Training of staff for the delivery of PET/CT services in the UK.

Evidence for the cost effectiveness of PET/CT imaging is now driving the widespread introduction of PET/CT services throughout the UK. The provision of PET/CT facilities will require a workforce of medical, scientific, technical and engineering staff who are adequately trained and fit for purpose. Suitably trained staff in this speciality are scarce. The development and accreditation of training courses and other educational resources for training programmes in all disciplines will therefore be required at a national and regional level. The implementation of PET/CT training can be achieved more cost-effectively by developing multi-professional learning resources whenever possible. It is intended that the recommendations would be implemented by close co-operation of both public and private healthcare providers together with educational establishments.

Isoprenylation of polypeptides in the nematode Caenorhabditis elegans.

Covalent modification of eucaryotic proteins, involving addition of isoprenyl groups, is a widespread phenomenon. Here we provide direct evidence for this form of covalent modification in the free-living nematode, Caenorhabditis elegans. Following incubation in the presence of [3H]mevalonolactone, specific C. elegans polypeptides became labelled in both aqueous and detergent (Triton X-114)-enriched extracts. Chemical and GC-MS analysis of modifying groups, cleaved from C. elegans polypeptides, revealed that geranylgeranylation and, to a lesser extent, farnesylation of target polypeptides occurred. Immunoblot analysis provided preliminary evidence that the ras-like let-60 polypeptide was a target for isoprenylation in C. elegans.

The use of [99mTc]-HM-PAO in the diagnosis of primary degenerative dementia.

The clinical value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia due to cerebral atrophy was evaluated by comparing the pattern of distribution [99mTc]-HM-PAO in three dementing conditions. Imaging was carried out in 26 patients with suspected Alzheimer's disease, 14 with dementia of the frontal-lobe type, and 13 with progressive supranuclear palsy. Images were evaluated and reported without knowledge of clinical diagnosis with respect to regions of reduced uptake of tracer. Reduced uptake in the posterior cerebral hemispheres was characteristic of Alzheimer's disease, while selective anterior hemisphere abnormalities characterized both dementia of the frontal-lobe type and progressive supranuclear palsy. The latter conditions could be distinguished on the basis of the appearance of integrity of the rim of the frontal cortex. The technique has an important role in the differentiation of degenerative dementias.

Excretion of iodine-123-hippuran, technetium-99m-red blood cells, and technetium-99m-macroaggregated albumin into breast milk.

The amount of radioactivity excreted in breast milk following three different nuclear medicine procedures on twelve nursing mothers has been measured. Some of this information has already been incorporated into the latest guidelines on suspension of feeding after maternal radiopharmaceutical administration. The overall radiation dose that the patients' babies would have sustained had breast feeding not been interrupted has been estimated as an effective dose equivalent. A model has been developed to describe the relationship between clearance of activity from the milk, time between expressions, and the fraction of milk expressed. Some simple guidance is given on calculation of suitable interruption times for any individual mother from counts on her milk samples.

Identification of methyl farnesoate in the cypris larva of the barnacle, Balanus amphitrite, and its role as a juvenile hormone.

Previous investigations have shown that insect juvenile hormone (JH) and its analogues induce precocious metamorphosis of barnacle cypris larvae. In the present study, methyl farnesoate (MF; structurally identical to JH III, except for the absence of an epoxide group) has been shown to have a concentration-dependent effect on the development of cyprids of the barnacle Balanus amphitrite. Analysis of cypris extracts by gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) confirmed the presence of endogenous MF. These data provide evidence that MF functions as a juvenilizing hormone in barnacle cyprids, an effect that hitherto has not been noted.

Negative ion ammonia chemical ionization and electron impact ionization mass spectrometric analysis of steryl fatty acyl esters.

Synthesis of steryl palmitates, varied in the nature of the steryl moiety, provided model compounds for investigation of the mass spectrometric behavior of steryl long-chain fatty acyl esters. The structure of the steryl moiety was varied according to: (i) position and degree of unsaturation in the steroid nucleus and C-17 side-chain, (ii) position and degree of methylation, (iii) presence or absence of a 9 beta, 19-cyclopropane ring. Compounds were chosen so as to be representative of biochemically important steryl esters. Electron impact (EI) behavior of steryl palmitate esters closely resembles that of their short-chain (e.g. acetate) counterparts. M+.ions were generally weak or absent and the major high mass ions arose from characteristic fragmentations of the steroid nucleus following loss of the acyl moiety ([M-RCO2H]+.). Fragment ions characteristic of the acyl moiety were lacking. Negative ion chemical ionization (NICI) using ammonia as reagent gas, on the other hand, afforded spectra containing characteristic fragment ions [RCO2]-, [RCO2-18]-, and [RCO2-19]- from which the nature of the fatty acyl moiety can be readily deduced. Hence, NICI and EI provide complementary means of ionization for the mass spectrometric determination of structures of steryl esters.

Thallium-201 myocardial imaging in patients with angina pectoris and anomalous aortic origin of the circumflex coronary artery.

Anomalous aortic origin of the circumflex coronary artery is the commonest coronary artery anomaly. In this study, the significance of anomalous aortic origin of the circumflex coronary artery was investigated in seven patients with exertional chest pain using exercise thallium scintigraphy. Five patients with circumflex coronary arterial disease served as controls. Myocardial perfusion was normal in the five patients with a nonstenosed anomalous artery. In these patients, exercise heart rate and blood pressure response were normal. Two patients with a stenosed anomalous circumflex coronary artery and four of the five control patients had posterolateral myocardial perfusion defects. It is concluded that anomalous aortic origin of the circumflex coronary artery does not cause impairment of myocardial perfusion unless it is the site of significant coronary arterial stenosis.

The importance of using anterior and posterior views in the calculation of differential renal function using 99Tcm-DMSA.

Radionuclide techniques for determining relative renal function are well established. One simple method uses the count rate from static images obtained using 99Tcm-dimercaptosuccinic acid (DMSA). We have reviewed 277 DMSA scans and shown that it is important to obtain the geometric mean of counts from the anterior and posterior views in order to correct for the different amounts of attenuation for each kidney. If counts were obtained from the posterior view only, erroneous results would be obtained in 8% of children under 13 years, in 28% of patients aged between 13 and 20 years and in 32% of patients over 20 years of age.

The incidence and severity of hypoxia associated with 99Tcm Technegas ventilation scintigraphy and 99Tcm MAA perfusion scintigraphy.

Inhalation of the ventilatory radiopharmaceutical 99Tcm Technegas leads, in some patients, to symptoms that may be attributed to temporary lowering of oxygen saturation. In order to evaluate this, oxygen saturation was measured by pulse oximetry in a series of patients undergoing Technegas ventilation scintigraphy. A decrease in oxygen saturation was recorded in 87% of the patient group. The mean change, as a percentage of the initial value, was 8.3% (range 1-24%). Hypoxia arising in association with Technegas administration may be reduced by pre-oxygenation. In patients who were pre-oxygenated, oxygen saturation did not fall below 85% (PaO2: 50 mmHg) but in 39% of those not pre-oxygenated the value fell below this level. Oxygen saturation was also monitored in a series of patients undergoing perfusion scintigraphy. In 17% of patients a decrease was recorded (range 2-11%). In view of the large number of perfusion scans performed annually in this department and elsewhere without untoward effect, such temporary decreases in oxygen saturation presumably present no hazard to the patient.

99Tcm-Technegas and krypton-81m ventilation scintigraphy: a comparison in known respiratory disease.

Krypton-81m gas, by virtue of its imaging characteristics, is often considered the "gold standard" for ventilation scintigraphy but its use is restricted by its high cost and limited availability. The new radiopharmaceutical 99Tcm-Technegas, a suspension of ultrafine technetium-99m labelled carbon particles, produces high-quality images of ventilation and has the advantage of continuous availability. As part of our evaluation of Technegas the two were compared in 40 patients with a variety of established respiratory diseases. Disparities were seen in five patients in five diagnostic groups and may be a consequence of the differing physical properties of the two agents and the different inhalation techniques used. In addition two interesting features were noted on the Technegas images. (1) Hot spots were seen in 50% of patients, particularly in those with a degree of airways obstruction; (2) preferential basal deposition of activity was seen in 30%, particularly in patients with idiopathic pulmonary fibrosis. Both features were significantly associated with parameters of pulmonary function indicating obstructive lung disease in the former case and restrictive lung disease in the latter.

Contamination levels and doses to staff arising from the use of Technegas.

The aim of this work was to assess the levels of airborne activity and contamination arising from Technegas ventilation scintigraphy and to estimate doses to staff. The maximum air concentration was below the 99Tcm-derived air concentration limit and considerably lower than reported levels for conventional radioaerosols. The level of contamination on staff gloves and aprons exceeded the body surface contamination limit in 63 and 9% of cases, respectively. Levels of contamination and air concentration were generally higher if the patient had difficulty with the administration procedure. Room surface contamination was very low. In 24% of cases activity was detectable on staff (either in the hair or nose) using gamma camera imaging. Annual skin doses from these sources are calculated to be below the limit for deterministic effects. Whole body effective doses are calculated to be similar to those received by staff performing other nuclear medicine studies. However, care should be exercised to keep exposure from both airborne and fixed sources to a minimum and a regular review of contamination levels is recommended. We recommend the wearing of gloves for all Technegas administrations and disposable hats and masks may be considered in certain cases.

Information for patients and staff concerning nuclear medicine.

Providing information to patients and staff is an important part of the practice of nuclear medicine. To assist in improving the standard of communications, guidance has been prepared covering the content, style and presentation of letters and leaflets for patients and for medical and nursing staff. Examples are provided which describe nuclear medicine procedures and related radiation safety precautions. They also attempt to answer questions frequently put by the various groups to whom they are addressed.

Surgical implications of anomalous aortic origin of the left coronary artery.

We report a patient with exertional chest pain and anomalous aortic origin of the left coronary artery from the right coronary sinus. This patient also had circumflex coronary and right coronary artery stenoses. Following coronary bypass grafting of the circumflex and right coronary arteries in this patient, angina persisted and there was abnormal septal perfusion shown on the exercise thallium imaging despite patent grafts. The angina and perfusion defect were improved by bypass grafting of the unstenosed left anterior descending coronary artery in this patient. Thallium imaging may be useful in the preoperative assessment of patients with this anomaly.

Metastable ions arising from pseudomolecular [M-H]- ions produced by fast-atom bombardment negative-ion mass spectrometry of ecdysteroids.

Metastable ions arising from pseudomolecular [M-H]- ions produced by fast-atom bombardment negative-ion mass spectrometry of a range of free ecdysteroids, ecdysteroid conjugates and polar metabolites were investigated by means of linked scanning at constant B/E. Free ecdysteroids displayed daughter-ion spectra which allow 20-hydroxyecdysteroids and ecdysteroids lacking C-20 hydroxylation to be readily distinguished. The ejection of acetic acid from acetylated ecdysteroids was also readily detectable. Characteristic metastable-ion decomposition of ecdysteroid acids was not observed, presumably as a result of charge localization. High-mass daughter ions were also lacking in the case of phosphate conjugates.

Cohort differences in genetic and environmental influences on retrospective reports of conduct disorder among adult male twins.

BACKGROUND: Rates of child and adolescent conduct disorder (CD) have increased steadily over the past several decades. What is not known is whether the underlying genetic and environmental influences on individual differences in CD have also changed. METHODS: Retrospective reports of antisocial behaviour prior to age 18 were obtained from a population-based sample of 2769 adult males from male-male twin pairs born between 1940 and 1974. Using a summary score of number of CD symptoms, structural equation modelling was used to investigate whether mean level and variation in CD increased with more recent cohorts, and whether any increase in variance could be explained by familial or non-familial factors. RESULTS: Both mean level CD symptoms and variation were increased in more recent cohorts. Model fitting indicated that the primary increase in variance was due to familial factors, most notably, an increase in the shared environmental influences on CD, from 0.01 (95 % CI = 0.00; 0.27) to 0.30 (95 % Cl = 0.01; 0-44). Heritability estimates remained largely unchanged, although an increase in genetic factors could not be ruled out. CONCLUSIONS: Secular changes in sociodemographic factors responsible for increasing rates of CD may also account for the greater magnitude of shared environmental influences on variation in CD found among more recent cohorts.

Quantitative determination of cholesterol sulphate in plasma by stable isotope dilution fast atom bombardment mass spectrometry.

A stable isotope dilution assay has been developed for the quantitative determination of cholesterol sulphate in plasma using negative ion fast atom bombardment (FAB) mass spectrometry. The assay is highly selective and avoids problems of contamination from free cholesterol and other conjugates of cholesterol present in plasma. (6,7,7-2H3)Cholesterol sulphate is used as the internal standard and solvent extraction and silica Sep-Paks are employed to isolate plasma cholesterol sulphate. Limited-range acceleration voltage scanning in FAB mass spectrometric analyses leads to sub-microgram detection limits. Comparison of results obtained by FAB mass spectrometry of the intact cholesterol sulphate, and by gas chromatography/mass spectrometry selected ion monitoring of the free cholesterol, released by solvolysis of the cholesterol sulphate, showed that the latter approach probably overestimates plasma levels of cholesterol sulphate.

Utilization of leucine and acetate as carbon sources for sterol and fatty acid biosynthesis by Old and New World Leishmania species, Endotrypanum monterogeii and Trypanosoma cruzi.

The relative roles of acetate and leucine in the provision of a carbon source for fatty acid and sterol biosynthesis in several trypanosomatid species were investigated using 14C- and 13C-labelled acetate, glucose and leucine as substrates. Promastigotes of Leishmania species synthesized a large proportion of their sterol from leucine. L. major (LV39), L. amazonensis and L. mexicana were the most efficient utilizers of leucine, producing at least 70-77% of their sterol from leucine; L. braziliensis, L. donovani and L. tropica apparently produced less sterol from leucine (23-36%) and L. major (LV561), L. adleri and L. panamamensis were intermediate, utilizing leucine to provide 51-58% of their sterol. In all the cases the balance of the sterol produced was apparently synthesized from carbon arising from acetate. The related trypanosomatid Endotrypanum monterogeii also produced a large amount (77%) of its sterol from leucine rather than acetate. By contrast Trypanosoma cruzi elaborated only 8% of its sterol from leucine and used acetate far more effectively than the Leishmania species for sterol biosynthesis. The fatty acid moieties of the triacylglycerols and phospholipids were produced from acetate. Leucine was also incorporated into the fatty acids to varying extents in the different organisms showing that leucine can also be metabolized in trypanosomatids to generate acetyl-CoA.

Value of thallium myocardial imaging in the prediction of future cardiovascular events in patients with end-stage renal failure.

Chronic renal failure is associated with an increased rate of premature death from cardiovascular disease. Non-invasive identification of asymptomatic cardiac disease should be valuable in the management of such patients, and in selection for transplantation. One hundred and three high-risk patients (66 male, 37 female) with chronic renal failure who were without cardiovascular symptoms were assessed by exercise-graded thallium myocardial perfusion imaging and followed prospectively for 4 years. The development of a cardiovascular event, or death, and the interval to event or death were recorded. Cardiovascular events were documented in 50 patients; in 44 of the 60 patients with a positive thallium test and in only six of the 43 patients with a negative thallium test (test sensitivity 88%, specificity 70%, predictive value of a positive test 73%). Forty patients died, 28 from cardiovascular causes, during the study period. Thallium myocardial perfusion imaging is of value in the prediction of future cardiovascular events in patients with chronic renal failure, and is a useful non-invasive screening technique in patients with end-stage renal failure being considered for transplantation.

Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia.

Single photon emission tomographic imaging of the brain using 99mTc HM-PAO was carried out in patients with a clinical diagnosis of Alzheimer's disease, non-Alzheimer frontal-lobe dementia, and progressive supranuclear palsy. Independent assessment of reductions in uptake revealed posterior hemisphere abnormalities in the majority of the Alzheimer group, and selective anterior hemisphere abnormalities in both other groups. The findings were consistent with observed patterns of mental impairment. The imaging technique has potential value in the differential diagnosis of primary cerebral atrophy.