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Biomedical subjects

D C Costa

Publications and source records attributed to D C Costa.

At least 91 records · Page 5Linked to original sources

Immunoscintigraphy with a 99Tcm-labelled anti-granulocyte monoclonal antibody in patients with human immunodeficiency virus infection and AIDS.

The value of immunoscintigraphy with technetium-99m (99Tcm) labelled anti-granulocyte monoclonal antibody (BW250/183) was studied prospectively in human immunodeficiency virus (HIV-1) antibody-positive patients presenting with fever without localizing symptoms or signs. Twenty-three studies were performed in 23 patients and the results of 99Tcm-anti-granulocyte imaging were compared with the definitive microbiological or cytological diagnosis. Twenty-one patients had an infective cause of pyrexia, one patient had disseminated lymphoma and one Kaposi sarcoma. 99Tcm-anti-granulocyte antibody imaging correctly identified the sites of infection in only five (24%) patients, four of whom had infective colitis (one also had bacterial pneumonia) and one of whom had cellulitis. Sixteen foci of infection were not localized by 99Tcm-anti-granulocyte immunoscintigraphy (false-negative scans). Six of these patients had Pneumocystis carinii pneumonia; other diagnoses in this group included bacterial or fungal pneumonia and bacteraemia secondary to line infections. 99Tcm-anti-granulocyte antibody did not accumulate in the patients with disseminated lymphoma and Kaposi sarcoma (true-negative scans). 99Tcm-anti-granulocyte imaging, therefore, appears useful in identifying extrathoracic infection in HIV-1 positive patients. Its lack of sensitivity for the identification of pulmonary infection means that its role in the investigation of HIV-1 antibody-positive patients with fever without localizing symptoms or signs is limited.

AIDS-Related Opportunistic Infections↗

Brain perfusion abnormalities in Gilles de la Tourette's syndrome.

BACKGROUND: Functional brain imaging with technetium-99m d,l-hexamethyl propyleneamine oxime (HMPAO) Single Photon Emission Tomography (SPET) allows us to explore the cerebral pathophysiology of Gilles de la Tourette's Syndrome (GTS). METHOD: Fifty patients and 20 controls were examined. Patients were rated for tic severity and mood. Scans were analysed quantitatively using internal ratios to the occipital cortex. RESULTS: Patients different from controls on measures of relative blood flow to the left caudate, anterior cingulate cortex and the left dorsolateral prefrontal cortex. Severity of tics was related to hypoperfusion of the left caudate and cingulate and a left medial temporal region. Hypoperfusion in the left dorsolateral prefrontal region was related to mood. CONCLUSIONS: The areas found to be hypoperfused in this study are consistent with known functions of fronto-striatal circuits. A wide range of perfusion patterns is seen, however, and no characteristic patterns for behavioural subgroups has been documented with this technique.

Adolescent↗

Regional cerebral blood flow in obsessive-compulsive disordered patients at rest. Differential correlates with obsessive-compulsive and anxious-avoidant dimensions.

BACKGROUND: We tested whether cortical and subcortical regional cerebral blood flow (rCBF) differs between patients with obsessive-compulsive disorder (OCD) and healthy controls. We then explored the relationship between rCBF and OCD mental state. METHOD: Thirty out-patients from the Maudsley Hospital with OCD as defined in DSM-III-R were scanned at rest using brain-dedicated, high-resolution, single photon emission tomography. RCBF was measured as uptake of 99mTc-HMPAO in 15 regions of interest and compared with rCBF data in 30 healthy people matched for age, sex and handedness. Symptom ratings were obtained using standard measures on the scanning day. Principal components factor analysis identified two distinct clinical dimensions: obsessive-compulsive (OC) and anxious-avoidant (AA). These were correlated with patients' rCBF measurements, using Spearman's rank correlation coefficient, and multiple regression coefficients calculated. RESULTS: We found significant reductions in rCBF measurements of OCD patients compared with resting, healthy controls (F = 1.92, P = 0.04) in seven brain regions: the right and left superior frontal cortex, right inferior frontal cortex, left temporal cortex, left parietal cortex, right caudate nucleus and right thalamus. Regional differences were not secondary to generalised reduction in patients' brain perfusion. Reduced blood flow to the right inferior frontal cortex correlated significantly with illness severity (r = 0.37, P = 0.02). There was no relationship with age, age-of-onset, sex, handedness, depression or medication status. OC clinical dimension, concerning obsessions, compulsions and low mood, was significantly negatively correlated with left inferior frontal, medial frontal and right parietal rCBF. AA dimension, concerning anxiety and avoidance, was significantly positively associated with left and right superior frontal, right inferior frontal, medial frontal cortical, and right and left caudate and thalamic rCBF. CONCLUSIONS: rCBF differs significantly between resting OCD patients and healthy controls, and separate clinical dimensions are associated with functionally distinct rCBF patterns.

Adult↗

Radionuclide brain imaging in acquired immunodeficiency syndrome (AIDS).

Infection with the human immunodeficiency virus-type 1 (HIV-1) may produce a variety of central nervous system (CNS) symptoms and signs. CNS involvement in patients with the acquired immunodeficiency syndrome (AIDS) includes AIDS dementia complex or HIV-1 associated cognitive/motor complex (widely known as HIV encephalopathy), progressive multifocal leucoencephalopathy (PML), opportunistic infections such as Toxoplasma gondii, TB, Cryptococcus and infiltration by non-Hodgkin's B cell lymphoma. High resolution structural imaging investigations, either X-ray Computed Tomography (CT scan) or Magnetic Resonance Imaging (MRI) have contributed to the understanding and definition of cerebral damage caused by HIV encephalopathy. Atrophy and mainly high signal scattered white matter abnormalities are commonly seen with MRI. PML produces focal white matter high signal abnormalities due to multiple foci of demyelination. However, using structural imaging techniques there are no reliable parameters to distinguish focal lesions due to opportunistic infection (Toxoplasma gondii abscess) from neoplasm (lymphoma infiltration). In this manuscript we review the use of radionuclide brain imaging techniques in the investigation of HIV infected patients. Brain perfusion single photon emission tomography (SPET), neuroreceptor and positron emission tomography (PET) studies are reviewed. Greater emphasis is put on the potential of some radiopharmaceuticals, considered to be brain tumor markers, to distinguish intracerebral lymphoma infiltration from Toxoplasma infection. SPET with 201Tl using quantification (tumour to nontumour radioactivity ratios) appears a very promising technique to identify intracerebral lymphoma.

AIDS Dementia Complex↗

Combined rest thallium-201/stress technetium-99m-tetrofosmin SPECT: feasibility and diagnostic accuracy of a 90-minute protocol.

UNLABELLED: Technetium-99m tetrofosmin is a recently developed compound that clears from background organs rapidly. Tetrofosmin has a good correlation with 201Tl. This study assesses the feasibility and diagnostic accuracy of a combined protocol involving rest 201Tl SPECT and stress imaging with 99mTc-tetrofosmin. METHODS: Twenty-five patients (23 men, 2 women; aged 36-73 yr) with known coronary artery disease underwent the combined protocol. Twenty minutes after the resting injection of 201Tl, resting SPECT data were acquired using low-energy, high-resolution collimators. A stress test using adenosine infusion combined with low-level dynamic exercise was performed. The stress data were collected 20 min later. The reconstructed vertical long-axis, horizontal long-axis and short-axis slices were analyzed qualitatively. Analysis was carried out using nine segments of the left ventricle. The segments were reported either as fixed or reversible. The results were compared to coronary angiography results. RESULTS: The sensitivity and specificity for the detection of diseased coronary vessels were 85% and 70% for the left anterior descending territory, respectively, 78% and 71% for the right coronary artery, and 69% and 70% for the left circumflex. Overall, the sensitivity was 80% and the specificity 70%. CONCLUSION: Combined rest 201Tl/stress 99mTc-tetrofosmin SPECT provides a protocol of short duration which displays similar diagnostic accuracy to a protocol using tetrofosmin as a single agent.

Adult↗

Brainstem perfusion is impaired in chronic fatigue syndrome.

We looked for brain perfusion abnormalities in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). An initial pilot study revealed widespread reduction of regional brain perfusion in 24 ME/CFS patients, compared with 24 normal volunteers. Hypoperfusion of the brainstem (0.72 +/- 0.05 vs. 0.80 +/- 0.04, p < 0.0001) was marked and constant. We then tested whether perfusion to the brainstem in ME/CFS patients differs from that in normals, patients with major depression, and others with epilepsy. Data from a total of 146 subjects were included in the present study: 40 normal volunteers, 67 patients with ME/CFS (24 in the pilot study, 16 with no psychiatric disorders, 13 with ME/CFS and depression, 14 with ME/CFS and other psychiatric disorders), 10 epileptics, 20 young depressed patients and 9 elderly depressed individuals. Brain perfusion ratios were calculated using 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) and single-photon emission tomography (SPET) with a dedicated three-detector gamma camera computer/system (GE Neurocam). Brain-stem hypoperfusion was confirmed in all ME/CFS patients. Furthermore, the 16 ME/CFS patients with no psychiatric disorders and the initial 24 patients in the pilot study showed significantly lower brainstem perfusion (0.71 +/- 0.03) than did depressed patients (0.77 +/- 0.03; ANOVA, p < 0.0001). Patients with ME/CFS have a generalized reduction of brain perfusion, with a particular pattern of hypoperfusion of the brainstem.

Adolescent↗

Striatal dopamine receptor binding in epileptic psychoses.

In order to study the nature of dopaminergic activity in epileptic psychoses we investigated striatal dopamine receptor binding in 14 patients with epilepsy. Seven of the patients were acutely psychotic when studied, having recently developed a periictal schizophreniform psychosis. The remaining patients were not psychotic. All patients were scanned using single photon emission tomography (SPET) with 123I-IBZM, a specific dopamine D2 receptor ligand. A region of interest analysis was performed. Comparison of mean basal ganglia to occipital cortex activity ratios in the two groups demonstrated significantly reduced specific binding of 123I-IBZM to striatal D2 receptors in the psychotic patients compared to those without psychosis.

Adult↗

Dopamine receptor availability in Tourette's syndrome.

A large body of evidence suggests that abnormal dopaminergic activity is present in Gilles de la Tourette Syndrome (GTS). To investigate whether dopamine dysregulation involving the D2/D3 receptor occurs in GTS, we performed single slice dynamic single photon emission computed tomography (SPECT) with 123iodo-6-methoxybenzamide (123I-IBZM) in 15 GTS patients (eight unmedicated) and six healthy volunteers. After intravenous administration of 5 mCi (185 MBq) of 123I-IBZM, dynamic SPECT (5 minutes per slice) studies were performed at the level of the basal ganglia for 55 minutes. The mean activity per pixel in the basal ganglia was compared with the mean activity per pixel in the visual cortex. Unmediated GTS patients showed no differences from control subjects. However, GTS patients taking D2 blocking medications had significantly decreased 123I-IBZM binding compared with control subjects in both the right and left basal ganglia. Thus, D2/D3 receptor availability, as measured by 123I-IBZM SPECT, is not abnormal in GTS.

Adolescent↗

Stereotypy, schizophrenia and dopamine D2 receptor binding in the basal ganglia.

Animal models suggest a relationship between disturbed striatal dopaminergic function and stereotyped behaviour. Several studies show increased stereotypy in schizophrenic patients compared to normal controls. We investigated the performance of 12 antipsychotic-drug-free schizophrenic patients, and 15 healthy control subjects on a neuropsychological measure of stereotypy--the two-choice guessing task--and correlated this with in vivo striatal dopamine D2 receptor binding, as measured by 123I-iodobenzamide single photon emission tomography. Patients and controls did not differ with respect to the measures of stereotypy derived from the task. However, there was a significant correlation between one of these measures (RR Information) and the degree of striatal D2 receptor binding asymmetry in the patient group only. In view of research connecting striatal and frontal lesions with stereotypy in animals and cognitive inflexibility in humans, these data could suggest a similar disturbance underlying the phenomenon in schizophrenia.

Adolescent↗

Regional cerebral blood flow (rCBF) in schizophrenia during verbal memory activation: a 99mTc-HMPAO single photon emission tomography (SPET) study.

Regional cerebral blood flow (rCBF) was investigated in a group of medicated DSM-III-R schizophrenic patients and age, sex and handedness matched normal volunteers using a split-dose 99mTc-HMPAO Single Photon Emission Tomography (SPET) protocol. Measures were taken during the performance of a verbal memory task aimed at activating the left medial temporal lobe, a region repeatedly suggested to be structurally abnormal in schizophrenia. In normal subjects, the performance of the task was associated with significant rCBF increases in the left medial temporal, left inferior frontal and anterior cingulate cortices, and right cerebellum. Despite their significantly poorer performance on the memory task, the degree of medial temporal activation measured in the schizophrenic patients was not significantly different from that found in the control group. This finding suggests that memory deficits in schizophrenia do not necessarily imply failure to activate the left medial temporal lobe as assessed by 99mTc-HMPAO SPET.

Adult↗

Clinical experience with a multidetector SPET system (Toshiba GCA-9300A).

The clinical experience with the Toshiba GCA-9300A single photon emission tomography (SPET) system is discussed along with typical acquisition protocols for various SPET studies. The system was used to perform SPET studies in normals and in a variety of brain and body disorders. Its three Anger-type gamma cameras forming a triangular aperture offer a substantial increase in sensitivity compared to a single rotating gamma camera. This has allowed the routine use of lead fanbeam super high-resolution collimators (SHR FB) for 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain SPET studies and high-resolution parallel-hole collimators (HR PH) for cardiac and other body studies. The resulting improvement in spatial resolution coupled with the ease of patient positioning and the greater patient throughput compared to a conventional tomographic gamma camera, will enhance the role of brain and body SPET for both routine and research purposes.

Bone and Bones↗

HMPAO SPECT in Parkinson's disease before and after levodopa: correlation with dopaminergic responsiveness.

Regional cerebral perfusion was evaluated by SPECT with technetium 99m hexamethylpropyleneamine oxime (99mTc HMPAO) as a tracer in 21 patients presenting with Parkinson's disease and in 11 normal controls. In the parkinsonian patients, scans were performed both off treatment, and after levodopa, and clinical dopaminergic responsiveness was evaluated. Uptake of HMPAO by the basal ganglia was significantly decreased in the parkinsonian subjects, compared with normal controls. This reduction was seen in both responders (n = 14) and non-responders (n = 7) to dopaminergic treatment. Uptake of HMPAO by the basal ganglia rose after treatment with levodopa, but the change was similar in both responders and non-responders. By contrast a striking difference in cortical HMPAO uptake was found between responders and non-responders, with significantly lower uptake in the medial temporal and posterior parietal cortex in the non-responders. This reduction was symmetrical. Basal ganglia perfusion assessed by this technique is unlikely to be of use in the diagnosis of Parkinson's disease that is responsive to dopaminergic treatment. The presence of extensive cortical involvement on a baseline scan correlates with a lack of dopaminergic responsiveness, however, and this may be useful diagnostically.

Aged↗

D2 dopamine receptor binding in the basal ganglia of antipsychotic-free schizophrenic patients. An 123I-IBZM single photon emission computerised tomography study.

We used SPECT to examine striatal D2 receptor binding in 20 antipsychotic-free DSM-III-R schizophrenic patients and 20 age- and sex-matched normal controls. Dynamic single-slice SPECT, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq of 123I-IBZM. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. There was no overall elevation of D2 receptor binding between patients and controls. A male sex-specific left lateralised asymmetry of striatal D2 receptor binding was found in the patient group. Age-dependent decline of striatal D2 receptors was confirmed in controls, but not in patients. These results suggest that alterations in striatal D2 receptor distribution and density do occur in schizophrenia, and possibly reflect wider disruptions in prefrontal-striatal-limbic circuits.

Adolescent↗

99mTc-HMPAO single photon emission tomography in late life depression: a pilot study of regional cerebral blood flow at rest and during a verbal fluency task.

Relative regional cerebral blood flow (rCBF) was measured at rest and during a verbal fluency task in ten elderly patients with major depressive disorder and nine controls. At rest, depressed patients showed significant reductions in the cortico-cerebellar ratios of tracer uptake in the right and left parietal, left temporal and left occipital regions. During the task relative rCBF increased in patients such that these differences disappeared. Relative rCBF did not correlate with severity of depressed mood or endogenous features but did correlate positively with severity of psychotic symptoms. Frontal relative rCBF correlated negatively with somatic symptoms and anxiety.

Aged↗

Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 123I IBZM SPET (single photon emission tomography) study.

The hypothesis that poor response to antipsychotic medication is due to inadequate occupancy of central D2 receptors was tested in vivo. We assessed striatal D2 dopamine receptor availability for binding with the specific ligand 123I IBZM by single photon emission tomography (SPET) in two groups of DSM-III-R diagnosed schizophrenic patients on typical antipsychotic medication, and a group of healthy controls (N = 20). Patients were characterized by clinical ratings as antipsychotic responders (N = 10) or non-responders (N = 8). Dynamic single slice SPET, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq 123I IBZM. Semiquantitative analysis generated indices of D2 receptor availability for binding. There was no difference in striatal D2 receptor availability between the patient groups, both showing a similar degree of occupancy by antipsychotic medication compared to the control group. Thus, poor clinical response does not appear to be accounted for by differential blockade, or inadequate occupancy of striatal dopamine D2 receptors by antipsychotic medication.

Adult↗

Alterations in regional cerebral blood flow, with increased temporal interhemispheric asymmetries, in the normal elderly: an HMPAO SPECT study.

Single photon emission computed tomography (SPECT) with the tracer 99Tcm-hexamethylpropyleneamine oxime (HMPAO) provides images allowing semiquantitative estimation of regional cerebral blood flow (rCBF). Despite its widespread use there is little data on patterns of rCBF obtained using this tracer in normal elderly subjects, although other methods of measurement suggest a fall in cerebral blood flow with age. Furthermore, the detection of interhemispheric asymmetries on HMPAO SPECT is often used to identify areas of pathological abnormality yet there is little data on the prevalence of asymmetries in the normal elderly. An increased prevalence of asymmetries in the elderly may explain the difficulties recently reported in using functional imaging in the diagnosis of Alzheimer's dementia. Patterns of HMPAO uptake were compared in 10 young (mean age 24.9 years; range 21-34 years) and 10 elderly (mean age 74.1 years; range 70-76 years) normal subjects. Percentage interhemispheric asymmetry ratios were calculated and found to be greater in the elderly, particularly for the temporal cortex (young 0.87%, elderly 3.73%, P < 0.001). The proportion of injected HMPAO taken up by the head was 29% higher in the younger age group. Analysis of regional uptake revealed that this trend towards reduced uptake in the elderly was a global phenomenon affecting all brain regions. The increased interhemispheric asymmetries seen in the elderly imply that a higher threshold for interpreting asymmetries as abnormal must be used in the elderly, particularly for the temporal cortex.

Adult↗