Search PubMed⌕ Search

Biomedical subjects

P J Ell

Publications and source records attributed to P J Ell.

At least 73 records · Page 4Linked to original sources
PubMed2000

Levels of gamma-aminobutyric acid-benzodiazepine receptors in abstinent, alcohol-dependent women: preliminary findings from an 123I-iomazenil single photon emission tomography study.

BACKGROUND: Although alcohol dependence in women is an increasing problem, little is known about the effects of alcohol on the female brain. Evidence from a few structural and functional neuroimaging studies suggests that the female brain may be more susceptible than the male brain to the harmful effects of alcohol. However, no in vivo studies of the neuropharmacology of alcohol dependence in women have been carried out. The aim of this preliminary study was to test the hypothesis that alcohol dependence in women is associated with greater reduction in gamma-aminobutyric acid (GABA)-benzodiazepine receptor levels than in men with an equivalent drinking history. METHODS: We used single photon emission tomography and 123I-iomazenil to label the central GABA-benzodiazepine receptor and to compare semiquantified levels in 9 abstinent alcohol-dependent and 13 control women. These groups were further compared with equivalent male groups from a previous study. RESULTS: There was a trend toward a reduction in GABA-benzodiazepine receptor levels in alcohol-dependent women, but this did not reach significance. These lower levels were seen primarily in the cerebellum, occipital lobes, and parietal cortex (left > right). This was in marked contrast with the pattern of reduction seen in the previous study of male dependence, where significant reductions were seen primarily in the frontal cortex. CONCLUSIONS: Due to the semiquantitative analysis performed and the relatively small number of subjects in this study, which resulted in a nonsignificant trend, we can only comment on the differences in the pattern of lower levels of GABA-benzodiazepine receptors seen in alcohol dependence in men and women. Although we are not able to ascertain whether the female brain is more susceptible to the effects of alcohol, it appears that alcohol has a differential effect on the central GABA-benzodiazepine receptors in men and women. Recent animal evidence supports this hypothesis. Future studies should explore whether other neuropharmacological differences exist between men and women in alcohol dependence that could have implications for pharmacotherapy.

Adult↗
PubMed1999

Nuclear medicine in neurology and psychiatry.

Progress in nuclear medicine has always been a function of technological advances, and applications in neurology and psychiatry illustrate the point. Improvements in radiation detectors now allow for three-dimensional and quantitative mapping of the distribution of a labelled compound in the human brain. New ligands permit the study of specific functioning signals of the blood/brain barrier, blood flow, metabolism (oxygen, glucose, aminoacids), and neurotransmission (dopamine, benzodiazepine, serotonin receptors). The picomolar sensitivity of nuclear medicine can now be coupled to a wide group of ligands which offer specific information that can be obtained in no other way in the living patient.

Animals↗
PubMed1999

Automatic segmentation of dynamic neuroreceptor single-photon emission tomography images using fuzzy clustering.

The segmentation of medical images is one of the most important steps in the analysis and quantification of imaging data. However, partial volume artefacts make accurate tissue boundary definition difficult, particularly for images with lower resolution commonly used in nuclear medicine. In single-photon emission tomography (SPET) neuroreceptor studies, areas of specific binding are usually delineated by manually drawing regions of interest (ROIs), a time-consuming and subjective process. This paper applies the technique of fuzzy c-means clustering (FCM) to automatically segment dynamic neuroreceptor SPET images. Fuzzy clustering was tested using a realistic, computer-generated, dynamic SPET phantom derived from segmenting an MR image of an anthropomorphic brain phantom. Also, the utility of applying FCM to real clinical data was assessed by comparison against conventional ROI analysis of iodine-123 iodobenzamide (IBZM) binding to dopamine D2/D3 receptors in the brains of humans. In addition, a further test of the methodology was assessed by applying FCM segmentation to [123I]IDAM images (5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio] benzyl alcohol) of serotonin transporters in non-human primates. In the simulated dynamic SPET phantom, over a wide range of counts and ratios of specific binding to background, FCM correlated very strongly with the true counts (correlation coefficient r2>0.99, P<0.0001). Similarly, FCM gave segmentation of the [123I]IBZM data comparable with manual ROI analysis, with the binding ratios derived from both methods significantly correlated (r2=0.83, P<0.0001). Fuzzy clustering is a powerful tool for the automatic, unsupervised segmentation of dynamic neuroreceptor SPET images. Where other automated techniques fail completely, and manual ROI definition would be highly subjective, FCM is capable of segmenting noisy images in a robust and repeatable manner.

Animals↗
PubMed1999

Economics of myocardial perfusion imaging in Europe--the EMPIRE Study.

BACKGROUND: Physicians use myocardial perfusion imaging to a variable extent in patients presenting with possible coronary artery disease. There are few clinical data on the most cost-effective strategy although computer models predict that routine use of myocardial perfusion imaging is cost-effective. OBJECTIVES: To measure the cost-effectiveness of four diagnostic strategies in patients newly presenting with possible coronary artery disease, and to compare cost-effectiveness in centres that routinely use myocardial perfusion imaging with those that do not. METHODS: We have studied 396 patients presenting to eight hospitals for the diagnosis of coronary artery disease. The hospitals were regular users or non-users of myocardial perfusion imaging with one of each in four countries (France, Germany, Italy, United Kingdom). Information was gathered retrospectively on presentation, investigations, complications, and clinical management, and patients were followed-up for 2 years in order to assess outcome. Pre- and post-test probabilities of coronary artery disease were computed for diagnostic tests and each test was also assigned as diagnostic or part of management. Diagnostic strategies defined were: 1: Exercise electrocardiogram/coronary angiography, 2: exercise electrocardiogram/myocardial perfusion imaging/coronary angiography, 3: myocardial perfusion imaging/coronary angiography, 4: coronary angiography. Primary outcome measures were the cost and accuracy of diagnosis, the cost of subsequent management, and clinical outcome. Secondary measures included prognostic power, normal angiography rate, and rate of angiography not followed by revascularization. RESULTS: Mean diagnostic costs per patient were: strategy 1: 490 Pounds, 2: 409 Pounds, 3: 460 Pounds, 4: 1253 Pounds (P < 0.0001). Myocardial perfusion imaging users: 529 Pounds, non-users 667 Pounds (P = 0.006). Mean probability of the presence of coronary artery disease when the final clinical diagnosis was coronary artery disease present were, strategy 1: 0.85, 2: 0.82, 3: 0.97, 4: 1.0 (P < 0.0001), users 0.93, non-users 0.88 (P = 0.02), and when coronary artery disease was absent, 1: 0.26, 2: 0.22, 3: 0.16, 4: 0.0 (P < 0.0001), users 0.21, non-users 0.20 (P = ns). Total 2-year costs (coronary artery disease present/absent) were: strategy 1: 4453 Pounds/710 Pounds, 2: 3842 Pounds/478 Pounds, 3: 3768 Pounds/574 Pounds, 4: 5599 Pounds/1475 Pounds (P < 0.05/0.0001), users: 5563 Pounds/623 Pounds, non-users: 5428 Pounds/916 Pounds (P = ns/0.001). Prognostic power at diagnosis was higher (P < 0.0001) and normal coronary angiography rate lower (P = 0.07) in the scintigraphic centres and strategies. Numbers of soft and hard cardiac events over 2 years and final symptomatic status did not differ between strategy or centre. CONCLUSION: Investigative strategies using myocardial perfusion imaging are cheaper and equally effective when compared with strategies that do not use myocardial perfusion imaging, both for cost of diagnosis and for overall 2 year management costs. Two year patient outcome is the same.

Angioplasty↗
PubMed1999

Langer's axillary arch in association with sentinel lymph node.

Langer's axillary arch is a relatively rare anatomical variation of latissimus dorsi muscle insertion. The clinical importance of this condition in axillary lymph node dissection (ALND) and lymphoedema as well as latissimus dorsi flap reconstruction has been described previously. Axillary vein obstruction in association with this condition has also been reported. We report two cases of Langer's axillary arch encountered during sentinel lymph node (SLN) biopsy which had some bearing on the procedure.

Journal Article↗
PubMed1999

Changes in articular synovial lining volume measured by magnetic resonance in a randomized, double-blind, controlled trial of intra-articular samarium-153 particulate hydroxyapatite for chronic knee synovitis.

OBJECTIVE: Magnetic resonance techniques have recently been investigated as tools with which to monitor inflammatory joint disease. Our aim was to use a contrast-enhanced T1-weighted protocol to monitor the short-term changes in knee synovial lining volume in a double-blind, randomized, controlled trial of intra-articular samarium-153 particulate hydroxyapatite (Sm-153 PHYP). METHODS: Twenty-four out-patients with chronic knee synovitis, from a cohort who had been recruited to a long-term clinical efficacy trial, were recruited for this study. Patients received either intra-articular Sm-153 PHYP combined with 40 mg triamcinolone hexacetonide or 40 mg intra-articular triamcinolone hexacetonide alone. Synovial lining volumes were calculated from three-dimensional T1-weighted contrast-enhanced images made before and after contrast enhancement with thresholding and pixel counting, immediately before and 3 months after treatment. RESULTS: Paired pre- and post-treatment magnetic resonance data were obtained for 18/24 (75%) patients. There was no significant difference in mean pre-treatment synovial volume between the two treatment groups (139 vs 127 ml). A mean reduction in synovial lining volume was detected in the Sm-153 PHYP/steroid-treated group (139 to 110 ml, P = 0.07) and in the steroid-treated group (127 to 58 ml, P < 0.001). The reduction was significantly greater in the steroid-treated group (-61% vs -23%, P < 0.05). CONCLUSIONS: Short-term changes in articular synovial lining in response to intra-articular treatment for chronic synovitis may be monitored by magnetic resonance imaging. After 3 months, a greater mean reduction in synovial lining volume had occurred in response to intra-articular steroid alone compared to combined Sm-153 PHYP/steroid injection.

Adult↗
PubMed1999

Chromosomal analysis of peripheral lymphocytes of patients before and after radiation synovectomy with samarium-153 particulate hydroxyapatite.

OBJECTIVE: Radiation synovectomy may be indicated for the treatment of chronic synovitis. A number of factors may affect its current use, including availability, limited evidence for its efficacy compared to intra-articular glucocorticoid, and concerns regarding the potential long-term effects of radiation exposure, particularly in younger patients. Specific chromosome-type abnormalities in peripheral lymphocytes can be useful indicators of whole-body radiation exposure. The frequency of these aberrations has been shown to increase in patients who have had radiation synovectomy using yttrium-90 by up to five times compared to baseline levels. Samarium-153 particulate hydroxyapatite (Sm-153 PHYP) is a new radiopharmaceutical currently on trial which appears to have less extra-articular leakage than yttrium-90 compounds. The aim of this study was to identify any increase in specific chromosome-type abnormalities, using published criteria, in patients following Sm-153 PHYP synovectomy of the knee. The 10 patients (five men, five women) in whom the analyses were performed had a mean age of 47 yr (range 28-70 yr). RESULTS: There was no increase in scored chromosome-type abnormalities after Sm-153 PHYP synovectomy. CONCLUSION: This study further supports the relative safety of Sm-153 PHYP compared to other radiopharmaceuticals.

Adult↗
PubMed1999

The practice of medical and surgical synovectomy: a UK survey.

Radiation, chemical and surgical synovectomy are therapeutic options in the treatment of chronic synovitis, but the evidence for their efficacy is limited. The aim of this survey was to compare the frequency of, and the factors affecting the use of, the three types of synovectomy in the last 2 years in the UK. Questionnaires were sent to all consultant rheumatologists and orthopaedic surgeons in the UK. Completed questionnaires were received from 294 rheumatology and 832 orthopaedic NHS consultants currently practising in the UK. Replies from the rheumatologists showed that surgical synovectomy was used most frequently, followed by radiation synovectomy (175 and 160 consultants respectively). Only 33 consultants had used chemical synovectomy. Only 314 of the 832 (38%) orthopaedic consultants who replied had performed surgical synovectomies in the last 2 years; 195 had used an arthroscopic procedure and 193 an open procedure. For all three therapies, the knee was the most commonly treated joint.

Ankle Joint↗
PubMed1999

Double blind glucocorticoid controlled trial of samarium-153 particulate hydroxyapatite radiation synovectomy for chronic knee synovitis.

BACKGROUND: Samarium-153 particulate hydroxyapatite (Sm-153 PHYP) is a relatively new radiation synovectomy agent developed for the treatment of chronic synovitis. Although it has been shown that the levels of unwanted extra-articular radiation are lower after intra-articular injection of Sm-153 PHYP than yttrium-90 colloid, its clinical efficacy has not been rigorously studied. OBJECTIVES: To establish whether Sm-153 PHYP radiation synovectomy results in a clinically useful benefit sustained at one year. METHODS: In a randomised double blind study, patients received either intra-articular 40 mg triamcinolone hexacetonide alone or 40 mg triamcinolone hexacetonide combined with Sm-153 PHYP in an outpatient clinic. RESULTS: Sixty patients (28 male, 32 female), median age 51 (18-75) with chronic knee synovitis were studied. Diagnoses included: rheumatoid arthritis (n=29); psoriatic arthritis (n=9); ankylosing spondylitis (n=3); reactive arthritis (n=2); undifferentiated seronegative oligoarthritis (n=13) and miscellaneous inflammatory conditions (n=4). More patients who received Sm-153 PHYP/triamcinolone hexacetonide sustained clinical benefit a year after treatment compared with patients who received corticosteroid alone (12 of 31 (39%) v 6 of 29 (21%), a difference of 18% more patients (95% CI -5% to 41%)) though the difference was not significant (chi(2)=2.31, 0.2>p>0.1, n=60). Despite the variation in injected activity (median 563 MBq, range 218-840 MBq), there was no obvious relation between low levels of injected activity (<555 MBq) and relapse within 12 months of treatment (chi(2) =2.61, 0.2>p>0.1, n=31). CONCLUSIONS: There was no clear beneficial clinical effect of combined Sm-153 PHYP/triamcinolone hexacetonide injection over triamcinolone hexacetonide alone a year after treatment for chronic knee synovitis.

Administration, Topical↗
PubMed1999

In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs. [123I]epidepride single photon emission tomography (SPET) study.

BACKGROUND: The dopamine hypothesis proposes that antipsychotic drugs act primarily through limbic cortical D2/D2-like dopamine receptor blockade. AIM: To evaluate this hypothesis with the D2/D3-selective SPET probe [123I]-epidepride. METHOD: [123I]-epidepride SPET scans were performed on 12 patients with schizophrenia treated with antipsychotics and II age-matched healthy controls. [123I]-epidepride 'specific binding' to D2/D3 dopamine receptors was estimated, and relative percentage D2/D3 receptor occupancy by typical antipsychotic drugs determined. RESULTS: Mean (s.d.) daily dose was 669.12 (516.8) mg chlorpromazine equivalents. Mean percentage D2/D3 receptor occupancy was 81.6 (8.1) and 73.2 (13.9) in the temporal cortex and striatum respectively. CONCLUSIONS: Typical antipsychotic drug treatment is associated with substantial temporal cortical D2/D3 receptor occupancy. The relationship between this and efficacy is poor in patients with treatment-resistant schizophrenia.

Adult↗
PubMed1998

Comparison of 201Tl, 99mTc-tetrofosmin, and dobutamine magnetic resonance imaging for identifying hibernating myocardium.

BACKGROUND: Both radionuclide perfusion tracers and contractile response to dobutamine have been used to identify hibernating myocardium. The aim was to compare 201Tl (thallium) single photon emission CT (SPECT), 99mTc-tetrofosmin (tetrofosmin) SPECT, and dobutamine cine MRI for identifying regions of reversible myocardial dysfunction. METHODS AND RESULTS: Thirty patients with 3-vessel coronary artery disease and impaired left ventricular function (mean LVEF, 24.0%; SD, 8.3%) scheduled for coronary bypass grafting were recruited. All underwent rest/dobutamine stress (5 to 10 microg . kg-1 . min-1) cine MRI, stress/rest tetrofosmin SPECT, and stress/redistribution and separate-day rest/redistribution thallium SPECT before surgery. Stress/redistribution thallium SPECT and resting MRI were repeated after surgery. In a 9-segment model, SPECT images were scored visually for tracer uptake, which was also measured from a polar plot of myocardial counts. MRI was scored visually for endocardial motion, myocardial thickening, and thickness. Five patients died before follow-up, and 2 declined postoperative investigation. In the remaining 23 patients, mean LVEF increased from 24.0% (SD, 8.3%) to 29.7% (SD, 11.1%) (P<0.05). Of 207 segments analyzed, 145 had significantly abnormal wall motion before surgery, and 82 of these improved function after revascularization. The criteria for predicting recovery of severely hypokinetic segments on preoperative imaging were tracer uptake graded "moderately reduced" or better, or positive inotropic response on dobutamine MRI. Late-rest thallium images showed the highest sensitivity (76%), compared with stress-redistribution thallium (68%) and rest tetrofosmin (66%) (P<0.05). All 3 tracer techniques were nonspecific (44%, 51%, and 49%, respectively). Redistribution of thallium after the resting injection was insensitive (18%) but highly specific (83%). Inotropic response to dobutamine was also insensitive (50%) but specific (81%). CONCLUSIONS: Radionuclide uptake is a sensitive but nonspecific predictor of myocardial functional recovery, whereas dobutamine MRI is specific but insensitive.

Adult↗