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Biomedical subjects

D C Costa

Publications and source records attributed to D C Costa.

At least 37 records · Page 2Linked to original sources
PubMed2002

Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand.

BACKGROUND: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine. OBJECTIVE: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life. METHODS: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, (123)I-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method. RESULTS: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with AD (p<0.001) and controls (p<0.001) in the caudate nucleus and the anterior and posterior putamen. CONCLUSION: FP-CIT SPET provides a means of distinguishing DLB from AD during life.

Aged↗
PubMed2002

Effect in vitro of cyclic nucleotides-elevating agents on nitric oxide production by human granulocytes from type 2-diabetic patients.

BACKGROUND: The present study was designed to investigate the hypothesis that cells from ill patients and from healthy subjects may have different reactivities under metabolic stimulation. METHODS: The study was performed with granulocytes from non-diabetic subjects and from type II -Non Insulin Dependent Diabetes mellitus (NIDDM) patients. The nitric oxide (NO) generation was comparatively determined by the nitrite concentration (micromolar of nitrite) after cell incubation in the presence of cyclic nucleotide-elevating agents. RESULTS: Our results showed an inverse reactivity for granulocytes from diabetic patients when compared to non-diabetic subjects. Granulocytes were incubated in the presence of drugs that elevate the intracellular level of cyclic AMP aminophylline (AMF), dibutyryl cyclic AMP (dbcAMP)], cyclic GMP [8.Br. cyclic GMP(8.Br.cGMP) or levamisole (LEV)]. The cyclic AMP-elevating agents (AMF and d bcAMP) inhibited NO production by granulocytes from non-diabetic subjects and activated cells from diabetic patients. By contrast, cyclic GMP-elevating agents (8.Br.cGMP and LEV) activated cells from non-diabetic subjects and inhibited granulocytes from diabetic patients. The activation of NO generation by cyclic nucleotides was blocked by pretreatment of granulocytes with L-NAME. CONCLUSION: The authors describe for the first time that both cyclic AMP and cyclic GMP were able to modulate nitric oxide production in human granulocytes and that cell reactivity in ill patients (diabetic) showed altered and inverse response in comparison to granulocytes from healthy subjects. This inverse reactivity possibly reflects a disease-induced adapted metabolic response. The consequences of this altered metabolic response on host defense and inflammation may be speculated, but further experiments are needed to confirm this hypothesis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

SPECT imaging of the dopamine transporter in juvenile-onset dystonia.

Juvenile-onset dystonia that improves after levodopa may occur in both dopa-responsive dystonia (DRD) and juvenile parkinsonism (JP), clinically similar conditions with different prognoses and management goals. The authors show normal striatal uptake of the dopamine transporter ligand FP-CIT with SPECT in a clinically atypical case of DRD, in contrast to the reduced uptake observed in JP.

Adolescent↗
PubMed2001

Functional imaging of malignant paragangliomas and carcinoid tumours.

Complete staging is mandatory for the management and therapy of neuroendocrine tumours. Various radiotracers are available but the best imaging strategy has yet to be defined. In this study we retrospectively compared 123I-MIBG, 111In-[D-Phe1]-DTPA-octreotide and 18F-FDG (PET) imaging in 15 patients with metastatic neuroendocrine tumours (11 carcinoid tumours, 4 paragangliomas). Planar images were acquired 1, 4, 24 and 48 h following the injection of 111In-[D-Phe1]-DTPA-octreotide and 123I-MIBG. Whole-body PET scans were performed 45 min after injection of 18F-FDG. 111In-[D-Phe1]-DTPA-octreotide was positive in 11/15 patients and identified 44 lesions, 18F-FDG PET was positive in 11/15 patients and identified 107 lesions and 123I-MIBG was positive in 8/15 patients and identified 67 lesions. No single scintigraphic technique identified all metastatic sites. In one patient all studies were negative. 18F-FDG PET identified more abnormal sites than the other two modalities. Combination of all three imaging modalities with X-ray CT helps to provide a more comprehensive map of the disease.

3-Iodobenzylguanidine↗
PubMed2001

Clinical role of positron emission tomography in oncology.

Positron emission tomography (PET) is now in routine use in oncology, through the success of metabolic imaging, mainly with fluorodeoxyglucose (FDG). Clear benefit is obtained with FDG PET in the assessment of patients with recurrent or residual disease, especially colorectal cancer and lymphoma. Preoperative staging of non-small-cell lung cancer with FDG PET is of proven benefit. Staging and restaging of patients with melanoma of stage II or greater is useful, and FDG PET has also been successfully used to investigate single pulmonary nodules. Tumour grading has been assessed, especially in the brain, but an important and emerging indication is the evaluation of tumour response with PET. Rapid decline of FDG uptake has been observed in responsive cancers. Further advances are being made with other fluorine-18-labelled and generator-based PET tracers, the only ones that can be used in units without dedicated cyclotrons.

Colorectal Neoplasms↗
PubMed2001

Positron emission tomography and colorectal cancer.

BACKGROUND: The oncological applications of positron emission tomography (PET) have gained widespread acceptance. This rapidly evolving technology has been applied successfully to colorectal cancer, but has not yet become part of routine clinical practice. This review considers (1) the biological basis for the use of PET in colorectal cancer, (2) the technical aspects of PET relevant to the referring clinician and (3) the application of PET to the management of primary and recurrent disease. METHODS: A Medline database search was performed for the period 1980-2000. Experience was also drawn from the first 40 patients with colorectal cancer investigated at this institution. RESULTS AND CONCLUSION: PET has a proven role, and is cost effective in the management of recurrent cancer and the monitoring of therapy. However, further evaluation is still required to justify its routine use for other indications in colorectal cancer. Development of new positron-labelled radio- pharmaceuticals, in parallel with advances in detector technology and innovative models for tracer production and distribution, means that the availability of PET and its applications in the management of colorectal cancer will expand over the coming years.

Colorectal Neoplasms↗
PubMed2001

The role of [18F]fluoro-2-deoxyglucose-PET scanning in the diagnosis of paraneoplastic neurological disorders.

The detection of an occult tumour in a patient with a suspected paraneoplastic neurological disorder (PND) may be difficult because of the limitations of conventional imaging techniques. [(18)F]fluoro-2-deoxyglucose-PET (FDG-PET) can visualize a small tumour anywhere within the body. We retrospectively reviewed the case notes of 43 unselected patients with suspected PND referred for FDG-PET scanning to determine how useful this technique was when conventional imaging was negative. All patients had undergone standard radiological investigations and bronchoscopy (where appropriate) prior to PET scanning. There were discrete areas of hypermetabolism suggestive of malignancy (positive) in 16 patients (37%). A tissue diagnosis of cancer was subsequently made in seven patients (two at post-mortem), further radiological studies were suggestive of cancer in one patient, one patient subsequently presented with a metastatic deposit which was biopsied, and four patients died shortly afterwards without a post-mortem. In three patients, subsequent investigations were negative for cancer. Serum anti-neuronal antibodies were present in 43% and CSF oligoclonal bands were present in 46% of patients with positive PET scans compared with 16 and 26%, respectively, in PET-negative patients, but this was not significant. Only one patient with a negative scan has been diagnosed subsequently as having malignancy on prolonged follow-up. These findings confirm that FDG-PET scanning is a useful technique in the detection of small tumours in patients with suspected PND. False positives and false negatives do occur, but at a sufficiently low frequency to justify the clinical usefulness of this technique.

Adult↗
PubMed2001

Functional imaging as an aid to decision-making in metastatic paraganglioma.

Malignant paraganglioma is a rare and slow growing tumour of neuroendocrine origin. At the time of diagnosis, the tumour is usually widespread, with limited therapeutic options. A variety of functional imaging studies are available for staging the disease, guiding therapy and monitoring treatment response. These include 123I-MIBG or 131I-MIBG, 111In-pentetreotide or 111In-lanreotide (somatostatin analogues), and 18F-FDG positron emission tomography. Various radionuclides, including 131I and 90Y, can be targeted to the tumour using MIBG or pentetreotide. Such targeted radionuclide therapy may provide valuable long-term palliation in such patients. We present two cases with metastatic paragangliomas who had widespread soft tissue and bone metastases. One patient was treatment naive and the second had received previous chemotherapy. The functional imaging work-up performed and the targeted radionuclide therapies considered in these patients are described. Both patients were treated with 131I-MIBG. Partial tumour response and complete symptomatic and hormonal response was achieved in one patient; in the second patient there was no change.

3-Iodobenzylguanidine↗
PubMed2001

Influence of OSEM and segmented attenuation correction in the calculation of standardised uptake values for [18F]FDG PET.

Standardised Uptake Values (SUVs) are widely used in positron emission tomography (PET) as a semi-quantitative index of fluorine-18 labelled fluorodeoxyglucose uptake. The objective of this study was to investigate any bias introduced in the calculation of SUVs as a result of employing ordered subsets-expectation maximisation (OSEM) image reconstruction and segmented attenuation correction (SAC). Variable emission and transmission time durations were investigated. Both a phantom and a clinical evaluation of the bias were carried out. The software implemented in the GE Advance PET scanner was used. Phantom studies simulating tumour imaging conditions were performed. Since a variable count rate may influence the results obtained using OSEM, similar acquisitions were performed at total count rates of 34 kcps and 12 kcps. Clinical data consisted of 100 patient studies. Emission datasets of 5 and 15 min duration were combined with 15-, 3-, 2- and 1-min transmission datasets for the reconstruction of both phantom and patient studies. Two SUVs were estimated using the average (SUVavg) and the maximum (SUVmax) count density from regions of interest placed well inside structures of interest. The percentage bias of these SUVs compared with the values obtained using a reference image was calculated. The reference image was considered to be the one produced by filtered back-projection (FBP) image reconstruction with measured attenuation correction using the 15-min emission and transmission datasets for each phantom and patient study. A bias of 5%-20% was found for the SUVavg and SUVmax in the case of FBP with SAC using variable transmission times. In the case of OSEM with SAC, the bias increased to 10%-30%. An overall increase of 5%-10% was observed with the use of SUVmax. The 5-min emission dataset led to an increase in the bias of 25%-100%, with the larger increase recorded for the SUVmax. The results suggest that OSEM and SAC with 3 and 2 min transmission may be reliably used to reduce the overall data acquisition time without compromising the accuracy of SUVs.

Fluorodeoxyglucose F18↗
PubMed2001

The clinical application of positron emission tomography to colorectal cancer management.

Colorectal cancer (CRC) is the second commonest cancer in the Western World. Successful treatment relies significantly on accurate detection and staging of primary disease as well as the early identification of the presence and extent of recurrence. Morphological imaging techniques, particularly computed tomography (CT), are well established and widely available to carry out these tasks in addition to predicting and monitoring response to therapy. This review analyses the current inadequacies for imaging CRC and critically assesses the potential role of functional imaging with positron emission tomography (PET). We review the current literature, use our experience from the first 1000 PET studies carried out at our Institution and the perspective of surgical colleagues. We find little evidence for the use of 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET for screening asymptomatic individuals and current modalities appear better suited for detection of symptomatic primary CRC. There is evidence of increased accuracy for FDG-PET in staging primary disease, but this area remains controversial and larger studies are necessary. The situation is quite the reverse with respect to imaging suspected recurrent disease with FDG-PET being more sensitive and specific than conventional techniques. This benefit manifests itself through alteration in patient management and results in cost savings. PET also appears to have a specific place in the evaluation of patients undergoing radiotherapy and chemotherapy, a role that will expand. The evidence suggests that PET will ultimately become routinely incorporated into CRC patient management algorithms. Technological advances coupled with novel tracer research will facilitate this.

Colorectal Neoplasms↗
PubMed2000

A SPECT study of the effect of vagal nerve stimulation on thalamic activity in patients with epilepsy.

The mechanism by which vagal nerve stimulation (VNS) exerts an anticonvulsant effect in humans is unknown. This study used (99m)Tc-HMPAO single photon emission tomography (SPECT) to examine the effects of VNS on regional cerebral activity in thalamic and insular regions. Seven subjects with epilepsy who had been receiving vagal nerve stimulation for at least 6 months underwent SPECT scanning with simultaneous scalp electroencephalographic (EEG) recording. Subjects were studied in two states; during VNS activity and during a comparison condition of VNS inactivity. A region of interest analysis demonstrated that rapid cycling stimulation (7 seconds on, 12 seconds off) was associated with relatively decreased activity in left and right medial thalamic regions. No systematic stimulation-related changes were observed on visual or spectral analysis of EEG data. The thalamus is involved in modulation of ongoing cortical EEG activity in animals. Our results support the hypothesis that VNS may exert an antiepileptic action by an effect on thalamic activity.

Adult↗
PubMed2000

Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.

OBJECTIVE: To evaluate whether visual assessment of [123I]-FP-CIT (DaTSCAN, Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET). METHODS: [123I]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken. RESULTS: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection. CONCLUSION: Visual assessment of [123I]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

Adult↗
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

In-vivo demonstration of dopaminergic degeneration in dementia with Lewy bodies.

With the dopaminergic presynaptic ligand FP-CIT and single photon emission tomography we have shown a severe dopaminergic degeneration in a patient with a necropsy confirmed diagnosis of dementia with Lewy bodies (DLB). We suggest that functional imaging of the nigrostriatal dopamine pathway helps to distinguish DLB from Alzheimer's disease during life.

Aged↗
PubMed1999

Patterns of brain activity in patients with epilepsy and depression.

Depression is a recognized feature of epilepsy. This study tested the hypothesis that depression arising in patients with epilepsy would be associated with decreased activity in brain regions previously demonstrated to be hypoperfused both in primary depression and in depression secondary to movement disorders. Two groups of patients with temporal lobe epilepsy were studied, one of which also met DSM IV criteria for a major depressive episode. All underwent a SPECT scan using the blood flow marker,(99m)Tc-HMPAO. An automated voxel-based analysis demonstrated no regions of relatively decreased activity in the depressed compared with the non-depressed patients. Sites of relative hyperactivity in the depressed group were concentrated in the left hemisphere, particularly in dorsolateral prefrontal cortex, striatum, thalamus and temporo-parietal regions. Comparison of these data with normal population data revealed that in the depressed epilepsy group regional activities were within the normal range whilst corresponding results from the non-depressed group were below it. Depressed patients with epilepsy have cerebral regions with greater perfusion than non-depressed people with epilepsy, although they are not hyperperfused compared with normals. Our results suggest that depression in people with epilepsy may arise from a mechanism which differs from that underlying the development of depression in patients with movement disorders.

Adult↗