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Biomedical subjects

P J Ell

Publications and source records attributed to P J Ell.

At least 91 records · Page 5Linked to original sources

Cognitive functioning and GABAA/benzodiazepine receptor binding in schizophrenia: a 123I-iomazenil SPET study.

BACKGROUND: The role of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in schizophrenia has previously been investigated using postmortem material. Recently, using single photon emission tomography (SPET) with the selective benzodiazepine antagonist 123I-Iomazenil as the radioligand, we have demonstrated an in vivo relationship between reduced GABAA/benzodiazepine receptor binding and the severity of positive symptomatology in schizophrenia. The present study aimed to build on this using the same in vivo scanning techniques, and relating findings to cognitive functioning. METHODS: Ten nonpsychiatric control subjects and 15 schizophrenic patients, matched for age and handedness, were scanned. A battery of neuropsychologic tests was also administered. RESULTS: Correlational analysis revealed a pattern of increased correlations between GABAA/benzodiazepine receptor binding and task performance, in the schizophrenic group compared to the control group. CONCLUSIONS: Findings are preliminary but suggest a relationship between reduced GABAA/benzodiazepine receptor binding and poorer cognitive functioning, involving memory and visual attention processes, in the schizophrenic group but not in the control group. A role for GABA in the pathophysiology of schizophrenia is suggested. Limitations of the present study and suggestions for future research are discussed.

Adult↗

Technetium-99m human immunoglobulin imaging in patients with subacromial impingement or adhesive capsulitis.

Although recognised as useful in detecting soft-tissue inflammation and infection, technetium-99m human immunoglobulin (Tc-99m HIG) has not been widely studied in evaluating regional inflammatory musculoskeletal conditions. Tc-99m HIG scintigraphy was undertaken for consecutive patients referred to a rheumatology clinic with unilateral shoulder pain, diagnosed with either subacromial impingement (n = 12) or adhesive capsulitis (n = 4) from clinical examination, radiographic, and in some cases arthrographic findings. In all patients there were no differences in Tc-99m HIG images between symptomatic and asymptomatic shoulders. The findings are discussed, with reference to patterns of tissue inflammation which have been associated with each of the two conditions and in the context of patients referred to hospital relatively late after onset of symptoms (4-6 months).

Bursitis↗

Early detection of melanoma metastases with radioiodinated methylene blue.

Melanin synthesised in melanoma cells presents a unique target to which the treatment can be selectively addressed, provided the pigment is recognised by a suitable drug. Methylene blue (MTB) possesses a high affinity for melanin and, therefore, accumulates preferentially in melanoma cells. Since not directly toxic to the tumour, MTB serves as a carrier for radioisotopes and, once taken up by melanoma cells, acts as a selectively localised source of radiation. Hence, radioderivatives of the compound can be used for both diagnosis and therapy of disseminated melanoma. Eleven patients with confirmed metastatic melanoma and one with a recent local recurrence were studied using radioiodinated (iodine-123 or iodine-131) MTB and a gamma camera. Biopsies of cutaneous lesions were taken to determine directly the compound uptake in tumours. This first clinical investigation concerning the diagnostic potential of radioiodinated MTB in patients with disseminated melanoma confirmed the existence of approximately 80% of internal lesions previously identified by routine methods and, additionally, enabled detection of unknown secondaries in 6 of 12 patients studied. There were no false-positive gamma camera images regardless of whether 123I or 131I was used. 131I proved to be more suitable than 123I for detecting melanoma metastases with radioiodinated MTB. Hazy images of the lesions treated with external beam radiation and/or some drugs suggest that initial radio- and chemotherapy might affect MTB uptake in melanoma metastases and reduce the clarity of the scintigrams obtained from a gamma camera. However, small, untreated internal lesions that cannot be visualised easily with the standard diagnostic methods are revealed with 131I-MTB regardless of their localisation. It is concluded that use of radioiodinated MTB in conjunction with gamma camera or positron emission tomographic imaging might prove to be a useful and accessible tool for the detection of early melanoma dissemination.

Adult↗

Foot pain: specific indications for scintigraphy.

Bone scintigraphy is requested as part of the investigation of foot pain, but its contribution to clinical management has not been comprehensively documented. Previously published data are limited; the most comprehensive series identified scintigraphic abnormalities in patients with primarily orthopaedic problems and a control group was not included (Maurice HD et al. J Bone Joint Surg 1987;69B:448 52). The aim of this study was to evaluate whether bone scintigraphy may be useful in different clinical circumstances indicated by referral request details. Regions of scintigraphic abnormality were scored and compared with clinical details drawn from case notes of 60 patients with foot pain. The commonest clinical indications for scans were: confirmation of the clinical suspicion of plantar fasciitis, documentation of the extent of inflammatory arthritis and location of focal pathology. A group of 30 asymptomatic, age- and sex-matched controls were also studied. In 14 out of 19 symptomatic feet in the plantar fasciitis group, focal uptake at the medial calcaneal tubercle was present, confirming the diagnosis. In patients with non-specific, diffuse foot pain, the bone scan identified focal abnormalities in 11 out of 14 cases, thus directing the clinician to the site of pathology. Scintigraphy also proved useful in mapping local inflammatory disease. Technetium-99m methylene diphosphonate image abnormalities occurred in the control group most commonly in the midfoot (16 regions in 13 subjects) and first metatarsophalangeal joint (19 regions in 14 subjects).

Adolescent↗

Magnetic resonance imaging, thallium-201 SPET scanning, and laboratory analyses for discrimination of cerebral lymphoma and toxoplasmosis in AIDS.

OBJECTIVES: To compare the results of magnetic resonance imaging (MRI) and thallium-201 (201Tl) SPET scanning with laboratory analyses including CSF DNA detection, brain biopsy, and necropsy in the discrimination of cerebral lymphoma and toxoplasmosis in patients with AIDS. METHODS: A retrospective study of 32 patients infected with HIV who had focal CNS lesions on MRI as a result of either lymphoma or toxoplasmosis. RESULTS: 18 patients had lymphoma, 12 had toxoplasmosis, and two had both. Toxoplasma IgG antibodies were detected in only seven patients--four with toxoplasmosis, two with lymphoma, and one with both diagnoses. Epstein-Barr virus DNA was detected in CSF of all six patients with lymphoma and none of two with toxoplasmosis. MRI showed multiple lesions in 23 patients, appearances did not discriminate between lymphoma and toxoplasmosis; nine patients had single lesions, of these eight had lymphoma (p = 0.044, two tailed Fisher's exact test) 201Tl SPET showed accumulation in 17 with lymphoma and six with toxoplasmosis (p = 0.034, two tailed Fisher's exact test). Of nine patients with single lesions on MRI and 201Tl SPET with focal accumulation eight had lymphoma. 201Tl SPET uptake ratios of > or = 2.9 were only seen with lymphoma. CONCLUSION: Knowledge of patients' toxoplasma serostatus does not aid discrimination between lymphoma and toxoplasmosis. Single lesions on MRI with focal accumulation of 201Tl strongly suggest lymphoma. Multiple lesions on MRI with 201Tl SPET uptake ratios > or = 2.9 also suggest lymphoma; uptake ratios less than 2.1 do not aid discrimination. Detection of Epstein-Barr virus DNA in CSF is highly sensitive and specific for cerebral lymphoma.

AIDS-Related Opportunistic Infections↗

Reduced levels of GABA-benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy.

BACKGROUND: We tested the hypothesis that reduced levels of the GABA-benzodiazepine receptor occur in alcohol dependency using single photon emission tomography (SPET) and the specific GABA-benzodiazepine ligand, 123I-iomazenil. METHOD: Neurologically and cognitively unimpaired abstinent alcohol-dependent (n = 12) and non-alcohol-dependent male subject (n = 14) underwent a 123I-iomazenil SPET scan. SPET and magnetic resonance images were co-registered and voxel-based statistical tests performed. Subjects' clinical and alcohol history were obtained with standard questionnaires. The relationships between clinical and alcohol variables and the regional level of GABA-benzodiazepine receptors were investigated using multiple regression analysis. RESULTS: Abstinent alcohol-dependent subjects had decreased levels of GABA-benzodiazepine receptor compared with non-alcohol-dependent subjects within the frontal, parietal and temporal cortices, including regions in which grey matter atrophy was absent. CONCLUSIONS: Alcohol dependency is associated with reduced GABA-benzodiazepine receptor levels in the absence of grey matter atrophy in some cortical regions, such as within the parietal lobe. Regional variability of reduction in GABA-benzodiazepine receptors demonstrates that alcohol does not have a global, toxic effect on the brain.

Adult↗

5-HT2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine. A SPET study using the novel 5-HT2A ligand 123I-5-I-R-91150.

BACKGROUND: 5-HT2A receptor antagonism may be crucial to the action of atypical antipsychotics. Previous work has related 5-HT2A receptor blockade to clinical efficacy and protection from extrapyramidal side-effects. METHOD: We developed a SPET imaging protocol for assessing 5-HT2A receptor binding using the selective ligand 123I-5-I-R91150. Six healthy volunteers, five clozapine- and five risperidone-treated subjects with DSM-IV schizophrenia were studied. Multi-slice SPET was performed on each subject. RESULTS: Cortex:cerebellum ratios were significantly lower in both clozapine- and risperidone-treated subjects compared with the healthy volunteers in all cortical regions. There was no difference in occupancy between the two drug-treated groups. No correlation was found between the percentage change in the Global Assessment Scale (GAS) and 5-HT2A receptor binding indices in the drug-treated groups. CONCLUSIONS: Clozapine and risperidone potently block 5-HT2A receptors in vivo. The lack of relationship between receptor binding indices and change in GAS suggests that 5-HT2A receptor blockade may be unrelated to clinical improvement. Future studies will substantiate this finding by studying 5-HT2A receptor binding in large groups of patients treated with both typical and novel atypical antipsychotics.

Adult↗

Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Adult↗

Recurrent follicular carcinoma-oxyphilic cell type (Hürthle cell carcinoma) of the thyroid, imaging with iodine-131 and technetium-99m tetrofosmin before and after radiotherapy.

A 68-year-old male with recurrence of malignant follicular carcinoma-oxyphilic cell type of the thyroid after surgery underwent whole body scintigraphy with 131I-sodium iodide and 99Tcm-tetrofosmin (Myoview). 131I scanning demonstrated local uptake most likely to be in the normal remnant, but 99Tcm-Myoview images delineated recurrence of the carcinoma in the neck, with more extensive involvement. We believe that a combination of 131I and 99Tcm-tetrofosmin imaging may be useful to assess the extent of disease in patients with recurrent Hürthle cell type carcinoma of the thyroid.

Adenocarcinoma↗

Iodine-131-MIBG therapy of a patient with carcinoid liver metastases.

UNLABELLED: Iodine-13I-metaiodobenzylguanidine (MIBG) is highly concentrated by >60% of carcinoid metastases and thus provides a therapeutic opportunity. METHODS: A symptomatic patient with carcinoid liver metastases, unresponsive to chemotherapy combined with interferon-alpha, was subsequently treated with 131I-MIBG. RESULTS: Radionuclide therapy, which was without significant side effects, resulted in symptomatic improvement and reduced urinary 5-hydroxyindoleacetic acid levels. No new metastases were observed for 15 mo after 131I-MIBG therapy. Gross cystic change occurred in existing liver metastases, presumably as a result of ischemic necrosis. Surgical deroofing and aspiration of cysts led to regeneration of normal liver tissue. CONCLUSION: Iodine-131-MIBG therapy can provide prolonged symptomatic relief and improved quality of life in patients with metastatic carcinoid disease unresponsive to other therapies. The antitumor effect of 131I-MIBG was accompanied by few side effects, suggesting that this therapy should be considered in symptomatic patients with an early stage of disease.

3-Iodobenzylguanidine↗

Caudate regional cerebral blood flow in obsessive-compulsive disorder, panic disorder and healthy controls on single photon emission computerised tomography.

We compared regional cerebral blood flow (rCBF) in 15 patients with DSM IIIR obsessive-compulsive disorder (OCD), 15 patients with DSM IIIR panic disorder and 15 healthy controls matched for age, sex and hand preference, using uptake of technetium-99m-D,L-hexamethyl-propylene amine oxime (99mTc HMPAO), on single photon emission computerised tomography (SPECT). Caudate rCBF was significantly reduced in OCD patients compared to healthy subjects and panic disorder patients. When four patients were excluded from each group, right caudate rCBF remained significantly lower in OCD patients than in panic disorder patients or healthy subjects. The data suggest functional involvement of the right caudate nucleus is present in OCD.

Adult↗

Effect of attenuation correction on myocardial thallium-201 distribution in patients with a low likelihood of coronary artery disease.

Regional variation of tracer distribution is seen in uncorrected thallium-201 images of normal hearts. This study evaluates the effect of attenuation correction on myocardial 201T1 distribution in patients with low risk of coronary artery disease. An L-shaped dual-detector single-photon emission tomographic system equipped with a pair gadolinium-153 scanning line sources was used for sequential emission/transmission imaging in 36 patients (14 men and 22 women) with less than 5% risk for coronary artery disease. Uncorrected emission images were reconstructed using filtered back-projection (FBP) whereas the attenuation corrected (AC) images were iteratively reconstructed using the attenuation map computed from the transmission data. Both sets of images were reorientated into short axis, vertical long axis and horizontal long axis images. For quantification data were reconstructed into polar plots and count density estimated in 17 myocardial segments. The population % standard deviation for each segment of AC data was significantly smaller than that for FBP data, indicating improved homogeneity of tracer distribution. In men the anterior-basal inferior activity ratio improved from 1.20 for FBP to 0.96 for AC (stress) and from 1.23 for FBP to 0.98 for AC (delay) (P < 0.0001). In women the anterior-basal inferior activity ratio changed from 1.08 for FBP to 0.94 for AC (stress) and from 1.08 for FBP to 0.93 for AC (delay) (P < 0.001). These ratios reflect appropriate compensation for basal attenuation but a lack of scatter correction. The lateral-septal activity ratio in men changed from 1.05 for FBP to 0.99 for AC (stress) and from 1.02 for FBP to 0.96 for AC (delay), while in women it changed from 1.05 for FBP to 0.98 for AC (stress) and from 1.04 for FBP to 0.98 for AC (delay) (P < 0.005 in all cases). The apex of AC images showed a decrease in activity consistent with wall thining at this site. It is concluded that the use of attenuation correction yields improved homogeneity of myocardial tracer distribution in patients with low risk of coronary artery disease. The diagnostic benefits of attenuation correction are yet to be fully assessed.

Adenosine↗

Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine D2 receptor images in schizophrenia.

This paper describes the application of a multivariate statistical technique to investigate striatal dopamine D2 receptor concentrations measured by iodine-123 iodobenzamide (123I-IBZM) single-photon emission tomography (SPET). This technique enables the automatic segmentation of dynamic nuclear medicine images based on the underlying time-activity curves present in the data. Once the time-activity curves have been extracted, each pixel can be mapped back on to the underlying distribution, considerably reducing image noise. Cluster analysis has been verified using computer simulations and phantom studies. The technique has been applied to SPET images of dopamine D2 receptors in a total of 20 healthy and 20 schizophrenic volunteers (22 male, 18 female), using the ligand 123I-IBZM. Following automatic image segmentation, the concentration of striatal dopamine D2 receptors shows a significant left-sided asymmetry in male schizophrenics compared with male controls. The mean left-minus-right laterality index for controls is -1.52 (95% CI -3.72-0.66) and for patients 4.04 (95% CI 1.07-7.01). Analysis of variance shows a case-by-sex-by-side interaction, with F=10.01, P=0. 005. We can now demonstrate that the previously observed male sex-specific D2 receptor asymmetry in schizophrenia, which had failed to attain statistical significance, is valid. Cluster analysis of dynamic nuclear medicine studies provides a powerful tool for automatic segmentation and noise reduction of the images, removing much of the subjectivity inherent in region-of-interest analysis. The observed striatal D2 asymmetry could reflect long hypothesized disruptions in dopamine-rich cortico-striatal-limbic circuits in schizophrenic males.

Benzamides↗