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Biomedical subjects

T Jones

Publications and source records attributed to T Jones.

At least 361 records · Page 20Linked to original sources

Quantification of regional V/Q ratios in humans by use of PET. I. Theory.

With positron emission tomography, quantitative measurements of regional alveolar and mixed venous concentrations of positron-emitting radioisotopes can be made within a transaxial section through the thorax. This allows the calculation of regional ventilation-to-perfusion (V/Q) ratios by use of established tracer dilution theory and the constant intravenous infusion of 13N. This paper considers the effect of the inspiration of dead-space gas on regional V/Q and investigates the relationship between the measured V/Q, physiological V/Q, and V/Q defined conventionally in terms of bulk gas flow (VA/Q). Ventilation has been described in terms of net gas transport, and the term effective ventilation has been introduced. A simple two-compartment model has been constructed to allow for the reinspiration of regional (or personal) and common dead-space gas. By use of this model, with parameters representative of normal lung the effective V/Q ratio for 13N [(VA/Q)eff(13N)] is shown to overestimate VA/Q by 18% when VA/Q = 0.1 but underestimate VA/Q by 68% when VA/Q = 10. For physiological gases, the model predicts that the behavior of O2 should be similar to that of 13N, so that, in terms of gas transport, V/Q ratios obtained using the infusion of 13N closely follow those for O2. Values of the effective V/Q ratio for CO2 [(VA/Q)eff(CO2)] lie approximately halfway between (VA/Q)eff(13N) and VA/Q. These results indicate that dead-space ventilation is far less a confounding issue when V/Q is considered in terms of net gas transport (VAeff), rather than bulk flow (VA).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Quantification of regional V/Q ratios in humans by use of PET. II. Procedure and normal values.

Regional measurements of tissue isotope concentration, made using positron emission tomography (PET), allow tracer models to be used in a quantitative manner to provide topographic distributions of many structural and functional parameters, each derived for the same well-defined lung element. In this paper we describe a technique to measure regional ventilation-perfusion ratios (V/Q), in absolute units, by use of PET and the continuous intravenous infusion of an inert gas isotope, 13N, and report on measurements made in 12 normal subjects (4 smokers). Data were obtained from a single lung section (slice thickness, 1.7 cm full width at half-maximum response to a line source) at the level of the right ventricle in the supine posture during quiet breathing. For the 12 subjects, volume-weighted mean values of V/Q, averaged over individual right and left lung fields, ranged from 0.50 to 1.29. Analysis of these means showed no difference between lungs: right, 0.80 +/- 0.23 SD; left, 0.76 +/- 0.20 SD. Topographically, a systematic fall of V/Q in the ventrodorsal direction was observed in eight of the subjects (mean ventrodorsal difference 0.39, range 0.19-0.90), whereas two showed a clear increase toward dependent lung regions (range 0.16-0.26). Seven of the subjects with a falling ventrodorsal V/Q gradient also exhibited discrete regions of low V/Q at the dorsal lung border. We conclude that, in normal subjects, ventilation and perfusion are generally well matched in the supine posture, but isolated mismatching often occurs in dependent lung regions.

Humans↗

Psychology of computer use: XVI. Effect of computer-pointing devices on children's processing rate.

Computer-pointing devices for input into microcomputers have become a commonplace component in direct manipulation interfaces. Use of these peripheral devices by children should result in processing rates comparable to those obtained when children are pointing with their fingers or other means. Recent research suggests that children's processing rates are substantially lower when they are manipulating computer devices. One possibility is that a child's motor system is subjected to a greater load because the child's hands are not visible while the action of pointing with a computer is being carried out. The effect of two conditions (viewing hands, not viewing hands) on 6-, 8-, and 10-yr.-old children's processing rates was investigated. Results showed that there was no difference between the two conditions although low processing rates similar to those previously obtained were recorded.

Attention↗

Validity and repeatability of the IUATLD (1984) Bronchial Symptoms Questionnaire: an international comparison.

The International Union against Tuberculosis and Lung Disease (IUATLD) Bronchial Symptoms Questionnaire (1984) was developed for use in studies of asthma and its reliability measured in an earlier survey in England. The association of the symptoms elicited by this questionnaire to bronchial response to histamine has also been described. This paper presents the results of studies of the questionnaire in four clinical centres in Europe. The reliability of the questionnaire and its ability to predict the bronchial response to histamine were compared for English, Finnish, French and German translations of the questionnaire in samples of diagnosed asthmatics and controls in Nottingham, Berlin, Helsinki and Paris. The answers to questions showed good repeatability, especially in Finland and Germany, particularly those questions on asthma and wheeze. The most sensitive symptom for predicting hyperresponsiveness was the question on wheeze, the most specific questions were those on waking at night with shortness of breath (Paris and Nottingham) and morning tightness (Helsinki and Berlin). This study shows that the IUATLD (1984) questionnaire may provide useful, valid and comparable data even in translation but these studies will need to be repeated in representative samples before such a possibility is accepted as fully demonstrated.

Adult↗

Easing transitions in care delivery with a core training group.

A collaborative approach was used by the nursing staff of a state psychiatric hospital to make a transition from traditional nursing services to a self-care model on one ward. The core training group, including representatives from all levels of nursing staff, developed and evaluated a personal hygiene protocol for 30 patients with chronic mental illness. Underwood's adaptation of Orem's self-care model of nursing was modified to provide the framework for this protocol. Evaluation of the project demonstrated both improved personal hygiene for the patients and greater job satisfaction for the nursing staff. The collaborative core training group approach was effective in facilitating the transition to the self-care nursing model.

Hospital Bed Capacity, 300 to 499↗

SV 40-transformed normal and DNA-repair-deficient human fibroblasts can be transfected with high frequency but retain only limited amounts of integrated DNA.

The ability of simian virus 40-transformed human fibroblasts to integrate and maintain transfected genomic DNA has been investigated in two normal and six DNA-repair-deficient human cell lines. These cell lines were transfected with DNA containing two selective markers (G418 and hygromycin (Hyg) resistance) separated by random pieces of human DNA of 0-40 kb in length. The transfection frequency for the selected (G418R) marker was between 2 x 10(-4) and 2 x 10(-3) for all cell lines, comparable to many other mammalian systems. About 50% of the G418R colonies were also initially resistant to Hyg. Analysis of the DNA from individual clones expanded for a further month revealed, however, that about one to three copies of the selected marker but only about 0.1 copy per cell of the unselected marker were maintained. Our results were broadly similar for all eight cell lines. Thus the amount of integrated DNA that is stably maintained in these cells is in general very small (less than 50 kb). This may provide an explanation for the difficulties encountered in many laboratories in attempts to correct the defect in DNA-repair-deficient human cells by transfection with genomic DNA. Our results also show that none of several defects in DNA repair has any obvious effect on either the transfection frequency or the amount of stably integrated foreign DNA.

Cell Transformation, Viral↗

Intraventricular administration of interferon and administration of methisoprinol by mouth in the treatment of adult-onset subacute sclerosing panencephalitis.

This is thought to be the first report of the use of interferon therapy by intraventricular administration in adult-onset subacute sclerosing panencephalitis. A 22-year-old female patient with subacute sclerosing panencephalitis was treated for three months with interferon by the intraventricular route and methisoprinol (inosiplex) by mouth. There was no obvious clinical improvement during this time, and the cerebrospinal-fluid measles antibody titre remained elevated. The lack of effect of therapy could be attributed partly to the patient's age and to the rapidly progressive deterioration in her condition before treatment. No significant side-effects were associated with this therapy. Further trials of these medications in adult-onset subacute sclerosing panencephalitis are indicated.

Administration, Oral↗

Abnormalities in myocardial metabolism in patients with unstable angina as assessed by positron emission tomography.

Regional myocardial perfusion and glucose metabolism were assessed in six normal volunteers and 29 patients with coronary heart disease and stable or unstable angina using rubidium-82 (Rb-82) and F-18 fluoro 2-deoxy-D-glucose (FDG) with positron emission tomography. All normals and patients were studied following overnight fasting, at rest, with no angina or electrocardiographic signs of acute myocardial ischemia or necrosis. Rb-82 myocardial cross-sectional images were obtained employing the continuous infusion technique, while dynamic FDG imaging was employed after intravenous tracer bolus injection. Regional Rb-82 and FDG myocardial concentrations were then calculated by drawing regions of interest over the interventricular septum, anterior and lateral wall of the left ventricle. The mean Rb-82 uptake for each left ventricular region analyzed was found to be similar between both groups of patients and normal volunteers. The mean myocardial glucose utilization was found to be similar in normal volunteers and patients with stable angina (0.023 +/- 0.032 vs. 0.012 +/- 0.008 microns ml/min p less than 0.42). However, myocardial glucose utilization was found to be significantly higher in patients with unstable angina compared with both normals and patients with stable angina (0.048 +/- 0.047 microM/ml/min p less than 0.001 for both comparisons). Thus, in patients with severe coronary artery disease and unstable angina, myocardial glucose utilization was enhanced in spite of the absence of clinical, electrocardiographic, or detectable perfusion evidence of acute ischemia.

Adult↗

Regional cerebral opioid receptor studies with [11C]diprenorphine in normal volunteers.

The results are described of the cerebral uptake and heterogeneous retention of [11C]diprenorphine after intravenous injection in 4 normal volunteers. This potent opioid antagonist (Kd = 0.2 nM) was chosen because of its safety, lack of side-effects at trace doses in human pilot studies, rapid cerebral uptake and high percentage (80-90%) specific binding in animal in vivo studies. High uptake of [11C]diprenorphine was demonstrated in regions such as the thalamus, caudate nucleus, temporal, frontal and parietal cortices, which are known from postmortem studies to have high concentrations of opioid receptors. A stable level of activity or a very slow decline in activity was observed between 20 and 50 min after injection in areas such as the caudate nucleus and thalamus. Conversely, rapid washout of activity was observed in the occipital cortex, which is known to have low opioid receptor concentrations. Some 80-90% of maximum binding was naloxone reversible. These results with a ligand that is safe and without side-effects, suggest that this technique is suitable for studies of opioid physiology in man.

Brain↗

Stability of arterial concentrations during continuous inhalation of C15O2 and 15O2 and the effects on computed values of CBF and CMRO2.

Stability of arterial whole blood and plasma concentrations is a basic requirement in the application of the oxygen-15 (15O2) steady-state inhalation technique for measuring regional cerebral blood flow and oxygen use. The level of stability obtainable in practice is reported in the form of retrospectively analysed blood data from 626 consecutive studies in patients with a range of clinical conditions. Serial arterial whole blood and plasma concentrations were measured during both C15O2 and 15O2 inhalations, and coefficients of variation were calculated. In addition, these concentrations were compared with the corresponding values recorded at the start of each study and maximum variations were calculated. For all four concentrations, mean and median coefficients of variation were around 5 and 4%, respectively. Mean and median maximum variations were around 9 and 7%, respectively. The effects of these variations on the calculations of regional cerebral blood flow, oxygen extraction, and oxygen use were estimated. Mean expected errors were found to be between 4 and 9%, and median expected errors between 3 and 6%. Inherent blood sampling errors were assessed from blood volume studies using 11CO-labeled red cells. These errors were found to be less than 3%.

Arteries↗

The synthetic human growth hormone fragment (32-38) increases glucose uptake in the conscious dog.

hGH32-38 was tested to determine if the peptide could affect hepatic glucose production in the conscious dog under basal conditions (euglycemia) or if it could enhance glucose uptake when hyperglycemia was induced. hGH32-38 (1.6 nmol.kg-1.min-1) or vehicle was infused in a cross-over design study into each of 4 conscious 16 h-fasted dogs for 3 h (0-180 min) following a 40 min control period. At 90 min, plasma glucose was raised to and maintained at 9.4 mmol/l by glucose infusion for 3 h (until 270 min). Neither hGH32-38 nor vehicle infusion had a significant effect on insulin and glucagon levels or on tracer determined [( 3-3H]glucose) glucose production. As a result, neither treatment changed plasma glucose (5.72 +/- 0.17 to 5.78 +/- 0.17 mmol/l with hGH32-38; 5.50 +/- 0.22 to 5.50 +/- 0.17 mmol/l with vehicle). Induction of hyperglycemia (9.4 mmol/l) caused glucagon concentrations to fall similarly to about 50 ng/l with and without hGH32-38. Insulin rose to similar levels in both protocols, yet more glucose was required to maintain the same hyperglycemia with hGH32-38 (135-180 min) (74.9 +/- 12.7 vs 43.7 +/- 7.1 mumol.kg-1.min-1, P less than 0.05). In summary, hGH32-38 significantly increased glucose disposition during hyperglycemia and this effect may be attributed to enhanced insulin action or to an insulin independent action of the peptide.

Animals↗

Glucose utilization in vivo by human pulmonary neoplasms.

Neoplastic tissue in general shows a high rate of glucose consumption under both anaerobic and aerobic conditions. Using positron emission tomography (PET) we measured the rate of uptake of the glucose analogue 18fluoro-2-deoxy-D-glucose (18FDG) in 12 patients with carcinoma of the lung. The tumor types were six squamous cell, two large cell, two oat cell, one adenocarcinoma, and one undifferentiated carcinoma. In each patient a transaxial plane was selected that contained the bulk of the tumor tissue. Regional density and blood volume were measured. Following the intravenous injection of 18FDG, the rates of uptake in the tumor and normal lung tissue were assessed from sequential scans over 1 hour. In each patient the rate of uptake of 18FDG in the tumor tissue was significantly increased relative to normal lung tissue. For the group the rate of uptake by the tumor was 211.4 +/- 69.4 ml/100 g/hr (mean +/- SD) compared to 31.9 +/- 13.2 in the contralateral lung (P less than 0.05). The tumor-to-normal tissue ratio of 6.6 (range, 2.7 to 14.6) was higher than previously reported ratios for brain and liver tumors. In contrast to brain tumors there was little correlation between tumor type and rate of 18FDG uptake. Measurements of glucose metabolism taken in vivo in human pulmonary tumors may lead to advances in screening, staging, and therapy.

Adult↗

Beneficial effect of nitrates on myocardial glucose utilization in unstable angina pectoris.

Myocardial uptake of the glucose analog F-18-2-fluoro-2-deoxy-D-glucose (FDG) was assessed by positron emission tomography in 6 normal volunteers, 7 patients with chronic stable angina and 22 patients with unstable angina at rest in fasting conditions. Regional myocardial perfusion was assessed by rubidium-82. The study was repeated a few days later after intravenous infusion of isosorbide dinitrate. FDG uptake was similar in control subjects and patients with stable angina (0.023 +/- 0.032 vs 0.012 +/- 0.008 mol/ml/min, p less than 0.42) but was about 4-fold higher on the average in patients with unstable angina (0.084 +/- 0.047, p less than 0.01). The severity of coronary obstructions in stable and unstable angina patients was similar. The increased uptake involved the whole heart, including areas not distal to critically stenosed vessels; it was not associated with reduced myocardial perfusion and was not related to a recent episode of transient ischemia as assessed by symptoms and by Holter monitoring. After continuous infusion of nitrates, FDG uptake was consistently and significantly reduced toward normal levels both in areas perfused by critically stenosed coronary arteries and by noncritically stenosed vessels.

Adult↗

Absence of irradiation induced ischaemic temporal lobe damage in patients with pituitary tumours.

This study was undertaken to confirm the belief that modern day external beam radiotherapy for patients with pituitary tumours should not be associated with any ischaemic temporal lobe damage. Using the oxygen-15 steady state inhalation technique and positron emission tomography regional temporal lobe blood flow, oxygen extraction fraction and oxygen utilisation were measured in 10 normal volunteers and 11 patients with pituitary tumours treated by irradiation. The patients were studied between 1 and 10.9 years after radiotherapy. We found that temporal lobe oxygen utilisation in the irradiated group (mean 2.11 +/- 0.23 ml of O2/100 ml tissue/min) did not differ from the normal group (mean 2.13 +/- 0.26 ml of O2/100 ml tissue/min). This suggests that total doses of between 35 and 56 Gy, delivered in fractions of less than 2 Gy, can be given to a pituitary tumour without demonstrable damage to normal temporal lobe.

Adult↗