Search PubMed⌕ Search

Biomedical subjects

D C Costa

Publications and source records attributed to D C Costa.

At least 55 records · Page 3Linked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

Dementia with lewy bodies: a study of post-synaptic dopaminergic receptors with iodine-123 iodobenzamide single-photon emission tomography.

Dementia with Lewy bodies (DLB) can at present only be diagnosed with certainty by neuropathological examination. Diagnosis during life remains at best probable, based on the presence of symptoms known from autopsy studies to be frequently associated with DLB. The greatest practical clinical problem lies in distinguishing DLB and Alzheimer's disease (AD). In DLB there is a considerable degeneration of nigral neurones with depletion of striatal dopamine. In contrast, AD is not associated with significant changes in dopamine metabolism. Iodine-123 iodobenzamide single-photon emission tomography (IBZM-SPET) measures post-synaptic dopamine D2 neuroreceptor availability in the corpus striatum, but is nevertheless a method for assessing the integrity of the nigrostriatal dopaminergic pathway. Sixteen clinically diagnosed DLB patients, 15 normal controls and 13 AD patients underwent IBZM-SPET. All subjects were scanned 1.5-2 h after intravenous injection of 185 MBq of 123I-IBZM. Circular regions of interest were employed to calculate radioactivity ratios in each hemisphere as follows: caudate nucleus/frontal cortex, putamen/frontal cortex and caudate nucleus/putamen. The DLB patients had significantly lower left caudate/putamen ratios (95% confidence intervals: DLB 0.893-0.965, AD 0.972-1.175, controls 1.031-1.168) than either controls or AD patients, and significantly lower right caudate/putamen ratios (95% confidence intervals: DLB 0.926-1.019, AD 0.954-1.103, controls 1. 027-1.144) than controls. Our data suggest that patients with DLB diagnosed by clinical criteria have changes in striatal post-synaptic D2 receptors. This may be of value in distinguishing DLB from AD during life.

Aged↗
PubMed1997

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↗
PubMed1997

Initial evaluation of 123I-5-I-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects.

The mapping of 5-HT2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-io do-2-methoxybenzamide (123I-5-I-R91150 or 123I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A receptors. This study reports on preliminary 123I-5-I-R91150 SPET, whole-body and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i. ). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SME-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100-120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT2A receptors in humans (cerebral cortex>striatum>cerebellum). These findings suggest that 123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the living human brain with SPET.

Adult↗
PubMed1997

In vivo effects on striatal dopamine D2 receptor binding by the novel atypical antipsychotic drug sertindole--a 123I IBZM single photon emission tomography (SPET) study.

The novel antipsychotic drug sertindole has an atypical pharmacological profile. We have estimated striatal D2 dopamine binding in schizophrenic patients treated with sertindole using 123I iodobenzamide (IBZM) SPET. Patients were recruited from a clinical trial of sertindole's tolerability and efficacy. Striatal D2 binding in sertindole-treated patients (n = 5), was compared with previously reported data from clozapine (n = 10); olanzapine (n = 6); typical antipsychotic responsive (n = 10); and risperidone (n = 6)-treated groups. Mean PANSS (structured clinical interview for the positive and negative syndrome scale) scores showed clinical improvement in the sertindole group. Few extrapyramidal side effects (EPS) were recorded [average Simpson-Angus (SAS) score = 2.6]. Sertindole-treated patients had mean D2 binding indices (+/-SE) significantly lower than clozapine-treated patients (1.19 +/- 0.04) versus (1.49 +/- 0.04), and olanzapine-treated patients (1.41 +/- 0.06); and similar to those of risperidone (1.24 +/- 0.04) and typical antipsychotic responsive (1.25 +/- 0.05) treated patients. In this patient sample the preliminary evidence suggests that sertindole's decreased tendency to induce EPS at clinically therapeutic doses is not due to limited occupancy of striatal D2 receptors in vivo, and as is the case for risperidone, patients are protected from EPS by some other intrinsic effect of the drug.

Adult↗
PubMed1997

HMPAO SPET does not distinguish obsessive-compulsive and tic syndromes in families multiply affected with Gilles de la Tourette's syndrome.

BACKGROUND: Gilles de la Tourette's syndrome (GTS) is a familial neuropsychiatric disorder characterized by tics and obsessive-compulsive behaviours (OCB). Previous HMPAO SPET studies of subjects with GTS have shown hypoperfusion of striatal and frontal areas. Studies of patients with primary obsessive-compulsive disorder have shown, in contrast, hyperperfusion of similar areas. METHODS: Twenty subjects from five families affected by GTS, including individuals with OCB but no tics, were examined using HMPAO SPET. RESULTS: There were abnormalities of regional cerebral perfusion in individuals with GTS, OCB and tics. Hypoperfusion was in striatal, frontal and temporal areas. There was no hyperperfusion. CONCLUSIONS: Regional cerebral blood flow patterns in individuals with OCB in families affected by GTS are comparable to their relatives with GTS and differ from individuals with primary OCD in the absence of a family history of tic disorders.

Adolescent↗
PubMed1997

Wisconsin Card Sorting Task (WCST) errors and cerebral blood flow in obsessive-compulsive disorder (OCD).

We compared Wisconsin Card Sorting Task (WCST) performance in 19 obsessive-compulsive disorder (OCD) patients and 19 individually matched healthy controls. Measures of intelligence and mood were taken into account for all participants. Within the patient group, factors such as duration and severity of symptoms (as assessed using the Yale-Brown Obsessive-Compulsive Scale, Y-BOCS) were considered. We explored the relationship between OCD WCST errors and regional cerebral blood flow (rCBF) on brain dedicated, high resolution, single photon emission tomography (SPET). We used uptake of 99mTc-hexamethylpropylamine oxime (HMPAO) on SPET to estimate rCBF, and regional values were quantified as ratios of cerebellar blood flow. WCST results confirmed OCD patients were significantly impared when compared with age- and sex-matched healthy volunteers. Patients made significantly more trials, more preseverative errors, and more null-sorts. OCD patients Y-BOCS 'obsessive' subtotal significantly correlated with many WCST errors. Furthermore OCD WCST null-sorts correlated significantly with SPET OCD left inferior frontal cortical rCBF (r(18) = .47, p = .05) and left caudate rCBF (r(18) = .72, p = .01). The implications of these findings are discussed in the context of other studies which examine functional imaging and neuropsychology in OCD.

Adult↗
PubMed1997

Psychiatric profiles and patterns of cerebral blood flow in focal epilepsy: interactions between depression, obsessionality, and perfusion related to the laterality of the epilepsy.

OBJECTIVES: In a study of patients with focal epilepsy the hypothesis was explored that different measurements of psychopathology are related to specific distributions of cerebral perfusion. METHODS: Forty patients had SPECT performed with (99m)Tc-HMPAO. In addition, patients received a psychiatric evaluation with the following psychiatric questionnaires: the Beck depression inventory, the Leyton obsessionality inventory, the Bear-Fedio questionnaire, and the social stress and support interview. Patients were analysed in two groups according to the laterality of the epilepsy. Nine patients were excluded based on poor quality scans (n = 1), unlateralised epilepsy (n = 4), and left or ambidextrous handedness (n = 4). RESULTS: There were no overall differences between the left and right epilepsy groups on measures of psychopathology. Associations were found between scores on some of the rating scales and regional cerebral blood flow. Specifically, for patients with left sided epilepsy, higher scores on the Beck depression inventory were associated with lower contralateral temporal and bilateral frontal perfusion, and higher occipital perfusion. For patients with right sided epilepsy higher scores on the Leyton obsessionality inventory were associated with increased perfusion in ipsilateral temporal, thalamic, and basal ganglia regions and bilateral frontal regions. CONCLUSION: The results do not support the notion that lateralised epileptogenic lesions are associated with different levels of depression, obsessionality, or personality traits. They support the view that certain psychopathological symptom patterns are related to specific regional dysfunctions depending on the laterality of a hemispheric lesion.

Adolescent↗
PubMed1997

Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia.

OBJECTIVE: Although there is evidence from postmortem studies suggestive of deficient inhibitory neurotransmission of gamma-aminobutyric acid (GABA) in schizophrenia, no direct in vivo evidence has been obtained to date. The authors used single photon emission computed tomography (SPECT) with iodine-123-labeled iomazenil ([123I]iomazenil), a radioligand that selectively binds with high affinity to the benzodiazepine subunit of the GABAA receptor complex in the human brain, to investigate the presence of benzodiazepine receptor abnormalities in the cerebral cortex of living subjects with schizophrenia. METHOD: Dynamic [123I]iomazenil SPECT was performed in 15 patients (14 patients with DSM-III-R schizophrenia and one with schizophreniform disorder) and 12 healthy subjects over a period of 2 hours. The time-integral method was used to generate ratios of "specific" to "nonspecific" [123I]iomazenil binding at equilibrium for several cortical regions. RESULTS: No overall between-group differences in benzodiazepine receptor binding were found, but significant correlations emerged between the severity of schizophrenic symptoms and [123I]iomazenil binding in limbic cortical regions: positive symptom scores were negatively correlated with benzodiazepine receptor binding in the left medial temporal region, and negative symptoms were inversely related to receptor binding in the medial frontal region. These correlations were not significant when a Bonferroni correction for multiple comparisons was applied. CONCLUSIONS: These preliminary results are consistent with previous research implicating limbic cortical regions in the pathophysiology of schizophrenia, suggesting that reduced inhibitory GABAergic tone in these areas may contribute to the appearance of schizophrenic symptoms.

Adolescent↗
PubMed1997

Brain blood flow in anxiety disorders. OCD, panic disorder with agoraphobia, and post-traumatic stress disorder on 99mTcHMPAO single photon emission tomography (SPET).

BACKGROUND: We compared regional cerebral blood flow (rCBF) in three groups of patients with DSM-III-R anxiety disorders. METHOD: Fifteen patients with obsessive -compulsive disorder (OCD), 15 with panic disorder with agoraphobia (PA), and 16 with post-traumatic stress disorder (PTSD) and a similar group of healthy controls were assessed on brain-dedicated high-resolution SPET. RESULTS: MANOVA revealed significant rCBF differences between diagnostic groups (F = 4.4; d.f. = 3, 57; P = 0.007) and between cerebral regions (F = 6.4; d.f. = 1, 57; P = 0.01) in OCD and PTSD compared with PA and healthy controls, limited to bilateral superior frontal cortices and right caudate nuclei. Whole brain blood flow correlated positively with anxiety (r = 0.24, n = 46, P = 0.05). Beck depression scores correlated significantly negatively with left caudate rCBF (r = -0.24, n = 46, P = 0.05) and right caudate rCBF (r = -0.31, n = 46, P = 0.02). PTSD syndrome severity correlated significantly negatively with the left caudate (r = -0.49, n = 16, P = 0.03) and with right caudate rCBF (r = -0.7, n = 16, P = 0.001). CONCLUSIONS: Functional rCBF differences in anxiety disorders could relate to repetitive, intrusive, distressing mental activity, prominent in both OCD and PTSD.

Adult↗