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Biomedical subjects

G Lucignani

Publications and source records attributed to G Lucignani.

104 records · Page 6Linked to original sources

Reexamination of glucose-6-phosphatase activity in the brain in vivo: no evidence for a futile cycle.

Glucose-6-phosphatase activity in the rat brain in vivo was estimated by measuring the differential loss of tritium and carbon-14 from the glucose pool labeled by a mixture of [2-3H]glucose and [U-14C]glucose. The results provide no evidence of significant dephosphorylation of glucose-6-phosphate and do not support the hypothesis of a futile cycle involving glucose-6-phosphatase activity in the brain.

Animals↗

Metabolic and kinetic considerations in the use of [125I]HIPDM for quantitative measurement of regional cerebral blood flow.

The metabolic degradation and the kinetics of the cerebral uptake of N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-[125I]iodobenzyl)-1, 3-propanediamine ([125I]HIPDM) have been studied in conscious, adult male Sprague-Dawley rats to determine its suitability as a tracer for the quantitative measurement of regional CBF (rCBF). rCBF was calculated by the indicator fractionation and the tissue equilibration methods in experiments of different durations up to 1 h. The values of rCBF obtained with [125I]HIPDM were compared with those obtained in concurrent measurements with [14C]iodoantipyrine in the same animals. Results of the experiments demonstrate that [125I]HIPDM is an inadequate tracer for use with the indicator fractionation method and that any method that employs [125I]HIPDM for the determination of rCBF must take into account its metabolic degradation, diffusion limitations, and bidirectional flux across the blood-brain barrier. With the tissue equilibration method, consistent determinations of rCBF may be possible with [125I]HIPDM by measurement of the time course of its concentration in arterial blood, corrected for the presence of 125I-labeled metabolic products, and its concentration in the brain at any time up to 1 h after its administration. The method may be adapted to measure rCBF in humans by means of single-photon emission tomography with [123I]HIPDM.

Animals↗

Correlation of dose-dependent effects of acute amphetamine administration on behavior and local cerebral metabolism in rats.

Rates of local cerebral glucose utilization were measured by means of the quantitative autoradiographic 2-[14C]deoxyglucose technique in conscious rats following the acute administration of D-amphetamine (0.2-5.0 mg/kg, i.v.). Changes in locomotor and stereotypic behavior in similarly treated rats were examined as well. Administration of low doses (0.2 and 0.5 mg/kg) of amphetamine resulted in increased locomotor activity, accompanied by elevations in glucose utilization limited mainly to the nucleus accumbens. A moderate dose of D-amphetamine (1.0 mg/kg) produced locomotion and stereotypic sniffing. Metabolic activity at this dose was increased in the nucleus accumbens, throughout neocortical areas, and in components of the extrapyramidal system. A high dose of amphetamine (5.0 mg/kg) produced stereotypic gnawing and licking and was associated with significant increases in glucose utilization in the extrapyramidal system, most prominently in the subthalamic nucleus. These data demonstrate that the acute administration of D-amphetamine produces effects on local cerebral glucose utilization and on behavior that differ with dose. The results also show a strong coupling between locomotion and the level of metabolic activity in the nucleus accumbens and demonstrate that the different forms of stereotypic behavior elicited by high and moderate doses of amphetamine are correlated with distinct patterns of distribution of local cerebral glucose utilization, indicating mediation by different neuronal circuits.

Animals↗

Effects of acute administration of caffeine on local cerebral glucose utilization in the rat.

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the effects of acute intravenous injections (15 min prior to study) of caffeine on brain energy metabolism. With doses of 0.1 mg/kg the effects of caffeine on cerebral glucose utilization were limited to the habenula, spinal trigeminal and paraventricular nuclei. After the 1.0 mg/kg dose significant increases were additionally seen in the caudate, ventral tegmental area and medial septum. After the injection of 10 mg/kg of caffeine, average glucose utilization of the brain as a whole was increased by 15%, and of 71 structures examined 31 structures were statistically significantly affected. Among these were all brainstem monoaminergic cell groupings, components of the extrapyramidal motor system, anterior cingulate, and medial prefrontal cortex. In the hypothalamus glucose utilization increased only in the paraventricular nucleus, arcuate nucleus, and median eminence. This study demonstrates that there is a correlation between the known stimulant effects of caffeine on behavior and widespread increases in glucose utilization throughout the brain.

Animals↗

Effects of systemically administered cholecystokinin-octapeptide on local cerebral metabolism.

The effects of systemically administered cholecystokinin-octapeptide on local cerebral glucose utilization in rats were studied by means of the 2-[14C]deoxyglucose method. Decreases in cerebral glucose utilization were observed in discrete regions of the cerebral cortex, mesencephalon, and brainstem, including the lateral habenula, ventral tegmental area, substantia nigra pars compacta, and the nucleus of the solitary tract. These data demonstrate changes in metabolic activity in specific cerebral regions following systemic cholecystokinin administration.

Animals↗

Positron emission tomography in neuronal ceroid lipofuscinosis (Jansky-Bielschowsky disease): a case report.

We report on a 13-year-old girl with late infantile neuronal ceroid lipofuscinosis (NCL) in whom PET scanning with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]/FDG) was performed. Early psychomotor development was normal. At the age of 2 years, neurological signs such as hypotonia and incoordination appeared, followed by visual failure and ataxia. At the age of 4, funduscopic examination showed macular degeneration and papillary atrophy. At the age of 9, myoclonic jerks were observed; subsequently, generalized seizures together with failing vision, mental deterioration, and visual and auditory hallucinations appeared. Brain MRI showed severe cortical and subcortical atrophy. A skin biopsy detected the presence of 'finger-print' inclusions in the cytoplasm of smooth muscle fibers. Late infantile NCL (Jansky-Bielschowsky disease) was diagnosed. FDG/PET revealed a severe reduction of metabolism in all the cortical and subcortical structures. A regional analysis of the distribution of the tracer revealed marked bilateral hypometabolism, particularly in calcarine, lateral, occipital, and temporal cortices and in the thalamus.

Adolescent↗

MRI, antibody-guided scintigraphy, and glucose metabolism in uveal melanoma.

To evaluate the usefulness of structural and biochemical imaging techniques for the diagnosis of uveal melanoma, 12 patients with choroidal melanoma were examined. Magnetic resonance imaging was used in 11 of 12 patients, as one had a metal prosthesis. All the subjects underwent single photon planar scintigraphy (SPPS) and single photon emission computed tomography (SPECT) using the 99mTc-labeled F(ab')2 of the anti-melanoma monoclonal antibody 225.28S ([99mTc]MoAb) and positron emission tomography (PET) using [18F]fluorodeoxyglucose ([18F]FDG). Magnetic resonance identified 6 of 11 melanotic lesions (definite melanomas) and 4 of 11 hypomelanotic lesions (probable melanomas), whereas in one case it was inconclusive. [99mTc]MoAb uptake was observed in 5 of 12 lesions using SPPS and 8 of 12 lesions using SPECT. [18F]FDG uptake was observed in 3 of 12 lesions by PET. These results demonstrate that both MR and radioimmunoscintigraphy are sensitive techniques for the diagnosis of choroidal melanomas and suggest that the detection of melanomas by MR, SPPS, and SPECT is largely dependent upon their size. The validity of these conclusions was verified in four subjects in whom the diagnosis was based on MR and/or SPECT findings only and confirmed by histology. The finding that only some of the uveal melanomas of larger size are visualized based on [18F]FDG uptake suggests that melanomas can have either high or low glucose consumption.

Choroid Neoplasms↗

Patient survival and cardiovascular events after kidney-pancreas transplantation: comparison with kidney transplantation alone in uremic IDDM patients.

In diabetic patients cardiovascular morbidity and mortality is still a major problem. Our aim was to study the effect of kidney-pancreas transplantation on survival, cardiovascular events, and causes of death in diabetic type 1 uremic patients. Three hundred and thirty-three uremic IDDM patients were enrolled in our waiting list for kidney-pancreas transplantation: 107 underwent kidney-pancreas transplantation (KP), 34 underwent kidney transplantation alone (KA), whereas 192 patients remained on dialysis (WL). Actuarial survival and causes of death were recorded over a period of 7 years. Seven-year survival rate was 75% for the KP group, 63% for the KA group, and 37% for the WL group (p = 0.001). Cardiovascular death rate was 9.8% in the KP group, 17.6% in the KA group, and 18.1% in the WL group (KP vs. WL, p = 0.05). Rate of acute myocardial infarction in the KP group was lower than in the KA group (2.4% vs. 17.6%, p = 0.005) as well as rate of acute pulmonary edema (0.8% vs. 23.5%, p = 0.0001) and rate of hypertensive patients at 1 (40.9% vs. 85.0%, p = 0.0001) and at 2 years (57.6% vs. 80%, p = 0.03). Kidney-pancreas transplant helped to obtain euglycemia with positive effects on survival and cardiovascular events.

Adult↗

Accuracy and clinical correlates of two different methods for chromogranin A assay in neuroendocrine tumors.

Measurement of chromogranin A (CgA) plays a major role in the management of neuroendocrine tumors (NET); however, reliable assaying of CgA is made difficult by the rapid hydrolysis following its release into the bloodstream. This study was aimed at the assessment of two assays for CgA in NET patients. CgA was measured in 93 patients by means of an enzyme-linked immunosorbent assay (ELISA) and an immunoradiometric assay (IRMA). The specificity and sensitivity of CgA were evaluated in relation to tumor histology. The clinical accuracy of the two assays was evaluated by receiver-operating characteristic (ROC) curve analysis. Regression analysis demonstrated different immunoreactivity for CgA of the antibodies used in the two kits (r = 0.61). The two assays had different accuracy also in classifying patients according to their clinical condition (91% vs 64% specificity and 79% vs 79% sensitivity for the ELISA and IRMA assay, respectively) and tumor histology (81% vs 85% sensitivity for the ELISA and IRMA assays, respectively, in carcinoids; 92% vs 67% sensitivity for the ELISA and IRMA assays, respectively, in pancreatic islet cell tumors). The different clinical accuracy of the two assays was confirmed by the ROC analysis (AUC = 0.90 vs AUC = 0.87 for the ELISA and IRMA assays, respectively). In conclusion, because of the poor standardization of the commercially available measurement tools the clinical accuracy of CgA measurement depends on the assay used. This makes it difficult to compare CgA values measured with different kits and affects the clinical accuracy of the different assays for CgA.

Adolescent↗

Positron emission tomography for the assessment of myocardial viability: a synopsis of methods and indications.

An improvement of regional and global left ventricle dysfunction can be achieved in patients with coronary artery disease either by coronary revascularization with percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. Several techniques have been developed to identify dysfunctional but viable myocardium. In the last decade, positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) has been used for the detection of hibernating myocardium. It can accurately predict the recovery of abnormal wall motion in hibernating segments prior to surgery. In particular, assessment of viability with 18F-FDG is indicated in high-risk surgical candidates being considered for revascularization or transplantation. Moreover, patient selection criteria and economic consideration are also relevant for cost-effective use of the technique.

Angioplasty, Balloon, Coronary↗

[Correction measured by attenuation in tomographic heart studies with single photon emission with thallium 201. Comparison with positron- emission tomographic studies with ammonium marked with nitrogen].

PURPOSE: We investigated 201Tl myocardial uptake with(out) nonuniform attenuation compensation in ischemic myocardiopathy patients. The segmental patterns of the two types of SPECT images were compared with PET [13N]NH3 studies performed in the same patient. PET images were taken as reference and the diagnostic accuracy of SPECT with(out) attenuation correction was evaluated. MATERIAL AND METHODS: During the SPECT study transmission and emission data were simultaneously recorded by a triple head gamma camera equipped with fan beam collimators and a 99mTc transmission line source (740MBq). SPECT and PET images, the former reconstructed with(out) attenuation correction, were corecorded and reoriented along the short axis. The left ventricular wall was divided into 11 segments and segmental activity normalized to maximum in each study. RESULTS: Statistically significant differences were found between PET/(un)corrected SPECT ratios in posterior and septal segments. In these myocardial regions, attenuation correction compensates for attenuation artifacts, by correcting the underestimation of radioactivity concentration caused by radiation absorption. A statistically significant difference was also found in midventricular anterior and apical segments (p < .05). However, in these regions attenuation correction results in a decrease in corrected relative to uncorrected SPECT activity. The agreement rate with PET data is higher for corrected SPECT (mean differences were 3.12 +/- 11.51 and 2.19 +/- 8.63 for uncorrected versus corrected SPET). We had 50% positive and 77% negative predictive value without attenuation correction, versus up to 69% and 90%, respectively, with attenuation correction. CONCLUSIONS: The attenuation correction procedure with simultaneous transmission-emission effectively reduces attenuation artifacts in SPECT myocardial imaging. While diagnostic accuracy increases in posterior and septal myocardial regions, anterior and apical data need careful interpretation because a relative decrease in radioactivity concentration can be observed after attenuation correction.

Adult↗

[Positron emission tomography in pharmacokinetics and pharmacodynamics].

Positron emission tomography (PET) allows the non invasive and quantitative measurement of regional distribution of molecules labeled with positron emitting isotopes such as: nitrogen, oxygen, carbon and fluorine. The aim of the present paper is to review the applications of this methodology for the in vivo study of the kinetics and of the mechanism of action of drugs in humans.

Animals↗