Search PubMed⌕ Search

Biomedical subjects

A K Jones

Publications and source records attributed to A K Jones.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography.

The localised PET cerebral correlates of the painful experience in the normal human brain have previously been demonstrated. This study examined whether these responses are different in patients with chronic atypical facial pain. The regional cerebral responses to non-painful and painful thermal stimuli in six female patients with atypical facial pain and six matched female controls were studied by taking serial measurements of regional blood flow by PET. Both groups displayed highly significant differences in responses to painful heat compared with non-painful heat in the thalamus, anterior cingulate cortex (area 24), lentiform nucleus, insula, and prefrontal cortex. These structures are closely related to the "medial pain system". The atypical facial pain group had increased blood flow in the anterior cingulate cortex and decreased blood flow in the prefrontal cortex. These findings show the importance of the anterior cingulate cortex and the reciprocal (possibly inhibitory) connections with the prefrontal cortex in the processing of pain in patients with this disorder. A hypothesis is proposed to explain the mechanisms of cognitive and pharmacological manipulation of these pain processes.

Adult↗
PubMed1993

A comparative study of labelled neutrophil behaviour in patients with rheumatoid arthritis and normal volunteers.

A comparative study of neutrophil pharmacokinetics and distribution between normal volunteers and patients with rheumatoid arthritis (RA) is presented. White cell viability was confirmed by prominent localization of activity in the spleen with minimal liver uptake and lack of retention in the lungs in both normal volunteers and RA patients. There were no significant differences between both groups in granulocyte clearance from the lungs and their subsequent distribution in the spleen, bone marrow and liver. The results of this study demonstrate that the behaviour of granulocytes in RA patients is essentially unchanged from that of normal volunteers.

Aged↗
PubMed1993

Investigation of the opioid system in absence seizures with positron emission tomography.

The neuroanatomical and pathophysiological basis of primary generalised absences is uncertain. Administration of endogenous opioids has been shown to result in absence-like seizures in animal models. Positron emission tomography scans were performed in eight patients with primary generalised epilepsy and eight control subjects. Regional cerebral blood flow was measured interictally with C15O2, after which a 90 minute dynamic study with the opioid-receptor ligand 11C-diprenorphine was performed. Serial absences were precipitated by hyperventilation for 10 minutes, starting 30-40 minutes after injection of diprenorphine. Absences, with generalised spike-wave discharges on the EEG, occurred for between 10% and 51% of the provocation period. No individual (normal or patient) had any interictal focal abnormalities of cerebral blood flow. After provocation of serial absence seizures, there was increased diprenorphine elimination from the association cortex, but not from the thalamus, basal ganglia, or cerebellum, compared with control subjects and patients scanned without provocation of absences. It was possible to simulate the observed increased diprenorphine elimination following seizures in cerebral cortex using a two tissue compartment model, with an estimated 15-41% decrease in the specific tracer uptake rate constant (k3). These results suggest that endogenous opioids are released in the association cortex at the time of serial absences, lead to increased receptor occupancy, and may have an important role in the pathophysiology of generalised absences.

Adult↗
PubMed1992

The response of 99Tcm-methylene diphosphonate and 99Tcm-hexametazime-labelled neutrophils to intra-articular steroid injection in rheumatoid arthritis.

The synovial and bone uptake of tracer in the knees of patients with rheumatoid arthritis (RA) was quantified using 99Tcm-hexamethyl propylene amine oxime-labelled leucocytes and 99Tcm-methylene diphosphonate (MDP), respectively. Significant neutrophil migration and MDP uptake occurred in the knees of patients with RA irrespective of the disease duration. In all but one patient neutrophil migration was reduced after intra-articular steroid injection. The change in MDP uptake after steroid injection was variable. There was a significant correlation between the percentage reduction in neutrophil migration and pain score, while the latter correlated poorly with the change in MDP uptake. The quantification of the neutrophil component of the inflammatory process is a sensitive index for monitoring RA activity and response to pharmacological interventions, while quantitative bone scintigraphy should not be employed to monitor changes in joint inflammation in patients with RA.

Aged↗
PubMed1991

In vivo distribution of opioid receptors in man in relation to the cortical projections of the medial and lateral pain systems measured with positron emission tomography.

In vivo opioid receptor binding in the cortical projections of the medial (cingulate and prefrontal cortex) and lateral pain system (primary somatosensory cortex) in male volunteers has been quantitated using [11C]diprenorphine and positron emission tomography. High levels of opioid receptor binding were seen in the cortical projections of the medial pain system in the cingulate and prefrontal cortex as has previously been observed in post-mortem studies. However, a focal reduction of opioid receptor binding was observed and quantitated in the primary motor/sensory strip when compared to surrounding parietal cortex. This new finding suggests that the medial pain system is likely to be more susceptible to exogenous and endogenous opioid neuromodulation than the so-called lateral pain system.

Adult↗
PubMed1991

Cortical and subcortical localization of response to pain in man using positron emission tomography.

A quantitative study of the regional cerebral responses to non-painful and painful thermal stimuli in six normal volunteers has been done by monitoring serial measurements of regional blood flow measured by positron emission tomography (PET). In comparison to a baseline of warm stimulation no statistically significant changes in blood flow were seen in relation to increasing non-painful heat. However, highly significant increases in blood flow were seen in response to painful heat in comparison to non-painful heat. These changes were in the contralateral cingulate cortex, thalamus and lenticular nucleus. These findings are discussed in relation to previous physiological observations of responses to nociceptive stimuli in man and primates.

Adult↗
PubMed1991

In vivo leukocyte migration in arthritis.

We quantitated in vivo migration of neutrophils into the knees of patients with rheumatoid arthritis (RA) and osteoarthritis, using 99mtechnetium-hexamethyl-propylene-amineoxime-labeled leukocytes and gamma scintigraphy. Significant neutrophil migration occurred in patients with RA irrespective of disease duration, and it was reduced by 60% following intraarticular steroid injection. The reduction in neutrophil migration correlated with reduction in pain. Leukocyte migration into osteoarthritic joints was also demonstrated, although it was much less than that seen in rheumatoid joints. No significant leukocyte migration into the joints of patients without arthritis was demonstrated. This technique appears to provide a sensitive method for quantitatively assessing the neutrophil component of inflammation in individual joints of patients with arthritis.

Adult↗
PubMed1991

Dynamic monitoring of [11C]diprenorphine in rat brain using a prototype positron imaging device.

The present work tests the feasibility of using the most recently developed positron emission tomograph detector technology to image positron-emitting radioligands in small experimental animals. A prototype imaging device, using two opposing multicrystal, high-resolution (approximately 4 mm) block detectors of bismuth germanate to produce a 2-dimensional image in the centre of the field of view, is described. To evaluate the probe's potential as a non-invasive experimental tool, the dynamic regional distribution of the established opiate receptor ligand, [11C]diprenorphine was determined in rat brain following intravenous injection. The distribution of counts in the images was consistent with the localisation of diprenorphine binding sites and the specificity of the signal obtained was confirmed by administration of non-radioactive diprenorphine and naloxone. Although the signal-to-noise ratio was reduced compared with data obtained by post mortem dissection, the dynamic data acquisition capabilities of the system demonstrate the feasibility of monitoring the kinetics of ligand binding in individual animals and encourages further design of a small-diameter detector system with tomographic capabilities.

Animals↗
PubMed1991

Positron emission tomography as a research tool in the investigation of psychiatric and psychological disorders.

The principles of positron emission tomography (PET) are described, and illustrations of how these can be applied to clinical psychiatric questions relating to schizophrenia and depression are delineated. The metabolic changes in the frontal lobes which have been described in both depression and schizophrenia and depression are reviewed and discussed. More recent PET techniques allow several serial measurements of changes in regional blood flow in response to either a pharmacological challenge or a specific psychological task. This method provides a promising new approach to the study of the dopaminergic system in schizophrenia. New tracer methods of quantitating changes in in vivo concentrations of opioid receptors allow direct pharmacological access to the endogenous opioid system in the brain. Observations of regional cortical differences in opioid receptor concentration in relation to the medial and lateral pain systems are described. In addition, changes in receptor occupancy during sleep using [11C]diprenorphine and changes in the mu-specific tracer [11C]carfentanil in temporal lobe epilepsy are discussed.

Brain↗
PubMed1991

Compartmental analysis of diprenorphine binding to opiate receptors in the rat in vivo and its comparison with equilibrium data in vitro.

The regional binding of the opiate receptor ligand diprenorphine has been examined in rat brain both in vivo and in vitro. The time course of total label in specific brain regions was followed up to 2 h after intravenous bolus injection of [3H]diprenorphine, with or without a pulse chase of unlabelled diprenorphine at 30 min. In addition, total label was measured 30 min after injection of labelled diprenorphine at nontracer concentrations over a range of specific activities. Total data sets for each region were fitted simultaneously to a compartmental model to give estimates of maximal binding capacity (Bmax), the second-order apparent association rate constant, and the first-order dissociation rate constant of the receptor-ligand complex. The model incorporated the use of a reference region with low specific binding (cerebellum). The binding of diprenorphine to rat brain homogenates was measured in vitro under equilibrium conditions at 37 degrees C, pH 7.4, in the presence and absence of naloxone, to give corresponding regional estimates of Bmax and the half-saturation constant Kd. The results showed a close correlation between in vitro and in vivo regional estimates of Bmax over a wide range. There were no significant interregional differences either in Kd in vitro or in the Kd derived from the in vivo analysis, although in vitro and in vivo estimates differed by an order of magnitude. This work was carried out as part of a validation study with a view to the application of the compartmental model to data obtained in vivo in humans using positron emission tomography, when successive studies over a range of specific activities are not feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A method of studying pharmacokinetics in man at picomolar drug concentrations.

1. We describe a new method that enables the tissue kinetics of picomolar concentrations of drugs to be measured in man. The method is based on the administration of a drug, labelled with a short-lived positron-emitting radioisotope, such as carbon-11 (t1/2 = 20.4 min, beta + = 99.8%) or fluorine-18 (t1/2 = 109.8 min, beta + = 96.9%), which is then detected in vivo by an array of 10 large uncollimated sodium iodide scintillation detectors, arranged as five opposing pairs, with each pair collecting data over one major organ or region of the body. 2. To illustrate the scope of the new method we report the results of administering [O-methyl-11C]-diprenorphine, an established radioligand for central opiate (mu, kappa, and delta) receptors and L-6-[18F]-fluoro-DOPA, a marker for dopaminergic neurons. 3. Only 2-10 muCi (74-370 kBq) of radioactivity are used and, as a consequence of the high specific activities with which carbon-11 and fluorine-18 labelled compounds can be prepared, the method requires less than a nanomole of drug to be administered. In many cases, this amount of drug might be considered low enough to avoid any adverse biological effect. Furthermore repeat studies are possible in many without delivering unacceptable radiation burdens. 4. The high sensitivity realised for both radioactivity and mass suggests a mean for determining the human biodistribution of a new drug at a very early stage in its development. This has potential benefit to drug discovery programmes and to ensuing drug therapies.

Blood-Brain Barrier↗
PubMed1991

Endogenous opiate response to pain in rheumatoid arthritis and cortical and subcortical response to pain in normal volunteers using positron emission tomography.

Identification of the main areas in the brain that respond specifically to the "suffering" components of pain has been achieved by using serial dynamic measurements of blood flow as an index of synaptic activity. Specific response to a repeated painful thermal stimulus as compared to a non-painful thermal stimulus in normal male volunteers identified the anterior cingulate cortex and the thalamus contralateral to the side of stimulation as the main sites of significant response. It was concluded that it was these areas where pain was likely to be experienced. Changes in opioid receptor binding in the brain was measured using 11C-diprenorphine and positron emission tomography in three patients with rheumatoid arthritis. In the two patients with active rheumatoid arthritis substantial changes in opioid receptor binding in the brain are described. The significance of these findings are discussed.

Arthritis, Rheumatoid↗
PubMed1988

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↗