Clinical uses of 82Sr/82Rb generators.
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Brain↗
Biomedical subjects
T Jones
Publications and source records attributed to T Jones.
Measurement of glucose utilisation with [18F]2-fluoro-2-deoxy-D-glucose: a comparison of different analytical methods.
A number of different analytical methods were applied to dynamic scans obtained with [18F]2-fluoro-2-deoxy-D-glucose and positron emission tomography. In particular, methods applying three, four, standard, or no rate constants were compared in four studies on three normal subjects. In addition, regional cerebral blood flow, oxygen utilisation, and blood volume were measured using the oxygen-15 steady-state inhalation technique. There was a large difference between values of glucose utilisation obtained with the various analytical methods, in particular between methods using three or four rate constants. This difference was not due to contamination of the tracer with [18F]2-fluoro-2-deoxy-D-mannose. For dynamic techniques, the separate measurement of regional cerebral blood volume was essential. Static techniques (single scans with standard or no rate constants) were best related to dynamic techniques utilising four rate constants. From the results, it followed, however, that these static techniques can only be applied clinically if relatively large disturbances of glucose metabolism and no changes in rate constants are anticipated. The lumped constant was assessed from the combined measurement of oxygen and glucose utilisation and was higher than previously reported.
Deoxy Sugars↗
Correction for intravascular activity in the oxygen-15 steady-state technique is independent of the regional hematocrit.
The oxygen-15 steady-state technique to measure the regional cerebral metabolic rate for oxygen requires a correction for the nonextracted intravascular molecular oxygen-15. To perform this correction, an additional procedure is carried out using RBCs labeled with 11CO or C15O. The previously reported correction method, however, required knowledge of the regional cerebral to large vessel hematocrit ratio. A closer examination of the underlying model eliminated this ratio. Both molecular oxygen and carbon monoxide are carried by RBCs and are therefore similarly affected by a change in hematocrit.
Brain↗
Effect of nifedipine on myocardial metabolism in patients with unstable angina.
Myocardial glucose metabolism was assessed using 18F-fluorodeoxyglucose and positron emission tomography in 6 normal volunteers, 7 patients with coronary artery disease and stable angina and 15 patients with unstable angina. All studies were carried out on resting, fasting patients. The patients were off treatment and had no evidence of acute myocardial necrosis or ischaemia. A second study investigated the myocardial glucose metabolism of 5 of the patients with unstable angina after treatment with oral nifedipine. In the first study, the metabolic rate for glucose (MRG) was found to be similar in patients with stable angina and normal volunteers (0.023 +/- 0.032 vs 0.012 +/- 0.008 mumol ml-1 min-1, P less than 0.42), whereas the MRG was significantly higher in patients with unstable angina compared with both that of normal volunteers and patients with stable angina (0.084 +/- 0.047 mumol ml-1 min-1, P less than 0.001). In the second study, the MRG of all of the 5 patients with unstable angina studied after the administration of nifedipine was significantly reduced (P less than 0.05), but was still higher than that of the normal controls. The possibility of spontaneous metabolic changes cannot be excluded, but the consistent reduction of the MRG in all 5 patients after the administration of nifedipine suggests that nifedipine has a beneficial effect on myocardial metabolism that could be related to either an increase in myocardial blood flow or to a direct metabolic effect of nifedipine.
Adult↗
Multiplicity of causes for adrenal damage in AIDS.
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Acquired Immunodeficiency Syndrome↗
Use of short- and long-lived rubidium tracers for the study of transient ischemia.
Positron emission tomography (PET) with rubidium-82 (82Rb) has been developed to measure regional myocardial perfusion and to detect transient ischemia both in the experimental laboratory and in humans. There are known and separate contaminating effects of the 82Rb signal by disturbances in wall motion, wall thinning, and the partial volume effect that occur during transient ischemia. In nine anesthetized greyhounds, PET with 82Rb (T1/2 = 78 sec) was used to determine the regional myocardial uptake of this cation during a control period that consisted of a mild stenosis of the left anterior descending coronary artery in the absence of ischemia (to limit reactive hyperemia), during 10 min of total occlusion and, finally, at 30 and 60 min of recovery with release of the occlusion but not of the stenosis. Separately, rubidium-81 (81Rb); T1/2 = 4.58 hr) was given as a peripheral intravenous injection 2 hr before the study to allow this long-lived tracer to distribute in the potassium space of the myocardium. Observations during control and ischemia revealed marked decreases in 82Rb uptake (0.84 +/- 0.12 to 0.28 +/- 0.12, p = 0.001) in affected regions and were paralleled by similar decreases in microsphere blood flow (0.88 +/- 0.08 to 0.12 +/- 0.10 ml/min/g, p = 0.003), which gradually recovered by 60 min postischemia. Lesser decreases in 81Rb activity (0.84 +/- 0.11 to 0.76 +/- 0.17, p = 0.83) were observed in the same regions during ischemia, but these were immediately reversible. Separate in vitro postmortem experiments in eight rabbits confirmed a linear relationship between plasma and myocardial activities of stable potassium and 81Rb although there was a greater concentration of 81Rb in the myocardium that in the plasma relative to potassium (y = -3.29 +/- 0.79 x, s.e.e. 1.91, r = 0.95). These studies demonstrate that if 81Rb is given intravenously to distribute into the potassium pool, tomograms of the heart may be recorded to measure the potassium-rich mass of myocardium providing information about the acute effects of wall thinning during ischemia. Rubidium-81 used in this way may be helpful in assessing the effects of wall thinning and/or scar when other tracers are being used to assess perfusion or metabolism.
Animals↗
The clinical recognition of venous disease.
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Humans↗
Healthcare costs. The 2 per cent debate.
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Financing, Government↗
Studies on regional cerebral haematocrit and blood flow in patients with cerebral tumours using positron emission tomography.
Regional cerebral haematocrit has been measured in seven patients with brain tumours, and in one normal subject, using positron emission tomography (PET). Red cell and plasma volumes of distribution were assessed using 11CO and [methyl-11C]albumin, respectively. Haematocrit values were compared with values of regional cerebral blood flow (rCBF) measured using steady-state inhalation of C15O2. Only two of the seven cerebral tumours studied showed any increase in uptake of [methyl-11C]albumin over 45 min. Values of r, the regional ratio of cerebral small-to-large vessel haematocrit, varied from 0.52 to 0.84 for the seven tumours studied. No correlation between r and tumour blood flow was observed. The normal subject yielded an r value of 0.69 for the mean whole brain small-to-large vessel haematocrit ratio. No significant difference between gray and white matter r values was found. The contralateral hemispheres of the seven tumour patients studied yielded an overall mean r value of 0.71 +/- 0.05. We conclude that it is reasonable to assume an r value of 0.7 in tomographic calculations of regional cerebral blood volume (rCBV) from red cell or plasma volumes of distribution in normal brain. Such an assumption for tumours, however, may lead to errors of 35% in estimated rCBV.
Blood Volume↗
Glucose transport across the blood-brain barrier in normal human subjects and patients with cerebral tumours studied using [11C]3-O-methyl-D-glucose and positron emission tomography.
The kinetics of the regional cerebral uptake of [11C]3-O-methyl-D-glucose ([11C]MeG), a competitive inhibitor of D-glucose transport, have been studied in normal human subjects and patients with cerebral tumours using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and blood flow enabled corrections for the contribution of intravascular tracer signal in PET scans to be carried out and regional unidirectional cerebral [11C]MeG extractions to be determined. A three-compartment model containing an arterial plasma and two cerebral compartments was required to produce satisfactory fits to experimental regional cerebral [11C]MeG uptake data. Under fasting, resting conditions, normal controls had mean unidirectional whole-brain, cortical, and white matter [11C]MeG extractions of 14, 13, and 17%, respectively. Mean values of k1 and k2, first-order rate constants describing forward and back transport, respectively, of tracer into the first cerebral compartment, were similar for [11C]MeG and [18F]2-fluoro-2-deoxy-D-glucose (18FDG), a second competitive inhibitor of D-glucose transport. k3, a rate constant describing FDG phosphorylation, was 20 times higher for cortical FDG uptake than the k3 fitted for [11C]MeG cortical uptake. Glioma [11C]MeG extractions ranged from normal levels of 12% to raised levels of 30%. Transport of [11C]MeG in and out of contralateral cortical tissue was significantly depressed in patients with gliomas. It is concluded that under fasting, resting conditions, regional cerebral glucose extraction remains relatively uniform throughout normal brain tissue. Gliomas, however, may have raised levels of glucose extraction. The nature of the second cerebral compartment required to describe [11C]MeG uptake is unclear, but it could represent either a useless phosphorylation-dephosphorylation cycle or nonspecific tracer uptake by a cerebral subcompartment.
3-O-Methylglucose↗
Regional cerebral glucose transport in insulin-dependent diabetic patients studied using [11C]3-O-methyl-D-glucose and positron emission tomography.
Regional cerebral [11C]3-O-methyl-D-glucose ([11C]MeG) uptake kinetics have been measured in five insulin-dependent diabetic patients and four normal controls using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and CBF enabled corrections for the presence of intravascular [11C]MeG signal in cerebral regions of interest to be carried out, and regional cerebral [11C]MeG unidirectional extraction fractions to be computed. Four of the five diabetic subjects were studied with their fasting plasma glucose level clamped at a normoglycaemic level (4 mM), and four were studied at hyperglycaemic plasma glucose levels (mean 13 mM). The four diabetic subjects whose fasting plasma glucose levels were clamped at a normoglycaemic level of 4 mM had mean fasting whole-brain, cortical, and white matter [11C]MeG extraction fractions of 15, 15, and 16%, respectively, values similar to those found for the four normal controls (whole brain, 14%; cortex, 13%; white matter, 17%). Mean regional cerebral [11C]MeG extraction fractions were significantly reduced in diabetic subjects during hyperglycaemia whether their plasma insulin levels were undetectable or whether they were raised by continuous intravenous insulin infusion. Such a reduction in [11C]MeG extraction under hyperglycaemic conditions can be explained entirely in terms of increased competition between [11C]MeG and D-glucose for the passive facilitated transport carrier system for hexoses across the blood-brain barrier (BBB). It is concluded that the number and affinity of D-glucose carriers present in the BBB are within normal limits in treated insulin-dependent diabetic subjects. In addition, insulin appears to have no effect on the transport of D-glucose across the BBB.
3-O-Methylglucose↗
Studies on regional cerebral pH in patients with cerebral tumours using continuous inhalation of 11CO2 and positron emission tomography.
Regional cerebral pH (rpH) was measured in 12 patients with cerebral tumours and in 5 normal subjects using continuous inhalation of 11CO2 and positron emission tomography (PET). Cerebral tumours with a disrupted blood-brain barrier (BBB) on computed tomography scanning had a similar rpH to that of equivalent regions of contralateral brain tissue (mean tumour rpH, 6.98; mean contralateral brain pH, 6.99). Cerebral tumours with an intact BBB were consistently found to be more alkaline than contralateral brain tissue (mean tumour rpH, 7.09). There was no significant difference between the mean rpH values obtained for peripheral cortical gray and central white matter in normal subjects (7.02 and 6.98, respectively). It is concluded that in spite of reports of raised levels of aerobic glycolysis in neoplastic tissue, there is no evidence that cerebral tumour rpH values are depressed.
Blood-Brain Barrier↗
Studies on cerebral oxygen metabolism, blood flow, and blood volume, in patients with hydrocephalus before and after surgical decompression, using positron emission tomography.
Cortical oxygen utilization, oxygen extraction, blood flow, and blood volume, have been measured in patients with hydrocephalus before and after surgical decompression using positron emission tomography (PET). The hydrocephalus subjects fell into two categories: patients with recent-onset obstructive hydrocephalus and symptoms of raised intracranial pressure due to obstruction of cerebrospinal fluid (CSF) drainage by posterior fossa or third ventricular cerebral tumours, and patients with hydrocephalus of more insidious onset that was associated either with congenital abnormalities, or which was idiopathic. The hydrocephalus subjects had a significantly reduced level of mean cortical oxygen utilization (rCMRO2) and mean cortical blood flow (rCBF) compared with age-matched normal controls. Patients with recent-onset obstructive hydrocephalus associated with cerebral neoplasia had inappropriately low levels of cortical blood flow compared with their levels of cortical oxygen utilization, all having elevated levels of cortical oxygen extraction (rOER). Levels of cortical blood flow in the group of patients with more insidious-onset hydrocephalus matched levels of cortical rCMRO2, all these subjects having normal levels of rOER. All those hydrocephalus subjects who had a raised cortical oxygen extraction preoperatively increased their cortical blood flow following cerebral decompression. No improvement, however, was noted in their mean cortical oxygen utilization. By contrast, those hydrocephalus subjects with normal baseline levels of cortical extraction showed no improvement in mean cortical blood flow, oxygen utilization, or cognitive function after surgical intervention. It is concluded that if cortical oxygen extraction is elevated, hydrocephalic patients are likely to improve their cortical blood flow following cerebral decompression.
Adult↗
Myocardial glucose utilization in ischaemic heart disease: preliminary results with F18-fluorodeoxyglucose and positron emission tomography.
Regional myocardial utilization of glucose can be assessed non-invasively in man with the sugar analogue F18-2-fluoro-2-deoxyglucose (FDG) and positron emission tomography (PET). The preliminary observations made in patients with different clinical forms of ischaemic heart disease using FDG and PET are reported. In patients with stable angina pectoris at rest, regional myocardial glucose utilization was comparable to that in normal volunteers whilst an increased utilization of glucose was found in the recovery from exercise-induced ischaemia in the regions that showed an abnormal perfusion during the stress test. These metabolic changes persisted in the recovery phase when all the parameters that were altered during the exercise, including myocardial perfusion, had normalized. In patients with unstable angina, characterized by repeated episodes of spontaneous ST depression, myocardial glucose utilization was regionally or globally increased already at rest in the absence of symptoms or signs of ischaemia at the time of study and most often without evident perfusion abnormalities. In patients with a recent infarction, two different patterns of glucose utilization in the infarcted area have been described: a concordant decrease of myocardial perfusion and glucose utilization; a disproportionately increased glucose utilization relative to perfusion interpreted as an index of the presence of ischaemic, but still viable myocardium.
Angina Pectoris↗
Diagnosis of cerebral toxoplasmosis using fluorescein-labeled antitoxoplasma monoclonal antibodies.
The direct immunofluorescence technique using monoclonal antitoxoplasma antibodies was used to detect Toxoplasma organisms in 13 brain touch preparations and six smears of cerebrospinal fluid. For comparison, Giemsa-stained smears and histologic sections of the same cases were also studied. Positive results were obtained from two cases of acquired immunodeficiency syndrome (AIDS) with all three methods. Toxoplasma cysts, pseudocysts, and tachyzoites were easily identified by the immunofluorescence technique, and no false-positive results were encountered in nine cases of AIDS with different kinds of encephalitides. It was difficult to identify tachyzoites in histologic sections and time-consuming to search for pseudocysts and cysts. The parasite was even more difficult to recognize in Giemsa-stained brain touch preparations due to the easy distortion of the organisms. In the present study, immunofluorescence technique was more sensitive than hematoxylin--eosin or Giemsa staining in terms of the number and range of forms demonstrated in tissue. Therefore, immunofluorescence technique using monoclonal antibodies appears to be the preferred method for a rapid diagnosis of cerebral toxoplasmosis as compared to Giemsa staining and histology.
Antibodies, Monoclonal↗
RASM, a "new' low-frequency blood group antigen.
A 'new' low-frequency red cell antigen, RASM, was found in 3 generations of a Caucasian family. It is inherited as a Mendelian dominant character. The propositus, a newborn, had a positive direct antiglobulin test; overt haemolytic disease of the newborn was not present.
Antigens, Surface↗
A comparison between regional cerebral blood flow measurements obtained in human subjects using 11C-methylalbumin microspheres, the C15O2 steady-state method, and positron emission tomography.
Regional cerebral blood flow (rCBF) values were measured in nine normotensive subjects with known previous myocardial infarctions using 15 mu 11C-methylalbumin microspheres and positron emission tomography (PET). Microspheres were injected directly into the left ventricle of each subject during routine cardiac angiography and blood flow calibrated using the reference sample technique. rCBF values were compared with those obtained for a group of fifteen age-matched normal controls using the C15O2 steady-state inhalation technique. Using 1 cm radius circular regions of interest, the 11C-microspheres approach yielded mean blood flow values of 51 ml/100 ml/min and 48 ml/100 ml/min for regions of interest dominated by temporal and frontal cortical grey matter respectively. An rCBF value of 32 ml/100 ml/min was obtained for regions of interest dominated by frontal white matter. Mean rCBF values obtained for these regions using the C15O2 method were not significantly different (52 ml/100 ml/min, 44 ml/100 ml/min, and 28 ml/100 ml/min respectively), but the C15O2 approach gave a significantly lower rCBF value than the 11C-microspheresfor regions of interest dominated by occipital grey matter. Although the two groups of subjects studied were not strictly equivalent, the good agreement between blood flow values obtained using the 11C-microspheres and the C15O2 techniques is of interest, and suggests that the assumptions of the C15O2 steady-state approach do not lead to large errors in practice.
Aged↗
Desmoplastic malignant melanoma masquerading as chalazion.
Desmoplastic malignant melanoma is a rare and highly malignant tumour, which usually occurs in the head and neck. This is demonstrated by a case history of a patient with this lesion on the lower lid, which has not been previously described in the British ophthalmological literature. The lesion often presents considerable problems of histological diagnosis.
Aged↗