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Biomedical subjects

A Alavi

Publications and source records attributed to A Alavi.

At least 307 records · Page 17Linked to original sources

Pulmonary arterial hypertension: value of perfusion scintigraphy.

Records of 34 patients with established causes of pulmonary arterial hypertension were retrospectively reviewed. The ventilation-perfusion scans were blindly classified according to standardized criteria as normal or high, low, or intermediate probability of pulmonary embolism as the cause of pulmonary arterial hypertension. Twelve of 13 patients with primary pulmonary hypertension had normal or low-probability scans, but the perfusion pattern was not helpful in distinguishing between histologic subtypes. All eight patients with large-vessel thromboembolic hypertension had high-probability scans; however, three of 13 patients with nonembolic secondary pulmonary hypertension also had high-probability scans. While a normal or low-probability scan excluded proximal pulmonary emboli as a cause of pulmonary hypertension, a high-probability scan may be associated with a variety of other nonembolic causes of secondary pulmonary hypertension.

Adult↗

Local cerebral metabolic changes in acute ischemic strokes.

Positron emission tomography (PET) studies with 18F deoxyglucose were completed in 35 patients with acute ischemic strokes. Twelve cases were studied within 72 h, 23 between 4 and 14 days. Results indicate the functional and prognostic significance of early tomography studies of metabolism, and anticipate possible use of metabolic imaging in the evaluation of treatment.

Brain↗

Metabolic and clinical correlates of acute ischemic infarction.

We studied cerebral metabolism, anatomy, and clinical status in 36 patients with acute cerebral ischemia. Results from FDG-PET were compared with CT to find the relationships between the metabolic, anatomic, and clinical findings. Metabolic abnormalities seen on PET frequently were more extensive than the corresponding CT findings. The pattern of metabolic abnormality was significantly related to both the type of clinical syndrome and the degree of eventual recovery. No such relationships were found for the CT results. We conclude that studies of cerebral metabolism are of value in establishing prognosis after acute cerebral ischemia. Also, knowledge of the patterns of cerebral dysmetabolism provides a powerful means for the localization of clinical function.

Aged↗

MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging.

The type, frequency, and extent of MR signal abnormalities in Alzheimer's disease and normal aging are a subject of controversy. With a 1.5-MR unit we studied 12 Alzheimer patients, four subjects suffering from multiinfarct dementia and nine age-matched controls. Punctate or early confluent high-signal abnormalities in the deep white matter, noted in 60% of both Alzheimer patients and controls, were unrelated to the presence of hypertension or other vascular risk factors. A significant number of Alzheimer patients exhibited a more extensive smooth "halo" of periventricular hyperintensity when compared with controls (p = .024). Widespread deep white-matter hyperintensity (two patients) and extensive, irregular periventricular hyperintensity (three patients) were seen in multiinfarct dementia. Areas of high signal intensity affecting hippocampal and sylvian cortex were also present in five Alzheimer and two multiinfarct dementia patients, but absent in controls. Discrete, small foci of deep white-matter hyperintensity are not characteristic of Alzheimer's disease nor do they appear to imply a vascular cause for the dementing illness. The frequently observed "halo" of periventricular hyperintensity in Alzheimer's disease may be of diagnostic importance. High-signal abnormalities in specific cortical regions are likely to reflect disease processes localized to those structures.

Aged↗

Activation of liver macrophages in murine malaria is enhanced by vaccination.

During blood-stage infection of mice with a lethal variant of Plasmodium yoelii, cells in both spleen and liver became activated to reach a peak at day 5. In mice protected by vaccination, activation was accelerated after infection. The most striking difference observed was in the 10-fold greater yield of infiltrating cells, including macrophages, obtained from the liver just before the mice recovered. Their capacity to give an oxidative burst and their cytotoxic activity against tumour cells was also more than 10 times normal. This suggests that the recruitment of inflammatory cells to the liver plays an important role in the protection of vaccinated mice against malaria.

Animals↗

Positron emission tomography in aging and dementia: effect of cerebral atrophy.

The spatial resolution of current positron emission tomography (PET) scanners does not allow a distinction between cerebrospinal fluid (CSF) containing spaces and contiguous brain tissue. Data analysis strategies which therefore purport to quantify cerebral metabolism per unit mass brain tissue are in fact measuring a value which may be artifactually reduced due to contamination by CSF. We studied cerebral glucose metabolism (CMRglc) in 17 healthy elderly individuals and 24 patients with Alzheimer's dementia using [18F]fluorodeoxyglucose and PET. All subjects underwent x-ray computed tomography (XCT) scanning at the time of their PET study. The XCT scans were analyzed volumetrically, in order to determine relative areas for ventricles, sulci, and brain tissue. Global CMRglc was calculated before and after correction for contamination by CSF (cerebral atrophy). A greater increase in global CMRglc after atrophy correction was seen in demented individuals compared with elderly controls (16.9% versus 9.0%, p less than 0.0005). Additional preliminary data suggest that volumetric analysis of proton-NMR images may prove superior to analysis of XCT data in quantifying the degree of atrophy. Appropriate corrections for atrophy should be employed if current PET scanners are to accurately measure actual brain tissue metabolism in various pathologic states.

Aged↗

Quantitative autoradiography of parathyroid glands in rats with carbon-14-labeled amino acids.

We have utilized a quantitative autoradiographic method as a means of evaluating amino acid uptake of the rat parathyroid gland for the ultimate purpose of finding agents potentially suitable for position emission tomographic scanning of parathyroid glands. L-[1-14C]leucine and L-[guanido-14C]arginine were evaluated because of their relatively high content in the synthetic products of the parathyroid glands compared with other neck tissues, thyroid gland, and muscle. Carbon-14 leucine disappeared rapidly from plasma following intravenous injection and there was relatively selective uptake of the [14C]leucine and [14C]arginine by the parathyroid glands when compared with uptake by the thyroid gland and neck muscle. These data suggest that both agents warrant further investigation for their potential utility in positron emission tomographic scanning of the parathyroid gland.

Amino Acids↗

Cerebellar glucose consumption in normal and pathologic states using fluorine-FDG and PET.

We studied cerebellar metabolism in 118 subjects including young and elderly controls and patients suffering from stroke, supratentorial brain tumor and Alzheimer's disease using fluorine-18 fluorodeoxyglucose ([18F]FDG) and position emission tomography (PET). Alzheimer's disease and normal aging did not alter mean cerebellar metabolism. In stroke and tumor mean cerebellar metabolism was lower in the hemisphere contralateral to the supratentorial lesion. In tumor bilaterally significant reductions in absolute cerebellar metabolism also were noted, unlike stroke. Primary sensory stimulation did not alter absolute or relative cerebellar metabolism. These results show that absolute and relative values for cerebellar metabolism vary depending on the process under study. Thus analysis schemes employing normalization of regional metabolic data to cerebellar values may be subject to error.

Adult↗

Slowly progressive aphasia without generalized dementia: studies with positron emission tomography.

Slowly progressive aphasia without generalized dementia is a degenerative syndrome selectively affecting dominant hemisphere language areas. We report changes in regional glucose metabolism measured by positron emission tomography in two patients with this condition. Striking abnormalities of glucose utilization in the left cerebral cortex were demonstrated in both patients. The findings of other neurodiagnostic studies were relatively unremarkable. The first patient had a 3-year history of progressive anomia and impaired auditory verbal recall. An electroencephalogram was normal, and computed tomography showed mild left perisylvian atrophy. Positron emission tomography revealed profound hypometabolism in the left temporal regions. The second patient also had a 3-year history of progressive anomia. Electroencephalography, computed tomography, and magnetic resonance imaging scans were normal. Positron emission tomography showed a major reduction in left parietal glucose utilization, with a lesser decrement in left temporal metabolism. Neither patient demonstrated significant contralateral or global abnormalities such as those reported in positron emission tomographic studies of Alzheimer's disease with or without focal clinical features. These observations support the concept of adult-onset progressive aphasia without dementia as a clinical syndrome distinct from Alzheimer's disease.

Aphasia↗

Radioimmunodetection of human tumor xenografts by monoclonal antibody F(ab')2 fragments.

Experimental procedures are described for the radiolocalization of human tumors by murine monoclonal antibodies (MAb) in animal model systems. Visualization of tumor xenografts was clearer in nude mice as compared to experimentally immunosuppressed mice due to the higher viability of the tumors in nude mice. MAb localization in tumor tissue was greatly enhanced when F(ab')2 fragments rather than intact antibody molecules were used. Although tumors could be visualized with either 131I-, 123I- or 111In-labeled MAb fragments without using background subtraction, tumor-to-background ratios of radioactivity were highest for 131I-labeled fragments. 131I-labeled F(ab')2 fragments of eight MAb against human colorectal carcinoma, melanoma or lung carcinoma localized specifically only in those tumors that bound the MAb in vitro and not in unrelated tumors. Radiolabeled fragments of MAb with other specificities (anti-hepatitis virus MAb) did not localize in tumors. All MAb that inhibited tumor growth in nude mice effectively localized these tumors by gamma-scintigraphy. On the other hand, some MAb were effective in localizing tumors but ineffective in inhibiting their growth. The ability of the specific radiolabeled F(ab')2 fragments to localize in tumor grafts correlated significantly with MAb binding affinity and density of antigenic sites on tumor cells together, but not with either in vitro binding parameter alone. Thus, Scatchard analysis of MAb binding to tumor cells may be an effective means to screen for MAb with tumor radiolocalization potential.

Animals↗

Positron emission tomography imaging of regional cerebral glucose metabolism.

The (F-18) fluorodeoxyglucose (FDG) technique to measure local cerebral metabolic rate for glucose (LCMRglu) is well accepted and widely used by many institutions around the world. A large number of studies has been carried out in normal volunteers and patients with a variety of CNS disorders. Several investigators have noted that no significant age-related changes in cerebral glucose use occur with normal aging. Some important and interesting findings have been revealed following sensory, motor, visual, and auditory stimulations. Functional imaging with FDG in certain neurologic disorders has dramatically improved our understanding of their underlying pathophysiologic phenomena. Some abnormalities detected on the positron emission tomography (PET) images have no corresponding changes on either x-ray computed tomograms (XCT) or magnetic resonance images (MRI). In patients with Alzheimer's disease, primary sensorimotor, visual, and cerebellar metabolic activity appears relatively preserved. In contrast, parietal, temporal, and to some degree, frontal glucose metabolism is significantly diminished even in the early stages of the disease. Patients with Huntington's disease and those at risk of developing this disorder have a typical pattern of diminished CMRglu in the caudate nuclei and putamen. In patients with stroke, PET images with FDG have demonstrated abnormal findings earlier than either XCT or MRI and with a wider topographic distribution. FDG scans have revealed interictal zones of decreased LCMRglu in approximately 70% of patients with partial epilepsy. The location of the area of hypometabolism corresponds to the site of the epileptic focus as determined by electroencephalography and microscopic examination of the resected tissue. Ictal scans during partial seizures demonstrate areas of hypermetabolism corresponding to the sites of seizure onset and spread. Several investigators have reported relative hypofrontal CMRglu in patients with schizophrenia. In our center, FDG scans from patients with schizophrenia were successfully differentiated from those obtained in normal controls. Finally, our preliminary data (using PET, XCT, and MRI) in patients with CNS disorders indicate that MRI provides excellent delineation of the structural abnormalities. It may prove to be superior to XCT in the evaluation of certain diseases such as cerebral ischemia and infarcts, head injury, tumors, and white matter lesions. Metabolic imaging with FDG provides functional information not obtainable with either MRI or NMR spectroscopy. Therefore, PET studies will play a complementary role to the anatomic imaging in the management of patients with CNS disorders.

Aging↗

A false-positive indium-111 labeled leukocyte scintigram in a patient with a painful hip prosthesis.

A Tronzo hip prosthesis is designed to elicit an inflammatory reaction in order to promote prosthesis stability. A three-phased bone scan and Ga-67 imaging in conjunction with physical examination and laboratory findings failed to demonstrate evidence for osteomyelitis in a patient with a painful hip prosthesis, in whom images obtained with In-111-labeled leukocytes were positive. This observation demonstrated that the interpretation of the latter technique in demonstrating inflammation can cause a false impression of an infectious process.

Diagnosis, Differential↗

Avascular necrosis of the hip: comparison of MR, CT, and scintigraphy.

The capabilities of MRI, radionuclide bone scanning, and X-ray CT in diagnosing avascular necrosis of the hip were compared in a controlled statistical study. Diagnostic ability was measured as the area under the receiver-operating-characteristic curve. Differences in efficacy among various case pools and the standard errors of those differences were calculated. MR was better than both other techniques over the entire case pool, with the difference between MR and radionuclide scanning exceeding 2 standard errors (p less than 0.01). In the subsample of patients including more early cases, MR was better than CT by greater than 2 standard errors and better than radionuclide scanning by over 3 standard errors. This is evidence that MR is the most sensitive imaging technique for the early diagnosis of avascular necrosis.

Adult↗

Computerized tomography, magnetic resonance imaging, and positron emission tomography in the study of brain trauma. Preliminary observations.

Results of computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), xenon-133 measurement of cerebral blood flow (CBF), and neuropsychological assessments are described in three head-injured patients. The patients were selected because they presented with intracranial hemorrhage diagnosed by CT. Two of the patients were studied acutely and again approximately 6 months later. In the acute stage, MRI was superior to CT in identifying the precise location and extent of intracranial hemorrhage and associated edema. Small subdural hematomas diagnosed on MRI were missed with CT scanning. The extent of apparent encephalomalacia in the chronic stages of injury was also better defined with MRI. Positron emission tomography showed disturbances of glucose metabolism that extended beyond the structural abnormalities demonstrated by MRI and CT; anterior temporal lobe dysfunction was particularly evident in all three patients. Regional CBF studies failed to detect a number of the abnormalities seen on MRI and CT, and even ignored the metabolic dysfunction evident on PET that should have been accompanied by changes in regional CBF. The neuropsychological studies localized frontal lesions, but did not reveal abnormalities attributable to the structural lesions and the reduced metabolism in the anterior temporal lobes.

Adult↗

Changes in oxidative burst capacity during murine malaria and the effect of vaccination.

Adherent spleen and liver cells from mice infected with Plasmodium yoelii 17X or P. chabaudi AS were tested for production of reactive oxygen intermediates to measure their state of activation. Phorbol myristate acetate (PMA) was used to trigger the respiratory burst and production of superoxide anions was measured by the reduction of nitroblue tetrazolium. Spleen cells from mice infected with P. chabaudi showed an early increase in oxidative activity on day 3, and when the oxidative capacity of the whole spleen was calculated, it was maximal on day 9, just as the mice began to recover. In mice infected with P. yoelii, spleen cells showed an early peak in activity on day 5, and then returned to normal, although the mice did not recover for a further 2-3 weeks. However the total oxidative capacity of the spleen remained high throughout the infection. Mice vaccinated against P. yoelii with a killed blood-stage vaccine showed increased activity on day 3 (spleen) and day 5 (liver), compared with infected control mice. Thus macrophages in these organs could, if given an appropriate trigger, release high levels of these potentially toxic molecules during infection.

Animals↗

Imaging of lymph node uptake after intravenous administration of indium-111 metalloporphyrins.

Indium-111- (111In) labeled tetra (N,N,N-trimethylanilinium) porphyrin (TTAP), tetra (N-methyl-4-pyridyl)porphyrin (TMPyP), and tetra(4-sulfonatophenyl)porphyrin (T4SPP) were synthesized and lymph node uptake was measured in animals after intravenous administration. In rats [111In] TTAP had maximum lymph node to muscle uptake ratios which averaged 85:1 between 24 and 48 hr postinjection. Total lymph node uptake was nearly 1% at that time. Lymph nodes in rabbits were clearly visualized by gamma scintigraphy at 48 hr after i.v. injection of labeled TTAP. These results suggest that 111In-labeled TTAP may be a prototype for the development of a class radiopharmaceuticals which permits visualization of lymph nodes after i.v. administration.

Animals↗

Detection of deep venous thrombosis by indium-111 leukocyte scintigraphy.

Indium-111-labeled leukocyte ([111In]WBC) scintigraphy has been used successfully for detection of inflammation. Occasionally, noninflammatory collections of white blood cells such as hematomas or hemorrhage have been localized. We report a case in which unsuspected femoral deep venous thrombosis was diagnosed on an [111In]WBC leukocyte scan performed for detection of osteomyelitis. Readers are advised to avoid interpreting all vascular [111In]WBC localization as necessarily infectious. This may be of particular significance in patients with vascular grafts.

Femoral Fractures↗

Improved radioimmunoimaging of human tumor xenografts by a mixture of monoclonal antibody F(ab')2 fragments.

F(ab')2 fragments of monoclonal antibodies (MAbs) GA 73-3 and CO 29.11, with specific binding reactivity in vitro to human tumors of the gastrointestinal tract, were radioiodinated and injected into nude mice bearing human colon carcinoma xenografts. Fragments of both MAbs preferentially localized in tumor tissue compared with normal mouse tissue, as determined by differential tissue counting of radioactivity. The fragments localized specifically only in those tumors to which they bind in vitro and not in unrelated tumors. Radiolabeled fragments of an anti-hepatitis virus MAb did not localize in the tumors. Whole-body scintigraphy demonstrated tumor localization with 131I-labeled fragments without background subtraction. Best tumor contrast, as quantitated by analyzing digital computer scans, was obtained between Days 2 and 5 after injection. Tumor contrast was significantly enhanced when a mixture of both MAb F(ab')2 fragments was used. The biologic half-life of the MAb mixture in the tumor was significantly greater than that of either MAb alone, suggesting the use of the MAb mixture in radioimmunotherapy.

Animals↗