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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. 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.

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.

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...

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...

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 development of gamma -ray imaging techniques can be traced from the pinhole camera with X-ray film recording of the image-a hopelessly insensitive technique. A major step towards improved sensitivity was to increase the absorption of incident gamma -radiation in the detector by using a suitable crystal. Detection of the emitted light quanta improved from the photographic film by way of the image intensifier until high gain photomultiplier tubes became commercially available. By about 1955 and for the next decade, the rectilinear scanner dominated the field of clinical gamma -ray imaging; this was also the period when 131I was by far the most widely used radionuclide in medicine. By 1958 Anger had already built the first gamma camera, probably five years before its time, closely followed by the positron camera. Probably the most important advance in the 1960s was not the rapid technical developments in instrumentation but a modest paper presented by Harper in 1964 on the clinical use of 99Tcm. Recently there have been technical developments in computer data reduction and processing. The dominant role of the gamma camera and 'region of interest' facilities has tended to encourage the superstition that the human body is a two-dimensional object. The increasing interest in tomographic imaging represents a return to reality, but the increased amount of information required means the use of even shorter lived radionuclides.

The contribution from radioactivity in bladder contents to dose commitments to the embryo, ovaries, red marrow, kidney, bladder wall and total body has been estimated for various renal radiopharmaceuticals, assuming a bladdervoiding period of 3.5 h. For hippuran and GFR agents this contribution is 70-97% of the embryo dose and 50-93% of the ovary dose. The embryo dose exceeds the ovary dose by a factor of two or more. For the radiopharmaceuticals with no significant kidney retention, the surface dose to the bladder wall is higher, by more than an order of magnitude, than doses to other organs and is largely responsible for the effective dose equivalent exceeding the estimated whole-body dose by factors of up to 25. Since the estimation of cumulated activity in bladder contents is necessary for bladder dosimetry, a nomogram based on a 3.5 h voiding period is presented as a convenient aid for this purpose.

A transportable apparatus for isotope renography, which allowed deconvolution analysis, was used to study the prevalence and prognosis of abnormalities associated with urinary schistosomiasis. Before carrying out studies in a heavily infected community, observations were made in a non-endemic area to allow derivation of criteria for abnormality. Comparison of the findings in the two areas showed that changes suggesting urinary tract obstruction were more common in the endemic area in subjects between nine and 45 years but not in older subjects. Measurements of effective renal plasma flow showed renal function was impaired in the endemic area in subjects older than 17 years but not in younger subjects. In the endemic area the results of renography were unrelated to the urinary egg count of the subjects examined, but there was an improvement in the abnormal renograms in a group of subjects aged between nine and 20 years who were re-examined a year after treatment with metrifonate. Follow-up data about 316 subjects was obtained two years after renography. Nine subjects had died, including four of the five subjects with abnormalities suggesting both obstruction and over-all loss of renal function. These findings, which are comparable to the results of similar studies using radiological techniques, suggest urinary schistosomiasis may be a significant cause of mortality in adults in intensely infected communities.

Summary Twelve patients with a diagnosis of schizophrenia and thirteen control subjects were injected with 77Br-bromospiperone and scanned using single photon emission tomography after 16 h. Although a statistically significant increase in patients by comparison with controls could be demonstrated, wide variations in specific activity of the ligand preclude a firm conclusion. In two patients but no controls an asymmetry in striatal uptake was noted, the uptake on the left being less than that on the right.

We have noted the strong reaction of the Council of the British Nuclear Medicine Society (Croft and Maisey, 1978) to our paper on the “ten-day rule” and its possible relevance to nuclear medicine. This reaction would appear to contradict the current advice given in ICRP 26 para. 206, the NCRP Report No. 53, and the WHO Technical Report Series No. 611. All these publications emphasize the need to consider what action should be taken to avoid irradiation of the embryo particularly in its early stage of development.

Summary 1.I 131 protein tissue clearance tests, serial limb volume studies during postural drainage and refilling, and differential pressure measurements have been carried out on a series of sixteen patients with idiopathic lymphœdema or secondary lymphœdema. The results obtained have been correlated with clinical findings, lymphangiograms and venograms, and also with data obtained from normal persons. 2.The data obtained enable the patients to be classified into two groups. The patients in Group 1 are those whose symptoms are due to lymphatic obstruction. In Group 2 the primary ˦tiological factor is thought to be venous obstruction. 3.The tissue protein clearance rate was greatly reduced in both groups. In Group 1 this was attributable to reduced lymphatic drainage. Correlation with limb volume studies suggested that the reduced clearance rate in Group 2 patients was due to an increase in the tissue fluid protein pool rather than to a reduction in the lymphatic drainage of protein. 4.Subcutaneous tissue hydrostatic pressures in normal females are approximately 7 mm. Hg lower than those in normal males. It is suggested that this might account for the greater incidence of lymphœdema in women. 5.In normal women the subcutaneous pressure is lower than the muscle pressure but in patients with lymphœdema this gradient is reversed. This provided the rationale for surgical operations designed to drain fluid from the subcutaneous tissues into underlying muscle. 6.The I 131 protein clearance studies are of little value for the initial assessment of individual patients but may well prove to be the most sensitive method for evaluating the response to treatment. Limb volume and drainage measurements and tissue pressure measurements are easy to perform and are likely to be clinically useful, but further studies on tissue pressure-volume relationships are needed for normal men and women and lymphœdema patients.

In a report which predicted the availability of fission product 132Te (Winsche, Stang and Tucker, 1951) it was suggested that its daughter product, 132I, might be of value in the diagnosis and treatment of thyroid disorders. It soon became apparent that 132I would be valuable for many other clinical applications, such as haemodynamic studies and plasma volume measurements, since the short half-life of 2·26 hours (Emery and Veall, 1954) would permit the administration of comparatively large tracer doses without appreciable radiation hazards to the patient (see note A below); and measurements could be repeated at frequent intervals without interference from residual activity. For such applications it was first necessary to develop a method whereby the isotope could be prepared in the form of sterile iodinated human serum albumin, and which unlike the procedures currently employed for 131I, could be carried out in an hour or less. The following procedure, which was based on that employed by Francis, Mulligan...

Isotopes, both radioactive and stable, have proved to be very valuable research tools when used as tracers in the study of many of the dynamic processes, both physical and chemical, which occur in the living organism. In many cases, where a particular disease is associated with a characteristic disturbance in one of these processes, the isotope technique could provide a useful diagnostic method were it not necessary to take serial samples of a particular tissue, or samples from various tissues, for analysis. However, in the case of the radioactive isotopes, it is often possible to avoid this difficulty by using what have now come to be known as in vivo counting techniques. The present discussion is confined to what is probably the most generally useful type of measure-ment in this category, namely, the detection and measurement of a radioactive isotope within the patient's body by means of externally placed instruments which are sensitive to γ radiation. Although such measurements account for only a small...

Regional cerebral cortex perfusion (CPR) rates were measured in 34 patients who were being considered for extracranial vascular surgery in the Professorial Surgical Unit at St. Mary’s Hospital, London. 10 patients eventually had an operation and the measurements were then repeated postoperatively. The cerebral blood flow data were not used in the selection of patients for surgery. Simultaneous bilateral measurements of regional cerebral cortex perfusion rates were estimated by the inhalation method. This technique is particularly suitable for the study of the effect of carotid lesions on cortex perfusion rates and has some advantages over other methods of blood flow measurement currently available. First it gives simultaneous bilateral measurements, and in the present series this has shown to give valuable additional information, secondly all sources of blood supply to the hemisphere are labelled with tracer, third no carotid puncture or internal carotid artery catheterization is necessary. This is particularly useful for carrying out postoperative measurements after the acute effect of the operation has passed and where there is no indication for repeat angiography. In addition the response to the inhalation of 5% CO2 was measured in 10 patients, in 4 of these the measurements were repeated postoperatively. The lesions were divided into 4 grades according to the single-plane angiographic appearances; Grade I being atheromatous irregularity only. Grade II a moderate stenosis but not significant in terms of local vessel flow. Grade III stenoses were thought to be significant in terms of local blood flow and Grade IV were complete occlusions.

Increasing attention is being paid to the potential radiation hazards to infants being breast-fed by mothers who have been administered various radiopharmaceuticals. In a recent letter to the Editor, Palmer (1979) considered the particular problem of breast-feeding an infant by a mother who received 3.7 MBq (100 μCi) 125I-labelled fibrinogen, and predicted a dose commitment of over 4 Gy (400 rad) to the infant's thyroid, had breast-feeding not been discontinued. Whilst sharing the author's desire to warn of problems of this nature, we believe the dosimetry has been over-estimated for the case in question.

The ability to measure the radioactivity of a sample in liquid form is particularly useful in biological and medical work, as it usually eliminates the necessity for chemical separations before the samples are counted. The counting tube Type CV2145 (Veall, 1948) is widely used for this purpose, but has the disadvantage of a low sensitivity for the softer β emitters; some time must be spent in cleaning the counter between samples, and solid samples such as tissues or animal organs must be digested before counting. The apparatus described here cannot be regarded as an appreciable improvement on the liquid counter from the point of view of sensitivity, but it is not subject to the last two disadvantages, and in many cases its use can result in a considerable saving of time and labour.

Thymoxamine administered intravenously (30 mg.) or locally by subcutaneous injection (1 μg. per ml.) produces a striking increase in the nutritional blood-flow of tubed skin pedicles and flaps, but has no effect on normal skin. The same effect is found in completely detached denervated flaps and has been observed in the calf skin in one patient who had had a bilateral lumbar sympathectomy some years previously.