was in the duodenum and upper jejunum. During the acute phase of the disease there was a striking reduction in bidirectional sodium movement across the mucosa. The movement from lumen to plasma was the more depressed, and this resulted in net accumulation of sodium in the intestinal lumen. These findings do not support previous concepts of predominant effects of cholera on a sodium pump or excess filtration and secretion, but raise wider issues relating to mucosal-cell function and the splanchnic circulation. These disturbances may not be unique to cholera, and their elucidation may explain the pathogenesis of other diarrhœal states.

1. We have measured glomerular filtration rate (GFR), extracellular fluid volume (ECF), oxalate distribution volume (OxDV), plasma oxalate concentration (POx.), plasma total clearance of oxalate (PCOx.), oxalate metabolic pool size [(OxDV) × (POx.)], renal clearance of oxalate (RCOx.), oxalate excretion, tissue clearance of oxalate (TCOx.) and tissue oxalate accumulation rate [(TOx.A) = (TCOx.) × (POx.)] in three patients with type I primary hyperoxaluria (hyperoxaluria with hypergrycollic aciduria) when they were taking pyridoxine and after discontinuation of the vitamin. 2. Seven days after stopping pyridoxine the plasma oxalate concentration, oxalate metabolic pool size and the urinary excretion of oxalate had all increased between seven- and eight-fold in two of the patients. The third patient showed no changes on stopping pyridoxine. 3. These results support the view that pyridoxine acts by reducing oxalate biosynthesis in some patients with type I primary hyperoxaluria. 4. The possible biochemical basis for this effect is discussed.

With the possible exception of ECF, body electrolyte spaces and pools can be measured with fair accuracy and are useful in their proper experimental context. The use of improved tracer techniques and mathematical analysis to study transfer rates between pools and the physiological factors which influence these rates offer a promising means of further progress in this field.

A case is reported of a patient with renal failure and developing systemic and renal oxalosis due to pyridoxine-resistant type I primary hyperoxaluria. In spite of vigorous haemodialysis and hydration before and after operation, an allografted cadaveric kidney failed because of oxalate deposits in the transplant. The patient was treated by combined hepatic and renal transplantation. The liver allograft functioned well but the kidney had poor function due to primary acute tubular necrosis aggravated by steroid-associated acute pancreatitis, systemic cytomegalovirus infection and high cyclosporin A levels. The patient died from generalised cytomegalovirus infection. The early course after operation was associated with a reduced rate of oxalate production, which would slow the rate of oxalate deposition in the tissues. The size of the oxalate metabolic pool was also diminished. These observations are compatible with the grafted liver having corrected the metabolic lesion.

The whole-body retention of intravenously administered [99mTc]DTPA was measured by urine analysis and whole-body counting in eight normal subjects. On average, the elimination of [99mTc]DTPA was faster in these subjects than in 11 patients under study for hypertension whose whole-body retention data were used in MIRD Dose Estimate Report No. 12. The average residence time for [99mTc]DTPA in total body, less bladder contents, was only 65% of the MIRD value. However, despite this difference, the dosimetry is similar in both cases largely owing to the influence of radioactivity in bladder contents. Approximately 2-3% of the administered radioactivity was retained in the body for a time that was long relative to the physical half-life of 99mTc, and probably reflects a small amount of protein binding of the DTPA preparation.