Search PubMed⌕ Search

Biomedical subjects

A Alavi

Publications and source records attributed to A Alavi.

At least 127 records · Page 7Linked to original sources

[Impact of the correction of the attenuation in myocardial perfusion image with SPECT].

BACKGROUND: The aim of this study was to assess the effect of attenuation correction on gender differences in normals and to evaluate its effect on the size and severity of lateral wall perfusion defects in patients with circumflex artery disease. MATERIAL AND METHODS: Tomographic myocardial perfusion imaging with and without attenuation correction was performed on 32 patients with circumflex artery stenosis and compared with patients with less than 5% likelihood of coronary disease. Images were acquired with a triple headed scanner and reconstructed using an iterative algorithm and re-sliced in the short axis plane. Regional count densities were measured on selected short axis slices from the base to the apex in both patients and normals. RESULTS: All attenuation corrected images were found to be more uniform than the non attenuation corrected images on the patients with less than 5% likelihood of coronary artery disease. The coefficient of variation was 12.5% for non attenuation corrected images versus 9.9% for attenuation corrected images (p < 0.0001). When female and male segmental count distributions were compared, significant differences were found which were resolved after attenuation correction. In patients with circumflex artery stenosis, the anterolateral and lateral count densities were lower at all levels with attenuation corrected images with an increasing difference from base to apex. CONCLUSIONS: The use of attenuation correction results in a greater uniformity in normals and an improved estimation of extent and severity of perfusion defects in the territory of the circumflex artery.

Adult↗

Tissue-specific galactosyltransferase abnormalities in an experimental model of rheumatoid arthritis.

OBJECTIVE: To investigate whether the observed pathophysiological similarities that develop in both the collagen induced experimental model of arthritis (CIA) and rheumatoid arthritis (RA) are associated with similar glycosylation changes, and to evaluate possible differences in the relative activity of the glycosylation enzyme beta, 1-4 galactosyltransferase (GTase) within various tissues, and thus provide a new insight into the potential pathogenic mechanisms controlling glycosylation changes. METHODS: Lymphocytic membrane-bound GTase activity was examined in 30 mice with CIA, 30 age matched controls and 10 adjuvant treated non-arthritic DBA/1 mice. Tissue-specific changes were assessed by comparison of GTase activity in peripheral (P.GTase) and paired splenic lymphocytes. In addition, we also investigated the effect that these changes may exert on the overall extracellular level of this enzyme, by assaying serum GTase (S.GTase) activity in these and a further group of 27 arthritic and 20 control mice. To analyse this synthetic abnormality in greater depth and to investigate the relevance of these glycosylation changes to the pathogenesis of arthritis, we also examined the humoral regulatory component associated with this system by assaying for both anti-collagen as well as anti-GTase antibodies. RESULTS: The induction of arthritis in DBA/1 mice results in a marked reduction in P.GTase activity, compared with age-matched unimmunised mice and the adjuvant controls. In contrast to the P.GTase, splenic GTase activity was found to be similar in all the groups examined. Correspondingly, serum GTase activity was also found to be significantly lower in the collagen induced arthritic mice. This overall reduction in beta, 1-4 GTase activity reflects the clinical severity of arthritis and is associated with increased levels of naturally occurring anti-GTase antibodies. CONCLUSIONS: The GTase defect seen in the peripheral B and T cells in rheumatoid arthritis is also evident in the arthritic DBA/1 mouse model of RA. This may indicate a common pathological process in both rheumatoid disease and CIA, in which changes in glycosylation are dependent on the aberrant modulation of GTase in circulating, but not splenic lymphocytes. The relative expression and activity of glycosyltransferases within various tissues may not only contribute to immunoglobulin G (IgG) glycosylation changes, but perhaps also the aberrant expression of cell surface carbohydrates and thus cell trafficking.

Animals↗

Biodistribution and dosimetry of TRODAT-1: a technetium-99m tropane for imaging dopamine transporters.

UNLABELLED: Technetium-99m TRODAT-1 is an analog of cocaine that selectively binds the presynaptic dopamine transporters. The primary purpose of this study was to measure its whole-body biokinetics and radiation dosimetry in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacological safety to be assessed simultaneously. METHODS: The sample included 4 men and 6 women ranging in age from 22-54 yr. An average of 20 whole-body scans were acquired sequentially on a dual-head camera for up to 46 hr after the intravenous administration of 370+/-16 MBq (10.0+/-0.42 mCi) 99mTc TRODAT. The renal excretion fractions were measured from 12-24 discrete urine specimens. The fraction of the administered dose in 17 regions of interest and each urine specimen was quantified from the attenuation and background corrected geometric mean counts in conjugate views. Multiexponential functions were iteratively fit to each time-activity curve using a nonlinear, least squares regression algorithm. These curves were numerically integrated to yield source organ residence times. Gender-specific radiation doses were then estimated with the Medical Internal Radiation Dose technique for each subject individually before any results were averaged. RESULTS: There were no pharmacological effects of the radiotracer on any of the subjects. The early planar images showed differentially increased activity in the nose, pudendum and stomach. SPECT images demonstrated that the radiopharmaceutical localized in the basal ganglia in a distribution that was consistent with selective transporter binding. Image analysis showed that the kidneys excreted between 20% and 32% of the injected dose during the first 22-28 hr postadministration, after which no more activity could be recovered in the urine. The dose limiting organ in both men and women was the liver, which received an average of 0.046 mGy/MBq (0.17 rads/mCi, range 0.14-0.22 rad/mCi). In the worst case, which was clearly an over-estimation, it would have taken 22.7 mCi to deliver 5 rad to the liver. CONCLUSION: TRODAT may be a safe and effective radiotracer for imaging dopamine transporters in the brain and the body.

Adult↗

PET evaluation of therapeutic limb perfusion in Merkel's cell carcinoma.

An 87-yr-old woman diagnosed with recurrent Merkel's cell carcinoma was treated with therapeutic limb perfusion and underwent PET scanning with 18F-fluorodeoxyglucose (FDG). PET studies were obtained before and after treatment to determine the response to the intervention. A baseline whole-body study was obtained to assess the extent and degree of disease activity. This was followed by a repeat PET scan 2 mo. later after treatment with isolated limb chemotherapy with high-dose melphalan and tumor necrosis factor-alpha. The initial scan demonstrated multiple foci of high FDG uptake in the left calf, a left supraclavicular lesion and also detected concurrent keratinizing squamous cell metastasis in the right axilla. A repeat PET study showed complete metabolic resolution of the lesions in the left calf after treatment. FDG PET may be a useful technique for staging Merkel cell carcinoma and for assessing the tumor response after therapy of this rare tumor.

Aged↗

I-123 iofetamine single-photon computed emission tomography in rapid cycling bipolar disorder: a clinical study.

The regional distribution of I-123 iofetamine (IMP) in the brain of 12 patients with rapid cycling bipolar disorder was studied by single-photon computed emission tomography imaging. Patients who were either medication free (n = 4) or on lithium monotherapy (n = 8) were assessed serially in depressed/dysphoric, manic/hypomanic, or euthymic states. In 23 imaging studies, IMP images of the brain were taken on a GE Starcam system 20 min after injection of 3-4 mCi of I-123 labeled IMP. The I-123 IMP distribution in the anterior part of the temporal lobes was asymmetric in both depression/dysphoria and mania/hypomania but not in euthymia. Images taken sequentially on the same patient showed temporal lobe asymmetry in the pathological mood states that diminished or disappeared in the euthymic state. The observed changes most likely reflect an altered cerebral blood flow and changes in high-affinity IMP binding to amine receptors in the temporal lobes. This pilot study suggests the presence of a state-dependent temporal dysfunction in bipolar disorder.

Adult↗

Lateralized changes in regional cerebral blood flow during performance of verbal and facial recognition tasks: correlations with performance and "effort".

Functional neuroimaging has been used to investigate neural substrates of mnemonic processes, and cerebral blood flow (CBF) measures have been sensitive to activation with memory tasks. Studies of memory with two-dimensional 133Xenon clearance techniques found that word and face recognition tasks produced contralateral CBF changes in mid-temporal cortical regions. This study replicated the activation paradigm, expanding to the three-dimensional resolution of positron emission tomography (PET). Word and face recognition, and a control baseline task were administered to 19 healthy right-handed volunteers (11 men, 8 women) during successive 10 min PET 15O-water measures of CBF. Quantitative CBF rates were calculated with the arterial input function and the equilibrium model. Redistributions of blood flow were compared across tasks-using both absolute and relative (region/ whole brain) CBF. Replicating the 133Xenon clearance findings, CBF was "appropriately" lateralized during task performance (left-right for words > left-right for faces) in the mid-temporal region. Contrary to predictions, the recognition tasks did not activate expected mesolimbic or prefrontal areas. The task-induced CBF changes also correlated with performance. Bilateral CBF in mid-temporal and parahippocampal gyrus regions of interest correlated with the ability to correctly identify word targets (sensitivity). Left-lateralized CBF in the amygdala and hippocampus correlated with better word sensitivity as well as specificity (ability to correctly reject foils). Complementally, right-lateralized CBF in the parahippocampal gyrus correlated with better face specificity performance. In addition, left-lateralized CBF in the amygdala and right-lateralized CBF in the parahippocampal gyrus and hippocampus correlated with "mental effort" indices (task performance relative to basal ability) for word and face memory tasks, respectively. Thus, whereas this recognition task showed the expected lateralized increase in the mid-temporal region and not in frontal and limbic areas, lateralized activation in some of these areas was associated with better performance. Exploratory analyses on other regions showed lateralized changes in one additional temporal region, the occipital-temporal, and several limbic regions.

Adult↗

A detailed lectin analysis of IgG glycosylation, demonstrating disease specific changes in terminal galactose and N-acetylglucosamine.

Serum IgG from rheumatoid arthritis patients contains a decreased number of oligosaccharide structures ending in galactose and thus there is an increase in N-acetylglucosamine as the terminal sugar, compared with healthy individuals. The relationship between these two sugars varies depending on the disease examined: IgG from patients with rheumatoid arthritis, juvenile onset chronic arthritis and Crohn's disease are at one extreme, and exhibit a reciprocal galactose:N-acetylglucosamine relationship, while Sjögren's syndrome and osteoarthritis IgG are at the other extreme, exhibiting a parallel increase in the expression of both galactose and N-acetylglucosamine. These results may occur as a consequence of more than one glycosylation site which is differentially glycosylated, but more likely by changes in the level of bisecting N-acetylglucosamine.

Acetylglucosamine↗

Lack of T cell response to cardiac myosin and a reduced response to PPD in patients with idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDCM) is the main cause of cardiac transplantation in young adults in the 20-40 years age group in the Western world. Recent evidence supports a possible role for autoimmune pathogenesis in IDCM and it has been suggested that T cells could mediate the disease. Cardiac myosin is one of the putative autoantigens recognized by antibodies from patients with IDCM, but T cell responses to cardiac myosin have not previously been assessed. Proliferation to cardiac myosin by peripheral blood mononuclear cells (PBMC) from patients, their relatives and controls was assessed in a lymphoproliferation assay specifically designed to measure low frequency T cell precursor responses. The study group consisted of 23 patients with IDCM and 29 relatives. The control groups consisted of 10 patients with heart failure secondary to ischaemic heart disease (IHD) and 22 healthy laboratory controls. A response to myosin was observed in 16.7% of the subjects studied. However, these responses were all of low precursor frequency and no dose response for antigen-specific proliferation could be observed. More importantly, there was no correlation between myosin-specific T cell responses and IDCM, as only one IDCM patient and four IDCM relatives (three out of the four with left ventricular enlargement (LVE)) were among the 14 subjects whose PBMC exhibited a proliferative response. However, proliferation of PBMC to purified protein derivative of Mycobacterium bovis (PPD) was significantly suppressed in IDCM patients when compared with the laboratory control group (P<0.05). PPD response data suggested that the PPD suppression correlated with disease progression. The results of our present study indicate an absence, or lack, of cardiac myosin-specific peripheral blood T cells in IDCM patients, along with the possibility of underlying impaired cell mediated immunity, reflected in the suppressed responses to PPD. Future studies looking at T cell immune mechanisms in IDCM should concentrate on the analysis of T cells from the heart itself, or look at other potential cardiac antigens from normal and diseased heart tissue.

Adolescent↗

Effects of aging on the cerebral distribution of technetium-99m hexamethylpropylene amine oxime in healthy humans.

Some brain functions decline at a linear rate throughout adulthood. Others remain relatively stable until very late in the life cycle. This study characterized the effects of aging on the regional cerebral distribution of hexamethylpropylene amine oxime (HMPAO) in healthy human volunteers. The sample consisted of 26 men and 18 women with a mean age of 41.6+/-14.9 years (range: 19-73). Their past medical histories, physical examinations, and laboratory screening tests were normal. Single-photon emission tomography (SPET) scans of the brain were performed with a standardized acquisition and processing protocol on a triple-headed camera equipped with fan beam collimators. A 3-D restorative filter and a correction for uniform attenuation were applied before the images were reinterpolated in planes parallel to the line connecting the frontal and occipital poles. Mean counts per pixel were measured in multiple regions of interest (ROIs) within each hemisphere by custom fitting a set of templates to the images. The mean activity in each ROI was compared with the mean activity per pixel in the whole brain. Regression analyses were used to relate the activity ratios to age with both linear and nonlinear models. The relative concentration of radioactivity decreased significantly with age in most, but not all, gray matter structures. It increased in the white matter regions. The nonlinear model of aging fit the data significantly better than a straight line did. Most of the changes with age occurred during young adulthood. No further changes were detectable after the onset of middle age. The median breakpoint age at which the rate of change became negligible was 36.6 years. Aging significantly affects the relative uptake of HMPAO in healthy humans. It decreases in many gray matter regions and increases in most white matter regions. However, the changes do not appear to be linear. Most seem to occur during young adulthood before people reach their late thirties. The distribution then appears to remain relatively stable throughout middle age.

Adult↗

PET regional cerebral blood flow change during working and declarative memory: relationship with task performance.

Functional and anatomical relationships between working and declarative memory were investigated by contrasting regional cerebral blood flow (rCBF) change during standard working (Wisconsin Card Sorting Test, WCST) and declarative memory (Paired Associate Recognition Test, PART) tasks using identical stimulus-response modalities. The tasks and a resting baseline were administered to 30 participants (16 men, 14 women) during successive 10-min positron emission tomography 15O-water measures of rCBF. For both tasks, rCBF increased over baseline in inferior frontal and occipitotemporal regions, with more consistent dorsolateral prefrontal activation for WCST than PART. Additional orbitofrontal increases and dorsomedial decreases were seen for the PART. Activation patterns diverged when performance was considered. For the WCST, high performers activated dorsolateral and inferior frontal regions, whereas top PART performers activated only the occipitotemporal region. These results suggest operation of a frontotemporal network subserving both types of memory function that becomes more focal as performance increases.

Adolescent↗

The 'mouse face' appearance of the vertebrae in Paget's disease.

Paget's disease is occasionally found as an incidental finding on bone scans performed for the evaluation of metastatic disease, which causes a diagnostic and a subsequent therapeutic dilemma. We have previously described the "Mouse Face" appearance of vertebrae on bone scans (increased uptake in the vertebral body, posterior elements, and the spinous process), which was fairly specific for Paget's disease in a small series. This retrospective study was undertaken to determine if this observation holds true in a larger series. Bone scans performed in 2,881 patients were randomly selected, and were reviewed by 2 physicians. Thirty-nine cases with a "Mouse Face" appearance were identified. Diagnosis was established in 30 of the 39 patients by correlative radiographic studies and/or clinical follow-up. Twenty patients were referred for the evaluation of possible metastases, and 7 were found to have metastases at the sites of "Mouse Face". The other 13 had Paget's disease. However, 6 of the 7 patients with metastases had extravertebral findings compatible with multiple metastases, and the remaining patient had a "Mouse Face" lesion only, with a question of metastases. Ten patients were evaluated for Paget's disease or others, and none of them had metastases at the site of the "Mouse Face". The "Mouse Face" appearance is more suggestive of Paget's disease than metastases even in patients with cancer. These patients should be assumed unlikely to have vertebral metastases, unless proven by another correlative radiologic study.

Adult↗

Constraints on the cerebral basis for semantic processing from neuroimaging studies of Alzheimer's disease.

OBJECTIVE: Functional activation studies of semantic processing in healthy adults have yielded conflicting results. The purpose was to evaluate the relative role of the brain regions implicated in semantic processing with converging evidence from imaging studies of patients with impaired semantic processing. METHODS: Semantic memory was assessed in patients with Alzheimer's disease using two measures, and these performance patterns were related to profiles of reduced cerebral functioning obtained with high resolution single photon emission computed tomography (SPECT). Patients with frontotemporal degeneration were similarly evaluated as a control group. RESULTS: Reduced relative cerebral perfusion was seen in parietal and posterior temporal brain regions of patients with Alzheimer's disease but not patients with frontotemporal degeneration. Impairments on semantically guided category membership decision tasks were also seen in patients with Alzheimer's disease but not those with frontotemporal degeneration. Performance on the semantic measures correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere only in Alzheimer's disease. Relative perfusion was significantly lower in these regions in patients with Alzheimer's disease with semantic difficulty compared with patients with Alzheimer's disease with relatively preserved semantic processing. CONCLUSION: These findings provide converging evidence to support the contribution of superior temporal and inferior parietal regions of the left hemisphere to semantic processing.

Aged↗

Regression of advanced refractory ovarian cancer treated with iodine-131-labeled anti-CEA monoclonal antibody.

Advanced chemotherapy-resistant ovarian cancer has a poor prognosis, thus requiring new therapeutic modalities. A complete clinical remission, using two cycles of 131I-labeled murine MN-14 anti-CEA monoclonal antibody (MAb), given intravenously, is reported in a patient with advanced ovarian cancer refractory to paclitaxel (Taxol) therapy. The patient first received radioimmunotherapy with approximately 74 mCi 131I-MN-14 IgG, followed 4 mo later by a similar dose of radiolabeled MAb. A partial remission was seen by CT 1 mo after the first radioimmunotherapy, and a further objective response was documented after the second radioimmunotherapy. CT scans performed 6 and 11 mo after the second radioimmunotherapy showed stable and minimal residual changes. However, a whole-body PET scan with [18F]fluorodeoxyglucose (FDG-PET) was negative in these regions. The CA-125 also decreased to only 13 U/ml, compared to the baseline value of 7700 U/ml. Based on CT, FDG-PET, serum CA-125 and physical exam, the patient was in complete clinical remission for 8 mo when the CA-125 levels rose. CT also showed a new suspicious lesion, presumably a peritoneal implant. No toxicity was seen after the first injection, and only Grade 1 thrombocytopenia and Grade 2 leukopenia developed after the second injection, both reversing within 6 wk. This is a report of a complete clinical remission with radiolabeled anti-CEA antibodies in a patient with chemotherapy-refractive metastatic ovarian cancer.

Aged↗

Right and left ventricular volume and ejection fraction by tomographic gated blood-pool scintigraphy.

UNLABELLED: Tomographic techniques separate overlying structures, permitting measurements of absolute ventricular volumes. The purpose of this study was to determine absolute right and left ventricular volume and ejection fraction measurements with tomographic gated equilibrium blood-pool scintigraphy (TMUGA) compared to MRI and conventional planar scintigraphy. METHODS: Eighteen patients were studied. Ventricular volumes for TMUGA and MRI were calculated by modified Simpson's rule. TMUGA regions were defined by constraints including phase analysis, intensity threshold and visual inspection. MRI studies were acquired with a fast gradient-echo, ECG-gated, breath-hold technique and boundaries were defined by a semiautomated contour method. Conventional gated first-pass radionuclide angiography (FP) and planar gated equilibrium blood-pool scintigraphy (PMUGA) were performed for RV EF and LV EF, respectively. RESULTS: TMUGA absolute right ventricular volumes showed excellent-correlation with MRI for both right ventricular volumes (r = 0.91, slope = 0.90, s.e.e. = 15.7) and left ventricular volumes (r = 0.96, slope = 0.88, s.e.e. = 18.2). For left ventricular ejection fraction, TMUGA also showed excellent correlation with MRI (r = 0.94, slope = 1.10, s.e.e. = 9.0) and planar MUGA (r = 0.97, slope = 1.23, s.e.e. = 6.2). For right ventricular ejection fraction, TMUGA showed good correlation with both MRI (r = 0.88, slope = 0.79, s.e.e. = 6.0) and first-pass planar scintigraphy (r = 0.86, slope = 1.2, s.e.e. = 7.9). CONCLUSION: Tomographic gated blood-pool scintigraphy absolute right and left ventricular volumes and ejection fractions show good correlation with accepted techniques. Further studies are necessary to define the reproducibility of this method.

Cardiac Volume↗